Objective: 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. Methods: 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. Results: Four-hundred and forty-four datasets were available for analysis (primary AI (PAI), nZ254; secondary AI (SAI), nZ190). 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%, PZ0.003). 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)Z2.02, 95% confidence interval (CI) 1.05-3.89, PZ0.036). In SAI, female sex (ORZ2.18, 95% CI 1.06-4.5, PZ0.035) and diabetes insipidus (ORZ2.71, 95% CI 1.22-5.99, PZ0.014) were associated with higher crisis incidence. Conclusion: 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.

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SummaryContext Recent studies suggest that current glucocorticoid replacement therapies fail to completely restore well-being in patients with adrenal insufficiency (AI). Objective The objective of this study was to investigate healthrelated quality of life (QoL) in patients with AI depending on dose and frequency of daily intake of hydrocortisone (HC). Design and patients In a cross-sectional study, primary and secondary AI patients were contacted and asked to complete three validated self-assessment questionnaires , Giessen Complaint List (GBB-24), Hospital Anxiety and Depression Scale (HADS)]. HC doses were corrected for body surface area. Results were compared with sex-and age-matched controls drawn from the questionnaire-specific reference cohort. Results Completed questionnaire sets were available from 334 patients on HC (primary AI n = 194; secondary AI n = 140). Patients on higher doses of HC (>30 mg/day) showed significantly impaired subjective health status in two of eight SF-36 dimensions, and three of five GBB-24 scales compared with those on lower HC doses. No significant differences in QoL were found between lower HC doses (15-30 mg/day) or between primary or secondary AI. Patients on HC with thrice daily intake showed significantly impaired QoL in one of eight SF-36 dimensions (15-20 mg/day, 20-25 mg/day), in one of five GBB-24 scales (15-20 mg/day), as well as higher anxiety scores. Conclusions Health-related QoL was impaired in patients with primary and secondary AI. HC doses above 30 mg/day were associated with a worse health status. Thrice daily intake of HC was not superior to twice daily intake. Our data support the perception that current replacement strategies are still insufficient to fully restore well-being and daily performance.

Context: Recent studies have suggested that current glucocorticoid replacement therapies fail to fully restore well-being in patients with adrenal insufficiency (AI). Objective: 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. Results: Of the 883 patients identified, 526 agreed to participate in the study. Completed questionnaire sets were available from 427 patients (primary AI nZ232; secondary AI nZ195). 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. Conclusions: 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.European Journal of Endocrinology 159 811-817

HRQoL in CAH is only mildly impaired and significantly less than in PAI patients. Differences between PAI and CAH in HRQoL suggest relevant modulating factors of HRQoL other than hormone replacement therapy itself.

Mutations in the gene encoding 21-hydroxylase cause the most common form of congenital adrenal hyperplasia (CAH) [1,2]. Clinical management aims at replacement therapy with glucocorticoids and mineralocorticoids to correct hypocortisolism, hypoaldosteronism and to normalize hyperandrogenism, which often results in higher glucocorticoid doses than in primary adrenal insufficiency (PAI) [3]. Physicians face the problem to adjust to ideal dosage of glucocorticoids in order to avoid under-as well as overtreatment [4,5]. Undertreatment may result in higher risk of adrenal crisis, disturbed pubertal development, reduced final height, infertility, and androgen-driven insulin resistance, however overtreatment results in obesity, impaired glucose homeostasis, infertility and reduced bone mineral density (BMD) [1]. However, the best regimen and approach to Improvement of health-related quality of life in adult women with 21-hydroxylase deficiency over a seven-year period Adjustment for age and sex was performed by transformation of score values into age-and sex-adjusted Z-scores using data sets from respective normative groups. Data regarding glucocorticoid therapy, clinical and hormonal parameters were assessed. We found that two of eight scales of SF-12 showed a significant improvement and four of eight scales a positive trend to better scores. No significant changes were seen in scores for HADS or for steroid hormone levels. Daily hydrocortisone equivalent dose per body surface significantly decreased over the study period. No changes in BMI were observed over the study period. We conclude that improvement of HRQoL in adult female 21-OHD patients is possible. Several factors might be involved in this improvement including reduced daily hydrocortisone equivalent dose per body surface.

The serum proteins were fractionated on Sephadex G 200, their hydroxyproline content determined. Three protein peaks (I-III) containing different hydroxyproline concentrations could be separated. In connective tissue disorders accompanied by increased collagen synthesis or collagen degradation, an elevation of hydroxyproline was found in peak II. An increase of hydroxyproline always was associated with an increase of the serum proteins in the same fractions. Hydroxyproline serum levels above normal obviously are due to a certain capacity of the serum proteins binding free hydroxyproline and collagen metabolites.

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