At a Glance
Growth hormone (GH) deficiency in adults is difficult to identify, because its manifestations are subtle and nonspecific. As such, laboratory investigations are performed in adults who are known to have pituitary disease. Clinically, GH deficiency in adults can result in a decrease in lean body mass, dyslipidemia, and impaired cardiovascular function. There are several causes of GH deficiency due to either pituitary or hypothalamic disease. Pituitary or extrapituitary tumors account for approximately 90% of all adults with GH deficiency. Sarcoidosis and Sheehan syndrome each account for approximately 1% of cases. Cause is often unknown in the remainder.
GH deficiency in children can be either genetic or acquired. In all cases, growth failure is the most important clinical manifestation of the deficiency. Children who are of marked short stature (>2 standard deviations) for their age, sex, and ethnic background should be further evaluated for possible GH deficiency, as should those with severe growth deceleration, history of brain tumor, cranial irradiation, or radiologic evidence of a pituitary abnormality. Other causes of short stature should be ruled out prior to investigating GH deficiency. These include hypothyroidism, chronic systemic disease, Turner syndrome, Prader-Willi syndrome, and skeletal disorders.
What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?
In adults, GH secretion is pulsatile and, therefore, unreliable for the evaluation of GH deficiency. Insulin-like growth factor 1 (IGF-1) or provacative testing is required. Hepatic synthesis of IGF-1 is stimulated by GH, and its concentration in the blood remains relatively stable. A serum IGF-1 concentration below the age-specific reference limit confirms GH deficiency in an individual with known pituitary disease. GH secretion is induced by certain stimuli and is the basis of provocative tests:
Insulin tolerance test: Hypoglycemia stimulates the release of GH, and this test is considered the gold standard test for GH deficiency. After administering insulin to induce hypoglycemia, samples are obtained over 120 minutes. A below normal increase in the GH concentration indicates GH deficiency. The test is risky because of the resulting hypoglycemia and requires constant physician supervision.
Arginine-GHRH: Arginine and growth hormone-releasing hormone (GHRH) are administered, and samples are obtained over 120 minutes. A below normal increase in the GH concentration indicates GH deficiency. The response of GH to this stimuli is weaker than it is to hypoglycemia.
Glucagon: Glucagon is administered to stimulate the release of GH. Samples are obtained every 30 minutes for 4 hours. A below normal increase in the GH concentration indicates GH deficiency. The response of GH to this stimuli is weaker than it is to hypoglycemia.
In children, GH secretion is pulsatile and, therefore, unreliable for the evaluation of GH deficiency. Insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 1 (IGFBP-3), and provocative testing are required. Because IGF-1 and IGFBP-3 can be decreased because of other causes for growth failure, such as poor nutrition, they cannot be relied on to diagnose GH deficiency. Provocative testing is similar to that used in adults, except GH concentration cutoff used to identify a “normal” response is frequently higher in children. The insulin tolerance test is less commonly used in children because of safety concerns.
Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?
Age- and gender-specific reference intervals are required for accurate interpretation of IGF-1. Starvation, obesity, and diabetes mellitus decrease and pregnancy increases concentrations of IGF-1.
Provocative tests are affected by obesity and may produce false positive (deficient) results.
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