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Desmopressin stimulation test shows promise in treating Cushing's disease
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The desmopressin stimulation test appears to be a reliable method for determining the pituitary effects of Cushing’s disease, according to researchers.
“The present results provide a cellular and molecular basis to support the desmopressin stimulation test as a reliable, specific test for the diagnosis and postsurgery prognosis of [Cushing’s disease],” Raúl M. Luque, PhD, of the department of cell biology, physiology and immunology at the University of Córdoba in Spain, and colleagues wrote. “Furthermore, our data indicate that AVPR1b [or V3R] is responsible for the direct/exclusive desmopressin stimulatory pituitary effects observed in [Cushing’s disease], thus opening the possibility of exploring AVPR1b antagonists as potential therapeutic tools for [Cushing’s disease] treatment.”
Desmopressin is a synthetic analog of arginine-vasopressin (AVP), which binds with high affinity to the different AVP receptors — AVPR1a (or V1R), AVPR1b, and AVPR2 (or V2R) — and stimulates adrenocorticotropic hormone (ACTH) secretion and cortisol levels in patients with Cushing’s disease.
The researchers analyzed eight normal pituitaries, 23 corticotropinomas, 14 nonfunctioning pituitary adenomas, 17 somatotropinomas and three prolactinomas for AVPR expression via quantitative real-time reverse-transcription polymerase chain reaction.
According to the data published in the Journal of Clinical Endocrinology and Metabolism:
- Patients with Cushing’s disease or other pituitary tumors exhibit differential expression profiles of AVPR.
- Desmopressin directly stimulates ACTH release, proopiomelanocortin expression and [Ca2+]i kinetics in corticotropinoma cells.
- Selective antagonists identify AVPR1b as the most likely mediator of desmopressin stimulator effects in corticotropinoma cells.
- Desmopressin also exerts homologous regulation of AVPR1b gene expression in vitro.
- Expression levels of AVPR1b are correlated to responses to the desmopressin test (plasma ACTH levels) before surgery of patients with Cushing’s disease.
- Desmopressin increased cell proliferation in corticotropinomas in vitro.
“Further studies, using larger numbers of [Cushing’s disease] culture samples and different types of assays, which are beyond our current capabilities, will be required to unequivocally establish whether desmopressin and AVP do increase proliferation rate,” the researchers wrote.
Disclosure: The researchers report no relevant financial disclosures.
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