SAT-286 A Previously Undescribed Combination of Aromatase Deficiency and Non-Classical Congenital Adrenal Hyperplasia in an Hispanic Teenage Male

Abstract

Background: Aromatase deficiency (AD) is a rare autosomal recessive genetic disorder caused by loss of function mutation in CYP19A1 leading to normal androgen but low estrogen levels. As a result men with this condition have increased linear bone growth, osteoporosis, insulin resistance and glucose intolerance, dyslipidemia, and require estradiol treatment to stop growth. Non-classical CAH (NCCAH) displays variable and possibly asymptomatic androgen excess. We present a case of adolescent with genetically confirmed both of these conditions, a combination that has not been previously described, whose clinical picture is different than previously describe AD patients, as he experienced short stature and slow growth velocity. Clinical case: A 15-year-old Hispanic male presented to the Pediatric Endocrinology clinic for evaluation after his older identical twin sisters were found to have AD. His height was at the 13th percentile while his mid-parental height was at 50th percentile. A bone age performed at chronological age 15 years 2 months was consistent with 14 years, and final height prediction based on bone age was at mid-parental height. He went through puberty at age 13. His LH and FSH were both in the normal range [LH 0.8 mIU/mL (0.29-4.77 mIU/mL), FSH 3.11 mIU/mL (0.85-8.74 mIU/mL)] but estradiol was low at <2 pg/mL (</= 31 pg/mL) as expected in AD. Interestingly, an elevated 17-hydroxyprogesterone (17-OHP) of 911 ng/dL (16-283 ng/dL) was noted. Since this is not typically seen in AD he underwent an ACTH stimulation test with 250 mcg of Cosyntropin. His repeat baseline 17OHP was 794 ng/dL and stimulated 17-OHP rose to 3431 ng/dL, consistent with NCCAH. Repeat estradiol was undetectable at <2 pg/mL (</= 31 pg/mL), as was estrone at <10 pg/mL (</= 64 pg/mL). Total testosterone mildly elevated at 1182 ng/dL (120-1000 ng/dL). Genetic testing confirmed both AD and NCCAH. Gene testing of CYP19A1 revealed a heterozygous whole gene deletion in CYP19A1, classified as pathogenic and autosomal dominant in heritance, as well as a hemizygous p.Tyr81Cys substitution in CYP19A1, also pathogenic and autosomal dominant—both of which are consistent with aromatase deficiency. He was also homozygous for a variant in the CYP21A2 gene (pVal282Leu substitution) that is associated with mild NCCAH. He did not have any symptoms of NCCAH, such as advanced bone age or early pubertal development. Conclusion: A combined picture of aromatase deficiency and NCCAH in male adolescent has not been described previously. Our patient’s phenotype does not conform to the typical clinical picture of excessive growth of long bones, as he is expected to only meet his midparental height. The cause of poor growth in this adolescent remains to be determined.