Studies of patients with adult-onset GHD have served to clarify the important role of GH in maintaining the skeleton once peak bone mass is reached. Such individuals have acquired hypothalamic or pituitary dysfunction in adult life, typically owing to neoplasms of the pituitary or adjacent structures. Compromise of secretory function may occur owing to mass effect of the lesion, or, as a result of surgical or radiation treatment. The best approach in diagnosing GHD in adults remains a major unresolved issue, and the presence of GH deficiency is typically determined by means of provocative tests. In contrast to children, in whom growth is an objective parameter used in the assessment of GHD, there is no defined physiological endpoint that can be used in the diagnosis of GH deficiency in adults. GH secretion is age-, sex-, and nutritional-dependent. The variabil ity of GH secretion in normals and the lack of objective endpoints have made the determination of absolute and relative GH deficiency problematic.
One study of 95 adults, ranging in age from 21-74 yr and identified as GH deficient on the basis of provocative tests, showed low bone density of the lumbar spine compared to normal controls. This significant deficit in bone density persisted when patients with untreated hypogonadism were excluded (20). Two smaller studies showed reduced bone density of the total body (21), femoral neck, Ward's triangle, and greater trochanter (22) in patients with adult-onset GHD compared to normals. In both of these studies, a significant correlation was found between bone density and serum levels of IGF-1, an integrated marker of GH secretion. Because patients with adult-onset GH deficiency were by definition endocrinologically intact through adolescence, they presumably had normal skeletal development and reached a normal peak bone mass. Therefore, osteopenia in such patients, can only be explained on the basis of accelerated loss of bone during adulthood.
Adult-onset GHD is often associated with other hormone deficiencies. Therefore, the studies cited previously could not entirely exclude gonadal steroid deficiency as a contributing cause of bone loss. Although patients in the majority of these studies received testosterone or estrogen replacement, it is possible that the period of gonadal steroid deficiency before the initiation of hormone treatment may have led to osteopenia. Holmes et al. (23) addressed this issue in a study of 26 GH-deficient adults who had been treated with surgery and/or radiation for tumors of the pituitary or brain. As a group, these patients displayed reduced bone density of the forearm and lumbar spine. A subgroup of patients with isolated GHD were also shown to have low bone density of the lumbar spine and forearm. These data indicate that GHD acquired in adulthood may lead to osteoporosis, presumably on the basis of bone loss occurring after the attainment of normal peak bone mass.
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