Acute intravenous acyl ghrelin infusion induces thirst but does not affect sodium excretion: two randomized, double-blind, placebo-controlled crossover studies in hypopituitary patients

in European Journal of Endocrinology
Correspondence should be addressed to E T Vestergaard; Email: etv@clin.au.dk
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Objective

Acyl ghrelin, which is the endogenous ligand for the growth hormone secretagogue receptor, potently stimulates pituitary growth hormone release, and to some degree adrenocorticotropic hormone and prolactin. Ghrelin is also orexigenic and has recently been shown to stimulate renal sodium absorption in rodent models. Increased thirst sensation has been observed as a side effect of acyl ghrelin administration in some human studies. The objective of this clinical trial was to investigate the direct effects of acyl ghrelin on thirst sensation and sodium excretion in hypopituitary patients.

Design

Hypopituitary patients on stable replacement with hydrocortisone and growth hormone were investigated in two double-blind and placebo-controlled crossover studies. The patients received a 5-h intravenous infusion of acyl ghrelin (5 pmol/kg/min in the first study and 1 pmol/kg/min in the second study). Thirst sensation was measured on a Visual Analog Scale (VAS). In the second study plasma osmolality, vasopressin, copeptin, water intake, diuresis and urinary excretion of sodium and creatinine were measured.

Results

In the initial study, acyl ghrelin (5 pmol/kg/min) increased thirst sensation (time × treatment analysis of variance for the effect of acyl ghrelin infusion P = 0.003). In the second study acyl ghrelin (1 pmol/kg/min) also increased thirst (P = 0.04) but did not affect urinary excretion of either sodium or water.

Conclusions

We demonstrate that acyl ghrelin infusion increases thirst sensation, without affecting sodium excretion or diuresis in human subjects.

 

     European Society of Endocrinology

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Figures

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    Thirst and fluid intake during acyl ghrelin and saline infusion. (A and B) Thirst score increased in response to AG infusion in both study 1 (A) and 2 (B). (C) Oral water intake was equal on the two study days with AG and saline infusion in study 2. (D) The total fluid intake which includes both oral water intake and intravenous infusions was also similar on both study days in study 2.

  • View in gallery

    Diuresis and fluid balance during acyl ghrelin and saline infusion in study 2. (A) Diuresis was similar during AG and saline infusion in the basal period and in the clamp period. (B) There was no difference in fluid balance as estimated by the difference in total fluid intake and diuresis on the two study days.

  • View in gallery

    Urine excretion of sodium and creatinine during AG and saline infusion in study 2. Acyl ghrelin did not have an impact on sodium excretion (A), creatinine excretion (B) or the sodium-to-creatinine ratio (C) during the basal or the clamp periods.

  • View in gallery

    Plasma vasopressin and osmolality during acyl ghrelin and saline infusion in study 2. AG did not affect plasma vasopressin (A), serum copeptin (B) or plasma osmolality (C) as compared to saline infusion.

  • View in gallery

    Correlation analyses of plasma osmolality and vasopressin concentration during acyl ghrelin and saline infusion in study 2. During saline infusion, there was a positive association between osmolality and vasopressin, but the association was abrogated by AG infusion.

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