THYROID

1. THYROID James Taclin C. Banez, M.D., FPSGS, FPCS

2. ANATOMY: • Location / Parts • Arteries / Venous drainage • Nerve Supply • Sympathetic (cervical ganglion) • Parasympathetis (vagus) • Histology: • Thyroid follicle (thyroglobulin) • C cells (neuroectoderm – 4th and 5th ultimo brachial bodies).

3. PHYSIOLOGY: • Synthesis & secrets thyroid hormone (thyroid follicle) • Iodide uptake • Oxidation of iodide to iodine • Organification (thyroxin-iodine) MIT / DIT • Coupling of inactive iodotyrosine T4 /T3 • Stored ----> released by protease / peptidase • Calcium Level • Calcitonin (C cell)

4. Evaluation of Thyroid Diseases • Clinical history and physical examination • Serum T3 & T4, TSH determination • Thyroid scan • Thyroid ultrasound • CT scan / MRI • FNAC

5. HYPERTHYROIDISM (Thyrotoxicosis) • With increase thyroid hormone secretion • Grave’s disease • Toxic nodular goiter • Toxic thyroid adenoma • With out increased thyroid hormone secretion • Sub-acute thyroiditis • Functioning metastatic thyroid cancer • Struma ovarii

6. HYPERTHYROIDISM GRAVE’S Disease (Diffuse Thyroid Goiter) • Most common form of thyrotoxicosis • Autoimmune • Female > male; most prevalent 20-40 y/o • Thyroid stimulating antibody (immunoglobulin) directed at the TSH receptor or the thyroid follicular cells. • LATS (long acting thyroid stimulating antibody) • TRAb (thyroid receptor antibody)

7. HYPERTHYROIDISM GRAVE’S Disease (Diffuse Thyroid Goiter) • Manifestations: • Signs/symptoms of thyrotoxicosis: • heat intolerance • sweating • weight loss, muscle wasting • tachycardia/atrial fibrillation • fine tremors • easy fatigability • hypoactive tendon reflexes • amenorrhea • decrease fertility • easy fatigability, agitation and excitability • diarrhea

8. HYPERTHYROIDISM GRAVE’S Disease (Diffuse Thyroid Goiter) • Triad: • diffuse goiter • thyrotoxicosis • exopthalmos • Other: • hair loss • pretibial myxedema • gynecomastia • splenomegally

9. HYPERTHYROIDISM GRAVE’S Disease: Exopthalmos: • Due to increase retro-bulbar tissue: • Spasm of the upper eyelid, revealing the sclera above the corneoscleral limbus (Dalrymple’s sign) • Lid lag (von graefes sign) • External ophthalmoplegia (inability to move the eyeball) • Supra and infraorbital swelling • Congestion and edema of the conjunctiva and sclera (chemosis) ----> ulceration • Progression --> damage of optic nerve --> decreases visual acuity and impairment of color vision (malignant exopthalmos) not corrected surgically --> blindness

10. HYPERTHYROIDISM • Diagnosis: • Autonomous thyroid function • Low TSH • Elevated T3 / T4 • Thyroid scan ---> diffuse elevated iodine uptake • Treatment: • Choices: • Antithyroid drugs • Radioactive iodine therapy • Surgery • Choice depends on: • Age • Severity of the disease • Size of the gland • Coexistent pathology (Ophthalmoplegia) • Other factors: • Patient’s preference • Pregnancy

11. HYPERTHYROIDISM Antithyroid Drugs: • Propyl thiouracil (PTU) = 100-300mg TID • Methimazole (Tapazole) = 10-20 TID then OD • Carbimazole = 40mg OD • Inhibits the organic binding of iodine and coupling of iodotyrosine • PTU can also lower conversion of T4 to T3; it can also decrease thyroid autoantibody levels • Disadvantage of these drugs. • Crosses the placenta --> inhibits fetal thyroid function • Excreted in breast milk • Side effects: • Skin rashes • Fever • Peripheral neuritis • Polyarteritis • Granulocytopenia (reversible) • Agranulocytosis / aplastic anemia (poor prognosis)

