Endocrine Abstracts

JOINT873

Background: Lipoid congenital adrenal hyperplasia (LCAH) is caused by pathogenic variants in STAR, encoding steroidogenic acute regulatory protein. LCAH is characterized clinically by impaired steroidogenesis and pathologically by cholesterol ester accumulation in the adrenal glands and gonads. Most 46,XX patients with the classic form of LCAH undergo spontaneous puberty but develop premature ovarian failure in later life. In addition, approximately 33% of women with LCAH experienced large ovarian cysts or ovarian torsion requiring cystectomy or ovariectomy, respectively (Ishii T, et al. J Clin Endocrinol Metab 2020;105:1870–1879). These ovarian complications are potentially associated with hypergonadotropinemia; however, effective interventions to prevent such complications remain unclear. Here, we report a 46,XX female with LCAH who underwent GnRH analog followed by estrogen and progestin, with detailed monitoring of ovarian morphology.

Case Presentation: The patient was an 18-year-old Japanese female diagnosed with LCAH after presenting primary adrenal insufficiency and adrenal hyperplasia with low CT attenuation in the neonatal period. Genetic analysis of STAR identified compound heterozygous pathogenic variants (p.Gln258* and p.Glu218Val). With glucocorticoid and mineralocorticoid replacement, she exhibited breast development at 10 years of age and pubertal response of serum gonadotropins to GnRH stimulation. After thorough discussions with her guardians, subcutaneous injections of leuprorelin acetate were initiated and maintained until the transition to estradiol and norethindrone at 14 years of age. Ovarian morphology, including the maximum cyst diameter and ovarian volume, was regularly assessed using ultrasonography and MRI. Before leuprorelin therapy, the maximum cyst diameter was 13 mm (greater than 9 mm, corresponding to +2.0 SD for her age), which reduced to 6 mm after 6 months of treatment and remained within the reference range. Ovarian volume SD scores decreased from +0.82 and -0.12 before therapy to -0.85 and -0.72 at 12 months, respectively, and stabilized within the normal range. At the most recent follow-up, she had not developed ovarian cysts or hyperplasia under the control of estradiol and norethindrone.

Discussion and Conclusion: This is the first reported case of LCAH who underwent ovarian suppression with GnRH analog followed by estrogen and progestin. Despite the presence of a large ovarian cyst before therapy, no subsequent large ovarian cysts, ovarian hyperplasia, or ovarian torsion were observed during the therapy. These findings suggest that this therapeutic approach may prevent such ovarian complications in patients with the classic form of LCAH. Further clinical studies are warranted to evaluate the efficacy and safety of this intervention.