Hypothalamus-pituitary-adrenal axis in central diabetes insipidus: ACTH and cortisol responsiveness to CRH administration

A strong relationship has been found between arginine-vasopressin (AVP) and hypothalamus-pituitary-adrenal. axis in humans. The aim of the current study was to evaluate baseline and CRH-stimulated ACTH and F levels in patients with central diabetes insipidus (CDI), before and after replacement therapy with desamino-D-AVP (DDAVP). Twenty-five patients with CDI, and 25 sex- and age- and BMI-matched healthy subjects entered the study. A standard CRH test (measurement of plasma ACTH and serum F before and every 15 min for 2 h after the administration of 100 mug of human CRH) was performed in all subjects. In patients with CDI, CRH test were repeated after 1 week of DDAVP at standard doses. At study entry, ACTH and F levels were significantly higher in patients with CDI than in controls either at baseline (ACTH: 45.5 +/- 4.8 vs 18.5 +/- 3.3 ng/l, p<0.05; F: 375.1 +/- 55.7 vs 146.6 +/- 19.4 mug/l, p<0.05) or after CRH test considered as a peak (ACTH: 90.8 +/- 14.4 vs 42.5 +/- 7.4 ng/l, p<0.05; F: 501.6 +/- 65.7 vs 226.3 +/- 25.6 mug/l, p<0.05) and AUC (ACTH: 3997.0 +/- 571.7 vs 2136.0 +/- 365.8 ng/l/120 min, p<0.05; F: 31489.0 +/- 4299.4 vs 14854.5 +/- 1541.5 mug/l/120 min, p<0.05). In patients with CDI, 1 week of replacement with DDAVP brought down ACTH (peak: 56.9 +/- 9.3 ng/l; AUC: 2390.7 +/- 480.7 ng/l/120 min) and F (peak: 310.3 +/- 39.5 mug/l; AUC: 17555.5 +/- 2008.7 mug/l/120 min) responses to CRH to normal but did not significantly modify baseline hormone levels (ACTH: 29.6 +/- 3.6 ng/l; F: 239.0 +/- 32.3 mug/l). In conclusion, CDI is associated to increased baseline ACTH and F levels and increased responsiveness of ACTH and F to CRH administration. In addition, replacement treatment with DDAVP normalized CRH-induced but not baseline ACTH and F secretion.