Serum ghrelin levels are suppressed in hypopituitary patients following insulin-induced hypoglycaemia irrespective of GH status

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Abstract

Objective

Circulating ghrelin is suppressed during insulin-induced hypoglycaemia in healthy subjects, but it is unknown whether this is determined by feedback inhibition from counter-regulatory hormones. We therefore investigated the impact of GH and cortisol on ghrelin secretion during insulin-induced hypoglycaemia.

Design

Serum levels of ghrelin, GH, and cortisol were measured in 41 adult patients with suspected hypopituitarism during insulin-induced hypoglycaemia. Based on their peak GH response (cut-off level: 3 μg/l), the patients were divided into a GH-sufficient group (GHS) and a GH-deficient group (GHD).

Results

The GHS patients (n = 16) were younger (P < 0·01), had lower baseline cortisol levels [255 ± 37 vs. 372 ± 38 nmol/l (P = 0·04)], and tended to have a lower body mass index (P = 0·09) as compared to GHD patients (n = 25). By definition, peak GH (μg/l) was higher in GHS patients [15·0 ± 1·8 vs. 1·0 ± 0·2 (P < 0·0001)].The increase in serum cortisol during the ITT (insulin-tolerance test) was higher and occurred later in GHS patients [Cmax (nmol/l): 561 ± 41 vs. 412 ± 50 (P = 0·04); Tmax (minutes): 65 ± 5 vs. 49 ± 5 (P = 0·03)]. Serum ghrelin levels changed significantly with time during ITT in both groups (P < 0·0001), characterized by a moderate decline during the initial 50–60 min and a return to baseline after 2 h. No significant differences were recorded in AUCghrelin during the ITT between the two groups. No gender differences in ghrelin levels were recorded.

Conclusions

(i) Like in healthy subjects serum ghrelin levels are suppressed during an ITT in patients with suspected hypopituitarism. (ii) The suppression of ghrelin was similar in GHD and GHS subjects and was not determined by cortisol. (iii) We hypothesize that insulin rather than hypoglycaemia accounts for ghrelin suppression during an ITT.

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