A 29-year-old female presents with restlessness, anxiety, a heart rate of 135 bpm, and tremors. Examination reveals a 3cm nodule on her thyroid gland. In the meantime, propranolol could be given to acutely reduce her physical symptoms as laboratory tests are pending to confirm a diagnosis of hyperthyroidism.

1. DR. UMA K. Thyroid Hormones & Drugs BY DR.UMA KADAM M.B.B.S. MD ASSOCIATE PROFESSOR PHARMACOLOGY SKNMC

2. A 29 YO female complains of restlessness and increasing anxiety. HR 135 bmp, PE: Tremors. Palpation on the neck reveals a 3cm nodule on her thyroid gland. Laboratory test are sent to confirm the diagnosis. In the meantime, with drug could be given to acutely reduce her physical symptoms? Propylthiouracil. Furosemide. Prednisone. Iodine. Propanolol. DR. UMA K.

3. Hormones and Your Health What Is a Hormone? Which Ones Especially Affect Women? What Can Go Wrong? Thyroid Disease - a “Hidden” Problem for Women Staying Healthy DR. UMA K.

4. What Are Hormones? Chemicals That Are Released Into the Bloodstream Regulators of Specific Body Functions DR. UMA K.

5. Hormones of Special Interest to Women Thyroxine (T4) Thyronine (T3) Progesterone Estrogen

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7. Thyroid Disease The “Hidden” Health Problem DR. UMA K.

8. Who do you know with thyroid disease? DR. UMA K.

9. What Does Your Thyroid Gland Do for You? Produces Three Hormones Called Calcitonin, important in calcium homeostasis. Thyroxine (T4) Thyronine (T3), important in growth and metabolic function Regulates Metabolism so Your Cells Function Properly Affects Every Cell in the Body DR. UMA K.

10. Thyroid Hormones lodide is necessary for thyroid hormone synthesis. Iodide is obtained from the diet and is absorbed from the gastrointestinal tract. Once in the gland iodide is oxidized to an active iodine intermediate, which iodinates tyrosine residues of thyroglobulin. An aerobic condensation of iodinated tyrosine molecules results in production of T3 and T4. DR. UMA K.

11. Synthesis & release of thyroid hormones: DR. UMA K.

12. Pharmacokinetics: Thyroid Hormones 99% of T3 and T4 are bound to plasma proteins (TBG: thyroid-binding globulin). They are excreted in the bile and urine. T4 has a half-life of 6-7 days; T3 has a half-life of 1-2 days. Some of the circulating T4 is deiodinated to T3, the more potent and rapidly acting form. DR. UMA K.

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14. Regulation of thyroid hormones: (Negative Feedback Loop) DR. UMA K.

15. Thyroid Hormones T4 and T3 are iodine-containing hormones that are analogs of tyrosine. Regulated by TSH, which increases the Synthesis and secretion of these hormones. TSH secretion is regulated by negative feed-back of the thyroid hormones; it is positively influenced by TRH from the hypothalamus. DR. UMA K.

16. DR. UMA K. Thyroid hormones: Mechanism of action

17. Thyroid Hormones: Mechanism of action Activation of nuclear nonhistone protein receptors attached to DNA. Binding leads to increased transcription of messenger RNA (mRNA). Increasing the synthesis of specific proteins. (T3 x 10 potent). Cell membranes receptors: increase amino acid and glucose uptake. Inner mitochondrial membrane receptors: regulate energy metabolism. DR. UMA K.

18. Thyroid Hormone Affects Many Organs and General Health DR. UMA K. Thyroid Uterus Heart Liver Kidney Brain Skin GI Tract Lungs Eyes

19. Thyroid Hormones Effects in most major systems, including normal growth and development. Increased basal metabolic rate and activation of oxygen consumption. Thermogenic effect (increased heat production). Increased plasma glucose and free fatty acids, reduction in plasma cholesterol and triglycerides. Increased HR, maturation of the CNS. DR. UMA K.

20. When the Thyroid Doesn’t Work DR. UMA K. Hyperthyroidism Too Much Thyroid Hormone Metabolism Speeds Up Hypothyroidism Too Little Thyroid Hormone Metabolism Slows Down

21. Thyroid Disease Affects Many Body Systems and Overall Health DR. UMA K. Thyroid Disease Can Have Widespread Effects Thyroid Increased LDL Cholesterol Elevated Triglycerides Liver Constipation Decreased GI Activity Intestines Decreased Fertility Menstrual Abnormalities May Harm Development of Infant Reproductive System Depression Decreased Concentration General Lack of Interest Brain Decreased Heart Rate Increased/Decreased Blood Pressure Decreased Cardiac Output Heart Decreased Function Fluid Retention and Edema Kidneys

22. Thyroid drugs DR. UMA K.

23. Thyroid Drugs Replacement therapy. Treatment for hypothyroidism. Suppress TSH secretion. Levo isomers are more potent in increasing basal metabolic rate. Once absorbed, their pharmacokinetic and dynamic properties are identical to endogenous thyroid hormones. DR. UMA K.

