237 - The role of the laboratory in the investigation of adrenal disease: Logic and tools
Autor(s): R.M. Dorizzi,P. Maltoni
Issue: RIMeL - IJLaM, Vol. 6, N. 4, 2010 (MAF Servizi srl ed.)
Page(s): 237-47
Cushing syndrome (i.e. sustained hypercortisolism) may result from several conditions (ACTH-producing pituitary tumors, benign or malign adrenal tumours secreting cortisol, extrapituitay tumours producing ACTH or CRH). The pituitary syndrome, Cushing disease, is the most common accounting for approximately 70% of the cases (generally women of childbearing age). According to Nugent’s pioneering Bayesian approach the patients suffering from central obesity, weakness, plethora, acne, striae, hirsutism, ec chymoses, osteoporosis and edema the calculated probability of disease is approximately 95%. In 2008 Endocrine Society and European Society of Endocrinology jointly published guidelines for the diagnosis of Cushing syndrome. The initial testing requires a high diagnostic accuracy: urinary cortisol (at least 2 assays), late-night salivary cortisol (2 assays), 1 mg overnight dexamethasone suppression test (DST); longer low dose DST (2 mg/d 48h). On the contrary, the following tests are not recommended: random serum cortisol and ACTH, urinary 17 ketosteroids, insulin tolerance test, loperamide test, tests designed to determine the cause of Cushing disease (e.g.pituitary and adrenal imaging, 8 mg DST).The assay of cortisol in urine and saliva are pivotal in the diagnosis of adrenal diseases but laboratorians and clinicians must understand their features and their limits. The accuracy of the different assays can be very different and the results near the functional sensitivity of the assay can be due to the analytical variability. The RIA methods have been almost completely superseded by non isotopic automated analyzers while chromatographic techniques, much more accurate, are employed almost exclusively by research laboratories. Liquid chromatography and LC-MS/MS allow separation and quantitation of total cortisol also in presence of other steroids and metabolites. Many papers report the use of saliva sample for carrying out investigations in Endocrinology, Neuro-endocrinology, Sport medicine even if very few clinical laboratories measure analytes in saliva. We have recently introduced in our laboratory the cortisol measurement in saliva after we: 1) discarded the urinary assay for inaccuracy of the extraction step, 2) verified with indirect methods both the reference interval in serum and in saliva (midnight).