Macro-Thyrotropin Syndrome: Prevalence and Clinical Profile of an Under-Recognised Rare Entity in Thyroidology.

Introduction: Macro-thyrotropin syndrome (macro-TSH) is a rare condition characterised by the formation of a complex between thyroid-stimulating hormone (TSH) and an unknown component, resulting in elevated TSH levels that do not accurately reflect thyroid status. This study aimed to investigate the prevalence and clinical profile of macro-TSH among patients with subclinical hypothyroidism (SCH). Methods: A total of 1500 patients were evaluated, with 135 exhibiting elevated TSH levels (>10 IU/mL) and normal free-thyroxine levels. Macro-TSH was diagnosed based on persistent elevated TSH levels despite serial dilutions and confirmed by less than 60% TSH recovery following polyethylene glycol (PEG) precipitation. Results: Finally, 115 were diagnosed with SCH, 15 with macro-TSH, and 1245 were categorised into non-thyroid groups. The prevalence of macro-TSH, SCH, and heterophilic antibodies interfering with immunoassay was 1.09%, 8.36%, and 0.36%, respectively. Among macro-TSH patients, 13.33% exhibited classical hypothyroid features, contrasting with the 52.0% observed in SCH patients. Female gender and a family history of hypothyroidism were associated with higher odds of having macro-TSH. Diabetes mellitus, clinical symptoms of hypothyroidism (except lethargy), higher TSH level, and post-PEG TSH recovery were significantly associated with SCH compared to macro-TSH. The mean TSH level was five times higher in macro-TSH compared to SCH. Conclusion: Macro-TSH syndrome represents a distinct clinical entity within the spectrum of SCH, characterised by disproportionately high TSH levels. Recognising macro-TSH is crucial for accurate diagnosis and appropriate management of SCH.