Prospective study of reproducibility and utility of growth hormone inhibition by oral glucose tolerance test for the diagnosis of acromegaly, in acromegalic and non-acromegalic subjects, with a randomized double-blind crossover over placebo arm in the group of acromegalic patients
Rational: The initial step of biological diagnosis of acromegaly is based on assessment of IGF-I. According to current recommendations, the diagnosis must be confirmed by an oral glucose tolerance test (OGTT) to show that there is no growth hormone (GH) decrease lower than 1 μg/L (Katznelson , et al., 2014). Reproducibility of GH suppression by the OGTT has never been evaluated in either acromegalic or healthy subjects, although it is essential to determine the reliability of this test. Spontaneous fluctuations in GH in acromegaly could significantly influence the response of GH to the OGTT and cause low reproducibility of the test in this population. In particular, this reliability could be different according to the typical or moderate clinical presentation because of the persistence of a residual ultradian rhythm of GH secretion. The usefulness of oral glucose loading and the resulting hyperglycemia (which may limit GH secretion) has never been compared to an appropriate placebo (aspartame, at a dose equivalent to 75 g glucose), which does not cause hyperglycemia. Ingestion of 75 g of glucose is often responsible for nausea and vomiting. More rarely, the drop in blood glucose reactive to hyper insulinemia at the end of the test, can be the cause of discomfort. Primary objective: To determine the reproducibility of the GH response to OGTT in acromegaly by studying, in subjects with acromegaly, changes in GH concentration within 2 hours after oral administration of 75 g of glucose at 2 repeated tests in the same subject. Secondary objectives: 1. To analyze the reproducibility of the GH response to the OGTT as a function of the severity of acromegaly ("typical" form, "intermediate" form of acromegaly) and in a group of non-acromegalic subjects. 2. To evaluate the diagnostic value (utility) of OGTT in acromegaly by comparing, in subjects with acromegaly, the response of GH to oral administration of 75 g of glucose (OGTT) and 375 mg of aspartame (placebo). 3. Evaluate OGTT-stimulated insulin secretion in acromegalic and non-acromegalic subjects.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
109
After inclusion, the study will include the sequential realization of 3 dynamic GH secretion tests, separated by a period of 24 hours to 30 days. Each subject will have two OGTT tests (oral administration of 75 g of glucose in 200 mL of water) and a placebo test (oral administration of 375 mg of aspartame in 200 mL of water). The order of the three tests (2 OGTT and 1 placebo) in acromegalic patients will be randomized. The tests will be performed under the same conditions
After inclusion, the study will include the sequential realization of 2 dynamic GH secretion tests, separated by a period of 24 hours to 30 days. Each subject will have two OGTT tests (oral administration of 75 g of glucose in 200 mL of water). The tests will be performed under the same conditions (fasting, semi-recumbent position, start of the test at 9 am) and will include a measurement of blood glucose, GH, insulinemia at -15, 0, 30, 60, 90, 120 min after ingestion of glucose or placebo.
AP-HP, Bicêtre Hospital
Le Kremlin-Bicêtre, France
Compare Nadir GH concentration in μg/L obtained in two OGTT in the same subject with acromegaly
GH will be measured by an immunometric chemiluminescent assay on an Immulite 2000XPi (Siemens Healthcare Diagnostics, Erlangen, Germany) on venous blood samples at -15 min, 0 min, 30 min, 60 min, 90 min, 120 min after ingestion of 75g of glucose
Time frame: The two test will be separated by the preiod of 24h - 30 days
Severity of acromegaly ("typical" form, "intermediate" form of acromegaly)
"Typical" form of acromegaly defined by an IGF-I concentration\> 200% of the upper limit of normal, in the presence of a somatotropic pituitary adenoma • moderate or "intermediate" form of acromegaly defined by an IGF-I concentration value between 100% and 200% of the upper limit of normal, in the presence of a somatotropic pituitary adenoma. The IGF-I reference values determined by sex and age in the "Variety" study will be used for this classification
Time frame: The two test will be separated by the preiod of 24h - 30 days
Nadir GH in mIU / L (conversion 1 μg / L = 3 mIU / L) obtained in the two OGTT tests and the placebo (aspartame) test repeated in the same subject (acromegalic and non acromegalic)
Nadir GH in ug/L obtained in the two OGTT tests and the placebo (aspartame) test repeated in the same subject. GH will be measured by an immunometric chemiluminescent assay on an Immulite 2000XPi (Siemens Healthcare Diagnostics, Erlangen, Germany) on venous blood samples at -15 min, 0 min , 30 min , 60 min , 90 min , 120 min after ingestion of 75g of glucose / 375g of aspartame
Time frame: Each test will be separated by the preiod of 24h - 30 days
Peak glucose level in both OGTT and placebo tests
Verification of hyperglycemia induced or not depending on the product administered
Time frame: Each test will be separated by the preiod of 24h - 30 days
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