Thyroid Disorders

1. Thyroid Disorders Hasan AYDIN, MD Yeditepe University MedicalFaculty Department of Endocrinology and Metabolism

2. Thyroid Regulation HYPOTHALAMUS - TRH ANT. PITUITARY - TSH THYROID T4 and T3 PLASMA T4 + FT4 PLASMA T3 + FT3 TISSUES FT4 to FT3 TSH -R

3. ThyroidHormones THEY ARE NOT ESSENTIAL FOR LIFE, BUT ARE EXTREMELY HELPFUL

4. THYROID GLAND DISORDERS • THYROID HORMONE EFFECTS: • Affects every single cell in the body • Modulates: • Oxygen consumption • Growth rate • Maturation and cell differentiation • Turnover of Vitamins, Hormones, Proteins, Fat, CHO

5. Thyroid Gland Disorders • Overproduction of thyroidhormones • Underproduction of thyroidhormones • Thyroidnodules • Thyroiditis • Thyroidneoplasms

6. Hyperthyroidism

7. Thyroid Gland Disorders • TSH High usually means Hypothyroidism • Rare causes: • TSH-secreting pituitary tumor • Thyroid hormone resistance • Assay artifact • TSH low usually indicates Thyrotoxicosis • Other causes • First trimester of pregnancy • After treatment of hyperthyroidism • Some medications (Steroids-dopamine)

8. Thyroid Gland Disorders • THYROTOXICOSIS: • is defined as the state of thyroid hormone excesss • HYPERTHYROIDISM: • is the result of excessive thyroid gland function

9. Abnormalities of Thyroid Hormones • Thyrotoxicosis • Primary • Secondary • Without Hyperthyroidism • Exogenous or factitious • Hypothyroidism • Primary • Secondary • Peripheral

10. Causes of Thyrotoxicosis Primary Hyperthyroidism • Grave´s disease • Toxic Multinodular Goiter • Toxic adenoma • Functioning thyroid carcinoma metastases • Activating mutation of TSH receptor • Struma ovary • Drugs: Iodine excess

11. Causes of Thyrotoxicosis • Thyrotoxicosis without hyperthyroidism • Subacute thyroiditis • Silent thyroiditis • Other causes of thyroid destruction: • Amiodarone, radiation, infarction of an adenoma • Exogenous/Factitia • Secondary Hyperthyroidism • TSH-secreting pituitary adenoma • Thyroid hormone resistance syndrome • Chorionic Gonadotropin-secreting tumor • Gestational thyrotoxicosis

12. Symptoms: Hyperactivity Irritability Dysphoria Heat intolerance & sweating Palpitations Fatigue & weakness Weight loss with increased appetite Diarrhea Polyuria Sexual dysfunction Signs: Tachycardia Atrial fibrillation Tremor Goiter Warm, moist skin Muscle weakness, myopathy Lid retraction or lag Gynecomastia Exophtalmus Pretibial myxedema Thyrotoxicosis

13. Manifestations of Thyrotoxicosis

14. DifferentialDiagnosis • Panic attacks • Psychosis • Mania • Pheochromocytoma • Hypoglycemia • Occult malignancy

15. Treatment • Reducing thyroid hormone synthesis: • Antithyroid drugs (Methimazole, Propylthyouracil) • Radioiodine (131I) • Subtotal thyroidectomy • Reducing Thyroid hormone effects: • Propranolol • Glucocorticoids • Benzodiazepines • Reducing peripheral conversion of T4 to T3 • Propylthyouracil • Glucocorticoids • Iodide (Large oral or IV dosage) (Wolf-Chaikoff effect)

16. Treatment: Special Considerations • Thyrotoxic crisis or Thyroid storm: • It´s a life-threatening exacerbation of thyrotoxicosis, acompanied by fever, delirium, seizures, coma, vomiting, diarrhea, jaundice. • Mortality rate reachs 30% even with treatment • It´s usually precipitated by acute illness, such as: • Stroke, infection,trauma, diabetic ketoacidosis, surgery, radioiodine treatment • Propylthyouracil IV or Nasogastric tube • Radioiodine (131I) • Propranolol • Glucocorticoids • Benzodiazepines • Iodide (Large oral or IV dosage) (Wolf-Chaikoff effect)

17. HYPOTHYROIDISM

18. Definition • A deficiency of thyroid hormones, which in turn results in a generalized slowing down of metabolic processes. • In infants and children => marked slowing of growth and development, with serious permanent consequences including mental retardation. • In adulthood => a generalized slowing down of the organism, with the clinical picture of myxedema.

