An update on thyroid surgery

European Journal of Nuclear Medicine Vol. 29, Supplement 2, August 2002

Abstract. Surgery has been the treatment of choice formany disorders of the thyroid gland, both benign andmalignant, for many decades. However, surgery has notbeen invariable but has continued to change in accor-dance with research results. In benign cases, surgery hasgenerally evolved to be as organ preserving as possible.In several instances, however, a more radical extent ofresection seems justified in order to ensure that the riskof recurrence is as low as possible. For instance, totalthyroidectomy may be beneficial in patients with endem-ic multinodular goitre or young patients with Graves’disease and accompanying cold nodules or high levels ofautoantibodies. Several tools, e.g. magnifying glasses,bipolar coagulation forceps and neuromonitoring, areavailable to identify and preserve the recurrent laryngealnerve and the parathyroid glands, hence keeping themorbidity at a low level. Most recently, minimally inva-sive surgery has been successfully used in treating bothbenign and malignant disorders of the thyroid gland. Inthe case of malignant disorders, minimally invasive sur-gery may become an attractive alternative to open sur-gery if a limited surgical extent is justified, e.g. in pa-tients with micro-PTC (papillary thyroid carcinoma,diameter less than 1 cm). Whether a limited surgical ap-proach is also justified in other cases, e.g. in any patientwith intrathyroidal PTC or patients with micro-FTC (fol-licular thyroid carcinoma), remains to be shown and isthe subject of ongoing investigations. One of the mostintriguing recent discoveries is the identification of gen-otype-phenotype correlations in patients with hereditarymedullary thyroid carcinoma. In these patients, the tim-ing and extent of surgery may depend not only on the pa-tient’s age and serum levels of the tumour marker calci-tonin but also on the specific germline RET proto-onco-gene mutation. Surgery will certainly continue to play animportant role in the treatment of thyroid diseases and

may be increasingly based on individual findings insteadof general recommendations.

Keywords: Thyroid – Surgery – Advances

Eur J Nucl Med (2002) 29 (Suppl. 2):S447–S452DOI 10.1007/s00259-002-0913-3

Introduction

The Swiss surgeon Emil Theodor Kocher can be calledthe father of endocrine surgery, and especially thyroidsurgery. Before he and Theodor Billroth set out to im-prove surgery of the thyroid gland, it had been per-formed only in life-threatening situations since the mor-tality rate was reported to be as high as 40%. Due toKocher’s growing surgical expertise, his own mortalityrates dropped from about 14% in 1884 to 2.4% in 1889and 0.18% in 1898. In addition, morbidity rates droppeddramatically and surgery became an effective therapeutictool for thyroid diseases, both benign and malignant. In1909, Kocher received the Noble Prize for his achieve-ments concerning the physiology, pathology and surgeryof the thyroid gland. Almost 100 years later, surgery isstill the treatment of choice for many thyroid disorders.

In this article, we give a brief summary on the currentsurgical practice in patients with thyroid diseases, withparticular focus on recent developments concerningstrategies of surgical resection and surgical techniques.

Extent of resection

Benign goitre

In general, surgery of benign thyroid disorders hasevolved to be as organ preserving as possible. However,several disorders may be best treated by performing amore radical resection (Table 1). This issue has been ad-dressed by several recent publications. For instance, pa-

O. Gimm (✉ )Universitäts- und Poliklinik für Allgemein-, Viszeral- und Gefäßchirurgie, Martin-Luther-Universität Halle-Wittenberg,Ernst-Grube-Strasse 40, 06097 Halle, Germanye-mail: [email protected].: +49-345-5572314, Fax: +49-345-5572551

An update on thyroid surgeryO. Gimm, M. Brauckhoff, P. N. Thanh, C. Sekulla, H. Dralle

Universitäts- und Poliklinik für Allgemein-, Viszeral- und Gefäßchirurgie, Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Strasse 40,06097 Halle, Germany

Published online: 11 July 2002© Springer-Verlag 2002

tients with Graves’ disease may benefit from total thy-roidectomy as compared with less than total thyroidecto-my for the following reasons: (a) there is no risk of re-currence; (b) total thyroidectomy may have a beneficialeffect on endocrine ophthalmopathy; (c) the risk of ma-lignant thyroid tumours in patients with Graves’ diseaseis generally low (about 4%), though it may be up to 15%if cold nodules are present [1]. It needs to be taken intoaccount that subtotal thyroidectomy generally is accom-panied by decreased morbidity as compared with totalthyroidectomy. The risk of recurrence, however, is in-creased in patients with high serum levels of autoanti-bodies and a young age (<20 years). Hence, a more spe-cific approach appears to be appropriate, i.e. patientswith high serum levels of autoantibodies (high level ofimmunoactivity), patients younger than 20 years and pa-tients with presence of cold nodules may be treated withtotal thyroidectomy while patients with low serum levels

of autoantibodies and patients older than 20 years whodo not have cold nodules may be treated with less thantotal thyroidectomy.

