JIMSA April

Special Issue

Thyroid Disorders - New Horizons

Guest Editor

Prof. Maharajan Chandrasekaran

Special Issue

Thyroid Disorders - New Horizons

Official Publication of

International Medical Sciences AcademyEditor:Dr. P. D. Gulati

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ISSN 0971 - 071X

April - June 2015, Vol. - 28, Issue - 2

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April - June 2015Vol. 28 No. 2

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BOARD OF TRUSTEES

PresidentDr. K. Jagadeesan

Vice-PresidentDr. Harvinder S. Luthra (U.S.A.)

MembersDr. (Miss) S. PadmavatiDr. Ramdas M. PaiDr. Sandip MukerjeeDr. Shaheena Asif (Pakistan)Dr. B. Bhaskar RaoProf. Nadey Hakim

Central ExecutiveCommittee (CEC)

Dr. M. RamanathanChairman, India Region

Dr. R. K. ThukralExecutive Director &Secretary General

Dr. P. D. GulatiEditor, JIMSA

Dr. A. GovindanMember

International Advisors

Sir Roy Calne EnglandAllistair D. Beattie GlasgowH. Klinkmann GermanySusan Lim Singapore

JOURNAL OF INTERNATIONAL MEDICAL SCIENCES ACADEMY

EditorP. D. Gulati, Delhi

EDITORIAL BOARD

Joint EditorS.N.A. Rizvi, Delhi

Assoc. EditorS. C.Tiwari, Delhi

MembersSandip Mukerjee, DelhiN P Singh, DelhiR K Thukral, Delhi

Section EditorManish Kohli, U.S.A

Section EditorN. S. Neki, Amritsar

InternationalAlistair D Beattie, USAH. Klinkmann, GermanySusan Lim, SingaporeH. S. Luthra, USA

Swaraj Singh, USALeela Prasad, USAJ. Heinrich Joist, USASir Roy Calne, UK

Kamal Bose, SingaporeNadey Hakim, UKDinesh BhugraMakhan Lal Burgh, UK

K Jagadeesan, ChennaiS K Bhargava, DelhiP S Gupta DelhiP K Dave, DelhiK B Logani, DelhiA K Attri, ChandigarhIndra Bahl, DelhiD K Raut, DelhiS P Aggarwal, DelhiNaresh Trehan, DelhiS A Tabish, SrinagarR K Bali, Delhi

P N Renjen, DelhiS S Trivedi, DelhiRicha Dewan, DelhiAshok Grover, DelhiB B Agarwal, DelhiJ Shanmugam, PondicherryS Jayachandran, ChennaiHarshwardhan, DelhiRajesh Chawla, DelhiA K Mahapatra, DelhiRohini Handa, DelhiV Raveenthiran, Chennai

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Kamlesh Chopra, DelhiTarun Gupta, DelhiPravesh Mehra, Delhi

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JIMSA April - June 2015 Vol. 28 No. 27272

Contents

ORIGINAL RESEARCH ARTICLE

Can the Expression Pattern of Estrogen Receptor Alpha and BetaProteins in Papillary Thyroid Carcinoma be of Prognostic Value?Kannan Annapoorna, Maria Joseph Michael Aruldhas, MaharajanChandrasekaran, Jone Arulrajadurai Stanley , RamalingamNeelamohan, Esakky Suthagar, Liaquat Alikhan Sheerin Banu,Narasimhan Srinivasan, Sakhila K Banu

ORIGINAL ARTICLE

Iodine Excess and Thyroid Dysfunction K.Ramadevi, V.Sucharita

Estimation of Viability of Grafts after ParathyroidAutotransplantation in Total Thyroidectomy Himagirish K Rao,Maharajan Chandrasekaran, Sucharita Vedachalam

Papillary Micro Carcinoma of thyroid: Institutional Experience.PV Pradeep

Single Centre Experience of Radioiodine Therapy in theManagement of Thyrotoxicosis: Retrospective analysis of 14 years.Sureshkumar Chandran, Shelley Simon, Indirani Elangovan

Low Dose or High Dose Radioiodine for Remnant Ablation inDifferentiated Thyroid Carcinoma? : A Single Centre Experience.Karuppiah Kumaresan

Surgical Management of Vocal Cord Palsy Lekshmy R Kurup,Srikamakshi Kothandaraman, Rayappa Chinnusamy

Evolving Trends in Orbital Decompression for Thyroid RelatedOrbitopathy Priti Udhay

ORIGINAL SURGICAL TECHNIQUE

Excision of Lingual thyroid - How I do it? MaharajanChandrasekaran

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73JIMSA April - June 2015 Vol. 28 No. 2

IMSAINTERNATIONAL MEDICAL SCIENCES ACADEMY


Dear Fellows, Members and Associates,

This issue of our journal carries one of the common problems forphysicians, surgeons and the endocrine specialists. The thyroidassociated conditions are becoming quite common of late; it will

be worthwhile looking in to the pre and post iodization of salt, whichwill throw some light. Since it is a national problem, it requires theattention of all concerned to help in the registry of thyroid diseases.Further work may be needed on this as the iodized salt is a daily item inour diet. In the larger interest of the society, especially the youngergeneration, it is worth realising that the occurence of developing papillarycarcinoma is on the increase. I am sure a comprehensive review of thyroiddisorders will be useful for the creation of the thyroid registry and willhelp to develop a concrete policy for the future. Further research in thisdirection will be needed.

Our annual convention is fast approaching; its and is to be held on the10th and 11th of October 2015 at Wayanad. Looking forward to meetyou all there.

Dr. K. Jagadeesan

President, IMSA

PRESIDENT WRITES

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JIMSA April - June 2015 Vol. 28 No. 27474 IMSA NEWS

Awards and Honours

Dear Colleagues,

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The main objectives of IMSA is to bring together national and international medical scientists, medical educationists, medical and public health administrators and research workers in medicaland health sciences on a world wide basis for advancement of health of all the people in the world. The academy also arranges courses, training programs, CME programs and Rural CMEprograms. IMSA publishes quarterly journal, JIMSA in which original articles, updates, symposia, special issues on topics of current interest are published.

An annual conference - IMSACON is a regular feature; being an International organization every alternate year, the annual conference is held outside India. This year’s IMSACON was held atGulf Medical University, Ajman, UAE on 6thand 7th October 2012 and was an extremely successful event.

Though IMSA has been in service of medical profession and has been encouraging development of medical sciences by bringing information technology into the profession thus improving thehealth of nations, yet we do not have our own building to work more effectively. Our organization is committed to the medical profession for promoting Continuing Medical Education and alsohold educational programmes on topics of National and public health importance. We need to conduct more seminars, organise lectures by National and International experts and hold regularworkshops and group discussions. For arranging such activities we are badly in need of our own building with adequate infrastructure and facilities like an Auditorium , projection room, library,committee rooms for interactive sessions etc. So far we have been operating from small rented space which can hardly accommodate our office.

Friends, we have been fortunate to get a piece of land about 500 sq.mtrs allotted to us by the Lt. Governor of Delhi for developing the IMSA World Head Quarters at Delhi. I am approaching allFellows and Members to donate at least Rs. 5000/- each to meet the cost of the land as well as for construction of our own building. The donations are exempted from tax under 80G; the chequemay please be made in the name of “IMSA – Building Fund” payable at New Delhi, and sent to the Headquarters.

Thanking you in anticipation and warm regards, Yours Sincerely,

Dr. K.Jagadeesan, President, IMSA,WHQ

APPEAL FOR IMSA BUILDING FUND

IMSA Jammu ChapterCME’s Conducted:16.04.15: Dr Ravinder K Gupta: Topic: Sports Injuries in Children18.04.15: PHYSIQUIZ: Annual Undergraduate Quiz Competition: Dept. of Physiology, ASCOMS, Jammu.01.05.15: Dr Prenika Shangloo: Topic: NOSOCOMIAL INFECTIONS IN NICU30.05.15: Dr Ravinder K Gupta: Topic: CHOLESTASIS IN CHILDREN

IMSA Tamil Nadu ChapterCME’s Conducted:10.05.15: Dr V Raveenthiran: Topic: Entomophthoromycosis Mimicking Soft Tissue Tumors In Children;

Dr. S M Rajendran,Topic: Standard Of Care For Diabetes

IMSA Chapter Activities/ CME Programmes

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The President Dr K Jagadeesan and the members of Board of Trustees of IMSA, WHQ, request all the fellows & members of IMSA to contributeat least Rs. 5000.00 towards Building Fund for IMSA, WHQ, New Delhi. Cheque may please be drawn in favour of “IMSA Building Fund”

IMSA WHQ. Building Fund - List of Donors

IMSA Annual Conference cum Convocation 2015Date: Saturday 10th & Sunday 11th, October, 2015,

Vythiri Village Resorts, Vythiri, Wynaadu District, Kerala State, INDIAConference Secretariat: PVS Hospital, Railway Station Road, Calicut, Kerala State, INDIA

Organizing Committee Contact: [email protected]: IMSA World Headquarters: [email protected], www.imsaonline.com

IMSACON 2015 Conference News

FellowsDr Gulshanjit Singh, New DelhiDr Paul Mazhuvanchary Jacob, Tamil NaduDr Jugal Kishore, New DelhiDr G Kulanthaivel, Tamil NaduDr M Ram Prabahar, Tamil NaduDr Susanta Behera, OdishaDr Sandeep Babu B, KeralaDr P Thangavelu, Tamil NaduDr Mohan Rajan, Tamil NaduDr Karthik Gunasekaran, Tamil NaduDr N K Thulaseedharan, KeralaDr Shikha Sharma, J & KDr PVS Prasad, Tamil Nadu

Dr Abhinav Dixit, RajasthanDr Shilpi Gupta, RajasthanDr R Shivakumar, Tamil NaduDr Shiji P V, KeralaDr Shenoy Rajgopal Kallya, KarnatakaDr Nasser Yusuf, KeralaDr Sanjay Bhat, J & KDr Satyawan Gangaramji Damle, ChandigarhDr B V Murali Mohan, KarnatakaDr Pratima Murthy, KarnatakaDr Rajneesh Kumar Mishra, HaryanaDr Ummer Karadan, KeralaDr Murali R, Tamil Nadu

Dr Himagirish K Rao, KarnatakaDr K Muhammed, KeralaDr Abdul Latheef E N, KeralaDr E Mahesh, KarnatakaDr Vijay Khajuria, J & KDr Sonu Hangma Subba, SikkimDr Sujata SiwatchDr Venugopala DDr Hanumanthaiah K SDr Geeta Rani GargDr Manish GuptaDr Suresh Kumar S K

MembersDr C Balaji, Tamil NaduDr Ashwin T, Tamil NaduDr Uday Prasad PV, Tamil NaduDr Nitika Mehta, J & KDr Saurabh Sharma, J & KDr Sakul, J & KDr M J Jayakanth, KarnatakaDr Neha Gupta, J & KDr Lisha P V, KeralaDr Arjit Agarwal, Utter PradeshDr Malick Batcha Sathik Babu, Tamil Nadu

Prof. (Dr.) Satish Kumar Bhargava, Member JIMSA Editorial Board has been awarded NBE Awards for Excellence in Medical Education 2014 for Distinguished DNB Teacher(s) Prof. (Dr.) by Prof. (Dr) BipinBatra, Executive Director, National Board of Examinations.

Dr S Jayachandran, Member, Editorial Board, JIMSA. Dr. S. Jayachandran MDS, PhD; MAMS; Prof. & Head Dept. Of Oral medicine & Radiology Tamil Nadu Government Dental College &Hospital Has beeninducted as PRESIDENT Indian Academy Of Oral Medicine & Radiology in National Conference held at Mangalore 21, 22 and 23rd November 2014

Dr. N.S. NEKI, Prof. of Medicine, Govt. Medical College, Amritsar (India), Section Editor, JIMSA, Fellow of IMSA has been appointed as Senior Editor of Journal of Pioneering Medical Sciences, Pakistan

Dr (Wg Cdr) JSAhluwalia MS,DOMS, MAeMS, FIMSA, Fellow International Medical Sciences Academy has been awarded fellowship of Joslin Diabetes Centre and Johnson &Johnson Diabetes InstituteHarvard USA.

Dr Ravinder K Gupta, Professor, Deptt of Pediatrics, ASCOMS and General Secretary IMSA, J&K chapter received prestigious Fellowship in Pediatrics (FIAP) at the National Conference of INDIAN ACADEMYOF PEDIATRICS-2015 (PEDICON) in New Delhi. Dr Gupta was selected for his outstanding contribution to the field of Pediatrics and was among 19 awardees selected from a list of about 25000 pediatriciansfrom India.

V. Raveenthiran, MS., MCh. FRCS, FIMSA, Professor of Pediatric Surgery, SRM University, Chennai, India, has been elected as President of Association of Tamil Nadu & Pondicherry Pediatric Surgeons.

Prof. S K Bhargava, Member Editorial Board, JIMSA, Fellow of International Medical Sciences Academy, Past President, ‘Indian Radiological and Imaging Association”, receiving the Delhi Medical Association

Vishisht Chikistik Ratan Award, from Dr Mahesh Sharma, Hon’ble Union Minister of Civil Aviation, Tourism and Culture on July 5, 2015.

Election of Fellows and Members March 2015 Dr Santhosh Sampath, Tamil NaduDr R Senthil Nathan, Tamil NaduDr Prakruti Dash, OdishaDr Mahesh Kumar K B, KarnatakaDr Velayutharaj ADr R Magesh BabuDr Jaideep BhatiaDr Anandraj Vaithy K

Associate MembersDr Mary Christiana Edith S, KeralaDr Dinesh Kumar S, Tamil Nadu


JIMSAJOURNAL OF INTERNATIONAL MEDICAL SCIENCES ACADEMY


Dear Colleagues,

This special issue ‘Thyroid Disorders - New Horizons’ comprises of 9articles authored by outstanding experts from the field of endocrinology.The issue highlights some of the new concepts in the understanding and

management of common thyroid disorders: there are new guide lines and newvistas for research for the younger endocrinologists and endocrine surgoens.

This publication is the outcome of hard work and untiring efforts of Prof.Maharajan Chandrasekaran, a pioneer in the field of endocrine surgery fromChennai, India. His team of contributors has done a magnificent job in preparingthe various manuscripts. I am confident this publication will be of immensebenefit to the readers of JIMSA.

No doubt, a commendable task has been achieved, for which I am extremelygrateful to Prof. Maharajan Chandrasekaran.

P. D. Gulati

FROM EDITOR’S DESK

JIMSA BEST PUBLISHED ARTICLE AWARDS 2014- Declared

The following articles have been selected for the “JIMSA Best Published Article Awards – 2014” as per ranking given below:

Rank 1: Pediatric Bladder Augmentation in Developing Country: Lessons Learnt From an Experience of 195 Cases -Sen S, Chacko J, Karl S, Mathai J, Thomas R, Dastidar A, Ravi Kishore BSS, Ninan PJ, George J.

Rank 2: Correlation between Placental Location and Uterine Artery Flow Waveforms in Uncomplicated Pregnancies –Neema Agarwal, Vishal Gupta

Rank 3: Role of Intravenous Immunoglobulin in Neurological Recovery and its effect on Circulating TNF-α Levels inGullian- Barre Syndrome - G. Avasthi, Prashant Bhatt, Amit Kumar Soni, Rajinder Bansal

Each award consists of a medal, citation and cash prize: the awardee is required to preferably receive the award at the forthcomingIMSACON 2015 being held on 10th & 11th October, 2015 at Calicut, Kerala. (Contact urgently Dr R K Thukral, ExecutiveDirector & Secretary General, IMSA, World Headquarters, New Delhi). In case the awardee is unable to attend IMSACON2015, he/she should intimate the Editor, JIMSA, accordingly.

Editor



EDITORIAL

OUR GUEST EDITOR

Prof. Maharajan Chandrasekaran, a pioneer in the field of Endocrine Surgery,has made significant contributions to the field over the past 27 years. MaharajanChandrasekaran graduated from Madras Medical College in the year 1976 andlater obtained his Masters in General Surgery from the same college in 1981. Afterjoining the Department of Endocrine Surgery in the year 1987, he has constantlyendeavoured to take Endocrine Surgery to greater heights. During his tenure as theHead of the Department he started a super speciality course - M.Ch in EndocrineSurgery in the year 2007. He has been an undergraduate and post-graduate teacher for 30 long years.

Prof.Chandrasekaran was the founder secretary and past President of the “Indian Association ofEndocrine Surgeons.” He also donned the role of Editor in Chief of the “Indian Journal ofEndocrineSurgery” for three years. He designed and launched Med-ej, the official e-journal of theTamilnadu Dr.M.G.R.Medical University - the first of its kind in India.

He has performed over 6,000 thyroidectomies and has devised a unique surgical technique to excisethe Lingual thyroid. You can read more about this technique in the Article titled “ Excision of Lingualthyroid - How I do it.”

In recognition of his achievements in the field of surgery, Royal College of Physicians and Surgeonsof Glasgow conferred upon him FRCS and the Tamilnadu Dr.M.G.R.Medical University conferredupon him the Scroll of Honour twice.

Dear Fellows,

It gives me immense pleasure to bring out this special issue of JIMSA on “Thyroid Disorders - NewHorizons”. Most of the pioneering work in the field has been published in this issue. Michael Aruldhasand his team has shown, in their original research work, that hormonal manipulation is likely to beintroduced as one more modality of treatment for papillary carcinoma in the days to come. Article on“Iodine excess and thyroid dysfunction” has stressed upon the need for the availability of uniodisedsalt in the market so that patients with thyrotoxicosis, thyroiditis and cancer thyroid can be treatedeffectively.

A new surgical procedure has been described in the article on Excision of Lingual Thyroid.There aremany more interesting articles on various topics related to thyroid and I am sure the readers wouldfind them really interesting and beneficial.

