RF02 | PSAT119 AMH and Spontaneous Puberty in a Diverse US Turner Syndrome Clinic Cohort: A Cross-sectional study

Abstract

Abstract Background Turner syndrome (TS) is caused by the absence of whole/part of the second X-chromosome. Primary ovarian insufficiency (POI) is common in TS and serum anti-Mullerian hormone (AMH) of <4 pmol/L (0.56 ng/mL) is suggestive of POI and lack of spontaneous puberty. Objective To describe the distribution of AMH and spontaneous puberty in a cross-sectional cohort of patients in a newly-established pediatric TS specialty clinic. Methods Data on all TS patients seen in the multidisciplinary clinic between 1/1/2019 and 10/27/2021 were abstracted from retrospective chart review into a REDCap database. Descriptive analysis, one way ANOVA and two sample t-tests for pair-wise comparisons was completed (SPSSv28.0 and Excelv2102), with statistical significance set at p<0.05. Results Ninety-six patients (9% Asian, 13.5% African American and 37.5% Caucasian, and rest unknown/other self-reported race, and 29.2% Hispanic ethnicity) were enrolled in our clinic. While the majority were diagnosed postnatally (74%, median age 5 years), 6% were prenatal and 20% had positive prenatal screen with postnatal confirmation. Karyotype distribution: 41% non-mosaic monosomy X, 17% Xq (including 14% isochromosome Xq) and 14% Xp structural abnormalities, 10% ringX, 7% 45,X/46,XX mosaicism and 9% with Y-chromosome. Median age at first TS clinic visit was 10 years (IQR 9.7) with median height at 2%ile, weight 31%ile and BMI 73%ile. AMH was measured in 88 patients and only 33 (37.5%) had detectable (>0.015 ng/mL) AMH; 8 (9%) had AMH >0.56ng/mL. Mean AMH was significantly lower in 45,×monosomy (0.03+/- 0.14) vs. other karyotypes (0.44+/-1.13)(p=0.01). A one-way ANOVA revealed a statistically significant difference in AMH between 45,X, structural abnormalities in Xp/Xq and, mosaic 45,X/46,XX karyotypes (p<0.001). Pair-wise comparisons confirmed mean AMH in 45,X/46,XX was significantly higher (3.1ng/mL) (p<0.001) compared with 45,×(0.03ng/mL), Xq (0.02ng/mL) and Xp (0.08ng/mL) abnormalities but no other comparisons were statistically significant. Spontaneous thelarche was reported in 23/58 (39.6%) pubertal patients with mean AMH (0.65ng/mL +/-1.3) compared to absent spontaneous thelarche (N=35, 0.02 +/- 0.04) (p=0.03). Spontaneous menarche was reported in 9 patients, with mean AMH 1.8+/- 1.7ng/mL; 4/9 had 45,X/46, XX karyotype and 1 each had 45,X, Xp, Xq, isoXq, and ringX karyotypes. The mean age at spontaneous thelarche was lower than age at thelarche with hormonal induction (11 + 1 years vs. 14 + 2 years, p < 0.001). Median age at estrogen initiation was 12 years (IQR 3); 86% received transdermal estradiol with menarche at a median age of 15 years. While 78/96 (81%) received fertility preservation counseling at a mean age of 11 + 6 years, only 4 utilized fertility preservation options (1 oocyte cryopreservation and 3 ovarian tissue cryopreservation). Although cross-sectional data limit inferences on AMH as a marker of puberty, our data represents a large and diverse cohort of TS patients in the US. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:24 p.m. - 1:29 p.m., Saturday, June 11, 2022 1:24 p.m. - 1:29 p.m.