Tools for Practice


#249 Helping physicians fatigued by TSH Screening and Subclinical Hypothyroidism


CLINICAL QUESTION
Is there evidence for screening for thyroid function or treating subclinical hypothyroidism?  

BOTTOM LINE
There is no randomized controlled trial (RCT) of screening for thyroid function [ordering thyroid stimulating hormone (TSH) in non-pregnant healthy people]. Despite approximately 20 RCTs, there are no patient-oriented benefits (like preventing cardiovascular disease or reduced fatigue or weight) in treating subclinical hypothyroidism. Guidelines recommend against both.


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EVIDENCE
Screening for thyroid function: No RCTs or controlled observational studies assess screening for thyroid function or the use of TSH test for screening.1,2  Treating subclinical hypothyroidism (TSH 4-10 but T3/T4 normal): 
  • Clinical endpoints: Four systematic reviews (with 18-21 RCTs)1-4 from the last 5 years report on 18-21 RCTs.1-4 Treatment of subclinical hypothyroidism (levothyroxine typically) versus placebo had no effect on: 
    • Mortality or new cardiovascular disease.2-4 
    • Quality of life, depressive symptoms, fatigue, or thyroid-related symptoms scores.1-4 
    • Cognitive function.1-4 
    • BMI/Weight.1-4 
    • Newest RCT, 251 elderly patients (mean age 85), no benefit on any outcome (~1.5-year follow-up).5 
  • Surrogate markers: 
    • Blood Pressure (BP): Three systematic reviews found no difference,1,2,4 while another found systolic BP reduced 2.5 mmHg (not diastolic).6 
    • Lipids: Of four systematic reviews, two found no effect and two found treatment reduced total cholesterol or LDL 0.1-0.6 mmol/L (no change in HDL or triglycerides).7,8 
    • There is no evidence these small, inconsistent changes matter clinically. 
Context: 
  • Subclinical Hypothyroidism generally defined as TSH ~4-10mIU/L, with normal T3/T4 and no clear symptoms of hypothyroidism. 
  • TSH may vary up to 50% between tests9 and daily fluctuations10 in individuals can be 26%. 
  • Prevalence of subclinical hypothyroidism (in the developed world) is 4-10%, with 2-6% of these developing overt hypothyroidism. Subclinical hyperthyroidism prevalence is ~2% with 1-2% of these developing overt hyperthyroidism.2,11 
    • 40% subclinical hypothyroidism revert to normal over ~2.5 years.12 
    • Symptoms are often poor predictors. Example: one study found ~18% of euthyroid, ~22% subclinical hypothyroid, ~26% overt hypothyroid patients reported ≥4 symptoms of hypothyroidism.13 
  • Canadian Task Force on Preventive Health Care recommends against screening for thyroid function in asymptomatic non-pregnant patients or treating subclinical hypothyroidism.14 
 
December 9, 2019

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Author(s):

  • G. Michael Allan MD CCFP
  • Jennifer Young MD CCFP-EM

1. Rugge JB, Bougatsos C, Chou R. Ann Intern Med. 2015; 162:35-45.

2. Reyes Domingo F, Avey MT, Doull M.  Syst Rev. In press

3. Bekkering GE, Agoritsas T, Lytvyn L, et al. BMJ 2019; 365:l2006 doi: 10.1136/bmj.l2006

4. Feller M, Snel M, Moutzouri E, et al.  JAMA. 2018; 320:1349-59.

5. Mooijaart SP, Du Puy RS, Stott DJ, et al.  JAMA. 2019 Oct 30:1-11. doi: 10.1001/jama.2019.17274.

6. He W, Li S, Zhang JA, et al.  Front Endocrinol (Lausanne). 2018; 9:454.

7. Li X, Wang Y, Guan Q, et al. Clin Endocrinol (Oxf). 2017; 87:1-9.

8. Abreu IM, Lau E, de Sousa Pinto B, et al. Endocr Connect. 2017; 6:188-99.

9. McCormack J, Holmes DT.  BMJ. In press.  

10. Scobbo RR, VonDohlen TW, Hassan M, et al. W V Med J. 2004; 100:138-42.

11. Gharib H, Tuttle RM, Baskin HJ, et al.  J Clin Endocrinol Metab. 2005; 90:581-5.

12. Díez JJ, Iglesias P. J Clin Endocrinol Metab. 2004; 89:4890-7.

13. Canaris GJ, Manowitz NR, Mayor G, et al. Arch Intern Med. 2000; 160:526-34.

14. Birtwhistle R, Morissette K, Dickinson JA, et al. CMAJ 2019; 191 (46): E1274-E80.

Authors do not have any conflicts of interest to declare.