Maharajan ChandrasekaranGuest Editor

Endocrine SurgeonMcArthy Thyroid Clinic


Can the Expression Pattern of Estrogen Receptor Alpha and Beta Proteins inPapillary Thyroid Carcinoma be of Prognostic Value?Kannan Annapoorna1, Maria Joseph Michael Aruldhas1, Maharajan Chandrasekaran2,Jone Arulrajadurai Stanley1,3, Ramalingam Neelamohan1, Esakky Suthagar1, Liaquat Alikhan Sheerin Banu1,Narasimhan Srinivasan1, Sakhila K Banu3

1Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences,University of Madras,Taramani Campus, Chennai, TN, India.2Department of Endocrine Surgery, Madras Medical College, Chennai3, TN, India.3Department of Veterinary Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, TexasA&M University, College Station, TX 77843, USA.

Correspondence: Prof. M. Michael Aruldhas, Prof & Head,Department of Endocrinology, Dr. ALM Post Graduate Institute ofBasic Medical Sciences University of Madras, Taramani Campus,Chennai-600113, Tamil Nadu, Indiae-mail: [email protected]

Abstract : Increasing incidence of papillary thyroid carcinoma (PTC) in women suggests a potential role for estrogenand its receptor (ER) subtypes. In this study, we investigated the functional activity and expression pattern of estrogenreceptor subtypes in PTC. We measured serum and thyroid tissue estradiol (E2) level, functional activity of ER byassessing its ligand binding activity (LBA), expression level of ER a and ER ß proteins in 68 patients with PTC. ERLBA significantly increased in all PTC patients tested. ER a expression increased in 58.82% male and 50.98%female PTC. ER ß expression decreased in 72.54% female but increased in 88.23% male PTC samples indicating asex specific differential expression. In female PTC increased ER a positively correlated with LBA. ER ß negativelycorrelated with LBA and ER a subtype. In male PTC, increased ER a positively correlated with ER ß. However, nosignificant correlation was observed between ER LBA and either of ER subtypes.Conclusions: Change in the level of expression of ER subtypes in PTC tissues significantly affects papillary thyroidtumor growth with ER a showing pro-mitogenic property, while ER ß appears to be antimitogenic. Hence, analyzingthe expression pattern of estrogen receptors may have good prognostic value in the diagnosis of PTC.Key words: 17b-Estradiol, ER a, ER b, thyroid carcinoma.

INTRODUCTION

Thyroid cancer is the most common endocrine malignancyand its prevalence is continuously increasing over the pastthree decades worldwide1. The age-adjusted incidence rate

of thyroid cancer has been increasing worldwide mainly due tothe rise of PTC in females2. Peak increase in the incidence ofPTC in women during the active reproductive period indicatesactivation of sex steroid associated signaling pathways in theprogression of the disease. The biological effect of 17β-estradiol(E2) results from its specific binding to estrogen receptor (ER)subtypes, α and β, which belong to the nuclear receptorsuperfamily of ligand regulated transcription factors3. Studies fromour laboratory and other investigators indicated the mitogeniceffect of E2 on immortalized human thyroid cancer cell lines andin normal thyroid follicular cells4-10. The precise role of ERsubtypes responsible for PTC tumor growth is not well defined.In this study, we tested the association of ER a and ER β inmodulating PTC tumor growth by correlating its expression withthe ligand binding activity (LBA) in human PTC.

MATERIAL AND METHODS

Human Papillary Thyroid Carcinoma tissuesThis study included human PTC tissue samples collected from 68patients (male-17; female-51) who underwent surgical resection atthe Department of Endocrine Surgery, Madras Medical College,Chennai, India (Table 1). The tumor type was confirmed based onthe histopathological report from the Department of Pathology,Madras Medical College.Normal tissues removed from the oppositelobe of the thyroid gland of 13 patients subjected to totalthyroidectomy (3 males, mean age 35.0±12.0; and 10 females, meanage 28.2±4.28) and confirmed based on the histopathological reportwere used as controls. This study was carried out in accordance withthe Helsinki Declaration (2000) of the World Medical Association,and was approved by our institutional ethical committee for researchin humans (UNOM/HEC/2003/9). Written informed consent wasobtained from all patients. Thyroid tissues and blood samples werecollected as described previously4.

Enzyme Linked Immunosorbent Assay (ELISA)Serum and thyroid tissue E2 was assayed by ELISA according to themanufacturer’s instruction (DRG Instruments GmbH, Marburg,Germany).

Radio receptor assayThe functional activity of ER in terms of its LBA was quantified inthyroid tissue using [3H] E2 as elaborated earlier (Banu et al., 2002,Stanley et al., 2010).


Western blot analysisTotal protein from thyroid tissue was separated on 10% SDS–PAGEgel and transferred to PVDF membrane. The membrane was thenused for detection of ER α (MC-20) or ER β (H10) by westernblotting. The band intensity of respective protein was normalizedwith β-actin and the results were expressed as optical density unitsrelative to β-actin.

Statistical analysisAll data were analyzed using SPSS®17.0 students version (SPSSInc., Chicago, USA). Mann-Whitney U test for non-parametricsamples and MedCalc®9.6.0.0 statistical software (MedCalc,Mariakerke, Belgium) were used to compare the means of normaland PTC tissue samples. Pearson’s correlation coefficient analysis

was performed to assess the strength of association between ER LBAand ER subtypes. Results were considered statistically significantat P<0.05.

RESULTS

Patient baseline characteristics, serum and tissue E2Anthropometric measurement details about the patients are given inTable 1. Serum and thyroid tissue E2 levels (bioavailability) remainedwithin the normal level in male and female PTC.

ER ligand binding activity and expression of ERsubtypes in human PTC tissuesThere was a significant increase in the LBA of ER in both female(66.66%) and male (100%) PTC when compared to normal thyroidtissue (P<0.05) (Fig. 1A, Table 2). ER a expression significantlyincreased in a majority of PTC irrespective of the sex (Female-50.98%; Male-58.82%) when compared to normal thyroid tissue(P<0.05) (Fig. 1B, Table 2). Unlike ER α, ER β showed a sex specificvariation in its expression level, it significantly decreased in female(72.54%) but increased in male (88.23%) PTC, when compared tonormal thyroid tissue (Fig.1C,Table 2).

Association of ER subtypes with ER LBA in humanPTC tissuesPearson’s correlation analysis showed a significant positive

Table 1: Patient baseline characteristics, serum and papillary thyroidcarcinoma (PTC) tissue 17β - estradiol (E2) level.

FIG.1: Functional activity of ER, expression of ER subtypes (ER a and ER ß) in human PTC tissues. ER LBA (A); ER a (B); ER ß (C). The box and whiskerplot comprises three components. The horizontal line in the box indicate the central tendency of location (median value), a box to indicate variability(standard error) that represents values from the lower to the upper quartiles (25th to 75th percentile), the line extends from the minimum (5th percentile) to themaximum (95th percentile) values, excluding ‘outside’ values (<) i.e., values smaller than the lower quartile minus 1.5-fold the inter quartile range, or largerthan the upper quartile plus 1.5-fold the inter quartile range, plotted as a square marker. Please refer Table 1 for number of cases and characteristicsof tumorsamples. Correlation between ER a protein expression and ER ligand binding activity in female PTC (D). Correlation between ER ß protein expression andER ligand binding activity in female PTC (E). Correlation between ER a and ER ß subtypes in female PTC (F).


correlation between increased ER LBA and ER a protein expression(r= 0.619; P<0.01), whereas there was a negative correlation betweenincreased ER LBA and ER β protein expression (r= -0.404; P<0.05),indicating that increased LBA may result from ER a subtype in PTCfemales (Fig. 1D, E). We then analyzed the relation between ER αand ER β in individual samples. ER β protein showed a negativecorrelation with ER a in PTC from female patients (r= -0.487; P<0.01)(Fig. 1F). In PTC males, no significant correlation was observedbetween ER LBA and either of ER subtypes (Fig. 2A, B).Interestingly, in most of the PTC samples from male withoverexpression of ER a, there was a positive correlation with ER ß(r= 0.813; P<0.01) (Fig. 2C).

DISCUSSIONOur results indicate a boost in ER LBA with a parallel increase inER a expression in human PTC tissues. We reported a positive and

direct effect of 17β-E2 on N-bis (2-hydroxypropyl) nitrosamine(DHPN)-induced thyroid tumorigenesis in rats, which was associatedwith an increased ER level in thyroid tumor tissue12. Our earlier studiesalso showed a homologous up regulation of ER in rat thyrocytes andthyroid carcinoma cell lines after E2 stimulation to activate itsmitogenic effect supporting the clinical observation6,7 thatoverexpression of ER a may be responsible for E2-induced growthand progression of PTC in females. Subsequently, a consistent higherER α labeling index in PTC tissue of premenopausal women thannormal thyroid was reported by Kawabata13 validating the view thatER α plays a major role in thyroid tumorigenesis and can be used asa differential diagnostic marker to assess the disease prognosis.

Functionally, ER α and ER β exerts opposite effects in many cell types,with ER α showing a pro-mitogenic effect in the breast, uterus and prostatewhile, ER β showing antimitogenic effect in the prostate, mammary gland,colon and lung14. The opposing effect of the two ERs was also reported in

Fig. 2: Correlation between ER a protein expression and ER ligand binding activity in malePTC (A). Correlation between ER ß protein expression and ER ligand binding activity in malePTC (B). Correlation between ER a and ER ß subtypes in male PTC (C).

Table 2: The overall trend and the percentage of difference obtained in various assays.

PTC, Papillary thyroid carcinoma; ER – estrogen receptor↑ - Increased level; ↓ - Decreased level; ~ - Unaltered level.


various thyroid cancer cell lines10. An increase in the ratio of ER α: ER βexpression may therefore, favor thyroid tumor progression in female PTC.Consequently, loss of ER β in female PTC individuals appears to be aprimary factor in facilitating the mitogenic effect of ER a in thyroid tumorprogression. The protective effect of ER β seems to be compromised insubjects expressing a normal ER α where ER β expression is low. Suchupset in the ER α : ER β ratio was more conserved among females thanmales. In our previous study, we observe decreased expression of AR inmost of the PTC females and overexpression of AR in PTC malesemphasizing that AR expression pattern in thyroid cancer tissues of menand women may predispose to the sex specific incidence of thyroidtumors11. Thus, in men who have a relatively low incidence of PTC thanwomen, AR appears to play a major role in promoting the progression ofthe cancer, despite a parallel increase in ER subtypes. However,investigations in more number of samples may throw more light on theissue. In the light of our earlier report on AR protein11, results from thepresent study on ER subtypes suggest that a fine balance between ARand ER subtypes may determine the nature and progression of thyroidcancer in humans. The differential expression pattern of these receptorsbetween male and female PTCs may contribute to the sex specific variationin the incidence of PTC with female predominance. The present studyalso suggests that increased expression of ER a with a general decline inthe expression of ER ß as a possible mechanism underlying the progressionof papillary thyroid tumor in women as in the case of classical estrogendependent tumors like breast cancer. Alterations in the ratio of ER a : ERß might determine the growth and progression of PTC with ER a actingas pro-mitogenic factor. We suggest that ER a represents a novel prognosticmarker for PTC. Taken together, our earlier findings of varied expressionof AR protein in malignant and non-malignant thyroid tissues, dependingupon the expression of micro RNA 124 a11 and the present study, it issuggested that sex steroid receptors status may have good prognosticvalue in the diagnosis of thyroid cancer.

REFERENCES1.) Curado MP, Edwards B, Shin HR, et al. Cancer Incidence in five continents Vol. IX of

IARC scientific publications, 2007, No. 160, Lyon, France.2.) Siegel R, Naishadham D, Jemal A. Cancer statistics, CA Cancer J. Clin. 2012, 62:10-

29.3.) Marino M, Galluzzo P, Ascenzi P. Estrogen signaling multiple pathways to impact

gene transcription, Curr. Genomics 2006, 7:497-508.4.) Annapoorna Kannan. Estradiol induces proliferation of human papillary thyroid can-

cer cells by activating the mitogen activated protein kinase (MAPK) signaling path-way through its specific receptor subtype, PhD thesis, University of Madras, Chennai,India, 2012.

5.) Banu KS, Govindarajulu P, Aruldhas MM. Testosterone and estradiol have specificdifferential modulatory effect on the proliferation of human thyroid papillary and fol-licular carcinoma cell lines independent of TSH action, Endocr. Pathol. 2001, 12:315-327.

6.) Banu SK, Arosh JA, Govindarajulu P, et al. Testosterone and estradiol differentiallyregulate thyroid growth in Wistar rats from immature to adult age, Endocr. Res. 2001,27:447-463.

7.) Banu SK, Govindarajulu P, Aruldhas MM. Developmental profiles of TSH, sex ste-roids, and their receptors in the thyroid and their relevance to thyroid growth in imma-ture rats, Steroids 2002, 67:137-144.

8.) Furlanetto TW, Nguyen LQ, Jameson JL. Estradiol increases proliferation and down-regulates the sodium/iodide symporter gene in FRTL-5 cells, Endocrinology 1999,140:5705-5711.

9.) Sharmila S. Do platelet derived growth factors mediate the mitogenic effect of sexsteroids on thyrocytes? PhD thesis, University of Madras, Chennai, India, 2015.

10.) Zeng Q, Chen GG, Vlantis AC, et al. Oestrogen mediates the growth of human thyroidcarcinoma cells via an oestrogen receptor-ERK pathway, Cell Prolif. 2007, 40:921-935.

11.) Stanley JA, Aruldhas MM, Chandrasekaran M, et al. Androgen receptor expression inhuman thyroid cancer tissues: a potential mechanism underlying the gender bias inthe incidence of thyroid cancers, J. Steroid Biochem. Mol. Biol. 2012, 130:105-124.

12.) Thiruvengadam A, Govindarajulu P, Aruldhas MM. Modulatory effect of estradiol andtestosterone on the development of N-nitrosodiisopropanolamine induced thyroid tu-mors in female rats, Endocr. Res. 2003, 29:43-51.

13.) Kawabata W, Suzuki T, Moriya T, et al. Estrogen receptors (alpha and beta) and17beta-hydroxysteroid dehydrogenase type 1 and 2 in thyroid disorders: possible insitu estrogen synthesis and actions, Mod. Pathol. 2003, 16:437-444.

14.) Warner M, Gustafsson JA. The role of estrogen receptor beta (ER beta) in malignantdiseases-a new potential target for antiproliferative drugs in prevention and treatmentof cancer, Biochem. Biophys. Res. Commun. 2010, 396:63-66.

Fig.3: Immunoblots of ER α (A) and ER β (B) in normal and PTC tissues.


Iodine Excess and Thyroid Dysfunction1K.Ramadevi, 2V.Sucharita1Institute of Biochemistry and 2Department of Endocrine Surgery,Madras Medical College & RGGGH, Chennai, India

Correspondence: Dr. K. Ramadevi, Director & Professor, Instituteof Biochemistry, Madras Medical College & Rajiv Gandhi Govt.General Hospital, Chennai - 600 003, Indiae-mail : [email protected]

Abstract : The Iodine deficiency disorders have been effectively managed by the universal salt iodisation programmes all overthe world. However, continued and unmonitored supplementation of iodine has triggered development of iodine excess disordersin many countries. A study on the thyroid disorders in a tertiary care hospital from an iodinesufficient area was undertaken to assess the iodine status and to correlate with the thyroid status of the individuals. Urinaryfindings reveal excess iodine to be the hall mark of various thyroid disorders among the patients. Hence iodine supplementationprogrammes should be carefully monitored and customized according to the demographic conditions.Key words: Iodine, thyroiditis, thyrotoxicosis, urinaryiodine –excretion, hypothyroidism

INTRODUCTION

Iodine is an essential micronutrient of human nutrition, as it is anintegral part of the thyroid hormones. Only few food groups arefound to contain significant amounts of iodine. The sources may

vary between countries, but the main foods with natural high iodinecontent are fish and seafood1.

The iodine content in soil and drinking water is highly dependent onits geological origin, which is why the iodine content in animal meat,crops and water varies appreciably within different geologicallocalities1.

In Denmark alone, variations of iodine content in drinking waterwas observed from less than 2 µg/L to more than 30 µg/L, with asmall town reaching 100 µg/L2. Furthermore, in some countriesiodine is given to dairy cattle along with mineral supplements, andfor countries consuming high amounts of milk and dairy products,this may be the most important source of iodine. Iodine added infood processing and iodine fortifications, such as iodised salt, arestill the most important sources internationally.

However, even in countries with iodine fortification, intake of otheriodine-rich foods can have a significant impact on the total iodineintake1.

IODINE REQUIREMENTSIodine cannot be stored in the body for long period sand therefore adaily supply is required.

Table-1. Shows the iodine intake recommended by the WHO andthe Institute of Medicine US Food, and Nutrition Board (IOM). Therecommendations by the WHO are based on the intake estimated tocover the needs of “nearly all” healthy individuals in the specifiedlife stage3.

TOLERABLE UPPER LEVEL INTAKES OFIODINEWhile a physiological amount of iodine is required for insuring anormal thyroid function, a large excess of iodine can be harmful aswell.

Although the upper limit of iodine intake among lactating womenhas not yet been defined by the WHO, the WHO has suggested thata daily intake above 500µg should not be exceeded by pregnant andlactating women, as it would not provide any additional benefit forhealth. Levels above may on the contrary be associated with impairedthyroid function4.

IODINE AND THYROID METABOLISMIodine is crucial in the synthesis of thyroid hormones thyroxin (T4)and tri iodothyronine (T3), which are vital regulators of the metabolicrate, physical and mental development in humans5.

Most iodine in gested, is reduced in the gut and absorbed almostcompletely in the proximal small in test in eas iodide. Some iodine-containing compounds, such as thyroid hormones, are absorbed intact.In the circulation, iodide is removed by the thyroid gland and thekidney. With an adequate iodine supply, approximately 10% ofabsorbed iodine is taken up by the thyroid.

However, this fraction can exceed to 80 % in the presence of chroniciodine deficiency6. Other tissues may concentrate iodine, such as thesalivary glands, choroid plexus and the lactating mammary gland.The set issues employ a similar mechanism as the thyroid for theuptake of iodide.

The total iodine content of the human body is about15 20mg of which

Table 1


around 70-80% is found in the thyroid gland. The iodide is selectivelyconcentrated in amount is required for adequate thyroid hormonesynthesis, while the remaining iodine is removed from the blood bythe kidney and excreted in urine.

