Thyroid disorders

1. Thyroid Gland Disorders

2. Thyroid Gland: Introduction The largest pure endocrine gland (15-25 gm), located in the anterior neck Consists of two lateral lobes connected by a median tissue mass called the isthmus. 2

3. Thyroid Gland: introduction Blood supply Arterial blood supply Superior thyroid artery from external carotid Inferior thyroid artery from subclavians Blood flow 4-6 ml/min/gm Venous blood supply Three pairs of veins supply blood to the gland

4. The thyroid gland is made up of closely packed sacs called thyroid follicles . The structural and functional unit of thyroid gland. Cyst-like structure 0.2 – 0.9 mm in diameter Simple cuboidal epithelial (follicular cells) surrounding a lumen filled with colloid . T 4 and T 3 present in colloid bound to a large protein called thyroglobulin . Thyroid Gland: introduction

5. Thyroid follicles

6. Development from the floor of the primitive pharynx during the third week of gestation developing gland migrates along the thyroglossal duct to reach its final location in the neck rare ectopic location of thyroid tissue at the base of the tongue (lingual thyroid) occurrence of thyroglossal duct cysts along this developmental tract

7. Thyroid gland secret 3 hormones Thyroxin or (T4) Tri- iodotyronine or (T3) Main hormones secreted by thyroid gland Secreted by follicular cells Amino acid derivatives (tyrosine) Calcitonin Produced by parafollicular cells – C cells Thyroid Gland: Introduction

8. Regulation of Thyroid Axis TSH – Thyrotrope cells of ant. Pituitary 31 kDa hormone α and β subunits α subunit similar to LH, FSH and hCG Stimulated by TRH TSH, TRH supressed by Thyroxine

9. Actions of Thyroid Hormones Increase the body’s overall basal metabolic rate Increase oxygen consumption Essential for normal growth Mental development Sexual maturation Increase the sensitivity of CVS and CNS to catecholamines (↑COP and HR)

10. Thyroid disorders Hypothyroidism Underactive thyroid Hyperthyroidism Overactive thyroid Goiter Thyroid enlargement

11. 12 Hypothyroidism Definition A clinical and biochemical syndrome that results from a deficiency in thyroid hormone secretion from thyroid gland or in the action

12. 13 Hypothyroidism Prevalence It is a common disorder with prevalence ranges from 2-15% population ♀ > ♂ Female to male ratio = 10:1 ↑ with age; ♀ = ♂ Mean age at diagnosis is 60 years

13. Iodine deficiency remains the most common cause of hypothyroidism worldwide areas of iodine sufficiency, autoimmune disease (Hashimoto's thyroiditis) and iatrogenic causes (treatment of hyperthyroidism) are most common

14. Primary Hypothyroidism Disease of the thyroid gland Secondary Hypothyroidism Hypothalamic-pituitary diseases (reduced TSH) Hypothyroidism

15. Causes of Hypothyroidism PRIMARY Congenital Agenesis Ectopic thyroid remnants Defects of hormone synthesis Iodine deficiency Dyshormonogenesis Antithyroid drugs Other drugs (e.g. lithium, amiodarone , interferon)

16. Causes of Hypothyroidism Autoimmune Atrophic thyroiditis Hashimoto's thyroiditis Postpartum thyroiditis Infective Post- subacute thyroiditis

17. Causes of Hypothyroidism Iatrogenic Radioactive iodine therapy External neck irradiation post-surgery Infiltration amyloidosis, sarcoidosis , hemochromatosis, scleroderma

18. SECONDARY   Hypopituitarism: tumors , pituitary surgery or irradiation, infiltrative disorders, Sheehan's syndrome, trauma, genetic forms of combined pituitary hormone deficiencies Isolated TSH deficiency or inactivity Hypothalamic disease: tumors , trauma, infiltrative disorders, idiopathic

19. HASHIMOTO THYROIDITIS Most common cause of hypothyroidism Autoimmune, non- Mendelian inheritance 45-65 years, F:M = 10-20:1 Painless symmetrical enlargement Risk of developing B-cell non-Hodgkin’s lymphoma Other concomitant autoimmune diseases Endocrine and non-endocrine

20. Hashimoto Thyroiditis Pathogenesis Immune systems reacts against a variety of thyroid antigens Progressive depletion of thyroid epithelial cells which are gradually replaced by mononuclear cells → fibrosis Immune mechanisms may includes: CD8+ cytotoxic T cell-mediated cell death Cytokine-mediated cell death Binding of antithyroid antibodies → antibody dependent cell-mediated cytotoxicity

21. Symptoms and Signs

22. Investigation of primary hypothyroidism Serum TSH The investigation of choice. A high TSH level confirms primary hypothyroidism. Serum T4 low free T4 level confirms the hypothyroid state. Thyroid and other organ-specific antibodies TPO antibodies

23. Investigations of other abnormalities: Anaemia. Increased serum aspartate transferase levels, from muscle and/or liver Increased serum creatine kinase levels, with associated myopathy Hypercholesterolaemia Hyponatraemia due to an increase in ADH and impaired free water clearance.

24. Treatment Replacement therapy with levothyroxine ( thyroxine , i.e. T4) is given for life. In the young and fit, 100 - 150 μg daily is suitable. thyroid function tests after at least 2 months on a steady dose the aim is to restore T 4 and TSH to well within the normal range An annual thyroid function test is recommended .

25. Subclinical Hypothyroidism biochemical evidence of thyroid hormone deficiency in patients who have few or no apparent clinical features of hypothyroidism guidelines do not recommend routine treatment when TSH levels are below 10 mU /L low dose of levothyroxine (25–50 g/d) with the goal of normalizing TSH

26. Myxoedema coma Severe hypothyroidism, associated with: - confusion or even coma. - hypothermia. - severe cardiac failure. - Hypoventilation. - Hypoglycaemia . - hyponatraemia . patients require full intensive care.

