1. LABORATORY ASSESSMENT OF THYROID FUNCTION MALIK ALQUB MD. PHD.

2. Thyroid Gland  Thyroid Gland:  Highly vascular flat structure.  Located at the upper portion of the trachea.  Composed of twp lobes joined by an isthmus.

3. Follicles: the Functional Units of the Thyroid Gland Follicles Are the Sites Where Key Thyroid Elements Function: Thyroglobulin (Tg) Tyrosine Iodine Thyroxine (T 4 ) Triiodotyrosine (T 3 )

4. Actions of Thyroid Hormones  Thyroid hormones are essential for normal growth of tissues, including the nervous system.  Lack of thyroid hormone during development results in short stature and mental deficits (cretinism).  Thyroid hormone stimulates basal metabolic rate.

5. The Thyroid Produces and Secretes 2 Metabolic Hormones  Two principal hormones  Thyroxine (T 4 ) and triiodothyronine (T 3 ) Required for homeostasis of all cells Influence cell differentiation, growth, and metabolism Considered the major metabolic hormones because they target virtually every tissue

6. Production of T 4 and T 3  T 4 is the primary secretory product of the thyroid gland, which is the only source of T 4  The thyroid secretes approximately 70-90  g of T 4 per day  T 3 is derived from 2 processes  The total daily production rate of T 3 is about 15-30  g  About 80% of circulating T 3 comes from deiodination of T 4 in peripheral tissues  About 20% comes from direct thyroid secretion

7. T 4 : A Prohormone for T 3  T 4 is biologically inactive in target tissues until converted to T 3  Activation occurs with 5' iodination of the outer ring of T 4  T 3 then becomes the biologically active hormone responsible for the majority of thyroid hormone effects

8. Sites of T 4 Conversion  The liver is the major extrathyroidal T 4 conversion site for production of T 3  Some T 4 to T 3 conversion also occurs in the kidney and other tissues

9. T 4 Disposition  Normal disposition of T 4  About 41% is converted to T 3  38% is converted to reverse T 3 (rT 3 ), which is metabolically inactive  21% is metabolized via other pathways, such as conjugation in the liver and excretion in the bile  Normal circulating concentrations  T 4 4.5-11  g/dL  T 3 60-180 ng/dL (~100-fold less than T 4 )

10. Transport of Thyroid Hormones Thyroid hormones are not very soluble in water (but are lipid-soluble). Thus, they are found in the circulation associated with binding proteins: - Thyroid Hormone-Binding Globulin (~70% of hormone) - Pre-albumin, (~15%) - Albumin (~15%) Less than 1% of thyroid hormone is found free in the circulation. Only free and albumin-bound thyroid hormone is biologically available to tissues.

11. Regulation of Thyroid Hormone Levels  Secretion of the thyroid hormones T4 (thyroxine) and T3 (triiodothyronine) is regulated by pituitary thyrotropin (TSH).  Thyrotropin-releasing hormone (TRH) increases the secretion of thyrotropin (TSH), which stimulates the synthesis and secretion of trioiodothyronine (T3) and thyroxine (T4) by the thyroid gland. T3 and T4 inhibit the secretion of TSH, both directly and indirectly by suppressing the release of TRH. sites.

13.  TSH  Free T4 (thyroxine)  Free T3 (triiodothyronine) LABORATORY TESTS USED TO ASSESS THYROID FUNCTION

14. Overview of Thyroid Disease States  Disorders of the thyroid are common and consist of 2 general presentations:  changes in the size or shape of the gland or changes in secretion of hormones from the gland. Hypothyroidism refers to the inadequate production of thyroid hormone or diminished stimulation of the thyroid by TSH; hyperthyroidism refers to those conditions in which thyroid hormones are excessively released due to gland hyperfunction.

15. Overview of Thyroid Disease States  Hypothyroidism  Hyperthyroidism

16. Hypothyroidism

17.  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

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

19. Typical Thyroid Hormone Levels in Thyroid Disease TSHT 4 T 3 Hypothyroidism HighLow Low Hyperthyroidism LowHigh High

20.  Measurement of the total plasma hormone concentration may not provide an accurate assessment of thyroid gland activity because total hormone concentration is affected by changes in either the amount of thyroxine-binding globulin (TBG) or the affinity of hormones to TBG in plasma.

21. TSH Low High FT4 FT4 & FT3 Low Hypothyroidism Low Central Hypothyroid High Hyperthyroidism High thyrotoxicosis

22. Hypothyroidism

23. Hypothyroidism: Types  Primary hypothyroidism  From thyroid destruction  Central or secondary hypothyroidism  From deficient TSH secretion, generally due to sellar lesions such as pituitary tumor or craniopharyngioma  Infrequently is congenital  Central or tertiary hypothyroidism  From deficient TSH stimulation above level of pituitary—ie, lesions of pituitary stalk or hypothalamus  Is much less common than secondary hypothyroidism Bravernan LE, Utiger RE, eds. Werner & Ingbar's The Thyroid. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2000. Persani L, et al. J Clin Endocrinol Metab. 2000; 85:3631-3635.