IODINE DEFICIENCY DISORDERSInsufficient iodine intake results in inadequate production of thyroidhormones. This has multiple adverse health effects grouped underthe heading of “Iodine Deficiency Disorders” (IDD)6.

For assessing the impact of the USI program, and to ensure sustainability, the World Health Organisation has recommended themeasurement of urinary iodine as the standard method to assess thedietary intake of iodine by the community4.

IODINE EXCESSExcess intake has been found to be associated with iodine inducedhyperthyroidism (IIH) and autoimmune thyroid it is, due to thestimulation of proliferation of thyroid follicular cells and therebyincreasing the chance of mutations7. This is all the more so if iodinedeficiency is corrected rapidly and drastically as in endemic areas.IIH has been reported in almost all iodine supplementation programs.The outbreak of endemic goiter in Tasmania in the late 1960, resultedin an increase in the incidence of IIH from 24/100,000 to 125/100,000in a span of 3-4 years due to excess iodine supplementationthrough salt, bread and milk8.

Excess intake of Iodine has also been reported by several other studiesIodine excess can impair thyroid function, causing Iodine inducedhyperthyroidism, Thyroid cancer and Thyroiditis9.

Similar observations have been made by Indian researchers, whohave reported the association of iodine excess with the developmentof goiter, hyperthyroidism and thyroiditis10,11.

Post iodisation studies in the Kangra valley by Kapil Umesh et al.also reported a total goiter rate of 19.8% among 6939 school childrendespite adequate intake12.

Although iodine deficiency disorders have been eliminated bysuccessful salt iodisation programme, the prevalence of goitre hasnot decreased, which on the other hand has only increased13.

In the Rajiv Gandhi Government General Hospital, Chennai, whichis a premier tertiary care hospital in South India, there has been asteady increase in the occurrence of thyroid related disorders overthe past decade. The department of Endocrine Surgery of this hospitalhas registered a steady increase in the number of cases with thyroidrelated disorders (Fig.1). The common thyroiddisorders observed inthis hospital are: Goiter (solitary nodule, multi nodular, diffuse) invarious physiological states of thyroid dysfunction, Thyroid it is andcancer of Thyroid.

The patients attending this hospital are referred from all over thestate of Tamilnadu. As the coastal regions are generally havingadequate iodine content in the soil and water and Tamilnadu whichis a coastal state the increasing occurrence of thyroid related disordersis not normally expected. Hence we have undertaken a study toinvestigate the iodine status among the patients of this hospital (withthyroid dysfunction) and to correlate with the thyroid function.

AIMS AND OBJECTIVES1. To assess the iodine status of the individuals with thyroid disorders

by measuring the urinary iodine excretion .

2. To compare the Iodine nutritional status with the thyroid functionand correlate with the type of thyroid disease.

Type of Study: Case- Control Study.Cases : 300 patients with thyroid disorders following specific

inclusion criteria.Controls : 100 age and sex matched healthy volunteers

Materials and MethodsThree hundred patients who fulfilled the inclusion criteria wererecruited for this study and their thyroid hormone status and urinaryiodine excretion were analysed.

TSH and Urinary Iodine were measured by standard protocols.14.Fine Needle Aspiration Cytology (FNAC) was performed on all thepatients with goitre to diagnose the pathophysiology, the antibodiesAnti Microsomal Antibodies (AMA) and Anti Thyroglobulin (ATG)were measured wherever necessary for further confirmation.

Results and Discussion: Control groupThe individuals in the control group were all in euthyroid state withoutany thyroid glandular enlargement. The mean urinary iodine excretionwas 160.95 ìg/L, suggesting adequate dietary intake of iodine. Thisvalue also falls within the median urinary excretion of 100 -200 ug/L.

Further, based on the thyroid hormone profile, FNAC report and antibodytitres, the 300 patients were divided into four groups (Table 2).

Fig. 1: Cases of Thyroid Disorders from department of Endocrine Surgery ofa tertiary care hospital in South India

Study Group1. Thyroiditis accounts for one-third of all the cases, while benign

goiters account for another one–third of the total cases. The

Table 2


remaining is almost equally distributed between Thyrotoxicosisand cancer Thyroid.

2. Urinary iodine excretion is above the median excretion value(100-200 ìg/L) in all the patient groups, suggesting no dietarydeficiency. When compared with the control roup, there seemsto be an excess of urinary iodine excretion suggesting excessintake causing deranged metabolism of the thyroid gland.

3. The patients with cancer thyroid and thyrotoxicosis has maximalexcretion of Urinary Iodine (UI), followed by patients withthyroiditis.

Increased excretion of iodine in the urine is the common factor amongall the patients with thyroid disorders. In this study, the urinary iodineexcretion of all the patients is above the median excretion value of 100-200 ìg/L. As the urinary excretion reflects the dietary intake, the studypopulation does not have any nutritional deficiency, while on the otherhand there appears to be an excess of iodine intake, as is evident from theincreased excretion.

All the complications known to be associated with excess iodine, vizz,goiter (35%), iodine-induced

hyperthyroidism or thyrotoxicosis (34%), thyroiditis (16%) and cancerof thyroid (15%) have been observed in this study.

High iodine intake may trigger and exacerbate autoimmune thyroiditis,increasing the likelihood of overt hypothyroidism.

Two types of antibodies have been documented in thyroiditis-functionstimulating/blocking and growth stimulating/blocking. Depending on thetype of antibodies produced, the patient may present with eitherhypothyroidism or hyperthyroidism with or without goiter.

Children are more likely to develop thyroiditis leading to hypothyroidism,requiring lifelong thyroxin replacement,while in adults (above 20 yearsof age), thyrotoxic goiter is the common presentation, and they requireexpensive treatment measures involving medical, surgical or radio iodinetreatment for control of toxicity apart from investigative procedures. Thoseundergoing surgery or radio iodine treatment will ultimately develophypothyroidism, and will need lifelong thyroxin replacement.

Our study population comprises of adults (above 20 years of age) andhence the number of patients with benign goiter and thyrotoxicosis aremaximum than Thyroiditis, which is more commonly seen in children.

Papillary carcinoma of thyroid is the predominant form of malignancy inour study which is also reported in studies with excess iodine.

CONCLUSIONThe universal salt iodisation program has been successful in drasticallybringing down the iodine deficiency disorders all over the country.However, iodine supplementation especially in already iodine sufficientareas such the coastal regions has triggered disorders of iodine excess.The scenario in Tamilnadu reflects this shift in the pathophysiology toone of iodine induced thyroid disorders.

All the complications known to be associated with excess iodine, viz.,goiter (35%), iodine-induced hyperthyroidism or thyrotoxicosis (35%),thyroiditis (16%) and cancer of thyroid (15%) have been observed in this

study (Fig.2).

Therefore, continued supplementation of edible salt fortified with iodineshould be monitored carefully, and supplementation programs should betailored to the particular region.

Uniodised salt should also be available in the market so that patients withthyroiditis, thyrotoxicosis and cancer of thyroid can be treated effectively.

REFERENCES1. Rasmussen, Boas, Malene; Main, Katharina M, Ulla. Environmental chemicals and thyroid func-

tion: an update. Current Opinion in Endocrinology, Diabetes & Obesity:October 2009 - Volume 16 -

Issue 5 - p 385–391.

2. L B Rasmussen, E H Larsen and L Ovesen, Iodine content in drinking water and other beverages in

Denmark. January 2000, Volume 54, Number 1, Pages 57-60.

3. Comprehensive Handbook of Iodine: Nutritional, Biochemical, Pathological and therapeutic aspects,

editedby Victor R. Preedy, Gerard N. Burrow, Ronald Ross Watson.

4. M.Andersson , B de Benoist , F Delange and J Zupan Prevention and control of iodine deficiency in

pregnant and lactating women and in children less than 2-years-old:conclusions and recommendations of

the Technical Consultation. WHO Secretariat on behalf of the participants to the Consultation. M Public

Health Nutrition:10 (12A), 1606– 1611. doi: 10. 1017 / S 136898 0007361004. World Health Organiza-

tion 2007.

5. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron,

Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: The National Academ-

ics Press; 2001.

6. Michael B. Zimmermann Iodine Deficiency, Endocrine Reviews, DOI: http://dx.doi.org/10.1210/er. 2009-

0011. edrv.endojournals.org Endocrine Reviews, June 2009, 30 (4):376 – 408.

7. Dunn JT. (2006). Iodine. In M.E. Shils et al. (Eds.), Modern Nutrition in Health and Disease, 10th ed. (pp.

302–311).Philadelphia PA: Lippincott Williams& Wilkins.

8. Stanbury JB, Ermans AE, Bourdoux P, Todd C, Oken E, Tonglet R, et al. Iodine-induced hyperthyroidism:

Occurrence and epidemiology. Thyroid 1998;8:83-100.

9. Jonckheer MH, Velkeniers B,Vanhaelst L, Van Blerk M. Further characterization of iodide-induced hy-

perthyroidism based on the direct measurement of intrathyroidal iodine stores. Nucl Med Commun

1992;13:1148.

10. Chandra AK, Ray I. Dietary supplies of iodine and thiocyanate in the etiology of endemic goiter in

Tripura. Indian J Pediatr 2001;68:399-404.

11. Marwaha RK, Tandon N, Karak AK, Gupta N, Verma K, Kochupillai N. Hashimoto’s thyroiditis: Coun-

trywide screening of goitrous healthy young girls in postiodization phase in India. J ClinEndocrinolMetab

2000;85:3798 802.

12. Kapil U, Sharma TD, Singh P. Iodine status and goiter prevalence after 40 years of salt iodization in the

Kangra District, India. Indian J Pediatr 2007;74:135-7.

13. Marwaha RK, Tandon N, Gupta N, Karak AK, Verma K, Kochupillai N. Residual goiter in the postiodization

phase: Iodine status, thiocyanate exposure and autoimmunity. ClinEndocrinol (Oxf) 2003;59 :672-81.

14. Dunn JT, Crutchfield HE, Gutekunst R, Dunn AD.Two simple methods for measuring iodine in urine.

Thyroid 1993;3:119-23.

Fig. 2: Distribution of Thyroid Disorders

Special Issues� Injury/Trauma: An epidemic of Modern times

Symposia� Dental and Oral Maxillofacial Surgery - A Coming of Age of a Speciality� Influenza: A dangerous pandemic; needs to be defeated� Parkinson’s Disease

Future Special Issuses/ Symposia


Estimation of Viability of Grafts after ParathyroidAutotransplantation in Total ThyroidectomyHimagirish K Rao1, Maharajan Chandrasekaran2, Sucharita Vedachalam3

1Assistant Professor (Endocrine Surgery), Department of Surgery,Pondicherry Institute of Medical Sciences, Pondicherry.2Former Professor and Head, 3Former Associate Professor,Department of Endocrine Surgery, Madras Medical College, Chennai, India

Correspondence: Dr. Himagirish K Rao, Assistant Professor,(Endocrine Surgery), Department of Surgery, Pondicherry Instituteof Medical Sciences, Pondicherry, Indiae-mail: [email protected]

Abstract : Transient hypocalcemia after total thyroidectomy is no longer a complication. With an incidence that approaches50%, it is considered a sequel. Permanent hypoparathyroidism can sometimes complicate thyroidectomy. This can be preventedby performing parathyroid auto-transplantation (PTAT) after thyroidectomy. Eucalcemia after PTAT reflects graft viability andfunction indirectly. Direct evidence of graft function, as evidenced by proof of parathyroid hormone (PTH) secretion, has notbeen widely reported. With this background, a study was conducted to assess the viability and function of the graft after totalthyroidectomy and PTAT. Total thyroidectomy with PTAT was performed in patients for whom total thyroidectomy was indi-cated. One of the parathyroids was harvested, minced and transplanted into one of the brachioradialis muscles. Three monthsafter surgery, serum levels of intact PTH (iPTH) were estimated from venous blood samples which were taken from the cubitalfossa. Samples were taken from the right and left side simultaneously. Grafts were deemed viable if the test:control ratio of iPTHwas 1.5 or more. Values were tabulated an analyzed. A total of 48 patients who underwent total thyroidectomy and PTAT wereincluded in the final analysis. Viable grafts were found three months after surgery in 35 of the 48 patients (72.9%).Conclusion: In the present study, the overall rate of functionality of the parathyroid grafts after total thyroidectomy and PTATwas 72.9%. This was significantly influenced by cold ischemia time of the harvested gland. The overall rate of transient post-operative hypocalcemia was 37.5%. None of the patients included in this study developed permanent post-operative hypopar-athyroidism.Key words : Parathyroid, Grafts, Viability, Autotransplantation, PTAT.

INTRODUCTION

With a reported incidence of 2% - 51%, transienthypocalcemia after total thyroidectomy is so frequent thatit is considered as a mere sequel and not a post-operative

complication1. Incidence of permanent hypoparathyroidism after totalthyroidectomy ranges between 0% and 43%2.

Risk of post-operative hypocalcemia is significantly increased ifinadvertent parathyroidectomy and devascularisation of theparathyroid glands occur at surgery.Thyroid malignancy, necessitatingneck dissections, and recurrent goitre, which necessitates revisionthyroidectomy are other risk factors3-5. Conversely, preservation oftwo or more viable and functional glands has been shown to correlatewith normal levels of intact parathormone (iPTH) levels in the post-operative period. Uncontrolled thyrotoxicosis can result In post-operative hypocalcemia2,5. In addition, macrodilution of theintravascular compartment, general anesthesia, hypomagnesemia,prolonged operating time and hypothermia are some of the otherfactors which may result in post-operative hypocalcemia6.

A procedure which was first reported by Lahey in 1926, parathyroidauto-transplantation (PTAT) offers the possibility of prevention ofpermanent hypoparathyroidism7.

Immediately after PTAT, the auto-transplanted tissue survives bymeans of imbibition. This tissue then induces angiogenesis, by virtueof which it survives, thrives and later functions.It has beenrecommended that the graft be transplanted within 120 minutes ofharvest in order to preserve optimum graft function9.

On this background, a study was conducted in the department ofEndocrine Surgery, Madras Medical College with an objective toestimate the viability and function of parathyroid auto-transplantsafter total thyroidectomy.

MATERIAL AND METHODSPatients who underwent total thyroidectomy and PTAT after informedconsent in the Department of Endocrine Surgery, Madras MedicalCollege, were included in the study.

The thyroid status, parathyroid status and renal function were assessedpre-operatively. Those who had hyperthyroidism or hypothyroidismwere adequately treated with pharmacotherapy (anti-thyroid drugsor replacement with levo-thyroxine) for a period of at least six weeks.The decision to proceed with surgery was taken after confirmationof clinical and biochemical euthyroidism.

Exclusion criteria: Patients with renal insufficiency andhyperparathyroidism were excluded. If the whole of the thyroid glandwas not removed (hemi-thyroidectomy), or if the anatomy wasanomalous (ectopic thyroid, thyroid hemi-agenesis), such patientswere excluded from this study.


Operative procedureThe operative procedure was standardized and was followed by allthe surgeons who operated on the patients.The thyroid wasapproached through a collar crease incision. The number, position,colour, shape and vascularity of parathyroids were recorded. If threeor more parathyroid glands with normal morphology and intact bloodsupply were seen, one of them was harvested and placed in 2 ml ofice-cold saline. The thyroid was removed after identification andpreservation of the recurrent laryngeal nerves and the parathyroids.

The harvested gland was finely minced to particles of size 1mm3 orsmaller. This process produced a suspension of parathyroid in saline.The brachioradialis muscle was exposed through an overlying skinincision, about 10mm long.Bleeding, if any, was controlled by digitalpressure. Diathermy was avoided. The parathyroid-saline suspensionwas then injected into the muscle belly through a wide bore (14-guage) needle. The cubital wound was then closed.

Post-operative monitoringIf and when clinically overt hypocalcemia presented, (muscleweakness, perioral and acral paresthesias, positive Chvostek’s signor positive Trousseau’s sign) the above-said findings were noted andS. Calcium estimated. In asymptomatic patients, the S. Calcium wasestimated on the third post-operative day. Biochemical hypocalcemia(S. Ca < 8.5 mg/dl), if present, was recorded. When diagnosed,hypocalcemia was treated appropriately.

Assessment of graft functionAfter a minimum of 90 days following surgery, the patients werereviewed. Simultaneous bilateral cubital vein sampling was doneand S. PTH was estimated in the samples. The graft was deemedviable if the test-to-control S. PTH ratio was at least 1.5. All thosepatients inwhom the ratio was less than 1.5 were reviewed 6 monthsafter the procedure. Bilateral cubital vein sampling andiPTHestimation was repeated. If the test-to-control ratio was lessthan 1.5 after 6 months, the graft was deemed nonfunctional. Findingswere noted, tabulated and analyzed.Graft function was correlatedwith thyroid pathology, presence of thyroiditis, type of procedureperformed and the cold-ischemia time of the graft.

Analysis was performed using the Chi-squared test with Pearson’scorrelation. Multivariate analysis was performed with the help ofthe one-way ANOVA test. Statistical analysis was conducted withthe help of the SPSS software (version 17.0).

RESULTSThis study was conducted over a period of 18 months from March2011 to September 2012. Out of the 57 patients who were initiallyincluded in the study, 3 or more parathyroids were identified in 51patients. In the remaining 6 patients, only two glands were identifiedand so, PTAT was abandoned. Among those who underwent PTAT,3 were lost to follow-up. A total of 48 patients who were followed-up with post-operative iPTH estimation were included in the finalanalysis.

The mean age in years of the patients included in this study was 41.1± 13.7 (17-75). 42 patients (87.5%) were women and 6 (12.5%) weremen. As regards to thyroid status, the majority of patients (26 of 48,54.2%) were euthyroid at diagnosis, while 9 of them (18.7%) werehyperthyroid at diagnosis and the remaining 13 (27.1%) werehypothyroid at diagnosis.

With respect to thyroid pathology, 28 patients (58.3 %) had non-toxic nodular colloid goitre. A further 7 of them (14.6%) had diffusegoitre. 6 patients (12.5%) had toxic multinodular goitre and the other7 patients (14.6%) had thyroid malignancy.Two of the patients withthyroid malignancy were hyperthyroid at the time of diagnosis. In17 out of 48 patients (35.4%), chronic thyroiditis was evident in thefinal histology, either as the predominant feature or as a co-existingfeature with the dominant histology.

