Case Presentation: A 70-year-old male former smoker with diabetes mellitus and hypertension presented with cognitive impairment, lower extremity edema, weakness, and 20-pound weight loss over two months. The patient was alert and oriented but had word-finding difficulty. He denied fever, chills, cough, dyspnea, or chest pain. Exam revealed intermittent hypertension, flushing, diaphoresis, hyperpigmented upper extremities, symmetric lower extremity pitting edema and proximal muscle weakness. Initial laboratory data showed hypokalemia (2.9 mEq/L), hyperglycemia (HbA1c 10% from 6.8% two months earlier), and leukocytosis (14,900/μL). Chest CT showed a 2.9cm-left lower lobe (LLL) nodule and 1.5cm-right lower lobe (RLL) nodule concerning for malignancy. Brain MRI was negative for metastasis. Echocardiogram did not demonstrate a cardiac cause of edema.

Endocrine studies revealed AM serum cortisol of 179.8 μg/dL (5.5-20 μg/dL) that was not significantly suppressed by low-dose dexamethasone (152 μg/dL). Elevated 24-hour urine free cortisol of 20,801.9 μg (4-50 μg) confirmed hypercortisolism. Serum ACTH was greatly elevated at 264 pg/mL (6-50 pg/mL). High-dose dexamethasone failed to suppress cortisol (147.9 μg/dL), suggesting ectopic Cushing syndrome (CS). Repeat CT showed a rapidly enlarging and cavitary RLL nodule and new apical nodules. RLL lesion pathology showed Nocardia. Trimethoprim-sulfamethoxazole was initiated for nocardiosis and ketoconazole for cortisol suppression. Octreoscan identified uptake in the apical nodules but biopsy was only consistent with Nocardia. Finally, biopsy of the unchanged LLL nodule revealed typical carcinoid tumor staining for chromogranin A, synaptophysin, and ACTH. The patient was referred for surgery.

Discussion: The patient did not have the classic signs of CS such as a buffalo hump or abdominal striae but had many nonspecific findings including hyperglycemia, cognitive impairment, weakness, and hypokalemia. Ectopic CS is less likely to present with the classic signs than Cushing disease due to more rapid disease progression. Ectopic CS is also associated with skin hyperpigmentation, and can present with weight loss rather than gain. Hospitalists should keep hypercortisolism on the differential for these findings in the appropriate scenarios.

Optimal therapy is surgical resection, which requires identifying the ACTH-secreting tumor. In our case, the search was complicated by concurrent nocardiosis. Hypercortisolism causes immunosuppression that puts the patient at risk of opportunistic infections including nocardiosis. Nocardia most commonly infects the lungs, and can present as asymptomatic nodules. Hospitalists should know this association in order to reach the appropriate diagnosis and treatment.

Conclusions: Cushing syndrome should be suspected even in the absence of classic signs and symptoms. Hospitalists should recognize nonspecific features of the disease, and be aware of the associated risk of opportunistic infections.