Index case and aims
A 26 year old woman was referred to our endocrine clinic with infertility and raised testosterone levels. Clinical examination was completely normal, with no hirsuitism or virilizing features. She had normal gonadotropin and SHBG levels, but had elevated testosterone (6.6 nmol/l (0.52.8) and dehydroepiandrosterone sulphate (DHEA-S) levels (13.5 umol/l (1.411.1)). To exclude the possibility of interference in our direct assay, serum testosterone was measured using liquid chromatography-mass spectrometry (LC-MS) and was normal at 1.8 nmol/l (0.012.8). As assay interference is a potential cause of spuriously elevated serum testosterone levels in women, we studied the prevalence of interference in our direct assay.
We retrospectively identified 63 samples from women with high serum testosterone levels (> 2.8 nmol/l) as measured by our direct assay, over a 7 month period. Serum testosterone was also measured by LC-MS in a reference laboratory. A difference of < 1.0 nmol/l was considered as low interference.
Mean serum testosterone concentration by direct assay was 3.8±0.1 nmol/l whilst by LC-MS was 1.9±0.1 nmol/l (mean difference 1.9±0.1 nmol/l, P<0.001). 17 samples (26%) had a significant interference with a difference more than 2.5 nmol/l and 36 (58%) samples had a medium interference with a difference between 1.02.5 nmol/l. Only 10 samples (16%) had a low interference after measurement of testosterone by LC-MS.
Interference in direct immunoassay is an important cause of spuriously high testosterone levels in women and serum testosterone measurement by LC-MS is mandatory for optimal clinical interpretation. Although, the exact interferent is not known, DHEA-S has been suggested be partly responsible and further studies are required to clarify the interferents.
06 - 07 Nov 2006
Society for Endocrinology