Total thyroidectomy (TT) was performed in 41 patients (85.4%).Five patients (10.4%) underwent total thyroidectomy with centrallymph node dissection (CLND). MRND was performed in additionto TT and CCLND in two patients (4.2%).

Out of the 48 patients included, the auto-transplanted parathyroidwas functioning in 35 patients (72.9%) at the end of six months aftersurgery, as evidenced by a test-to-control iPTH ratio of 1.5 or more.

The correlation of graft viability with pathological diagnosis is asshown in Table 1. The difference in rates of viability was found to bestatistically significant (p = 0.04)on univariate analysis. However,on multivariate analysis, this difference was not found to besignificant.Table 1: Correlation of graft viability and function with histopathological

diagnosis including thyroiditis

When correlated with thyroiditis (Table 2), the graft was functioningin 70.6% of patients with thyroiditis, as opposed to 74.2% of thosewith no thyroiditis.

Table 2: Correlation of graft viability and function with thyroiditis

The rate of graft viability was 69% after total thyroidectomy. Inpatients who underwent total thyroidectomy with lymph nodedissection (CLND, MRND or both), the rate of viability was 100%.The apparent difference was not statistically significant (p = 0.62)

The mean time between harvesting and transplantation of the glandwas 45±6.5 minutes in those who had functioning grafts. That in thesubset of patients with nonviable grafts was 58.5±13.2 minutes. Thisdifference was statistically significant (p < 0.001).

On multivariate analysis, graft survival correlated with cold ischemiatime of the harvested gland. None of the other factors consideredhad any significant association with graft survival rate.

Post-operative sequelae and complicationsHypocalcemia was seen as a sequel of the procedure in 18 out of thetotal number of 48 patients (37.5%). Among them, 8 patients (45.4%)had overt hypocalcemia as evidenced by positive symptoms and signs,while the other 10 patients (45.4%) had clinically occulthypocalcemia.

DISCUSSIONThere are various studies in literature that recommend prophylactic


PTAT during parathyroidectomy as well as total thyroidectomy10,11.Various studies have been conducted to estimate the parathyroidfunction after PTAT in thyroid surgery.However, most authors havereported indirect evidence of graft function in the form of post-opeucalcemia10,12. Direct assessment of the graft function has not beenreported much. This is the first study reported from this part of theworld.

In their study, Wells SA Jr., et al.reported that 99% of the grafts wereviable after thyroidectomy and PTAT9.

In the present study, the overall rate of graft function, as evidencedby a test-to-control ratio of 1.5 or more, was 72.9% (35 out of the 48patients who were included in the study).

While the rate of functionality is consistent with that seen in otherstudies, as mentioned above, the goal of the procedure should be toachieve a 100% functionality rate.

Wells SA Jr, et al. have recommended transplantation within 120minutes of harvesting the glands9.

In this study, all the grafts were transplanted within 120 minutes ofharvest. However, when this was correlated with functionality, asignificant difference was observed in the mean cold ischemia timebetween the viable and the non-viable subsets of patients. So, itfollows that sooner the transplant after harvesting, better the chancesof viability.

However, it was also discovered that by placing the harvested glandsin iced saline, the grafts were rendered firmer in consistency and so,mincing was easier.

It is evident that bleeding in the graft bed, resulting in a hematoma ora seroma, is one of the factors which influence graft survival11.

In the present study, diffuse ooze was sometimes noted from thegraft bed. Diathermy was avoided in order to preserve the perfusionof the graft bed. This may have led to a delayed hematoma or seromapost-operatively.

Extrusion of the harvested tissue may be another factor which willimpact the overall functionality rate. In the present study, thelikelihood of graft extrusion is very minimal as the graft was mincedin saline and the resultant suspension was injected into the musclebelly.

Assessment of graft function is influenced by the pattern of venousdrainage of the forearm. Anatomical variations are extremely commonin the cubital fossa. While the graft may be viable and functional inreality, it may be interpreted as nonviable due to a misrepresentativesample.

Various other factors may influence PTH gradients, leading toconfounding results, although the patients have viable grafts. PTHsecretion itself may be intermittent. The iPTH gradient may beinfluenced by the regional specificity of the iPTH assay employed.

While the protective role of PTAT in definitive hypoparathyroidismhas been generally accepted, the effect on transienthypoparathyroidism is still debated. While some authors havereported transient hypocalcemia after thyroidectomy and PTAT, 93others have reported that PTAT is protective against transient post-operative hypocalcemia11.

There may be a transient release of PTH immediately following PTAT.Although the transplanted glands seem to start functioning after aminimum of 2 weeks, high levels of PTH in the minced tissue havebeen shown13.

Nevertheless, it is believed that auto-transplants are unlikely to restorePTH secretion in the immediate postoperative period.

The authors found that it was preferable to harvest the superiorparathyroid glands in view of the relatively constant anatomy.Asregards the graft bed, transplantation can also be done into thesternomastoid muscle. This is advantageous in that the muscle isalready exposed and a separate incision is not required. However,assessment of graft function is possible in case of grafts into thebrachioradialis, especially in the setting of euparathyroidism wherethe other glands are preserved in their normal position. By graftinginto the brachioradialis,

through a skin incision, the authors found that identification of thetest arm and control arm was easier.

In the present study, among the patients who were analyzed, post-operative hypocalcemia was seen in 18 patients (37.5%). This wasnot significantly different from that seen after thyroidectomy alone.In addition, none of the patients who were operated had hypocalcemiaor hypoparathyroidism 6 months after the procedure.

CONCLUSIONIn the present study, the overall rate of functionality of the parathyroidgrafts after total thyroidectomy and PTAT was 72.9%. This wassignificantly influenced by cold ischemia time of the harvested gland.The authors recommend immediate auto-transplantation of theharvested parathyroid. There was no correlation between graftviability and pathology. So, that factor need not be a deterrent toPTAT.

The overall rate of transient post-operative hypocalcemia was 37.5%.None of the patients included in this study developed permanentpost operative hypoparathyroidism.

REFERENCES1. Friguglietti CUM, Lin CS, Kulcsar MA. Total thyroidectomy for benign thyroid

disease. Laryngoscope 2003; 113: 1820 -1826.2. Demeester-Mirkine N, Hooghe L, Van Geertruyden J, et al. Hypocalcemia after

thyroidectomy. Arch Surg 1992; 127: 854 -858.3. Pattou F, Combemale F, Fabre S, et al. Hypocalcemia following thyroid surgery:

Incidence and prediction of outcome. World J Surg 1998; 22: 718-244. Friedman M,Vidyasagar R, Bliznikas D, et al. Intraoperative Intact Parathyroid

Hormone Level Monitoring as a Guide to Parathyroid Reimplantation after Thy-roidectomy. Laryngoscope 2005; 115: 34-8

5. Wingert DJ, Frisen SR, Iliopoulos JI, et al: Post-thyroidectomy hypocalcaemia.Am J Surg 1986; 152: 606

6. Wilson RB, Erskine C, Crowe PJ. Hypomagnesemia and hypocalcemia after thy-roidectomy: prospective study. WorldJ Surg 2000; 24: 722-6.

7. Lahey FH. The transplantation of parathyroids in partial thyroidectomy. SurgGynaecol Obstet 1926; 42: 508-9.

8. Wells SAJ, Gunnells JC, Shelburne JD, et al. Transplantation of the parathyroidglands in man: clinical indications and results. Surgery 1975; 78: 34-44

9. Olson JA, DeBenedetti MK, Baumann D, et al. Parathyroid autotransplantationduring thyroidectomy: Results of long-term follow-up. Ann Surg 1996; 223: 472-80

10. Zedenius J, Wadstrom C, Delbridge L: Routine autotransplantation of at leastone parathyroid gland during total thyroidectomy may reduce permanent hypo-parathyroidism to zero. Aust NZ J Surg 1999; 69: 794

11. Testini M, Nacchiero M, Miniello S, et al: Risk factors of morbidity in thyroidsurgery: analysis of the last 5-years experience in a general surgery unit. Int Surg2004; 89: 125

12. El-Sharaky MI, Kahalil MR, Sharaky O, et al: Assessment of parathyroid au-totransplantation preservation of parathyroid function after total thyroidectomy.Head Neck 2003; 25: 799-807.

13. Lo CY, Chan WF, Leung P, et al: Applicability of tissue for quick parathyroidhormone assay to confirm parathyroid tissue identify during parathyroidectomyfor primary hyperparathyroidism. Arch Surg 2005; 140: 146.


Papillary Micro Carcinoma of thyroid: Institutional Experience.PV PradeepAssociate Professor, Dept of General Surgery,KMCT Medical College, Mukkam, Kozhikode, Kerala, India.

Correspondence: Dr. PV Pradeep, Associate Prof, Dept of GeneralSurgery KMCT Medical College, Manasseri, Mukkum, Kozhikodee-mail : [email protected]

Abstract: Diagnosis of papillary microcarcinoma (PMTC) of the thyroid is increasing. The aim of the study was to look atthe incidence of PMTC in our institute and compare with the macro carcinoma (PTC) and also discuss the managementand prognostic factors.Key words: Papillary Carcinoma, Papillary Micro Carcinoma

INTRODUCTION

Malignancy has been reported in 5-15% of the thyroidnodules1. Vast majority of these cancers are differentiatedthyroid cancers (DTC). This includes the papillary (PTC)

and follicular thyroid cancers (FTC)2. Davies et al observed that theyearly incidence of DTC has increased from 3.6 per 1,00,000 in 1973to 8.7 per 1,00,000 in 2002 in the US3. Papillary micro carcinoma(PMTC) is a subgroup of PTC and includes tumors less than 1cm insize. With the advent of ultrasound and the ultrasound guided FNACthe incidence of PMTC is on the rise. The aim of the current studywas to look at the incidence of PMTC in a two endocrine surgeryunits from South India over the last five years, compare with papillarymacro carcinoma, look at the prognostic factors and discuss themanagement.

MATERIAL AND METHODSRetrospective study at two tertiary care hospitals in South India.Period of study is from Feb 2008- Dec 2014. All patients who wereoperated upon for multi nodular goitre and in which thehistopathology revealed PMTC were included. Patients whounderwent surgery for a pre operatively diagnosed PMTC were alsoincluded in this study. Patients whose tumour was more than onecentimetre were excluded. A comparison of the patients with PMTCand PTC was performed. The demographics, intra operative factorsand pathology was compared. Statistical analysis was done with SPSS15 software.

Continuous variables were described as mean/ standard deviation,categorical variables as actual numbers/ percentages. Comparisonof means between groups was performed with independent sampleT Test. Proportions were compared by Chi square test and Fischerexact test. Statistical significance was set at P<0.005.

RESULTSA total of 1616 patients underwent surgery for multi nodular goitreand 249 patients were operated for DTC during this period. Amongthe patients with MNG (n=1616) 18% (n=290) had incidentallydetected DTC, 22.76% (n=66) of which was PMTC. Among thepatients operated for DTC; 10% (n=25) had PMTC. Hence a total of91 patients of PMTC were operated during this period. The overallincidence of PMTC was 16.88%, (n=91) of which 12.29% (n=66)was incidental detection.

Comparison of the patients with PMTC and PTC are shown in Table1. Operative findings and post operative complications are comparedin Table 2. Among the PMTC group 78% (n=71) had single tumourfoci, however multifocality (12.1%) and multi centricity (9.89%)was also noticed. Lymph node involvement (In central compartmentalone or combination of central and lateral compartment) was noticedin 26.37% (n=24). Histopathology in the PMTC revealed classicaltype in 90.1% (n=82), tall cell variant 5.49% (n=5) and columnarcell variant 4.39% (n=4). In patients with non classical variant ofPMTC all had either central or jugular chain nodes involved.Comparison of the pathology is given in Table 3. In our centre allpatients who undergo hemithyroidectomy for benign thyroid lesionsand in whom a post operative diagnosis of PMTC is made undergocompletion total thyroidectomy. All patients undergo diagnostic wholebody radio iodine scan (DxWBS) after 4 weeks of the surgery withat least TSH >30mIU/L. Based on the uptake the radio iodine ablationtherapy is given. Dose in our centre depends on whether the uptakeis limited to thyroid bed alone or to the lateral/distant areas. In noneof our patients with PMTC distant metastasis was seen. Further followup is similar for both PMTC and PTC with six monthly TSH andserum thyroglobulin (Tg).

DISCUSSIONPapillary micro carcinoma is defined as tumour less than 1cm insize. The incidence of which has been reported up to 30%4. As moreand more imaging studies are being performed in the neck smallincidental thyroid nodules are being detected. Ultrasound guidedFNAC has increased the diagnosis of PMTC. In our series theincidence of PMTC was 16.68% however the incidental detectionduring surgery for MNG was 12.29%. Only 27.47% of the cases ofPMTC was picked up pre operatively at our centre, the rest werediagnosed after the histopathology was available. Even though allour patients with thyroid nodule undergo a pre operative ultrasoundand FNAC nearly 73% of the PMTC were missed before surgery.For lesions which are less than 1.5cm we perform USG guided FNAChowever the diagnostic yield to satisfactorily diagnose PMTC waspoor. Yang GC et al5 has shown a very high yield of positive resultswith USG guided FNAC for micro carcinomas of the thyroid.

We observed that the patients with PTC had shorter duration ofappearance of goitre and presentation where as the patients withPMTC had longer history of having thyroid nodules. Even thoughboth PMTC and PTC were commoner in women it was seen that themales were more likely to harbour PMTC.

(Table 1).This suggests that male patient with goitres should be takenup for thyroidectomy since PMTC is more common. In our study it


was observed that both PTC and PMTC occurred equally in the agegroups less than as well as more than 45 years. Another interestingobservation was that the symptoms of hypothyroidism was morecommon in patients with PMTC (Table 1).

In our study it was observed that the patients with PMTC had lesserincidence of multifocality and multi centricity. The involvement ofcentral and lateral compartment nodes were less likely in PMTC(Table 2).

The pathological tumour type was not different between the patientswith PMTC and PTC. In both the groups classical PTC was common(Table 3).

The management of PMTC has been controversial. In patients withno lymph node involvement and those where incidentally PMTC isdetected in pathological specimens aggressive treatment may not beneeded. Ito et al4 observed that in 70% of their 163 patients withPMTC the disease did not progress on follow up. Another study hasrevealed that 6.7% of these low risk PMTC progressed on followup6. In Indian patients the follow up is difficult and hence we opt for

Total Thyroidectomy in pre operatively diagnosed PMTC andcompletion thyroidectomy if PMTC is detected in the pathologyspecimen later. In our study the patients who had non classical variant,multi centric, multifocal PMTC had central and lateral compartmentnodes. Similar observation where made by other authors7,8. Hencesuch patients are categorised as high risk PMTC and in them Totalthyroidectomy, therapeutic central and lateral compartment neckdissections as appropriate is done. This is followed by radio activeiodine therapy. Prophylactic lymph node dissection in high risk PMTCis disputed9. Routine prophylactic central compartment dissectionhas been recommended by So YK et al10. Our practice is to performcentral compartment dissection only if the frozen section of the nodeis positive for metastasis since the central compartment involvementin our patients with PMTC is much lower than the macro carcinoma(Table 2).

We did not observe any cases of skip metastasis in lymph nodes(Involvement of lateral compartment without central compartmentinvolvement). Skip metastasis has been reported in up to 7.7% byChung et al11.

Table 1: Demographic profile

Table 2: Operative Findings

Table 3: Comparision of the pathological variants

NS: Non significant


In conclusion our study demonstrates that incidence of PMTC isincreasing. The ultrasound and FNAC fails to pick up a significantnumber of these cases. Males with goitres are more likely to harbourPMTC. Multi focal, multi centric, non classical variants are havingaggressive disease since the lymph node positivity is higher in thesepatients. Evidence for prophylactic neck dissections in both centraland lateral compartment is lacking. Therapeutic lymph nodedissection is recommended. Radio active iodine therapy is betterreserved for high risk PMTC.

REFERENCES1) Hegedus L 2004 Clinical practice. The thyroid nodule. N Engl J Med 351:1764–17712) Sherman SI 2003 Thyroid carcinoma. Lancet 361:501–5113) Davies L, Welch HG 2006 Increasing incidence of thyroid cancer in the United States, 1973

– 2002. JAMA 295:2164–21674) Ito Y, Tomoda C, Uruno T et al. Papillary microcarcinoma of the thyroid: how should it be

treated? World J Surg 2004;28:1115-215) Yang GC, LiVolsi VA, Baloach ZW. Thyroid microcarcinoma: fine needle aspiration diag-

nosis and histologic follow up. Int J Surg Pathol 2002;10:133-96) Ito Y, Miyauchi A. A therapeutic strategy for incidentally detected papillary micro carci-

noma of the thyroid. Nat Clin Pract Endocrinol Metal 2007;3:240-8.7) Giordano D, Gradoni P, Oretti G, Molina E, Ferri T. Treatment and prognostic factors of

papillary thyroid carcinoma. Clin Otolaryngol 2010;35:118-248) Pelizzo MR, Boschin IM< Toniato A, Piotto A, Bernate P. Papillary thyroid microcarcinoma

(PTMC): prognostic factors, management and outcome in 403 patients. Eur J Surg Oncol2006;32:1144-8

9) Ito Y, Higashiyama T, Takamura Y, Miya A, Kobayashi K. Prognosis of patients with benignthyroid disease accompanied by incidental papillary carcinoma undetectable on pre opera-tive imaging tests. World J Surg 2007;31:1672-6

10) So YK, Seo MY, Son YL. Prophylactic central lymph node dissection for clinically nodenegative papillary thyroid micro carcinoma.: influence on serum thyroglobulin level, recur-rence rate, and post operative complications. Surgery 2012;151:192-8

11) Chung YS, Kim JY, Bae JS. Lateral lymph node metastasis in papillary thyroid carcinoma:results of therapeutic lymph node dissection. Thyroid 2009;19:241-6.

