Endocrine Abstracts

Background: Metyrapone inhibits 11-β hydroxylase and causes a subsequent rise in the cortisol precursor, 11-deoxycortisol. Cortisol measurements by immunoassays are susceptible to interference and reagent antibody cross-reactivity with cortisol precursors when used in patients receiving metyrapone treatment. Clinicians rely on clinical and biochemical features of cortisol excess for dose titration of this medical blockade. The extent of this interference remains unclear. We compared serum cortisol measurement using immunoassay versus liquid chromatography-tandem mass spectrometry (LC-MS/MS) and assessed to see its correlation with metyrapone doses.

Method: We conducted a retrospective analysis of samples from 2015 that had paired measurements of cortisol using both immunoassay and LC-MS/MS. Only patients on metyrapone as a single medical blockade agent were included. Immunoassay of cortisol was performed using Centaur XP analyser.

Results: Nineteen patients were identified. 42% (8/19) had ACTH-dependent Pituitary Cushing’s disease and the rest were ACTH-independent, of which 73% (8/11 patients) had ACTH-independent macronodular adrenal hyperplasia. 72 paired cortisol samples were analysed in total. With increasing daily metyrapone doses of 500, 750, 1,000, 1,500 and 2,250 mg, the mean delta cortisol (difference between immunoassay and LC-MS/MS cortisol levels) also increased by 15, 84, 68, 69 and 210 nmol/l respectively. Cortisol discordances were 7, 33, 33, 44 and 100% respectively. With most patients being on more than 1,500 mg of metyrapone daily, there was significant overestimation of cortisol using immunoassays, which can lead to erroneous clinical decisions for metyrapone dose titrations. Moreover, with target range of mean cortisol of 150–300 nmol/l, this overestimation can mask genuine hypocortisolaemia and result in life-threatening consequences.

Conclusions: There is an exponential rise in cortisol discordance with increasing doses of metyrapone and clinicians need to be aware if using immunoassays for metyrapone day curves. Liquid chromatography-tandem mass spectrometry should be the gold standard platform used for cortisol measurement for patients on metyrapone treatment.