GP140 Cyclical cushing’s syndrome: a diagnostic challenge

Aims Cyclic Cushing’s syndrome is an uncommon disorder, defined by intermittent episodes of excess cortisol secretion. These episodes occur sporadically. The fluctuating clinical picture and conflicting biochemical findings make Cyclic Cushing’s syndrome challenging to diagnosis. We report a case of Cyclic Cushing’s syndrome is a 6 year old boy and discuss the challenges in diagnosis. Methods A detailed chart review was performed. Data extracted from the medical records included presenting complaint, disease progression, laboratory results, imaging and clinical measurements. Results At 4 years of age the patient presented with a two week history of rapid weight gain, increased appetite, lethargy, polydipsia and polyuria. The child has a background history of speech delay, obesity (weight 29 kg, >99.6thcentile, BMI 23.3 kg/m2), macrocephaly (OFC 56cm, > 97thcentile), and facial freckling. During an in-patient stay, six hourly serum cortisol levels taken over a 48 hour period followed by a dexamethasone suppression test and a 24 hour urinary cortisol collection failed to support a diagnosis of Cushing’s Syndrome. His significant facial freckling -with lip sparing and no mucosal involvement - prompted a Clinical Genetics referral. A diagnosis of Carney Complex (CNC) with a mutation in the PRKAR1A gene was made. The patient continued to have episodes that would suggest episodic hyper-secretion of cortisol. Each episode lasted 3–4 weeks and then resolved. Parents reported 2 episodes in 2016, 1 episode in 2017 and 1 episode in 2018. In early 2018, the patient was admitted to hospital during an acute episode. A diagnosis of Cyclical Cushing’s syndrome was confirmed by very elevated serum cortisol levels, elevated 24 hour urine free-cortisols, failure to suppress to dexamethasone and a very suppressed ACTH level during this admission. MRI and CT of abdomen however failed to reveal any adrenal lesions. Following discussions at multidisciplinary team meetings and with colleagues in adult Endocrinology, a decision was made to proceed with a bilateral adrenalectomy. The patient tolerated the procedure well. His adrenal histology was consistent with subtle changes suggestive of a mild Primary pigmented nodular adrenocortical disease (PPNAD) picture. Following adrenalectomy his symptoms have completely resolved but he will require lifelong Hydrocortisone and Fludrocortisone replacement. Conclusion Our patient has a background history of CNC and PPNAD which has been linked in very occasional cases with Cyclical Cushing’s syndrome. PPNAD is the most common endocrine manifestation of CNC. This case report highlights the difficulty in diagnosing Cyclic Cushing’s syndrome.