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Division of Endocrinology, Metabolism and Molecular Medicine
Northwestern University Feinberg School of Medicine
Mark E. Molitch, MD, has disclosed that he has received funds for research support from Bayer, Chiasma, Crinetics, Novartis, Recordati, and Strongbridge; consulting fees from Chiasma, Recordati, and Strongbridge; and other financial or material support from Corcept and Janssen.
There are an estimated 6000 new cases of adult growth hormone deficiency (GHD) every year in the United States, and these can be divided into cases of childhood onset with persistence into adulthood and those developing during adulthood. The benefits and risks of growth hormone (GH) treatment are discussed elsewhere. Testing for GHD should be carried out only if a decision has been made to treat the deficiency, if found. This raises questions about who should be tested (and who should not), when testing should occur, and which tests and selection criteria should be used.
Whom to Test?
Most children diagnosed with GHD have idiopathic GHD rather than organic causes, such as genetic defects or anatomic lesions affecting the hypothalamus/pituitary. On retesting as adults, 90% of those with idiopathic GH will have normal GH responses, but the converse is true for those with organic causes. Why some children with GHD have normal GH responses as adults is not clear, but there is imprecision in diagnosing GHD at both stages, and it may require a greater amount of GH to stimulate growth than to maintain body composition and quality of life in adulthood. In any case, retesting during the transition period (a few years after achieving final height) is important to determine who should continue to receive GH as adults.
With adult-onset GHD, the idiopathic variety is very rare; almost all cases have organic causes, such as pituitary/hypothalamic tumors or infiltrative disease. Nontumoral disorders also have been recognized, including head trauma (eg, sports injury, accidents) and subarachnoid hemorrhage. Often, GH is the first hormone lost among the pituitary hormones, and testing is needed to determine if it is present.
When to Test?
The ideal timing of GHD testing for any given patient is unclear. Should they be evaluated as soon as GHD is suspected (eg, immediately after surgery)? Should it be done after all other deficient hormones have been replaced? Should it be done in the patient who feels perfectly normal after hormone replacement or only in those who still don’t feel like they’re back to normal? Or, should it be done only after signs and symptoms of GHD appear, such as fatigue, decreased muscle mass/strength, increased fat mass, and decreased quality of life?
Testing is generally not required if 3 or more other pituitary axes have been determined to be deficient, especially if the insulin-like growth factor 1 (IGF-1) level is low. Previous studies have shown that more than 95% of individuals with IGF-1 deficiency have GHD. For those not meeting such criteria, 3 tests are now available that have sufficient sensitivity and specificity to permit diagnosing GHD with high accuracy. The insulin tolerance test has been the gold standard, with a GH level <5.1 ng/mL after achieving adequate hypoglycemia being indicative of GHD. Glucagon stimulation testing (1 mg intramuscularly) is indicative of GHD when the GH level is <3 ng/mL, although some studies indicate 1 ng/mL in patients with obesity. Finally, macimorelin is an orally active ghrelin mimetic that binds to the ghrelin GHS-R1a receptor; when given orally (0.5 mg/kg), a GH level <5.1 ng/mL is diagnostic of GHD. The combination of arginine plus GH-releasing hormone (GHRH) also has high accuracy as a stimulation test, but GHRH is not available in the United States.
The choice of which test to use depends on the abilities of a given clinical practice to carry out such testing, but all of these are acceptable tests for diagnosing GHD in the appropriate patient.
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