The grey zone of thyroid function: Clinical significance and management controversies in subclinical hypothyroidism

Abstract

Subclinical hypothyroidism (SCH) is defined by elevated serum thyroid-stimulating hormone (TSH) levels with normal thyroxine (T4) concentrations, representing a diagnostic grey zone in thyroid function. Its prevalence ranges from 4–10% among adults, particularly affecting women, yet it often eludes detection due to the subtlety of symptoms. This spectrum is notably heterogeneous: the majority of SCH cases (~3–8% of adults) exhibit mild disease with TSH levels between 4.5 and 10 mIU/L, whereas a smaller fraction (~0.5–1%) presents with severe SCH, characterised by TSH levels ≥ 10 mIU/L — a differentiation that entails significantly divergent prognostic and therapeutic consequences. This review investigates the complexities of SCH, including its potential associations with cardiovascular risk, neurocognitive changes, and progression to overt hypothyroidism (OH). The efficacy of levothyroxine therapy remains contentious, with conflicting studies regarding its role in symptom relief and cardiovascular event reduction. Additionally, the variability in clinical progression complicates the distinction between benign biochemical variations and clinically significant thyroid disorders. By highlighting special clinical scenarios and management controversies, we present approaches to inform clinical decision-making and promote individualised patient care.