Total thyroidectomy may also be the treatment ofchoice in patients with endemic multinodular goitre, ashas been demonstrated by Mishra et al. [2]. However, inthe presence of only a few nodules and the absence ofrisk factors, subtotal thyroidectomy may be the preferredsurgical option.

In patients with follicular thyroid adenoma, total lo-bectomy is generally recommended (Table 1) since fol-licular thyroid carcinoma (FTC) may not be excludedpre- or intraoperatively. Whether a less extended ap-proach may be justified remains to be shown, as thereare no studies proving the benefit of either therapy.

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Table 1. What’s new in thyroid surgery?

Extent of resection Surgical technique

1. Benign goitre Aim: Minimising the risk of surgical morbidity while maintainingthe quality of conventional techniques

1.1. Follicular adenoma 1. Recurrent laryngeal nerve: identification/preservation of the nerve recommended; neuromonitoring may be helpful in the hand of a less experienced surgeon

Lobectomy recommended (not proven by studies) 2. Parathyroid glands: preservation of at least 2 glands (in situ or autotransplanted) minimises the risk of hypoparathyroidism significantly

1.2. Graves’ disease and multinodular goitre 3. Minimally invasive surgery: can be performed without increasing the morbidity; benefit not clear

Total vs subtotal resection: tendency towards a more extended resection

2. Malignant tumours2.1. Differentiated thyroid carcinoma

Papillary thyroid carcinoma

Limited resection (pT1 tumour) vs radical resection (pT2–4 tumour)

Lymph node dissection: central compartment mandatory, beyond central compartment optional

Follicular thyroid carcinomaLimited resection in pT1 tumours? (Not proven by studies)

Lymph node dissection: extent to be determined in studies

2.2. Medullary thyroid carcinomaSporadic: Limited resection in pT1 tumours? (Success proven in single studies)

Hereditary: Time and extent of surgery may depend on the patient’s age, calcitonin level and RET mutation (genotype-phenotype correlation)

2.3. Undifferentiated thyroid carcinomaExtended surgery in combination with radiation (>30 Gy) may be beneficial for pN0, R0/R1 patients

Malignant tumours

Surgery is the treatment of choice for thyroid cancer, arare disorder with either a benign clinical course, as inpatients with papillary thyroid carcinoma (PTC), or arapidly progressive course, as in patients with undiffer-entiated thyroid carcinoma (UTC).

Differentiated thyroid carcinoma

The majority of malignant thyroid neoplasms derivefrom epithelial cells. PTC, deriving from follicular cells,is generally the most common type. Its frequency variesdepending on the iodine intake, with higher frequenciesin iodine-rich regions. FTC, also deriving from follicularcells, is rare in iodine-rich regions.

According to the guidelines of the German Society ofEndocrine Surgeons (CAEK), total thyroidectomy is rec-ommended in patients with differentiated thyroid carci-noma (DTC). The rationale behind this recommendationis as follows:

1. Morbidity: In experienced hands, total thyroidectomycan be performed without increased morbidity ascompared with less than total thyroidectomy. How-ever, completion and re-operation due to tumour rem-nant/recurrence may be accompanied by increasedmorbidity.

2. Multifocality: PTC, whether unilateral or bilateral, isoften multifocal (40%–50%). FTC is multifocal in on-ly about 10% of cases. However, due to its biologicalbehaviour, FTC with small foci of PTC is classified asPTC. Since preoperative differentiation may be im-possible, total thyroidectomy appears to be preferred.

3. Recurrence: Again, due to the high proportion of mul-tifocal tumours, recurrence rates have been shown tobe higher after less than total thyroidectomy.

4. Dedifferentiation: Tumour tissue left in situ may de-differentiate and even become undifferentiated.

5. Radioiodine and thyroglobulin: Radioiodine can beused as a tool to diagnose and treat local tumour re-currence and/or metastases. Also, in patients withDTC, the tumour marker thyroglobulin can be used toassess tumour recurrence. The prerequisite is total re-moval of the thyroid gland.

