ESPE Abstracts

Introduction: The absence of menarche in a girl aged > 15 yrs requires extensive endocrinological and gynecological diagnostics. Amenorrhea occurs with a frequency of 3–4% among women of reproductive age. The most common causes of primary amenorrhea are: primary ovarian failure (48.5%), agenesis of the Müllerian ducts (16.2%), gonadotropin deficiency (8.3%) and constitutional delay in growth and puberty (6%).

Material and Methods: A 17-year-old female patient with primary amenorrhea and no signs of puberty (Tanner I) was diagnosed at gynecology department, where the followings were found: high ACTH concentration with low cortisol concentration, low estradiol with high gonadotropin concentrations. The measurements of blood pressure showed elevated values and antihypertensive drug was introduced. Aldosterone levels were within normal reference ranges. Doppler ultrasound of the renal arteries revealed no abnormalities. Pelvic ultrasound described a prepubertal image of the uterus and ovaries. Next, she was transferred to the Department of Pediatric Endocrinology - laboratory tests revealed: mild hypokalemia, normal sodium concentrations, signs of hypergonadotropic hypogonadism, undetectable DHEAS concentration, high ACTH with low cortisol concentration in the circadian rhythm. The bone age was estimated at 12-13yrs. The Synacthen test revealed a lack of adrenal reserve. Due to the diagnosis of adrenal insufficiency, the treatment included hydrocortisone and fludrocortisone acetate was started. In steroid metabolome the steroidogenesis disorders were diagnosed at the level of 17alpha-hydroxylase / 17,20-lyase. Molecular diagnosis is ongoing.

Discussion: 17α-hydroxylase deficiency is a rare form of congenital adrenal hyperplasia, occurring in 1:50,000 people and affecting both the adrenal glands and gonads. The disease is the result of a mutation in the gene encoding P450c17, which leads to deficiency of 17α-hydroxylase/17,20-lyase activity and impaired conversion of pregnenolone to 17-OH-pregnenolone and DHEA and progesterone to 17-OH-progesterone. Disturbance of cortisol synthesis causes increased ACTH secretion and excessive production of 11-deoxycorticosterone (DOC) and corticosterone. High DOC concentrations cause hypertension with hypokalemia and suppression of the RAA axis. The lack of 17α-hydroxylase and 17,20-lyase activity in the gonads results in a deficiency of sex hormones and disorders of sex differentiation in male newborns in the form of incomplete masculinization, and in girls - primary amenorrhea.

Conclusion: 17α-hydroxylase deficiency should be considered in adolescents with hypertension, hypokalemia and primary amenorrhea.