Endocrine 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 oestrogen 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, 60 girls (median chronological age-CA 7.8 years, range IQ 7.0-8.3) referring to our 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-βoestradiol levels, pelvic ultrasound (US) and hand and wrist X-ray for bone age (BA) assessment.

Results: Median DHEAS values were 506 mg/l (range IQ 265-872), 0.77 SDS (range IQ -0.72-2.15), being >2 SDS in 19/60 patients. In all patients, other adrenal function tests were in the normal range. Out of 60 girls, 27 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 SDS, range IQ 0.09-2.76 SDS vs -0.07 SDS, range IQ -0.87-1.28 SDS, P=0.004). At logistic regression DHEAS SDS was negatively associated with LH response to GnRH test (P=0.006). Similarly, at multiple regression, DHEAS values were negatively associated with LH peak (P=0.04) and oestradiol levels (P=0.04). Patients with elevated DHEAS concentrations showed higher levels of testosterone (P=0.04) and androstenedione (P=0.02). No other differences were found between the two groups regarding clinical presentation, pelvic US and BA.

Conclusion: In the presence of signs of HPG axis activation and oestrogen exposure, pubertal GnRH test response confirms PP. Our data suggest that elevated DHEAS concentrations, in the absence of HPG axis activation, may drive estrogenization signs. Indeed, an oestrogen receptor concentration-dependent transactivity action of DHEAS has already been described in 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.