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Thyroid Function and Disease

Thyroid Function and Disease. Prof.Dr. Mohamed Abd-elaziz. The Thyroid Gland and Thyroid Hormones. Anatomy. The gland lies at the front of the lower part of the neck Located in the anterior compartment of the neck It weights 20 - 25 gram, pinkish in colour

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Thyroid Function and Disease

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  1. Thyroid Functionand Disease Prof.Dr. Mohamed Abd-elaziz

  2. The Thyroid Gland and Thyroid Hormones

  3. Anatomy • The gland lies at the front of the lower part of the neck Located in the anterior compartment of the neck • It weights 20 - 25 gram, pinkish in colour • Consists of two lobes, isthmus and Its upper pole reaches the oblique line of the thyroid cartilage • Its lower pole reaches the sixth tracheal ring • Isthmus lies in front of 2, 3 & 4 tracheal rings

  4. Anatomy of the Thyroid Gland

  5. Follicles: the Functional Units of the Thyroid Gland • Follicles Are the Sites Where Key Thyroid Elements Function: • Thyroglobulin (Tg) • Tyrosine • Iodine • Thyroxine (T4) • Triiodotyrosine (T3)

  6. The Thyroid Produces and Secretes 2 Metabolic Hormones • Two principal hormones • Thyroxine (T4 ) and triiodothyronine (T3) • Required for homeostasis of all cells • Influence cell differentiation, growth, and metabolism • Considered the major metabolic hormones because they target virtually every tissue

  7. Thyroid-Stimulating Hormone (TSH) • Regulates thyroid hormone production, secretion, and growth • Is regulated by the negative feedback action of T4 and T3

  8. Hypothalamic-Pituitary-Thyroid AxisNegative Feedback Mechanism

  9. Biosynthesis of T4 and T3 The process includes • Dietary iodine (I) ingestion • Active transport and uptake of iodide (I-) by thyroid gland • Oxidation of I- andiodination of thyroglobulin (Tg) tyrosine residues • Coupling of iodotyrosine residues (MIT and DIT) to form T4 and T3 • Proteolysis of Tg with release of T4 and T3 into the circulation

  10. Iodine Sources • Available through certain foods (eg, seafood, bread, dairy products), iodized salt, or dietary supplements, as a trace mineral • The recommended minimum intake is 150 g/day

  11. Physiology of the gland • Iodide Trapping. • Iodide oxidation to iodine. • Binding to tyrosine to form mono & Di –iodotyrosine. • Coupling to form tri-iodothyronine (T3) or T4. • Stored in the colloid .with thyroglobulin. • Release occurs after separation from TG. • In blood mostly carried with TBG and the rest as free T3 & T4.

  12. Proteolysis of Tg With Release ofT4 and T3 • T4 and T3 are synthesized and stored within the Tg molecule • Proteolysis is an essential step for releasing the hormones • To liberate T4 and T3, Tg is resorbed into the follicular cells in the form of colloid droplets, which fuse with lysosomes to form phagolysosomes • Tg is then hydrolyzed to T4 and T3, which are then secreted into the circulation

  13. Conversion of T4 to T3 in Peripheral Tissues

  14. Production of T4 and T3 • T4 is the primary secretory product of the thyroid gland, which is the only source of T4 • The thyroid secretes approximately 70-90 g of T4 per day • T3 is derived from 2 processes • The total daily production rate of T3 is about 15-30 g • About 80% of circulating T3 comesfrom deiodination of T4 in peripheral tissues • About 20% comes from direct thyroid secretion

  15. T4: A Prohormone for T3 • T4 is biologically inactive in target tissues until converted to T3 • Activation occurs with 5' iodination of the outer ring of T4 • T3 then becomes the biologically active hormone responsible for the majority of thyroid hormone effects

  16. Sites of T4 Conversion • The liver is the major extrathyroidal T4 conversion site for production of T3 • Some T4 to T3 conversion also occurs in the kidney and other tissues

  17. T4 Disposition • Normal disposition of T4 • About 41% is converted to T3 • 38% is converted to reverse T3 (rT3), which is metabolically inactive • 21% is metabolized via other pathways, such as conjugation in the liver and excretion in the bile • Normal circulating concentrations • T4 4.5-11 g/dL • T3 60-180 ng/dL (~100-fold less than T4)

  18. Hormonal Transport

  19. Carriers for Circulating Thyroid Hormones • More than 99% of circulating T4 and T3 is bound to plasma carrier proteins • Thyroxine-binding globulin (TBG), binds about 75% • Transthyretin (TTR), also called thyroxine-binding prealbumin (TBPA), binds about 10%-15% • Albumin binds about 7% • High-density lipoproteins (HDL), binds about 3% • Carrier proteins can be affected by physiologic changes, drugs, and disease

  20. Free Hormone Concept • Only unbound (free) hormone has metabolic activity and physiologic effects • Free hormone is a tiny percentage of total hormone in plasma (about 0.03% T4; 0.3% T3) • Total hormone concentration • Normally is kept proportional to the concentration of carrier proteins • Is kept appropriate to maintain a constant free hormone level

  21. Thyroid Hormone Action

  22. Thyroid Hormone Plays a Major Role in Growth and Development • Thyroid hormone initiates or sustains differentiation and growth • Stimulates formation of proteins, which exert trophic effects on tissues • Is essential for normal brain development • Essential for childhood growth • Untreated congenital hypothyroidism or chronic hypothyroidism during childhood can result in incomplete development and mental retardation

  23. Physiological effects of thyroxin hormone • Increased basal metabolic • Increase mobilization & metabolism of lipid • Increases heart rate • Increased motility of the GIT • Weakness of skeletal muscles • Excessive sweating • Neuritis

  24. Thyroid Hormones and the Central Nervous System (CNS) • Thyroid hormones are essential for neural development and maturation and function of the CNS • Decreased thyroid hormone concentrations may lead to alterations in cognitive function • Patients with hypothyroidism may develop impairment of attention, slowed motor function, and poor memory • Thyroid-replacement therapy may improve cognitive function when hypothyroidism is present

  25. Thyroid Hormone Influences Cardiovascular Hemodynamics Thyroid hormone Mediated Thermogenesis (Peripheral Tissues) Local Vasodilitation Release Metabolic Endproducts Decreased Systemic Vascular Resistance T3 Elevated Blood Volume Cardiac Chronotropy and Inotropy Decreased Diastolic Blood Pressure Increased Cardiac Output Laragh JH, et al. Endocrine Mechanisms in Hypertension. Vol. 2. New York, NY: Raven Press;1989.

