SAT-463 - Lipoid Congenital Adrenal Hyperplasia Due to Star Deficiency in A 46,XY Patient with A Female Phenotype: A Case Report and Literature Review

Introduction: Primary adrenal insufficiency in childhood is predominantly associated with hereditary disorders, with congenital adrenal hyperplasia being the most common cause. Lipoid congenital adrenal hyperplasia secondary to pathogenic variants in the StAR gene is a rare form that results from impaired mitochondrial cholesterol transport, leading to combined deficiencies of glucocorticoids, mineralocorticoids, and sex steroids. In 46,XY individuals, this condition is typically associated with female external genitalia.

Case Presentation: We report the case of a 5-year-old patient raised as a girl with female external genitalia , with primary adrenal insufficiency diagnosed at 3 months of age and treated with hydrocortisone (7.5 mg/day) and fludrocortisone (0.1 mg/day). Biochemical evaluation showed persistently elevated ACTH (2000 pg/mL) with suppressed morning cortisol (0.06 µg/dL). Steroidogenesis profiling demonstrated a global deficiency of adrenal and sex steroids: androstenedione < 0.24 ng/mL, 17-hydroxyprogesterone < 0.07 ng/mL, free testosterone < 0.01 pg/mL, and DHEA-S 0.2–3.4 µg/dL, along with low aldosterone ( < 3.7 ng/dL). Karyotype was 46,XY. Genetic testing identified a pathogenic truncating homozygous variant in STAR (NM_000349.3: c.577C>T; p.Arg193*), confirming lipoid congenital adrenal hyperplasia due to StAR deficiency in a 46,XY patient with a female phenotype

Discussion: Disorders of steroidogenesis represent an important cause of primary adrenal insufficiency in childhood, with congenital adrenal hyperplasia being the most frequent entity. Unlike other forms of congenital adrenal hyperplasia, StAR deficiency (lipoid CAH) is characterized by a global impairment of steroidogenesis, resulting in severe adrenal and gonadal dysfunction. Molecular identification of pathogenic variants in STAR is pivotal for the differential diagnosis against other causes of pediatric primary adrenal insufficiency.

Conclusion: This case highlights the importance of an integrated endocrine and genetic approach in pediatric primary adrenal insufficiency to establish the etiologic diagnosis, guide clinical management, and provide appropriate genetic counseling for the patient and family.
Keywords: STAR; Congenital Adrenal Hyperplasia; Primary Adrenal Insufficiency.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*