Thyroid Disorders

1. Thyroid Disorders Safia M Sherbeeni, MD, FRCPE Consultant Endocrinologist Specialized Diabetes & Endocrine Center (SDEC) KFMC

2. Learning objectives Student will gain knowledge in definition, clinical features, different causes, basic diagnostic tests and pharmacologic treatment of hypo and hyperthyroidism.

3. Contents: Hypothyroidism: Etiology Clinical features Diagnosis Treatment Hashimoto’s disease Thyrotoxicosis Etiology Clinical Features Diagnosis Graves’ Disease Thyroiditis

4. Structural Abnormalities Thyroid Agenesis/Dysplasia or Aplasia Goiter Diffuse MNG Thyroid Nodules Thyroid Carcinoma Epithelial: Differentiated Carcinoma Papillary Thyroid Carcinoma Follicular Carcinoma Medullary Cell Carcinoma Anaplastic carcinoma Primary non-epithelial (lymphoma, sarcoma, others) Secondary

5. Hormonal Abnormalities Hypothyroidism Thyrotoxicosis / Hyperthyroidism

6. Hypothyroidism: A condition result from impaired thyroid hormone production.

7. Hypothyroidism Primary Hypothyroidism Congenital: Agenesis Defects in hormone synthesis Iodine deficiency Dyshormogenesis Anti thyroid drugs Destruction by: Autoimmune Hashimoto’s Thyroiditis GD Radiation Infiltration by tumors Thyroidectomy Transient Subacute Thyroiditis Post-partum Thyroiditis Secondary Hypothyroidism (Central) Hypopituitarism Isolated TSH deficiency Hypothalamic-Pituitary anomaly Peripheral Resistance to Thyroid Hormones Primary hypothyroidism accounts for approximately 99 % of the cases. < 1 % are due to central causes.

8. Clinical Feature: Hypothyroidism Symptoms Fatigue Lethargy Myalgia Arthralgia Excessive sleep Cold intolerance Impaired memory Weight gain Decreased sweating Constipation Hoarseness of voice Hair loss Menstrual disturbance Numbness and tingling of extremities Decreased hearing Headache Depression Stunted growth in children

9. Clinical Feature: Hypothyroidism Signs: Bradycardia Hypothermia Hypertension Non-pitting edema Dry rough and cold skin Brittle nails Slow sluggish movement

10. Clinical Feature: Hypothyroidism Signs: Dry coarse fragile hair Alopecia Loss of outer pat of eyebrow Periorbital puffiness Xanthelasma Puffy sallow face

11. Clinical Feature: Hypothyroidism Signs: Hoarse croaky voice Slow slurred monotonous speech Perceptive deafness Slow relaxation of deep tendon reflexes

12. Clinical Feature: Hypothyroidism Other Signs: Pericardial effusion Cardiomegaly Pleural effusion Respiratory II failure Obstructive Sleep Apnea Galactorrhea

13. Diagnosis Primary Hypothyroidism ? TSH FT4: low (low normal) FT3: low (low normal) Secondary Hypothyroidism ? or low normal TSH FT4: low (low normal) FT3: low (low normal)

14. Special Aspect: Cretinism: Is severe hypothyroidism occurring during infancy and leads to mental and growth retardation and characteristic radiologic features Juvenile Hypothyroidism: Hypothyroidism that begins during childhood, leads to retardation of linear growth and delay in sexual maturation. Subclinical Hypothyroidism: Asymptomatic patient who has modest elevation of TSH and low normal FT4. It affects about 7-10 % women.

15. Other Laboratory Tests Hyponatremia, SIADH Hypercholesrolemia Anemia ? AST, LDH, CK EKG: Bardycardia Low voltage ST changes ? Prolactin CXR: Cardiomegaly

16. Primary vs. Secondary Hypothyroidism Hoarse voice Weight gain Skin dry and coarse Cardiomegaly TSH is elevated No hoarse voice No weight gain, may decrease Skin dry and thin with fine wrinkling No Cardiomegaly TSH is low or low normal

17. Complications Myxedema Coma Pericardial tamponade (rare)

18. Treatment Levothyroxine 1.4-1.6 mcg/kg

19. Hashimot’s Disease Is an autoimmune disease Is common 3.5/1000/year The most common cause of goiterous hypothyroidism in areas with iodine sufficiency No age group is exempted Diffuse lymphocytic infiltration with germinal center formation, obliteration of follicles by fibrosis In most cases there is destruction of epithelial cells

20. Clinical Features: Goiter: Is the hallmark Generally moderate in size Firm Smooth or irregular Hypothyroidism Euthyroid Transient hyperthyroidism in the first3-6 months.

