Unusual Presentation of Cyclic Cushing’s Syndrome

Abstract

Abstract Introduction: About 20–40% of patients with Cushing’s syndrome present with cyclic Cushing’s Syndrome characterized by episodes of cortisol excess interspersed with periods of normal cortisol secretion. A high degree of suspicion is needed to identify patients with cyclical hypercortisolism. Fluctuations in cortisol levels can make this a diagnostic challenge. Rarely, hypocortisolemia and frank adrenal insufficiency can occur. Case Report: A 77-year-old female with history of Cushing’s syndrome and transsphenoidal surgery with no adenoma identified on pathology presented with fatigue and concern for recurrence with ACTH of 358 pg/mL (6–50 pg/mL) and morning serum cortisol of 41.4 mcg/dL. Brain MRI showed a possible 4 mm pituitary adenoma. However, when she was transferred to our hospital, there was no evidence of hypercortisolism with cortisol of 9.5 mcg/dL, ACTH of 33pg/mL, 24 hr urine free cortisol (UFC) of 4.4ug/d (<45ug/d) and she was discharged home after neurosurgery recommended no surgical intervention. A week later, the patient returned to the hospital with nausea and weakness, and found to have cortisol of 4.4mcg/dL, ACTH of 12 pg/mL and UFC of 2.8 ug/d requiring short course of hydrocortisone for adrenal insufficiency. One year later, she presented with hip fracture, worsening weakness, plethora, and facial swelling. UFC was 1,338.3mcg/24 hr(4.0–50.0 mcg/24 hr), AM serum cortisol 58.8mcg/dL and ACTH 304.7 pg/mL. In addition to severe osteoporosis with hip fracture, she had hypertension and impaired fasting glucose. She was treated with Ketoconazole 200mg daily which was titrated until AM cortisol levels decreased from 58.8 mcg/dL to 20 mcg/dL. Patient was discharged on Ketoconazole with plan to complete a Dotatate scan to evaluate for ectopic ACTH production which resulted negative. Shortly thereafter, she returned with hypotension, nausea, and fatigue. Repeat cortisol level was 2.3 mcg/dL with ACTH of 27.6 pg/ml. Ketoconazole was discontinued and patient was started on hydrocortisone for adrenal insufficiency. Hydrocortisone was gradually tapered off. Pituitary MRI and IPSS are planned for further evaluation. Discussion: Cyclic Cushing’s syndrome is diagnosed with three peaks and two troughs of cortisol production. Diagnosis and treatment are challenging since the cycles of hypercortisolism can occur sporadically and rapid fluctuations in cortisol makes it difficult to localize a source. Cortisol fluctuations can affect quality of life and result in complications such as diabetes, hypertension, and osteoporosis. Prompt identification of the source of the Cyclic Cushing’s syndrome is vital to pursue definitive therapy. However, in 9% of cases, there is no identifiable source. In such cases, medical therapy is warranted.