This patient likely has an ectopic ACTH production from a tumor in the abdomen or thorax. High resolution CT will localize the tumor in the majority of cases.
This patient's symptoms of fatigue, central obesity, and proximal muscle wasting with an elevated 24-hour urinary cortisol level are indicative of hypercortisolism. His elevated ACTH suggests that this is an ACTH-dependent process. The failure of the high-dose dexamethasone to suppress his cortisol level indicates this is an ectopic source of ACTH.
Kirk et al. review the manifestations and diagnosis of Cushing syndrome and disease. The most common endogenous cause of Cushing syndrome is Cushing disease. Clinical findings include weight gain, truncal obesity, striae, hypertension, glucose intolerance and infections. In the case of an enlarging pituitary adenoma, cranial nerve II may be affected. The authors caution that obesity, chronic illness, alcoholism, and depression can cause false-positive results (pseudo-Cushing's syndrome) on the 1-mg dexamethasone suppression test and mildly elevated free cortisol values on the 24-hour urine collection.
Newell-Price et al. review Cushing syndrome. They report that the most common causes of ACTH-producing tumors are small cell carcinoma of lung, bronchial-derived adenocarcinoma of lung, pheochromocytoma, and carcinoid tumor.
Illustration A depicts the various signs and symptoms of Cushing syndrome. An enlarged sella turcica would suggest Cushing disease as the cause. Illustration B depicts a broad diagnostic algorithm for determining the etiology of Cushing syndrome.
Answer 1: Bilateral inferior petrosal sampling is considered the gold standard for identifying a pituitary ACTH-producing tumor. However, it is generally preceded by a brain MRI.
Answer 2: While metyrapone is the first-line adrenolytic due to its rapid onset of action, it should not be initiated until the diagnosis is confirmed. Identification and removal of the ACTH secreting tumor is also of primary importance.
Answer 3: Ketoconazole is a second-line adrenolytic agent. Pharmacologic treatment should not be initiated until the diagnosis is confirmed. Identification and removal of the ACTH secreting tumor is also of primary importance.
Answer 5: Brain MRI would be the test of choice if a pituitary adenoma was suspected. However, due to this patient's failure to suppress cortisol levels in response to dexamethasone, the likely lesion is ectopic.
Kirk LF Jr, Hash RB, Katner HP, Jones T. Cushing's disease: clinical manifestations and diagnostic evaluation. Am Fam Physician. 2000 Sep 1;62(5):1119-27, 1133-4. Review. Erratum in: Am Fam Physician 2002 Feb 1;65(3):386. PubMed PMID: 10997535.
PMID:10997535 (Link to Abstract)
Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing's syndrome. Lancet. 2006 May 13;367(9522):1605-17. Review. PubMed PMID: 16698415.
PMID:16698415 (Link to Abstract)