HYPERTHYROIDISM: DIAGNOSTIC CRITERIA, TREATMENT

1. HYPERTHYROIDISM: DIAGNOSTIC CRITERIA, TREATMENT Department of Internal Medicine №2 as.-prof. Martynyuk L.P.

2. Plan of lecture • Anatomy of thyroid gland. • Physiologic effects of thyroid hormones. • Definition of the term “Hyperthyroidism” (DTG) . • Frequency of DTG . • Etiology and predisposing factors. • Pathogenesis of DTG. • Changes of the nervous system. • Changes of the cardiovascular system. • Changes of the gastrointestinal tract. • Changes of the endocrine system. • Changes of the urinary system. • Changes of the pulmonary system. • Degrees of thyroid gland enlargement(WHO, 1986, 1994). • Degrees of severity of DTG. • Diagnostic criteria of DTG. • Treatment of DTG. • Thyroid storm: diagnostic criteria and treatment.

3. Plan of lecture • Definition of the term “Hypothyroidism”. • Frequency of hypothyroidism . • Etiology of hypothyroidism . • Pathogenesis of hypothyroidism. • Classification of hypothyroidism. • Skin and hair. • Changes of the nervous system. • Changes of the cardiovascular system. • Changes of the gastrointestinal tract. • Changes of the endocrine system. • Changes of the urinary system. • Changes of the pulmonary system. • Congenital hypothyroidism. • Diagnostic criteria of hypothyroidism. • Treatment of hypothyroidism. • Myxedema coma: diagnostic criteria and treatment. • Thyroiditis: classification, diagnostic criteria, treatment.

6. Physiologic effects of thyroid hormones • Increasing of protein metabolism in virtually every body tissue • Increasing of O2 consumption by increasing the activity of Na+ H+ ATPase (Na pump), primarily in tissues responsible for basal O2 consumption (i.e., liver, kidney, heart and skeletal muscle).) • Stimulation of erythropoesis • Positive chrono- inotropic effects on myocardium • Achievment of formation of nervous system and skeleton in perinatal perion

7. Hyperthyroidism (thyrotoxicosis)Toxic diffuse goiter. Grave’s disease - is the condition resulting from the effect of excessive amounts of thyroid hormones on body tissues. Thyrotoxicosis is a main syndrome Enlargment of thyroid gland

8. Epidemiology At one time or another, approximately 0,5 % of the population suffers from hyperthyroidism. Graves disease is the most common cause of hyperthyroidism and is fairly common in the population. It is responsible for over 80 % of hyperthyroid cases. It occurs most often in young women, but it may occur in men and at any age.

9. Defect of T lymphocytes suppressors Genetic predisposition, conferred by genes close proximity to the major histocompatibility complex (HLA DR3, B8) Autoimmune disorders, which can be provoked by: insolation; stress; acute infections; hormone disbalance (pregnancy and others) Etiology and predisposing factors

10. Pathogenesis

12. Clinical manifestations The clinical presentation may be dramatic or subtle. Dysfunction of • the nervous system • the cardiovascular system • the gastrointestinal system • the pulmonary system • the endocrine organs • katabolic syndrome • ectodermal changes

17. Degrees of thyroid gland enlargement(WHO, 1986, 1994)

18. Degrees of severity

19. Treatment • 1. Antithyroid drugs. 2. Drugs to ameliorate thyroid hormone effects . • 131I - therapy • Surgery.

20. Thyroid storm Thyroid storm is a life- threatening emergency requiring prompt and specific treatment. In is characterized by abrupt onset of more severe symptoms of thyrotoxicosis, with some exacerbated symptoms and signs atypical of uncomplicated Graves disease: • fever; • marked weakness and muscle wasting; • extreme restlessness with wide emotional swings; • confusion; • psychosis or even coma; • hepatomegaly with mild jaundice; • the patient may present with cardiovascular collapse or shock.

21. Thyroid storm results from:- untreated or inadequately treated thyrotoxicosis It may be precipitated by: • infection; • trauma • surgery; • embolism; • diabetic acidosis; • fright; • toxemia of pregnancy; • labor; • discontinuance of antithyroid medication; • radiation thyroiditis.

22. Treatment of thyroid storm • Iodine-30 drops Lugol’s solution/day orally in 30g 4 divided doses; or 1 to 2 gr. sodium iodide slowly by i/v drip • Propylthiouracil (merkazolil) - 900 to 1200 mg/day orally or by gastric tube. • Propranolol - 160mg/day orally in 4 divided doses; or 1mg slowly i/v g 4h under careful monitoring; a rate of administration should not exceed 1mg/min; a repeat 1mg dose may be given after 2 min i/v glucose solutions . • Correction of dehydration and electrolyte imbalance cooling blanket for hypertermia. • Digitalis if necessary. • Treatment of underlying disease such as infection. • Corticosteroids-100 to 300mg hydrocortisone/day i/v. • Iodine in pharmacological doses inhibits the release of T3 to T4 within hours and inhibits the organification of iodine, a transitory effect lasting from a few days to a week (”escape phenomenon”.)

