The Glucagon Stimulation Test for Evaluation of Adult Growth Hormone Deficiency and Adrenocorticotropic Axis
Condition: Adult Growth Hormone Deficiency; Hypothalamic-pituitary Disorders
MeSH terms: Dwarfism, Pituitary; Pituitary Diseases; Endocrine System Diseases
Study type: Interventional

Summary: 
      The purpose of this study is to find out if the Glucagon Stimulation Test (GST) is a reliable
      alternative to the Insulin Tolerance Test (ITT) for diagnosis of Growth Hormone Deficiency
      (GHD) and adrenal insufficiency. In some patients the accuracy of the GST for evaluation of
      adrenal insufficiency is compared to the adrenocorticotropin hormone (ACTH ) stimulation
      test.
    

Detailed description: 
      Growth hormone is a protein that is produced by the pituitary gland and influences the
      metabolism (how fast things work) of other proteins, carbohydrates, and fats in the body.
      This allows the growth hormone to help humans keep a healthy balance between fat, muscle and
      bone throughout their life. Some people have what is called Growth Hormone Deficiency (GHD),
      which means that they do not produce enough growth hormone. GHD may lead to a tendency to be
      fat, (especially around the abdominal area), a reduced ability to exercise, heart disease, an
      increased possibility of breaking bones, and a general reduced quality of life.

      GHD is usually evaluated through growth hormone stimulation test(s). One of the most reliable
      tests to evaluate if someone has GHD is by using arginine + Growth Hormone Releasing Hormone
      (GHRH) test. However, Since 2008 GHRH is no longer available in the USA. For this reason
      there has been a significant gap for an alternative test for evaluation of patients suspected
      to have GHD that can be easily performed and be reliable. The Insulin Tolerance Test (ITT) is
      generally considered the gold standard test for evaluation of growth hormone (GH) deficiency.
      The ITT involves giving insulin intravenously (through a plastic tube inserted in your vein)
      to lower your blood sugar followed by the collection of blood samples to evaluate how your
      body handles low blood sugar. There are side effects of the ITT including hypoglycemia (low
      blood sugar causing you to become weak, perspire, shaky and have some mental cloudiness)
      which can be unpleasant. ITT can not be performed in patients older than 65 years of age and
      in those with certain medical conditions such as history of heart disease, seizure disorder
      or stroke. At the same time, the ITT needs to be done by an experienced clinician and
      requires trained staff to perform. For this reason there is a need for an alternative
      reliable test for evaluation of GHD.

      The second purpose of this study is to find out if you have adrenal insufficiency. Cortisol
      is a hormone produced by the adrenal gland and is released in response to stress. Cortisol
      production is regulated through the hypothalamus and the pituitary gland. Its primary
      functions are to increase blood sugar, regulate the immune system and aid in fat, protein and
      carbohydrate metabolism. Patients with low cortisol may experience fatigue, body ache, sleep
      disturbance, nausea and mood changes. Pituitary disorders may lead to low cortisol levels and
      can cause symptoms associated with adrenal insufficiency. The Insulin Tolerance Test (ITT)
      can also be used for the evaluation of adrenal function. Patients who can not undergo ITT,
      can be evaluated by the ACTH (adrenocorticotropic hormone) Stimulation Test, which is
      generally very well tolerated. Preliminary results from previous studies indicate that the
      Glucagon Stimulation Test (GST) may be used to evaluate adrenal function. The investigators
      in this study will compare your cortisol levels during two different GSTs with the cortisol
      levels achieved during ITT or ACTH stimulation test.

      Since the 1970s, the Glucagon Stimulation Test (GST) has been used by several research
      studies for evaluation of GHD and adrenal insufficiency. Glucagon is a hormone produced in
      the pancreas and is secreted during times of low blood sugar or in response to growth
      hormone. It is used to raise very low blood sugar and in diagnostic testing of the stomach
      and other digestive organs. Glucagon is readily available, relatively inexpensive and
      generally well tolerated; the major side effects include upset stomach that can lead to
      vomiting and headaches. It can be used in patients with diabetes and those older than 65
      years of age.

      The glucagon stimulation test (GST) has been suggested as an alternative test to ITT for
      evaluation of growth hormone deficiency (GHD) and adrenal insufficiency. The test is similar
      to the ITT and ACTH Stimulation Test in that blood samples are taken both before and after
      the medication is given. Glucagon is given intramuscularly (as in injection in your muscle).
      The fewer side effects make this an attractive substitute for the ITT. The 2007 consensus
      guideline by the GH Research Society considers GST as a test that may be used for evaluation
      of patients suspected to have GHD. However, the same statement does not provide any
      diagnostic cut-off value for GH during the GST. The purpose of this study is to see if the
      GST can be an accurate substitute for the ITT in the evaluation of both GHD and adrenal
      insufficiency.
    

Intervention name(s): Glucagon stimulation test and insulin tolerance test; glucagon stimulation test and insulin tolerance test
Intervention type(s): Procedure; Procedure
Intervention description(s): glucagon stimulation test using 1 mg (1.5 mg if weigh >90 kg) glucagon stimulation test using 0.03 mg/kg (maximum dose 3 mg) insulin tolerance test using 0.10-0.15 U/kg ACTH stimulation test in subjects with type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), cerebrovascular disease (CVD), seizure; glucagon stimulation test using 1 mg (1.5 mg if weigh >90 kg) glucagon stimulation test using 0.03 mg/kg (maximum dose 3 mg) insulin tolerance test using 0.10-0.15 U/kg ACTH stimulation test in subjects with type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), CVD (cerebrovascular disease), seizure
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Glucagon; Glucagon-Like Peptide 1
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: glucagon stimulation test; insulin tolerance test; growth hormone deficiency; hypothalamic-pituitary disorders