Effect of Arginine on the Hypothalamic-Pituitary-Adrenal Axis in Individuals With and Without Vasopressin Deficiency

J Clin Endocrinol Metab. 2020 Jul 1;105(7):dgaa157. doi: 10.1210/clinem/dgaa157.

Abstract

Context: Arginine stimulates pituitary hormones, like growth hormone and vasopressin, but its effect on the hypothalamic-pituitary-adrenal (HPA) axis is unknown. Arginine may also stimulate the HPA axis, possibly through a mechanism involving vasopressin.

Objective: To investigate the effect of arginine on adrenocorticotropic hormone (ACTH) and cortisol in subjects with and without vasopressin deficiency.

Design: Prospective study, University Hospital Basel.

Participants: 38 patients with central diabetes insipidus, 58 patients with primary polydipsia, and 50 healthy controls.

Intervention: Arginine infusion with measurement of ACTH, cortisol and copeptin at baseline and 30, 45, 60, 90, and 120 minutes.

Results: We found different response patterns to arginine: in patients with diabetes insipidus (and low stimulated copeptin levels) median (interquartile range [IQR]) ACTH and cortisol increased from 22.9 (16.8, 38.7) to 36.6 (26.2, 52.1) ng/L and from 385 (266, 463) to 467 (349, 533) nmol/L, respectively. In contrast, median (IQR) ACTH and cortisol levels decreased in patients with primary polydipsia (despite high stimulated copeptin levels): ACTH from 17.3 (12.3, 23) to 14.8 (10.9, 19.8) ng/L and cortisol from 343 (262, 429) to 272 (220.8, 360.3) nmol/L; likewise, in healthy controls: ACTH from 26.5 (17.6, 35.7) to 14.8 (12.1, 22.7) ng/L and cortisol from 471 (393.3, 581.8) to 301.5 (206.5, 377.8) nmol/L.

Conclusion: Diabetes insipidus is associated with increased responsiveness of ACTH/cortisol to arginine. In contrast, arginine does not stimulate the HPA axis in healthy controls or in primary polydipsia.

Trial registration: ClinicalTrials.gov NCT00757276.

Keywords: ACTH; copeptin; corticotropin; cortisol; diabetes insipidus; primary polydipsia; vasopressin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Adult
  • Arginine / pharmacology*
  • Diabetes Insipidus, Neurogenic / blood
  • Diabetes Insipidus, Neurogenic / physiopathology*
  • Female
  • Glycopeptides / blood
  • Humans
  • Hydrocortisone / blood
  • Hypothalamo-Hypophyseal System / drug effects*
  • Hypothalamo-Hypophyseal System / physiopathology
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / drug effects*
  • Pituitary-Adrenal System / physiopathology
  • Polydipsia, Psychogenic / blood
  • Polydipsia, Psychogenic / physiopathology*
  • Prospective Studies
  • Young Adult

Substances

  • Glycopeptides
  • copeptins
  • Adrenocorticotropic Hormone
  • Arginine
  • Hydrocortisone

Associated data

  • ClinicalTrials.gov/NCT00757276