Diseases of Thyroid and Parathyroid Gland

8/13/2019 Diseases of Thyroid and Parathyroid Gland

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DISEASES of THYROID and

PARATHYROID GLANDBy:

Shalimar C. Cortez, M.D. FPSGS, FPCSSurgical Oncology


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OBJECTIVES-To review the anatomy of Thyroidand Parathyroid gland.

- To review Thyroid and Parathyroid

gland physiology

- To discuss the different diseases andits pathophysiology

-To discuss the different treatmentoptions.


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Thyroid Gland

Arises as an outpouching of the primitive

foregut during 3rdweek of pregnancy.

Originates at the base of the tongue in the

foramen ceacum.

Descends in the neck anteriorly.

Follicles are apparent by 8 weeks and colloidformation begins at 11 weeks of pregnancy.


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Thyroid Physiology


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Iodine Metabolism

Average daily requirement is 0.1 mg.

Iodine is converted to iodide in the stomach

and jejunum.

Iodide is actively transported into follicular

cells.

Thyroid is major storage site for 90% of iodinein the body.


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Iodine transport

Na+/I-symport proteincontrols serum I-uptake

Based on Na+

/K+

antiport potential

Stimulated by TSH

Inhibited by Perchlorate


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Thyroid hormone formation

Iodide trapping: transport of iodide intothyrocyte through Na/I symport.

Oxidation of iodide and Iodination of

tyrosine residues on thyroglobulinforming MITs and DITs.

Coupling: DIT+DIT = T4 (thyroxine); MIT +

DIT = T3 (triiodothyronine). Hydrolysis to release T3 and T4 hormone.


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Thyroid Hormone

T4 is produced and released entirely by

the thyroid gland.

Thyroid gland produced 20% of T3 (morepotent).

Thyroid hormones are bounded by

thyroxine-binding globulin, thyroxinebinding pre albumin, and albumin.


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Thyroid Hormone Control


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Thyroid Hormone Function

Affects almost every system in the body. Important for fetal brain development and

skeletal maturation.

Increases oxygen consumption, basalmetabolic rate and heat production.

Positive inotropic and chronotropic effect on

the heart. Increase gastrointestinal motility; bone and

protein turnover; speed of muscle contraction

and relaxation.


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Thyroid Function Evaluation

TRH TSH

Total T3, T4

Free T3, T4

Thyroglobulin

Antibodies: Anti-Tg; anti-TPO;TSI(thyroid stimulating Ig)

Thyroid Imaging (Radionuclide Imaging;

Ultrasound; CT/MRI)


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Thyroid Evaluation


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Iodine states

Normal Thyroid

Inactive Thyroid

Hyperactive Thyroid


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Common Thyroid Disorders


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GOITER (guttur)

Recognized since 2700 B.C.

In 1619, recognized that goiter arose from the

thyroid gland.

As ductless gland with functions ranging fromlubrication of the larynx; reservoir for blood;

beautifying womens neck.

In 1170, first account of thyroid surgery (RogerFrugardi)

In 1909, physiology, pathology, and surgery of

the thyroid gland were recognized.


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Goiter Goiter: Chronic enlargement of the thyroid gland not

due to neoplasm Endemic goiter

Areas where > 5% of children 6-12 years of age havegoiter

Common in China and central Africa Sporadic goiter

Areas where < 5% of children 6-12 years of age havegoiter

Multinodulargoiterin sporatic areas often denotesthe presence of multiple nodules rather than grossgland enlargement

Familial


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Goiter Etiology

Hashimotos thyroiditis

Early stages only, late stages show atrophicchanges

May present with hypo, hyper, or euthyroid states

Graves disease Due to chronic stimulation of TSH receptor

Diet Brassica (cabbage, turnips, cauliflower, broccoli)

Cassava

Chronic Iodine excess Iodine excess leads to increased colloid formation and can

prevent hormone release If a patient does not develop iodine leak, excess iodine can

lead to goiter

Medications Lithium prevents release of hormone, causes goiter in 6% of

chronic users Neo lasm


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Goiter Pathogenesis

Iodine deficient areas Heterogeneous response to TSH

Chronic stimulation leads to multiple nodules

Iodine replete areas Thyroid follicles are heterogeneous in their growth and activity

potential

Autopsy series show MNG >30%.

