Background: In adult life considerable overlap in IGF-I status exists between normal and severely 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 hypoprolactinaemia are not well described in humans but laboratory studies suggest a role for prolactin in hepatic IGF-I release, possibly through a STAT5 pathway. The purpose of this study was to evaluate a potential contribution of prolactin to IGF-I status in severely GHD adults.

Patients and Methods: Using multiple regression analysis techniques, contributions of the following variables to age-adjusted IGF-I SDS were evaluated in 162 (85 female) GHD adults; gender, timing of onset of GHD (childhood=CO, adult=AO), presence or absence of prolactin deficiency, BMI, number of additional pituitary deficits and underlying pathology.

Results: CO-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 SDS were -2.55 and -2.67 respectively. Gender (P = 0.06), BMI (P = 0.99), number of additional pituitary deficits (P = 0.64) and underlying pathology (P = 0.06) did not significantly influence IGF-I status.

Conclusions: 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 STAT5 pathway.