Chapter 49 Thyroid

1. Chapter 49 Thyroid

2. Chapter 49 Thyroid • Affects 5-15% of the population • 3:1 F:M • Two active thyroid hormones T3 (triodothyronine) and T4 (thyroxine) produced by thyroid in response to TSH (thyroid stimulating hormone) released from pituitary (negative-feedback system)

3. Thyroid continued • T4 converted to T3 by deiodination in the pituitary and peripherally as well • T3 is 4x as potent as T4 • T3 concentration < T4 • DRUGs and diseases affect conversion, Table 49-1 • 99.97% of T4 is bound (70% to thyroxin binding globulin, 15% to thyroxine-binding pre-albumin, and albumin)

4. Thyroid continued • 0.03% T4 is Free • extensive binding results in long 1/2 life • (5-10 days) • T3 - 99.7% bound (less than T4) • 0.3% of T3 is Free (shorter 1/2 life (1.5 days) and increased potency

5. Hypothyroidism • Deficiency of thyroid hormone • 1.4-2% in females, 0.1-0.2% in males • >60 yo - 6% in females, 2.5% in males • Primary hypothyroidism - problem with thyroid gland • secondary hypothyroidism • hypothalamic- pituitary malfunction • table 49-2 • (primary more common than secondary)

6. Hypothyroidism continued • Hashimoto’s thyroiditis - (autoimmune) most common cause of primary hypothyroidism. • Can present with hypothyroidism and goiter (thyroid gland enlargement) or without goiter, or euthyroid with goiter. • Clinical and lab findings • Table 49-3

7. Hypothyroidism continued • Myxedema coma-end-stage hypothyroidism- 60-70% mortality • hypothemia,confusion, stupor,coma, CO2 retention, hypoglycemia, hyponatremia, ileus • Older patient with hypothyroidism can present with minimal or atypical symptoms (weight loss, deafness, tinnitus, carpal tunnel syndrome) • mild/subclinical hypothyroidism may have few or no symptoms

8. Drug Therapy of hypothyroidism • Levothyroxine is preferred • DOSING Table 49-4 • myxedema coma- large doses of levothyroxine (400 mcg) are necessary - saturates empty thyroid binding sites • subclinical hypothyroidism controversial whether to give T4 or not (lab values are normal)

9. Drug Therapy of Hypothyroidism continued • Goal of therapy- reverse signs and symptoms of hypothyroidism and normalize TSH and thyroxine levels • Improvement can be seen in 2-3 weeks of therapy • Excessive replacement (low TSH) associated with osteoporosis and cardiac changes

10. Drug Therapy of hypothyroidismcontinued • Optimal dosage continued for 6-8 weeks (to reach steady state) then Retest thyroid function tests. • After euthyroid state reached then test q 3-6 months for 1 year, then yearly thereafter • Don’t administer interacting medications (eg. Iron, aluminum, calcium, cholesterol resin binders, raloxifene) at same time as thyroid preparation.

11. Hyperthyroidism (thyrotoxiois) • Hypermetabolic syndrome • excessive thyroid hormone • 2% females, 0.1% males • causes- Table 49-5 • GRAVES disease - most common cause • autoimmune • 1 or more of following: hyperthryroidism, diffuse goiter, ophthalmopathy (exophthalmos), dermopathy, acropachy (thickening of fingers or toes)

12. Hyperthyroidism continued • IgG or thyroid receptor antibodies - • TSH- like ability to stimulate hormone. • Peak incidence 30-40 years old • Clinical and lab findings • Table 49-6 • Elderly patient- usual symptoms may be absent, pt. may present as “apathetic”

13. Hyperthyroidism continued • Consider hyperthyroidism in elderly patient with new or worsening cardiac findings (eg. a fib.) • untreated can lead to thyroid storm - exaggerated thyrotoxicosis symptoms and high fever

14. Treatment • Antithyroid drugs (thioamides), radioiodine, surgery • Radioactive iodine - older patients, patients with cardiac disease, ophthalmopathy, toxic nodular goiter • surgery - preferred if obstructive symptoms, malignancy is suspected • Pregnant patients- thioamides, surgery, radioactive iodine contrainidicated.