24. Thyroid Drugs Adverse reactions : Hyperthyroidism (or symptoms of hyperthyroidism). Cardiovascular toxicity (tachyarrhythmias, angina, and infarction) CNS stimulation, insomnia. DR. UMA K.

25. Hypothyroidism: The Hidden Health Problem Affects Up to 25 Million People But Approximately 12 Million Are Undiagnosed

26. Hypothyroidism Affects Multiple Body Systems Central Nervous System Female Reproductive System Cardiovascular System Hypothyroidism Can Cause Serious Harm to Your Health

27. Signs and Symptoms of Hypothyroidism DR. UMA K. Tiredness Forgetfulness/Slower Thinking Moodiness/ Irritability Depression Inability to Concentrate Thinning Hair or Hair Loss Loss of Body Hair Dry, Patchy Skin Weight Gain Cold Intolerance Elevated Cholesterol Muscle Weakness or Cramps Constipation Infertility Menstrual Irregularities/ Heavy Period Slower Heartbeat Difficulty Swallowing Persistent Dry or Sore Throat Hoarseness/ Deepening of Voice Swelling (Goiter) Puffy Eyes

28. Common Signs and Symptoms of Hypothyroidism Tiredness Loss of Interest and/or Pleasure Forgetfulness Dry, Coarse Hair Loss of Lateral Eyebrow Hair Puffy Face and Eyes Goiter Slow Heartbeat Dry Skin Cold Intolerance Weight Gain Heavy Menstrual Periods Constipation Brittle Nails DR. UMA K. May Include:

29. Hypothyroidism: The “Hidden” Disease Cardiovascular: Slow Heartbeat Elevated Cholesterol Aging: Dry, Scaly Skin Sparse or Coarse Hair Gynecological: Irregular Menstruation Infertility Gastrointestinal: Constipation Weight Gain Muscular: Muscle Weakness Stiffness Ear, Nose & Throat: Hoarse Voice Psychiatric: Impaired Concentration Depression Lethargy, Fatigue Blood: Anemia

30. How to Remember the Signs and Symptoms of Hypothyroidism S leepiness, Fatigue, Lethargy L oss of Memory, Trouble Concentrating U nusually Dry, Coarse Skin G oiter (Enlarged Thyroid) G radual Personality Change, Depression I ncrease in Weight, Bloating or Puffiness (Edema) S ensitivity to Cold H air Loss, Sparseness of Hair DR. UMA K.

31. DR. UMA K. Hypothyroidism After Before

32. Levothyroxine Synthetic levo isomer of T4. PO and IV available. Preferred drug for hypothyroidism. Better standardization and stability and long duration. Long half-life of T4. Facilitates maintenance of a steady physiologic replacement. DR. UMA K.

33. Liothyronine Synthetic L-T3. More difficult to monitor than T4. More expensive. Shorter duration of action. Treatment of choice for Myxedema coma. DR. UMA K.

34. Liotrix Combination of Levothyroxine and Liothyronine. Ratio of 4:1. No advantage over Levothyroxine. DR. UMA K.

35. Antithyroid Drugs DR. UMA K.

36. Antithyroid Drugs Inhibit the formation of thyroid hormones. Used in the treatment of hyperthyroidism. DR. UMA K.

37. DR. UMA K. Signs and Symptoms Of Hyperthyroidism Bulging Eyes/Unblinking Stare Menstrual Irregularities or Light Period Excessive Vomiting in Pregnancy First-Trimester Miscarriage Family History of Thyroid Disease or Diabetes Nervousness Irritability Difficulty Sleeping Swelling (Goiter) Frequent Bowel Movements Warm, Moist Palms Hoarseness or Deepening of Voice Difficulty Swallowing Rapid or Irregular Heartbeat Infertility Weight Loss Heat Intolerance Increased Sweating Persistent Sore or Dry Throat

38. Common Signs and Symptoms of Hyperthyroidism Nervousness Irritability Difficulty Sleeping Bulging Eyes Unblinking Stare Goiter Rapid Heartbeat Increased Sweating Heat Intolerance Unexplained Weight Loss Scant Menstrual Periods Frequent Bowel Movements Warm, Moist Palms Fine Tremor of Fingers DR. UMA K. May Include:

39. DR. UMA K. Hyperthyroidism Before After

40. If You Have Hyperthyroidism, You’re in Good Company DR. UMA K. Barbara Bush 1984 Pre-treatment Barbara Bush 1991 Post-treatment

41. lodide Small amounts of iodine (75-100 ng/day) are required for hormone synthesis. But high concentrations (+ 50 mg/day) produce autoinhibition. lodide blocks the uptake of iodide, inhibiting synthesis and release of thyroid hormones. Diminishes vascularity of the gland. DR. UMA K.

