Gonadotropin-Releasing Hormone 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. In 46,XX patients, gonadotropin-driven cholesterol ester accumulation leads to premature ovarian insufficiency, with approximately one-third developing large ovarian cysts or torsion often requiring surgical intervention. No preventive strategy is established. We report a 46,XX patient treated with a gonadotropin-releasing hormone (GnRH) analog followed by estrogen and progestin, with longitudinal ovarian monitoring.

CASE PRESENTATION: An 18-year-old Japanese female was diagnosed with lipoid CAH neonatally based on failure to thrive, skin hyperpigmentation, electrolyte abnormalities, and bilateral adrenal hyperplasia with low attenuation on CT. Compound heterozygous STAR variants (p.Gln258* and p.Glu218Val) were identified. After spontaneous breast development at age 10 years, leuprorelin acetate was administered from age 10 years 4 months to 15 years 7 months. Transdermal estradiol was started at age 14 years and norethindrone at 14 years 11 months. The right ovarian cyst (13 mm, exceeding +2 SD before leuprorelin therapy) decreased to 6 mm within 6 months, and ovarian volumes normalized within 12 months. At age 18 years, no cysts, 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. Both ovarian cyst diameter and volume improved and remained within the normal range over 8 years. This staged approach may prevent ovarian complications, although long-term effects on bone health, uterine maturation, and fertility require evaluation.