LITERATURE REVIEW

DRUG-INDUCED ANAPHYLACTIC REACTIONS IN INDIAN POPULATION: A SYSTEMATIC REVIEW

Tejas K Patel, Parvati B Patel, Manish J Barvaliya, CB Tripathi; Ind. J. Criti. Care Medicine 2014, 18,796-806

Epidemiological data on drug-induced anaphylactic reactions are limited in India and are largely depending on studies from developed countries. The aim was to analyze the published studies of drug-induced anaphylaxis reported from India in relation with causative drugs and other clinical characteristics. The electronic databases were searched for Indian publications from 1998 to 2013 describinganaphylactic reactions. The information was collected for demographics, set up in which anaphylaxis occurred, causative drugs, incubation period, clinical features, associated allergic conditions, pastreactions, co-morbid conditions, skin testing, IgE assays, therapeutic intervention and mortality. Reactions were analyzed for severity, causality, and preventability. Data were extracted and summarizedby absolute numbers, mean (95% confidence interval [CI]), percentages and odds ratio (OR) (95% CI). From 3839 retrieved references, 52 references describing 54 reactions were included. The meanage was 35.31 (95% CI: 30.52-40.10) years. Total female patients were 61.11%. Majority reactions were developed in perioperative conditions (53.70%), ward (20.37%) and home (11.11%). Themajor incriminated groups were antimicrobials (18.52%), nonsteroidal antiinflammatory drugs-(NSAIDs) (12.96%) and neuromuscular blockers (12.96%). Common causative drugs were diclofenac(11.11%), atracurium (7.41%) and â-lactams (5.96%). Cardiovascular (98.15%) and respiratory (81.48%) symptoms dominated the presentation. Skin tests and IgE assays were performed in 37.03%and 18.52% cases, respectively. The fatal cases were associated with complications (OR =5.04; 95% CI: 1.41-17.92), cerebral hypoxic damage (OR =6.80; 95% CI: 2.14-21.58) and preventablereactions (OR =14.33; 95% CI: 2.33-87.97). Antimicrobials, NSAIDs, and neuromuscular blockers are common causative groups. The most fatal cases can be prevented by avoiding allergen drugs.


Single Centre Experience of Radioiodine Therapy in the Management ofThyrotoxicosis: Retrospective Analysis of 14 years.Sureshkumar Chandran, Shelley Simon, Indirani ElangovanDepartment of Nuclear medicine, Apollo main Hospitals, Chennai, Tamilnadu, India.

Correspondence: Dr. Shelley Simon, Department of Nuclearmedicine, Apollo hospitals, 21, Greams Lane, off Greams Road,Chennai - 600 006, India e-mail: [email protected]

Abstract : The study is a retrospective analysis and relates to our experience in the efficacy of fixed dose RAI therapy in the treatmentof thyrotoxicosis and to assess the outcome of radioactive iodine [RAI] therapy. Nuclear medicine department of Apollo hospitals gotreferral for RAI treatment for 872 patients.The diagnosis of hyperthyroidism was based on clinical examinations, biochemical, thyroidantibody assay and increased uptake on thyroid scintigraphy.A fixed dose between 296 to 555 MBq was administered to all patients afteradequate beta blockade.Thyroid function was measured at 6 weeks and at 3, 6 and 12 months following RAI therapy. Development ofeuthyroidism orhypothyroidism was considered as response. Appropriate statistical analysis was done. Between January 2000 andDecember 2014, 840 patients were treated for hyperthyroidism with radioiodine with a mean age of 45.8 ± 12.5 years.Out of 840 cases,456 cases of Grave’s disease (GD), 297 cases of toxic multi-nodular goitre (TMNG) and 87 cases of toxic adenoma. Among 840 patients,611 patients with group A (8.0-12.0 mCi) and 229 patients with group B (greater than 12.0 mCi).Among 611 of group A, 243 patientswere euthyroid [39.7%], 180 were hypothyroid [29.5%] and 188 remained hyperthyroid [30.8%]. In 229 group B patients, 69 wereeuthyroid [30.1 %], 99 were hypothyroid [43.2 %] and 61 remained hyperthyroid [26.7 %]. Graves’ ophthalmopathy remained stablein 20 cases (45.5 %), improved in 19 patients (43.1%) and worsened in 5 cases (11.4 %).The second dose of RAI was administered to 95patients (15.5%) of group A and 24 patients (10.5 %) of group B patients. In addition, 9 patients (1.8 %) of group A and 4 patients (1.6%)of group were treated with third dose of RAI.Conclusion: RAI treatment is safe, non-invasive and effective in treating hyperthyroid patients with better success in short duration.Fixed dose method is convenient and cost effective and it does not require any expertise calculations. High fixed dose regimen overcomesthe refractoriness of the long standing use of antithyroid drugs and chronic thyroid illness.Keywords: Radioiodine therapy, fixed dose, Graves’ disease,Graves’ ophthalmopathy

INTRODUCTION

Hyperthyroidism is a pathological syndrome in which the body ofthe affected individual is exposed to an excessive amount ofcirculating thyroid hormones. The most common cause of

hyperthyroidism is Graves’ disease, followed by toxic multi nodular goitre,and solitary hyper functioning nodules1. The modes of treatment availableare antithyroid drugs, surgery and radioiodine (RAI) and although eachof these is highly successful in controlling or curing hyperthyroidism.None of these represents an optimal treatment for the hyperthyroidism,and complications are associated with each one of the therapeutic option.Antithyroid drug therapy with thionamides is associated with side-effectsand a high relapse rate even after prolonged therapy2. High remissionrates were achieved by thyroidectomy, but for invasiveness and it canresult in hypoparathyroidism or dysphonia in 1-2% of patients. RAI hasbeen commonly used as a therapy for hyperthyroidism since the 1940’s,and it was proved clinically efficient, simple, and cost-effective incomparison with the other therapeutic alternatives. Originally, the aim ofthe RAI treatment was to destroy thyroid tissue sufficiently to curehyperthyroidism and to render the patient euthyroid. However, it wassoon realized that while RAI treatment was highly effective, it led to thedevelopment of hypothyroidism in up to 70-80 % of the patients3. Foryears, clinicians tried to titrate the dose of RAI individually on the basisof the size and RAI uptake of the thyroid gland to ensure a euthyroidoutcome. In spite of potential benefits of the calculated doses, severalstudies failed to demonstrate improvements in the cure rate or developmentof hypothyroidism over fixed doses of RAI4. Presently, most clinics use afixed dose of RAI in the treatment of hyperthyroidism. However, no

consensus exists about the optimum dose of RAI to be used in the fixeddose scheme.

Since 1985, a fixed-dose method had been used at Apollo hospitals,Chennai. In which a fixed radioactivity of between 148 MBq and 222MBq of RAI was given to all patients irrespective of the variables till1995. On the basis of the clinical assessment of the patient and globaltrend of using RAI in the thyrotoxicosis treatment, a fixed radioactivityof RAI is prescribed to the patient, which usually ranges from 296 to 555MBq, depending on the gland size, disease status, and associated medicalconditions. Pertechnetate (99mTco4-) thyroid scanning was performedfor confirmation and to exclude thyroiditis.

The purpose of this analysis was to share our experience in the efficacy offixed dose RAI therapy in the treatment of thyrotoxicosis and to assessthe outcome of radioactive iodine [RAI] therapy.

MATERIALS AND METHODSWe had analysed data of 872 patients referred to the Nuclear medicinedepartment, Apollo hospitals over a period of 14 years for the treatmentof hyperthyroidism retrospectively. Out of these, 32 patients did notcomplete follow-up, hence they were not included in final outcome. Thediagnosis of hyperthyroidism was based on clinical examinations,biochemically on raised levels of total/free Triiodothyronine T3, total/free Thyroxine T4 and suppressed serum Thyroid Stimulating Hormone(TSH) using immune assay, thyroid antibody assay and in most of thecases increased uptake of pertechnetate (99mTc04-) on Thyroidscintigraphy (uptake more than 3 %) as in fig. 1.

Most of patients (798/840) with moderate to severe hyperthyroidism wasrendered euthyroid by antithyroid drugs (ATD). Goitre classified accordingto WHO goitre grading system. Graves’ ophthalmopathy was assessedas per NO-SPECS classification. Anti-thyroid drugs were withdrawn 4


The second dose of RAI was administered to 95 patients (15.5%) ofgroup A and 24 patients (10.5 %) of group B patients. In addition, 9patients(1.8 %) of group A and 4 patients (1.6%) of group were treated with thirddose of RAI.

Out of 840 patients, 42 patients were not administered premedicationantithyroid drugs. After 12 months cumulative response percentage was86 % (36 patients) for patients without premedication history comparedto 74 % (591 patients) for patients with premedication history. Graves’ophthalmopathy remained stable in 20 cases (45.5 %), improved in 19patients (43.1%) and worsened in 5 cases (11.4 %). Patients with thyrotoxicatrial fibrillation (4 patients) showed symptomatic improvement within

Figure 1: Thyroid scintigraphy with pertechnetate (99mTCo4).A. Normal Thyroid, B. HyperthyroidC. Thyroiditis, D. Toxic adenoma

to 7 days prior to RAI therapy. Pregnancy was excluded in females ofchild-bearing potential. A fixed dose between 296 to 555 MBq wasadministered to all patients after adequate beta blockade. Propranololwas the most commonly used beta-blocker. Selective beta-blockers likenadolol and atenolol were used in COPD patients. Thyroid function wasmeasured at 6 weeks and at 3, 6 and 12 months following RAI therapy.Development of euthyroidism or hypothyroidism was considered asresponse. At the end of six months if a patient remained hyperthyroid,another dose of RAI was administered. The follow-up period would beanalysed from data of first RAI therapy and continued until the patientbecame euthyroid/hypothyroid or until December 2014.Statistical analysiswas done using SPSS software version 17 (SPSS Inc., Chicago). Allcontinuous data were summarized as mean and standard deviation (SD).Chi-square test was used to compare categorical variables. A ‘p’ value ofless than 0.05 was considered statistically significant.

RESULTSBetween January 2000 and December 2014, 840 patients were treatedfor hyperthyroidism with radioiodine and these patients consisted of 651(77.5%) women and 189 men (22.5 %) with a mean age of 45.8 ± 12.5years.(Table 1). Hyperthyroidism was more common in women than inmen (3.1:1 ratio).

Out of 840 cases of thyrotoxicosis, 456 cases were diagnosed to haveGrave’s disease, 297 cases diagnosed as toxic multi-nodular goitre(TMNG) and 87 cases diagnosed as toxic adenoma.

Goitre was present in 90% of cases with Grave’s disease and all the casesof TMNG. Additional findings included Graves’s ophthalmopathy (44patients), thyroid dermopathy (3 patients), atrial fibrillation (4 patients),hepatic dysfunction (3 patients) and heart failure (2 patients).

Among 840 patients, 611 patients were treated with 296-444 MBq (8.0-12.0 mCi) considered as group A and 229 patients were treated withgreater than 444 MBq (> 12.0 mCi,) considered as group B. No significantdifferences between the two groups were observed with respect to any ofthe baseline patient demography. At theend of 12 months, the outcome ofpatients was confirmed by clinical examination and thyroid functiontests. After 1 year, among 611 patients of group A, 243 were euthyroid[39.7%], 180 were hypothyroid [29.5%] and 188 remainedhyperthyroid[30.8%]. In 229 patients of group B 69 were euthyroid [30.1%], 99 were hypothyroid [43.2 %] and 61 remained hyperthyroid [26.7%] (Table.2 and figure.2).

Table 1: Baseline patient demography with hyperthyroidism

RAI OUT COME AFTER 1 YEAR

43.20%

Group A (8-12mCi) Group B (>12mCi)

29.50%

39.70%

30.10% 30.80%26.70%

HYPOTHYROID EUTHYROID HYPERTHYROID

Figure 2: Outcome of RAI therapy after 12 months

Figure 3: Outcome comparison between two groups irrespective of numberof therapies.

Group B (>12mCi)

Outcome Comparision

120.00%

100.00%

80.00%

60.00%

40.00%

20.00%

0.00%

Group A (8-12mCi)

Months

3 6 9 12 24 36 48 60

Cu

mu

lati

ve P

erc

en

tag

e


10 days and became biochemically euthyroid during their first follow up.

DISCUSSIONThe most obvious objective in the treatment of hyperthyroidism is torender the patient hypothyroid or euthyroid and off drug therapy.Radioiodine is increasingly considered the treatment of choice becauseof its safety and ease of administration. Over the last 30 years, muchattention has focused on achieving euthyroidism by optimizing the doseof radioiodine. Despite this, the evidence from several studies is thatcalculated doses of radioiodine do not have any benefit over fixed doses,in terms of improving cure rates4,5 or in preventing the development ofhypothyroidism6. Therefore many clinicians prefer the use of a fixed-dose regimen.

Although low fixed doses [185 MBq] are associated with a reduced earlyincidence of hypothyroidism, they often result in unacceptably low curerates. Some clinicians now prefer to give a large ablative dose [555MBqand upwards], which results in early hypothyroidism, so that the need forlong-term follow-up of thyroid function in euthyroid patients is obviated.Several factors have been considered to influence the outcome ofradioiodine treatment. Many studies have demonstrated that patients withlarger-volume thyroid glands7 and severe hyperthyroidism6,8 are morelikely to fail to respond to a single dose of radioiodine.

American thyroid association (ATA) and American Association of ClinicalEndocrinologists (AACE) guidelines recommend a single dose of 10-15mCi for optimal treatment of Graves’ disease9. Some of the older studiesshowed that 10 mCi results in hypothyroidism in 69% at 1 year and 15mCi results in hypothyroidism in 75% at 6 months4. In our study, wehave compared outcome of treatment with two single fixed-dose regimensof radioiodine (8-12mCi and > 12 mCi). At the end of 12 months, 423patients (69.2 %) of group A and 155 patients (73.2 %) of group Bresponded to the treatment. Overall, 95 % of the patients had a successfuloutcome from treatment with no significant difference between the twodifferent fixed dose regimens. Santos RB et al10 concluded that that largerdoses of radioiodine (>600 MBq) will lead to a larger percentage of patientsbecoming euthyroid or hypothyroid more quickly than smaller doses(<400 MBq). Our study was also demonstrates the same, after 1 year43.2 % patients became hypothyroid in group B and only 29.5 % patientsin group A.

Our study also demonstrated that 10-15 mCi (370- 555 MBq) of RAI canbe given to patients with hyperthyroidism as an optimal dose.

About 35 yr ago, Einhorn and Sa¨terborg11 proposed that thioureasconferred radio resistance due to their sulfhydryl groups. Goolden et al.12

found equal cure rates from 131I with and without carbimazole pre-treatment, but carbimazole was discontinued 3–5 days before 131I therapy.But in our study we observed that 86 % of patients without the premedication history responded to the treatment in 12 months compared to74% of patients with premedication history. This observation at presentdoes not have a valid explanation. It is also not very clear that howantithyroid drugs exerts its radio protective effect. However studiesconcluded that a higher dose of radioiodine may partly ameliorate the

radio protective effects of antithyroid drugs. The use of anti-thyroid drugshas to be individualized.

Graves’ ophthalmopathy (GO) activation after RAI has been reported inabout 15–20% of patients13. 131I-induced autoantigen release from thethyroid, which cross-reacts with tissue components in the orbit leads toactivation of GO. 131I-induced activation of GO can be prevented inpatients recognized at risk of relapse by administering steroids14. In ourinstitute, we have decided to treat GO patients with prophylactic steroidslike prednisolone in the dose of 0.5 to 1.0 mg/kg/day two days prior toRAI therapy and tapering down the dose discontinued after two months.Worsened GO was managed conservatively with the guidance ofophthalmologist.

Unlike other factors, glandular size plays an important role in the responseof I-131 RAI therapy7. So we compared goitre status in both groups. Sizeof goitre had a direct relationship; larger goitres showed greater treatmentfailure.

CONCLUSIONRAI treatment is safe, non invasive and effective in treating hyperthyroidpatients with better success in short duration. Fixed dose method isconvenient and cost effective and it does not require any expertisecalculations. High fixed dose regimen overcomes the refractoriness ofthe long standing use of antithyroid drugs and chronic hyperthyroid illness.

REFERENCES1. Siegel RD, Lee SL. Toxic nodular goiter. Toxic adenoma and toxic multinodular goiter.

Endocrinol Metab Clin North Am 1998 27: 151-168.2. Cooper DS Antithyroid drugs. N Engl J Med 2005 352: 905-917.3. Holm LE, Lundell G, Israelsson A, et al. Incidence of hypothyroidism occurring long after

iodine-131 therapy for hyperthyroidism. J Nucl Med 1982 23: 103-107.4. Peters H, Fischer C, Bogner U, et al. Radioiodine therapy of Graves’ hyperthyroidism:

standard vs. calculated 131iodine activity. Results from a prospective, randomized, multicentrestudy. Eur J Clin Invest 1995 25:186–193.

5. Catargi B, Leprat F, Guyot M, et al. Optimized radioiodine therapy of Graves’ disease:analysis of the delivered dose and of other possible factors affecting outcome. Eur J Endocrinol1999 141:117–121.

6. Sridama A, McCormick M, Kaplan EL, et al. Long-term follow up study of compensatedlow dose 131 I therapy. New England Journal of Medicine 1984 311 426–432.

7. Nordyke RA, Gilbert Jr FI, Optimal iodine-131 dose for eliminating hyperthyroidism inGraves’ disease. J Nucl Med 1991 32:411–416

8. Franklyn JA, Daykin J, Holder R, et al. Radioiodine therapy compared in patients withtoxic nodular or Graves’ hyperthyroidism.QJMed 1995 88:175–180

9. Bahn RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis:Management guidelines of the American Thyroid Association and American Association ofClinical Endocrinologists. Endocr Pract 2011;17:456-520.

10. Santos RB, Romaldini JH, Ward LS, et al. A Randomized Controlled Trial to Evaluate theEffectiveness of 2 Regimens of Fixed Iodine ( I) Doses for Graves Disease Treatment. ClinNucl Med. 2012~˜3:241–4.

