Effects of oral macimorelin on copeptin and anterior pituitary hormones in healthy volunteers
Open Access
- 22 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Pituitary
- Vol. 24 (4), 555-563
- https://doi.org/10.1007/s11102-021-01132-9
Abstract
Purpose The test with the highest diagnostic accuracy for diabetes insipidus is copeptin measurement after hypertonic saline infusion. However, the procedure is cumbersome and unpleasant due to rapid sodium increase. An oral stimulation test would be highly desirable. Macimorelin, an oral ghrelin agonist, is a newly approved diagnostic test for growth hormone (GH) deficiency, but its effects on copeptin/vasopressin are unknown and the effects on other pituitary hormones only scarcely investigated. Methods In this prospective, interventional, proof-of-concept study Copeptin and anterior pituitary hormones were measured in 28 healthy volunteers on two test days at baseline, 30, 45, 60, 90 and 120 min after a single dose of macimorelin (first visit: 0.5 mg/kg, second visit: 0.75 mg/kg). Results Baseline copeptin levels were 5.26 pmol/L [1.57, 6.81] and did not change after macimorelin intake (0.5 mg/kg: maximal median change 0.40 [− 0.49, 0.65] pmol/L, p = 0.442; 0.75 mg/kg: − 0.13 [− 0.45, 0.17] pmol/L, p = 0.442. Median GH levels increased from 3.67 mU/L with a maximal median change of 94.66 [IQR 56.5; 110.96] mU/L, p < 0.001. No effect was seen on cortisol, ACTH, LH and FSH levels. Prolactin (max. median change 100 [2.5; 146.5] mU/L, p = 0.004) and free thyroxine (fT4) (0.5 [0.2; 0.8] pmol/L, p < 0.001) increased, whereas TSH decreased (− 0.18 [− 0.22, − 0.09] mU/L, p < 0.001). Conclusion We confirm an increase of GH upon macimorelin in healthy volunteers. However, macimorelin did not stimulate copeptin and therefore does not provide an oral test alternative for the diagnosis of diabetes insipidus. Additionally, a stimulatory effect was seen for prolactin and fT4, but not for ACTH and gonadotropic hormones. Registration The trial was registered on ClinicalTrials.gov (NCT03844217) on February 18, 2019.Keywords
Funding Information
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (320030_182753)
- Schweizerische Gesellschaft für Endokrinologie und Diabetologie (Young Investigator Award 2019)
- Universität Basel
This publication has 23 references indexed in Scilit:
- Diagnosis and management of adrenal insufficiencyThe Lancet Diabetes & Endocrinology, 2015
- The Effect of Ghrelin and Estradiol on Mean Concentration of Thyroid HormonesInternational Journal of Endocrinology and Metabolism, 2015
- Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency.Journal of Clinical Endocrinology & Metabolism, 2013
- The effects of ghrelin/GHSs on AVP mRNA expression and release in cultured hypothalamic cells in ratsPeptides, 2011
- Pharmacokinetics and Pharmacodynamic Effects of an Oral Ghrelin Agonist in Healthy SubjectsJournal of Clinical Endocrinology & Metabolism, 2007
- EP1572: A novel peptido-mimetic GH secretagogue with potent and selective GH-releasing activity in manJournal of Endocrinological Investigation, 2002
- Role of Ghrelin in the Regulation of Vasopressin Release in Conscious RatsEndocrinology, 2002
- Consensus Guidelines for the Diagnosis and Treatment of Growth Hormone (GH) Deficiency in Childhood and Adolescence: Summary Statement of the GH Research Society1Journal of Clinical Endocrinology & Metabolism, 2000
- The Growth Hormone Secretagogue Hexarelin Stimulates the Hypothalamo-Pituitary-Adrenal Axis via Arginine VasopressinJournal of Clinical Endocrinology & Metabolism, 1999
- The Effect of Growth Hormone Secretagogues and Neuropeptide Y on Hypothalamic Hormone Release from Acute Rat Hypothalamic ExplantsJournal of Neuroendocrinology, 1999