Ghrelin and leptin serum levels during an oral glucose tolerance test in active and inactive acromegalic patients

Introduction: Leptin is secreted in adipose tissues and is positively correlated to BMI, fat mass and food intake. Ghrelin is a gastrointestinal and hypothalamic peptide which stimulates growth hormone (GH) secretion. Ghrelin levels are elevated during fasting and reduced by food intake. Oral glucose tolerance tests (OGTT) decrease ghrelin in healthy humans and increase leptin only in obese humans. This prospective cross sectional study was performed in order to investigate the interaction of leptin, ghrelin and GH levels in acromegalic pat.

Methods: We measured glucose, insulin, ghrelin, leptin and GH concentration during a 3h OGTT and IGF-I in 36 acromegalic pat (19f/17m, med. age 53.3y (20–75)). 29/36 pat underwent surgery. None of the pat had received radiotherapy or any medication for acromegaly. Concentration of GH and IGF-1 were determined by a single lab using the same immunoassay. IGF-1 levels were given as multiple of the upper limit of age- and sex-adjusted normal [xULN], active disease was defined as xULN>1.

Results: 11 pat had active acromegaly, 25 were inactive. Baseline ghrelin levels were significantly reduced in active compared to inactive pat. Baseline leptin was also reduced in active pat (p=n.s.). OGTT leads to a significant decrease of ghrelin and leptin (active: p<0.01; inactive: p<0.001). The ghrelin decline was significantly higher in inactive pat (s. table).

	xULN	BMI (kg/m2)	GH baseline (µg/l)	Ghrelin baseline (pg/ml)	Ghrelin nadir (pg/ml)	Ghrelin delta (pg/ml)	Leptin baseline (ng/ml)	Leptin nadir (ng/ml)	Leptin delta (ng/ml)
active median	2.09	27.47	10.6	40.9	32.6	8.2	9.4	7.1	1.8
active min/max	1.1/5.0	20.1/30.7	1.7/70	26.8/169.7	20.3/124.9	3.3/60.1	1.6/18.6	1.3/15.7	0.3/6.5
inactive median	0.61	27.57	0.9	129.9	100.7	22.3	10.7	9.5	1.5
inactive min/max	0.9/1.0	20.5/34.9	0.2/5.7	69/292.3	22/200.9	5.3/213.5	0.7/53.2	0.6/43.5	0.1/12.4
p-value	<0.001	n.s.	<0.001	<0.01	<0.01	<0.05	n.s.	n.s.	n.s.

Conclusion: The decreased ghrelin levels and the reduced ghrelin decline during OGTT in active pat compared to inactive pat is probably due to the negative feedback of GH and IGF-I on ghrelin secretion. The tendency of lower leptin levels in active acromegalic pat might be explained by less fat mass.