The Early Dehydroepiandrosterone Sulfate Rise of Adrenarche and the Delay of Pubarche Indicate Primary Ovarian Failure in Turner Syndrome

Girls with Turner syndrome provide the first human model in which adrenal puberty (adrenarche) takes place without gonadal puberty. A wide range of serum dehydroepiandrosterone sulfate (DHEAS) concentrations has been observed, ranging from normal to very elevated. This study attempted to determine whether the course of adrenarche and pubarche is independent of ovarian function. A total of 867 serum DHEAS estimates were made over time in 111 girls with Turner syndrome. Puberty began spontaneously in 22 of these girls, whereas 45 had primary ovarian failure (POF). Serum DHEAS levels were compared with those of 322 healthy girls 3 to 17 years of age. POF was defined as a lack of spontaneous breast development and at least 1 follicle-stimulating hormone (FSH) level of 50 IU/L or higher before estrogen replacement therapy. Age-related serum concentrations of DHEAS were significantly higher in girls with Turner syndrome than in control girls from ages 7 to 17 years. Those with POF had significantly higher age-related levels than did girls experiencing spontaneous puberty at ages 9 to 15 years. Adrenarche occurred at a median age of 8.3 years in girls with POF, compared with 10.5 years for girls with spontaneous puberty and 11 years in normal girls. In both groups with Turner syndrome, mean DHEAS levels correlated closely with mean FSH and luteinizing hormone levels. Pubarche was delayed in girls with POF despite their high serum DHEAS levels. Puberty occurred more than 4.5 years after adrenarche, at a median age of 13 years, in girls with Turner syndrome, whereas in girls with spontaneous puberty, the interval was 1.4 years and the median age at pubarche was 11.9 years. These findings indicate that normally timed adrenarche depends on gonadal function. Normal pubarche represents the conversion of DHEAS to active androgens in the ovaries. Premature adrenarche and pubarche in an otherwise healthy girl may be the first clinical sign of functionally defective ovaries.