PubMed · 15753818
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2005. Making headlines.. https://pubmed.ncbi.nlm.nih.gov/15753818/
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17alpha-Hydroxyprogesterone is a metabolic precursor of cortisol; elevated levels of 17alpha-hydroxyprogesterone are indicative of congenital adrenal hyperplasia. Traditional determination by immunoassay is plagued by poor antibody specificity, resulting in significant interferences. This study explores an LC-MS/MS method for the quantitation of 17OHP in serum. Deuterated 17alpha-hydroxyprogesterone was added as internal standard, followed by solid-phase extraction, HPLC separation with a C16-amide reverse-phase column with run time of 7 min, and quantification by MS/MS (positive electrospray ionisation) in the selected reaction monitoring mode (SRM). Transitions monitored were 331>109 for the analyte and 339>113 for the deuterated internal standard. Intra-assay precision (%R.S.D.) was 7.4% at 7 nmol/L, inter-assay precision (%R.S.D.) at 2, 7 and 27 nmol/L was 15.4, 10.0 and 7.9% and accuracy at 0.9 nmol/L was 100%. The method was linear from 0.156 to 80 nmol/L. Lower limit of quantitation was 0.2 nmol/L, providing meaningful data for patients within normal range as well as those with elevated levels.
CONTEXT: Anti-Müllerian hormone (AMH) is produced by the granulosa cells and reflects follicular development. Adult women with polycystic ovary syndrome (PCOS) have increased levels of AMH associated with an excessive number of growing follicles. However, it is not known whether these abnormalities are present before the clinical onset of PCOS. OBJECTIVE: Our objective was to investigate whether prepubertal daughters of women with PCOS have increased AMH levels. DESIGN: Fourteen female infants (2-3 months old) and 25 prepubertal girls (4-7 yr old) born to PCOS mothers were studied. As a control group, we studied 21 female infants and 24 prepubertal girls born to mothers with regular menses and without hyperandrogenism. The group with PCOS mothers and the control group had normal birth weight and were born from spontaneous singleton pregnancies. Circulating concentrations of gonadotropins, testosterone, androstenedione, estradiol, 17-OH-progesterone, SHBG, inhibin B, and AMH were determined by specific assays. RESULTS: Serum concentrations of AMH were significantly higher in the PCOS group compared with the control group during early infancy (20.4 +/- 15.6 vs. 9.16 +/- 8.6 pmol/liter; P = 0.024) and during childhood (14.8 +/- 7.7 vs. 9.61 +/- 4.4 pmol/liter; P = 0.007). Gonadotropin and serum sex steroid concentrations were similar in both groups during the two study periods, except for FSH, which was lower during childhood in girls born to PCOS mothers. CONCLUSIONS: We conclude that serum AMH concentrations are increased in prepubertal daughters of PCOS women, suggesting that these girls appear to show evidence of an altered follicular development during infancy and childhood.
CONTEXT: Follicular phase secretion of inhibin B, like that of estradiol (E(2)), correlates with the quantity and quality of developing follicles. However, it has not been established whether inhibin B responses to gonadotropin stimulation parallel those of E(2) as a reflection of granulosa cell functional capacity. OBJECTIVE: Our objective was to determine whether inhibin B responses to FSH stimulation are similar to those of E(2) in women with polycystic ovary syndrome (PCOS) and normal women. DESIGN AND SETTING: We conducted a prospective study to compare ovarian responses in two groups of women at a general clinical research center in a tertiary academic medical center. PATIENTS: Women with PCOS, 18-35 yr (n = 19), and normal ovulatory controls, 18-35 yr (n = 7), were recruited for study. INTERVENTIONS: Serum samples were measured over a 24-h period after an iv injection of recombinant human FSH, 150 IU. MAIN OUTCOME MEASURES: Serum E(2), inhibin A, and inhibin B responses after FSH administration were assessed. RESULTS: In PCOS women, the 24-h production of inhibin B and E(2) after FSH was significantly greater than that of normal controls. Within the PCOS group, the fold change in inhibin B was significantly greater than that of E(2). Inhibin A responses between groups were similar and of markedly lower magnitude. CONCLUSIONS: FSH-stimulated inhibin B responses may be employed to assess the functional capacity of granulosa cells in PCOS and normal women.