An exception to this general recommendation is small(less than 1 cm in diameter) PTCs (Table 1), also calledmicro-PTCs (pT1 category). These tumours may befound in up to 30% of thyroid glands resected for puta-tive benign thyroid disorders. In these instances, lessthan total thyroidectomy may be justified if there is nosuspicion of tumour remnant, i.e. the following must ap-ply: (a) unifocal primary tumour, (b) no sign of lymphnode or distant metastases, (c) non-oxyphilic (non-onco-cytic) tumour type, (d) no history of prior neck radiationand (e) negative family history. It is unknown whetherthis limited extent of resection may also be justified in

any intrathyroidal PTC. The criteria could be the same asthe aforementioned. However, studies supporting such alimited approach do not exist. It is also unknown whetherpatients with pT1 FTC may be treated by a limited ap-proach.

In patients with PTC, lymph node metastases are of-ten (>30%) present initially. Their significance for sur-vival appears to be uncertain. However, an influence onthe rate of recurrence is widely accepted. Hence, theCAEK guidelines recommend routine dissection oflymph nodes of the cervicocentral compartment. The in-dication for performance of lymph node dissection be-yond this compartment is, however, less clear. If lymphnode metastases are present, the indication is certainlygiven. However, lymph node metastases of PTC may bevery small and not identifiable preoperatively or intraop-eratively. Still, lymph node involvement of the cervico-lateral lymph node compartment has been found in up to25%–30% of patients with PTC, while lymph node me-tastases in the upper mediastinum are rare. The lattermay, however, be found more frequently in patients withpT4 tumour (extrathyroidal tumour extension).

In patients with PTC, lymph node dissection shouldbe performed en bloc, i.e. lymph nodes should be resect-ed with the surrounding adipose tissue while nerves, ves-sels and muscles are preserved. This technique is alsoknown as systematic lymph node dissection. Systematiclymph node dissection should be performed since manylymph node metastases are small and hence not identifi-able intraoperatively (see above). In addition, soft tissueinfiltrates, which would remain in situ in the case ofselective lymph node dissection (“berry picking”), havebeen found in up to 13% [3].

Since pre- and intraoperative techniques often fail toidentify lymph node metastases, the search for more reli-able techniques is ongoing. Sentinel lymph node biopsyhas been shown to be of value in determining the extentof lymph node dissection in patients with melanoma andbreast cancer. In thyroid cancer, however, the value ofthe sentinel lymph node is less clear. The success rate inidentifying a sentinel lymph node in thyroid cancer rangesfrom 65% to 95%. The false negative rate has been re-ported to be as high as 17% [4]. However, well-designedstudies are still lacking, and the value of sentinel nodedissection in thyroid cancer remains to be determined.

Medullary thyroid carcinoma

In contrast to DTC, medullary thyroid carcinoma (MTC)derives from parafollicular C cells. C cells secrete cal-citonin, which may serve as a sensitive and specifictumour marker at diagnosis and during follow-up. Aboutone-quarter of all MTCs are hereditary and part of themultiple endocrine neoplasia syndrome type 2 (MEN 2).Activating germline mutations in the RET proto-onco-gene have been found in >95% of these patients.

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There is no doubt that patients with hereditary MTCshould undergo total thyroidectomy since every single Ccell harbours the potential risk of becoming malignant.However, the necessity of total thyroidectomy in patientswith sporadic MTC has recently been questioned [5](Table 1). It has been shown that excellent results can beachieved in patients with sporadic MTC by means ofunilateral surgery of the thyroid gland together with cer-vicocentral and ipsilateral cervicolateral lymph node dis-section.

Similar to PTC, lymph node metastases may often(>50%) be present in patients with MTC. In general,lymph node metastases in MTC are believed to affectboth recurrence rate and survival. Hence, routine lymphnode dissection of at least the cervicocentral compart-ment is recommended. The indication for lymph nodedissection of the cervicolateral compartments, however,is less clear. Nevertheless, routine cervicolateral dissec-tion has been recommended by several authors both inpatients with sporadic and in those with hereditary MTCbecause metastases are often found (30%–50% of cases).An exception may be young screening patients, i.e.asymptomatic patients harbouring a germline RET muta-tion. In these patients, timing and surgical extent maydepend on calcitonin levels, age and the specific RETmutation (Fig. 1). As in patients with PTC, lymph nodedissection should be performed en bloc.

