Practice Uncertainties

Are we overtreating subclinical hypothyroidism in pregnancy?

BMJ 2015; 351 doi: https://doi.org/10.1136/bmj.h4726 (Published 12 October 2015) Cite this as: BMJ 2015;351:h4726
  1. Kate Sophie Wiles, NIHR doctoral research fellow1,
  2. Sheba Jarvis, academic specialist registrar in endocrinology2,
  3. Catherine Nelson-Piercy, professor of obstetric medicine34
  1. 1Women’s Health Academic Centre, St. Thomas’ Hospital, London SE1 7EH, UK
  2. 2Imperial College, London SW7 2AZ
  3. 3Guy’s and St Thomas’ NHS Foundation Trust, London SE1 7EH
  4. 4Imperial College Healthcare NHS Trust, London W12 0HS
  1. Correspondence to: K S Wiles kate.wiles{at}kcl.ac.uk
  • Accepted 30 June 2015

The bottom line

  • Base the diagnosis of subclinical hypothyroidism in pregnancy on a normal thyroxine concentration and thyroid stimulating hormone above the local gestation specific reference range, rather than a universal threshold of 2.5 mU/L

  • Base any change in thyroxine dose in pregnancy on thyroid function tests interpreted according to gestation specific normal ranges

  • No consistent evidence shows that subclinical hypothyroidism in pregnancy causes adverse outcomes or that empirical treatment has clear benefit or harm

Overt hypothyroidism is diagnosed with a high serum thyroid stimulating hormone (TSH) concentration in conjunction with a low serum thyroxine concentration or an isolated TSH concentration above 10 mU/L. Subclinical hypothyroidism is a biochemical diagnosis based on a high TSH concentration with normal thyroxine.

The benefits of treating overt hypothyroidism during pregnancy include improved obstetric and neonatal outcomes. However, evidence for the management of subclinical hypothyroidism and appropriate treatment targets in pregnancy are lacking. Despite this, international guidelines have set a low TSH threshold for the diagnosis and treatment of both new and pre-existing hypothyroidism in pregnancy.1 2 This threshold potentially increases the prevalence of subclinical hypothyroidism in pregnancy and may “medicalise” women despite a lack of clear evidence that treatment improves outcome.

What is the evidence of the uncertainty?

We reviewed the evidence used to produce international guidelines on hypothyroidism and pregnancy.1 2 In addition, we searched PubMed, Web of Science, and Google Scholar by using the terms subclinical hypothyroid*, thyroxine, thyroid, and thyrotropin in combination with pregnan* and miscarriage to find additional data from randomised trials, cohort studies, systematic reviews, and meta-analyses published between 1990 and 2014.

What is a “normal” TSH in pregnancy?

The upper limit for TSH outside of pregnancy is 4.12 mU/L.3 However, guidelines recommend a TSH concentration of less than 2.5 mU/L in the first trimester,1 despite the fact that observational studies give a much broader normative range for TSH, especially when …

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