  26. Thyroid Hormone Influences the Female Reproductive System • Normal thyroid hormone function is important for reproductive function • Hypothyroidism may be associated with menstrual disorders, infertility, risk of miscarriage, and other complications of pregnancy Doufas AG, et al. Ann N Y Acad Sci. 2000;900:65-76. Glinoer D. Trends Endocrinol Metab. 1998; 9:403-411. Glinoer D. Endocr Rev. 1997;18:404-433.

  27. Thyroid Hormone is Critical for Normal Bone Growth and Development • T3 is an important regulator of skeletal maturation at the growth plate • T3 regulates the expression of factors and other contributors to linear growth directly in the growth plate • T3 also may participate in osteoblast differentiation and proliferation, and chondrocyte maturation leading to bone ossification

  28. Investigations of the Thyroid Gland The pituitary thyroid axis: Synthesis and liberation of thyroid hormones is controlled by TSH from the anterior pituitary • Measurements of thyroid hormones in blood • Measurements of serum TSH • Tests using Radioactive iodine I123 • Thyroid auto-antibodies • Miscellaneous tests

  29. Measurements of thyroid hormones in blood: • Total serum thyroxin (T4) (55-150 mmol/l). • Total serum tri-iodothyronin (T3) (1.2-3.1 mmol/l). • Free serum thyroxin (T4) (8-26 pmol/l). • Free serum tri-iodothyronine(T3) (3-9 pmol/l). Estimation of free hormone level is more accurate as total serum level is under the influence of carrying proteins: • False elevated level accompanies pregnancy & CP. • False low results occur with hypoprotinaemia ( nephrotic syndrome & cirrhosis).

  30. 2. Estimation of serum TSH: This test is routinely done with estimation of thyroxin as it is: • Elevated in hypothyroidism • Below normal in thyrotoxicosis

  31. 3. Tests using radioactive iodine I123: • Radioactive iodine uptake • Thyroid scanning - Hot nodule or warm uptake - Cold nodule uptake Some times technetium 99 perchlorate ( Tc99m ) is used if patient is sensitive to iodine

  32. 4.thyroid autoantibodies: • Anti-peroxidase antibody • Anti-thyroglobulin antibody 5. Other tests: • BMR • ECG • Serum cholesterol • Measurements of tendon reflexes • T3 suppression test These tests are of little use in clinical practice

  33. Labs • Serum Total T4 (Thyroxin) reflects thyroid hormone activity. Measures both free and bound T4 in healthy patients. • Serum Total T3 (Triiodothyronine) measures both free and bound T3. • (TBG) is the major thyroid hormone binding proteins. • Other proteins with binding capacity: transthyretin (thyroxine-binding prealbumin) and albumin. • TSH is the only test that can detect small changes of thyroid hormone excess or deficiency. • Free Thyroid Hormone • (rarely ordered) Usually what is reported is an estimate of free T4 which is a calculated Free T4 Index (FT4 I)

  34. Labs ╬ Serum TSH is the best SCREENING test for the diagnosis of hypothyroidism or hyperthyroidism in healthy ambulatory individuals. • TSH is the initial test done to assess thyroid function and the only test needed if it is normal.

  35. ╬ Possible Test Question Which of the following is the best screening test for the diagnosis of hypothyroidism or hyperthyroidism in healthy ambulatory individuals. • Radioiodine I-123 uptake • Free T3 • Free T4 Index • TSH (Correct answer) • TSH and functional scan

  36. Thyroid Disorders

  37. Overview of Thyroid Disease States • Hypothyroidism • Hyperthyroidism

  38. Function Tests Serum TSH is probably the most sensitive and the best function test in the diagnosis of any thyroid disorder. Serum TSH is probably the best test to evaluate the result of any treatment in any thyroid disorder.

  39. Hypothyroidism • Hypothyroidism is a disorder with multiple causes in which the thyroid fails to secrete an adequate amount of thyroid hormone • The most common thyroid disorder • Usually caused by primary thyroid gland failure • Also may result from diminished stimulation of the thyroid gland by TSH

  40. Hyperthyroidism • Hyperthyroidism refers to excess synthesis and secretion of thyroid hormones by the thyroid gland, which results in accelerated metabolism in peripheral tissues

  41. Typical Thyroid Hormone Levels in Thyroid Disease TSHT4T3 Hypothyroidism HighLow Low HyperthyroidismLow High High

  42. Myxedematous Coma This elderly patient, came to the ER, Cherry Hill Campus,, in coma and was admitted to the ICU.

  43. Myxedematous Coma • Coma • Dry skin • Hypothermia • Bradycardia • Cardiomegaly & Bradycardia • High morbidity, 50% mortality • Use triiodothyronine (T3) via NG tube if possible • Treat with IV thyroxine 0.1 mg q 4 hr. to 12 hr. in the first 24-48 hr.

  44. y

  45. Treated With IV levothyroxine (T4) and NG tube liothyronine (T3)

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