23. Hypothyroidism (myxedema) is the characteristic reaction to thyroid hormone deficiency.

24. Historical perspective • The first full clinical description of the hypothyroidism and mixedeme was made in 1874 by Gull (by the cretinoid state supervening in adult life in women) • Term “myxedeme” first used by Ord in 1978

25. Epidemiology -Hypothyroidism occurs in 3 to 6 % for the adult population, but is symptomatic only in a minor of them. • Usually develops after the age of 30 • It occurs 8 to 10 times more often in women than in men

26. I. Congenital II. Acquired A.Transient B.Permanent 1. Primary (thyroid gland disturbances). 2. Secondary (due to pituitary disease). 3.Tertiary (due to hypothalamic disease). 4.Peripheral. Classification

27. I. Congenital II. Acquired A.Transient B.Permanent 1. Primary (thyroid gland disturbances). 2. Secondary (due to pituitary disease). 3.Tertiary (due to hypothalamic disease). 4.Peripheral. Classification

28. 1. Subclinical (laboratory) hypothyroidism. 2. Clinical (overt) hypothyroidism Degrees of severity: Mild Moderate Severe Stages of compensation 1. Compensation. 2. Subcompensation. 3. Decomposation. Presence of complications 1. Without complications. 2. With complications (myopathy, polyneuropathy, encephalopathy, coma). Classification of hypothyroidism

29. Pathogenesis • Clinical signs develops due to decreased metabolism in the organism

30. Clinical features • Hypothyroidism can be presented in many different ways and can mimic other disorders • Because many manifestations of hypothyroidism are non-specific, the diagnosis is particularly likely to be overlooked in patients with other chronic illnesses and elderly and can lead to significant morbidity and even mortality

31. Clinical manifestations The clinical presentation may be dramatic or subtle. Dysfunction of • the nervous system • the cardiovascular system • the gastrointestinal system • the pulmonary system • the endocrine organs • metabolic syndrome • musculosceletal changes

36. Congenital hypothyroidism • Children are born with increased weight • Subcutaneous edema • Hypotermia • Prolonged jaundice • Physical (dwarfism) and • mental retardation (cretinism) Treatment < 3 month – 25 mkg/day 3 -12 month – 37,5 mkg/day 1 – 5 years – 75 mkg/day 5 – 7 years – 75 – 100 mkg/day > 7 years – 100 mkg/day

37. Subclinical (laboratory) hypothyroidism It is a state in which we can’t find clinical features of hypothyroidism and euthyroidism is reached by compensatory increasing of TSH secretion and that’s why synthesis and secretion of such level of thyroid hormone that will be enough for organism. It is an asymptomatic state in which serum T4 and free T4 are normal, but serum TSH is elevated.

38. Diagnostic of hypothyroidism • History • Clinical features • Blood analysis: anemia; hypercholesterolemia • Levels of thyroid hormone: both serum T4 and T3 are decreased (but in 25% of patients with primary hypothyroidism may be normal circulating levels of T3), TSH hormone disturbances (in primary hypothyroidism serum levels of TSH are very high (feedback), low level of circulating TSH in secondary) • ECG; • Examination of tendon reflexes • Ultrasonic examination

39. Treatment of hypothyroidism

40. Replacement therapy

42. Myxedema coma It is a life-threatening complication of hypothyroidism

43. Precipitating factors include • exposure to cold • infection • Trauma • Surgery • Myocardial infarction • Bleeding • Stress situation • Drugs that suppress the CNS

44. Clinical signs of myxedema coma • Slow development (weakness, somnolence, coma) • extreme hypothermia (temperatures 24 to 32) • Areflexia • Seizures • Bradycardia, hypotension • Polyserositis • CO2 retention, and respiratory depression caused by decreased cerebral blood flow, nonreversible brain changes • Rapid diagnosis (based on clinical judgment, history, and physical examination) is imperative because early death is likely.

45. Treatment of myxedema coma • large doses of T4 (250-500 mkg i/v bolus 3 – 4 times a day) or T3 if available (40 – 100 mkg I/v bolus 3 times a day), because TBG must be saturated before any free hormone is available for response. • The maintenance dose for T4 is 50 mkg/day i/v and for T3 10 20 mkg/day I/v until the hormone can be given orally. • Corticosteroid therapy (hydrocortisone 200 – 400 – 600 mg/day i/v dr. • The patient should not be rewarmed rapidly because of the threat of cardiac arrhythmia. • Hypoxemia is common, so PaO2 should be measured at the outset of treatment. If alveolar ventilation is compromised, immediate mechanical ventilatory assistance is required.

46. Thyroiditis The various types of thyroiditis encompass a heterogeneous group of inflammatory disorders of diverse etiologies and clinical features.

47. Classification • Acute thyroiditis. • Subacute thyroiditis: • subacute granulamatous thyroiditis; • subacute lymphocytous thyroiditis. • Chronic thyroiditis: • Hashimoto thyroiditis; • Ridel struma. • Specific thyroiditis. • Thyroiditis caused by mechanical or physical factors.

50. References • The Merck Manual of Diagnosis and Therapy (fourteenth Edition)/ Robert Berkow and others. – published by Merck Sharp & Donhme Research Laboratories, 1982. – P.997 – 1010. • Manual of Endocrinology and Metabolism (Second Edition)/ Norman Lavin. – Little, Brown and Company.- Boston-New York-Toronto-London, 1994. - P. 357 - 380. • Endocrinology (A Logical Approach for Clinicians (Second Edition)). William Jubiz.-New York: WC Graw-Hill Book, 1985. - P. 68 – 100.