Weight gain reversibility and BMI following treatment for Cushing's syndrome: long-term outcomes and potential predictors.

Abstract

Background: Patients with Cushing's syndrome (CS) have higher weight and body mass index (BMI) compared to matched controls. We aimed to assess reversibility of weight gain (absolute weight and BMI decrease) following treatment for CS and identify predictors for weight loss.

Methods: A retrospective study using the Clalit Health Services database analyzed a cohort of patients with CS and age-, sex- and BMI-matched controls (up to five controls per case). Weight and BMI were assessed at baseline, one-year post-diagnosis and at the end of follow-up. Patients taking GLP-1 have been excluded from the analysis.

Results: The cohort included 308 CS patients (67.2% female, mean age 51.6 ± 17.4 years) and 1,020 controls (69.7% female, mean age 54.8 ± 16.9 years). After one year, CS patients who achieved remission experienced significant weight reduction from 85.1 ± 21.0 to 80.8 ± 22.7 kg and BMI decrease from 31.6 ± 7.4 to 29.9 ± 7.4 kg/m² (p < 0.01). By the end of 8.6 years of follow-up, CS patients continued to show significant reductions in both weight (85.0 ± 22.3 to 81.3 ± 22.8 kg, p < 0.01) and BMI (31.2 ± 7.6 to 29.9 ± 7.6 kg/m², p < 0.01), while controls showed slight increases in both. Among patients in remission by the end-of-follow-up, 44.0% (77/175) achieved ≥ 5% and 30.3% (53/175) achieved ≥ 10% weight loss. Patients with persistent CS exhibited no significant weight changes. Multivariate analysis identified female gender, baseline BMI ≥ 30 and a BMI decrease ≥ 1 kg/m² at one year, as predictors for ≥ 5% weight loss.

Conclusion: Approximately half of CS patients in remission achieved at least 5% decrease in BMI with long-term follow-up, and a third achieved more than 10% decrease. Disease remission, female gender, baseline BMI ≥ 30, and early BMI reduction, predicted a clinically significant weight loss.