11. Einhorn J, Sa¨terborg N-E. Antithyroid drugs in iodine 131 therapy of hyperthyroidism.Acta Radiol. 1962 58:161–167.

12. Goolden AWG, Fraser TR. Effect of pretreatment with carbimazole in patients with thyro-toxicosis subsequently treated with radioactive iodine. Br Med J.1969 3:443– 444.

13. Bonnema SJ, Bartalena L, Toft AD, et al.Controversies in radioiodine therapy: relation toophthalmopathy, the possible radioprotective effect of antithyroid drugs, and use in largegoitres. Eur J Endocrinol 147:1–11.

14. Bartalena L, Marcocci C, Bogazzi F, et al.Use of corticosteroids to prevent progression ofGraves’ ophthalmopathy after radioiodine therapy for hyperthyroidism. N Engl J Med321:1349 –1352.

Next Issue Highlights

• New Thoughts on the etiology of Kidney Stones• Seizuers in the Elderly• Symposium: Dental & Oral Maxillofacial Surgery


Low Dose or High Dose Radioiodine for Remnant Ablation in DifferentiatedThyroid Carcinoma? : A Single Centre Experience.Karuppiah KumaresanKK Nuclear Scans, Basement, Nava Bharat Chambers6-3-1109/1, Raj Bhavan Road, Somajiguda, Hyderabad, India

Correspondence: Dr. Karuppiah Kumaresan, KK Nuclear Scans,Basement, Nava Bharat Chambers, 6-3-1109/1, Raj Bhavan Road,Somajiguda, Hyderabad – 500082, Indiae-mail: [email protected]

Abstract : Radioiodine I-131 therapy for post-operative ablation of remnant thyroid tissue is an accepted treatment world overin the management of thyroid cancer patients since it has been proved to improve prognosis and reduce recurrence. Initiallyhigher activity of I-131 3.7 GBq (100 mCi) was being used empirically to achieve assured remnant ablation in maximumnumber of patients. Of late there is a paradigm shift in the protocol towards using lower dose for remnant ablation. In this study,the efficacy of 25 mCi I-131 is being compared as against the conventional higher dose (70-100 mCi). In a consecutive series of145 patients, (Age Range 8 to 71 years, 95 Females 66%), Histologically102 patients (70%) had pure papillary carcinoma, 36(25%) had papillary variants and 8 (5%) had follicular carcinoma.. 45(31 %) had tumor size less than 4 cms.; 64(44%) hadcervical lymph metastases dissected during surgery. 39 patients (Group I) received 25 mCi I-131 on outpatient basis and 106patients (Group II) received 70 to 100 mCi and were kept in isolation ward for 24 hours. Scan confirmed uptake by remnantthyroid in all patients; Simultaneous estimation of serum Thyroglobulin (Tg) in 53 patients showed poor negative predictivevalue for presence of significant remnant. Silent metastases were detected in 12 patients all within high risk group of tumor size> 4 cms. Excluding the patients with metastases, remnant ablation was evaluated in 133 patients. Ablation was more successfulwith higher activity 96 % in Group II n=39 versus 85 % in Group I n= 94 (p<0.05) irrespective of the size of the tumor.Outpatient treatment with 30 mCi I-131 can be acceptable for low risk patients whereas treatment with higher dose is definitelypreferable in high risk patients for assured ablation.Key words : Differentiated Thyroid Carcinoma, Radioiodine Remnant Ablation

INTRODUCTION

Differentiated thyroid carcinoma has good prognosis if treatedwith total thyroidectomy followed by TSH suppression.Studies world over have shown that the incidence of post-

operative remnant thyroid tissue in the neck is very high. Hence it isprudent to use therapy dose of radioiodine to ablate the remnant inthe post-operative period to prevent recurrence as well as to enablefollow up with radioiodine scan and serum Tg assay. Since the thyroidcancer cells are known to have much lesser efficiency to take upiodine, higher dose of radioiodine is justified in the treatment ofresidual non-resectable loco-regional cancerous disease and distantmetastasis, whereas lesser activity can possibly be used for ablationof remnant normal thyroid tissue. Due to radiation safetyconsiderations for the family and the public, treatment with higheractivity more than 30 mCi can be performed only by hospitalizationin isolation facility in many countries including India. Between 1994and 2002, we have been treating our patients only with 100 mCi.From 2003 onwards, we had the option to treat the patients with 25mCi on outpatient basis. A comparative study was performed in aconsecutive series of 145 patients to compare the efficacy of thisnew low dose (25 mCi) protocol against the standard high doseprotocol.

MATERIAL & METHODSThe Study group included consecutive 145 patients of differentiatedthyroid carcinoma referred for post-thyroidectomy radio-iodine work

up. The demographic, surgical and histological details are given inTable 1.

Table 1: Profile of the Patient (Study Group.) N = 145

* No patient was suspected to have non-resectable residual disease in theneck according to the surgeon’s notes.


Radio-Iodine Workup ProtocolTherapy was carried out between 4th to 6th week post-op duringwhich period an iodine depleted diet was recommended. Serum TSHat the time of therapy was found to be >30 mIU/L on all patients.Clinically there was no palpable remnant in the neck in any of thepatients.

Blood sample was collected in 53 patients just before radioiodineadministration to estimate the serum Tg. Thirty nine patients 27 %(Group I) received 25 mCi iodine I-131 on outpatient basis and theremaining 106, 73% (Group II) received 70 to 100 mCi byhospitalization into isolation facility for 24 hours.

Whole body scan (therapy dose scan) was performed using GammaCamera between 5th & 7th day after therapy. Scans were examinedfor localization of therapy dose of I-131 in thyroid bed, outside thyroidbed in the neck and anywhere else in the whole body.

Patient was kept on TSH suppressive dose of Levothyroxine untilfirst follow-up evaluation which was carried out after an interval of5-6 months. Thyroxine was withdrawn for 4 weeks, diagnostic doseof I-13, 111 MBq (3 mCi) was administered orally and scan wasobtained after 48 to 72 hours. In 12 patients who had surpriseevidence of regional lymph node or distal metastasis in the firsttherapy dose scan, the follow up scan was performed with a second

Gr I (25 mCi) Gr II (>70 mCi)

n = 39 n = 106

Age Range in Yrs 17-51 8-71

Females 32 (82%) 63 (59%)

Papillary carcinoma 37 (94%) 103 (97%)

Stage T1 N0 M0 8 (21%) 7 (7%)

T2 N0 M0 19 (49%) 11 (10%)

T3 / N1a 9 (23%) 27(25%)

T4a / N1b 3 (8%) 61 (58%)

Thyroid Bed Activity 39 (100%) 106 (100%)

Additional Findings 0 12 (11%)

(Metastasis) Cervical Lymph Node-8,

Lung-2, Skeletal-2

Pre scan Stage of these 12 cases Stage III in 5 and IVa in 7

Outcome in follow up:

Complete Ablation 17 (44 %) 95 (90 %) p<0.05

Faint remnant 16 (41 %) 7 ( 6 %) p<0.05

Persistent remnant 6 (15 %) 4 ( 4 %) p<0.05

Stage of disease

T1 / T2 N0 M0

(n=27 (n=18) (n= 45)

Complete Ablation 13 (48%) $ 16 (89%) # 29 ( 64 %) *

Faint Remnant 11 (41%) 2 (11% 13 ( 29 %)

Persistent Remnant 3 (11 %) 0 (0 % 3 ( 7 %)

T3/N1a & T4a/N1b N0 (n = 12) (n= 76) (n=88)

Complete Ablation 4 (33 %) $ 69 (91%) # 73 ( 83 %) *

Faint Remnant 5 (42 %) 5 ( 6 %) 10 ( 11 %)

Persistent Remnant 3 (25 %) 2 ( 3 %) 5 ( 6 %)

*p<0.05, $ p=NS, # p=NS

Gr I Gr II

)

Table 2: Comparision of results of treatment in two groups


therapy dose which is usually 100 200 mCi.

The first therapy dose scan and the first follow up diagnostic scanwere compared and categorized as complete remnant ablation,faint remnant and persisting significant remnant. We have notperformed any neck uptake measurements and we have not usedserum Tg criterion to assess the ablation. The outcome of theradio-iodine treatment was tabulated in relationship to the stageof the disease, extent of surgery and the activity of I-131administered. (Table 2). Student T test was carried out whereverrelevant to assess the significance of any difference observed andp value less than 0.05 was considered significant.

RESULTSOut of 145 consecutive patients 97 were of age less than 45 (67%) and 95 were females (66%). The staging of the disease wasT1 in 15 (10%), T2 in 30 (21%), T3/N1a in 36 (25 %) and T4a/N1b in 64 (44%). Histopathology indicated low risk category ofclassical papillary carcinoma in 102 (70 %). Significant thyroidbed activity was seen in all 145 patients.

Extra-thyroidal bed activity was detected in 12 patients - metastaticto cervical lymph nodes in 8, lungs in 2 and skeleton in 2. Amongthe patients with metastases, 7 out of 12 (58 %) were of age below45 years (5 were below 30 years), No patient in whom metastasiswas detected was from low risk stage group like T1 or T2; 5(42%) were from T3/N1a group and 7 (58%) were from T4a/N1bgroup.

In the follow up scan, thyroid bed activity disappeared completelyin 112 (77%), faintly seen in 23 (16%) and significantly persistentin 10 (7%). Complete ablation of remnant was achieved in 44%(17/39) of Group I as compared to 90% (95/106) in Group II(p<0.05). Faint thyroid bed activity was seen on follow up in41% (16/39) of Group I as compared to 6% (7/106) of GroupII.(p<0.05).

The patients with scan evidence of metastasis were excluded andfurther analysis of outcome was carried out in 133 patients. Sinceno further treatment was advised for patients with faint thyroidbed activity, these patients could be considered as havingsatisfactory response along with complete ablation, which totaledto 33 out of 39 patients (85%) in Group I as compared to 102 outof 106 (96%) in Group II (p<0.05).

The variables associated with persistent remnant were examined.The remnant was persistent in 7 out of 91 (8%) patients who hada single session of surgery as compared to 3 out of 46 (6%) whohad 2 surgeries(p=NS), 8 patients for whom first surgery detailswere not available were excluded. The remnant was persistent in7% of T1 and T2 stage patients (3/45) and in 6% of (5/88) patientspresenting in higher stage (T3/N1a and T4a/N1b) (p=NS). Theremnant was persistent more often after lower dose of I-131treatment 15% (n=39) as compared with the patients treated withhigher activity 2 % (n=94) (p<0.05); Particularly the failure rateis 25 % within the high risk subgroup (n=12) when 25 mCi wasused as compared to only 3 % failure rate within high risksubgroup (n=76) which received higher dose.

DISCUSSIONRadio-iodine I-131 has been used after thyroid surgery for severaldecades in the management of differentiated thyroid cancer withdocumented better outcome in terms of mortality and disease

recurrence1-3. Several guidelines have addressed the indicationfor radioiodine treatment based on risk stratification of the diseaseusing various criteria4-7. Except for less than 1 cm unifocal tumorsremoved by total thyroidectomy, all other patients used to beadministered radio-iodine I-131 for ablation of possible thyroidremnant tissue in the neck. The activity required for successfulablation depend on the size of the remnant, uptake of I-131 andeffective half life. The uptake of I-131 in turn is dependent on thestimulation by elevated TSH and is affected adversely if the stableiodine pool is high in the patient’s body. In the absence ofindividual dosimetry to take into consideration all theseparameters, a simple empirical approach of using fixed dose of100 mCi for all patients was found to be associated with high rateof ablation. Pacini et al8 used 100 mCi I-131 and reported 86%success based on scan alone, and success in remaining 14% withvisible thyroid activity having uptake less than 0.1%. Pilli et al9

reported 89% ablation when the dose used was 100 mCi or 50mCi, when the recombinant human TSH stimulation protocol wasused. Few other investigators have reported satisfactory remnantablation using 30 mCi and have reported minimum ablation rate76%10-11. Lee et al12 has reported 91% success of ablation using30 mCi. Mallick et al13 has used scan criterion and reported 92 %success with 30 mCi as compared with 95 % success with 100mCi. Bal et al14 has reported success rate of about 80% whenpatients are administered any activity within the range of 25 mCito 50 mCi, and the ablation rate drops to 62 % when activity usedis 20 mCi or lesser. Clerc et al15 has found no remnant in 2% oftheir patients, insignificant thyroid bed activity in 12 % andsignificant in 86 %. They have tried a minidose protocol using 2sequential doses of 20 mCi. They report 52 % success in ablatingthe remnant with the first dose when hypothyroid stimulationprotocol was used.

In our experience also, the success rate for remnant ablation isvery high (more than 95 %) with activity of 70100 mCi which iscomparable to what is reported in the literature. However, wehave found definitely lesser success when lesser activity is used44 % only by strict criterion for ablation and 85 % by lax criterionof accepting faint thyroid bed activity. Other authors too haveignored the faint thyroid bed activity if the uptake is measuredand found to be less than 0.1% and we have not included I-131neck uptake measurement in our protocol. Though the faint thyroidbed activity is mentioned by other investigators, the clinicalmeaning of this finding is not known and unlike serum Tg valuemeasured at this point of time which has predictive value fordisease recurrence, there is no follow up study on this scan findingin the literature16. In practice, simultaneous estimation ofstimulated serum Tg is used for decision making regardingretreatment with I-131. If the value is > 10 ng/ml, repeat I-131treatment is advocated others are to be followed up with the faintthyroid bed activity as reference baseline finding. Even otherwise,in our series failure of ablation is significantly higher with 25mCi treatment, 15% in the entire study group and 25% within thehigh risk sub group which is unacceptable.

No role for pre-ablation diagnostic scanIn this series, thyroid bed activity was detected in all 145 patients(100%) in the therapy dose scan. This confirms the concept that apre ablation diagnostic iodine scan has little to contribute regardingthe decision to ablate or not and to decide on the dose. Absenceof thyroid bed activity has been reported in as high as 10% in


certain other parts of the world. Yet even in those centres, non-beneficial radiation (due to non-existing remnant) has beenconsidered acceptable for a minority of the patients (<10%) anddirect remnant ablation is offered to all so as to provide standardcare to the majority (>90%).

Incidence of silent metastasisIn our study group, we have seen surprise silent metastasis in 12%similar to what is reported in the literature. It is to be noted that allthese occurred only among patients with tumor more size more than4 cms. It is to be noted that these metastases were detected with ahighly sensitive therapy dose scan and it is possible that some ofthem might have been missed if a pre-ablation diagnostic scan wasperformed with lesser activity.

Practical issues while choosing the activity for remnant ablationIn reality, there are few other logistic factors which determine theactivity chosen for a given patient. In India and many othercountries, government regulations permit administration of upto30 mCi I-131 on outpatient basis whereas higher activity ispermissible in some other countries17. Definitely outpatienttreatment has the advantage of lower cost than by hospitalization.At the same time, a scan performed with the therapy dose is moreaccurate than one performed with a diagnostic dose of 2 to 4 mCi.Other than the slightly extra cost of the isotope, the patientpreparation, number of clinic visits, and time spent in the lab aresame as for a diagnostic scan; hence a therapy dose on outpatientbasis coupled with a scan is attractive and preferred over just adiagnostic radioiodine scan. Only when ablation is warrantedbased on definite high risk criteria, more activity is preferred.

From Low Dose Ablation to No Ablation based on serumThyroglobulin ?Now the debate has moved further whether remnant ablation canbe limited to only those patients with post-operative serumthyroglobulin more than 10 ng/ml (in low risk patients). In ourstudy group, pre-ablation serum Tg level was available in 49patients with significant thyroid bed activity and the value wasmore than the prescribed cut off of 10 ng only in 37% whichindicates poor negative predictive value.

CONCLUSIONRemnant ablation after thyroid surgery will continue to be animportant integral component of treatment protocol for thyroidcancer patients. Outpatient based treatment using lesserradioiodine (25 to 30 mCi) can be used in low risk patients (withtumor less than 4 cms size and not having any other high riskfeature) with satisfactory outcome but it is preferable that high

risk patients are treated with higher activity for assured betteroutcome. The optimal activity for high risk patients is likely tobe in the range of 50 to 100 mCi as what is in current practice inmost of the centres in India.

REFERENCES1. Sawka AM , Thephamongkhol K, Brouwers M et al. A Systematic Review and

Metaanalysis of the Effectiveness of Radioactive Iodine Remnant Ablation for Well-Differentiated Thyroid Cancer. The Journal of Clinical Endocrinology & Metabo-lism 89 (8):3668-3676, 2004

2. Pacini F, Schlumberger M, Dralle H et al. European Consensus for the Manage-ment of patients with differentiated thyroid carcinoma of the follicular epithelium.European Journal of Endocrinology 154: 787-803, 2006

3. Cooper DS, Doherty GM , Haugen BR et al. Revised American Thyroid Associa-tion Management Guidelines for Patients with Thyroid Nodules and Differenti-ated Thyroid Cancer. Thyroid 19:11, 1167-1214, 2009

4. Samuel AM , Guidelines for Management of Thyroid Cancer. JAPI 59:51-59,20115. NCCN Guidelines for Thyroid Carcinoma Version 2.20146. Pacini F, Ladenson PW, Schlumberger M et al. Radioiodine Ablation of Thyroid

Remnants after Preparation with Recombinant Human Thyrotropin in Differenti-ated Thyroid Carcinoma: Results of an International, Randomized Controlled Study.The Journal of Clinical Endocrinology & Metabolism 91:926-932, 2006

7. Pilli T , Brianzoni E , Capoccetti F et al. A Comparison of 1850 (50 mCi) and3700 MBq (100 mCi) 131-Iodine Administered Doses for Recombinant Thyrotro-pin-Stimulated Postoperative Thyroid Remnant Ablation in Differentiated Thy-roid Cancer. The Journal of Clinical Endocrinology & Metabolism 92(9): 3542-3546, 2007

8. Pacini F , Molinaro E , Castagna M G et al, Ablation of Thyroid Residues with 30mCi I-131: A Comparison in Thyroid Cancer Patients Prepared with Recombi-nant Human TSH or Thyroid Hormone Withdrawal. The Journal of Clinical En-docrinology & Metabolism 87(9), 4063-4068, 2002

9. Barbaro D, Boni G, Meucci G et al. Recombinant human thyroid-stimulatinghormone is effective for radioiodine ablation of post-surgical thyroid remnants.Nuclear Medicine Communications. 27:627-632, 2006

10. Lee J, Yun MJ , Nam KN et al. Quality of Life and Effectiveness Comparisons ofThyroxine Withdrawal, Triiodothyronine Withdrawal, and Recombinant Thyroid-Stimulating Hormone Administration for Low-Dose Radioiodine Remnant Abla-tion of Differentiated Thyroid Carcinoma. Thyroid 20:2, 173-178, 2010

11. Mallick U , Harmer C , Yap B et al. Ablation with Low Dose Radioiodine andThyrotropin Alfa in Thyroid Cancer. The New England Journal of Medicine. 366:1674-1685, 2012

12. Bal CS , Kumar A and Pant GS. Radioiodine Dose for Remnant Ablation in Dif-ferentiated Thyroid Carcinoma: A Randomized Clinical Trial in 509 Patients. TheJournal of Clinical Endocrinology & Metabolism 89(4): 1666-1673, 2004

13. Clerc J, Perrard MB , Malleray CP De et al. Outpatient Thyroid Remnant Abla-tion Using Repeated Low 131-Iodine Activities (740 MBq/20 mCi x 2) in Patientswith Low-Risk Differentiated Thyroid Cancer. The Journal of Clinical Endocri-nology & Metabolism 97:871-880, 2012

14. Parthasarathy KL and Crawford ES. Treatment of Thyroid Carcinoma: Empha-sis on High Dose I-131 Outpatient Therapy. Journal of Nuclear Medicine Tech-nology 30:165-171, 2002

15. Tuttle RM and Sabra MM. Selective use of RAI for ablation and adjuvant therapyafter total thyroidectomy for differentiated thyroid cancer: A practical approachto clinical decision making. Oral Oncology 49:7, 676-683, 2013.

