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  • Title: The differential diagnosis of Cushing's syndrome.
    Author: Newell-Price J, Grossman AB.
    Journal: Ann Endocrinol (Paris); 2001 Apr; 62(2):173-9. PubMed ID: 11353890.
    Abstract:
    The diagnosis of Cushing's syndrome remains one of the most challenging tasks in clinical neuroendocrinology. The diagnostic procedure can be divided into two distinct steps: diagnosis of the neuroendocrine disorder and differential diagnosis of the precise aetiology. The goal of the first laboratory tests is to obtain biochemical proof of Cushing's syndrome. Patients with Cushing's syndrome are relatively insensitive to glucocorticoid feedback and exhibit an oversecretion of cortisol devoid of a circadian cycle. In our experience, a low-dose dexamethasone suppression test provides the most reliable confirmation of steroid resistance, a cortisol level of<50 nmol/l at 9 a.m. having 98% sensitivity. A cortisol level below 50 nmol/l at midnight rules out active Cushing's syndrome with, in our experience, 100% sensitivity and a specificity depending on numerous other variables. A very high level of free urinary corticol can be a useful sign. After having established the diagnosis of Cushing's syndrome, a persistently low level of ACTH (<10 pg/ml), or preferentially an undetectable level unresponsive to CRH (100 microgram iv), is suggestive of an ACTH-independent disorder, and consequently of primary adrenal disease. The precise location of the lesion can identified with CT or MRI imaging, generally prior to surgical cure. If the ACTH level is detectable, patients with pituitary Cushing's syndrome, or Cushing's disease, should be differentiated from those with ectopic ACTH secretion. The secreting tumour may be difficult to localise and diagnosis is never 100% sure with dynamic tests. Catheterisation of the petrosal sinus with CRH stimulation provides the best sensitivity for differentiating the two aetiologies. We consider a central to peripheral gradient of>3 to confirm the pituitary origin of the disorder with a 98% sensitivity. Chest or abdominal CT can be helpful to identify an ectopic tumour but very small tumours may go undetected. MRI can detect 60 or 70% of all pituitary adenomas but is virtually non-contributive to the diagnosis of Cushing's disease in children.
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