Diseases of thyroid gland

1. Diseases of thyroid gland Dr. Krishna

2. Goitre

3. Classification of goitre 1. Simple (non-toxic) goitre – Diffuse – Multi-nodular – Colloid (large size, soft consistency, due to iodine deficiency) 2. Toxic – Diffuse (Graves’ disease) – Multi-nodular (Plummer’s disease) – Solitary nodule 3. Inflammatory : thyroiditis 4. Thyroid neoplasm: benign (adenoma),

5. Multi-nodular goitre (MNG)

6. Etiology 1. Iodine excess 2. Iodine deficiency : Endemic, Sporadic, Familial 3. Goitrogens ( eg. Cabbage, drugs like phenytoin)

7. Pathogenesis of goitre Iodine deficiency → Hypothyroidism →Increased TSH Diffuse goitre Follicles grow heterogeneo usly Nodular goitre Follicles continue to secrete T4 despite subsequent decrease in TSH levels Toxic goitre Diffuse hypertrop hy of thyroid follicles Increased TSH

8. Hypothyroidism

9. Etiology

10. A. Primary hypothyroid (99% cases) : defect in thyroid • Iodine deficiency: common in developing countries • Hashimoto’s : common in developed countries • Subacute thyroiditis • Thyroidectomy / iodine ablation / external RT to neck • Drug-induced: Lithium, amiodarone, anti- thyroid drugs

11. Common features of Hypothyroidism Symptoms Signs • Tiredness, weakness • Dry skin, hair loss • Feeling cold • Difficulty in concentration • Constipation • Weight gain with poor appetite • Dyspnea & hoarse voice • • Dry coarse skin • Cool peripheral extremities • Puffy face & extremities (myxedema) • Diffuse alopecia • Bradycardia • Peripheral edema • Delayed reflex

12. Thyroiditis

13. Classification of Thyroiditis 1. Acute: bacterial, fungal, post- radiation 2. Sub-acute – Granulomatous / painful (De Quervain's) – Lymphocytic / painless – Silent / post-partum 3. Chronic – Autoimmune: Hashimoto, atrophic

14. Hashimoto’s Thyroiditis • Commonest cause of hypothyroidism in U.S. • Associated with other autoimmune diseases – Pernicious anemia, rheumatoid arthritis, vitiligo, type 1 diabetes

15. Investigations • High TSH , Low T3 and T4 • Anti thyroid peroxidase antibodies (90%) • Anti thyroglobulin antibodies (20 - 50%) • Hyperthyroidism (5% ) • Histopathological exam – Lymphocytic infiltration , atrophy of thyroid follicles, absence of colloid,

16. Treatment • Oral Thyroxine: 25 µg & increase gradually to 100 -150 µg/day to get serum TSH in normal range • Primary adrenal insufficiency should be ruled out (with synthetic ACTH stimulation test) prior to initiating

17. Subacute Thyroiditis • Synonym: De Quervain’s or granulomatous thyroiditis • Commonest cause of painful thyroiditis • Etiology: inflammatory destruction of thyroid gland often following upper respiratory tract infection • Clinical course: painful thyrotoxicosis (3-6

18. Clinical phases

19. • Diagnosis : Elevated ESR , low or absent uptake of I 131 • Treatment – NSAIDs for pain – High doses of oral steroids in severe cases (↓ thyroid hormone binding proteins; ↓ peripheral conversion of T4 to T3; ↓ inflammation – Propranolol for symptomatic hyperthyroidism • Anti-thyroid drugs not indicated since hyperthyroidism results from release of T3 & T4 into circulation instead of thyroid hyper-function

20. Reidel’s Thyroiditis • Etiology: unknown (? auto-immune) • C/F: woody-hard thyroid gland with pain, dysphagia or stridor (due to compression), hypothyroidism, retroperitoneal fibrosis & sclerosing cholangitis • Diagnosis: MRI of thyroid, open biopsy • HPE: replacement of thyroid gland with dense fibrosis • Rx: surgical debulking for compressive symptoms, chemotherapy (tamoxifen or

21. Silent Thyroiditis • Synonym : post-partum (within 1 year) thyroiditis • Clinical course: Hyperthyroid at presentation → euthyroid → hypothyroid (resolves within 1 year) • Treatment

22. T4 T3 TSH Antibodies Hashimoto' s thyroiditis Low Normal or Low High Anti-TPO + ve in 90% Anti- Tg +ve in 50% Subacute thyroiditis Low Normal or Low High - Secondary hypothyroi d Low Normal or Low Low or norma l - Tertiary hypothyroi d Low Normal or Low Low or norma l -

23. Sick euthyroid syndrome • Low serum levels of T3 & T4 in clinically euthyroid patients due to non-thyroidal systemic illness • Etiology: starvation, protein-energy malnutrition, major trauma, myocardial infarction, chronic renal failure, diabetic

