Clinical and molecular studies aimed at optimizing glucocorticoid treatment and bone homeostasis in patients with Congenital Adrenal Hyperplasia

MARTIN S, MUÑOZ L, PEREZ A, SOBRERO G, PICOTTO G, OCHETTI M,CARPENTIERI A, SILVANO L, DIAZ DE BARBOZA G, RUPEREZ C, BERTOLOTO P, TOLOSA DE TALAMONI N, MIRAS M

NEW YORK, USA

Congreso; 8th Joint Meeting of the Lawson Wilkins Pediatric Society/ESPE; 2009

ESPE

Chronic glucocorticoid (GC) therapy can affect statural growth and induce disorders in bone metabolism. Patients with congenital adrenal hyperplasia (CAH) need a lifelong GC replacement therapy to reduce overproduction of adrenal androgens and prevent its adverse effects. Careful dose adjustment is necessary to obtain optimal bone mass and adult height according to their genetic potential. Polymorphisms of vitamin D receptor (VDR) and estrogen receptor (ER) genes have been associated with variations in bone homeostasis and in the therapeutic response in different diseases. AIMS: To determine clinical and biochemical indicators of the outcome of GC and mineralocorticoid (MC) therapy in patients with different clinical forms of CAH. To analyze the frequencies of gene polymorphisms of VDR and ER in CAH patients, and to determine possible associations with bone turnover markers and IGF systems. SUBJECTS AND METHODS: Data of 42 patients with CAH due to 21-OH deficiency (age range 1.8 - 26.8 years, 23 female,19 male), treated with GC and MC in cases with the salt-wasting form, were studied. They were analyzed in two groups according to the presence of an adequate clinical auxological and biochemical control based on levels of 17-OHP, delta-4 A (DPC), DHEA-S, testosterone (ECLIA). Osteocalcin (Oc) and B-crosslaps (BCL) (ECLIA), IGF1 and IGFBP3 (DSL) were determined. Two polymorphic sites of VDR gen (Bsm I and Fok I) and one of the ER gen (PVU II) were explored using PCR-RFLP method in CAH patients and in 27 normal controls of the same age and sex. RESULTS: The distribution of clinical forms was similar between groups. No significant differences in the relative frequencies of the analyzed polymorphisms between groups and the healthy controls were observed. CAH Fok I:FF 0.45, ff 0.15, Ff 0.40 Bsm I: BB 0.19, bb 0.26, Bb 0.55, Pvu II: PP 0.17, pp 0.4, Pp 0.43, versus Controls FF 0.30, ff 0.18, Ff 0.52; BB 0.16, bb 0.32, Bb 0.52; PP 0.27, pp 0.35, Pp 0.38. No significant associations were found between these genotypes and bone turnover markers, IGF1 or IGFBP3.CONCLUSIONS: Our data suggest that the genotypes analyzed, with a distribution comparable to the normal population, are not enough to explain the different results obtained with the treatment. The contribution of the other bone turnover markers and of other associated genes, should be evaluated.