Evaluation and Management of Hypothyroidism in the Primary Care Setting

1. Evaluation and Management of Hypothyroidism in the Primary Care Setting Christopher P. Paulson, Maj, USAF, MC Faculty, Eglin AFB Family Medicine Residency

2. Case Scenario While precepting residents the following case is presented for your review 45 yo female with abnormal thyroid labs discovered during an evaluation of mild fatigue of several months duration

3. Case Scenario Past Med Hx: negative for diabetes, autoimmune disorders, radiation exposure, and known thyroid disease or thyroid surgery Medications: none Family Hx: negative for autoimmune disorders and thyroid dysfunction

4. Case Scenario Labs: TSH 6.73 (0.46 - 4.68) mIU/ml FT4 1.32 (0.71 � 2.19) ng/dl Repeat labs in 6 weeks TSH 6.82 FT4 1.27

5. Case Scenario The patient desires thyroid replacement therapy The resident inquires about treatment guidelines for subclinical hypothyroidism How do you respond?

6. Learning Objectives Identify common risk factors and etiologies of hypothyroidism Be able to evaluate and initiate appropriate treatment for hypothyroidism Use an evidence-based approach for population screening and sub-clinical disease management Apply management guidelines to your patient population

7. Overview of Hypothyroidism Epidemiology Etiology Evaluation and Treatment Subclinical Disease and Screening Guidelines Conclusion/Key Points

8. Epidemiology Incidence of Hypothyroidism 1% in areas with adequate iodine (U.S.) Female to Male ratio 8:1 Incidence increases with age

9. Epidemiology Risk Factors Downs Syndrome Turners Syndrome Head and neck radiation exposure Type 1 Diabetes Family history of autoimmune disease History of previous thyroid disorder Presence of other autoimmune disorders Postpartum state Family history of thyroid disorders

10. Epidemiology Symptoms Fatigue Weight gain Headache Dry Skin Hoarseness of voice Irregular menses Decreased appetite Myalgias Parasthesias Somnolence Lethargy Depression Cold intolerance

11. Epidemiology Symptoms Fatigue � 90% Weight gain Headache Dry Skin Hoarseness of voice Irregular menses Decreased appetite Myalgias Parasthesias Somnolence Lethargy Depression Cold intolerance

12. Epidemiology Signs Nonpitting edema Constipation Memory defects Coarse skin Dry skin Brittle nails Bradycardia Ataxia Diminished libido Bleeding tendencies Alopecia Macroglossia Slowed speech Dementia Psychosis Slowed reflexes

13. Etiology Primary hypothyroidism (95 � 99%) Chronic autoimmune thyroiditis (Hashimoto�s) Goitrous Atrophic Iatrogenic Thyroidectomy Radioiodine treatment External beam radiation

14. Etiology Primary hypothyroidism Iodine deficiency (most common world-wide) Drugs Lithium, amiodarone, etc Infiltrative disease - rare Fibrous thyroiditis (Reidel�s thyroiditis) Hemochromatosis Scleroderma Others

15. Etiology Primary hypothyroidism Congenital Transient Hypothyroidism Postpartum Subacute (granulomatous) thyroiditis Subtotal thyroidectomy

16. Etiology Secondary and Tertiary hypothyroidism Tumor Postpartum pituitary necrosis (Sheehan�s) Hypophysitis Infiltrating disease TSH or TRH deficiency Trauma Radiation therapy

17. Etiology Other Thyroid hormone resistance � very rare

18. Evaluation When to evaluate Signs or symptoms suggestive of hypothyroidism Periodic assessment for high risk medications (amiodarone, lithium, etc.) Screening at risk populations? Controversial � addressed in screening section

19. Evaluation Assess risk factors for hypothyroidism Medications (lithium, amiodarone, etc) History of head or neck radiation exposure Presence of Downs or Turners Family or personal history of autoimmune or thyroid disorders Type 1 diabetes

20. Evaluation

21. Evaluation Primary hypothyroidism Proceed to treatment Further evaluation generally not indicated For postpartum hypothyroidism, serial TSH and FT4, treat only if significantly symptomatic

22. Evaluation Secondary or tertiary hypothyroidism Image the sellar and suprasellar regions with MRI to evaluate for mass Screen for other hypothalamic or pituitary disease Adrenocortical, posterior pituitary, and gonadal dysfunction Consider consultation

23. Evaluation Thyroid hormone resistance Exceedingly rare If suspected � consultation is appropriate Subclinical hypothyroidism Addressed in later section

24. Treatment Guidelines Standard Replacement Therapy Synthetic thyroxine (T4) 1.6 mcg/kg/day � lean body mass 112 mcg in 70kg adult Full dose recommended regardless of degree of hypothyroidism Reassess after 6 weeks with TSH

25. Treatment Guidelines Special situations Elderly patients Start at 50 mcg/day and increase by 25 mcg/day every 6 weeks until TSH is normalized Known CAD Start at 25 mcg/day and increase by 25 mcg/day every 6 weeks until TSH is normalized