Clinical and Immunological Profile of Systemic Lupus Erythematosus

V Pradhan, M Patwardhan, A Rajadhyaksha , K Ghosh Indian Pediatrics Volume 50 -April 16, 2013 405-407

Pediatric onset systemic lupus erythematosus (SLE) is not uncommon and female to male ratio varies. Pediatric SLE patients have moresevere disease at onset, higher rates of organ involvement and more aggressive clinical course than adults. We compared the clinical andimmunological parameters among pediatric SLE and adult SLE from Western India. Twenty five children and 60 adult patients fulfillingAmerican College of Rheumatology SLE criteria were included. Anti-nuclear antibodies, anti-dsDNA and complement (C3, C4) levelswere tested. Of 25 pediatric SLE patients studied, 24% showed CNS involvement vs. 8.3% in adults SLE (P=0.0499). Lupus nephritis wasseen in 75% adult patients vs. 52% among children. Hepatosplenomegaly was noted more among adult SLE 26.8% vs 12% amongchildren. Alopecia was an exclusive features among adult SLE.

LITERATURE REVIEW


Surgical Management of Vocal Cord PalsyLekshmy R Kurup, Srikamakshi Kothandaraman, Rayappa ChinnusamyApollo Speciality Hospital, Chennai, India

Abstract: This article is an account of our experience of the management of patients with vocal cord paralysis (unilateral andbilateral) and all its attendant problems, viz., voice change (breathy/hoarse voice), inadequate airway and aspiration. A total of30 patients from the past 15 years have been included in this retrospective study. A brief note of the pre-operative work up of thepatient has been made. The exact surgical technique undertaken in the respective settings (medialization thyroplasty in the caseof unilateral cord palsy and posterior cordotomy and arytenoidectomy in patients with bilateral cord palsy) and the resultsachieved have been described.Keywords: Vocal Cord Palsy, Medialization Thyroplasty, Arytenoidectomy, Posterior Cordotomy.

INTRODUCTION

Phonation and protection of lower air way are the most importantfunctions of the human larynx. Immobility of vocal cord mayresult from neural injury or mechanical fixation of vocal cord.

Vocal cords are defined as two fold –like structures which extendfrom the midline of the angle of the thyroid cartilage to the vocalprocess of the arytenoids cartilages. Changes in the length & tensionof the vocal folds control the pitch of the voice & are producednormally only when the vocal folds are in contact for phonation1.

Vocal cord paralysis must not be regarded as a disease alone, butrather symptomatic of an underlying pathology. Cord paralysis mayresult from lesions at the nucleus ambiguus, its supranuclear tracts,the main trunk of the vagus, or the recurrent laryngeal nerves. It maybe unilateral or bilateral, abductor or adductor. Unilateral paralysescould be of neoplastic or traumatic or idiopathic origin whereinbilateral vocal cord paralysis is almost always found in conjunctionwith thyroidectomy2. The result of vocal cord paralysis is dual. If thevocal cords do not approximate, voice will be poor and patient canhave aspiration. Furthermore, loss of sensation,either in the upper orlower laryngeal compartment will result in aspiration.

Bilateral abductor palsy occurs mainly as a consequence ofthyroidectomy, parathyroidectomy or mediastinal surgeries.6 It canlead to breathing difficulty, especially on exertion. Usually thepatient’s voice will be normal. Left untreated, patients may becometracheostomy dependent.

The beginning of treatment of vocal cord palsy can be traced to theyear 1855 when Garcia introduced mirror laryngoscopy. This methodwas later enhanced upon by Chevalier Jackson with his laryngoscopicresection of vocal cord. The technique of medializing a paralysedvocal cord with external access began in 1915 through the works ofPyer and this was adapted by Isshiki through using silicon block forexternal access7. Later he coined the term ‘thyroplasty’ for thistechnique.

Medialization thyroplasty technique has remained as a foundationfor the treatment of glottal insufficiency. Materials like fat, hydrogengel, teflon paste,collagen, hydroxyapetite are being utilized tomedialize the paralyzed cord through the endolaryngeal approachandsilicon sheet/block is used for extralaryngeal approach7.

MATERIALS AND METHODSThis study was conducted in Apollo Speciality Hospital from 2000 -2014. In the last 15 years, 25 patients had undergone medializationthyroplasty for unilateral vocal cord paralysis, 2 patients underwentposterior cordotomy and 3 patients underwent posterior cordotomywith arytenoidectomy. Thorough pre-operative evaluation was donefollowing a complete physical examination for all the cases with abattery of tests, viz., laryngoscopy (direct/indirect), panendoscopy,CT skull base to mediastinum.

Technique For Surgical Management Of UnilateralVocal Cord PalsyType I ThyroplastyMost of the cases with unilateral cord palsy will recoverspontaneously. Speech therapy helps hastening the recovery. Inspiteof this, if the patient has severe aspiration, surgery should be done asearly as possible.

This procedure is a type of laryngeal framework surgery which isdone to deal with the problems of aspiration and breathy voice dueto inadequate adduction of the vocal cord in patients with unilateralvocal cord palsy.Medialization thyroplasty provides support to vocalfolds that lack either the bulk or mobility or both. Most commonly itis used to correct the sequelae of a neurologic injury or a primaryCNS lesion that prevents full closure of the vocal fold or folds.

It is also frequently called a thyroplasty since the procedure isperformed by making a window in the thyroid cartilage. It was firstdescribed by Isshiki and is hence also known as Isshiki type Ithyroplasty. The basic concept is to push the vocal cord in cadavericposition to the midline, so that the opposite cord can approximatewell (Fig.1).

The procedure is done preferably under local anaesthesia, as theimprovement in voice quality can be assessed intra-operatively. Thepatient is put in supine position with neck extension.

Local infiltration is given using premixed solution of 2% lignocainewith 1 in 2,00,000 adrenaline over the ipsilateral thyroid cartilage.6cm long horizontal skin crease incision is made and sub-platysmalflaps elevated.

Thyroid cartilage is delineated after retracting the strap muscles.

The perichondrium overlying the cartilage is incised and carefullypeeled off to expose the ala. A cartilage window of 5mm x 13mm inmen and 5mm x 11mm in women is made over the ipsilateral thyroidala. The window is made 3mm above the inferior border and 5mm

Correspondence: Dr. Rayappa Chinnusamy, Apollo SpecialityHospital, No.320, Padma Complex, Annasalai, Chennai -600040, India e-mail : [email protected]


posterior to the midline of the thyroid cartilage, using an 11 sizeblade. These precise measurements are made using a Vernier caliper(Fig.2). If the cartilageis found to be calcified it is carefully drilledusing a small-sized diamond burr, avoiding any breach of the innerperichondrium. This inner perichondrial layer is elevated off thecartilage all around the window created. The amount of medializationwill vary from patient to patient. Intra-operatively the surgeonmanually displaces the cord medially, makes the patient phonate,and depending upon when the voice is optimal, the distance ismeasured and the silicon block is carved. Next the silicon block issnugly fit into the cartilage wedge and the patient’s voice assessed.The outer perichondrium is re-apposed over the ala and sutured intoposition. The wound is closed in layers after ensuring haemostasis.Ideally the procedure should be done under flexible laryngoscopiccontrol, to visualise the extent of medialization.

This is the technique employed in our institution. However, the latesttechnique of medialization involves use of readymade implants,wherein the implant comes in appropriate sizes for men and women5.

The other implant materials available for medialization are expandedpolytetrafluoroethylene (Goretex), hydroxylapatite, pre-fabricated

Figure 1 : The silicon block implant in situ medializing the vocal fold.

Figure 2. : Calibration of cartilage window3 mm – distance of the cartilage window from the lower border of thyroid ala5 mm – distance of the cartilage window from the midline of the thyroidcartilage11 mm to 13 mm x 5 mm – dimensions of the cartilage window

titanium implants etc.

Technique For Surgical Management of BilateralVocal Cord Palsy

POSTERIOR CORDOTOMY 3

The primary symptom of a patient with bilateral cord palsy isbreathing difficulty, mainly when the patient exerts or during episodesof upper respiratory infection.

Ideal treatment for these patients is tracheostomy with a speakingvalve, as it gives a good airway, at the same time not compromisingthe voice. But for those people who cannot digest the sight of a tubein their neck, posterior cordotomy is an option. Here one cannotpromise the patient that their voice will be normal immediately aftersurgery, because in this procedure, it is about striking a balancebetween airway and voice, one at the cost of the other. Hence thepatient should be thouroughly counselled before surgery. Initiallyafter surgery the voice will be poor as the cord retracts. But withtime the opening will contract and narrow, and voice will improve.

LASER posterior cordotomy is a very viable option in themanagement of upper airway obstruction in patients with bilateralvocal cord palsy. Carbon-dioxide LASER is used in our institution.

Figure 3 : Posterior cordotomy

A waiting period of 6 months is recommended, to await spontaneousrecovery, if the patient can tolerate it3.

ProcedureAn endoscope, which allows for a satisfactory view of the anteriorcommissure, is used together with an operating microscope connectedto a CO

2 laser. A wedge shaped portion of the posterior one-third of

either of the two vocal cords (at the level of tip of vocal process ofarytenoid) is removed along with a corresponding portion of the falsecord and fibres of thyro-arytenoid muscle upto the inner surface ofthe thyroid cartilage, so as to create an adequate airway (Fig.3).LASER precautions need to be taken.

ARYTENOIDECTOMY4

Arytenoidectomy is a permanant and irreversible procedure wherebythe laryngeal inlet is widened in its transverse axis, giving a betterairway for the patient. It is performed in cases of bilateral vocal cordimmobility due to either paralysis or fixation.

This procedure can be done both by an external and endoscopic


(LASER) approach. Arytenoidectomy isusually combined withposterior cordotomy for best

results in terms of airway. The absolute contraindication for it ispatients with aspiration and/or the presence of progressiveneurological disease.

The main complication of concern for these patients in the post-operative period is clinically evident/ sub-clinical aspiration. Henceit may be more prudent to retain the tracheostomy tube for thesepatients until they develop a satisfactory swallow.

RESULTSOf the 25 patients who underwent type I thyroplasty, 20 patients hadundergone different neurosurgical procedures following which theyhad developed unilateral vocal cord palsy. Of the remaining 5 patients,4 had developed the cord palsy following thyroidectomy and 1 wasidiopathic. Among the 25 patients who underwent medializationthyroplasty, 23 patients had significant improvement in voice qualityand 2 patients had initial improvement which deteriorated over timeprobably due to under-correction. Among the 5 patients who hadbilateral abductor palsy, the 2 who underwent posterior cordotomyhad satisfactory improvement in airway with no signs of aspiration.The 3 patients who underwent posterior cordotomy witharytenoidectomy also recovered well with adequate airway withoutany signs of aspiration.

CONCLUSIONThe primary objectives in all these procedures is the restoration of anadequate airway and also voice/phonation along with sphinctericfunction of the larynx. It is essential to strike the delicate balancebetween these opposing functions of the glottis for optimal quality oflife for the patient. The primary goal should be to get away withouthaving to perform a tracheostomy. However in cases wheretracheostomy becomes essential, decannulation at the earliest date/time should be the goal. The appropriate surgical technique from theabove described armamentarium would need to be individualisedbased on the type and degree of vocal fold paralyses and the underlyingetiology.

REFERENCES1. 1Stell and Muran’s, Head and Neck Surgery, 4th edition . 2004 pp 361-3632. Courey MS: Diagnosis and surgical management of unilateral and bilateral vocal fold palsy.Curr Opin

Otolaryngol Head Neck Surg 1995; 3: 120–124.3. Dennis, Donald P., and Haskins Kashima. “Carbon dioxide laser posterior cordectomy for treatment of

bilateral vocal cord paralysis.” Annals of Otology, Rhinology & Laryngology 98.12 (1989): 930-934.4. Ossoff, Robert H., et al. “Endoscopic laser arytenoidectomy for the treatment of bilateral vocal cord

paralysis.” The Laryngoscope 94.10 (1984): 1293-1297.5. Montgomery, William Wayne, and Stuart K. Montgomery. “Montgomery thyroplasty implant system.” The

Annals of otology, rhinology & laryngology. Supplement 170 (1997): 1-16.6. Holinger, Lauren D., Paul C. Holinger, and Paul H. Holinger. “Etiology of Bilateral Abductor Vocal Cord

Paralysis A Review of 389 Cases.” Annals of Otology, Rhinology & Laryngology 85.4 (1976): 428-436.7. Toran, K. C., And S. Shrestha. “functional Results After Vocal Cord Medialization Procedure With Sculp-

tured Silicon Block.” Journal of Nepal Medical Association 42.147 (2003): 133-136.


Evolving Trends in Orbital Decompression for Thyroid Related OrbitopathyPriti UdhayDRR Eye Care And Oculoplasty Hospital,Chennai.

Correspondence: Dr. Priti Udhay, Medical Director, DRR Eye Careand Oculoplasty Hospital, 399,Trunk Road, Karyanchavdi,Poonamalee, Chennai-600056.e-mail : [email protected]

Abstract : Surgery for thyroid related orbitopathy (TRO) has undergone several advancements. This evolution has tremendouslyimproved the surgical rehabilitation of these patients. To compare the reduction of proptosis and the incidence of new-onsetdiplopia after orbital bone and fat decompression in patients with thyroid ophthalmopathy. Orbital decompression was performedin 10 eyes of 8 patients. Fat decompression was performed in all patients and deep lateral wall was considered as the first wallfor bony decompression. This was followed by medial and inferior wall in that order depending upon the severity. The meanreduction of proptosis was 5.3mm . None of the patients had post operative new onset diplopia . Reducing post op diplopia hasbeen the major driving force for new techniques to evolve. Deep lateral wall and balanced decompression combined withorbital fat removal provides effective reduction in proptosis and reduces the incidence of postoperative new onset diplopia ascompared to inferomedial decompression.Keywords: Orbital decompression, Balanced decompression, Deep lateral wall decompression

INTRODUCTION

Principles and techniques of surgical rehabilitation of patientswith thyroid orbitopathy have evolved greatly. However thestaged nature of surgery remains unchanged. The major stages

of surgical rehabilitation are orbital decompression, extraocularmuscle surgery, eyelid repositioning, and volume restoration andskin rejuvenation in that order1,2. Not all patients require all fourstages .

Double vision is the most disabling sequela of thyroid relatedorbitopathy. Decreasing the rate of new onset diplopia afterdecompression surgery; has been a powerful motivator for the searchfor improved techniques3.

Traditional indications for decompression were extreme proptosis,exposure keratopathy and compressive optic neuropathy. Now it isincreasingly common and acceptable to perform orbitaldecompression for cosmetically disfiguring proptosis3,4. Opticneuropathy often can be managed medically. Another recentindication for decompression is congestive orbitopathy. Congestiveorbitopathy is a result of venous congestion created by the expansionof the orbital soft tissues. This can produce symptoms of pressure,pain, limitation of ocular movements and redness that mimic activeinflammation. It is important to differentiate it from inflammation;as inflammation is treated medically but congestive orbitopathyresponds to surgery3,4. Orbital decompression improves venousoutflow in these patients and relieves or substantially improves thecongestive symptoms.

Technical advancements in orbital decompression relate to the newareas of bone removal, removal of orbital fat, and use of smallerincisions. Historically, the inferior and medial wall, connecting tothe maxillary and ethmoid sinuses, was removed. Now, the transantralapproach, which creates an unbalanced inferomedial decompressionwith a relatively high incidence of consecutive strabismus4,5,numbness, and sinusitis; is performed less often. With modern orbitalsurgical techniques, the deep lateral wall bone can be accessed throughan orbital approach via lid crease incision; with substantially less

morbidity compared to an open craniotomy used earlier. Removingbone from the deep lateral wall causes less consecutive strabismusand eliminates the risk of sinusitis.

The medial wall and floor can be accessed through smaller, hiddenconjunctival incisions, including the transcaruncular incision.Removing orbital fat is a major technical change in orbitaldecompression.

MATERIALS AND METHODSDesign: Retrospective, noncomparative, interventional case series.

Retrospective analysis of 8 patients (10 eyes) who underwent orbitaldecompression were analysed. All patients underwent detailedophthalmic evaluation including visual field testing, colour vision,diplopia charting and Hertels exophthalmometry. All patients wereeuthyroid at the time of surgery. Only one patient had active diseaseat the time of surgery.

