Pubertal Development and Pregnancy Outcomes in 46,XX Patients With Nonclassic Lipoid Congenital Adrenal Hyperplasia

• Published in: The journal of clinical endocrinology and metabolism Vol. 104; no. 5; pp. 1866 - 1870
• Main Authors: Hatabu, Naomi, Amano, Naoko, Mori, Jun, Hasegawa, Yukihiro, Matsuura, Hiroki, Sumitomo, Naofumi, Nishizawa, Kazumichi, Suzuki, Mariko, Katakura, Satomi, Kanamoto, Naokazu, Kamimaki, Tsutomu, Ishii, Tomohiro, Hasegawa, Tomonobu
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.05.2019; Copyright Oxford University Press; Oxford University Press
• Subjects: 46, XX Disorders of Sex Development - complications; 46, XX Disorders of Sex Development - drug therapy; 46, XX Disorders of Sex Development - physiopathology; Adolescent; Adrenal glands; Adrenal Hyperplasia, Congenital - complications; Adrenal Hyperplasia, Congenital - drug therapy; Adrenal Hyperplasia, Congenital - physiopathology; Adrenogenital syndrome; Adult; Antagonists; Care and treatment; Children; Citric acid; Clomiphene; Disorder of Sex Development, 46,XY - complications; Disorder of Sex Development, 46,XY - drug therapy; Disorder of Sex Development, 46,XY - physiopathology; Estrogen; Female; Fludrocortisone; Genetic disorders; Gonads; Hormone Replacement Therapy; Humans; Hyperplasia; Menarche; Menopause; Menstruation; Ovulation; Patient outcomes; Patients; Physical growth; Pregnancy; Pregnancy Outcome; Pregnant women; Progesterone; Prognosis; Puberty; Puberty - physiology; Reproduction; Reproductive status; Steroidogenesis; Young Adult; Japan
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2018-01752

Abstract Context Lipoid congenital adrenal hyperplasia (LCAH) is characterized by a disorder of steroidogenesis in both adrenal glands and gonads. 46,XX patients with classic LCAH usually have thelarche and menarche but show anovulatory menstruations and subsequent premature menopause. Only three patients with classic LCAH have been reported to successfully achieve delivery with the aid of assisted reproductive therapies for conception and progesterone replacement therapy during early pregnancy. In contrast, pubertal development and pregnancy outcomes in patients with nonclassic LCAH have not been fully elucidated. Case Description We report four Japanese women who had a diagnosis of primary adrenal insufficiency during infancy or childhood and carried compound heterozygous STAR mutations (p.Gln258* and p.Arg188His, p.Gln258* and p.Met225Thr, and p.Gln258* and p.Arg272Cys). In all four patients, thelarche and menarche spontaneously occurred from 10 to 11 years of age and from 12 to 14 years of age, respectively. Subsequently, their menstruation cycles were regular at almost 1-month intervals. Patient 1 conceived naturally twice, and patient 2 conceived with the use of clomiphene citrate for ovulation induction. These two patients maintained the pregnancies without progesterone replacement therapy and successfully delivered children. Conclusion Patients with nonclassic LCAH maintain ovarian function, which enables normal pubertal development and a successful pregnancy outcome without progesterone replacement therapy. 46,XX patients with nonclassic lipoid congenital adrenal hyperplasia maintain ovarian function, which enables normal pubertal development and a successful pregnancy outcome without progesterone replacement therapy.