Thyroid function evaluation TSH, T4, T3

Overt hyperthyroidism (TSH low, T3/T4 high)

Subclinical hyperthyroidism (TSH low, T3/T4 normal)

Determination of thyroid state is key in determining

treatment


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Non-Toxic Goiter Cancer screening in non-toxic MNG

Longstanding MNG has a risk of malignancy identical tosolitary nodules ( 4cm should be

excised No FNA needed due to poor sensitivity Incidence of cancer (up to 40%)

FNA in MNG Sensitivity 85% - 95% Specificity 95% Negative FNA can be followed with annual US Insufficient FNAs should be repeated Inconclusive FNA or papillary cytology warrants

excision Hyperfunctioning nodules may mimic follicular neoplasm

on FNA


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Non-Toxic GoiterTreatment options (no compressive symptoms)

US follow-up to monitor for progression

Thyroid suppression therapy

May be used for progressive growth May reduce gland volume up to 50%

Goiter regrowth occurs rapidly following therapycessation

Surgery Suspicious neck lymphadenopathy

History of radiation to the cervical region

Rapid enlargement of nodules

Papillary histology

Microfollicular histology (?)


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Toxic Goiter Evaluate for

Graves disease

Clinical findings (Pretibial myxedema, Opthalmopathy)

Anti-TSH receptor Ab

High RAUI

Thyroiditis

Clinical findings (painful thyroid in Subacute thyroiditis) Low RAUI

Recent Iodine administration

Amiodarone

IV contrast

Change in diet

FNA evaluation Not indicated in hyperthyroid nodules due to low incidence of

malignancy

FNA of hyperthyroid nodules can mimic follicular neoplasms


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Toxic Goiter

Risks of hyperthyroidism

Atrial fibrillation

Congestive Heart Failure

Loss of bone mineral density

Risks exist for both clinical or subclinical disease

Toxic Goiter

Toxicity is usually longstanding

Acute toxicity may occur in hyperthyroid states (JodBasedow effect) with

Relocation to iodine replete area

Contrast administration

Amiodarone (37% iodine)


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Toxic Goiter Treatment for Toxic MNG

Thionamide medications Not indicated for long-term use due to complications

May be used for symptomatic individuals until definitivetreatment.

Radioiodine

Primary treatment for toxic MNG Small goiters

Absence of pressure symptoms

Disorders which preclude surgery

Refusal of an operation Surgery

Used for compressive symptoms

Hypothyroidism occurs in up to 70% of subtotalthyroidectomy patients

Pre-surgical stabilization with thionamide medications


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Graves Disease Most common cause of thyrotoxicosis in the industrialized

world. Autoimmune condition with thyroid stimulating antibodies

with female preponderance; peak at ages 40 and 60.

-Postpartum state, iodine excess, lithium therapy, infections as

possible triggers. Diagnosis

TSH, T4, T3to establish thyrotoxicosis; diffuse goiter; extrathyroidalconditions( ophthalmopathy;dermopathy..)

RAIU in Hyperthyroid StatesHigh Uptake Low Uptake

Graves Subacute Thyroiditis

Toxic MNG Iodine Toxicosis

Toxic Adenoma Thyrotoxicosis factitia


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Graves Disease

Treatment Beta blockers for symptoms Thionamide medications

May re-establish euthyroidism in 6-8 weeks

40% - 60% incidence of disease remission

20% incidence of allergy (rash, itching) 0.5% incidence of potentially fatal agranulocytosis

Radioiodine ablation 10% incidence of hypothyroidism at 1 year

55% - 75% incidence of hypothyroidism at 10 years

Avoid RAI in children and pregnancy. Surgery

Large goiters not amenable to RAI

Compressive symptoms

Children, pregnancy

Relapse after drug therapy Intractable side effects/ failure of compliance


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Toxic Adenoma

Thyrotoxicosis Hyperfunctioning nodules 3 cm.

Treatment Indications Post-menopausal female

Due to increased risk of bone loss

Patients over 60 Due to high risk of atrial fibrillation

Adenomas greater than 3 cm (?)


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Toxic Adenoma Treatments

Antithyroid medications Not used due to complications of long-term treatment

Radioiodine Cure rate > 80% (20 mCi I131)

Hypothyroidism risk 5% - 10%

Second dose of I131 needed in 10% - 20%

Patients who are symptomatically toxic may require control withthionamide medications before RAI to reduce risk of worseningtoxicity.