Surgical Procedure: Surgery was performed under generalanaesthesia. Intraconal fat decompression was performed in allpatients. The maximal available intraconal fat, located between thelateral and inferior rectus muscles; was bluntly dissected out of themuscle cone and excised. When 2mm or less of decompression wasrequired, only fat decompression was performed. Following the ruleof 1wall= 2mm of proptosis reduction; for a 2-4mm correction, onebony wall (lateral wall) was added, for 4-6mm correction, a balancedmedial and lateral wall decompression was performed. For requiredreduction >6mm, a three wall medial, lateral and inferior walldecompression was performed. Conjunctival fornix incision was usedfor inferior wall, superior lid crease incision for lateral wall andtranscaruncular incision for medial wall. Deep areas of lateral wallwere removed; as described by Dr Goldberg et al.7 The bone removalwas performed using neurosurgical drill till only a thin outer tablebone was left behind and in some areas full thickness bone of lateralwall was removed. Beginning with a wedge- shaped section of bonefrom the superolateral orbital rim extending into the fossa of thelacrimal gland and inferiorly blending into the thick trigone of thegreater wing of the sphenoid. Thus the thick posterior portion of thelesser wing of sphenoid was removed from the orbital side, providingsubstantial orbital volume expansion. Further the thick cortical boneof the greater wing of sphenoid between superior and inferior orbitalfissure was removed allowing posterior displacement of the globe(Figure 1). In maximal lateral wall decompression, the inferior orbital


fissure was deskeletonized. For additional decompression; the bodyof the zygoma lateral to inferior orbital fissure was sculpted untilthere is only a thin rim of bone along the lateral orbital rim was leftbehind. Medially, the bone was removed all the way to the zygomatic-

Figure1- (A,B) Coronal and (C,D) axial CT Scan showing the bone removalin lateral, medial and inferior walls(arrows) , (D)-3D reconstruction showingthe area of bone removal in lateral wall (circle)

maxillary suture7.

Medial wall was removed from the posterior lacrimal crest till justanterior to the optic canal where the bone became thick.

Inferior wall medial to the inferior orbital fissure was removed inthree patients leaving behind the inferomedial strut of bone. Fourpatients in our study underwent lower eyelid retraction surgery andone patient had upper eyelid retraction correction simultaneous withthe decompression (Figure 2,3). Lower lid blepharoplasty too wasperformed in two patients (Figure 2,3). One patient had a gold weightimplantation simultaneous with the decompression due toconcomitant facial palsy (Figure 3). He also had a lateral tarsorrhaphywhich was retained.

Optive nerve and pupil were monitored carefully in the intra andpost operative period.

RESULTSTen orbital decompression surgeries were performed on 8 patients(ten eyes). The patient demographics and clinical features are shownin Table-1. All surgeries were performed by one surgeon (Priti Udhay).

There were 6 males and 2 females. Age group was between 35-58years. Two patients underwent bilateral simultaneous decompressionand six unilateral. All patients had thyroid orbitopathy. Indicationfor surgery being cosmetically disfiguring proptosis in 6 patients,exposure keratopathy in one and congestive orbitopathy with oculardiscomfort in one. All patients except one had inactive disease duringsurgery. None of the patients had optic nerve compression due toTRO. One patient had exposure keratopathy with fungal corneal ulcerand active disease. As steroid use was contraindicated due to fungalcorneal ulcer, decompression was performed in active phase of TRO.Proptosis ranged from 3mm to 9mm.In bilateral cases 19mm wastaken as baseline Hertels value. In unilateral proptosis the differencebetween the two eyes was taken as the amount of proptosis. Averagereduction in proptosis was 5.3mm. Four patients in our study

Figure 2: A) Preop clinical photograph(B)Post op picture after right orbital decompression ,upper and lower lidretraction correction and lower lid blepharoplasty.

Figure 3- ( A,B,C)Preop picture showing right severe proptosis with facialpalsy, lagophthalmos and tarsorrhaphy(D,E,F,G)Post op after decompression and upper lid gold weight and lowerlid blepharoplasty and medial canthoplasty.Shows marked reduction inproptosis with improvement in eye closure.

underwent lower eyelid retraction surgery at the time of orbitaldecompression , one underwent upper eyelid retraction surgery andtwo had lower lid blepharoplsty. Patients were counseled thatadditional stages of eyelid repositioning may be needed, but duringfollow-up, none of these patients who underwent concomitanteyelidsurgery required additional eyelid repositioning surgery. Onlytwo patients had preoperative diplopia. Their diplopia remained thesame post operatively. They underwent squint surgery for the samesubsequently. None of the patients developed post operative newonset diplopia. No severe complications such as vision loss occurred.One patient had mild CSF leak which was plugged intraoperativelywith orbital fat. Numbness in the distribution of thezygomaticotemporal and zygomaticofacial nerves was seen in fourpatients. However these patients were warned of this preoperatively.

DISCUSSIONAs each stage can affect decision making for subsequent stages; it isgenerally accepted that the surgery should be staged in a specificsequence. However staged approach involves substantial time,costsare increased by multiple surgeries and multiple surgeries areadditionally emotionally taxing. Some patients in our study underwenteyelid retraction surgery at the time of orbital decompression. During


follow-up, none of these patients required additional eyelidrepositioning surgery9. Ben Simon et al9 have reported that correctionof eyelid retraction in mild to moderate TRO patients, performedsimultaneously with deep lateral wall orbital decompression, resultedin acceptable eyelid position in two thirds of patients. Goldberg et alhave demonstrated that deep lateral wall decompression can achievesuccessful volume expansion and reduction of proptosis (up to 6mm), in the absence of complications such as hypoglobus or dystopia7.The complications of lateral orbital decompression have beendiscussed in several articles. The bone is drilled in the region of thefrontal and middle cranial fossa, and small exposures of dura arecommon in aggressive bony removals.

Leaks of cerebrospinal fluid can occur if small dural perforations arecreated. These can be patched intraoperatively, and even if slightleakage is present at the end of surgery, it is generally self-limited.Intracranial bleeding associated with dural laceration could be lifethreatening; although this should be a rare complication with carefultechnique. Oscillopsia with chewing has been reported with lateralwall decompressions7. This can be avoided by leaving behind a thinshell of bone over as much of temporalis muscle as possible.

Fatourechi et al5 reported a high rate (73%) of postoperative diplopiain patients who underwent transantral decompression for cosmeticpurposes. This may be related to the large shift of muscle cone intothe sinus cavities placing additional stretch on the already tight inferiorand medial rectus muscle, exacerbating esotropia and hypotropia.6Overall the balanced or lateral decompression alone probably resultsin less new onset strabismus3.

Most of my patients receive dermal fillers and skin rejuvenation postoperatively as a final stage procedure. The major limitation of thisstudy is the small number of patients. However the results arecomparable to the other larger series using the same surgicaltechnique3.

A prospective study comparing different treatment modalities alongwith quality of life questionnaire, is required to accurately estimatethe effectiveness of various surgical techniques.

Table-1:Demographic and Clinical Characteristics of Patients

M-Male, F-Female, U/L-Unilateral, B/L-Bilateral, LL-Lower Lid, UL-Upper Lid, B-Blepharoplasty

SUMMARYIn summary, our techniques for the surgical rehabilitation of patientswith Graves’ orbitopathy have continued to improve. We have beenable to decrease the incidence of some of the worst complications;particularly new onset double vision.

REFERENCES1) Ben Simon GJ, Syed HM, Lee S, et al. Strabismus after deep lateral wall orbital decompres-

sion in thyroid-related orbitopathy patients using automated hess screen. Ophthalmology,113:1050-1055

2) Shorr N, Seiff SR. The four stages of surgical rehabilitation of the patient with dysthyroidophthalmopathy. Ophthalmology, 1986; 93:476-483.

3) Ben Simon G, Wang L, McCann JD et al. Primary-gaze diplopia in thyroid related orbitopathy(TRO) patients undergoing deep lateral orbital decompression with intra-conal fat debulking.Thyroid, 2004; 14:379-383

4) Goldberg RA.The evolving paradigm of orbital decompression.Arch Ophthalmol 1998,116:95-96.

5) Fatourechi V, Garrity JA, Bartley GB, et al. Graves’ ophthalmopathy. Results of transantralorbital decompression performed primarily for cosmetic indications. Ophthalmology;1994,101:938-942.

6) Garrity JA, Fatourechi V, Bergstralh EJ, et al. Results of transantral orbital decompressionin 428 patients with severe Graves’ orbitopathy. Am J Ophthalmol. 1993;116:533-547.

7) Goldberg RA, Kim A, Kerivan KM 2000 .The lacrimal keyhole, orbital door jamb, andbasin of the inferior orbital fissure .Three areas of deep bone in the lateral orbit. ArchOphthalmol 116:1618-1624.

8) Ben Simon GJ, Schwarcz RM, Mansury AM, et al. Minimally invasive orbital decompres-sion: local anesthesia and hand-carved bone.Arch Ophthalmol. 2005 Dec; 123(12):1671-5.

9) Ben Simon GJ, Mansury AM, Schwarcz RM, et al. Simultaneous orbital decompression andcorrection of upper eyelid retraction versus staged procedures in thyroid-related orbitopathy.Ophthalmology 112:923-932.

10) Shorr N, Neuhaus AW, Baylis HI. Ocular motility problems after orbital decompression fordysthyroid ophthalmopathy. Ophthalmology, 1982; 89:323-328.

11) Goldberg RA. Advances in Surgical Rehabilitation in Thyroid Eye Disease. Thyroid 2008;18 :989-995.

12) Eloy P, Trussart C, Jouzdani E, et al . Transnasal endoscopic orbital decompression andGraves’ ophtalmopathy. Acta Otorhinolaryngol Belg 54:165-174.

13) Unal IM, Ileri F, Konuk O,et al. Balanced orbital decompression combined with fat removalin Graves’ ophthalmopathy: do we really need to remove the third wall? Ophthal PlastReconstr Surg.2003; 19:112-118.

14) Wright ED, Davidson J, Codere F, et al. Endoscopic orbital decompression with preserva-tion of an inferomedial bony strut: Minimization of postoperative diplopia. J Otolaryngol1999; 28:252-256.

15) Linnet J, Hegedus L, Bjerre P . Results of a neurosurgical two-wall orbital decompressionin the treatment of severe thyroid associated ophthalmopathy. Acta Ophthalmol Scand 200179:49-52.


Excision of Lingual thyroid - How I do it.Maharajan ChandrasekaranEndocrine Surgeon, McArthy Thyroid Clinic, Chennai

Correspondence: Dr. Maharajan Chandrasekaran, McArthyThyroid Clinic, 14, Prakasam Street,T. Nagar, Chennai - 600017.Indiae-mail : [email protected]

Key words: Suprahyoid approach, Lingual Thyroid,Chandrasekaran Operation.

World over 3 Surgical approaches are commonly used to exciseLingual thyroid. They are

(1) Lateral pharyngotomy approach,(2) anterior approach where the tongue is bisected and the mandible

is split in the middle and(3) endoscopic trans oral approach.All three procedures are not only time consuming and morbid butare also associated with profuse bleeding.

Suprahyoid Approach:

CHANDRASEKARAN OPERATION- FORLINGUAL THYROIDI have designed a unique technique for excising Lingual thyroidthrough a different route - suprahyoid approach- in which the lingualthyroid is excised under direct vision . The entire procedure can beperformed within 45 minutes with minimal blood loss (less than30ml.) The results have been excellent in all cases and patients werestarted on liquid diet on the 6th post operative day. Above all, thisprocedure can be performed by a surgeon with ease and withoutcomplications and blood loss . Hence, I strongly recommend thisSuprahyoid approach for excising the Lingual thyroid.

Fig. 1 - A. Lingual Thyroid

Fig. 1 - B: Tc99m pertechnetate scan showing lingual Thyroid

Image showing the site of incision on the tongue


STEPS OF THE SURGICAL PROCEDURE ARE AS FOLLOWS.

Fig.2 - A,B.: Under general anaesthesia through a nasal intubation, patient is kept in the kocher's position with hyperextension of the neckwith a shoulder bag behind. Introduce Ryle's tube after securing the endotracheal tube. To hold the tongue, take a stitch at the tip of thetongue. (fig.2-A ). Insert orally a gauze on a sponge holding forceps and push the lingual thyroid anteriorly in the suprahyoid region to ensureexact placement of the incision over the mass. (fig.2-B )

Fig.3 - A,B: Make a 8 cm long suprahyoid skin crease incision. Divide the mylohyoid muscle in the superficial layer and then the deepermuscles geniohyoid and hyoglossus (Fig.3 A,B) and expose the ventral surface of the tongue.

Fig.4 - A,B: Incise the valecullar mucosa. Insert a finger into the oropharynx and divide the tongue horizontally to expose the lingual aspectof the epiglottis..(Fig.4-A). Hold the tongue with the babcocks forceps and flip it to expose the posterior third of the dorsum of the tongue(Fig.4-A). This maneuver will expose the lingual thyroid completely with the posterior third of the tongue. Under direct vision andpalpation, using ultrasonic shears excise the lingual thyroid completely.(Fig.4 - B)


Fig.5 - A,B.: Approximate the divided muscle layers with absorbable sutures, 2-0 vicryl (Fig.5-A). Close the wound in layers with a suctiondrain in the inter muscular plane (Fig.5-B). Feed the patient through the Ryle’s tube for the first 5 post operative days. Remove the Ryle’stube on the 6th postoperative day and start the patient on liquid diet.

The suprahyoid scar may not be visible as it merges with the skin crease under the chin.

In this surgical procedure, the Lingual thyroid is excised in toto under direct vision and palpation. Hence, securing haemostasis is very easyand there is no fear of leaving behind a part of lingual thyroid which may result in a recurrence.

Major vascular or neural structures are not encountered in this approach to lingual thyroid. There is no need to split the mandible and bisectthe tongue. This procedure can be performed by any trained surgeon without morbidity and profuse bleeding.

Excised Lingual Thyroid Cut section of the excised lingual thyroid

DapagliflozinComposition: Dapagliflozin propanediol monohydrate equivalent to Dapagliflozin, 5mg or 10 mg, titanium Dioxide IP & Iron oxideYellow Ph.Eur. Mechanism ofaction: Dapagliflozin is highly potent, selective and reversible inhibitor of sodium-glucose contransporter 2 (SGLT2) that improveglycemic control in patients with type2diabetes mellitus by reducing renal glucose reabsorption leading to urinary excretion of excess glucose (glucuresis). FORXIGA is orally available and requires once-dailydosing. INDICATIONS and USAGE: in adults aged 18 years and older with type 2 diabetes mellitus to improve glycemic control. As monitherapy when diet andexercise alone do not provide adequate glycemic control in patients for whom use of metformin is considered inappropriate due to intolerance. As add-on combinationtherapy in combination with other glucose lowering medicinal products including insulin, when these, together with diet and exercise, do not provideglycemic control.Dapagliflozin is not indicated for use in patients type 1 diabetes be diabetic ketoacidosis be used in patients with moderate to severe renal impairment (estimatedglomerular filteration rate [eGFR] persistently < 45mL/min/1.73m2 as calculatedby the Modification of Diet in Renal disease (MDRD)formula, or creatinine clearance(CrCl) persistently < 60 mL/min as calculated by Cockcroft Gualt formula) or end stage renal disease (ESRD). Dosage and administration: the recommended dose offorxiga is 10mg taken daily at anytime of the day regardless of meal. Monotherapy and add-on combination therapy: the recommended dose of forxiga is 10mg once dailyas monotherpy or as add-on to combination therapy with metformin, a thiazolidinedione/a sulfonylurea, a DPP4 inhibitor (with or without metformin) or insulin (with orwithout oral antidibetic therapy, either mettormin plus insulin deal therapy or mettomin plus sulfonylurea plus insulin triple therapy). Renal impairment: patients withmild renal impairment: (eGFR > 60 to < 90mL/min/1.73m2) The pool of 21 double bind, active and placebo-controlled, clinical safety and efficacy studies included53%(4906/9339) of patients with mild renal impairment. The mean change from baseline in haemoglobin A1C (HBA1C) and the placebo-corrected HBA1C change at24weeks was-1.03% and -0.54%, respectively , for forxiga 10mg (n=562). The safety profile in patients with mild renal impairment is similar to that in overall population.patients with moderate renal impairment (eGFR > 30 to < 60mL/min/1.73m2). the pool of 21 active and placebo-controllled clinical studies included 11% (1055/9339) ofpatients with moderate renal impairment. The mean change from baseline in HbA1c and placebo-corrected mean HBA1C change at 24 weeks was -0.87% and -0.39%,respectively, for forxiga 10 mg (n=85). Safety in patients with moderate renal impairment was assessed in pooled analysis of 12 clinical studies (384 patients, 88% witheGFR > 45 to < 60mL/min/1.73m2 in short term plus long term safety pool up to 102 weeks, the safety profile remained similar. Patients with severe renal impairmenteGFR < 30mL/min/1.73m2, or ESRD, were not included in clinical studies. Based on its mechanism of action forxiga was not anticipated to be effective in thesepopulations. Use in patients at risk for volume depletion: the diuretic effect of forxiga decreases intravascular volume. For patients at risk for volume depletion ordehydration due to co-existing conditions ( such as patients with extremely poor glycemic control, elderly patients and those on concomitant diuretics), a 5mg starting dosemay be appropriate. These patients should also be instructed to take water appropriate and carefully monitored. When symptoms of volume depletion arise, appropriatemeasures including fluid replacement or temporary interruption should be considered. Contradictions: forxiga is contradicted in patients with a history of any serioushypersensitivity reaction to the active substance or any of the excipients. Adverse reactions: the overall incidence of adverse events for the 13-study, short-term, placebo-controlled pool (short term treatment) in patients who received forxiga 10mg was 60% compared to 55.7 % for the placebo group. Discontinuation of therapy due toadverse events in patients who received forxiga 10mg was 4.3% compared to 3.6% for the placebo group. The most commonly reported event leading to discontinuationand reported in atleast3 forxiga 10mg patients were renal impairment (0.8%), decrease increatinine clearance (0.6%), increased blood (0.3%), Urinary tract infection(0.2%) and vuvovaginal mycotic infection (0.1%)


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