Undifferentiated thyroid carcinoma

DTC may dedifferentiate and may even become undif-ferentiated. Whether UTC can develop directly from fol-licular cells is not known. The overall survival rate is ex-tremely low: less than 5% of affected individuals survivethe first year after diagnosis. Cure is rarely possible, andcan only be achieved in patients undergoing surgery.Most patients present with a primary tumour beyond thethyroid gland (pT4 tumour). It could be shown that thesepatients only benefit from an extended surgical approachin the absence of lymph node metastases and in the caseof a macroscopically radical tumour resection (R0 or R1)[6] (Table 1).

Surgical technique

To keep the complication rate as low as possible, precisesurgical techniques and bloodless operation should beaimed for. Today, many helpful tools exist, such as mag-nifying glasses, neuromonitoring and bipolar coagulationforceps. They facilitate the identification, preparationand preservation of important structures (e.g. parathyroidglands, nerves).

The most commonly observed complications follow-ing surgery of the thyroid gland are hypocalcaemia andparesis of the recurrent laryngeal nerve. Depending onthe extent of lymph node dissection, additional compli-cations (e.g. paresis of the accessory nerve, Horner’ssyndrome) may also be observed.

Recurrent laryngeal nerve paresis

Risk factors

Paresis of the recurrent laryngeal nerve is a serious com-plication which may prevent the affected individual fromcontinuing his/her profession (e.g. in the case of teachersor singers). Several factors that increase the risk of per-manent laryngeal nerve paresis have been identified, in-cluding recurrent goitre (3.4-fold) and extent of surgicalresection (2.1-fold) [7].

Identification

For decades, there was controversy over whether identi-fication of the laryngeal nerve can lower the rate of re-current laryngeal nerve palsy or whether such attempts infact have a deleterious effect on preservation of thenerve’s function. In experienced hands, however, it hasrepeatedly been shown that identification of the nerve isnot accompanied by an increased rate of nerve palsy. Re-cently, analysis of the data concerning more than 7,500patients in a large, prospective multicentre study hasshown that identification of the recurrent laryngeal nerve

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Fig. 1. Timing and extent ofsurgery in hereditary MTC

reduces the risk of recurrent laryngeal nerve paresis by1.6-fold [7]. This holds true not only for malignant butalso for benign disorders. Only in rare instances (e.g.enucleation of a thyroid adenoma in the ventral thyroidlobe) may identification of the nerve be unnecessary.

Neuromonitoring

The benefit of monitoring the integrity of the recurrentlaryngeal nerve intraoperatively has recently been shownin several studies. Despite different methods, the rate ofparesis of the recurrent laryngeal nerve has been reportedto be as low as 0%–0.6% [8, 9, 10]. That neuromonitor-ing can significantly reduce the rate of permanent laryn-geal nerve paresis could also be shown in a large, pro-spective multicentre study analysing the data of morethan 7,500 patients [11].

Neuromonitoring itself may be helpful not only in re-ducing the rate of recurrent laryngeal nerve paresis butalso in identifying the nerve. Successful identification ofthe nerve has been reported in >97% of patients [8].Neuromonitoring has also been shown to be of help inpatients with non-recurrent laryngeal nerves [12].

Hypocalcaemia

Even though unpleasant, the symptoms of hypocalcae-mia can easily be treated by calcium intake either orallyor via intravenous injection. However, the long-term ef-fects are often underestimated. Hence, the developmentof hypocalcaemia must be avoided. In a large, prospec-tive multicentre study, several risk factors have beenidentified that are associated with an increase risk of hy-pocalcaemia: female gender (2.1-fold), Graves’ disease(2.8-fold), experience of the surgical department (1.5-fold), recurrence of goitre (1.9-fold) and extent of resec-tion (1.8-fold) [7]. It could also be shown that identifica-tion of at least two parathyroid glands intraoperativelyresults in a 2.5-fold reduction in the risk of developinghypocalcaemia [13].

Minimally invasive surgery

The technique of minimally invasive surgery has nowbeen well established for several organs and diseases(e.g. cholecystitis, appendicitis). In endocrine surgery,laparoscopic or endoscopic techniques have been usedfor years to treat neoplasms of the adrenal gland. Veryrecently, minimally invasive video-assisted parathyroi-dectomy (MIVAP) was introduced by Miccoli and col-leagues from Italy. The same group [14] and others [15,16] have also shown the feasibility of minimally inva-sive video-assisted thyroidectomy (MIVAT). At first,only benign thyroid diseases were treated. The operationtime has been reported to be as low as 80–100 min [14],

though others have reported longer operating times of120–330 min [16]. The complication rates have general-ly been low. Conversion to open surgery was necessaryin 3%–10% of cases.

