Acromegaly is a disease characterized by the excessive production of growth hormone (GH). More than 99% of cases of acromegaly result from a tumor of the pituitary gland secreting either GH or both GH and PRL. Gangliocytomas of the hypothalamus or pituitary and ectopic neuroendocrine tumors secreting GH-releasing hormone (GHRH) account for less than 1% (33).
Hypogonadism has been reported in 49% to 70% of patients with acromegaly (31,34). Secretion of PRL by the tumor, together with GH or stalk disruption by suprasellar growth, have been implicated in hypogonadism development (35). However, Katznelson et al. (35) described low testosterone levels in 39% of men with somatotroph microadenomas, most of whom had normal PRL levels. Therefore, other factors may contribute to the pathogenesis of hypogonadism in acromegaly. GH lowers the level of sex hormone-binding globulin (SHBG), so that free testosterone levels should be measured. Hypogonadism occurs more often in patients with macroadeno-
mas than in those with microadenomas (34,35) because of the tumor mass effect on surrounding normal tissue.
The primary factor mediating gonadal damage in acromegaly is GH excess. GH regulates testicular function, by stimulating the local production of insulin-like growth factor (IGF)-1, which modulates steroidogenesis and spermatogenesis. In fact, GH administration increases Ley dig and Sertoli cell responses to FSH and LH (36,37). However, high GH and IGF-1 levels induce severe testicular alterations and disrupt the hypothalamic-pituitary-testicular axis. Repeated administration of high doses of GH in dogs reduced testicular weight with germ cell degeneration and epithelial atrophy (38). The extent of testicular damage is related to the severity of acromegaly. In fact, serum GH and IGF-1 levels correlate negatively with serum DHT levels (see Fig. 2). Several mechanisms have been proposed to explain these findings, including a change in androgen metabolism (39), FSH and LH suppression by increased somatostatin tone, a decrease in the serum concentration of SHBG, and lactogenic effects of GH separate from those of PRL (40-43). In addition, prostatic dysfunction leading to alterations of the seminal fluid may occur in acromegaly. In fact, GH/IGF-1 excess causes prostate enlargement with a high prevalence of prostatic abnormalities (44,45).
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