ESPE Abstracts

Background: Classical salt wasting congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is a rare disorder, as is isolated growth hormone (GH) deficiency Type II (IGHD II) due to mutation of the growth hormone gene GH1. Here we describe the unusual case of a girl with concurrent 21OHD and IGHD II and its complex diagnostic work up. A 15.3-year-old girl presented with classical salt wasting CAH due to 21OHD and short stature (height 148.3cm, -2.8 SDS). The diagnosis of CAH had been made in early childhood by hormonal and genetic analyses. Regarding CAH, drug therapy consisted of hydrocortisone and fludrocortisone. Unusual for a patient with CAH, her bone age was delayed by 3 years. There was familial short stature (father’s height 158.6 cm, (-3,2 SDS), mother’s height 164.4 cm (-0,57 SDS), parental target height 155cm (-2,03 SDS)). IGF-1 level was low (84µg/l, SDS -3.39) while IGFBP-3 was normal (2.95mg/l, -0.54 SDS). A GH stimulation test using arginine test showed an inconspicuous result (GH increase to max. 12,6 ng/ml), so that biochemically the diagnosis of isolated GH deficiency could not be made. Further genetic examinations followed. Abnormalities in the SHOX gene could be excluded, so that a further investigation was carried out by means of next generation sequencing gene panel. A heterozygous variant c.235T>G p.(Cys79Gly) in exon 3 of the GH1 gene was detected which had not been described before. This mutation interrupts the disulfide bridge at position 53 of the mature GH peptide which is important for the correct tertiary structure. After additional genetic analysis of both parents, the same heterozygous variant of the GH1 gene was detected in the father and thus a paternally inherited, autosomal dominant form of IGHD type II was diagnosed.

Conclusion: The combination of CAH and IGHD II has not yet been described. We present a new mutation of GH 1 and speculate that the GH exon 3 mutation c.235T>G of our patient leads to the formation of partially bioinactive GH, as has been described for the mutation Exon 3, c.236G>C by Besson et al. It is important to note, that a normal GH stimulation test does not rule out growth hormone deficiency in any case!