Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline

Abstract

Clinical questionWhat are the benefits and harms of thyroid hormones for adults with subclinical hypothyroidism (SCH)? This guideline was triggered by a recent systematic review of randomised controlled trials, which could alter practice.Current practiceCurrent guidelines tend to recommend thyroid hormones for adults with thyroid stimulating hormone (TSH) levels >10 mIU/L and for people with lower TSH values who are young, symptomatic, or have specific indications for prescribing.RecommendationThe 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).How this guideline was createdA guideline panel including patients, clinicians, and methodologists produced this recommendation in adherence with standards for trustworthy guidelines using the GRADE approach.The evidenceThe systematic review included 21 trials with 2192 participants. For adults with SCH, thyroid hormones consistently demonstrate 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.Understanding the recommendationThe 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. Recommendations are made actionable for clinicians and their patients through visual overviews. These provide the relative and absolute benefits and harms of thyroid hormones in multilayered evidence summaries and decision aids available in MAGIC (https://app.magicapp.org/) to support shared decisions and adaptation of this guideline.

Triiodothyronine secretion in early thyroid failure: The adaptive response of central feedforward control

“…2,4 Conversely, the presence or absence of a thyroid gland alters the dependencies of system control, playing a much more adaptive role than can possibly be extrapolated from studies in healthy individuals. They discourage indiscriminate medical intervention at an early stage of thyroid autoimmune disease with a TSH-lowering drug such as LT4.…”

“…This syndrome is surrounded by considerable diagnostic uncertainty and continued disagreement about the need for LT4 substitution. 2,4 Here, we elucidated clinically observable mechanisms of defence against challenges presented by a declining thyroid reserve. Using applied mathematical modelling paired with clinical observation, we demonstrate a strong central dependency of both T3 secretion and T4-T3 conversion.…”

“…2 Conversely, the laboratory constellation of a TSH measurement above its reference range, accompanying an FT4 concentration still within its reference range, has been designated subclinical hypothyroidism. [2][3][4] Consequently, the process of clinical decision-making has been dominated by measuring TSH and FT4, the determination of the biologically more active thyroid hormone triiodothyronine (T3) being relegated to an insignificant role. [2][3][4] Consequently, the process of clinical decision-making has been dominated by measuring TSH and FT4, the determination of the biologically more active thyroid hormone triiodothyronine (T3) being relegated to an insignificant role.…”

“…2 Subclinical hypothyroidism is generally regarded as a thyroid disease, although the transition from the euthyroid to the hypothyroid state is poorly defined, resulting in a schism between guideline-based diagnostic criteria and therapeutic recommendations. [2][3][4] Consequently, the process of clinical decision-making has been dominated by measuring TSH and FT4, the determination of the biologically more active thyroid hormone triiodothyronine (T3) being relegated to an insignificant role. This view stemmed from a physiological understanding of thyroid hormone transporters actively importing or exporting T4 and T3, deiodinating enzymes converting T4 into the biologically more active metabolite T3 and thyroid hormone receptors binding to nuclear DNA, thereby exerting a plethora of genomic T3 actions.…”

Intrahepatic cholestasis of pregnancy and comorbidity: A 44‐year follow‐up study

“…It can be speculated that there might also be an autoimmune aspect to the pathogenesis of ICP. There might be overdiagnosis of hypothyroidism, but this can be regarded similar in both groups …”