The effect of adrenalectomy on ghrelin secretion and orexigenic action.

Ghrelin is an orexigenic peptide made both in the periphery and in the central nervous system. Relatively little is known about the factors that regulate ghrelin secretion. Because both ghrelin and glucocorticoids are increased during fasting, we hypothesised that ghrelin secretion from the stomach is stimulated by glucocorticoids. Plasma ghrelin concentrations were determined by radioimmunoassay in fed and fasted adrenalectomised (ADX) and sham-operated rats. Fasting plasma ghrelin concentrations were significantly increased in ADX relative to sham rats and were normalised by glucocorticoid replacement. Several lines of evidence suggest that the orexigenic action of ghrelin is mediated through neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurones. Because ADX reduces the orexigenic actions of NPY and AgRP, we hypothesised that ADX would also reduce the orexigenic action of ghrelin. Food intake was assessed in ADX and sham rats following an intra-third-ventricular injection of either saline or ghrelin (1, 5 or 10 microg in 2 microl). ADX rats were equally sensitive to the orexigenic action of ghrelin compared to sham rats. Given that ghrelin has been shown to stimulate glucocorticoid secretion, the current data imply the existence of a regulatory feedback loop whereby glucocorticoids inhibit further ghrelin secretion. The results also suggest that, unlike the orexigenic effects of NPY and AgRP, the ability of ghrelin to stimulate food intake is maintained in ADX rats.

Graft-dependent renal hyperparathyroidism despite successful kidney transplantation.

INTRODUCTION: Only a few reports can be found on the recurrence or persistence of hyperparathyroidism after total parathyroidectomy and autotransplantation (PTX + AT) following kidney transplantation (KTX). The objective of the present study was to assess the frequency and pathophysiological mechanisms responsible for the development of graft-dependent renal hyperparathyroidism (rHPT) after KTX. PATIENTS AND METHODS: Between 1986 and 2006, 69 patients underwent surgery for rHPT after KTX at our institution. Patients with reoperations at the parathyroid autograft (AT) were identified. Kidney graft function (KGF) was assessed by the glomerular filtration rate (GFR). Representative parts of the parathyroid gland chosen for autotransplantation during the initial parathyroidectomy and of the excised AT at reoperation were reanalyzed according to the morphologic pattern and the proliferative index. RESULTS: Eight of the 69 patients underwent reoperation of the AT. All patients had undergone initial PTX + AT before KTX. The GFR before parathyroid reoperation was 66.6 +/- 9.6 ml/min per1.73 m(2) (mean +/- SEM). Histopathological re-examination revealed nodular hyperplasia in the parathyroid tissue for autotransplantation and in the excised parathyroid autografts. The Ki67 index was increased in the glands chosen for autotransplantation prior to KTX, but was overall low in the excised autografts. DISCUSSION: Although not reported in the literature to date, tertiary hyperparathyroidism (tHPT) may arise from parathyroid autografts even in patients with a good KGF. In these cases, graft-dependent tHPT represents the inability of autonomous, nodular parathyroid tissue to regress despite the recovery of renal function. Non-nodular tissue should be selected for parathyroid autotransplantation to decrease the incidence of graft-dependent recurrent rHPT.