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      Cushing's storm secondary to a rare case of ectopic ACTH secreting metastatic breast cancer

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          Summary

          Ectopic ACTH secretion from breast cancer is extremely rare. We report a case of a 30-year-old woman with a history of breast cancer, who presented with psychosis and paranoid behaviour. CT of the head showed white matter disease consistent with posterior reversible encephalopathy syndrome (PRES). Despite using mifepristone with multiple antihypertensives including lisinopril, spironolactone and metoprolol, she was hypertensive. Transaminitis did not allow mifepristone dose escalation and ketoconazole utilization. Etomidate infusion at a non-sedating dose in the intensive care unit controlled her hypertension and cortisol levels. She was transitioned to metyrapone and spironolactone. She was discharged from the hospital on metyrapone with spironolactone and underwent chemotherapy. She died 9 months later after she rapidly redeveloped Cushing's syndrome and had progressive metastatic breast cancer involving multiple bones, liver and lungs causing respiratory failure.

          Learning points

          • Cushing's syndrome from ectopic ACTH secreting breast cancer is extremely rare.

          • Cushing's syndrome causing psychosis could be multifactorial including hypercortisolism and PRES.

          • Etomidate at non-sedating doses in intensive care setting can be effective to reduce cortisol production followed by transition to oral metyrapone.

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          Most cited references14

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          Posterior reversible encephalopathy syndrome: utility of fluid-attenuated inversion recovery MR imaging in the detection of cortical and subcortical lesions.

          Posterior reversible encephalopathy syndrome (PRES) is typically characterized by headache, altered mental functioning, seizures, and visual loss associated with imaging findings of bilateral subcortical and cortical edema with a predominantly posterior distribution. Our goal was to determine whether fluid-attenuated inversion recovery (FLAIR) imaging improves the ability to detect subtle peripheral lesions of PRES, as compared with conventional MR techniques. Sixteen patients with clinical and imaging findings consistent with PRES were studied. Thirteen patients had undergone transplantation and had cyclosporin A neurotoxicity. Fast-FLAIR images were compared with spin-echo proton density- and T2-weighted images. FLAIR imaging improved diagnostic confidence and conspicuity of the T2 hyperintense lesions of PRES, typically in the subcortical white matter of the parietooccipital regions bilaterally. On all 23 abnormal MR studies, FLAIR was judged superior to proton density- and T2-weighted images for the detection of PRES in the supratentorial brain. In a mean of 6.7 of 23 studies, FLAIR findings prompted a raise in the grade of disease severity. FLAIR also showed cortical involvement in 94% of patients with PRES and in a mean of 46% of the total lesion burden. In four cases, subtle lesions were virtually undetectable without FLAIR. Brain stem or cerebellar disease was encountered in 56% of patients. FLAIR improves the ability to diagnose and detect subcortical and cortical lesions in PRES as compared with proton density- and T2-weighted spin-echo images. We therefore believe that FLAIR should be performed in patients with suspected PRES to allow more confident recognition of the often subtle imaging abnormalities.
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            Medical Treatment of Cushing’s Syndrome: Adrenal-Blocking Drugs and Ketaconazole

            Cushing’s syndrome is associated with serious morbidity and increased mortality. Irrespective of its cause, i.e. a pituitary adenoma, ectopic ACTH production or an adrenal neoplasia, Cushing’s syndrome is primarily treated surgically. However, when surgery is unsuccessful or contraindicated, medical therapy is needed to treat hypercortisolism. The spectrum of available drugs includes adrenal-blocking agents, neuromodulatory drugs and glucocorticoid receptor antagonists. Adrenal blocking drugs suppress adrenal cortisol production via inhibition of steroidogenic enzymes. Ketoconazole and metyrapone are most frequently used for this purpose, but chronic treatment with these drugs can be limited by side effects like hepatotoxicity (ketoconazole) and increased androgen and mineralocorticoid production (metyrapone). Etomidate can be used to rapidly reverse cortisol excess in patients with acute complications of (severe) hypercortisolism like psychosis. In Cushing’s disease, combination therapy with drugs that target the corticotropic adenoma, i.e. the universal somatostatin analogue pasireotide and/or the dopamine agonist cabergoline, and low-dose ketoconazole seems a rational approach to achieve biochemical control.
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              Emergency and prolonged use of intravenous etomidate to control hypercortisolemia in a patient with Cushing's syndrome and peritonitis.

              We report the emergency and prolonged use of etomidate to control circulating cortisol levels in a patient with Cushing's syndrome secondary to ectopic ACTH production from a pancreatic islet cell tumor. Duodenal perforation and peritonitis complicated an episode of salmonella septicemia, precluding the use of conventional oral medical adrenolytic therapy. Endogenous cortisol secretion was abolished by parenteral etomidate, allowing serum cortisol levels to be controlled with an iv infusion of hydrocortisone over an 8-week period in intensive care before definitive pancreatic surgery.

                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                edm
                EDM Case Reports
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                2 September 2015
                2015
                : 2015
                : 150051
                Affiliations
                [1 ]Division of Endocrinology, Department of Medicine , Lehigh Valley Health Network , Allentown, Pennsylvania, 18103, USA
                [2 ]Department of Medicine , Lehigh Valley Health Network , Allentown, Pennsylvania, 18103, USA
                Author notes
                Correspondence should be addressed to V Magaji Email: vasudevgmagaji@ 123456gmail.com
                Article
                EDM150051
                10.1530/EDM-15-0051
                4626655
                26525183
                a8b4ea3f-a15a-46b6-af96-16e315a7296d
                © 2015 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

                History
                : 10 August 2015
                : 2 September 2015
                Categories
                Insight into Disease Pathogenesis or Mechanism of Therapy

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