SUN-184 - Clinical Correlates of Adrenal Zona Reticularis Function in Turner Syndrome

Background: Adrenarche is characterized by the maturation of the adrenal zona reticularis and increasing secretion of adrenal androgens, primarily DHEA and DHEA-S. In healthy girls, biochemical adrenarche is usually accompanied by pubarche. Turner syndrome (TS) provides a unique model in which adrenal androgen secretion occurs in the absence of normal ovarian function. However, data based on comprehensive androgen profiling are limited.

Objective: To evaluate the onset and tempo of pubic hair development and adrenal androgen profiles in girls with TS and Turner variant karyotypes involving Y-chromosome material (mixed gonadal dysgenesis (MGD); 45,X0/46,XY), compared with healthy Turkish controls.

Method: A total of 90 patients with TS were included in the study, including 12 with detectable Y-chromosome material. TS patients without Y-chromosome material were classified into two groups according to pubertal status: those with spontaneous puberty (n=16) and those with gonadal failure requiring oestrogen hormone replacement therapy (E2-HRT) (n=62). Pubic hair development and androgen profiles were evaluated using both immunoassay and liquid chromatography–tandem mass spectrometry (LC–MS/MS). All clinical and biochemical assessments were performed prior to the initiation of E2-HRT.
Result: Serum DHEA-S levels were significantly higher in girls with TS compared with age-matched healthy controls when measured by immunoassay (8–12 years: 96.29±37.82 vs. 64.11±48.96, p=0.03; 12–20 years: 205.7±91.63 vs. 158.5±89.89, p=0.02). These findings were confirmed using LC–MS/MS, showing higher DHEA-S concentrations in TS (8–12 years: 95.3±59.2 vs. 56.6±44.9, p=0.04; 12–20 years: 245.0±90.4 vs. 110.8±66.9, p< 0.001). When stratified by pubic hair stage, DHEA-S levels remained significantly elevated in TS across P1, P3, and P4 stages compared with controls (60.28±57.14 vs 20.19±24.17, 158.5±81.43 vs 70.75±21.31 and 246.6±81.74 vs 169.9±89.29 respectively; p=0.01, p< 0.001, and p=0.006). 17-hydroxypregnenolone concentrations were significantly higher in girls with TS across all age groups compared with healthy controls (p < 0.01). Despite elevated adrenal androgen levels, the age at pubic hair development was significantly delayed in patients with TS requiring E2-HRT (P2=12.52±2.59; P3=13.92±2.01; P4=13.8±1.7 years) and MGD (P2=12.04±2.12; P3=12.93±1.97; P4=13.23±1.21 years) compared with healthy girls (P2=11.0±1.0; P3=11.9±0.9; P4=12.4±0.8 years) (p < 0.01 for all comparisons).

Conclusion: Gonadal failure in TS, leads to a compensatory increase in androgen production from the adrenal zona reticularis; however, this increase remains insufficient, resulting in delayed onset and slower progression of pubarche. The presence of the Y chromosome in the karyotype leads to sexual dimorphism in adrenal zona reticularis function, independent of gonadal activity.