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.

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.

Inclusion Criteria:

• 18 to 80 years of age
• male and female
• hypothalamic pituitary disorders (study subjects)
• history of regular, age appropriate menses (control subjects)
• male subjects with normal serum testosterone and follicle stimulating hormone (FSH) (control subjects)
• normal FSH in post-menopausal subjects (control subjects)
• normal thyroid stimulating hormone (TSH), free thyroxine (T4), prolactin (control subjects)

Exclusion Criteria:

• unable to give consent
• pregnancy
• active acromegaly
• pheochromocytoma
• active Cushing's disease
• pituitary insult within past 6 weeks
• elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
• renal failure
• history of malignancy
• severe acute illness
• uncontrolled hypertension
• Diabetes mellitus (DM) type 1
• Hemoglobin (Hgb) A1c >9% in last 3 months in Type 2 DM
• severe coronary artery disease
• women <50 years of age with untreated hypogonadism
• men with untreated hypogonadism
• growth hormone treatment in the past 3 months