Tall stature in familial glucocorticoid deficiency

OBJECTIVE Familial glucocorticoid deficiency (FGD) has frequently been asso ciated with tall stature in affected individuals. The clinical, biochemical and genetic features of five such patients were studied with the aim of cl arifying the underlying mechanisms of excessive growth in these patients. PATIENTS AND METHODS Five patients with a clinical diagnosis of FGD are des cribed in whom the disorder resulted from a variety of novel or previously described missense or nonsense mutations of the ACTH receptor (MC2-R). All patients demonstrated excessive linear growth over that predicted from pare ntal indices and increased head circumference. RESULTS Growth hormone and IGF-I-values were normal. Growth charts suggest that the excessive growth is reduced to normal following the introduction o f glucocorticoid replacement. A characteristic facial appearance including hypertelorism, marked epicanthic folds and prominent frontal bossing was no ted. CONCLUSIONS These findings indicate that ACTH resistance resulting from a d efective ACTH receptor may be associated with abnormalities of cartilage an d/or bone growth independently of the GH-IGF-I axis, but probably dependent on ACTH actions through other melanocortin receptors.