Differential diagnosis of hypercortisolism
Diagnosis and differential diagnosis of Cushings syndrome belongs to the most difficult ones in clinical endocrinology and is essential for optimal management of this syndrome. Clinical presentation of Cushings syndrome and frequency of particular clinical signs with respect to their importance for diagnosis and differential diagnosis of Cushings syndrome will be discussed. Subsequently, biochemical tests used for confirmation of Cushings syndrome will be analysed including their sensitivities and specificities. Urinary free cortisol (UFC), elevated midnight cortisol and lack of suppressibility of cortisol levels in low-dose dexamethasone suppression test (LDDST) are main tools for confirmation of this diagnosis. Further tests e.g. dexamethasone suppressed CRH test or salivary cortisol determination could be employed if necessary. After confirmation of autonomous cortisol hypersecretion it is necessary to distinguish between ACTH-independent and ACTH-dependent forms of Cushings syndrome according to the ACTH production. ACTH-independent forms are in majority of cases caused by autonomous cortisol production by adrenal tumours. ACTH-independent bilateral adrenal hyperplasia is a rare cause of ACTH-independent Cushings syndrome, however, especially macronodular hyperplasia can be source of diagnostic errors and problems. Differential diagnosis of ACTH-dependent forms is supposed to be even more difficult. We can use various dynamic tests in distinguishing between pituitary and ectopic ACTH production with different sensitivities and specificities. Bilateral inferior petrosal sinus sampling (BIPSS) is considered to be the most specific and sensitive test. Besides dynamic biochemical tests it is necessary not only to employ appropriate imaging techniques to depict and confirm the source of cortisol or ACTH overproduction but also correctly interpret their results. Method of the first choice in pituitary imaging is magnetic resonance (MR) and in adrenal imaging computed tomography (CT) and/or MR. Specific problem represents imaging of ectopic sources of ACTH production. Finally, optimal algorithms for the diagnosis and differential diagnosis of Cushings syndrome will be discussed.