Endocrine Abstracts

The diagnosis and differential diagnosis of hypercortisolism can be a major clinical challenge and involves several stages. In each stage different approaches are currently followed. There are, however, some general principles. In brief, after critical judgement of clinical features, the first step is to assess whether endogenous hypercortisolism is present. First-line tests to screen for hypercortisolism include measurement of 24 h urinary cortisol excretion, cortisol diurnal rhythm, a 1 mg overnight dexamethasone suppression test and, since recently available, midnight salivary cortisol concentrations. Once hypercortisolism is biochemically established, causes of pseudo-Cushing states (due to e.g. psychiatric disorders or chronic alcoholism) should be excluded. Second-line tests for this purpose include midnight plasma cortisol measurement and dexamethason-CRF testing. Subsequently, ACTH-dependency of hypercortisolism should be assessed. In case of ACTH-independent hypercortisolism, imaging of the adrenals is performed to examine for adenoma, hyperplasia or carcinoma. When ACTH-dependent hypercortisolism is present, the work-up will be continued with pituitary imaging, eventually followed by bilateral sinus petrosus inferior sampling, since this form of Cushing’s syndrome is most frequently caused by a pituitary adenoma. The high-dose intravenous dexamethason suppression test and CRF test are also used to differentiate between pituitary and ectopic origin of ACTH overproduction. When indicated, imaging is performed to detect an ACTH producing neuroendocrine tumor with CT, somatostatin scintigraphy and/or PET scanning.

In each stage of this diagnostic process controversies can be found. In addition, there are considerable differences between, but also within countries, with respect to which tests are applied, how these tests are performed and how tests results are interpreted. Consensus statements and additional research should lead to an improvement of the evidence-based approach of the (differential) diagnosis of hypercortisolism.