Prolactin deficiency is independently associated with reduced insulin-like growth factor I status in severely growth...

In adult life, considerable overlap in IGF-I status exists between normal and severely GH-deficient (GHD) subjects defined by conventional dynamic testing of GH secretion. IGF-I is not therefore widely viewed as a reliable diagnostic marker for GHD. Recognized factors influencing serum IGF-I level in GHD include age, gender, timing of onset of GHD, and exogenous estrogen therapy, but these do not fully explain GH/IGF-I discordance in severe GHD. The primary structures of prolactin and GH are closely related. Effects of hypoprolactinemia are not well described in humans, but laboratory studies suggest a role for prolactin in hepatic IGF-I release, possibly through a signal transducer and activator of transcription 5 (STAT5) pathway. The purpose of this study was to evaluate a potential contribution of prolactin to IGF-I status in severely GHD adults.

Using multiple regression analysis techniques, contributions of the following variables to age-adjusted IGF-I sd scores were evaluated in 162 (85 female) GHD adults: gender, timing of onset of GHD, presence or absence of prolactin deficiency, body mass index, number of additional pituitary deficits, and underlying pathology.

Childhood onset GHD (P < 0.0001) and presence of prolactin deficiency (P < 0.0001) were independently associated with reduced IGF-I status. The contributions of these parameters to IGF-I sd scores were -2.55 and -2.67, respectively. Gender (P = 0.06), body mass index (P = 0.99), number of additional pituitary deficits (P = 0.64), and underlying pathology (P = 0.06) did not significantly influence IGF-I status.

Prolactin deficiency is independently associated with reduced IGF-I status in hypopituitary adults. It is possible that prolactin deficiency is a surrogate for the degree of severity of GHD, implying a GHD paradigm undetected by conventional GH provocative tests; alternatively, it remains plausible that circulating prolactin contributes to IGF-I release in the absence of GH, possibly through a signal transducer and activator of transcription 5 (STAT5) pathway.