Endocrine Abstracts

Case history: A 26 year old female with severe gastro-oesophageal reflux disease was seen in our service for assessment prior to roux-en-Y gastric bypass (RYGB) surgery for this condition. She had additional history of obesity, hypertension, insomnia, cholecystectomy for gallstones and anxiety-depression. At age 18 her weight was 85 kg, BMI 28 kg/m². She gained 40 kg over the subsequent 8 years and in clinic was 123 kg, BMI 41.1 kg/m² with a gynaecoid pattern (waist to hip ratio 0.8). HbA1c was elevated at 6.8% and metformin commenced. She had no features suggestive of endocrine disorders. RYGB surgery was performed in May 2015, but weight loss was disappointing, with a nadir weight of 111 kg reached in February 2016, and her diabetes failing to resolve. This was accompanied by severe upper abdominal pain and worsening psychiatric symptoms including self harm. Repeat examination revealed violaceous abdominal striae. Clinical suspicion of cortisol excess was sufficient to warrant formal exclusion.

Investigation results: An abdominal CT scan to investigate her pain did not find a cause. Intra-abdominal fat volume did not appear high and her adrenals were normal with the exception of a subcentimetre adenoma on the left.

An in-patient low-dose dexamethasone suppression test (LDDST) was conducted, with cortisol and ACTH markedly failing to suppress (nadirs of 559 nmol/l and 40 ng/l respectively). Urinary free cortisol (UFC), however, was only modestly elevated at 565 nmol/day. Both cortisol and ACTH fully suppressed following an 8 mg overnight dexamethasone suppression test (<5 ng/l and 35 nmol/l respectively). Pituitary MRI was equivocal, showing a possible small hypoenhancing lesion.

Discussion: The moderate pre-test suspicion, discrepant mean cortisol and UFC, lack of enlarged adrenals and relatively normal intra-abdominal fat lead to continued diagnostic uncertainty. The effect of RYGB on oral drug absorption, particularly lipophilic drugs such as dexamethasone, add an additional layer of difficulty to the already complex task of correctly diagnosing Cushing’s. Alternative investigative options include the use of an equivalent-dose intravenous low-dose dexamethasone suppression test (to circumvent any potential malabsorption) or scrutiny of serial at-home midnight salivary cortisols.