12. HYPERTHYROIDISM • Beta blockers (propranolol) – to alleviate peripheral adrenergic effects • Advised medical management • Small diffusely enlarge gland or larger glands that decreases in size due to antithyroid drugs • Toxic nodule goiters or large diffuse glands or hyperthyroidism when drug was discontinued ---> thyroidectomy / radioactive iodine

13. HYPERTHYROIDISM Radioactive Iodine Therapy: Advantages: • Avoidance of surgery (no injury to nerve / parathyroid gland) • Reduce cost & ease of treatment Disadvantages: • Lifelong thyroxin replacement therapy • Slower correction of hyperthyroidism • Higher relapse rate • Adverse effect of ophthalmopathy Suitable treatment: • Small or moderate size goiter • Relapse after medical and surgical therapy • Antithyroid drug and surgery are contraindicated Contraindicated: • Pregnant / breast feeding • Ophthalmopathy (progression of eye signs) • Isolated nodular goiter or toxic nodular goiter • Young age (children/adolescence ----> Infertility / carcinoma

14. HYPERTHYROIDISM Radioactive Iodine Therapy: Pt. is placed in euthyroid state with anti-thyroid drugs. Then discontinue the drugs for 2-3 wks before RAI tx is started (I 131 sodium iodide) Complication of RAI tx: • Exacerbations of thyrotoxicosis with arrhythmia • Overt thyroid storm • Hypothyroidism • Risk of fetal damage • Worsening of eye sign • Hyperparathyroidism

15. HYPERTHYROIDISM Thyroid Surgery: Indicated to: • Young patient • With Grave ophthalmopathy • Pregnant • With suspicious thyroid nodule in Grave’s gland • Large nodular toxic goiter w/ low level of radioactive iodine uptake. Placed patient to euthyroid state prior to thyroid surgery: • Antithyroid drugs • Lugol’s iodine solution (3 drops BID) • Propranolol Thyroidectomy: • Bilateral subtotal thyroidectomy • Total lobectomy & subtotal lobectomy contra-lateral (Hartley-Dunhill) • Total thyroidectomy Advantages over RAI: • Immediate cure of the disease • Low incidence of hypothyroidism • Potential removal of coexisting thyroid carcinoma Disadvantages: • Complication ---> nerve injury (1%) and hypoparathyroidism (13% transient/ 1% permanent). • Hematoma • Hypertrophic scar formation

16. HYPERTHYROIDISM • Recurrent thyrotoxicosis after surgery---> RAI Treatment of Exopthalmos: • Tape eyelids at night • Wear eyeglasses • Steroid eye drop / systemic steroid (60mg prednisone OD) alleviate chemosis. • Lateral tarsorrhaphy to oppose eyelids • Radio-orbital radiation or orbital decompression

17. HYPERTHYROIDISM Toxic Nodular Goiter (Plummers’ disease): • No extrathyroidal manifestation • Milder than Grave’s disease • Treatment: • Propranolol • Thyroidectomy (lobectomy with isthmectomy) Toxic adenoma: • Solitary toxic nodule (Follicular) tumor • Thyrotoxicosis is uncommon unless it is 3 cm in size or more.