21. Diagnosis: Is confirmed by presence of thyroid antibodies TPO-AB are more common than TG-Ab

22. Thyrotoxicosis Graves’ Disease Toxic Multinodular Goiter Toxic Adenoma (Plummer’s Disease) Iodine-induced hyperthyroidism (Jod Basedow) TSH overproduction Trophoblastic tumor Subacute thyroiditis (de Quervian’s thyroiditis) Functioning Ectopic Thyroid Tissue Thyroiditis with transient thyrotoxicosis Thyrotoxicosis Factitia

23. Thyrotoxicosis / Hyperthyroidism Thyrotoxicosis: biochemical and physiologic manifestation of excessive thyroid hormones from the thyroid gland or extra-thyroid origin Hyperthyroidism: is reserved for disorders that result from overproduction of thyroid hormones by the thyroid gland itself

24. Clinical Features: Hyperthyroidism Symptoms: Nervousness Excessive sweating Heat intolerance Palpitation Fatigue Weight loss Dyspnea Weakness Increased appetite Hyperdefecation Diarrhea

25. Clinical Features: Hyperthyroidism Signs: General Agitated, restless Fidgety Skin: Is warm, moist, soft velvety Tremor of hands Palmer erythema Hyperpigmentation Soft friable nails Onycholysis Eyes: Lid retraction Lid lag Globe lag CVS: Tachycardia AF in 20 % Wide pulse pressure Diffuse forceful apex beat Loud heart sound

26. Clinical Features: Hyperthyroidism Signs: Agitated, restless CNS: Agitated, restless Emotional liability Hyperkinesia Proximal muscle weakness Other manifestations: Hepatomegaly Oligemenorrhea Increased miscarriage

27. Complication: High Cardiac Output Failure Thyrotoxic Crisis Osteoporosis

28. Graves’ Disease Is an autoimmune thyroid disease First described by Parry in 1825 Is the most common cause of thyrotoxicosis Characterized by: Hyperthyroidism Diffuse goiter Infiltrative Orbitopathy Infiltrative Dermopathy

29. Graves’ Disease Prevalence: 2.7 % More common in men Most common in 3rd – 4th decades Rare before 10 years of age

30. Features: Infiltrative Orbitopathy: Exophthalmos Ophthalmoplegia Lids: red and edematous Chemosis Corneal ulcer Enlarged lacrimal glands Increased IOP Blindness Sublaxation of the globe Is evident in 50 % of patient clinically The exraocular muscle and adipose tissue are swollen by accumulation of glycosaminoglycan. Later as inflammation decreases muscle may become fibrosed

31. Features: Goiter: 2-3 times the normal size Diffuse Usually symmetrical Bruit Thrill in severe cases In 20 % no goiter Non-homogenous lymphocytic infiltration with no follicular destruction

32. Features: Infiltrative dermopathy: In 5-10 % of patients When present almost always accompanies by orbitopathy Hyperpigmented Non-pitting Indurations / nodules / plaques with smooth edge Over legs, commonly the peritibial

33. Diagnosis Low TSH, elevated FT4 in the presence of clinical features TSHR-Ab Thyroid Scan: diffuse enlargement with high uptake

34. Treatment Modalities RAI Medical Antithyroid Drugs Thionamides Methimazole Carbimazole Propylthiouracil Lithium carbonate (used if allergic or C/I to thionamides) Betablockers Surgery

35. Thyroiditis: Inflammation of thyroid gland caused by diverse inflammatory conditions: Autoimmune; HD GD Infections (bacterial and fungal) Subacute Thyroiditis Reidel’s Thyroiditis Others

36. Subacute Thyroiditis de Quervian's thyroiditis Garnulomatous giant cell thyroiditis Thought to result fro viral infection Painful tender goiter Fever and other constitutional symptoms Thyrotoxicosis with low RAIU Phases: Hyperthyroid Hypothyroidism Euthyroid Resolves within months

37. Subacute Thyroiditis Patchy infiltration of the follicles with mononuclear cells. Disruption of epithelial cells Well developed follicular lesion with colloid surrounded by giant cells and progresses to form granuloma. Normal histology is restored after the disease subsides

38. Post Partum Thyroiditis A syndrome characterized by: Transient thyrotoxicosis with low RAIU Developing within 3-6 months after delivery Followed by hypothyroid phase lasting few months Then eventually euthyroid state. Affects 10-30 % of women particularly those with + TPO-Ab

39. Reidel’s Thyroiditis Sclerosing thyroiditis A rare condition Characterized by fibrosis of the thyroid gland and adjacent structures Retroperitoneal fibrosis may be present Occurs usually in middle age Insidious onset Patient present with symptoms of compression on trachea, esophagus and recurrent laryngeal nerve Stony hard moderate asymmetric goiter