Attenuated nocturnal thyrotropin rise in metabolic dysfunction-associated steatotic liver disease: a prospective cross-sectional study

The liver performs most peripheral thyroid hormone metabolism, and thyrotropin (TSH) secretion normally rises overnight. This rise is blunted in non-thyroidal illness but has not been examined in metabolic dysfunction-associated steatotic liver disease (MASLD). We compared the morning-to-midnight change in TSH between patients with MASLD without known thyroid disease and controls. In this single-centre, prospective, cross-sectional study of hospitalised adults, 53 patients with ultrasound-defined steatosis fulfilling MASLD criteria and 32 controls without steatosis had thyroid function measured at 08:00 and 24:00. The primary analysis was a linear mixed model of TSH with a group × time interaction; the midnight minus morning difference (ΔTSH) was the summary measure. Adjusted linear regression and analyses stratified by glycaemic status and C-reactive protein (CRP) were performed. Patients with MASLD had higher body mass index (BMI), glycated haemoglobin and diabetes prevalence (66.0% vs. 21.9%). The overnight change in TSH differed between groups (interaction β − 0.49 mU/L, 95% confidence interval [CI] − 0.96 to − 0.01; p = 0.044): TSH rose in controls but not significantly in MASLD (ΔTSH median − 0.14 vs. 0.19 mU/L; p = 0.019), reflecting mainly a higher morning TSH in MASLD (1.40 vs. 1.18 mU/L; p = 0.020). The difference was similar in size but not significant after adjustment for age, sex, BMI and diabetes (β − 0.52, 95% CI − 1.09 to 0.06; p = 0.076) and significant after further adjustment for anti-thyroid peroxidase antibodies (β − 0.59, 95% CI − 1.11 to − 0.06). ΔTSH was close to zero in diabetic participants of both groups and lower in MASLD among those without diabetes (t test p = 0.028; Mann–Whitney p = 0.097). Post hoc, the difference was seen only with CRP above 10 mg/L (interaction p = 0.050). ΔTSH discriminated MASLD poorly (area under the curve 0.653). Midnight free triiodothyronine correlated inversely with the NAFLD fibrosis score ( r = − 0.54; q < 0.001). In hospitalised patients with MASLD, the nocturnal TSH rise was attenuated. Its independence from diabetes could not be established, and the attenuation coexisted with dysglycaemia and, post hoc, with systemic inflammation. These hypothesis-generating findings require confirmation in ambulatory cohorts. Not applicable.