Natural course of subclinical hyperthyroidism in primary care in the Netherlands

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.