It has been shown that changes in IGF-I and IGFBP levels in children with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) are correlated with different states of metabolic control. Our approach was to analyze the serum levels of IGF-I, IGFBP-3, their molar ratio IGF-I:IGFBP-3 (MR), and ALS in a cohort of CAH children and adolescents, and their associations with different clinical and biochemical parameters.
Design and patients: 56 patients, aged between 5.6 and 19.0 years were studied cross-sectionally. All patients had genetically proven CAH and received standard steroid substitution therapy. We measured serum levels of IGF-I, IGFBP-3, and ALS by commercial ELISA and calculated MR and assigned population-based SD scores (SDS).
Results: (median, quartiles) Overall IGF-I was not significantly altered (0.05 SDS, -1.21, 0.92), whereas IGFBP-3 was significantly elevated (1.50 SDS; 0.58, 1.95, p<0.0001) compared to the reference population. Consecutively, MR was decreased (-0.64 SDS; -1.38, 0.32; p=0.0017). ALS was clearly decreased (-1.95 SDS; -3.075, -1.00; p<0.0001). ALS, IGF-I, MR, and IGFBP-3 SDS were lower in pubertal than in prepubertal patients (p<0.05). ALS SDS were lower in girls (p=0.0038). Correlation analyses (r(s), p) revealed correlations between MR/ALS and chronological age (-0.583, <0.0001/-0.428, 0.0010), MR/ALS and Tanner stages (-0.500, <0.0001/-0.334, 0.0118), MR/ALS and bone age (0.407, 0.0075/0.426, 0.0049), and between MR and ALS (0.405, 0.0020), respectively. For MR and ALS, we found no significant correlations for BMI, HOMA-IR, hydrocortisone and fludrocortisone dosage, or parameters of metabolic control.
Conclusions: Our data provide evidence that the components of the trimeric IGF-I-IGFBP-3-ALS complex are altered in CAH children with possible implications on pubertal growth and final height.
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