24. Hypothyroidism: Underlying Causes  Congenital hypothyroidism  Agenesis of thyroid  Defective thyroid hormone biosynthesis due to enzymatic defect  Thyroid tissue destruction as a result of  Chronic autoimmune (Hashimoto) thyroiditis  Radiation (usually radioactive iodine treatment for thyrotoxicosis)  Thyroidectomy  Other infiltrative diseases of thyroid (eg, hemochromatosis)

25. Tiredness Slower Thinking Moodiness/ Irritability Depression Inability to Concentrate Thinning Hair/Hair Loss Loss of Body Hair Dry, Patchy Skin Weight Gain Cold Intolerance Elevated Cholesterol Family History of Thyroid Disease or Diabetes Muscle Weakness/ Cramps Constipation Infertility Menstrual Irregularities/ Heavy Period Slower Heartbeat Difficulty Swallowing Persistent Dry or Sore Throat Hoarseness/ Deepening of Voice Enlarged Thyroid (Goiter) Puffy Eyes Clinical Features of Hypothyroidism

26. Chronic Autoimmune Thyroiditis (Hashimoto Thyroiditis)  Occurs when there is a severe defect in thyroid hormone synthesis  Is a chronic inflammatory autoimmune disease characterized by destruction of the thyroid gland by autoantibodies against thyroglobulin, thyroperoxidase, and other thyroid tissue components  Patients present with hypothyroidism, painless goiter, and other overt signs  Persons with autoimmune thyroid disease may have other concomitant autoimmune disorders  Most commonly associated with type 1 diabetes mellitus

28. Mild Thyroid Failure  Elevated TSH level (>4.0  IU/mL)  Normal total or free serum T 4 and T 3 levels  Few or no signs or symptoms of hypothyroidism McDermott MT, et al. J Clin Endocrinol Metab. 2001;86:4585-4590. Braverman LE, Utiger RD, eds. The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000;1001.

29. Subacute (de Quervain’s) Thyroiditis  Preceding viral infection  Infiltration of the gland with granulomas  Painful goitre  Hyperthyroid phase  Hypothyroid phase

30. Hyperthyroidism

31. Nervousness/Tremor Mental Disturbances/ Irritability Difficulty Sleeping Bulging Eyes/Unblinking Stare/ Vision Changes Enlarged Thyroid (Goiter) Menstrual Irregularities/ Light Period Frequent Bowel Movements Warm, Moist Palms First-Trimester Miscarriage/ Excessive Vomiting in Pregnancy Hoarseness/ Deepening of Voice Persistent Dry or Sore Throat Difficulty Swallowing Palpitations/ Tachycardia Impaired Fertility Weight Loss or Gain Heat Intolerance Increased Sweating Family History of Thyroid Disease or Diabetes Signs and Symptoms of Hyperthyroidism Sudden Paralysis

32. Hyperthyroidism Underlying Causes  Signs and symptoms can be caused by any disorder that results in an increase in circulation of thyroid hormone  Toxic diffuse goiter (Graves disease)  Toxic uninodular or multinodular goiter  Painful subacute thyroiditis  Silent thyroiditis  Toxic adenoma  Iodine and iodine-containing drugs and radiographic contrast agents

33. Graves Disease (Toxic Diffuse Goiter)  The most common cause of hyperthyroidism  Accounts for 60% to 90% of cases  Incidence in the United States estimated at 0.02% to 0.4% of the population  Affects more females than males, especially in the reproductive age range  Graves disease is an autoimmune disorder possibly related to a defect in immune tolerance

35. Thyroid Nodular Disease  Thyroid gland nodules are common in the general population  Most thyroid nodules are benign  Less than 5% are malignant  Only 8% to 10% of patients with thyroid nodules have thyroid cancer

37. Multinodular Goiter (MNG)  MNG is an enlarged thyroid gland containing multiple nodules  The thyroid gland becomes more nodular with increasing age  In MNG, nodules typically vary in size  Most MNGs are asymptomatic  MNG may be toxic or nontoxic  Toxic MNG occurs when multiple sites of autonomous nodule hyperfunction develop, resulting in thyrotoxicosis  Toxic MNG is more common in the elderly

39. Thyroid Carcinoma  Thyroid carcinoma occurs relatively infrequently compared to the common occurrence of benign thyroid disease  Thyroid cancers account for only 0.74% of cancers among men, and 2.3% of cancers in women in the Us.