18. Thyroid storm: • Life threatening • Precipitated by: • Infection (pharyngitis / pneumonitis) • Iodine 131 treatment • Prophylactic treatment: --- Surgery in euthyroid state • Treatment: • Fluid replacement • Antithyroid drug • Beta blocker • Lugol’s iodine solution • Hydrocortisone • Cooling blanket • Sedation • Extreme cases ----> peritoneal dialysis or hemofiltration to lowe T4&T3 • Avoid ASPIRIN ---> increases free thyroid hormone levels

19. HYPOTHYROIDISM Causes: • Primary: • Autoimmune thyroiditis • Hashimotos thyroiditis • Primary myxedema • Iatrogenic • Thyroidectomy • Iodine 131 tx • Antithyroid drugs • Congenital (Cretinism) • Thyroid dysgenesis • Dyshormonogenesis • Inflammatory • Subacute thyroiditis • Riedels thyroiditis • Metabolism • Iodine deficiency • Secondary: • Hypopituitarism • Hypothalamic hypothyroidism • Peripheral resistance to thyroid hormone Treatment: L-thyroxine (50-100ug)

20. THYROIDITIS • Acute Suppurative Thyroiditis • Uncommon • Associated with URTI • Staphylococcuc, Streptococcus and Pneumococci E. Coli • Sx: - acute thyroid pain - dysphagia - fever • Dx: - FNA ----> smear and CS • Tx: - IV antibiotics / drain (abscess)

21. THYROIDITIS • Nonsuppurative Thyroiditis: • Hashimotos disease (Autoimmune lymphocytic thyroiditis) • Most common form of chronic lymphocytic thyroiditis • Autoimmune disease: • Antithyroglobulin / antimicrosomal antibodies • 10 x more in females; 30 – 60y/o • Familial; 50% in first degree relatives • Predisposing factors: • Down syndrome • Familial Alzheimer’s disease • Turner syndrome • Can co-exist with papillary CA • S/Sx: - Tightness in the throat (most common) - Painless, nontender enlargement of gland • Dx: - Increase TSH, decrease T3 & T4 - (+) Anti-thyroid antibodies - FNA ---> rule out CA (confirmatory) • Tx: - Medical if w/o compression ----> thyroid hormone - Surgical: 1. Obstructive 2. Cosmetically unacceptable 3. Thyroid carcinoma coexist

22. THYROIDITIS • Nonsuppurative Thyroiditis: • Subacute Thyroiditis (De Quervans Thyroiditis / Giant Cell Thyroiditis) • Exact cause unknown • Female 5x more the males • 20 – 40 y/o • S/Sx: - Tender enlargement of the gland - Fever, malaise w/ unilateral or bilateral thyroid pain • Dx: - FNA - ESR (increase) - Neutrophilia • Tx: - NSAIDS - Prednisone

23. THYROIDITIS • Nonsuppurative Thyroiditis: • Riedels’ Thyroiditis: • Marked dense invasive fibrosis that may involve surrounding structures • Can cause hypoparathyroidism • Unknown cause ( maybe part of fibrosclerosis – retroperitoneum, mediastinum, lacrimal gland and bile duct) • S/Sx: - Compression symptoms - Hoarseness - dyspnea - stridor - dysphagia • Tx: - Tamoxifen - Steroid - Isthmectomy – to relieve compression symptom - Thyroxine replacement

24. GOITER • Enlargement of the thyroid gland in a euthyroid pt not associated with neoplasm or inflammation: • Familial: • Inherited enzymatic defect (dyshormonogenesis) • Autosomal recessive • Hypothyroidism / euthyroid • Endemic: • Iodine deficiency • Sporadic: • No definite cause, excludes goiter caused by thyroiditis and neoplasm as well as endemic goiter

25. GOITER Pathology: • May be diffusely enlarged and smooth, or enlarged markedly nodular • Nodules are filled w/ gelatinous, colloid rich material and scattered between areas of normal thyroid tissues • With areas of degeneration, hemorrhage and calcification.

26. GOITER S/Sx: • Asymptomatic usually • Pressure symptoms usually • Dysphagia • Dyspnea • Paralysis of recurrent laryngeal nerve • Sudden pain associated with rapid enlargement of the gland ---> hemorrhage into a colloid nodule or cyst • Superior mesenteric syndrome due retro-sternal extension causing facial flushing that is accentuated by raising his arm above the head (Pemberton’s sign).