24. • Pathogenesis: decreased peripheral conversion of T4 to T3, decreased binding of thyroid hormones to thyroxine-binding globulin (TBG) caused by tumor necrosis factor-α & Interleukin -1 • Diagnosis: decreased T3 & increased reverse T3, T4 may be decreased, normal TSH

26. Thyrotoxicosis

27. Etiology

28. 1. Primary hyperthyroidism: low serum TSH – Graves' disease (commonest) – Toxic adenoma – Toxic multi-nodular goiter – Iodine excess 2. Secondary hyperthyroidism: normal serum TSH – TSH producing pituitary adenoma – Pituitary resistance to thyroid hormone suppression

29. 3. Thyrotoxicosis without hyperthyroidism: – Subacute thyroiditis – Thyrotoxicosis factitia – Thyroid cancer metastasis – Struma ovarii – Amiodarone thyroiditis – Radiation thyroiditis

30. Common symptoms & signs of thyrotoxicosis Symptoms • Hyperactivity, irritability • Heat intolerance, sweating • Palpitations • Fatigue • Weight loss with ↑ed appetite • Diarrhea • Polyuria Signs • Tachycardia • Graves’ ophthalmopathy • Atrial fibrillation in elderly • Tremor • Goitre (thyroid swelling) • Warm, moist skin • Proximal myopathy

31. Graves’ disease

32. • Commonest form of thyrotoxicosis (80- 90%) • Female : male = 5-10 : 1; • Age: 30-50 years • Etiology: – Thyroid Stimulating Immunoglobulins (TSI) • Antibodies against TSH receptor (TSHR- Ab) which act as TSH receptor

33. Clinical features • Symmetric, firm, rubbery, pulsating, warm, goitre • Thyrotoxicosis: palpitations, fine tremors, diarrhea, excessive sweating, heat intolerance, weight loss • Eye signs and Graves’ ophthalmopathy

34. Eye signs • Von Graefe: upper eyelid lag when pt looks down • Griffith: lower eyelid lag when pt looks up • Joffroy: absence of forehead wrinkling on looking up • Moebius: lack of medial convergence of eyeballs • Dalrymple: display of upper sclera • Stellwag: staring look due to absence of

35. Graves’ ophthalmopathy (seen in 3% cases) • Infiltrative: – Periorbital edema, proptosis, chemosis, extraocular muscle palsy (commonly inferior rectus), keratitis & loss of vision (optic nerve involvement) – Unaffected by thyrotoxicosis treatment • Non-infiltrative: – Lid retraction, stare & lid lag. Due to hyperactivity of sympathetically innervated

36. Graves’ ophthalmopathy

37. Graves’s dermopathy Thickening of skin in anterior tibial area due to deposition of glycos- aminoglycans which cause local fluid

38. Investigations • Increased total T4 and T3 levels • Ratio of T3 (ng/dL) to T4 (mcg/dL) > 20 • Suppressed serum TSH • Thyroid scan: diffuse, symmetric, increased uptake • Thyroid antibodies: TSI (TSHR-Ab) specific for Graves’ disease, anti-TPO and anti-Tg may be

39. Medical treatment • Carbimazole: 5-15 mg TID for 12-18 months • Propylthiouracil (PTU): 50-100 mg TID for 12-18 mth – After 12-18 mths, positive TSHR-Ab = 90% risk of recurrence, negative TSHR- Ab = 20% risk • Propranolol: 20 mg TID ( for tremor & tachycardia)

40. Radioactive iodine (I-131) • Indications: – Failed / refused / contraindicated medical therapy or surgery • Contraindications: – Pregnancy, age < 30 yr , ophthalmopathy, low RAIU (< 5%) • 5 - 10 m Ci orally for 4 -12 wk – Effective in 75% cases • For thyrotoxicosis after 12 wks: double dose

41. Total Thyroidectomy • Indications: – Age < 30 yr, pregnancy, compression of trachea by goitre, suspected cancer, ophthalmopathy • Pre-operative treatment: – Propylthiouracil / Carbimazole: to make pt euthyroid –

42. Toxic multi-nodular goitre • 2nd common cause of thyrotoxicosis after Graves’ • Emerges insidiously (over 10 years) from non-toxic multi-nodular goiter due to mutation in TSH receptor • Serum TSH suppressed; T4 & T3 marginally elevated • Thyroid scan shows areas of hot & cold

43. Plummer’s toxic adenoma • Occurs in younger pt (unlike Graves’ or toxic MNG) • Hyper-functioning thyroid nodule secretes excess T3 & T4 → inhibits pituitary TSH secretion → remaining thyroid gland becomes quiescent • I-123 thyroid scan shows hot nodule • Rx: Carbimazole , Radioactive iodine

44. Diagnosis Degree of thyrotoxicos is Radioactive iodine uptake Thyroid scan Grave’s disease + + + + + + + + Homogenous uptake Toxic multinodular goitre + / + + Normal or + + Multiple hot & cold nodules Toxic adenoma + / + + Normal or + + Dominant hot nodule Thyrotoxic subacute thyroiditis + + + + < 1% Absent uptake

