Serum Copeptin in Acromegaly with and Without Diabetes: A Comparative Cross‑Sectional Study

Background: Copeptin serves as a stable substitute marker for vasopressin and is emerging as a biomarker in endocrine disorders. Given the complex metabolic interactions in acromegaly and the role of growth hormone in fluid balance, this study examined copeptin levels in patients with acromegaly and diabetes mellitus, non-diabetic acromegaly, and healthy controls. Objectives: To compare serum copeptin concentrations among acromegalic patients with diabetes, acromegalic patients without diabetes, and healthy controls. Subjects and Methods: This is a comparative cross-sectional study that included 176 participants: acromegalic patients with diabetes, acromegalic patients without diabetes, and healthy controls. Serum copeptin was measured using a standardized ELISA method. A comprehensive biochemical profile was also assessed, including growth hormone, insulin-like growth factor-1, fasting glucose, glycated hemoglobin, and lipid parameters. One-way ANOVA with post-hoc least significant difference testing was used to analyze group differences. The study was conducted at the National Diabetes Center (Baghdad, Iraq) with fasting samples collected between November 2024 and March 2025. Results: Mean copeptin concentrations demonstrated a statistically significant variation between the groups (p = 0.012). Non-diabetic acromegalic patients exhibited the highest copeptin levels (72.6 ± 59.3 pmol/L), followed by diabetic acromegalic patients (57.3 ± 49.2 pmol/L) and control subjects (48.0 ± 25.7 pmol/L). Post-hoc analysis indicated a substantial elevation in copeptin levels among non-diabetic acromegalic patients compared to controls (p = 0.003; Cohen’s d = -0.45, 95% CI: -0.85 to -0.05), indicating a small-to-medium effect size. Copeptin demonstrated a positive correlation with growth hormone (r = 0.443, p = 0.003) and insulin-like growth factor-1 (r = 0.333, p = 0.027), while it correlated negatively with triglycerides (r = -0.326, p = 0.031) and VLDL (r = -0.332, p = 0.028). Conclusions: Serum copeptin levels were significantly higher in non-diabetic acromegalic patients than in controls, while diabetic acromegalic patients were not significantly different from controls.