27. GOITER Dx: • FNAC ---> specially if one nodule predominates, or painful or has recently enlarged. To rule out CA • TSH, T3 & T4 ---> usually normal ---> pts > 60y/o w/ long standing multinodular goiters (>17yrs) develops thyrotoxicosis (Plummer’s dse). Low TSH w/ increased T3 but normal T4 (T3 toxicosis) Tx: • No tx for euthyroid, small, diffuse goiter • Thyroxine ---> for large diffuse goiter; to depress TSH stimulation and reduce hyperplasia • Iodine ---> for endemic goiter • Surgery: • Cosmetically acceptable • Compression symptoms • Suspicion for malignancy

28. Solitary or Dominant Thyroid Nodule • Most are benign (colloid nodule/adenomas) Physician should: • Perform an accurate clinical assessment • Appreciate the risk factors for thyroid carcinoma • Which pts would benefit from surgery Risk factors for thyroid CA: • Low-dose radiation to head & neck (<2000 rad) - >2000rads causes destruction of thyroid gld. - tends to be papillary type, multi-focal w/ higher incidence of LN metastases. • Family hx of thyroid CA - Medullary CA – inherited as an autosomal dominanat trait - Papillary CA – 6% familial dse. • Age - thyroid nodule in children and elderly are more likely to be malignant. • Signs • Rapid enlargement of an old or new nodule • Symptoms of local invasion or compression symptoms • Consistency: Hard, gritty or fixed to surrounding structures • Palpable cervical lymphadenopathy • A cyst larger than 4 cm in diameter or in ultrasound is complex has 15% incidence of malignancy

29. Solitary or Dominant Thyroid Nodule Work up for Thyroid nodule: • FNAC– procedure of choice benign - 65% false (+) - 1% malignant - 5% false (-) - 5% Suspicious - 15% Non-diagnostic 15% • Limitation of FNAC: • Follicular or Hurtle cell neoplasm (needs vascular and capsular invasion) • Hx of head and neck radiation and family hx of thyroid CA usually has multifocal lesions. • If FNAC encountered a cyst ---> drain completely 75% is curative; if cyst persist after 3 attempts ---> unilateral lobectomy

30. Solitary or Dominant Thyroid Nodule Work up for Thyroid nodule: • Thyroid ultrasonography: • Use to a) follow up the size of suspected benign nodules diagnosed by FNAC b) to detect presence of non-palpable nodules to locate and differentiate it for cyst or solid • MRI / CT scan: • For large retro-sternal extension • For recurrent or persistent thyroid tumor and to differentiate recurrence from postoperative fibrosis • Detect the presence of invasion, sign of CA.

31. Solitary or Dominant Thyroid Nodule Work up for Thyroid nodule: • Thyroid isotope imaging: • Check the function and locate small lesions • Cold -----------> 10 – 25% malignant • Hot -----------> 1% malignant • Laboratory: • Thyroid function test: • Not useful in assessing thyroid nodule • Serum thyroglobulin level: • To detect presence of metastatic lesions • Check completion of thyroidectomy • Not used in medullary and anaplastic thyroid CA • Serum calcitonin: • Follow up in medullary CA • RET oncogens (+) pt should have 24 hrs urine determination of VMA, metanephrine and cathecolamine to rule out a coexisting pheochromocytoma (for medullary CA)

32. Solitary or Dominant Thyroid Nodule Approach for Thyroid Nodule

33. MALIGNANT THYROID • 90 – 95% are differentiated tumor w/ follicular origin • Papillary thyroid adenocarcinoma • Follicular adenocarcinoma • Hurtle cell carcinoma • 6% arise from parafollicular cells: • Medullary carcinoma of thyroid • 1% poorly differentiated • Anaplastic thyroid carcinoma