46. Thyroid nodule

48. Risk factors for malignancy in thyroid nodule • Age <20 or >45 years • Male sex • Size > 4 cm or rapid increase in size • Hard nodule • Fixed to adjacent structure • Lymph node metastasis • Vocal cord paralysis / hoarse voice • H/o irradiation or family h/o thyroid

49. Thyroid malignancy

50. Classification 1. Follicular: a. Differentiated: i. Papillary carcinoma (60 – 80% ) ii. Follicular carcinoma (10 – 20%) b. Undifferentiated: Anaplastic carcinoma (05 – 10%)

51. Clinical features of thyroid neoplasm

52. • Thyroid gland enlargement (diffuse / nodular) • Compression & infiltration features – Recurrent laryngeal nerve: stridor & hoarseness – Superior mediastinal syndrome: engorged neck veins – Esophagus: dysphagia – Sympathetic chain: Horner’s syndrome – Tethering of overlying skin & muscles • Mostly euthyroid ; hyper / hypothyroidism is rare

53. Papillary carcinoma • Etiology: previous external radiation to head & neck • 40 % rule: mean age 40 years, multi- centric in 40 % cases, neck node metastasis in 40% (to level 6) • Female : male ratio - 3:1

54. Follicular carcinoma • Mean age 50 years • Female : male ratio is 3:1 • Well-encapsulated ( mistaken for follicular adenoma) • Tendency to invade thyroid capsule & blood vessels

55. Medullary carcinoma • Malignancy of calcitonin -producing C-cells • Mutation of RET proto-oncogene present • Sporadic – 80% cases, no family history, other endocrine tumors absent, normal physical appearance, unilateral, unifocal, poorer prognosis, peak in middle age to elderly • Familial – 20% cases, autosomal dominant inheritance within family, multiple endocrine tumors

56. Anaplastic carcinoma • Non-encapsulated, rapidly growing, extra- thyroidal spread with compression of trachea & esophagus • Arise in pre-existing multi-nodular goiter or well-differentiated thyroid cancers • Node metastasis & pulmonary metastasis common

57. TNM classification

58. Tumor: T1: < 1 cm & limited to thyroid capsule T2: > 1 to < 4 cm & limited to thyroid capsule T3: > 4 cm limited to thyroid capsule T4: any size extending beyond thyroid capsule Neck lymph node enlargement: NO: absent N1a: ipsilateral

59. Treatment of thyroid malignancy

60. Papillary & follicular cancer • Tumor size < 1 cm = Near total thyroidectomy • Tumor size >1 to < 4 cm = Total thyroidectomy • Tumor size > 4 cm = Total thyroidectomy • N0 = antero-lateral neck resection (levels

61. Total thyroidectomy preferred in papillary cancer 1.Papillary carcinoma is multi-centric 2.Revision surgery more difficult than primary surgery 3.Limited surgery leads to: • Local recurrence & decreased survival rate • Transformation into anaplastic

62. Other Therapies 1. Radioactive I 131 : for recurrent / residual cancer 2. External radiotherapy: • Inoperable cancer (invasion of trachea / esophagus): 3000 cGy → debulking surgery → 1500 cGy post-op • Recurrent / residual cancer: 4500 – 5000 cGy

63. Medullary carcinoma • Total thyroidectomy + modified radical neck resection + resection of level 6 & 7 nodes if involved • Life long Thyroxine (250 µg / day) aiming to keep serum TSH level < 0.5 mU/L • Hypercalcemia present: remove 31/2 parathyroids • Pheochromocytoma present: B/L total

64. Anaplastic carcinoma • External radiotherapy (3000 cGy) → debulking surgery → post-op external radiotherapy (1500 c Gy) + I.V. Doxorubicin 20 mg / week • Total thyroidectomy + radical neck dissection + post-op external RT (4500 – 6000 c Gy) + I.V. Doxorubicin 20 mg / week

65. Thyroid lymphoma • 3-6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine & prednisone) followed by external radiotherapy to thyroid, bilateral neck, supraclavicular regions & mediastinum • Isthmusectomy for biopsy & relieving

66. Thyroid surgery

67. Why is right RLN commonly damaged in thyroid surgery? • More superficial position • Right nerve enters thyroid at 450 angle whereas the left lies within tracheo- esophageal groove • Right nerve mostly passes superior to or b/w branches of inferior thyroid artery;

68. • Lobectomy: removal of one thyroid lobe • Isthmusectomy: removal of complete isthmus • Hemi-thyroidectomy: lobectomy + isthmusectomy • Subtotal thyroidectomy : preservation of some thyroid tissue in same and opposite tracheo- esophageal groove (8 g) + 2 parathyroid glands on opposite side • Near-total thyroidectomy: preservation of thyroid tissue in opposite tracheo-esophageal groove (8 g) + 1 parathyroid gland on opposite

69. Types of Thyroid surgeries

Diseases of thyroid gland

Diseases of thyroid gland

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