Menstrual Bleeding in a Female Infant with Congenital Adrenal Hyperplasia: Altered Maturation of the Hypothalamic-Pituitary-Ovarian Axis

• Published in: The journal of clinical endocrinology and metabolism 1997-10, Vol.82 (10), p.3298-3302
• Main Authors: Uli, Naveen, Chin, Daisy, David, Raphael, Geneiser, Nancy, Roche, Kevin, Marino, Flavia, Shapiro, Ellen, Prasad, Kris, Oberfield, Sharon
• Format: Article
• Language: English
• Subjects: Adrenal Hyperplasia, Congenital - physiopathology; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Biological and medical sciences; Endocrinopathies; Female; Genitalia, Female - diagnostic imaging; Genitalia, Female - pathology; Hormones - blood; Humans; Hypothalamo-Hypophyseal System - growth & development; Infant; Magnetic Resonance Imaging; Medical sciences; Menstruation - physiology; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Ovarian Cysts - complications; Ovarian Cysts - diagnosis; Ovary - growth & development; Pelvis - diagnostic imaging; Tomography, X-Ray Computed; Ultrasonography
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jcem.82.10.4277

Vaginal bleeding during the neonatal period is commonly related to the withdrawal of maternal estrogens. Vaginal bleeding has also been reported in female infants with congenital adrenal hyperplasia and has been proposed to be due to a treatment-induced activation of the hypothalamic-pituitary-ovarian axis. We report a female infant with the salt-losing form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, who had the onset of vaginal bleeding at 3 months of life. Adrenal steroid suppression had been achieved by 2.5 weeks of age. At the time of bleeding, imaging studies revealed an enlarged right ovary with a dominant 3-cm cyst and additional small cysts that had not been seen on the newborn sonogram. The uterus was enlarged and stimulated. Three weeks later (1 week after the cessation of bleeding), repeat ultrasound demonstrated a marked decrease in the size of the right ovary, and the dominant cyst was no longer seen. The patient had a heightened FSH response to GnRH and elevated levels of estradiol for age. At 5 months of age, no further episodes of sustained vaginal bleeding were observed. Repeat hormonal levels were prepubertal, and pelvic sonogram demonstrated no evidence of stimulation. The findings in our patient suggest that a decline in adrenal androgens after glucocorticoid treatment resulted in an increase in gonadotropin levels, which then triggered a transient and augmented end-organ response (menses). Further, we suggest that our infant’s hormonal findings may reflect a delay in the timely development of the negative restraint by sex steroids on gonadotropins that is normally observed in infancy.