15. Thioamides • Methimazole (tapozole), propylthiouracil (PTU) • primary therapy for hyperthyroidism • prevent hormone synthesis - does not affect existing stores of thyroid hormone • hyperthyroid pt. will continue to have symptoms for 4-6 weeks after starting thioamide (need to use B-blockers)

16. Thioamides continued • PTU works more quickly than methimazole because • PTU also inhibits T4 to T3 conversion • PTU preferred in thyroid storm • PTU not secreted in breast milk • Methimazole easier to take (daily) than PTU (2-3xD)

17. Thioamides continued • Generally used for 1 to 1-1/2 yrs and hope spontaneous remission after D/C . (unfortunately not so common) • ADV effects - Skin rash, GI complaints, agranulocytosis, hepatitis • Other options - surgery, radioactive iodine • other considerations - malignancy

18. TFTThyroid function Tests • TSH, (thyroid stimulating hormone) , FT4 (Free T4), TT4 (total T4), TT3 (Total T3), FT3 (free T3), radioactive iodine uptake (RAIU), • Table 49-7 • FT3- expensive, difficult, unnecessary • calculated FT3- correlates well with FT3

19. TFT continued • FT4I and FT3I - indirect estimate of free T4 and T3 when TBG binding is altered - FT4 and FT3 are preferred.

20. TT4 and TT3 • TT4 total thyroxine and TT3 total triiodothyronine - measure of FREE and BOUND DRUGS • falsely elevated - common in euthyroid pregnant woman • peripheral conversion of TT4 to TT3 can be altered and TT3 can be low (eg. Older pts, acute/chronic nonthyroid illness)

21. TT4 and TT3 continued • TT3 helpful to detect relapse of Graves disease and to confirm hyperthyroidism despite normal TT4 level.

22. TSH Test of hypothalamic-pituitary Thyroid Axis • Thyroid stimulating hormone (TSH) also called thyrotropin • most sensitive test to evaluate thyroid function • TSH can be abnormal even when FT4 is WNL (TSH is specific for individual “set point”) FT4 appears normal but low for that individual

23. TSH test continued • High TSH - hypothyroid • Low TSH - hyperthyroid • TSH can be abnormal in euthyroid patients (with nonthyroid illness or pt recv. Drug interfere with TSH secretion - dopamine agonists and antagonists)

24. Test of gland function • RAIU - radioactive iodine uptake - measure of iodine utilization by gland and indirect measure of hormone synthesis. • Used to calculate dose of radioactive iodine for treatment of Graves disease.

25. Test of Autoimmunity • TPO (thyroperoxidase) and ATgA (antithyroglobulin) antibodies-indicate autoimmune process • 60-70% patients with Graves disease and 95% of patients with Hashimotos thyroditis have positive antibodies • 5-10% patients without disease have + antibodies

26. Test of Autoimmunity continued • TRAb (thyroid receptor antibodies) • IgG immunoglobulins - + in all pts with Graves • can stimulate thyroid to produce hormone • useful in select situation (pg. 49-8) • expensive, not helpful in “typical” Graves patient

27. Question 2 • What is euthyroid sick syndrome? • How often can this syndrome be found in chronically ill or hospitalized patients? • What are usual changes seen in TFT? • How valuable are T4 and T3 measurements in patients with significant non-thyroid illness?

28. Question 2 continued • Which TFT is useful to determine euthyroid state in sick pt? • When should TSH be repeated (in sick patient) to confirm euthyroidism?

29. Question 3 • How do anticonvulsants alter serum thyroid hormone levels? And by what mechanism? • What happens to TSH in these patients?

