GnRH Analog followed by Sex Hormone Therapy as a Preventive Strategy against Ovarian Complications in Congenital Lipoid Adrenal Hyperplasia: A Case Report

BACKGROUND: Congenital lipoid adrenal hyperplasia (lipoid CAH) is caused by pathogenic variants in STAR, encoding steroidogenic acute regulatory protein (StAR). In affected 46,XX patients, progressive cholesterol ester accumulation in the ovaries during puberty leads to premature ovarian insufficiency and, in approximately one-third of cases, large ovarian cysts or ovarian torsion requiring surgical intervention. These complications may relate to elevated gonadotropin levels, yet no preventive strategy exists. We report a 46,XX female with classic form of lipoid CAH who underwent gonadotropin suppression with a gonadotropin-releasing hormone (GnRH) analog followed by estrogen and progestin administration, with longitudinal monitoring of the ovarian morphology. CASE PRESENTATION: An 18-year-old Japanese female was diagnosed with lipoid CAH neonatally after presenting with failure to thrive, skin hyperpigmentation, hyponatremia, and hyperkalemia. Computed tomography revealed bilateral adrenal hyperplasia with low attenuation consistent with lipid accumulation. Genetic analysis identified compound heterozygous pathogenic STAR variants: p.Gln258* and p.Glu218Val. Glucocorticoid and mineralocorticoid replacement was initiated. The patient exhibited spontaneous breast development at age 10 years with pubertal gonadotropin responses and mildly elevated ovarian volume with a large ovarian cyst. After informed discussions with the guardians regarding the risks of ovarian complications, subcutaneous leuprorelin acetate was started at age 10 years 4 months and continued until age 15 years 7 months. Transdermal estradiol was introduced at at age 14 years, and oral norethindrone was added at 14 years 11 months, after which regular cycles were established. Before leuprorelin therapy, the maximum ovarian cyst diameter was 13 mm (right), exceeding the +2.0 standard deviation (SD) threshold for age; this decreased to 6 mm within 6 months of treatment and remained within the reference range thereafter. Ovarian volumes decreased from 3.1 mL (right) and 1.7 mL (left) before therapy to 1.1 mL and 1.0 mL at 12 months, respectively. At age 18 years, no large ovarian cysts, ovarian hypertrophy, or torsion had developed. CONCLUSIONS: This is the first reported case of lipoid CAH managed with GnRH analog-mediated gonadotropin suppression followed by estrogen and progestin administration. Despite a large ovarian cyst and mildly elevated ovarian volume at baseline, both measures improved and were maintained within the normal range over eight years of follow-up. This approach may be useful not only for preventing ovarian complications but also for improving and sustaining normal ovarian morphology, and warrants further evaluation, although its long-term effects on bone health, uterine maturation, and fertility require careful assessment.