BMJ Rapid Recommendations- a collaborative effort between the MAGIC group and The BMJ, has recently issued a clinical practice guideline which could alter practice in the treatment of adults with subclinical hypothyroidism. This guideline was triggered by a recent systematic review of randomised controlled trials that weighed the benefits and harms of thyroid hormones for adults with SCH.

Subclinical hypothyroidism (SCH) is defined as a biochemical state in which the thyroid stimulating hormone (TSH) level is elevated, but the free T4 (thyroxine) level is normal. About 90% of all patients with SCH have TSH levels between 4 and 10mIU/L. Some people may experience symptoms linked to the abnormality. Other data have suggested links to overt hypothyroidism and adverse outcomes such as increased risk of coronary heart disease.

Currently, the guidelines recommend thyroid hormones for adults with TSH levels >10 mIU/L and for people with lower TSH values who are young, symptomatic, or have specific indications for prescribing.

The BMJ guideline panel issues a strong recommendation against thyroid hormones in adults with SCH (elevated TSH levels and normal free T4 (thyroxine) levels). It does not apply to women who are trying to become pregnant or patients with TSH >20 mIU/L. It may not apply to patients with severe symptoms or young adults (such as those ≤30 years old).

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Guideline overview

Source: BMJ 2019;365:l2006

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Source: BMJ 2019;365:l2006

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Current guidance on thyroid hormone treatment for subclinical hypothyroidism

1. National Institute for Health and Care Excellence (NICE) CKS guidelines, 2018

• TSH >10mIU/L
  • Age <70 years, treat
  • Age ≥70 years, watch and wait
• TSH 4-10mIU/L
  • Age <65 years with symptoms, consider trial
  • Age ≥65 years, watch and wait

2. UpToDate, 2018

• TSH <7mIU/L
  • Age >65/70 years, observe
  • Age <65/70 years, treat if symptoms, observe without symptoms
• TSH 7-10mIU/L
  • Age >65/70 years, treat if symptoms, observe without symptoms
  • Age <65 years, treat
• TSH >10mIU/L: treat

3. European Thyroid Association (ETA), 2013

• Age <70 years
  • TSH >10mIU/L, treat
  • TSH <10mIU/L with symptoms, start trial
  • TSH <10mIU/L without symptoms, observe
• Age >70 years:
  • TSH <10mIU/L, observe
  • TSH >10mIU/L, consider treatment if clear symptoms or high cardiovascular risk

4. American Thyroid Association (ATA), 2012

• TSH >10mIU/L, consider treatment
• TSH <10mIU/L, consider treatment if symptoms suggestive of hypothyroidism, positive antibodies to thyroid peroxidase, or evidence of atherosclerotic cardiovascular disease, heart failure, or risk factors for these diseases

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Evidence for the guideline

A guideline panel including patients, clinicians, and methodologists produced this recommendation in adherence with standards for trustworthy guidelines using the GRADE approach. The systematic review that triggered this guideline compared the effects of thyroid hormone treatment to that of no treatment or placebo in adults with SCH.

The systematic review included 21 trials with 2192 participants. The results from the clinical trials showed that, for adults with SCH, thyroid hormones consistently demonstrated no clinically relevant benefits for quality of life or thyroid related symptoms, including depressive symptoms, fatigue, and body mass index (moderate to high quality evidence). Thyroid hormones may have little or no effect on cardiovascular events or mortality (low quality evidence), but harms were measured in only one trial with few events at two years’ follow-up.

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Understanding the recommendation

The panel concluded that almost all adults with SCH would not benefit from treatment with thyroid hormones. Other factors in the strong recommendation include the burden of lifelong management and uncertainty on potential harms. Instead, clinicians should monitor the progression or resolution of the thyroid dysfunction in these adults.

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Who does it apply to?

The recommendation applies to most adults, with SCH after at least two consecutive thyroid function tests, with or without mild to moderate symptoms, who are considering initiating thyroid hormone treatment.

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For who is the recommendation not applicable?

1. Women who are trying to become pregnant. Guidelines recommend levothyroxine for pregnant women depending on TSH level and presence of antibodies to thyroid peroxidase.
2. Those with very high TSH levels (>20mIU/L) and with normal T4 (thyroxine) levels.

Additionally, this recommendation may not apply to

• Those with severe symptoms
• Very young adults (such as ≤30 years old)
• Women at risk of unplanned pregnancy. Clinicians may consider offering thyroid hormones because pregnant women with SCH may be at increased risk of adverse outcomes for mother and baby
• Patients who already are on thyroid hormones