Introduction: Although involved in feeding and weight homeostasis, stimulation of pituitary GH secretion is the best established action of stomach-produced hormone ghrelin. However, its role in regulation of GH secretion is not yet clear. Some evidence indicates that circulating concentrations of GH and/or IGF-I could influence ghrelin levels. The pathophysiology of ghrelin secretion in acromegaly (specially aftar an oral glucose tolerance test (OGTT) is unclear.
Objectives: To study circulating fasting acylated and total ghrelin levels, and their response to an OGTT in active acromegalic patients and normal control subjects matched for age, sex, and BMI, and their relation with glucose, insulin, and GH.
Patients and methods: We included nine patients with active acromegaly, and nine age, BMI and percentage body fat matched healthy subjects as controls. Patients with any degree of hypopituitarism were under appropriate and stable hormone replacement therapy. We obtained blood samples for glucose, insulin, GH, total ghrelin and acylated ghrelin at times 0, 30, 60, 90 and 120 min after 75 g of oral glucose.
Results: Fasting GH and IGF-I were statistically different between patients and controls: GH (μg/l) 6.7±1.4 vs 0.8±0.4, P<0.01; IGF-I (ng/ml) 414±75 vs 86±6, P<0.01. Fasting total ghrelin (pg/ml) was similar in patients and control group, 916±132 vs 844±169, P=NS. Fasting acylated ghrelin levels (pg/ml) were also similar in both groups, 65±13 vs 74±14 (Figure 1). In both groups, total ghrelin levels decreased during OGTT, and nadir total ghrelin was lower than fasting total ghrelin: patients 916±132 vs 747±95, P<0.05; controls 844±169 vs 625±90, P<0.05 (Figure 2). Also, in both groups, acylated ghrelin levels decreased during OGTT, with nadir being lower than basal levels: patients 65±13 vs 42±6, P<0.05; controls 74±14 vs 37±4, P<0.05 (Figure 3). We have found a negative correlation between fasting ghrelin (both total and acylated) and insulin levels (both fasting and post OGTT).
Conclusions: Our data suggest that circulating total and acylated ghrelin in acromegaly is regulated by insulin and not by GH hypersecretion.
03 - 07 May 2008
European Society of Endocrinology