Delayed Bone Maturation and Extended Growth Phase As Distinctive Features of 17α‐hydroxylase/17,20‐lyase Deficiency: A Retro‐Prospective Study of a Large Patient Cohort

INTRODUCTION:Worldwide, combined 17-hydroxylase/17,20-lyase deficiency (CYP17D) is a rare form of congenital adrenal hyperplasia, but it is the second most prevalent type in Brazil. An absence of sexual differentiation and hypergonadotropic hypogonadism arise from a reduction in the usual pattern of sex steroid formation in the adrenals and the gonads, and virtually all affected individuals are phenotypically female, regardless of karyotype. The absence of sex steroids precludes bone maturation, allowing an extended growth phase, such that nontreated adult patients usually have a tall eunuchoid appearance. Mineralocorticoid hypertension is an associated feature. OBJECTIVE:To describe the clinical aspects of growth development, bone maturation, and body proportions of a large cohort of Brazilian patients with CYP17D. PATIENTS AND METHODS:The study involved an analysis of the records of 88 patients with CYP17D who were treated at the Federal University of São Paulo Medical School and other Endocrine Reference Centres in Brazil. RESULTS:At diagnosis, the median chronological age and bone age of non-adult patients were 15.8 years (range: 10-20 years; n = 41) and 11 years (7.5-15 years; n = 25), respectively. A delay of ≥ 2 years in bone age was present in 92.5% of cases. In 30 patients, the height and its Z-score were 157 cm (130-171.5 cm) and -0.4 (-3.0 to +1.6), respectively. The span-to-height ratio was high and consistent over time. Final heights were available for 51 patients, of which 77% (25 XY, 14 XX) were in the 50th percentile or higher, and 39% (14 XY, 6 XX) were in the 90th percentile or higher. Only 8% (1 XY, 3 XX) were in the 25th percentile or lower. Of the 42 patients with data available, 11 (26%) had lower Z-scores during childhood and adolescence, and it is plausible that they missed a growth spurt. CONCLUSION:In this large CYP17D cohort, we verified that the prolonged hypoestrogenism that led to delayed or absent puberty was associated with decreased bone age, lower stature in childhood and adolescence, missed growth spurts, an extended growth phase, and greater final heights with frequent eunuchoid appearance.