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 K. Stalla; Naila Aslam; Helen Coope; Kerry Maltby; John Porter; Jo Quirke; Richard John M. Ross

doi:10.1530/endoabs.99.P13

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Endocrine Abstracts (2024) 99 P13 | DOI: 10.1530/endoabs.99.P13

ECE2024 Poster Presentations Adrenal and Cardiovascular Endocrinology (95 abstracts)

Morning cortisol levels in patients with established primary adrenal insufficiency

Alessandro Prete ^1,1 , Verena Theiler-Schwetz ¹ , Wiebke Arlt ² , Irina-Oana Chifu ³ , Birgit Harbeck ^4,5 , Catherine Napier ⁶ , JohnD.C. Newell-Price ⁷ , Aled Rees ⁸ , Nicole Reisch ⁹ , GünterK. Stalla ¹⁰ , Naila Aslam ¹¹ , Helen Coope ¹¹ , Kerry Maltby ¹¹ , John Porter ¹¹ , Jo Quirke ¹¹ & Richard John M. Ross ⁷

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¹University of Birmingham, UK; ²MRC Laboratory of Medical Sciences, UK; ³University Hospital Würzburg, Würzburg, Germany; ⁴University Medical Center Hamburg-Eppendorf, Hamburg, Germany; ⁵amedes experts, Hamburg, Germany; ⁶Newcastle University, UK; ⁷The University of Sheffield, UK; ⁸Cardiff University, UK; ⁹Klinikum der Universität München, München, Germany; ¹⁰Ludwig Maximilian University of Munich, München, Germany; ¹¹Diurnal, UK

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 ². 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 ~0700 h and measured in a central laboratory by ADVIA Centaur® immunoassay with the lower limit of detection <14 nmol/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 >50 nmol/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 >50 nmol/l showed very similar results suggesting that the detectable cortisol was not an artefact and likely due to background cortisol secretion.

References: 1. Bornstein SR, et al. J Clin Endocrinol Metab 2016;101:364–89.