Acromegaly
Conditions
Keywords
Acromegaly, Acromegaly treatment, Long-acting somatostatin analogs, Pegvisomant, Insulin sensitivity, Gut hormones, Lipid metabolism, Adipokines
Brief summary
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.
Interventions
None listed
Sponsors
Pfizer
University Hospital, Ghent
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Diagnosis of acromegaly over 1 year ago, no changes in treatment schedule since at least 6 months (groups 1-3 and 5) OR healthy volunteer without diagnosis of acromegaly (group 4) * Patient is willing to participate and has signed the informed consent * Age \> 18 years and \< 80 years * Body Mass Index 18-40 kg/m²
Exclusion criteria
* Biochemistry: liver function tests \> 3x ULN; HbA1C \> 58 mmol/mol * All untreated endocrine disorders including uncontrolled diabetes mellitus type 2 (i.e. HbA1C \> 58 mmol/mol) * Bariatric surgery; malabsorptive syndromes; hepatic or renal failure * Current medication use: insulin, metformin, sulfonylurea, fibrates, incretin mimetics, dopamine agonists (for all but insulin, participation is allowed after a 2- week wash-out period) * Abuse of alcohol or drugs * Weight changes \> 10% of body weight during preceding 12 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| change in insulin sensitivity | before start of pegvisomant and 3 months after normalisation of IGF-1 after start of pegvisomant in group 5 | Glucose disposal rate during last half hour of hyperinsulinemic-euglycemic clamp procedure, corrected for lean body mass (in µmol/min/kgLBM) |
| insulin sensitivity | At enrollment in groups 1-4 | Glucose disposal rate during last half hour of hyperinsulinemic-euglycemic clamp procedure, corrected for lean body mass (in µmol/min/kgLBM) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| fasting and postprandial gut hormone levels | At enrollment in groups 1-4 | 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) |
| fasting and postprandial insulin | At enrollment in groups 1-4 | Insulin levels during standard mixed-meal test (cfr.supra) |
| fasting adipokine levels | At enrollment in group 1-4 | Fasting serum levels of leptin, adiponectin and interleukin 6 (IL-6) |
| fasting lipid levels | At enrollment in groups 1-4 | Fasting serum levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol |
| change in fasting and postprandial glucose | before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5 | 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) |
| change in fasting and postprandial insulin levels | before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5 | Insulin levels during standard mixed-meal test (cfr.supra) |
| change in fasting and postprandial gut hormone levels | before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5 | 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) |
| change in fasting adipokine levels | before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5 | Fasting serum levels of leptin, adiponectin and interleukin 6 (IL-6) |
| change in fasting lipid levels | before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5 | Fasting serum levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol |
| fasting and postprandial glucose | At enrollment in groups 1-4 | 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) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Waist and hip circumference | At enrollment in group 1-4 | — |
| Change in resting energy expenditure | before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5 | Resting energy expenditure determined using indirect calorimetry |
| Weight change | before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5 | — |
| Change in standing height | before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5 | — |
| Change in waist and hip circumference | before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5 | — |
| Weight | At enrollment in group 1-4 | — |
| Standing height | At enrollment in group 1-4 | — |
| Resting energy expenditure | At enrollment in group 1-4 | Resting energy expenditure determined using indirect calorimetry |
Countries
Belgium
Outcome results
None listed