7692 Morning Cortisol Levels In Patients With Established Primary Adrenal Insufficiency

Alessandro Prete, Verena Theiler-Schwetz, Wiebke Arlt, Irina Oana Chifu, Birgit Harbeck, Catherine Napier, John D C Newell-Price, Aled Rees, Nicole Reisch, Gunter Karl Stalla, Naila Aslam, Helen Coope, Kerry Maltby, John Porter, Jo Quirke, Richard John M Ross

Research output: Contribution to journalAbstractpeer-review

Abstract

Background: Primary adrenal insufficiency (PAI) is rare: prevalence ∼100-140/million and incidence 4:1 000 000/year in Western societies [1]. The diagnosis of PAI is suggested by an early-morning cortisol <140 nmol/L (5 µg/dL) [1]. The commonest cause in adults is autoimmunity (∼90% in Western countries) and it is generally considered progressive once the diagnosis is made, although it has been reported that residual cortisol secretion is present in ∼30% of patients. We have developed a modified-release formulation of hydrocortisone to replace the physiological cortisol circadian rhythm and are undertaking a Double-Blind, Double-Dummy, Two-Way Cross-Over, Randomised, Phase II Study of Modified-Release Hydrocortisones: Chronocort® Versus Plenadren® in PAI. During recruitment, we were surprised by the number of patients who were ineligible as they had detectable morning cortisol levels. 

Methods: Main inclusion criteria: Participants with known PAI on stable glucocorticoid replacement therapy and an early morning pre-dose cortisol <50 nmol/L (1.8 µg/dl). Baseline serum cortisol was taken at ∼0700h and measured in a central laboratory by ADVIA Centaur® immunoassay with the lower limit of detection <14nmol/l (<0.5 µg/dL). 

Results: 86 patients with PAI (autoimmune aetiology in 71), median age 52 years (range 20-73), 60 female, were screened in 8 centres in UK and Germany. 18 (21%) patients were excluded from the study based on morning cortisol >50 nmol/L (1.8 µg/dL), and of those 68 patients who qualified on the main inclusion criteria 51 (59% of screened) had a cortisol <14 nmol/L (<0.5 µg/dL). Of the 18 patients (autoimmune aetiology in 10) excluded based on their morning cortisol level, 9 (50%) were female and 11 (13% of screened), had morning cortisol ≥140 nmol/L (5.0 µ/dL). 12 patients with morning cortisol of >50nmol/L (1.8 µ/dL) were retested and only 2 then qualified; their initial morning cortisol levels were 70 and 51 nmol/L. In patients retested the median difference between retest and the initial sample was 13 nmol/L (range 1-421 nmol/L). 

Conclusions: In patients with an established diagnosis of PAI, the majority had undetectable morning cortisol, but cortisol was detectable in 41% of patients and above 140 nmol/L in 13% confirming previous publications 2. Retesting patients with a cortisol >50nmol/L showed very similar results suggesting that the detectable cortisol was not an artefact and likely due to background cortisol secretion. 1. Bornstein SR, et al. J Clin Endocrinol Metab 2016;101:364-89.2.Pearce SHS, et al. European Journal of Endocrinology (2021) 184, R61–R67
Original languageEnglish
Article numberbvae163.242
Pages (from-to)A130-A130
Number of pages1
JournalJournal of the Endocrine Society
Volume8
Issue numberSupplement_1
DOIs
Publication statusPublished - 5 Oct 2024

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