Oxytocin levels in response to CRH administration in hypopituitarism and hypothalamic damage: a randomized, crossover, placebo-controlled trial


Por: Asla, Q, Garrido, M, Urgell, E, Terzan, S, Santos, A, Fernández, M, Varghese, N, Atila, C, Calabrese, A, Biagetti, B, Plessow, F, Gich, I, Christ-Crain, M, Eckert, A, Webb, SM, Lawson, EA, Aulinas, A

Publicada: 18 ene 2025
Resumen:
Increasing evidence supports the presence of oxytocin deficiency (OXT-D) in patients with hypopituitarism and hypothalamic damage (HHD), that might be associated with neuropsychological deficits and sexual dysfunction, leading to worse quality of life (QoL). Therefore, identifying a provocative test to diagnose an OXT-D will be important. Corticotropin-releasing hormone (CRH) is a candidate for such a test as it increases oxytocin secretion in animal models. This study aimed to examine the effects of CRH on oxytocin release in HHD compared to healthy controls (HC) and to describe the psychopathology, sexual function and QoL and their associations with oxytocin. This is a single-blind, randomized, placebo-controlled, proof-of-concept study (NCT 04902235) with crossover assignment (CRH vs. placebo). Nineteen HHD patients (10 females) and 20 HC (11 females) completed two visits, receiving CRH or placebo in random order and completed validated questionnaires to assess psychopathology, sexual function and QoL. Samples were collected over 120 min to assess oxytocin. Linear mixed-effects regression model evaluated the change in oxytocin after CRH/placebo in HHD vs. HC. CRH administration did not impact oxytocin concentrations across groups over time (p = 0.97). HHD had greater psychopathology (most ps < 0.05), sexual dysfunction (p < 0.03) and worse QoL (p < 0.001) compared to HC, nevertheless, baseline oxytocin concentrations and area under the curve of oxytocin were not significantly associated with psychopathology, sexual function or QoL, neither in HHD or HC. In conclusion, CRH administration does not appear to be a suitable provocative test for diagnosing OXT-D in HHD. Identifying a reliable diagnostic test for OXT-D remains crucial. Alternative provocative tests or biomarkers should be explored.

Filiaciones:
Asla, Q:
 Hosp Santa Creu i St Pau, Dept Endocrinol & Nutr, IR ST PAU, CIBERER,U747 ISCIII,ENDO ERN, Barcelona, Spain

 Univ Vic, Cent Univ Catalonia UV UCC, Fac Med, Vic Manresa, Catalonia, Spain

Garrido, M:
 Ctr Invest Medicament CIM, IR ST PAU, Barcelona, Spain

Urgell, E:
 Hosp Santa Creu i St Pau, Dept Biochem, Barcelona, Spain

Terzan, S:
 Hosp Santa Creu i St Pau, Dept Biochem, Barcelona, Spain

Santos, A:
 Hosp Santa Creu i St Pau, Dept Endocrinol & Nutr, IR ST PAU, CIBERER,U747 ISCIII,ENDO ERN, Barcelona, Spain

 Univ Autonoma Barcelona, Dept Med, Bellaterra, Spain

Fernández, M:
 Hosp Maig, Hosp Santa Creu i St Pau, Dept Endocrinol & Nutr, Barcelona, Spain

Varghese, N:
 Univ Basel, Res Cluster Mol & Cognit Neurosci, Basel, Switzerland

 Univ Psychiat Clin Basel, Neurobiol Lab Brain Aging & Mental Hlth, Basel, Switzerland

Atila, C:
 Univ Spital Basel, Endocrinol Diabetol & Metab, Basel, Switzerland

 Univ Basel, Dept Clin Res, Basel, Switzerland

Calabrese, A:
 Univ Turin, S Luigi Hosp, Dept Clin & Biol Sci, Internal Med, Turin, Italy

Biagetti, B:
 Hosp Univ Vall dHebron, Dept Endocrinol & Nutr, ENDO ERN, Barcelona, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras, Unit 747, CIBER ER, Majadahonda, Spain

Plessow, F:
 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA USA

 Harvard Med Sch, Dept Med, Boston, MA USA

Gich, I:
 Hosp Santa Creu i St Pau, Dept Clin Epidemiol & Publ Hlth, Barcelona, Spain

 Inst Salud Carlos III, CIBER Epidemiol & Salud Publ CIBER ESP, Madrid, Spain

Christ-Crain, M:
 Univ Spital Basel, Endocrinol Diabetol & Metab, Basel, Switzerland

 Univ Basel, Dept Clin Res, Basel, Switzerland

Eckert, A:
 Univ Basel, Res Cluster Mol & Cognit Neurosci, Basel, Switzerland

 Univ Psychiat Clin Basel, Neurobiol Lab Brain Aging & Mental Hlth, Basel, Switzerland

Webb, SM:
 Univ Autonoma Barcelona, Dept Med, Bellaterra, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras, Unit 747, CIBER ER, Majadahonda, Spain

Lawson, EA:
 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA USA

 Harvard Med Sch, Dept Med, Boston, MA USA

Aulinas, A:
 Hosp Santa Creu i St Pau, Dept Endocrinol & Nutr, IR ST PAU, CIBERER,U747 ISCIII,ENDO ERN, Barcelona, Spain

 Univ Vic, Cent Univ Catalonia UV UCC, Fac Med, Vic Manresa, Catalonia, Spain
ISSN: 20452322





Scientific Reports
Editorial
NATURE RESEARCH, HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY, Reino Unido
Tipo de documento: Article
Volumen: 15 Número: 1
Páginas:
WOS Id: 001399005300003
ID de PubMed: 39824923
imagen Green Submitted, gold

MÉTRICAS