Surgery

Preferred for children and adolescents Preferred for very large nodules when high I131 doses needed

Low risk of hypothyroidism

Ethanol Injection Rarely done in the US

May achieve cure in 80%


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Hypothyroidism

Symptomsfatigability, coldness, weight gain,constipation, low voice

SignsCool skin, dry skin, swelling of face/hands/legs,

slow reflexes, myxedema NewbornRetardation, short stature, swelling of

face/hands, possible deafness Types of Hypothyroidism

PrimaryThyroid gland failureSecondaryPituitary failureTertiaryHypothalamic failurePeripheral resistance


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Hypothyroidism

Cause is determined by geography Hashimotos in industrialized countries

May be due to iodine excess in some costal areas

Diagnosis Low FT4, High TSH (Primary, check for antibodies)

Low FT4, Low TSH (Secondary or Tertiary, TRH

stimulation test, MRI)

Treatment Levothyroxine (T4) due to longer half life

Treatment prevents bone loss, cardiomyopathy,myxedema


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Hypothyroidism

Agenesis

Thyroid destruction Hashimotos thyroiditis

Surgery

I131ablation

Infiltrative diseases

Post-laryngectomy

Inhibition of function Iodine deficiency

Iodine administration

Anti-thyroid medications (PTU, Methimazole, Lithium, Interferon)

Inherited defects

Transient Postpartum

Thyroiditis


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Thyroiditis


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Hashimotos Thyroiditis Most common cause of goiter and hypothyroidism in the U.S.

Physical Painless diffuse goiter

Lab studies

Hypothyroidism

Anti TPO antibodies (90%)

Anti Thyroglobulin antibodies (20-50%)

Acute Hyperthyroidism (5%)

Treatment

Levothyroxine if hypothyroid

Triiodothyronine (for myxedema coma)

Thyroid suppression (levothyroxine) to decrease goitersize

Stop therapy if no resolution noted

Surgery for compression or pain.


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Silent ThyroiditisPost-partum Thyroiditis

Silent thyroiditis is termed post-partum thyroiditis if it occurs withinone year of delivery.

Clinical

Hyperthyroid symptoms at presentation

Progression to euthyroidism followed by hypothyroidism for upto 1 year.

Hypothyroidism generally resolves

Diagnosis

May be confused with post-partum Gravesrelapse

Treatment

Beta blockers during toxic phase No anti-thyroid medication indicated

Iopanoic acid (Telopaque) for severe hyperthyroidism

Thyroid hormone during hypothyroid phase. Must withdraw in6 months to check for resolution.


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Subacute ThyroiditisDeQuervains, Granulomatous

Most common cause ofpainful thyroiditis

Often follows a URI

FNA may revealmultinuleated giant cells orgranulomatous change.

Course

Pain and thyrotoxicosis(3-6 weeks)

Asymptomatic

euthyroidism Hypothyroid period

(weeks to months)

Recovery (complete in95% after 4-6 months)


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Subacute ThyroiditisDeQuervains, Granulomatous

Diagnosis Elevated ESR

Anemia (normochromic, normocytic)

Low TSH, Elevated T4 > T3, Low anti-TPO/Tgb

Low RAI uptake (same as silent thyroiditis)

Treatment NSAIDs and salicylates.

Oral steroids in severe cases

Beta blockers for symptoms of hyperthyroidism, Iopanoic acid for

severe symptoms PTU not indicated since excess hormone results from leak instead of

hyperfunction

Symptoms can recur requiring repeat treatment

Gravesdisease may occasionally develop as a late sequellae


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Acute Thyroiditis

Causes 68% Bacterial (S. aureus, S. pyogenes)

15% Fungal

9% Mycobacterial

May occur secondary to Pyriform sinus fistulae

Pharyngeal space infections

Persistent Thyroglossal remnants Thyroid surgery wound infections (rare)

More common in HIV


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Acute Thyroiditis

Diagnosis Warm, tender, enlarged thyroid

FNA to drain abscess, obtain culture

RAIU normal (versus decreased in DeQuervains)

CT or US if infected

Treatment High mortality without prompt treatment

IV Antibiotics Nafcillin / Gentamycin or Rocephin for empiric therapy

Search for pyriform fistulae (BA swallow, endoscopy)

Recovery is usually complete


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Riedels Thyroiditis

Rare disease involving fibrosis of the thyroid gland

Diagnosis Thyroid antibodies are present in 2/3

Painless goiter woody

Open biopsy often needed to diagnose

Associated with focal sclerosis syndromes (retroperitoneal,mediastinal, retroorbital, and sclerosing cholangitis)

Treatment Resection for compressive symptoms

Chemotherapy with Tamoxifen, Methotrexate, or steroidsmay be effective

Thyroid hormone only for symptoms of hypothyroidism


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ThyroidCancer


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Leading Cancer Sites in 2005, Philippines