34. MALIGNANT THYROID Oncogene associated w/ Thyroid carcinoma: • RET oncogene: • Seen in papillary and medullary thyroid CA • Located in chromosome 10 • TRK – A: • Chromosome 1 • Mutated ras oncogenes: • Follicular thyroid carcinoma, thyroid adenoma and multinodular goiter • Mutated p53 gene: • Anaplastic thyroid carcinoma

35. MALIGNANT THYROID Papillary Thyroid Carcinoma: • Most common (80%) • Predominant thyroid CA in children (75%) • Usually due to radiation exposure of the neck (85-90%) • Multi-focal (30-88%); has LN spread (para-tracheal & cervical LN). • Can invade trachea, esophagus and recurrent laryngeal nerve; late hematogenous spread. • Mixed tumor (papillary & follicular): variant of papillary CA, but classified as papillary for it biologically acts as papillary CA. • Orphan Annie Nuclei: • Characteristic cellular feature • Abundant cytoplasm, crowded nuclei and intra-nuclear cytoplasmic inclusion

36. MALIGNANT THYROID Papillary Thyroid Carcinoma: 3 forms of papillary CA (based on size and extent): • Minimal or occult / micro carcinoma • 1 cm or less, no capsular invasion • Non-palpable and usually an incidental finding intra-op or autopsy • Recurrence rate ----> 7% • Mortality ------------> 0.5% • Intra-thyroidal Tumors: • > 1cm and confined to the thyroid gland • (-) extra thyroidal invasion • Extra-thyroidal Tumors: • Locally advanced with invasion through the thyroid capsule into adjacent structures. • All types can be associated w/ LN metastases and intra-thyroidal blood vessel invasion or occasionally metastases

37. MALIGNANT THYROID Papillary Thyroid Carcinoma: S/Sx: • Euthyroid, slow growing painless mass • Signs of local invasions: • Dysphagia • Dyspnea • Hoarseness of voice • Palpable cervical LN more apparent than primary lesion (lateral aberrant thyroid) • Uncommon distant metastases (lung metastases in children) Diagnosis: • FNAC (specific and sensitive for papillary, medullary and anaplastic) • CT/MRI in pts w/ extensive local or sub-sternal extension

38. MALIGNANT THYROID Papillary Thyroid Carcinoma: Prognostic indicators: (85% 10yrs survival) • AGES scale: A- age G- grade E- extent S- size • MACIS scale: M- metastases A- age C- completeness of resection I- extra thyroidal invasion S- size • AMES • TNM • Distant metastases (bone): most significant prognostic indicator overall

39. MALIGNANT THYROID Papillary Thyroid Carcinoma: (SURGERY) • Lobectomy with isthmectomy acceptable for minimal papillary thyroid CA • Total thyroidectomy (near total) if: • Size: if tumor > 3cm • Age: male > 40y/o female > 50y/o • Angioinvasion • Distant metastases • Thyroidectomy w/ modified radical neck dissection: • If with clinically palpable cervical lymphadenopathy • Not done for prophylaxis • Reasons for total thyroidectomy: • 85% is multifocal • To decrease incidence of anaplasia in any residual tissue • Facilitate the diagnosis of unsuspected metastatic disease by RAI scanning or treatment • Greater sensitivity of blood thyroglobulin level to predict recurrent or persistent of the disease.

40. MALIGNANT THYROID Follicular Thyroid Carcinoma: • 10%; Female > Male (3:1), mean age= 50y/o • More frequent in Iodine deficiency area • Vascular invasion & hematogenous spread is more common (bone, lung and liver). • Types: • Minimally invasive tumor: • Invasion into but not through the tumor capsule • Previously called atypical adenoma • Invasive tumors (capsular/vascular) • 1% thyrotoxic • Dx / Tx: • FNAC not helpful ----> lobectomy and isthmectomy (frozen section) ----> (+) total thyroidectomy ----> iodine 131 to detect distant metastases and for ablation. • Prognosis: • Age over 50y/o • > 4cm size • Higher tumor grade • Marked vascular invasion • Marked extra-thyroidal invasion • Distant metastasis • Mortality: 40 % ----> 10 yrs

