Ghrelin has been found as a natural ligand of growth hormone secretagouges receptors (GHSR-1a) that exerts a marked stimulatory effect on growth hormone (GH) secretion. It is also thought to be involved of eating behavior and control of energy homeostasis. However, still little is known about the physiology of ghrelin secretion in acromegaly.
Objective: The objective of the study was to examine effects of surgical and pharmacological treatment in patients with acromegaly on serum ghrelin levels.
Material: 28 patients (17 women and 11 men) aged 47.7+/-11.4 years (mean+/-SD) with body mass index (BMI)=31.6+/-4.9 kg/m2. Diagnosis was based on: 1/peak GH in oral glucose tolerance test>or=1ng/mL, 2/serum IGF-1 levels above normal for gender and age, 3/ pituitary adenoma in magnetic resonance imagining. Patients were divided into two groups: Group I-surgically treated (transsphenoidal surgery): 10 women and 7 men aged 45+/-10.9 years with BMI=31.3+/-4.9 kg/m2. Criteria of cure in acromaegaly were: 1/peak GH<1 ng/ml in OGTT, 2/serum IGHF-1 levels according to gender and age. Group II-pharmacologically treated (Sandostatin LAR, Novartis Pharm. Ltd, 20 mg im, monthly): 7 women and 4 men aged 52+/-11 years, BMI=29.4 kg/m2. Criteria of good control of acromegaly were: 1/peak GH<1 ng/ml in OGTT, 2/serum IGHF-1 levels according to gender and age. Control group-healthy subjects: 10 women and 19 men aged 47.7+/-11.4 years, BMI=25.6 kg/m2.
Methods: In patients before and after treatment and in healthy subjects fasting serum levels of total ghrelin, leptin, growth hormone (GH), insulin-like growth factor I (IGF-1), glucose, insulin, total cholesterol and trigliceryde levels were measured. HOMA index of insulin resistance was calculated. The patients and control subjects underwent assessment of body height, weight and BMI.
Results: Body weight and BMI in patients before treatment were higher compared to healthy controls (87.3+/-18 to 74.4+/-16 kg, p<0.02 (body weight) and 31.6+/-4.9 to 25.5+/-4.1 kg/m2, p<0.0002 (BMI). Body weight and BMI after successful surgical treatment were still higher compared to healthy subjects (92.7+/-19 to 74.4+/-16 kg, p=0.02 (body weight) and 31.5+/-5 to 25.5+/-4.1 kg/m2, p<0.0003 (BMI). Body weight decreased during pharmacological treatment although BMI was still higher then in control subjects (30.1+/-6.3 to 25.2+/-4.1 kg/m2; p<0.003). Serum fasting GH and IGF-1 levels decreased after successful surgical treatment, from 26.3+/-29 to 1.6+/-2.5 microg/l (p<0.007) and from 926.1+/-325 to 337+/-213 microg/l (p<0.00003), respectively. Also during pharmacological treatment decrease in serum GH and IGF-1 levels were observed, from 29.4+/-40 to 5.8+/-7.6 microg/l and from 976.3+/-328 to 358.3+/-203 microg/l (p<0.002), respectively. Serum insulin levels decreased after successful surgical treatment, from 29.1+/-9.8 do 15.8+/-7.3 microU/ml (p<0.02). Also during pharmacological treatment serum insulin levels and HOMA index decreased, from 29.8+/-12.9 to 14.6+/-2.1 microU/ml (p<0.03) and from 9.1+/-3.6 to 3.5+/-0.4 (p<0.007), respectively. Serum fasting insulin and glucose levels and HOMA index were higher in patients before treatment compared to healthy subjects and didn't differ significantly after successful surgery and during pharmacotherapy. Serum ghrelin levels in patients with acromegaly were decreased compared to healthy subjects (1055.2+/-325 to 1266.8+/-374 pg/ml, p<0.04) and increased after successful surgical treatment, from 1164.2+/-321 to 1553.6+/-542 pg/ml (p=0.01). During pharmacotherapy decrease in serum ghrelin levels was observed, from 1038.7+/-344 to 568.5 +/-252 pg/ml (p<0.03). There were no significant differences in serum ghrelin level between healthy controls and patients after treatment. Significant negative correlation between serum ghrelin levels and body weight (r=-0.40, p=0.04) in healthy subjects was found. In patients with acromegaly significant negative correlation between serum ghrelin levels and insulin levels and HOMA index were found (r=-0.48; p<0.02 and r=-0.57; p<0.03, respectively.
Conclusions: In patients with acromegaly: 1/serum ghrelin levels are decreased compared to healthy subjects. It can be speculated, that its at least partially caused by negative feedback control of ghrelin production and by GH-induced hyperinsulinaemia. 2/serum ghrelin levels increase after successful transsphenoidal surgery. 3/ treatment with somatostatin analoges causes decrease in serum ghrelin levels, despite of serum GH and IGF-1 normalization.