Fellow University of Nebraska Medical Center Omaha, Nebraska, United States
Introduction: Cushing’s Syndrome has multiple metabolic and neurocognitive manifestations, but seizures are not commonly reported to occur from hypercortisolemia. We describe a case of severe adrenocorticotropic hormone (ACTH)-dependent hypercortisolism causing seizures that required emergent management.
Case Description: A 56-year-old male was transferred from outside hospital due to recurrent aphasic and grand mal seizures for 2 weeks. For the past 18 months, he had weight gain, proximal muscle wasting, and new onset progressive hypertension, hyperglycemia, and hypokalemia. Neurologic evaluation showed CNS inflammation without a clear etiology for which he was started on high-dose glucocorticoids empirically for presumed autoimmune or paraneoplastic encephalitis. Positron emission tomography (PET) revealed FDG-avid and enlarged bilateral adrenal glands, leading to endocrinology consultation. Review of prior hospitalization revealed serum aldosterone 3.6 ng/dL, renin <0.1 ng/mL/hr, random cortisol levels at 7:00 PM and 4:00 AM of 47.8 ug/dL and 49.7 ug/dL respectively, 24-hour urine free cortisol of 5940 ug/L. Following 5 days of high-dose glucocorticoids, random cortisol was 48.5 ug/dL with simultaneous ACTH of 437pg/mL, and seizures persisted.
His presentation was consistent with ACTH-dependent Cushing’s syndrome. He was urgently transferred to the ICU and started on oral ketoconazole and etomidate infusion with subsequent resolution of seizures when serum cortisol improved. Magnetic resonance imaging (MRI) showed a 1mm hypodensity in the pituitary. DOTATATE-PET/CT was non-localizing. Inferior petrosal sinus sampling was indeterminate while hypercortisolemic on therapy. The patient was unable to transition off etomidate due to severe thrombocytopenia worsened by ketoconazole use. As a result, bilateral adrenalectomy was performed after 10 days in ICU with resolution of hypercortisolemia and seizures. At 6-month follow-up, he remains seizure-free without medications, and continues hormone replacement for primary adrenal insufficiency. Extensive work-up including endoscopy and whole-body imaging has not revealed an ectopic source of ACTH.
Discussion: Cushing’s Syndrome is a diagnostic dilemma presenting with a wide range of symptoms which can obfuscate recognition. Our patient’s case was manifested by a rare symptom of seizures, which was responsive to etomidate. This case highlights that severe Cushing’s syndrome requires prompt recognition and treatment – if the underlying etiology for ACTH secretion is not identified then bilateral adrenalectomy should be performed to save the patient’s life.