Endocrine Abstracts

Introduction: Cyclic Cushing’s syndrome is a rare disease characterized by episodes of cortisol hypersecretion followed by periods of normal cortisol secretion, ranging from days to months. We report a case of cyclic Cushing’s syndrome whose diagnosis was delayed for years.

Case presentation: A 50-year-old female with a 16-year history of non-Hodgkin’s lymphoma was referred to the Endocrinology Unit due to suspected hypercortisolemia. She had a 2-year history of hirsutism, supraclavicular fat pads, irritability, and insomnia. During her first admission, ACTH-dependent hypercortisolemia [midnight serum cortisol: 404.5 nmol/l, cortisol levels post-dexamethasone suppression test (DST) 127.42 nmol/l, ACTH: 14.3 pg/ml] was confirmed. Patient was, also, diagnosed with osteoporosis, arterial hypertension, and dyslipidemia. Pituitary MRI was performed and a 4 mm lesion on the left side of the gland was identified. CRH and DDAVP stimulation tests were performed which were both indicative of Cushing’s disease. Given, however, the size of the pituitary lesion, an inferior petrosal sinus sampling (IPSS) was scheduled. Patient was re-admitted 2 weeks later for the IPSS, and, interestingly, her hormonal investigations were found to be normal [24h urinary free cortisol levels (31.5 mg/24h, NR<80), midnight serum cortisol (118 nmol/l), and cortisol post-DST levels (29.3 nmol/l)]. Because of the conflicting results between the later and the previous admission, the above-mentioned tests were repeated 1 month later, which, this time, confirmed hypercortisolemia [24h urinary free cortisol levels (178 mg/24h, NR<80), midnight serum cortisol (300 nmol/l), and cortisol post-DST levels (218 nmol/l)]. Taking into account the results of the hormonal tests, the presence of a pituitary microadenoma, and the patient’s sex, a working diagnosis of cyclical Cushing’s disease was made. To confirm the diagnosis, two days later, an IPSS with desmopressin stimulation was performed but ACTH-dependent hypercortisolemia was not detected indicating disease shift to another inactive phase. A second IPSS with desmopressin stimulation was performed 1 month later, with the patient’s disease being in active phase, as demonstrated by elevated midnight serum cortisol levels for 2 consecutive days prior to IPSS, and the results were consistent with left-sided pituitary ACTH hypersecretion. Subsequently, a transsphenoidal pituitary surgery was successfully performed and the patient’s Cushing’s disease is currently on remission.

Conclusion: Our case demonstrates that the diagnosis of cyclic Cushing’s syndrome is particularly challenging. During a period of inactivity, tests may be negative. However, if the clinical suspicion is high, follow-up with repeated screening tests are suggested to establish the final diagnosis.