Ghrelin is brain-gut peptide with potent growth hormone (GH) releasing activities. It has been suggested that the majority of circulating ghrelin originates from the stomach, with a smaller portion from the small intestine. Gastrectomy significantly reduces circulating ghrelin concentrations. The implication of decreased circulating ghrelin on the somatotropic axis post-gastrectomy has not been studied. Therefore we aimed to investigate the somatotropic axis in ten gastrectomized (GASTRX) patients who underwent total gastrectomy for various reasons at least two years ago. At baseline circulating total-ghrelin, GH, IGF-I, IGFBP-3 levels were measured. The GH stimulation test was: insulin-induced hypoglycemia (ITT), ghrelin in two i.v. bolus doses (0.1 and 1 µg/kg) and GHRH test. GH sensitivity was assessed by an IGF-1 generation test. All the tests were performed two weeks apart.

At baseline serum ghrelin levels were reduced by 55% in GASTRX compared with the control group (P < 0.05). IGF-I (P < 0.05) and IGFBP-3 (P < 0.01) levels were also significantly lower than in controls. GH response to ITT in both GASTRX and control subjects was of similar magnitude, while circulating plasma ghrelin levels in GASTRX patients were not modified during hypoglycemia. Both doses (0.1 and 1.0 µg/kg) of ghrelin stimulated GH release significantly more in GASTRX than in control subjects, respectively (peak mean GH ± SE: 18.2 ± 5.6 vs. 5.4 ± 1.3 µg/L, P < 0.03 and 58.7 ± 7.5 vs. 35.3 ± 1.9 µg/L, P < 0.01). There was no difference in GHRH-induced GH response between GASTRX patients and control subjects (P > 0.05). Concomitantly, increased increments in IGF-I and IGFBP-3 to a single bolus of GH were found (P < 0.03). In conclusion, our data suggest that low circulating ghrelin levels, found in GASTRX patients, are accompanied by enhanced ghrelin sensitivity in respect of GH response. This is associated with increased GH responsiveness. Gastrectomy is a state of acquired chronic hypoghrelinemia that may require replacement with ghrelin and it is tempting to speculate that this may affect the GH-IGF-IGFBP axis.