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


METHODS
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.


RESULTS
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.


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 signal transducer and activator of transcription 5 (STAT5) pathway.
Mukherjee
A
A
Department of Endocrinology, Christie Hospital, Wilmslow Road, Manchester M20 4BX, United Kingdom. annice.mukherjee@christie-tr.nwest.nhs.uk
Ryder
W D J
WD
Jöstel
A
A
Shalet
S M
SM
D000293:Adolescent; D000328:Adult; D000368:Aged; D015914:Estrogen Replacement Therapy; D005260:Female; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007018:Hypopituitarism / Q000150:complications; D007027:Hypothalamic Diseases / Q000150:complications / Q000209:etiology; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011388:Prolactin / Q000172:deficiency*; D012044:Regression Analysis
D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D011388:Prolactin