1. Bronchus,lung 17,238 16.1%

2. Breast 14,043 13.1%

3. Colon/Rectum 8,585 8.0 %

4. Liver 7,629 7.1%

5. Cervix,uteri 7,277 6.8%

6. Prostate 4,254 4.0%

7. Leukemia 4,202 3.9%

8. Stomach 3,932 3.7%

9. Thyroid 3,521 3.3%

10. Ovary 3,283 3.1%


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Leading Cancer Sites in 2005, Philippines

11. Oral Cavity 3,054 2.9 %

12.Nasopharynx 2,793 2.6 %

13.Non-Hodgkin lymphom 2,492 2.3 %

14.Pancreas 1,681 2.4 %15.Pancreas 1,873 1.8 %

16.Corpus uteri 1,777 1.7 %

17.Larynx 1,723 1.6 %

18.Kidney 1,518 1.4 %

19.Brain, nervous system 1,509 1.4 %

19.Bladder 1,360 1.3 %

20.Other pharynx 1,059 1.0 %


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Incidence of thyroid cancer

9thmost common for both sexes combined(3.3%), 15thleading site in men ( 1.5%) and6thamong females (5%)

In 2005, estimated 3,521 new cases, 755 inmales and 2,766 in females.

There will be 1,012 deaths, 245 in males and767 in females.


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Most common cancer of women at ages 15-

24

Incidence among female residents in the

Philippines is among the highest observed

worldwide


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Histologic Variants

PAPILLARYmost common form (60 -70%) withstrong association with radiation to the head andneck.

FOLLICULARaccount for 25% of cases with

female preponderance. More aggressive thanpapillary with tendency to spread viahematogenous route.

MEDULLARYneuroendocrine carcinoma (5-

10%). UNDIFFERENTIATED - accounts for 10 -15% of

cases with extensive local invasion.


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PARATHYROID GLAND


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Anatomy

Precise location is variable but tends to be

symmetrical.

Size is 1mm x 3mm x 5 mm; weighs 30 mg.

Blood supply for both pairs is from inferior

thyroid gland.


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Cellular Structre

Chief cellsmanufacture and secrete

parathyroid hormone

Oxophil cellsfunction is poorly understood.


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Parathormone

- Stimulation of the activity of osteoclast in

bone.

- Enhancement of the absorption of calcium

from the gut into the bloodstream.

- Increase in the reabsorption of calcium by the

renal tubules.


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PARATHYROID CARCINOMA

Condition is very, with invasion of local tissues and recurrenceafter excision.

Metastasis is uncommon

Death is caused hypercalcemia.

The criteria that should alert the clinician to the possibility of

this diagnosis can be divided into preoperative,intraoperative, and histopathologic findings.


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Preoperative Findings

2. Markedly abnormal biochemistry

- the biochemical parameters used for thediagnosis of hyperparathyroidism are highlyabnormal.

- Mean serum calcium levels usually aregreater than 13.0 mg/dL (normal range is 8.9to 10.1 mg/dL), parathyroid hormone levelsare elevated tenfold, and alkaline phosphatase

levels are elevated threefold.


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Preoperative Findings

3. Complications of hyperparathyroidism

- Bone disease, renal insufficiency, andnephrolithiasis occurred in 91 percent, 84percent, and 56 percent, respectively, ofpatients with parathyroid carcinoma, which

are considerably higher than the rates foundin nonmalignant hyperparathyroidism.


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Intraoperative Findings

- parathyroid mass that is firmer than the usual

soft, friable, nonmalignant parathyroid gland.

- when a gland has been transformed from the

normal bean shape and kidney color to an irregular,pale white and is adherent to any of the surrounding

structures, the diagnosis of malignancy is almostcertain.


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Histopathologic Findings

- Most weigh more than 2000 mg

- The hallmark of malignancy histologically are the presenceof a thick, fibrous capsule, fibrous septa interdigitatingthroughout the tumor, and the enlargement, hyperchromasia,and variation of nuclear size.

- Clear-cut invasion through the capsule to involve adiposetissue, nerves, thyroid gland, or surrounding muscle usually ispresent.


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Treatment :

- treatment of choice is en bloc surgical resection of thetumor and the involved surrounding structures.

- This treatment usually involves a total thyroid lobectomy onthe affected side.

- Regional nodal metastases are uncommon, but lymph nodes

should be assessed and, if involved, surgically treated byappropriate resection, which may include a modified radicalneck dissection.


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Treatment :

- When recurrent disease is seemingly localized,

repeat surgical resection.- Nonsurgical treatment modalities are inadequate.

-the 3-year and 5-year survival rates were 84 and 69

percent, respectively.

- the cause of death often was attributed to the

metabolic consequences of hypercalcemia and not to

the local effects of malignancy.

Documents

Diseases of Thyroid and Parathyroid Gland