41. MALIGNANT THYROID HURTLE CELL THYROID TUMOR: • 3 – 5%, intermediate, uni-focal • Male : Female (2:1), spread by lymphatics • Derived from oxyphilic cells of the thyroid gld. • Possess TSH receptors and produces thyroglobulin • Only 10% takes up iodine hence thallium scan is used to localize distant metastasis • Often multifocal and bilateral Dx: FNAC ----> 20% malignant Tx: - total thyroidectomy for RAI ablation usually fails - mod radical neck dissection if with palpable cervical LN - Thyroid suppression is suggested Prognosis: 60% ------> 5yr survival

42. MALIGNANT THYROID MEDULLARY THYROID CARCINOMA: • 5-7%; Aggressive tumor; 50-60y/o • Arise from parafollicular or C cells of the thyroid (neuroectodermal-ultimobrachial bodies 4th &5th branchial pouches. • Secrets calcitonin (95%); 85% secrets carcinoembryonic antigen (CEA) • Sporadic 90% • unifocal, usually 45y/o • worse prognosis • Familial 10% • Associated with: • MEN IIA or Sipples’ syndrome (MTC, hyperplastic parathyroid and pheochromocytoma • MEN IIB (MTC, pheochromocytoma, ganglioneuromatosis and Marfan,s syndrome) • Multifocal, usually 35 y/o • Better prognosis

43. MALIGNANT THYROID MEDULLARY THYROID CARCINOMA: • Does not concentrate Iodine 131, Thallium scan is used to localized distal metastasis. • Spread: • Lymphatics (neck and superior mediastinum) • Blood ---> liver, bone (osteoblastic) and lung • Local invasion • Can secrets: • Calcitonin • Histamine • Serotinin (causes diarrhea) • ACTH 2-4% causing Cushing syndrome • CEA • Prostaglandin E2 and F2 alpha Dx: • Hx ‘ PE; serum calcitonin, CEA, FNAC, Serum calcium

44. MALIGNANT THYROID Tx: • Total thyroidectomy • Radiotherapy and chemotherapy ---> failure • MRND is done for: • Palpable cervical LN • >2cm tumor for 60% nodal metastasis • Tumor debulking in cases of metastatic and local recurrence should be done to ameliorate symptoms of flushing and diarrhea and help to decrease the risk of death. • All pt should be screen for pheochromocytoma (MEN II) w/c shoud be resected first. • Selective removal of the parathyroid shd be done if preoperatively has hypercalcemia. Follow up: - serum calcium / CEA level Prognosis: • Localize -------> 80% 10 year survival (+) LN --------> 45% 10 year survival • Best ------------> Worst prognosis Familial non-MEN MTC -----> MEN IIA ----> Sporadic cases ------> MEN IIB

45. MALIGNANT THYROID Anaplastic Thyroid Carcinoma: • 1 – 3% most aggressive, few survive > 6 months • Most arise from previous differentiated thyroid CA • Low incident could be due to low iodine deficiency • 70 – 80 y/o Treatment: • Radiotherapy ----> doxorubicin ----> debulking thyroidectomy ----> completion with radiotherapy and chemotherapy

46. MALIGNANT THYROID LYMPHOMA: • 1 – 5% non-Hodgkin B cell • Usually develops in pts w/ chronic lymphocytic thyroiditis (Hashimotos thyroiditis) • S/Sx similar with anaplastic CA, compression symptoms is the most common • Tx: Chemotherapy • Cyclophosphamide • Doxorubicin • Vincristine • Prednison Radiotherapy Surgery: - done for diagnosis and to alleviate compression symptoms • 80% survival if confined to the gland; 40% it had spread Metastatic Carcinoma: • Rare; hypernephroma is the most common primary site

47. Thankyou