Immunoassay versus LC-MS/MS cortisol measurement during osilodrostat treatment of ACTH-dependent Cushing syndrome: a case report  — ASN Events
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Immunoassay versus LC-MS/MS cortisol measurement during osilodrostat treatment of ACTH-dependent Cushing syndrome: a case report  (#387)

Kajanan Parameshwaran 1 , Brian Su 1 , Jonathan Kwan 1 , Veronica Wong 1 , Linda Wu 1 , Kirtan Ganda 1 , Shailja Tewari 2 , Daniel Yagoub 3 , Kevin Mantik 3 , Mark Cooper 1 , Phoebe Stanford 4
  1. Department of Endocrinology and Metabolism, Concord Repatriation General Hospital, Concord , NSW, Australia
  2. Diabetes and Endocrinology, Canterbury Hospital, Campsie , NSW, Australia
  3. New South Wales Health Pathology, Prince of Wales Hospital, Randwick , 2031, Australia
  4. New South Wales Health Pathology, Concord Repatriation General Hospital, Concord, NSW, Australia

Background 

Osilodrostat is a steroidogenesis inhibitor effective in treating ACTH-dependent Cushing syndrome.1 Osilodrostat primarily inhibits 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2), and thus its mechanism of action is analogous to that of the older steroidogenesis inhibitor, metyrapone.1 The use of immunoassay to monitor serum cortisol in patients treated with metyrapone has been considered unreliable due to assay cross-reactivity with cortisol precursors (e.g. 11-deoxycortisol) leading to positive bias.2 It is unknown whether this concern applies to osilodrostat, particularly with newer, more specific immunoassays. 

 

Methods 

A 68-year-old female with severe ACTH-dependent Cushing syndrome was treated with osilodrostat whilst undergoing further investigations to identify the source of excess ACTH. Paired serum samples were collected for measurement of cortisol using immunoassay (Roche Cortisol II) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), as well as serum 11-deoxycortisol by LC-MS/MS, before and after commencement of osilodrostat. Differences in cortisol measurement between the two methods were assessed. 

 

Results 

Serum cortisol measurements using immunoassay and LC-MS/MS are provided in Table 1. Prior to commencement of osilodrostat, cortisol measured by immunoassay (1347 nmol/L) was over-estimated by 26% compared to LC-MS/MS (997 nmol/L). This relative difference was reduced after commencing osilodrostat 4 mg daily (12.0-13.3%) and decreased further with increasing dose (7 mg daily: 9.8%; 10 mg daily: 3.6%). Serum 11-deoxycortisol did not correlate with immunoassay bias; 11-dexoycortisol value was low at baseline (2.8 nmol/L) when bias was greatest and rose 3-fold during up-titration (7.4-9.4 nmol/L) while bias fell.  

 

Conclusion 

Discordance between immunoassay and LC-MS/MS decreased with osilodrostat treatment in our patient, with no consistent relationship to serum 11-deoxycortisol, suggesting an alternative cause for the initial positive bias. After commencing osilodrostat, the degree of discordance in this case was within acceptable limits (<15%) for the use of immunoassay to monitor treatment response and the development of adrenal insufficiency.  

  1. 1. Araujo-Castro M, Lamas C, Nowak E, Newell-Price J, Reincke M, Castinetti F. Update and Practical Recommendations for the Use of Medical Treatment of Cushing Syndrome. Endocr Rev. May 13 2026;47(3):301-328. doi:10.1210/endrev/bnaf042
  2. 2. Monaghan PJ, Owen LJ, Trainer PJ, Brabant G, Keevil BG, Darby D. Comparison of serum cortisol measurement by immunoassay and liquid chromatography-tandem mass spectrometry in patients receiving the 11β-hydroxylase inhibitor metyrapone. Ann Clin Biochem. Sep 2011;48(Pt 5):441-6. doi:10.1258/acb.2011.011014