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Purpose: Measurement of cortisol concentrations is method dependent. The study aimed to establish assay-specific cut-off limits for cortisol after adrenocorticotropic hormone (ACTH) stimulation, comparing Roche Elecsys Cortisol II immunoassay to liquid chromatography-mass spectrometry (LC-MS/MS), and to assess the impact of patient characteristics, estrogen containing oral contraceptives as well as relation to other adrenocortical steroid hormone dynamics., Methods: One hundred healthy participants underwent a 250 μg ACTH-test, with plasma samples analyzed using ElecsysCortI, ElecsysCortII, and LC-MS/MS. Cortisone, corticosterone, 17-OH-progesterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and testosterone were additionally analyzed with LC-MS/MS. Cut-off limit for a normal cortisol response to the ACTH-test was defined as: 2.5th percentile-1.96 × SE., Results: ElecsysCort II measured cortisol concentrations 21% (95% CI: 19-22%) lower than ElecsysCort I. Cut-off limits for cortisol 30 and 60 min after ACTH were 426 and 485 nmol/L (ElecsysCort II) and 411 and 470 nmol/L (LC-MS/MS). Cut-offs were unaffected by gender, or body-composition. The ACTH-test resulted in significantly increased adrenocortical steroid hormones, except for decreased cortisone concentrations (both sexes), and decreased testosterone in men (1.9 nmol/L, 95% CI: 1.3-2.5). Testosterone was increased in women (0.07 nmol/L, 95% CI: 0.02-0.13)., Conclusion: ElecsysCort II has high analytical performance and yields significantly lower cortisol concentrations than prior polyclonal immunoassays. This clinically relevant difference underscores the necessity for revised cut-off limits for improved diagnostic precision. Suggested 30-minute cortisol cutoff limits are 411 nmol/L (LC-MS/MS) and 426 nmol/L (ElecsysCort II). Adrenocortical steroids increased upon ACTH stimulation, except for cortisone in both sexes and testosterone in men, both of which decreased., (© 2024. The Author(s).)

Purpose: Studies have suggested improved metabolic profiles in patients with adrenal insufficiency treated with dual-release hydrocortisone (DR-HC) compared with conventional hydrocortisone (C-HC). This study investigates the effect of DR-HC compared with C-HC treatment on five health variables: diurnal salivary cortisol/cortisone, body composition, bone health, glucose metabolism, lipids, and blood pressure., Methods: Prospective study of 27 participants (24 men) with secondary adrenal insufficiency with measurements during stable C-HC and 16 weeks after treatment switch to DR-HC., Outcomes: Diurnal salivary-cortisol/cortisone, body composition assessed by Dual-Energy X-ray absorptiometry scan, bone status indices (serum type I N-terminal procollagen [PINP], collagen type I cross-linked C-telopeptide [CTX], osteocalcin, receptor activator kappa-B [RANK] ligand, osteoprotegerin, and sclerostin), lipids, haemoglobin A 1c (HbA 1c ), and 24-hour blood pressure., Results: After the switch to DR-HC, the diurnal salivary-cortisol area under the curve (AUC) decreased non-significantly (mean difference: -55.9 nmol/L/day, P = 0.06). The salivary-cortisone-AUC was unchanged. Late-evening salivary-cortisol and cortisone were lower (-1.6 and -1.7 nmol/L, P = 0.002 and 0.004). Total and abdominal fat mass (-1.5 and -0.5 kg, P = 0.003 and 0.02), HbA 1c (-1.2 mmol/mol, P = 0.02), and osteocalcin decreased (-7.0 µg/L, P = 0.03) whereas sclerostin increased (+41.1 pg/mL, P = 0.0001). The remaining bone status indices, lipids, and blood pressure were unchanged., Conclusion: This study suggests that switching to DR-HC leads to lower late-evening cortisol/cortisone exposure and a more favourable metabolic profile and body composition. In contrast, decreased osteocalcin with increasing sclerostin might indicate a negative impact on bones., Clinical Trial Registration: EudraCT201400203932., (© 2024. The Author(s).)

Purpose: Replicating the physiological cortisol secretion is key in the treatment of glucocorticoid insufficient individuals and optimization may enhance quality of life. The study investigates fatigue measured by ecological momentary assessments in patients treated with conventional hydrocortisone compared with once-daily dual-release hydrocortisone (Plenadren)., Methods: A 21-week open-label switch pilot trial included 30 patients with adrenal insufficiency due to hypopituitarism. Fatigue was assessed four times daily for 20 days using a momentary item version of the Multidimensional Fatigue Inventory on patients' usual hydrocortisone regimen. Participants switched treatment to an identical daily dose of Plenadren for 16 weeks where fatigue assessments were repeated. Change in fatigue and diurnal variation of fatigue was analyzed using mixed models for repeated measurements., Results: In four out of five fatigue subscales fatigue was significantly reduced 0.7-1.1 points (scales ranging from 4 to 20), when treated with Plenadren compared with conventional hydrocortisone, corresponding to small effect sizes below the scale-specific minimal important changes. However, 33% of the participants completing the study (9/27) experienced reductions in fatigue above the minimal important change. On Plenadren, we found larger between-person variances and smaller within-person variances. Finally, we identified diurnal fatigue curves for both treatments., Conclusions: The Plenadren-related reduction in fatigue was significant but not necessarily of clinical importance when looking at a group level. However, there was a large interindividual variation in treatment effect, why patients with a large benefit in quality of life should be identified. Future RCTs should be powered to detect the effect magnitudes identified here.