(63) Hormonal and Metabolic Profiles of Adolescents with Androgen Insensitivity Syndrome (AIS) and Intact Gonads

Background: Historically, those with AIS were referred for gonadectomy due to a risk of gonadal tumors; however, newer data has emerged suggesting a lower incidence of malignancy[1], prompting many adolescents to defer gonadectomy[2,3]. There is little data about the hormonal and metabolic profile for adolescents who maintain their gonads in this population[4-6]. Here, we report retrospective lab and imaging findings of 9 individuals who presented for evaluation from 6/2021-9/2023.

Case: Data from patients aged 13-23 with AIS are described in Table 1. Of this cohort, 78% have complete AIS (CAIS) and 22% have partial AIS (PAIS). 55% of our cohort (n=5) had elevated luteinizing hormone (LH) (median=27.6, IQR=9.1-38.0) and 33% (n=3) had elevated follicle stimulating hormone (FSH) (median=7.9, IQR=3.9,24.5). All of those with elevated FSH also had elevated LH, but a subset analysis of those 3 individuals did not show a correlation to any other hormonal parameter. Median estradiol (E2) was 18.0 (IQR=16.0-24.0), and total testosterone (T) was 689 (IQR=587,1300). Levels of T and E2 were found to be positively correlated [R2=0.42 (p < 0.05)].

A subset of individuals had metabolic parameters completed, which are reported in Table 2. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) scores were elevated for all subjects, whereas other signs of insulin resistance (IR)/metabolic syndrome were not consistently found in the cohort. 2 individuals had elevated LDL, 2 met criteria for pediatric overweight, and 1 met criteria for adult obesity. Only 1 individual had an elevated hemoglobin A1c (HbA1c) consistent with prediabetes. 6 individuals underwent bone mineral density (BMD) scans, and no low BMD for age (Z<-2) was found when either female or male standards were used to calculated height-adjusted z-scores (HAZ).

Comments: These data show that some individuals with AIS and intact gonads have elevated FSH levels; however, no pattern of association was found between FSH and any other hormonal parameter. It is known that LH is typically elevated in those with AIS[7], but the elevations in FSH are not as well established. Interestingly, all individuals in our cohort were found to have HOMA-IR scores >2, suggestive of IR[8,9], yet other measures of IR (fasting glucose, HbA1c) were not consistently elevated. Further research must be done to understand the mechanisms underlying IR and premature gonadal insufficiency. Reassuringly, decreased BMD for age was not seen in our cohort.

References:
1. PMID: 33819955
2. PMID: 31233832
3. PMID: 26428189
4. PMID: 19752598
5. PMID: 34333495
6. PMID: 32345305
7. PMID: 10086936
8. PMID: 10857969
9. PMID: 14633821