ESPE Abstracts

Background: Precocious puberty (PP) in girls is most frequently an idiopathic gonadotropin-releasing hormone (GnRH)-dependent PP, being thelarche the typical first sign. It is well established that increased dehydroepiandrosterone sulphate (DHEAS) levels are associated with premature adrenarche and may characterize PP too. However, its relationship with signs of hypothalamic-pituitary-gonadal (HPG) axis activation and estrogen exposure is still to be elucidated.

Aims: assessing the association between DHEAS levels and other parameters of HPG activation in girls with precocious thelarche.

Methods: at this aim, 37 girls (median chronological age-CA 7.7 years, range IQ 6.8-8.1) referring to the Endocrine Clinic for suspected PP were consecutively enrolled. In all patients the following data were collected: basal and stimulated (GnRH test at 2.5 mg/kg) LH and FSH levels, basal ACTH, cortisol, DHEAS, androstenedione, testosterone, 17-α hydroxyprogesterone, 17-β estradiol levels, pelvic ultrasound (US) and hand and wrist X-ray for bone age (BA) assessment.

Results: Median DHEAS values were 447 mg/l (range IQ 229-909), 0.81 SDS (range IQ -0.78-2.52), being >2 SDS in 13/37 patients. In all patients, other adrenal function tests were in the normal range. Out of 37 girls, 19 showed a pre-pubertal response to GnRH test (LH<5 mIU/L). Higher DHEAS levels were found in this group vs girls with pubertal LH peak (2.07±2.61 SDS vs 0.17±1.56 SDS, P=0.011). At logistic regression DHEAS values>2 SD for age-adjusted reference range were associated with pre-pubertal LH response to GnRH test (P=0.007) and lower levels of estradiol levels (P=0.03). No other difference was found between patients with elevated DHEAS concentrations and others regarding hormonal parameters and US values.

Conclusion: In the presence of signs of HPG axis activation and estrogen exposure, pubertal GnRH test response confirms PP. Our data suggest that elevated DHEAS concentrations, in the absence of HPG axis activation and detectable estradiol levels, may drive estrogenization signs. Indeed, an estrogen receptor concentration-dependent transactivity action of DHEAS has already been described in vitro studies. Moreover, this condition can be different from a mere normal variant of PP thus requiring an appropriate follow-up and eventual therapeutic approach. Further studies are needed to support our findings and to insight into their impact in patients’ management.