Steroid Mass Spectrometry for the Diagnosis of PCOS

Abstract

The most appropriate steroids to measure for the diagnosis of hyperandrogenism in polycystic ovary syndrome (PCOS) are still open to debate but should preferably be measured using a high-quality method such as liquid chromatography tandem mass spectrometry (LC-MS/MS). Measurement of testosterone is recommended in all of the current clinical guidelines but other steroids, such as androstenedione and dehydroepiandrosterone sulfate (DHEAS), have also been shown to be useful in diagnosing PCOS and may give additional information on metabolic risk. The 11-oxygenated steroids, and in particular 11KT derived mainly from the adrenal gland, are also increasing in prominence and have been shown to be the dominant androgens in this condition. Polycystic ovary syndrome is a complex syndrome and it is not surprising that each of the clinical phenotypes are associated with different patterns of steroid hormones; it is likely that steroid profiling with LC-MS/MS may be better at identifying hyperandrogensim in each of these phenotypes. Research into PCOS has been hampered by the small sample size of clinical studies previously undertaken and larger studies, preferably using LC-MS/MS profiling of steroids, are needed

Hyperandrogenism by Liquid Chromatography Tandem Mass Spectrometry in PCOS: Focus on Testosterone and Androstenedione

“…In our study, we found that fT concentrations correlated with metabolically adverse parameters (BMI, HOMA-index, and HbA1c), whereas there was no correlation between A and metabolic aspects. This is in contrast with the findings of O’Reilly et al that described a significant association between high A concentrations and an adverse metabolic phenotype, but confirms the results in the metanalyses by Amiri et al [ 11 , 12 , 13 , 14 , 15 ].…”

“…Moreover, some authors argue that a multi-steroid profile could be more sensitive in detecting hyperandrogenism in these patients [ 10 , 11 , 12 ]. It is likely that the use of liquid chromatography in tandem with mass spectrometry (LC-MS/MS), the gold standard for steroids measurements, allowing simultaneous measurement of several androgens, may improve the diagnosis and phenotyping of PCOS patients [ 13 ]. However, this technique has had limited application in clinical practice because of its complexity, and its difficulty in preparing quality control samples, which increased with the number of analytes.…”

Simultaneous quantitation of four androgens and 17‐hydroxyprogesterone in polycystic ovarian syndrome patients by LC‐MS/MS

“…14 Many studies have confirmed that the LC-MS/MS had good performance in the determination of T, DHEAS, A4 or other steroids, [16][17][18] offering an ideal alternative methodology in the determination of hyperandrogenism in PCOS. 19 Some previous studies have shown that the simultaneous determination of T and A4, or T and DHT was achievable with excellent accuracy and little matrix interference. 20,21 As part of the continual efforts to improve the laboratory diagnostic accuracy of hyperandrogenism in PCOS patients, we established an efficient LC-MS/MS method for simultaneous measurement of serum T, A4, DHEAS, DHT, and 17-OHP and evaluated the clinical utility of this androgen testing panel with the PCOS patients.…”

The Potential of Steroid Profiling by Mass Spectrometry in the Management of Adrenocortical Carcinoma

“…In fact, the diagnosis, prognosis, and management of such diseases strongly depend on accurate quantification of steroid hormones in biological fluids. Imbalances in production or metabolism of steroids lead to a wide range of steroid related disorders, sometimes complex adrenal diseases, including congenital adrenal hyperplasia (CAH) [ 71 , 72 , 73 , 74 , 82 , 83 ], adrenal cancer [ 4 , 6 , 7 , 45 , 75 , 76 ], hyperaldosteronism [ 45 , 84 , 85 , 86 , 87 ], Cushing’s syndrome [ 68 ], disorder of sexual development (DSD) [ 44 ], and polycystic ovary syndrome (PCOS) [ 44 , 69 , 88 ]. For some of these disorders, it is still open to debate on which steroids are most appropriate to be quantified for the related diagnosis.…”

“…About five decades ago, Gower et al described alterations in steroid hormones production as possible markers of malignancy in adrenal tumors [64,65]. Subsequently, the application of steroid profiling in the diagnosis of adrenocortical disorders has been described on many occasions: firstly, by using difficult chromatographic separations and colorimetric or immunoassay procedures [66,67], more recently replaced by targeted metabolomics techniques using GC-MS and LC-MS/MS, respectively [4,[68][69][70][71][72][73][74]. Even if not enough data on steroid profiling have been reported to be able to define a distinct malignant steroid fingerprint for ACC, biochemical evidence showed how most ACCs are characterized by accumulation of steroid precursor metabolites rather than by end products of steroidogenesis [75].…”