19. Causes of Hypothyroidism • Primary • Congenital • Acquired • Transient • Secondary • Pituitary • Hypothalamic

20. Symptoms: Tiredness Weakness Dry skin Sexual dysfunction Hair loss Difficulty concentrating Signs: Bradycardia Dry coarse skin Puffy face, hands and feet Diffuse alopecia Peripheral edema Delayed tendon reflex relaxation Carpal tunel syndrome Serous cavity effusions. Hypothyroidism

21. Hypothyroidism

22. Special Considerations • Myxedema coma • Reduced level of consciousness, seizures • Hypotension/shock • Hypothermia • Hyponatremia • Usually in elderly hypothyroid pts. • Usually precipitated by intercurrent illnesses that impairs ventilation • It´s an Emergency with a high mortality rate • Treatment: Lyotironine(T3) or T4, Hydrocortisone, external warming, IV fluids

23. Many Causes, One Treatment Goal : Normalize TSH level regardless of cause of hypothyroidism Treatment : Once daily dosing with Levothyroxine sodium (1.6µg/kg/day) Monitor TSH levels at 6 to 8 weeks, after initiation of therapy or dosage change

24. Treatment: Special Considerations • Elderly patients • Coronary Artery Disease • Poor adrenal gland reserve • Childrens • Pregnancy • Emergency surgery (Non thyroid related)

25. Goiter and Thyroid Cancer

26. Definitions Goiter is a diffuse or nodular enlargement of the thyroid gland resulting from excessive replication of benign thyroid epithelial cells. A thyroidnodule is a discretelesionwithinthethyroidglandthat is palpablyand/orultrasonog- raphicallydistinctfromthesurroundingthyroidparenchyma

27. Etiology of Nontoxic Goiter • Iodine deficiency • Goitrogen in the diet • Hashimoto's thyroiditis • Subacute thyroiditis • Inherited defect in thyroidal enzymes necessary for T 4 and T 3 biosynthesis • Generalized resistance to thyroid hormone (rare) • Neoplasm, benign or malignant

28. Multinodular GoiterClinical Issues • Hyperthyroidism • Suspicion of malignancy • Compressive/obstructive symptoms • Cosmetic concerns

29. MULTINODULAR GOITERPresentation • Asymptomatic • Neck mass discovered by patient or physician • Abnormal CXR • Symptomatic • Pressure symptoms • Hoarseness • Thyrotoxicosis

30. NODULAR GOITERSuspicious Nodule or Goiter • High suspicion • Family history of medullary thyroid carcinoma • Rapid tumor growth • A nodule that is very firm or hard • Fixation of the nodule to the adjacent structures • Paralysis of the vocal cord • Regional lymphadenopathy • Distant metastasis • Moderate suspicion • Age of either<20 or >70 years • Male sex • History of head and neck irradiation • A nodule >4 cm in diameter or partially cystic • Symptoms of compression, including dysphagia, dysphonia, hoarseness, dyspnea, and cough

31. Ultrasound • Ultrasonographic Cancer Risk Factors for a Thyroid Nodule • hypoechogenicity, • microcalcifications, • irregular margins, • increased nodular flow visualized by Doppler, • the evidence of invasion or regional lymphadenopathy

32. Multinodular Goiter: Evaluation • TSH • FT4, T3 • Radionuclide Scan/RAIU • US • CT Scan (without contrast) • FNA biopsy

33. Multinodular GoiterFine Needle Aspiration Evaluation • Biopsy all accessible nodule(s) • Biopsy suspicious nodule(s) cold on scan; firm by palpation; growing in size • Results less reliable in large goiters • Most common diagnosis is “colloid nodule”

34. Fine Needle Aspiration Evaluation

35. FNA results • Malignant- pt needs to have surgical management • Benign- observation with interval ultrasounds and clinical examinations • Indeterminate- radioisotope scan- perform suppression scan and if cold proceed to surgical management- if hot nodule consider observation • Non diagnostic-repeat FNA or U/S guided FNA

