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GH sensitivity of GH‐deficient adults is dependent on gender but not timing of onset
Author(s) -
Columb Breeda,
Smethurst Linda E.,
Mukherjee Annice,
Jostel Andreas,
Shalet Stephen M.,
Murray Robert D.
Publication year - 2009
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2008.03354.x
Subject(s) - medicine , endocrinology , basal (medicine) , biology , insulin
Summary Background Females secrete 2–3‐fold greater amounts of GH compared with males despite maintaining similar IGF‐I levels. IGF‐I generation tests in healthy subjects suggest this discordancy results from relative resistance to GH in females. In GHD females the presumed relative insensitivity to GH is reflected by a lower basal IGF‐I and the need for higher GH maintenance doses during replacement. Adults with severe GHD of childhood‐onset (CO) have lower basal IGF‐I SDS and require higher GH maintenance doses compared with adult‐onset (AO) patients with GHD of equal severity. We hypothesised CO‐GHD adults to be less sensitive to GH than AO‐GHD patients. Methodology In a single site study we analysed the incremental change in IGF‐I (ΔIGF‐I) in 116 GHD adults following initiation of GH replacement. The data were corrected to provide ΔIGF‐I/mg GH because of slight variances in initial GH dose. Results Following GH replacement ΔIGF‐I was 230 ± 245 and 356 ± 278 ng/ml/mg GH in females and males, respectively ( P = 0·01). In CO and AO patients ΔIGF‐I was 282 ± 206 and 294 ± 292 ng/ml/mg GH, respectively ( P = 0·83). Further analysis after stratification by both gender and timing of onset of GHD showed ΔIGF‐I was 226 ± 164, 324 ± 228, 231 ± 268, and 373 ± 304 ng/ml/mg GH in the CO females, CO males, AO females, and AO males, respectively (AO males vs. AO females, P = 0·03; CO males vs. CO females, P = 0·17; AO males vs. CO males, P > 0·05; AO females vs. CO females, P > 0·05). Multiple linear regression with ΔIGF‐I as the dependent variable and age, gender, BMI, baseline IGF‐I level, and timing of onset as independent variables showed ΔIGF‐I to be dependent on gender alone ( R = 0·28, P = 0·004). Age ( P = 0·44), BMI ( P = 0·54), baseline IGF‐I level ( P = 0·63) and timing of onset ( P = 0·61) had no effect on ΔIGF‐I. Conclusion We have shown gender to have a significant impact on GH sensitivity in GHD adults, which, at least in part, explains differences in maintenance dosages during replacement. None of the additional variables impacted significantly on GH sensitivity. The lower basal IGF‐I SDS and higher GH replacement requirement reported in CO compared with AO patients cannot be explained by differences in sensitivity to GH.