Identifying Sources of Hyperandrogenemia in Girls with Obesity

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 548-560-Hyperandrogenic Disorders
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-558
Christine Michele Burt Solorzano*1, Jessicah S. P. Collins2, Jennifer P Beller3, Amy Denise Anderson2, Ruchi Bhabhra1, R Jeffrey Chang4, John C Marshall2 and Christopher Rolland McCartney2
1Division of Endocrinology, University of Virginia, Charlottesville, VA, 2University of Virginia, Charlottesville, VA, 3Glens Falls Hospital, Queensbury, NY, 4University of California - San Diego, La Jolla, CA
Adolescent hyperandrogenemia (HA) is a forerunner to adult PCOS. Our data show HA in 70% of obese girls, even during pre-/early puberty (1-3), but the source(s) remain(s) unclear. In PCOS women, the primary source is ovarian, although some have adrenal HA. Since ovarian activity is considered to be limited before thelarche, we have proposed an adrenal contribution to obesity-related HA in early puberty. We previously reported that free testosterone (T) levels rise 70% overnight in pubertal girls, which dexamethasone (DEX) completely suppresses—implying an adrenal source for overnight T production in puberty. Free T responses to ACTH are increased in overweight (OW) versus normal weight (NW) girls during both early (2.1 ± 0.8 vs. 0.1 ± 0.1 pmol/L) and late (10.4 ± 1.6 vs. 3.6 ± 1 pmol/L) puberty, suggesting an adrenal source for obesity-related HA. Yet, DEX-suppressed free T remains >5-fold higher in OW versus NW late pubertal girls, indirectly implicating an ovarian source for HA later in puberty.

This study assessed adrenal and ovarian androgen production simultaneously in late pubertal girls (4 NW [BMI <85%] and 5 OW [BMI ≥85%], Tanner stages 3-5), using ACTH (250 µg IV, 0700h) and recombinant human chorionic gonadotropin ([r-hCG] 250 µg IV, 0800h) stimulation. Normal responses were defined by the response range in NW girls (n=6 for ACTH, n=4 for r-hCG).

Free T responses were increased to ACTH in 3/5 OW girls, to r-hCG in 3/5 OW girls, and to both in 2/5 OW girls. T precursor (17OHPreg, 17OHP, DHEA, and Andro) responses to ACTH were elevated in 3, 2, 3, and 4 OW girls, respectively. 17OHPreg, 17OHP, DHEA, and Andro responses to r-hCG were elevated in 1, 1, 0, and 2 OW girls, respectively. Overall, evidence of multiple elevations in precursor or free T responses were observed in 4/5 OW girls to ACTH, and in 2/5 OW girls to r-hCG. Both girls with increased ovarian responses also had adrenal elevations. Girls with increased adrenal responses alone had younger skeletal maturity (16.5 vs. 17.3 yr), lower morning free T levels (27.2 vs. 59.1 pmol/L) and lower overnight mean LH (3.45 vs. 5.9 mIU/mL) compared to girls with enhanced ovarian responses—suggesting adrenal involvement may develop before ovarian.

These data suggest that enhanced adrenal androgen production may occur more frequently or earlier in obesity-related pubertal HA—possibly preceding increased LH drive or ovarian abnormalities leading to PCOS.

(1) Knudsen KL et al., Obesity 2010; 18:2118. (2) McCartney CR et al., J Clin Endocrinol Metab 2006; 91:1714. (3) McCartney CR et al., J Clin Endocrinol Metab 2007; 92:430. (4) McCartney CR et al., J Clin Endocrinol Metab 2009; 94:56.

Nothing to Disclose: CMB, JSPC, JPB, ADA, RB, RJC, JCM, CRM

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Sources of Research Support: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)/National Institute of Health (NIH) K23HD070854-01 (CBS); through cooperative agreement U54HD28934 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research at NICHD/NIH (CBS, RJC, JCM, CRM); NICHD/NIH F32 HD066855 (JC); National Institute of Diabetes and Digestive and Kidney Diseases/NIH T32 DK07646 (JB, AA, RB); University of Virginia Children’s Hospital Grant-in-Aid (CBS).