932 J. Endocrinol. Invest. 25: 932-937, 2002 ABSTRACT. A strong relationship has been found between arginine-vasopressin (AVP) and hypotha- lamus-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 cen- tral diabetes insipidus (CDI), before and after re- placement 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 plas- ma ACTH and serum F before and every 15 min for 2 h after the administration of 100 μg 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 μg/l, p<0.05) or after CRH test con- sidered 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 μg/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 μg/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 μg/l; AUC: 17555.5±2008.7 μg/l/120 min) responses to CRH to normal but did not sig- nificantly modify baseline hormone levels (ACTH: 29.6±3.6 ng/l; F: 239.0±32.3 μg/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. (J. Endocrinol. Invest. 25: 932-937, 2002) © 2002, Editrice Kurtis INTRODUCTION Arginine vasopressin (AVP) is well known to exert a stimulatory effect on ACTH and F secretion in hu- mans (1-6). AVP secretion was demonstrated to be enhanced in hypocortisolism (7, 8). However, nor- mal or even elevated plasma AVP levels have been reported in Cushing’s disease, the pituitary-de- pendent hypercortisolism (9-12). These findings suggested a strong relationship between AVP and the hypothalamus-pituitary-adrenal axis in humans. However, few and controversial data are at present available on ACTH and F secretion in central dia- betes insipidus (CDI), a condition clinically charac- terized by a polyuria-polydipsia syndrome due to AVP deficiency. In fact, both enhanced (13-15) and normal (16-19) baseline ACTH and/or F levels were demonstrated in patients with CDI. Similarly, both enhanced (16, 17) and normal (18, 19) ACTH and F responses to CRH administration were demon- strated in these patients compared to healthy sub- jects. In addition, replacement therapy with de- samino-D-AVP (DDAVP) was reported to blunt the ACTH and F response to CRH administration in pa- tients with CDI (18). However, no definitive data are available on basaline and stimulated secretion of ACTH and F in CDI. The current study was designed with the aim of in- vestigating ACTH and F response to CRH test in a large series of patients with CDI, before and after standard replacement with DDAVP in comparison to healthy subjects. Key-words: Corticotropin-releasing hormone, corticotropin, glucocorti- coids, arginine vasopressin, diabetes insipidus, pituitary, adrenal. Correspondence: Prof. Annamaria Colao, Dipartimento di Oncologia e Endocrinologia Molecolare e Clinica, “Federico II” Università di Napoli, Via Sergio Pansini 5, 80131 Napoli, Italia. E-mail: rpivone@tin.it Accepted April 29, 2002. Hypothalamus-pituitary-adrenal axis in central diabetes insipidus: ACTH and cortisol responsiveness to CRH administration R. Pivonello, A. Faggiano, M. Filippella, C. Di Somma, M.C. De Martino, M. Gaccione, G. Lombardi, and A. Colao Department of Molecular and Clinical Endocrinology and Oncology, “Federico II” University, Naples, Italy