Is Diagnosis and Subclassification of Adrenal Insufficiency as Easy as It Looks?

The diagnosis of adrenal insufficiency (AI) is a challenge. Most signs and symptoms are nonspecific and vary considerably depending upon the underlying cause and degree of AI. Identification of AI is crucial because the disease may be life-threatening if left unrecognized. The diagnostic evaluation consists of three steps. The first step is establishing the presence of hypocortisolism. The second step is establishing the level of hypothalamus-pituitary-adrenal axis dysfunction. The third and final step is searching for the exact cause of AI by additional laboratory and imaging techniques. Each diagnostic step can have its own uncertainties. The optimal test in case of intermediate basal cortisol measurements is still a matter of debate. Furthermore, interpretation of the results of the tests is complicated by arbitrary definitions of normal cutoff responses, variability in the analytical accuracy of the cortisol assays used and factors influencing cortisol-binding globulin. This chapter aims to provide a concise stepwise approach for the diagnostic evaluation of AI, taking into account the possible pitfalls associated with the different tests.