Endocrine Abstracts

Background: Metyrapone is commonly used in medical management of Cushing’s syndrome. It inhibits 11-β hydroxylase, which catalyses the conversion of 11-deoxycortisol to cortisol. The adequacy of metyrapone blockade can be assessed either clinically or biochemically using a target mean serum cortisol 150–300 nmol/l. Cortisol is normally measured by immunoassay.

Case report: A 21-year-old female presented with clinical and biochemical features of cortisol excess. 0900 h cortisol and basal ACTH were elevated at 1,168 nmol/l and 49 ng/l respectively. 24-h urinary free cortisol was markedly raised at 2,014 nmol/24 h (NR<200 nmol/24 h). There was failure to suppress cortisol following 1 and 8 mg overnight dexamethasone suppression tests (cortisol 623 and 94 nmol/L). MRI revealed a 7 mm left-sided pituitary adenoma and baseline cortisol day curve demonstrated a mean cortisol of 751 nmol/l. Due to the severity of Cushing’s preoperative medical blockade was initiated. Mean cortisol values on subsequent monthly Metyrapone Day curves were 565, 541 and 867 nmol/l. As cortisol values were markedly above target, metyrapone was increased from 500 mg TDS to 750 mg TDS.

She reported feeling increasingly tired and light-headed and repeat metyrapone day curve demonstrated an elevated mean cortisol of 678 nmol/l. Liquid chromatography-tandem mass spectrometry assay (LC-MS/MS) was then utilised to re-assess her cortisol samples and revealed mean LC-MS/MS cortisol of 87 nmol/l; overestimating cortisol by 591 nmol/l. LC-MS/MS analyses of the previous three samples revealed low mean cortisols of 132, 96 and 104 nmol/L respectively.

Conclusion: Metyrapone causes elevated circulating levels of 11-deoxycortisol which can cross-react in immunoassays. This can result in serum cortisol appearing normal or increased despite genuine hypocortisolaemia. The clinical consequences of this include potentially fatal hypocortisolaemic crisis. This case demonstrates that using LC-MS/MS is essential for accurate assessment of medical blockade with metyrapone. Centres that conduct metyrapone day curves using immunoassay may be exposed to dangerous cortisol overestimation.