Endocrine Abstracts (2006) 11 P230

Lack of influence of an IGF-I gene polymorphism on circulating IGF-I levels in severely GHD adults

JAMJL Janssen2, A Mukherjee1, HK Gleeson1, S Lamberts2 & SM Shalet1


1Christie Hospital, Manchester, United Kingdom; 2Erasmus MC, Rotterdam, Netherlands.


Considerable overlap in IGF-I levels exists between normal and severely GHD subjects; the mechanisms underlying this observation remain poorly understood. Under various clinical circumstances therefore, IGF-I estimation is an unreliable marker of GH status. A polymorphism in the IGF-I gene influences IGF-I levels in normal populations; a higher IGF-I is associated with the presence of 2 wild type alleles of the IGF-I gene (WTG). The possibility that an IGF-I gene polymorphism could contribute to overlap of unstimulated IGF-I levels between normal and severely GHD adults is investigated.

The study was approved by the local research ethics committee. IGF-I genotype was determined in 128 (72 female, age range 18–82 years) severely GHD adults. Using multiple regression analysis, contributions of IGF-I genotype and the following variables capable of affecting age-adjusted IGF-I in severe GHD were evaluated; gender, timing of onset of GHD, presence or absence of prolactin deficiency, BMI, number of additional pituitary deficits and underlying pathology.

Ninety-eight (76.6%) and 30 (23.4%) subjects possessed WTG and variant IGF-I genotype (VG) respectively. Eighty-seven (68%) had adult-onset GHD. Median IGF-I level was 114.0 μg/l and 121.5 μg/l in WTG and VG respectively (P=0.45). There was no significant difference in weight and height between subjects with WTG and VG. Mean BMI was 29.4±7.22 and 25.7±5.75 for WTG and VG groups respectively (P=0.01). No independent contribution of IGF-I genotype (P=0.78), gender (P=0.38) BMI (P=0.48) and number of additional pituitary deficits (P=0.9) to IGF-I status were detected.

The higher IGF-I level associated with the presence of IGF-I WTG appears lost in severe GHD, consistent with the disturbed GH/IGF-I secretory physiology associated with this condition. Although the confidence intervals are wide for this observation, the presence of factors other than IGF-I genotype, appear to have a greater influence on IGF-I status in severely GHD adults.

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