Session: FP11-Pediatric Endocrinology
Room 104 (Moscone Center)
Poster Board SAT-598
We recruited 30 male patients with STSD (age 6-30 years) and 45 age-matched healthy controls. We genetically confirmed the diagnosis of STSD in all subjects identifying either complete (n=27) or partial deletions (n=1) of the STS gene; two patients harbored a hemizygous missense mutation (p.R454C). The KAL1 locus was intact in all patients. There were no apparent abnormalities in the physical development of the STSD patients. Urinary steroid metabolomics (gas-chromatography/mass-spectrometry) revealed decreased excretion of active androgen precursor metabolites (Androsterone, An and Etiocholoanolone, Et) over androgen precursor metabolites (DHEA, 16hydroxy-DHEA, pregnenediol and 5-pregnenetriol) as compared to controls (p<0.001). 5α-reductase activity assessed as the ratio of 5α-reduced tetrahydrocortisol (THF) over THF (5αTHF/THF) was significantly increased in STSD (p<0.001). Serum steroid measurements (liquid chromatography/ tandem mass spectrometry) revealed decreased DHEA levels in all STSD age-groups (p<0.001) but testosterone was only lower in the adult subgroup (p=0.009). Cholesterol-sulfate was grossly elevated in all STSD subjects but DHEAS levels did not differ significantly. However, the ratio of DHEA/DHEAS was lower in STSD patients (p<0.001).
Our study demonstrates that though physical/pubertal development does not seem to be impaired in STSD, the steroid metabolome of these patients indicate a mild androgen deficiency with elevation of androgen precursors. We hypothesize that this reflects a mechanism of compensation, with further evidence of up regulation of peripheral androgen activation due to increased 5α-reductase activity. This illustrates for the first time in vivo that STS contributes to androgen metabolism in the context of DHEA sulfation.
Nothing to Disclose: JI, AET, DMO, SS, RV, RD, ZKH, RA, TB, PMS, JK, CM, CHS, WA
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