Lavin Chapter 12

Chapter 12 • Growth Hormone in Adults   131

fairly risky, particularly in patients with known seizure disorders or cardiovascular disease, and in the elderly. It may result in hypoglycemic seizures and, possibly, even death. The combination of GHRH and arginine is safe and provides a strong stimulus to GH secretion. Other tests include arginine alone, clonidine, glucagon, levodopa, or the combination of arginine plus levodopa. 2. Because GHRH stimulates the pituitary directly, it can give a false-normal GH response in patients with GHD of hypothalamic origin. In this situation, arginine alone may be used, without concomitant GHRH, using a lower cutoff level. It is still not clear what the lower cutoff level should be, because different centers use different values. Many endocrinologists consider a level of < 5.1 m g/L as low on the insulin-tolerance test, and < 4.1 m g/L as low on the GHRH/arginine-stimulation tests; others consider < 8.0. Some use 10.0 as a cutoff value. 3. Obesity or acute overfeeding can markedly blunt the GH response from the insulin-tolerance test. 4. The sequential arginine and GHRH infusion requires 0.5 g/kg of arginine with a maximum dose of 30 g infused in saline over 30 minutes, followed by a single bolus injection of 1 m g/kg of GHRH with a maximum of 100 m g. C. Imaging studies. Neurologic imaging (such as magnetic resonance imaging) determines the presence of intracranial disease associated with GHD. A dual-energy X-ray absorptiometry (DEXA) scan may be needed to document the presence of osteoporosis. VI. PSEUDO-GHD STATES A. Reversible and/or apparent GHD may occur in a cold environment during exercise, postpartum, in obesity, hyperthyroidism, hypercortisolism, Addison disease, congestive heart failure, and protracted critical illness. B. A low IGF-1 level in the presence of increased GH secretion , as demonstrated by stimulation tests, may reflect a peripheral resistance to GH. 1. The history of childhood GHD is less predictive of adult GHD because from 26% to 81% of such patients “normalize” GH release in adulthood—that is, even though as children they had abnormal stimulation tests, repeat tests are now normal (the reasons are not clear, but may include inadequate GH investigation as a child). Idiopathic causes account for most GHDs in childhood, but there is not total consensus that this entity occurs in adults (see Endocrine Society Consensus Statement). Children with idiopathic GHD are less likely to have permanent GHD as adults and should be retested. 2. Children who had a congenital anomaly of the pituitary gland or a tumor in the hypothalamic/pituitary region, or previous surgery or radiotherapy in this area, or a proven genetic or molecular defect involving the capacity to secrete GH, probably do not need to be retested. B. Acquired deficiency secondary to structural lesions or trauma 1. Tumors in the pituitary and hypothalamic area may cause hypopituitarism. The most common cause of GHD in adults is a pituitary adenoma, or following specific treatment of the adenoma with surgery or radiation therapy. Irradiation is a common cause of hypopituitarism and may be progressive over time in as many as 50% of patients after a 10-year follow-up. 2. Other space-occupying lesions, such as craniopharyngiomas, Rathke cleft cysts, arachnoid cysts, meningiomas, dysgerminomas, metastatic tumors, astrocytomas, or gliomas can result in GHD following surgery and/or radiation. 3. GHD is sometimes a result of compression of the portal vessels in the pituitary stalk secondary to an expanding tumor mass, directly or by raised intracellular pressure. 4. Infiltrative diseases, such as histocytosis, sarcoidosis, and tuberculosis, are additional causes. VII. ETIOLOGY Adults with GHD can be grouped into three categories: A. Previous childhood-onset GHD (transition)