Should We Treat Subclinical Hypothyroidism

1. Should We TreatSubclinical Hypothyroidism? CQC Alap Shah Med/Peds PGY-1

2. History / Physical 41 y/o Male with PMHx DM II, HTN, ED presents for f/u Has continued problems with glycemic control with sugars 140-160s, problems with ED despite meds Had lost 10-15 lbs in 3 months � diet, exercise, but still felt it was �difficult to lose weight� FHx: �two sisters, one hypothyroid, one hyperthyroid� Meds: Glipizide, Sildenafil, Metformin PE: normal � no edema, no thyromegaly/nodularity, no arrhythmia, no obesity

3. Labs A1c � 14.5 (11/4/07), 9.6 (8/7/08) TSH � 10.29 (8/7/08) (nml 0.4 - 4.4) Anti TPO Ab � 1673.7 (nml < 9) Free T4 � 1.1 (nml 0.8 � 1.7) Testosterone � normal Lipids � Low HDL, High LDL, Normal TG

4. Next Step Would you� A. Start Levothyroxine therapy B. Monitor with TSH every 6 � 12 months C. Follow clinically D. Order additional tests

5. Subclinical Hypothyroidism State in which TSH is mildly elevated, indicating mild thyroid failure, but normal serum levels of T3 and T4 Most commonly caused by autoimmune thyroiditis, as in this patient By most studies, ~ 4 � 18% of patients with SH per year develop overt hypothyroidism Increased likelihood if Ab+, TSH>20, Hx radiation, chronic Li therapy Small amount of patients (not quantified) do recover normal thyroid function

6. Etiologies of (Non-Central) Hypothyroidism Chronic Autoimmune Thyroiditis Subacute Postpartum Thyroiditis Iodine Deficiency, Excess Thyroid surgery, I-131 exposure External Irradiation Infiltrative Disorders Sarcoid, Hemochromatosis, Leukemia, Lymphoma, Amyloid, TB, P jiroveci Drugs Lithium, Amiodarone, IFN-alpha, IL-2

7. When to Suspect SH Symptoms May be asymptomatic Can have vague complaints including fatigue, depression, weakness, sleep disturbance, memory problems, constipation, menstrual irregularities Signs May have no physical abnormalities Skin/hair changes, reflex delay, ataxia, hyperlipidemia, nonpitting edema, hoarseness, bradycardia, hypothermia

8. Initial Lab Evaluation What labs to order for workup and followup for subclinical hypothyroidism? TSH if any of the previously mentioned symptoms, or high suspicion with strong family history TSH is 98% sensitive and 92% specific for thyroid disease TSH is the definitive screening and monitoring lab for (non-central) thyroid disease If abnormal, repeat in 1 month and check Free T4

9. Initial Lab Evaluation Annals of Clinical Biochem (2006) Indications for Anti TPO Ab: Patients with subclinical hypothyroidism TSH from 4 - 10, normal Free T4 Goiter, regardless of TSH or Free T4 New onset thyrotoxicosis No indication to follow Ab once positive

10. Treatment Recommendations vary: USPSTF (2004) Consensus Conference Panel on Subclinical Thyroid Disease (2004) Endocrinology Clinics (2004) American Association of Clinical Endocrinologists Thyroid Task Force Various other groups, studies

11. Treatment USPSTF (2004) Treatment for subclinical hypothyroidism reduces symptoms of patients with history of Graves� and TSH > 10 Insufficient evidence for recommendations from other trials Most trials found there was no effect on lipid levels

12. Treatment Consensus Conference Panel on Subclinical Thyroid Disease (2004) For TSH between 4.5 and 10, no treatment Repeat TSH at 6 � 12 month intervals for change For TSH > 10, evidence inconclusive � agreement with USPSTF

13. Treatment Endocrinology Clinics (2004) Good evidence that treatment prevents overt hypothyroidism, but no convincing evidence that early treatment beneficial Improvement in lipid panel, but no hard studies on mortality benefits

14. Treatment National Guideline Clearinghouse (JAMA 2004) For TSH between 4.5 and 10, no treatment Follow up with TSH every 6 � 12 months Based on no clear cut benefit to these patients However, report stated that treatment may prevent signs and symptoms in those that do progress

15. Treatment ... And Followup AACE Thyroid Task Force (2006) � Treatment Guidelines Start at 25 � 50 micrograms / day Repeat TSH 6 � 8 weeks after starting treatment Titrate dose to keep TSH between 0.3 � 3 Once TSH stable, check levels and examine patient annually

16. Next Step Would you� A. Start Levothyroxine at 25-50 mcg/day B. Monitor with TSH every 6 � 12 months C. Follow clinically D. Order additional tests No definitive answer. Most importantly, remember to treat patient and not just the lab values.

17. When to Consult Endocrinology AACE recommends endocrine consult if: < 18 yrs Unresponsive to therapy Pregnant Cardiac history Presence of goiter or nodules Concurrent endocrine disease

18. Patient Due to initial SH, started Synthroid 25mcg daily x 2 wks, then 50mcg daily until follow up After TPO was +, called and instructed to continue regimen Follow up scheduled, pending�

19. References Devdhar et al. Hypothyroidism. Endocrinol Metab Clin N Am. 2007; 36:595-615. AACE Thyroid Task Force. Medical Guidelines For Clinical Practice For The Evaluation And Treatment Of Hyperthyroidism And Hypothyroidism. Endocrine Practice. 2006; 8:6. Herrick. Subclinical Hypothyroidism. American Family Physician. 2008; 77:7. Surks et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA.�2004; 291(2).

20. References Miller and Rogers. Which Lab Tests Are Best When You Suspect Hypothyroidism? Clinical Inquiries, Family Physicians Inquiries Network. 2008; 57:9. Downs and Meyer. How Useful Are Autoantibodies When Diagnosing Thyroid Disorders? Clinical Inquiries, Family Physicians Inquiries Network. 2008; 57:9. Sinclair. Clinical And Laboratory Aspects Of Thyroid Antibodies. Ann Clin Biochem. 2006; 43: 173-183. USPSTF. Screening For Thyroid Disease: Systematic Evidence Review. 2004.