Acromegaly is a rare hormonal disorder leading to increased morbidity and mortality. In the vast majority of cases, a pituitary somatotroph cell adenoma causes excess growth hormone (GH) secretion, leading to hepatic insulin-like-growth factor 1 (IGF-1) hypersecretion. Both the disease as well as its treatment with long-acting somatostatin analogs (LA-SMSA) and/or pegvisomant affect glucose and lipid metabolism, possibly contributing to increased cardiovascular risk. In this pilot study, the investigators want to explore insulin sensitivity, postprandial gut hormone response, lipid handling and adipocytokine profile in the following 4 groups: * controlled acromegalic patients on LA-SMSA (group 1) * controlled acromegalic patients on combination treatment of LA-SMSA and pegvisomant (group 2) * acromegalic patients without need for medical therapy after surgery (group 3) * healthy control subjects (group 4) Furthermore, a longitudinal exploration will be performed in uncontrolled acromegalic patients (i.e. patients with serum IGF-1 levels above age-specific thresholds and/or symptoms due to active acromegaly (excessive sweating , arthralgia)) on LA-SMSA monotherapy (group 5). In this group, insulin sensitivity, postprandial gut hormone response, lipid handling and adipocytokine profile will be explored before introducing pegvisomant and three months after normalisation of IGF-1 levels. The investigators hypothesize that lipid and glucose handling will be less efficient in the controlled acromegalic patients on LA-SMSA than in controlled patients on combination therapy or after surgery, and that there will be no difference in substrate metabolism between healthy controls and controlled acromegalic patients on combination treatment or after surgery. Further, they hypothesize that introducing pegvisomant in uncontrolled acromegalic patients will improve their postprandial lipid and glucose handling.
Study Type
OBSERVATIONAL
Enrollment
21
Ghent University Hospital, Department of Endocrinology, 9K12IE
Ghent, Belgium
change in insulin sensitivity
Glucose disposal rate during last half hour of hyperinsulinemic-euglycemic clamp procedure, corrected for lean body mass (in µmol/min/kgLBM)
Time frame: before start of pegvisomant and 3 months after normalisation of IGF-1 after start of pegvisomant in group 5
insulin sensitivity
Glucose disposal rate during last half hour of hyperinsulinemic-euglycemic clamp procedure, corrected for lean body mass (in µmol/min/kgLBM)
Time frame: At enrollment in groups 1-4
fasting and postprandial glucose
Serum glucose levels during mixed-meal test (before and 10, 30, 60, 120, 180, 240, 300 minutes after ingestion of standard mixed-meal (bread, margarine, cheese and milk) providing a caloric content of 1000 kCal whereby 45% of the energy comes from fat, 36% from carbohydrates and 19% from proteins)
Time frame: At enrollment in groups 1-4
fasting and postprandial insulin
Insulin levels during standard mixed-meal test (cfr.supra)
Time frame: At enrollment in groups 1-4
fasting and postprandial gut hormone levels
Serum levels of gastric inhibitory polypeptide (GIP), ghrelin, peptide YY, pancreatic polypeptide, glucagon-like peptide 1 (GLP-1), oxyntomodulin and cholecystokinin before start during standard mixed-meal test (cfr.supra)
Time frame: At enrollment in groups 1-4
fasting adipokine levels
Fasting serum levels of leptin, adiponectin and interleukin 6 (IL-6)
Time frame: At enrollment in group 1-4
fasting lipid levels
Fasting serum levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol
Time frame: At enrollment in groups 1-4
change in fasting and postprandial glucose
Serum glucose levels during mixed-meal test (before and 10, 30, 60, 120, 180, 240, 300 minutes after ingestion of standard mixed-meal (bread, margarine, cheese and milk) providing a caloric content of 1000 kCal whereby 45% of the energy comes from fat, 36% from carbohydrates and 19% from proteins)
Time frame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5
change in fasting and postprandial insulin levels
Insulin levels during standard mixed-meal test (cfr.supra)
Time frame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5
change in fasting and postprandial gut hormone levels
Serum levels of gastric inhibitory polypeptide (GIP), ghrelin, peptide YY, pancreatic polypeptide, glucagon-like peptide 1 (GLP-1), oxyntomodulin and cholecystokinin before start during standard mixed-meal test (cfr.supra)
Time frame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5
change in fasting adipokine levels
Fasting serum levels of leptin, adiponectin and interleukin 6 (IL-6)
Time frame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5
change in fasting lipid levels
Fasting serum levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol
Time frame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5
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