26. Treatment Guidelines Special situations Postpartum hypothyroidism Treat based on moderate or severe clinical symptoms not based on labs Only 1 in 4 will require treatment 50 to 100 mcg per day x 12 weeks Discontinue and recheck thyroid labs 6 wks later

27. Treatment Guidelines What about liothyronine (T3) replacement? Physiologically active 20% from thyroid directly and 80% from peripheral conversion of T4 Early studies indicated possible beneficial effects on mood, quality of life, and psychometric functioning

28. Treatment Guidelines Systematic review of the literature published in 2005 Levothyroxine (T4) compared with levothyroxine + liothyronine (T3) 9 controlled trials included Beneficial results in only a single study Quality of life, mood, psychometric performance

29. Treatment Guidelines Systematic review of the literature published in 2005 Increased incidence of side effects with T3 including palpitations, irritability, nervousness, dizziness, and tremor Overall patient preference for T3 Not explained by outcome measures No clear clinical benefit

30. Subclinical Hypothyroidism Generally defined as few or no symptoms of hypothyroidism with an elevated TSH and normal FT4 Historically unclear recommendations in the literature

31. Subclinical Hypothyroidism Possible benefits of treatment Symptom improvement Prevent progression to overt hypothyroidism Reduce lipid levels and subsequently lower risk of cardiovascular events Prevent poor developmental outcomes in children born to women with subclinical disease

32. Subclinical Hypothyroidism Possible risk of unnecessary treatment Development of osteoporosis Increased incidence of atrial fibrillation Cost

33. Subclinical Hypothyroidism What does the literature show? USPSTF review in 2004 No clear difference in lipid levels or cardiovascular outcomes for subclinical disease Except for patients with known thyroid disease No significant symptom improvement with treatment Except for patients with known thyroid disease

34. Subclinical Hypothyroidism What does the literature show? USPSTF review in 2004 Poor neurodevelopmental outcomes in children born to women with elevated TSH values in their first trimester Increase in fetal demise rate Average IQ at age 7 to 9 was 7 points less (significant) No studies on whether screening or treatment would impact outcome

35. Subclinical Hypothyroidism What does the literature show? USPSTF review in 2004 No increased risk of fracture or diminished bone density with levothyroxine treatment Except in those patients on suppressive therapy No increased risk of atrial fibrillation with treatment

36. Subclinical Hypothyroidism What does the literature show? Other considerations Annual rate of progression to overt disease No autoimmunity <2% No prior thyroid disease - < 2% Thyroid antibodies � 5-7% Elderly with thyroid antibodies � 20-24%

37. Case Scenario - revisited Initial labs: TSH 6.73 FT4 1.32 Repeat labs in 6 weeks TSH 6.82 FT4 1.27

38. Case Scenario - revisited The patient desires thyroid replacement therapy The resident inquires about treatment guidelines for subclinical hypothyroidism Now, how do you respond? What is the evidence based answer?

39. Case Scenario - revisited The evidence-based answer There is no clear indication to treat Likelihood of progressing on to overt hypothyroidism in this case is very low

40. Screening Guidelines The American Thyroid Association Screen ALL adults at age 35 and then every 5 years; more frequent for high risk or symptoms The American College of Physicians Screen women older than 50 with at least one symptom

41. Screening Guidelines The American Association of Clinical Endocrinologists Screen women of childbearing age or during the first trimester

42. Screening Guidelines The American College of Obstetricians and Gynecologists Be aware if signs and symptoms of postpartum thyroid dysfunction and evaluate when indicated

43. Screening Guidelines AAFP Recommends AGAINST routine screening in asymptomatic patients younger than age 60 No recommendation for those over 60

44. Screening Guidelines USPSTF Evidence is insufficient (I) to recommend for or against routine screening for thyroid disease in adults Fair evidence that TSH is useful in detecting subclinical disease Poor evidence that treatment improves clinically important outcomes

45. Screening Guidelines USPSTF � Clinical Considerations Clinicians should be aware of subtle thyroid dysfunction particularly in high risk groups Elderly Down Syndrome Post-partum women Radiation exposure (>20 mGy)

46. Screening Guidelines USPSTF � Clinical Considerations Subclinical hypothyroidism Is associated with poor obstetric outcomes and poor cognitive development in children Evidence for dyslipidemia, atherosclerosis, and decreased quality of life is inconsistent and less convincing

47. Screening Guidelines USPSTF � Discussion No controlled studies showing whether routine screening improved symptoms or health outcomes 2 of 3 small randomized studies demonstrated no benefit in treating subclinical disease No trials of treatment of subclinical disease for pregnant women

48. Screening Guidelines USPSTF � Discussion No clear benefit demonstrated on systematic review of the literature for either screening asymptomatic adults or treating subclinical thyroid disease

49. Conclusion/Key Points Hypothyroidism is commonly encountered in the primary care setting Be aware of signs and symptoms of hypothyroidism particularly in populations at risk There is insufficient evidence to recommend treatment with liothyronine (T3) over levothyroxine (T4)

50. Conclusion/Key Points There is insufficient evidence for screening asymptomatic patients without a history of thyroid disease There is no clear benefit in treating subclinical hypothyroidism Treatment is indicated in pregnancy due to known risk without treatment