Clinical Features of 57 Patients with Lipoid Congenital Adrenal Hyperplasia: Criteria for Nonclassic Form Revisited

Context: Lipoid congenital adrenal hyperplasia (LCAH) is caused by mutations in STAR. Classic (CLCAH) and nonclassic (NCLCAH) forms were reported as total and partial deficiencies, respectively, of adrenal and gonadal steroid hormones.The rarity of LCAH has precluded large-scale epidemiological and clinical investigations. Objective: To determine the epidemiological and clinical characteristics of 2 forms of LCAH. Design: A multicenter cross-sectional cohort study in Japan on December 1, 2017. Participants: Fifty-seven patients with LCAH (median age, 23.7 years; range, 0.0–47.5 years). Main Outcome Measures: Patient demographics, STAR genotype, Quigley grade, endocrinological and imaging data, treatment, and prognosis. Results: Fifty-three and 4 patients fulfilled definite and probable diagnostic criteria for LCAH, respectively. When NCLCAH was defined as either Quigley grade 1 in XY karyotype, no episode of salt losing or requirement of fludrocortisone, or onset of primary adrenal insufficiency (PAI) at 1 year or older, patients were divided into groups of 43 patients with CLCAH (75.4%), 11 with NCLCAH (19.3%), and 3 with unclassified LCAH (5.3%). All of the patients with CLCAH and 7/11 NCLCAH (63.6%) were treated with fludrocortisone. CLCAH was diagnosed at a significantly younger age than NCLCAH (median, 0.0 vs 4.0 years). STAR-Arg272Cys or -Met225Thr was identified only in NCLCAH (8/11, 72.7%). Conclusions: We demonstrated the relative proportions and clinical and molecular characteristics of NCLCAH and CLCAH in Japan.These criteria for NCLCAH correspond to all previously published cases and our cases whose masculinization of the external genitalia, ability of mineralocorticoid production, and onset of PAI were described.