27. occurs in the elderly usually precipitated by factors that impair respiration drugs (especially sedatives, anesthetics , antidepressants) pneumonia , congestive heart failure, myocardial infarction gastrointestinal bleeding cerebrovascular accidents Sepsis

28. Myxoedema coma Treatment: Levothyroxine as a single IV bolus of 500 g, which serves as a loading dose-50–100 ug /d oxygen (by ventilation if necessary) monitoring of cardiac output and pressures gradual rewarming hydrocortisone 100 mg i.v . 8-hourly glucose infusion to prevent hypoglycaemia .

29. Hyperthyroidism

30. Thyrotoxicosis - as the state of thyroid hormone excess Hyperthyroidism - result of excessive thyroid function major etiologies of thyrotoxicosis are hyperthyroidism caused by Graves' disease, toxic MNG, and toxic adenomas

31. Causes of hyperthyroidism Common Graves' disease (autoimmune) Toxic multinodular goitre Solitary toxic nodule/adenoma

32. Causes of Thyrotoxicosis Primary hyperthyroidism Graves' disease Toxic multinodular goiter Toxic adenoma Functioning thyroid carcinoma metastases Struma ovarii Drugs: iodine excess ( Jod-Basedow phenomenon)

33. Thyrotoxicosis without hyperthyroidism Subacute thyroiditis Silent thyroiditis Other causes of thyroid destruction: amiodarone , radiation, infarction of adenoma Ingestion of excess thyroid hormone (thyrotoxicosis factitia ) or thyroid tissue

34. Secondary hyperthyroidism TSH-secreting pituitary adenoma Chorionic gonadotropin-secreting tumorsa Gestational thyrotoxicosisa

35. Graves' disease The most common cause of hyperthyrodism It is an autoimmune disorder. where the thyroid is overactive, producing an excessive amount of thyroid hormones More common in adults - between 20 and 50 years Can be familial and associated with other autoimmune diseases Characterized by hyperthyroidism, ophthalmopathy with exophthalmos and dermopathy (pretibial myxedema)

36. Graves’ Disease Autoimmune disease with breakdown of helper-T-cell tolerance Excessive production of thyroid autoantibodies: Thyroid-stimulating antibody (TSI) Antibodies bind to the TSH receptor of the follicular cell Stimulation of the cell resulting in: Increased levels of thyroid hormones & Hyperplasia of the thyroid gland Hyperthyroidism and Thyroid gland enlargement

37. Hyperthyrodism Clinical features : due to Hypermetabolic state Overactivity of sympathetic nervous system

38. Symptoms Weight loss Increased appetite Irritability Tremor Goiter Restlessness Stiffness Muscle weakness Breathlessness Palpitation Heat intolerance Excessive sweating Itching Thirst Vomiting Diarrhoea Oligomenorrhoea Loss of libido

39. Signs Tremor Irritability Psychosis Tachycardia or atrial fibrillation Warm peripheries Systolic hypertension Cardiac failure

40. Signs Lid lag Proximal myopathy Proximal muscle wasting Onycholysis Palmar erythema

41. Eye disease

42. Graves' O phthalmopathy earliest manifestations - sensation of grittiness, eye discomfort, and excess tearing most serious manifestation is compression of the optic nerve at the apex of the orbit, leading to papilledema; peripheral field defects; and, if left untreated, permanent loss of vision

43. 0 = N o signs or symptoms 1 = O nly signs (lid retraction or lag), no symptoms 2 = S oft-tissue involvement ( periorbital edema ) 3 = P roptosis (>22 mm) 4 = E xtraocular -muscle involvement (diplopia) 5 = C orneal involvement 6 = S ight loss

44. Thyroid dermopathy / pretibial myxedema - most frequent over the anterior and lateral aspects of the lower leg Thyroid acropachy - clubbing found in <1% of patients with Graves' disease

45. Investigation Thyroid function test: Serum TSH is suppressed in hyperthyroidism . Diagnosis is confirmed with a raised free T 4 or T 3 . Measurement of TPO antibodies or TBII may be useful if the diagnosis is unclear clinically

46. Treatment Antithyroid drugs : 1. Carbimazole . 2. Propylthiouracil . These drugs inhibit the formation of thyroid hormones common side effects - rash , urticaria , fever, and arthralgia Rare but major side effects include hepatitis; an SLE-like syndrome; and, most important, agranulocytosis

47. Treatment Radioactive iodine RAI accumulates in the thyroid and destroys the gland by local radiation. It takes several months to be fully effective.

48. Treatment Surgery : subtotal thyroidectomy Only in patient who have previously been rendered euthyroid .

49. Goiter Goiter refers to an enlarged thyroid gland Biosynthetic defects, iodine deficiency, autoimmune disease, and nodular diseases can each lead to goiter diffuse nontoxic goiter - diffuse enlargement of the thyroid occurs in the absence of nodules and hyperthyroidism Worldwide, diffuse goiter is most commonly caused by iodine deficiency and is termed endemic goiter

50. Congenital Thyroid Diseases Agenesis /Aplasia Hypoplasia Accessory or aberrant thyroid glands Thyroglossal duct cyst

51. Thyroglossal Duct Cyst A thyroglossal duct cyst is a neck mass or lump that develops from cells and tissues remaining after the formation of the thyroid gland during embryonic development. Children Failure of regression Neck, medial Squamous or columnar lining often appears after an upper respiratory infection when it enlarges and becomes painful . Complications : inflammation, sinus tracts

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