Endocrine Abstracts

Background: Cyclical Cushing syndrome (CCS) is a rare variant of Cushing syndrome (CS) characterized by periodic cycles of cortisol excess. Diagnosis of CCS is difficult because cortisol excess occurs unpredictably and often limited to short periods. We present 2 unusual cases where the patients developed severe prolonged life-threatening “square wave” hypercortisolemic phase followed by eucortisolemia, both phases extending > 3 months. Case 1: A 75 year old male presented with acute atrial fibrillation, 9 kg weight loss over 3 months, facial plethora, leg edema, muscle weakness, hypertension, hyperglycemia, hypokalemia of 2.6 mEq/l and had UFC 20 × ULN, ACTH 3 × ULN and 11 PM cortisol 66 µg/dl. High-dose dexamethasone did not suppress his cortisol, no gradient on IPSS, and CT chest/abdomen/pelvis and ⁶⁸Ga-DOTATATE PET/CT studies did not reveal an ACTH source. Due to his clinical deterioration, ketoconazole was started. After 3 weeks of treatment, cortisol deficiency developed and ketoconazole was stopped. For the following 3 months thereafter without ketoconazole, UFC, 8 AM cortisol and LNSCs remain normalized with resolution of majority of symptoms enabling the patient to gradually increase his physical activity. Case 2: A 61 year old female presented with 3 kg weight loss over 2 months, muscle weakness, edema, spinal compression fractures, uncontrolled hypertension and hyperglycemia, hypokalemia of 2.2 mEq/l, UFC 5 × ULN, 8 AM ACTH 2 × ULN and 11 PM cortisol 63.2 µg/dl. Due to her severe comorbidities, she was treated with IV etomidate followed by ketoconazole. No gradient was found on IPSS, and CT chest/abdomen/pelvis and ⁶⁸Ga-DOTATATE PET/CT studies failed to reveal an ACTH source. After 5 months, 8 AM ACTH, UFC, 8 AM cortisol and fasting glucose normalized. Because she had some side effects to ketoconazole, the drug was stopped after 2 months. After 4 months being off ketoconazole, UFC, cortisol, LNSCs and blood pressure remain normalized.

Discussion: These two cases highlight the importance of identifying and effectively treating severe prolonged “square wave” hypercortisolemic phase of CCS, and to closely monitor for eucortisolemia development. During the eucortisolemic phase, close monitoring is recommended for re-emergence of hypercortisolemia by self-checking glucose, blood pressure, weight and PM salivary cortisol assessments so that treatment can be promptly instituted if and when hypercortisolemia resurfaces. To our knowledge, severe prolonged “square wave” hypercortisolemia followed by eucortisolemia has not been reported in CCS. Herein, we describe a new variant of presentation of severe cortisol excess of this entity.