Urinary steroid metabolites in a case of florid Ectopic Cushing's syndrome and clinical correlations

A 51-year old woman was admitted with multiple cerebral, pulmonary and intra-abdominal abscesses. The combination of apparent immunosuppression, obesity, diabetes mellitus, hypertension, hypokalaemia, osteoporotic fractures and bilateral shoulder avascular necrosis led to a clinical diagnosis of Cushing's syndrome (CS). This was biochemically confirmed as follows: midnight serum cortisol 4275 nmol/L (60-250), non-suppressed overnight dexamethasone suppression test, raised salivary cortisol 716 nmol/L (5-46) and ACTH 639 ng/L (0-46). Urinary free cortisol was elevated >75,000 nmol/L (<165). Urinary steroid metabolites measured by Gas Chromatography Mass Spectrometry were markedly increased: tetrahydrocortisol (THF) 219024 µg/24h and tetrahydrocortisone (THE) 88848 µg/24h. The (THF+5αTHF)/(THE) ratio was 2.8 (≤1). Pituitary MRI was unremarkable and whole body CT scanning showed a thymic tumour and bilateral adrenal hyperplasia. Urinary 5HIAA was marginally raised with a normal chromogranin A. She underwent a thymectomy which confirmed a 'paraganglioid' variant of a thymic carcinoid tumour. We describe a case of ACTH-secreting thymic carcinoid that presented with florid clinical and biochemical features of CS, but no carcinoid syndrome. The (THF+5αTHF)/(THE) ratio is reported to be a useful indicator in differentiating the aetiologies of CS, although this was not the case in our patient. In this article we examine the degree to which the various urinary steroid metabolites were raised in this patient with florid CS and compare them with some normative data obtained from patients with either Cushing's disease or the normal population. We hereby postulate that steroid metabolomics profiling may be helpful in establishing the differential diagnosis of CS.