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  • Title: The management of Cushing's disease - from investigation to treatment.
    Author: Juszczak A, Grossman A.
    Journal: Endokrynol Pol; 2013; 64(2):166-74. PubMed ID: 23653280.
    Abstract:
    Cushing's disease (CD) is caused by an adrenocorticotrophin (ACTH) secreting pituitary adenoma and it is the commonest cause of endogenous hypercortisolism. When high suspicion of Cushing's syndrome (CS) exists, recommended screening tests include the overnight dexamethasone suppression test, the low-dose dexamethasone suppression test, or late night salivary cortisol. If the initial test is positive on two occasions, the patient should be referred to a specialist endocrinologist for in-patient assessment, while elevated midnight serum cortisol and a low dose dexamethasone suppression test will confirm endogenous hypercortisolaemia. Plasma ACTH measurement at 9 am follows and, if elevated, MRI scan of the pituitary should be performed. Corticotrophin releasing hormone (CRH) test helps to distinguish pituitary from ectopic ACTH-dependent CS, though bilateral petrosal sinus sampling remains the gold standard. Transsphenoidal surgery is the recognised first-line treatment of CD, and can be repeated if unsuccessful. Second line therapy includes pituitary radiotherapy, bilateral adrenalectomy and medical treatment. Pituitary radiotherapy is very effective but it usually takes several years for its full effect to be seen. Bilateral adrenalectomy is useful in acutely unwell patients, who are unable to tolerate medical therapy. The most effective medical agents inhibit adrenal steroidogenesis and include metyrapone, ketoconazole, mitotane and etomidate. They are used in preparation for surgery, when an operation has been unsuccessful, or when the effects of radiotherapy are being awaited. Cabergoline and pasireotide decrease ACTH production, but are effective in only 30% and 25% of patients, respectively. It is crucial for patients with CD to be managed in specialist endocrine centres, as the expertise of multidisciplinary team members predicts the best outcome.
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