scholarly journals Endogenous Steroids Measured by High-Specificity Liquid Chromatography-Tandem Mass Spectrometry and Prevalent Cardiovascular Disease in 70-Year-Old Men and Women

2010 ◽  
Vol 95 (4) ◽  
pp. 1889-1897 ◽  
Author(s):  
Tord Naessen ◽  
Ulrika Sjogren ◽  
Jonas Bergquist ◽  
Marita Larsson ◽  
Lars Lind ◽  
...  

Abstract Context: There is a need for increased knowledge about endogenous sex hormone levels and clinical outcomes of risk/benefit. Immunoassays have poor specificity to reliably measure low steroid concentrations in elderly. Objective: The objective of the study was to evaluate plasma steroid concentrations with regard to prevalent cardiovascular disease (CVD) in elderly, using mass spectrometry. Setting: The study was conducted at a university hospital research unit. Design and Methods: Plasma samples were analyzed from 202 70-yr-olds as part of a large population-based study, Prospective Investigation of the Vasculature in Uppsala Seniors. Twenty-eight of these had prevalent CVD. Eleven steroids were quantified, using liquid chromatography-tandem mass spectrometry. Women with current/previous menopausal hormone therapy (n = 35) were excluded. Results: Men without prevalent CVD had higher plasma 17β-estradiol (E2), compared with women. Men with prevalent CVD, compared with those without, had lower 17-hydroxypregnenolone (17OHPregn), 17-hydroxyprogesterone, and higher estrone/androstenedione and E2/testosterone (T) (aromatase activity). Women with prevalent CVD had lower pregnenolone, 17OHPregn, and dehydroepiandrosterone (DHEA) but higher DHEA/17OHPregn, androstenedione/DHEA, E2/T, E2/estrone, and E2/SHBG. The aromatase index, E2/T, was higher for prevalent CVD in both sexes. Adjustment for statin use, smoking, and body mass index yielded additional significant differences in men, whereas some were lost in women. Logistic regression indicated strong associations between prevalent CVD and low 17OHPregn, adjusted odds ratio of 0.18, 95% confidence interval (0.06–0.61); P = 0.006, in women and low 17-hydroxyprogesterone, 0.45 (0.25–0.80); P = 0.007 in men, most likely caused by increased throughput (consumption) toward estrogen synthesis. Conclusions: Prevalent CVD was associated with indications of lower androgen precursors, increased aromatase activity, and higher estrogen levels in both sexes. Results might represent an endogenous response to a condition of developing atherosclerosis, rather than a causative relationship. Furthermore studies are needed.

Metabolites ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 284 ◽  
Author(s):  
Ilaria Cicalini ◽  
Stefano Tumini ◽  
Paola Irma Guidone ◽  
Damiana Pieragostino ◽  
Mirco Zucchelli ◽  
...  

Congenital adrenal hyperplasia (CAH) describes a group of autosomal recessive disorders of steroid biosynthesis, in 95% of cases due to 21-hydroxylase deficiency. The resulting hormonal imbalances lead to increased 17-hydroxyprogesterone and androgens levels, at the expense of decreased concentrations of glucocorticoids and, in some cases, of mineralocorticoids. A variety of clinical presentations accompany a range of severities, which are described as different forms of CAH, and are the result of these hormonal imbalances. The incidence of CAH worldwide is approximately 1 in 15,000 live births, and is population-dependent; thus, its inclusion in neonatal screening tests is widely discussed. Diagnosis of CAH is based on the quantification of 17-hydroxyprogesterone, usually by immunoassay, which has low specificity and high false-positive rates, resulting in a relatively high demand for a second-tier confirmation test. We report a case of a newborn recognized as female at birth, but showing ambiguous genitalia and other CAH clinical features, including hypernatremia, in the first days of life. In addition to the classical assays, liquid chromatography–tandem mass spectrometry was used to determine the serum steroid profile, allowing for the accurate and simultaneous quantification of seven steroids in the same analysis. Such an application immediately revealed an alteration in the levels of specific steroids related to CAH, leading to an early intervention by hormone replacement therapy. Subsequently, the diagnosis of classic CAH due to 21-hydroxylase deficiency was further confirmed by molecular testing.


Author(s):  
Qichen Long ◽  
Tianjiao Zhang ◽  
Ying Yan ◽  
Haijian Zhao ◽  
Weiyan Zhou ◽  
...  

AbstractObjectivesAccurate measurements of serum 17-hydroxyprogesterone (17OHP) are essential for diagnosis and treatment monitoring for congenital adrenal hyperplasia patients. The performance of serum 17OHP routine methods remains highly variable that calls for a candidate reference measurement procedure (cRMP) to improve the standardization of serum 17OHP measurements.MethodsSerum samples spiked with internal standards were extracted with a combination of solid-phase extraction and liquid-liquid extraction. The 17OHP was quantified by the isotope dilution coupled with liquid chromatography/tandem mass spectrometry (ID-LC/MS/MS) with electrospray ionization in positive ion mode. Nine structural analogs of 17OHP were evaluated for interferences. The precision and analytical recovery were assessed. Twenty native and 40 spiked serum for performance evaluation were measured by the cRMP and two clinical LC/MS routine methods.ResultsNo apparent interferences were found with the 17OHP measurement. The within-run, between-run, and total precision for our method were 0.4–0.8%, 0.6–2.0%, and 1.0–2.1% for four pooled serum (2.46–102.72 nmol/L), respectively. The recoveries of added 17OHP were 100.0–100.2%. For the performance of two LC/MS routine methods, they showed relative deviation ranges of −22.1 to 1.1% and −6.7 to 12.8%, respectively.ConclusionsWe developed and validated a reliable serum 17OHP method using ID-LC/MS/MS. The desirable accuracy and precision of this method enable it to serve as a promising cRMP to improve the standardization for serum 17OHP routine measurements.


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