Quantifying variability in ambulatory 24-hour tissue hormones for personalised management of hormonal replacement in patients with adrenal insufficiency

Ileana R. Botusan; Katarina Berinder; Paal Methlie; Thomas Upton; Eder Zavala; Georgina Russell; Katerina Simunkova; Dimitra Vassiliadi; Isabella Marinelli; Marianne Aardal Grytaas; Stylianos Tsagarakis; Stafford Lightman; Eystein Sverre Husebye; Olle Kampe; Marianne Oksnes; Sophie Bensing

doi:10.1530/endoabs.99.RC3.3

RC3.3

Prev Next

Section Contents Cite

Endocrine Abstracts (2024) 99 RC3.3 | DOI: 10.1530/endoabs.99.RC3.3

ECE2024 Rapid Communications Rapid Communications 3: Adrenal and Cardiovascular Endocrinology | Part I (7 abstracts)

Quantifying variability in ambulatory 24-hour tissue hormones for personalised management of hormonal replacement in patients with adrenal insufficiency

Ileana R. Botusan ^1,2 , Katarina Berinder ^1,2 , Paal Methlie ^3,4 , Thomas Upton ⁵ , Eder Zavala ⁶ , Georgina Russell ⁵ , Katerina Simunkova ³ , Dimitra Vassiliadi ⁷ , Isabella Marinelli ⁶ , Marianne Aardal Grytaas ^3,4 , Stylianos Tsagarakis ⁷ , Stafford Lightman ⁵ , Eystein Sverre Husebye ^3,4 , Olle Kämpe ^1,2 , Marianne Øksnes ^3,4 & Sophie Bensing ^1,2

Views

Author affiliations

¹Karolinska Institutet, Stockholm, Sweden; ²Karolinska University Hospital, Stockholm, Sweden; ³University of Bergen, Bergen, Norway; ⁴Haukeland University Hospital, Bergen, Norway; ⁵University of Bristol, Bristol, United Kingdom; ⁶University of Birmingham, Birmingham, United Kingdom; ⁷Evangelismos Hospital, Athens, Greece

Background: Recently, we have shown that ambulatory 24-hour dynamic steroid profiling using the newly developed U-RHYTHM system is possible and presented the circadian and ultradian rhythmicity of adrenal hormones in a healthy cohort. With U-RHYTHM, multiple hormones can be sampled simultaneously, and the free active hormones can be measured in local tissue where the effect is exerted. Thus the hormone fingerprint resulting from replacement therapy in individual patients can be visualized and compared to the normative references throughout the day.

Aim: To assess 24-hour profiles of free cortisol and metabolites in patients with Addison´s disease (AD) on different glucocorticoid replacement therapies (GRT) and compare the results with healthy volunteers (HV).

Material and Methods: The study was performed within the frame of a multi-center EU-funded H2020 ULTRADIAN study. HV group, enrolled 214 subjects, aged 18 to 68 years and with BMI 16 to 29.9 kg/m². Patients group enrolled 41 subjects with established AD within the same age span. All were 21 hydroxylase autoantibody positive. Median duration of AD was 6.5 years (IQR: 3.25-19.75). Median BMI was 25.2 kg/m². (IQR: 22.75-27). The enrollment was independent of their GRT regimes: 27 hydrocortisone, 9 cortisone-acetate, 4 modified release hydrocortisone and 1 pump. Their regular medication was not changed. Twenty-minute microdialysis fractions were collected ambulatory from subcutaneous tissue over 24 h using the portable fraction collector, U-RHYTHM. Steroid hormones were analyzed by ultrasensitive liquid chromatography tandem mass spectroscopy (LC-MS/MS). Dynamic biomarkers: area under the curve, concentration peak post -dose and time to peak were used to define hormone pattern differences, and to assess the “time in range” for patients compared with the profiles of HV.

Results: The U-RHYTHM ambulatory system was well tolerated, not disturbing the normal daily activities or sleep and 24-hour dynamic steroid profiling revealed marked interindividual variations partially depending on GRT and dosing-regime. Continuous overnight steroid profiling in patients was possible in ambulatory, without disturbing sleep. Tissue cortisol exposure expressed as a percentage of total (cortisol + cortisone) showed higher levels in patients AD compared with HV, throughout the day (8 am to 2 am) with levels even higher than in HV with high BMI (>25 kg/m²). The exception was during night when, cortisol was very low in patients with AD.

Conclusion: Ambulatory 24-hour microdialysis sampling may provide a tool for precision medicine in AD, creating the opportunity for individual dose adjustment particularly in patients who are not well on current GRT.