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Benjamin Bleicken, Stefanie Hahner, Melanie Loeffler, Manfred Ventz, Bruno Allolio, and Marcus Quinkler


Recent studies have suggested that current glucocorticoid replacement therapies fail to fully restore well-being in patients with adrenal insufficiency (AI).


To investigate the effect of different glucocorticoid preparations used for replacement therapy on subjective health status (SHS) in AI.

Design and patients

In a cross-sectional study, primary and secondary AI patients were contacted by mail. Individual glucocorticoid replacement regimens, underlying diagnoses and comorbidities were verified by questionnaires and review of medical records. Patients were asked to complete three validated self-assessment questionnaires (Short Form 36 (SF-36), Giessen Complaint List (GBB-24), and Hospital Anxiety and Depression Scale). Results were compared with sex- and age-matched controls drawn from the questionnaire-specific reference cohort.


Of the 883 patients identified, 526 agreed to participate in the study. Completed questionnaire sets were available from 427 patients (primary AI n=232; secondary AI n=195). AI patients showed significantly impaired SHS compared with controls irrespective of the glucocorticoid used for replacement. The only difference in SHS between patients on prednisolone (PR) and hydrocortisone (all patients and sub-analysis for primary AI) was significant higher bodily pain (lower Z-score in SF-36) in patients on PR (P<0.05, P<0.01 respectively). In patients with secondary AI, the PR group showed significantly (P<0.05) less heart complaints (lower Z-score) in the GBB questionnaire compared with the cortisone acetate group.


Glucocorticoid replacement therapy with PR seems to be equivalent to hydrocortisone regarding SHS in patients with AI. However, SHS remains impaired in all patient groups suggesting a need for further improved glucocorticoid replacement strategies.

Free access

Stefanie Hahner, Melanie Loeffler, Benjamin Bleicken, Christiane Drechsler, Danijela Milovanovic, Martin Fassnacht, Manfred Ventz, Marcus Quinkler, and Bruno Allolio


Adrenal crisis (AC) is a life-threatening complication of adrenal insufficiency (AI). Here, we evaluated frequency, causes and risk factors of AC in patients with chronic AI.


In a cross-sectional study, 883 patients with AI were contacted by mail. Five-hundred and twenty-six patients agreed to participate and received a disease-specific questionnaire.


Four-hundred and forty-four datasets were available for analysis (primary AI (PAI), n=254; secondary AI (SAI), n=190). Forty-two percent (PAI 47% and SAI 35%) reported at least one crisis. Three hundred and eighty-four AC in 6092 patient years were documented (frequency of 6.3 crises/100 patient years). Precipitating causes were mainly gastrointestinal infection and fever (45%) but also other stressful events (e.g. major pain, surgery, psychic distress, heat and pregnancy). Sudden onset of apparently unexplained AC was also reported (PAI 6.6% and SAI 12.7%). Patients with PAI reported more frequent emergency glucocorticoid administration (42.5 vs 28.4%, P=0.003). Crisis incidence was not influenced by educational status, body mass index, glucocorticoid dose, DHEA treatment, age at diagnosis, hypogonadism, hypothyroidism or GH deficiency. In PAI, patients with concomitant non-endocrine disease were at higher risk of crisis (odds ratio (OR)=2.02, 95% confidence interval (CI) 1.05–3.89, P=0.036). In SAI, female sex (OR=2.18, 95% CI 1.06–4.5, P=0.035) and diabetes insipidus (OR=2.71, 95% CI 1.22–5.99, P=0.014) were associated with higher crisis incidence.


AC occurs in a substantial proportion of patients with chronic AI, mainly triggered by infectious disease. Only a limited number of risk factors suitable for targeting prevention of AC were identified. These findings indicate the need for new concepts of crisis prevention in patients with AI.