30. Question 4 • Under what conditions can a patient have increased TT4 and decreased resin uptake and normal TSH and FT4? • What is the reason for this? • How long after oral contraceptive D/C will it take for TFT to return to normal?

31. Question 5 • How does Amiodarone affect TFT? • Can amiodarone cause hyper or hypothyroidism? • What occurs with dopamine agonists (eg. Dopamine, bromocriptine, levodopa) and TSH? • What occurs with dopamine antagonists (metoclopromide) and TSH?

32. Question 7 • Is initiation of dessicated thyroid in a hypothyroid patient justified? Why not? • What is approximate equivalent synthetic T4 to 60 mg of dessicated thyroid? • What is thyroid replacement of choice? • Why can we dose T4 once daily? • What is usual absorption of T4?

33. Question 7 continued • When should T4 be taken in relation to meals? • NOTE: since publication of text, many T4 products are now AB rated to each other which means they are considered interchangeable by FDA • why is triiodothyronine not recommended for routine thyroid replacement?

34. Question 7 continued • What have small studies found with combination of T4 and small dose of T3? • What are other disadvantages to T3? • What is primary use of T3? • What is liotrix?

35. Question 8 • What is usual replacement dose (using patient weight)? • What can happen if we administer excessive T4? • How often should TSH be checked in pt stabilized on T4? • What are some risk factors for cardiotoxicity that require careful dosage titration?

36. Question 8 continued • How was T4 started in MW? And when was testing performed? • In general, how should T4 dosing adjustments be handled?

37. Question 9 • Why should we wait 6-8 weeks after initiation of T4 to check TFT?

38. Question 10 • Which lab values are best indicators of euthyroidism in patients treated with levothyroxine? • TFT should be done at trough levels, this is because one study found that…..?

39. Question 12 • Which is preferred; IV or IM administration of levothyroxine? And why? • Why should parenteral doses of levothyroxine be decreased in relation to PO doses? • When is once-weekly IM levothyroxine injection an option?

40. Question 13 • What can occur to the fetus when the mother has inadequately treated hypothyroidism? • Does thyroid hormone cross the placenta?

41. Question 14 • What are early clinical findings of congenital hypothyroidism? • What can happen if hypothyroidism is untreated during first three years of life?

42. Question 15 • What are possible reasons for RT’s therapeutic failure? • What is the most likely explanation for failure? • What questions/intervention should be suggested? • What meds can interfere with thyroid bioavailability?

43. Question 16 • How does hypothyroidism affect cholesterol?

44. Question 17 • What is myxedema coma? What are the classic features? • Which medications should be used with caution in myxedema coma? • NOTE: treatment of myxedema coma is in text for reference

45. Question 19 • What are symptoms of “myxedema heart”? • NOTE: hypothyroidism should be excluded in all pts with new or worsening symptoms of CVD.

46. Question 20 • How does hypothyroidism aggravate subendocardial ischemia during an acute MI? • How do nitrates precipitate hypotension? • Why are cardioselective Beta Blockers preferred over non-cardioselective Beta Blockers?

47. Question 21 • What can occur when initiating T4 in patients with longstanding hypothyroidism, CAD, or advanced disease? • NOTE: you may want to address cardiac disease (eg angina) before T4 therapy • What dose should be used in “at risk” patient?

48. Question 21 continued • NOTE: some patients may not be able to tolerate full T4 replacement dose, in these patients, T4 dose is balance between prevention of myxedema coma and cardiac toxicity. • Why is T3 theoretically better for use in cardiac patients? • Even so, why is T3 not recommended?

49. Question 22 • NOTE: the treatment of subclinical hypothyroidism (ie no symptoms of hypothyroidism with elevated TSH) is controversial; see question 22 for details.

50. Question 23 • What did a randomized, double-blind, PCB-controlled determine about T4 supplementation in pts with symptoms of hypothyroidism (eg fatigue, cold intolerance, dry skin) and normal TSH and T4 levels?