Strategies for the investigation of hyperandrogenism and the principles of evidence based medicine

Article type
Authors
Phillipov G
Abstract
Introduction: Evidence based medicine is defined as the integration of individual clinical expertise with the best external clinical evidence. Best external clinical evidence results from a process where diagnostic tests and treatments are evaluated to select only those which are both more powerful and safer. In hirsutism and menstrual disturbances diagnostic tests are important to exclude any serious underlying causes such as congenital adrenal hyperplasia (CAH) and Cushing's syndrome (CS). Most review articles routinely advocate strategies based on a battery of plasma assays and dynamic adrenal testing.

Objective: To examine whether the prevailing clinical consensus on the diagnostic evaluation of hyperandrogenism is consistent with the notion of best external clinical evidence.

Results: Typically the following assays are recommended -plasma testosterone (ovarian tumour), DHEAS (hyperadrenal activity), 17_-hydroxyprogesterone (17_-OHP) (21-CAH) and urinary free cortisol following overnight dexamethasone therapy (CS). A further extension is ACTH stimulation of the adrenal gland and measurement of 17_-OHP to assess any latent existence of 21-CAH. However abnormal results from such assays usually do not allow a definite diagnosis of the underlying condition and the protocol provides no information on a variety of rare disorders, particularly for CAH. In contrast specific measurement of urinary steroids based on a single 24h urine specimen can uniquely define all forms of CAH, identify and partially differentiate CS and provide information on hypercortisolism, hyperandrogenism, thyroid disorders and various enzymatic activities.

Discussion: The most powerful and least invasive diagnostic assay for the definition of major endocrine disorders is currently overlooked in clinical reviews detailing the investigation of hyperandrogenism. This is a result of misconceptions entrenched in the literature and represents a failure to seek the best external evidence.