American Association for Clinical Chemistry
Better health through laboratory medicine
October 2011 Clinical Laboratory News: Lab Tests Key to Definitive Polycystic Ovary Syndrome Diagnosis

AM 2011

The educational offerings at the AACC 2011 Annual Meeting were as diverse as the attendees. Symposia, workshops, brown bag sessions, and more gave attendees the latest information, as well as practical advice, on a myriad of clinical lab topics. Below is a brief on one of the sessions.

Lab Tests Key to Definitive Polycystic Ovary Syndrome Diagnosis

By Genna Rollins

Speakers at a short course on polycystic ovary syndrome (PCOS), a condition that affects 4–8% of reproductive-age women and costs $4.36 billion annually, emphasized that because it shares clinical and biochemical features with other conditions, accurate test results are crucial to the diagnostic process. “The pathogenesis is very complicated. That’s what makes it such a challenge to diagnose,” said Alison Woodworth, PhD, assistant professor of pathology at Vanderbilt University Medical Center in Nashville. She explained that several etiologies for PCOS have been proposed, including CYP17 and CYP11a mutations, and defects in insulin action and secretion, androgen synthesis, and cortisol metabolism. However, researchers are uncertain as to whether hyperinsulinemia resulting in increased androgen levels occurs first or whether androgen levels rise first, causing hyperinsulinemia. “It’s all somewhat controversial at the moment, but depending on who you read, it seems to feedback to insulin resistance.”

Woodward stressed that making a definitive diagnosis is important not only because PCOS is the leading cause of anovulatory infertility, but also because PCOS patients typically have significant comorbidities like obesity, insulin resistance, and cardiac Syndrome X, and are at increased risk for cardiovascular disease, diabetes, and endometrial cancer. PCOS shares some symptoms and biomarker trends with other conditions like metabolic syndrome, congenital adrenal hyperplasia, Cushing’s syndrome, and androgen secreting neoplasms, so a complete clinical and laboratory picture is essential to recognizing the disease. New criteria adopted in 2006 define PCOS as clinical and/or biochemical hyperandrogenism with either oligo/anovulation and/or polycystic ovaries.

Key lab tests in making the differential diagnosis of PCOS include urine or serum human chorionic gonadotropin, free testosterone, 17-hydroxy progesterone, thyroid stimulating hormone, sex hormone binding globulin (SHBG), and prolactin. Clinicians might also consider several hormone tests, including follicle stimulating hormone, luteinizing hormone, progesterone, and estradiol. Other potentially helpful tests include a 2-hour glucose tolerance test or HbA1c, 24-hour urinary free cortisol, insulin-like growth factor 1, and liver function and creatinine testing if the clinician is considering prescribing metformin.

Woodward reminded the audience about the challenges of measuring testosterone in women. “Using a general testosterone immunoassay that we all have in our labs right now is not a good evaluation of patients with PCOS,” she cautioned. However, direct measurement of testosterone by gas chromatography mass spectrometry (MS) or liquid chromatography tandem MS after an extraction procedure are good methods, especially when coupled with a SHBG measurement. Woodward emphasized that laboratorians need to take care in establishing normal reference ranges for testosterone in women, ensuring that they exclude samples from women with menstrual or ovulatory dysfunction, hyperandrogenism, and other PCOS-related symptoms. Samples should be collected at the same time of day and at the same point in the menstrual cycle for all women.

Because PCOS is such a complex condition, definitive diagnosis and treatment depends on a multidisciplinary approach. “We’re trying to do this at Vanderbilt. Collaboration among caregivers, including primary care physicians, obstetrician-gynecologists, reproductive endocrinologists, radiologists, and laboratorians may actually improve our diagnostic efficiency,” she said. “If we work together, our PCOS patients will have a much more efficient diagnostic and management course in the end.”