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
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