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  • Title: Cushing's disease.
    Author: De Martin M, Pecori Giraldi F, Cavagnini F.
    Journal: Pituitary; 2006; 9(4):279-87. PubMed ID: 17077950.
    Abstract:
    Cushing's disease, i.e., pituitary ACTH-secreting adenoma causing excess glucocorticoid secretion, is a rare disease with significant mortality and morbidity. Timely diagnosis and appropriate treatment can alter the course of the disease and are therefore mandatory. First step of the diagnostic work-up is the endogenous glucocorticoid excess by measurement of urinary free cortisol, cortisol circadian rhythmicity or suppression by low doses of dexamethasone. In patients with equivocal results, second line tests, such as the dexamethasone-suppressed CRH test and desmopressin stimulation, usually enable the diagnosis to be confirmed. Measurement of plasma ACTH then allows the distinction between ACTH-dependent (e.g., pituitary or extrapituitary neuroendocrine tumors) and ACTH-independent causes (e.g., adrenal tumors). The last step in the diagnostic algorithm is often the most fraught with problems as the distinction between Cushing's disease and ectopic ACTH secretion relies on judicious interpretation of several diagnostic procedures. Positive responses to stimulation with CRH and inhibition by high doses of dexamethasone, if concurrent, enable a pituitary origin to be established whereas conflicting results call for inferior petrosal sinus sampling, the latter to be performed in experienced centres only. Visualisation of the tumor at pituitary imaging is helpful but not required for the diagnosis, as microadenomas often remain undectected by MRI and/or CT scan and, on the other hand, visualisation of a non-secreting incidentaloma may be misleading. Surgical removal of the pituitary tumor is the optimal treatment choice and should be attempted in every patient. Surgical failures as well as relapses can be treated by radiotherapy, medical therapy or, if necessary, bilateral adrenalectomy. Finally, patients cured of Cushing's disease require long-term monitoring given the risk of relapse and clinical burden of associated ailments.
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