Growth Hormone, IGF-1 and Medical Treatment in Acromegaly: Are There Effects on Gut Hormone Physiology and Postprandial Substrate Metabolism?
Growth Hormone, IGF-1 and Medical Treatment in Acromegaly: Are There Effects on Gut Hormone Physiology and Postprandial Substrate Metabolism?
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.
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