Endocrine Abstracts

A 41 year-old male was referred urgently from secondary care with high suspicion of Cushing’s syndrome. His past medical history included psychosis and bipolar disorder, previous low impact foot fractures, rib fractures on coughing and spinal wedge fractures on X-ray, all within the last 5 years. He was taking quetiapine 300 mg modified-release and amitriptyline 10 mg daily, and tramadol 50 mg as needed. The patient reported decreasing mobility with increasing back pain, easy bruising, a change in facial appearance and one stone in weight gain over the last 5 years. He was a non-smoker and rarely consumes alcohol. On examination, he exhibited florid cushingoid appearance with moon face, facial plethora, thin skin, multiple new purple striae, central adiposity, a very large interscapular fat pad and severe proximal myopathy. There were no visual field defects on confrontational bedside testing. Initial biochemical investigations revealed unsuppressed cortisol (576 nmol/l) on 1 mg overnight dexamethasone suppression test (ONDST). 24 hours urine cortisol concentration was raised at 683 nmol/day (NR<132). Confirmatory testing with 48 hours low dose dexamethasone suppression test (LDDST) demonstrated failure to suppress serum cortisol level at 588 nmol/l. A diagnosis of Cushing’s syndrome was made. His unsuppressed random ACTH (adrenocorticotropic hormone) level at 53 ng/l (NR 7.2-63 ng/l) pointed towards ACTH-dependent Cushing’s syndrome. Other pituitary hormonal profile revealed central hypogonadism (low testosterone level at 4.6 nmol/l (NR 8.6-29 nmol/l) with unstimulated gonadotrophins) and intact thyroidal axis. His bone density scan confirmed osteoporosis at the level of hip and lumbar spine. MR imaging of his pituitary gland did not identify any lesion within the fossa. Given that the pre-test probability for Cushing’s disease was high, we proceeded with a peripheral desmopressin (DDAVP) stimulation test using 10 mg intravenous desmopressin. The results showed a 100% rise in serum cortisol level and more than 100% rise in ACTH concentrations within 30 minutes of DDAVP injection, thus strongly suggesting Cushing’s disease. The patient is awaiting Inferior Petrosal Sinus Sampling (IPSS) before proceeding with trans-sphenoidal pituitary exploration by our dedicated neurosurgeon.

Conclusion: Diagnosis of Cushing’s disease requires a meticulous and systematic assessment along with clinical correlation and pre-test probability. No single test offers robust diagnostic performance but rather a combination of clinical assessment, biochemical investigations and specialised imaging is needed to guide multi-disciplinary approach to management.