Association between ACTH levels and metabolic syndrome in patients with mild autonomous cortisol secretion: a retrospective cross-sectional study

To examine whether lower adrenocorticotropic hormone (ACTH) levels are associated with metabolic syndrome (MetS) among patients with mild autonomous cortisol secretion (MACS) and to explore whether the association differs according to sex and body mass index (BMI). This was a retrospective, cross-sectional, single-center study of 194 patients with MACS. Patients were classified into MetS and non-MetS groups, and demographic, tumor-related, hormonal, and metabolic characteristics were compared. Exploratory analyses assessed interactions of ACTH with sex and BMI. ACTH was analyzed primarily as a continuous log₂-transformed variable using logistic regression with a joint likelihood to account for measurements coded as < 5 pg/mL. Unadjusted and age- and sex-adjusted odds ratios (ORs) were estimated. An exploratory supplementary analysis used an ACTH cutoff of 10 pg/mL. Formal interaction tests were performed for sex and BMI. All tests were two-sided, and P < 0.05 was considered statistically significant. Among 194 patients with MACS, 89 had MetS and 105 did not. The prevalence of hypertension and diabetes mellitus was 66.0% and 22.7%, respectively. Patients with MetS were older than those without MetS. All 194 patients were included in the ACTH analyses, comprising 88 left-censored and 106 exact observations. The unadjusted OR for MetS per doubling of ACTH was 0.787 (95% CI, 0.590–1.052; P = 0.106); after adjustment for age and sex, it was 0.705 (95% CI, 0.515–0.964; P = 0.029). Interaction tests did not provide statistically significant evidence of effect modification by continuous BMI (P = 0.606) or sex (P = 0.058). Lower ACTH levels were associated with prevalent MetS after adjustment for age and sex in surgically treated patients with MACS. These findings suggest an exploratory association between ACTH levels and metabolic burden. However, the absence of quantitative post-DST cortisol prevents determining whether ACTH provides information beyond cortisol autonomy. Further validation in independent cohorts is needed. This study examined the relationship between ACTH levels and MetS in patients with MACS. ACTH was analyzed continuously, retaining measurements coded as < 5 pg/mL. Lower ACTH levels were associated with prevalent MetS after adjustment for age and sex, although the unadjusted association was not statistically significant. Formal interaction tests did not establish differences by sex or BMI. These findings require confirmation in prospective studies with quantitative post-DST cortisol before the clinical predictive value of ACTH can be established.