“Long Tall Sallies” : Increased Linear Growth and Delayed Bone Maturation Are Typical of 17-Alpha Hydroxylase Deficient (17OHD) Patients from Diagnosis throughout Adulthood

Presentation Number: MON 385
Date of Presentation: April 3rd, 2017

Rafaela Fontenele*1, Denise Genaro Farinelli II2, Marivania da Costa Santos1 and Claudio E. Kater1
1Federal University of São Paulo, São Paulo, SP, Brazil, 2Universidade de Sao Paulo (UNIFESP), Sao Paulo SP, BRAZIL

Abstract

Introduction: 17OHD is the second most prevalent form of congenital adrenal hyperplasia in Brazil. Hypergonadotropic hypogonadism (HH) and mineralocorticoid hypertension are distinctive features of 17OHD. The disorder is due to reduced-to-absent activities of both 17-hydroxylase reactions: 17-hydroxylation, which impairs formation of cortisol, and 17,20-lyase activity, that impairs synthesis of sex steroids both in the adrenals and the gonads, with later increases in ACTH, gonadotropins, and cortisol precursors. Impaired production of estrogens and androgens results in absence of sexual differentiation and a peculiar state of HH with increased progesterone levels, which is typically evident around the time when puberty would occur. Both genotypic XX and XY 17OHD subjects present with a female phenotype with sexual infantilism and primary amenorrhea. Long-standing hypoestrogenism leads to delayed/ absent puberty, eunuchoid appearance, and osteopenia. Aim: to examine the impact of the lack of sex steroids upon growth development (height/span) and bone maturation from initial diagnosis (dx) throughout adulthood in patients with 17OHD, and correlate with familiar target height and the influence of estrogen replacement. Patients and methods: We revised data of 40 genotypically confirmed 17OHD patients (21XY/19XX) from distinct centers in Brazil, and collected pertinent physical, hormonal, and therapeutic information. Final data were assembled at the Division of Endocrinology, UNIFESP, São Paulo, SP, Brazil. Results: The median (Mi) age at dx was 17y (range: 11 to 40y), with a Mi height of 159cm (142-177 cm) and a height/span ratio of 0.98 (0.91-1.02). 27 of 29 patients who had a wrist X-ray available had delayed bone age (BA), with a Mi chronological age/BA ratio of 1.42 (1.20-2.22); the other two had BA slightly above chronological ages (ratios of 0.88 and 0.92). Three patients received estrogen therapy before dx of 17OHD, and most were estrogen-replaced soon thereafter. Current ages of 34 patients (6 had died or were lost to follow-up) range from 19 to 59y (Mi: 35y), and all have reached adult BA. 27 of 28 patients in whom parents’ height data were available reached a final height (Mi: 170cm; range: 158-186cm) 7.2% above the adult female target (range: 0.6% to 13.1%). Five of 14 XY patients (36%) also reached final heights above the adult male target. The Mi adult height/span ratio was maintained at 0.98 (0.93 to 1.02). Conclusion: At the time of final dx of 17OHD, which generally occurred around puberty, virtually all patients were tall and have a delayed BA. Regardless of genetic sex, most patients reached a higher than family target stature, and increased span. All these features are the result of primary hypogonadism and belated or poorly controlled estrogen therapy, leading to adult tall statures and frequent eunuchoid appearance.

 

Nothing to Disclose: RF, DGF II, MDCS, CEK