36. Thyroid Cancers

37. Benign Neoplasms of the Thyroid Thyroid adenoma is a benignneoplasticgrowthcontainedwithin a capsule. Embrional adenoma Fetal adenoma Microfollicular adenoma Macrofollicular adenoma Papillarycystadenoma Hurtlecell adenoma

38. ThyroidCancer • Papillary (mixed papillary and follicular)75% • Follicular carcinoma 16% • Medullary carcinoma 5% • Undifferentiated carcinomas 3% • Miscellaneous (lymphoma, fibrosarcoma, 1%squamous cell carcinoma, malignant hemangioendothelioma, teratomas, and metastatic carcinomas)

39. Papillary Carcinoma • very slowly growand remain confined to the thyroid gland and local lymph nodes for many years. • In older patients, more aggressive and invade locally into muscles and trachea. • in later stages, they can spread to the lung. • Death is usually due to local disease, with invasion of deep tissues in the neck less commonly, death may be due to extensive pulmonary metastases..

40. Follicular Carcinoma • is characterized by the presence of small follicles, colloid formation is poor. • capsular or vascular invasion. • more aggressive and local invasion of lymph nodes or by blood vessel invasion with distant metastases to bone or lung. • often retain the ability to concentrate radioactive iodine, to form thyroglobulin, and, rarely, to synthesize T3 and T4.

41. Follicular Carcinoma • rare ''functioning thyroid cancer'' is almost always a follicular carcinoma. • more likely to respond to radioactive iodine therapy. • In untreated patients, death is due to local extension or to distant bloodstream metastasis with extensive involvement of bone, lungs, and viscera.

42. Medullary Carcinoma • a disease of the C cells (parafollicular cells) derived • calcitonin, histamin, prostaglandins, serotonin, other peptides • more aggressive , but not undifferentiated thyroid cancer. • locally into lymph nodes and into surrounding muscle and trachea. • lymphatics and blood vessels and metastasize to lungs and viscera. • Calcitonin and CEA clinically useful markers for diagnosis and follow-up.

43. Medullary Carcinoma • About 80% are sporadic • the remainder are familial. four familial patterns: • without associated endocrine disease (FMTC); • MEN 2a medullary carcinoma, pheochromocytoma, and hyperparathyroidism; • MEN 2B, medullary carcinoma, pheochromocytoma, and multiple mucosal neuromas; • MEN 3 : with cutaneous lichen amyloidosis, a pruritic skin lesion located on the upper back.

44. Undifferentiated (Anaplastic) Carcinoma • small cell, giant cell, and spindle cell carcinomas. • usually occur in older patients with a long history of goiter in whom the gland suddenly -over weeks or months- begins to enlarge and produce pressure symptoms, dysphagia, or vocal cord paralysis. • Death from massive local extension usually occurs within 6-36 months These tumors are very resistant to therapy .

45. Lymphoma • only type of rapidly growing thyroid cancer that is responsive to therapy • as part of a generalized lymphoma or may be primary in the thyroid gland. • occasionally with long-standing Hashimoto's thyroiditis • characterized by lymphocyte invasion of thyroid follicles and blood vessel walls, which helps to differentiate thyroid lymphoma from chronic thyroiditis. • If there is no systemic involvement, the tumor may respond dramatically to radiation therapy

46. Cancer metastatic to the thyroid • Cancers of the breast and kidney, bronchogenic carcinoma, and malignant melanoma. • The primary site of involvement is usually obvious, • Occasionally , the diagnosis is made by needle biopsy or open biopsy of a rapidly enlarging cold thyroid nodule. • The prognosis is that of the primary tumor,

47. Management of Thyroid Cancer Papillary and Follicular Carcinoma: • Low-risk group under age 45 with primary lesions under 1 cm and no evidence of intra- or extraglandular spread. • For these patients, lobectomy is adequate therapy • All other patients high-risk, and for these total thyroidectomy and-if there is evidence of lymphatic spread -a modified neck dissection are indicated. • Prophylactic neck dissection is not necessary. • For the high-risk group, postoperative radioiodine ablation

48. Management of Thyroid Cancer • Follow-up at intervals of 6-12 months should include careful examination of the neck for recurrent masses. • If a lump is noted, needle biopsy is indicated to confirm or rule out cancer. • Serum TSH should be checked • SerumTg should be < 1ng/ml .

49. Thyroiditis

50. Definition Infectious or autoimmune inflammatory diseases of thyroid gland