Case Presentation: A 55 year-old man with a history of MSSA Bacteremia, Type II Diabetes, and Hypertension was admitted with pseudomonas bacteremia. Physical exam was notable for a cushingoid appearance. Laboratory studies were remarkable for hypernatremia, hyperkalemia and metabolic alkalosis. Serum morning cortisol was 162 mcg/dL and serum morning ACTH was 297 pg/mL (normal 7-63 pg/ml). He was diagnosed with Cushing’s Disease.. There was no pituitary adenoma on MRI. High-dose dexamethasone did not suppress ACTH. Ga68 Dotatate PET/CT did not localize a source of ectopic ACTH production. He was started on high dose ketoconazole which resulted in achievement of normotension, and normalization of electrolyte disturbances. He subsequently underwent bilateral adrenalectomy to prevent long-term risks of hypercortisolism.
Discussion: Endogenous Cushing’s Syndrome is rare and most commonly due to ACTH dependent disease either from pituitary microadenoma or ACTH producing tumor. (1) After extensive biochemical and imaging evaluation, no clear source was identified in this case. Therefore there was no source to be treated or isolated. The patient was hypertensive and with such profound electrolyte abnormalities he required inpatient management with frequent potassium repletion and multiple daily lab draws. The electrolyte abnormalities and hypertension responded to spironolactone. However he remained hyperglycemic and had evidence of immunocompromise with MSSA and pseudomonas bacteremia, so cortisol suppression was pursued, as he was not an immediate surgical candidate. Ketoconazole was started to inhibit the production of cortisol at the adrenal glands. (2) It was up-titrated to doses of 400mg three times daily with twice daily cortisol levels drawn to assess for its efficacy. Several days after initiating ketoconazole, the patient became hypotensive, fatigued and hypoglycemic. Subsequent cortisol levels were deficient. Ketoconazole dosing was decreased and titrated to achieve physiologic steroid levels. Once stabilized, he completed therapy for bacteremia before undergoing adrenalectomy. Following adrenalectomy, the patient was monitored as physiologic doses of glucocorticoid and mineralocorticoids were initiated. . This resulted in secondary adrenal insufficiency and will need to be monitored closely and treated aggressively in the event of systemic infection or stress. (2)
Conclusions: Cushing’s should be considered when healthy patient shows evidence of immunocompromise in the absence of other risk factors. Subsequently once identified and attempting to bridge to definitive surgery or therapy for the primary source, steroid inhibitors such as spironolactone can be used to manage electrolyte and blood pressure abnormalities. Additionally, production inhibitors such as ketoconazole can be used to return cortisol to physiologic levels. However, this should be done in an inpatient setting with frequent lab and vital sign monitoring and aggressive treatment of electrolytes. Ultimately if no isolated source of ectopic ACTH production is identified, bilateral adrenalectomy and subsequent replacement of physiologic steroids should be pursued to prevent the long-term complications of hypercortisolism.