Abstract
BACKGROUND: Subclinical hyperthyroidism (SHT), a low serum thyroid-stimulating hormone (TSH) and normal free thyroxine (FT4) concentration, has potential health implications, yet the epidemiology and factors influencing its natural course in a primary care setting remain unclear. OBJECTIVES: To investigate the incidence and natural course of SHT in primary care and assess guideline adherence to follow-up recommendations within Dutch primary care. METHODS: Using a retrospective cohort design in general practitioner data from the PHARMO Data Network in the Netherlands (2012-2021), patients with biochemically confirmed SHT were followed to assess progression to hyperthyroidism, recovery, or persistence. Adherence to the Dutch primary care SHT guideline was evaluated. RESULTS: The SHT annual incidence was approximately 200 per 100,000 person-years. Among the 11,163 SHT patients, 47% recovered, 11% persisted, and 8% progressed to overt hyperthyroidism over a median follow-up of 5 years. Lower TSH (<0.1 mU/L) and female sex were associated with lower odds of recovery (OR for TSH <0.1 mU/L: 0.50, 95% CI: 0.43-0.58; OR for women: 0.82, 95% CI: 0.70-0.96) and higher odds of progression to overt hyperthyroidism (OR for TSH <0.1 mU/L: 2.36, 95% CI: 1.97-2.83; OR for women: 1.69, 95% CI: 1.32-2.17). Guideline adherence evaluation showed that 33% received follow-up TSH measurement within 6 months, and 4% underwent TSH-receptor antibody testing. CONCLUSION: This study highlights that a small subset of SHT patients progress to overt hyperthyroidism. Factors increasing the odds for progression included lower baseline TSH and female sex. Our findings indicate a need for improved guideline adherence.