Naomi Hatabu1,2, Naoko Amano1,3, Jun Mori4, Yukihiro Hasegawa5, Hiroki Matsuura6, Naofumi Sumitomo1,7, Kazumichi Nishizawa1,7, Mariko Suzuki8, Satomi Katakura8, Naokazu Kanamoto9,10, Tsutomu Kamimaki1,11, Tomohiro Ishii1, Tomonobu Hasegawa1. 1. Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan. 2. Department of Pediatrics, National Hospital Organization Tokyo Medical Center, Tokyo, Japan. 3. Department of Pediatrics, Tokyo Saiseikai Central Hospital, Tokyo, Japan. 4. Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan. 5. Department of Endocrinology and Metabolism, Tokyo Metropolitan Children`s Medical Center, Tokyo, Japan. 6. Department of Pediatrics, Shinshu University School of Medicine, Nagano, Japan. 7. Department of Pediatrics, Japanese Red Cross Shizuoka Hospital, Shizuoka, Japan. 8. Department of Obstetrics and Gynecology, Japanese Red Cross Shizuoka Hospital, Shizuoka, Japan. 9. Department of Obstetrics and Gynecology, Nagahama City Hospital, Shiga, Japan. 10. Department of Obstetrics and Gynecology, Tenri Hospital, Nara, Japan. 11. Department of Pediatrics, Shizuoka City Shimizu Hospital, Shizuoka, Japan.
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.
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.