42. lodide Used only preoperatively to shrink the gland. (prior to surgical removal of the gland). Treatment of thyroid storm. It is given as Lugol's solution (iodine and potassium iodide). Effects are visible within 24 hours. It is no longer used in long-term therapy. DR. UMA K.

43. lodide Adverse reactions: Hypersensitivity reaction . Drug fevers, metallic taste, bleeding disorders. Gastric irritation. Long-term use can lead to sudden disinhibition of hormone synthesis, producing acute hyperthyroidism. DR. UMA K.

44. Thioamides Propyithiouracil (PTU), methimazole. Inhibit the peroxidase enzymes catalyzing the oxidation of iodide, thus reducing the synthesis of thyroid hormones. PTU also inhibits the peripheral deiodination of T4 to T3. Delay in onset (until preformed hormones have been metabolized). DR. UMA K.

45. Thioamides Used for control of hyperthyroidism until surgery. Suppression of thyroid hormone synthesis until the effect of radioactive iodide begins. Long-term therapy of mild-to-moderate hyperthyroidism. The drugs are given PO. DR. UMA K.

46. Thioamides Adverse reactions. Mild maculopapular rash, joint pain, headache, nausea, and loss of hair. Rare: agranulocytosis. Crosses the placenta and enter breast milk, which can lead to hypothyroidism in the fetus and nursing infant. Pregnancy ? DR. UMA K.

47. Radioactive iodine ( 131 I) PO or IV. Rapidly taken, then is incorporated into thyroglobulin. Leads to partial or total destruction of the gland by emission of beta particles. Damage to surrounding tissue is minimal. DR. UMA K.

48. Radioactive iodine ( 131 I) Used in the treatment of hyperthyroidism. Side effects and toxicity. Major: hypothyroidism . Should be avoided during pregnancy. DR. UMA K.

49.  -Blockers Excess thyroid hormones, upregulation of  -adrenergic receptors. Tachycardia, tremors, anxiety. Inhibits peripheral conversion of T4 to T3. DR. UMA K.

50. Propranolol Adjuncts in the treatment of hyperthyroidism. Reduce the symptoms of the disease (e.g., tachycardia. anxiety) until the antithyroid drugs can take effect. Propranolol also inhibits the peripheral conversion of T4 to T3 via 5' deiodinase. DR. UMA K.

51. Myxedema Both hypo or hyperthyroidism. Myxedema w/hypothyroidism Apathy, listlessness, edema accumulates in skin and other tissues. Broadening of facial features. DR. UMA K.

52. Myxedema Myxedema w/hyperthyroidism. Localized areas of hyperpigmentation. Usually in feet and lower legs. DR. UMA K.

53. Interactions w/receptors Amiodarone: Structurally resembles thyroid hormones. May cause hypo or hyperthyroidism. Lithium L-Dopa Estrogens DR. UMA K.

54. A 29 YO female complains of restlessness and increasing anxiety. HR 135 bmp, PE: Tremors. Palpation on the neck reveals a 3cm nodule on her thyroid gland. Laboratory test are sent to confirm the diagnosis. In the meantime, with drug could be given to acutely reduce her physical symptoms? Propylthiouracil. Furosemide. Prednisone. Iodine. Propanolol. DR. UMA K.

55. TSH Testing Thyroid “ Sends Telegram” Pituitary T3 & T4 TSH

56. Why Test Women Over 40? Early Detection Early Treatment Prevention of: Organ Damage Unpleasant Symptoms Other Negative Health Consequences DR. UMA K.

57. Treating Thyroid Disorders Radioiodine Therapy Stop Thyroid Hormone Production Anti-thyroid Drugs Often Helpful Replacement Therapy Often Needed Surgery Maybe Necessary Monitoring Tailored to Individual Patient Status and Needs DR. UMA K. Hyperthyroidism

58. Treating Thyroid Disorders Daily Oral Medication to Replace Missing Hormone Individualized Dosing Adjustment to Find the Right Dose for Each Patient Annual Monitoring DR. UMA K. Hypothyroidism

59. DR. UMA K. Thank you Thank you