ESPE Abstracts

Background: ‘Thelarche variant’ (TV), also known as ‘unsustained/slowly progressive puberty’ or ‘exaggerated thelarche’, is a term used to describe girls with premature thelarche and intermediate features between isolated premature thelarche (PT) and central precocious puberty (CPP). Despite being characterized by a FSH predominant response and by a peak LH response <5 IU/L to GnRH test, a univocal definition is lacking.

Methods: Retrospective monocentric analysis on 104 girls with premature thelarche (< 8 years) who underwent GnRH test from January 2019 to December 2022. Considering the heterogeneous literature definitions of TV, we relied on the laboratory diagnostic criteria. Patients were divided into the aforementioned groups: CPP (LH peak >5 IU/L; n=32, 31%); TV (FSH peak >20 IU/L, LH peak <5 IU/L; n=18, 17%) and PT (FSH peak <20 IU/L, LH peak <5 IU/L; n=54, 52%). Several auxological (height, target height, height velocity), laboratory (basal/peak LH / FSH, oestradiol) and radiological (bone age, uterine body-to-cervix ratio, ovarian volume) features were studied.

Results: TV (median age 5.51 years) were younger than both PT (7.49 years, p <0.01) and CCP (7.52 years, p <0.01), and presented no higher height or significant discrepancy between height and target height. At GnRH test, TV showed higher levels of both basal and peak FSH than PT (respectively 2.5 versus 1.9 IU/L, P<0.01 and 26.6 versus 12.8 IU/L, p <0.01) and higher levels of peak FSH than CCP (26.6 versus 16.2 IU/L, p <0.01). There were no significant differences between oestradiol levels between the three groups (median value 24 pg/mL in TV). Surprisingly, TV had lower difference between bone and chronological age (0.80 years) than PT (1.40 years, p 0.04) and CCP (1.42 years, p 0.02). The pelvic ultrasound showed a median smaller ovarian volume (0.60 cm3) in TV than both PT (1.35 cm3, p <0.01) and CCP (1.80 cm3, P<0.01) and a higher percentage of uterine body-to cervix ratio > 1 in the CPP group (82%), if compared with both PT (51%, p <0.01) and TV (36%, p <0.01).

Conclusions: Using solely the objective laboratory parameter of FSH peak >20 IU/L to define TV, we identified a group of patients that differs from the heterogeneous (and often confounding) literature definitions, showing no advanced bone age and no signs of activation on pelvic ultrasound. Our data are consistent with reported benign evolution and good stature prognosis of this condition.