In the meantime, several different endoscopic ap-proaches have been developed. Such approaches wereinitially developed to limit discomfort for the patientwhile keeping the cervical incision as small as possible,but others have made modifications due to “national” re-quirements. For instance, since even a small cervicalscar in some Asian women may render them less likelyto get married, subclavian and axillary approaches havebeen reported. The usefulness and safety of these proce-dures remains to be shown.

References

1. Kraimps JL, Bouin-Pineau MH, Mathonnet M, De Calan L,Ronceray J, Visset J, Marechaud R, Barbier J. Multicentrestudy of thyroid nodules in patients with Graves’ disease. Br J Surg 2000; 87:1111–1113.

2. Mishra A, Agarwal A, Agarwal G, Mishra SK. Total thyroi-dectomy for benign thyroid disorders in an endemic region.World J Surg 2001; 25:307–310.

3. Machens A, Hinze R, Lautenschlager C, Thomusch O,Dralle H. Prophylactic completion thyroidectomy for differen-tiated thyroid carcinoma: prediction of extrathyroidal soft tis-sue infiltrates. Thyroid 2001; 11:381–384.

4. Dixon E, McKinnon JG, Pasieka JL. Feasibility of sentinellymph node biopsy and lymphatic mapping in nodular thyroidneoplasms. World J Surg 2000; 24:1396–1401.

5. Miyauchi A, Matsuzuka F, Hirai K, Yokozawa T, KobayashiK, Kuma S, Kuma K, Futami H, Yamaguchi K. Unilateral sur-gery supported by germline RET oncogene mutation analysisin patients with sporadic medullary thyroid carcinoma. WorldJ Surg 2000; 24:1367–1372.

6. Machens A, Hinze R, Lautenschlager C, Thomusch O,Dunst J, Dralle H. Extended surgery and early postoperativeradiotherapy for undifferentiated thyroid carcinoma. Thyroid2001; 11:373–380.

7. Thomusch O, Machens A, Sekulla C, Ukkat J, Lippert H,Gastinger I, Dralle H. Multivariate analysis of risk factors forpostoperative complications in benign goiter surgery: prospec-tive multicenter study in Germany. World J Surg 2000; 24:1335–1341.

8. Jonas J, Bahr R. Intraoperative electromyographic identifica-tion of the recurrent laryngeal nerve [in German]. Chirurg2000; 71:534–538.

9. Hemmerling TM, Schurr C, Dern S, Schmidt J, Braun GG,Klein P. Intraoperative electromyographic recurrent laryngealnerve identification as a routine measure [in German]. Chirurg2000; 71:545–550.

10. Lamade W, Meyding-Lamade U, Buchhold C, Brauer M,Brandner R, Uttenweiler V, Motsch J, Klar E, Herfarth C. Firstcontinuous nerve monitoring in thyroid gland surgery [inGerman]. Chirurg 2000; 71:551–557.

11. Thomusch O, Sekulla C, Dralle H. Thyroid surgery with intra-operative neuromonitoring of the recurrent laryngeal nerve: aprospective study in Germany with 7617 patients. Br J Surg2000; 87:1276–1277.

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12. Brauckhoff M, Gimm O, Brauckhoff K, Ukkat J, Thomusch O,Dralle H. Calcitonin kinetics in the early postoperative periodof medullary thyroid carcinoma. Langenbecks Arch Surg 2001;386:434–439.

13. Thomusch O, Sekulla C, Dralle H. Risk analysis for hypopar-athyroidism in thyroid surgery. Prospective study with a multi-ple logistic regression analysis. Langenbecks Arch Surg 2000;385:431.

14. Miccoli P, Berti P, Raffaelli M, Conte M, Materazzi G,Galleri D. Minimally invasive video-assisted thyroidectomy.Am J Surg 2001; 181:567–570.

15. Mourad M, Ngongang C, Saab N, Coche E, Jamar F,Michel JM, Maiter D, Malaise J, Squifflet JP. Video-assistedneck exploration for primary and secondary hyperparathy-roidism: initial experience. Surg Endosc 2001; 15:1112–1115.

16. Gagner M, Inabnet WB 3rd. Endoscopic thyroidectomy forsolitary thyroid nodules. Thyroid 2001; 11:161–163.

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An update on thyroid surgery