A 53-year-old woman presented with poorly controlled type 2 diabetes and recent diagnosis of hypertension and depression. She reported weight gain, tiredness and weakness.
She had cushingoid appearance, thin skin, bilateral proximal myopathy and central adiposity with purple striae on abdomen.
She was on Metformin, Gliclazide, Dapagliflozin, Liraglutide, Amlodipine, Metoprolol and venlafaxine.
Investigations revealed elevated Cortisol 1049mmol/L (100-535), ACTH 149ng/L (9-51) and 24hour urinary free cortisol 3255nmol (<110) levels. Anterior pituitary assessment revealed hypogonadotrophic hypogonadism. A 1mg overnight dexamethasone suppression test failed to suppress cortisol (Pre- 700 and post-dex 750 nmol/L). A 8 mg overnight dexamethasone suppression test induced partial suppression (from 1,050 to 500 nmol/L). MRI showed no adenoma but a small thickening on the right side of the pituitary gland. CT scan of the chest, abdomen and pelvis showed mild bilateral adrenal hyperplasia and 3.5cm mass on the upper pole of left kidney. PET-FDG scan was suggestive of renal cell carcinoma.
Differential diagnosis suggests possible renal cell carcinoma either presenting with paraneoplastic manifestation or secreting ACTH from a pituitary lesion. Bilateral adrenal hyperplasia may suggest ectopic ACTH production.
Uneventful nephrectomy and histology confirmed clear cell renal carcinoma but ACTH staining was negative. She improved symptomatically and her cortisol and ACTH levels normalised.
Renal cell carcinoma is a rare cause of ectopic Cushing’s syndrome(1). Rapidly growing tumours mostly stain negative for ACTH and can be explained by high ACTH and low peptide hormone levels (2,3). Normalisation of ACTH and cortisol in conjunction with improvement in symptoms may suggest cure for Cushing’s syndrome.
However, based on above investigations, Cushing’s disease remains a differential whilst the source of the condition remains unclear. Postoperative improvement may only be coincidence in such cases and cure may not be concluded as cyclical Cushing’s syndrome is still a possibility.