High salivary testosterone-to-androstenedione ratio and adverse metabolic phenotypes in women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by a combination of hormonal and metabolic disturbances, such as insulin resistance, glucose intolerance, anovulation and hyperandrogenism. Clinical phenotypes of PCOS show different patterns of steroid hormones that have been investigated to some extent. This study aimed to establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of salivary testosterone and androstenedione and to describe the salivary testosterone-to-androstenedione (T/A4) ratio as a new tool for the assessment of hyperandrogenism and metabolic health. MATERIAL AND METHODS: Saliva and serum samples of 274 patients with PCOS and 51 healthy women were used for the quantification of steroid hormones. A comprehensive clinical and metabolic assessment was performed. Salivary testosterone and androstenedione were measured via LC-MS/MS. The salivary T/A4 ratio was calculated and correlated with hormones and metabolic parameters. RESULTS: Salivary testosterone (P < 0·001), androstenedione (P < 0·001) and the salivary T/A4 ratio (P < 0·001) were significantly higher in patients with patients compared to healthy women. In patients with PCOS, a high salivary T/A4 ratio was associated with an adverse metabolic phenotype, that is glucose intolerance (P = 0·019), insulin resistance (P < 0·001), metabolic syndrome (P < 0·001), obesity (P < 0·001) and oligo-/anovulation (P = 0·001). Significant correlations of the salivary T/A4 ratio with adverse metabolic parameters were found. CONCLUSION: Quantification of salivary androgens provides an attractive alternative to serum analysis and helps in characterizing metabolic health in women with PCOS. Our data show a strong link between a high salivary T/A4 ratio and an adverse metabolic phenotype in patients with PCOS.

Serial surveillance of carcinoid heart disease: factors associated with echocardiographic progression and mortality.

BACKGROUND: Carcinoid heart disease is a complication of metastatic neuroendocrine tumours (NETs). We sought to identify factors associated with echocardiographic progression of carcinoid heart disease and death in patients with metastatic NETs. METHODS: Patients with advanced non-pancreatic NETs and documented liver metastases and/or carcinoid syndrome underwent prospective serial clinical, biochemical, echocardiographic and radiological assessment. Patients were categorised as carcinoid heart disease progressors, non-progressors or deceased. Multinomial regression was used to assess the univariate association between variables and carcinoid heart disease progression. RESULTS: One hundred and thirty-seven patients were included. Thirteen patients (9%) were progressors, 95 (69%) non-progressors and 29 (21%) patients deceased. Baseline median levels of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and plasma 5-hydroxyindoleacetic acid (5-HIAA) were significantly higher in the progressors. Every 100 nmol l(-1) increase in 5-HIAA yielded a 5% greater odds of disease progression (OR 1.05, 95% CI: 1.01, 1.09; P=0.012) and a 7% greater odds of death (OR 1.07, 95% CI: 1.03, 1.10; P=0.001). A 100 ng l(-1) increase in NT-proBNP did not increase the risk of progression, but did increase the risk of death by 11%. CONCLUSIONS: The biochemical burden of disease, in particular baseline plasma 5-HIAA concentration, is independently associated with carcinoid heart disease progression and death. Clinical and radiological factors are less useful prognostic indicators of carcinoid heart disease progression and/or death.

A simplified liquid chromatography tandem mass spectrometry assay, using on-line solid-phase extraction, for the quantitation of cortisol in saliva and comparison with a routine DELFIA method.

BACKGROUND: We have developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for measuring salivary cortisol, which requires only 200 microL sample and no extraction. METHODS: Sample (200 microL) and 25 microL internal standard were added directly to a 96-deep-well plate. Of this, 50 microL was loaded onto a guard cartridge, the cartridge was then washed and the eluate was diverted to waste. The compounds were eluted from the guard cartridge onto the C18 analytical column. Cortisol and deuterated cortisol were monitored using transitions m/z 363.2 > 121.1 and 365.1 > 122.2, respectively. RESULTS: The method had a lower limit of quantitation of 2 nmol/L. Intra-assay and inter-assay imprecision were better than 9.5%. Comparison with an established dissociation enhanced lanthanide fluorescent immunoassay (DELFIA) gave good agreement for the majority of samples; LC-MS/MS = 1.0065 x DELFIA - 3.7 (n = 130). The reference range was determined to be 5.8-45.7 nmol/L at 08:00 h and <6.4 nmol/L at 23:00 h (n = 44). CONCLUSIONS: We have developed a simple, robust assay to measure salivary cortisol using on-line solid-phase extraction to reduce sample clean-up requirements.