Use of GHRH in Diagnosis

Part of the challenge of considering treatment in a heterogeneous aging population is identifying those individuals with the most severe reductions in endogenous GH secretion before testing whether that process helps define who might most benefit from treatment. Measuring 24-h pulsatile or even mean GH levels is impractical for population screening, and thus there has been a search for simpler tests or markers, including GH responses to GHRH, which might correlate with reductions in endogenous secretion. As with GH deficiency, a simple index has been an elusive goal. In early studies we found that the GH response to GHRH was well maintained in very healthy older subjects (Fig. 9) (41), but other authors have reported a decrease in responsiveness. This discrepancy may reflect differences in the populations studied, since the increase in adipose tissue which accompanies aging can blunt GH responses. This reduction is presumably related at least in part to an increase in somatostatin tone, given that argi-nine pretreatment, which reduces somatostatin, can almost completely restore the age-related decline (42).

In contrast to its use in adult-onset GHD, the variability in GH responses to GHRH alone, and the alteration of baseline responses by the use of somatostatin inhibitors both make GHRH a relatively poor tool for gaging the endogenous activity of the GH axis. Other tests, such as insulin-induced hypoglycemia, have so far proven to be better

Fig. 9. GH responses (± SEM) to the acute intravenous injection of GHRH(1-44)NH2, 1 ^g/Kg iv, in groups of healthy adults aged 20-49 (O), 50-69 (□), or 70-86 (A). From ref. 41.

discriminators between normal aging and adults with frank GH deficiency (43,44); but there are still no data to indicate whether this test or others might extend to the more general question of identifying those older individuals with the greatest decrement in GH secretion.

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