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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Context: Adrenal and extra-adrenal phaeochromocytoma are chromaffin cell-derived tumours that are discovered due to classical symptom triad with headache, sweating and palpitations combined with persistent or paroxysmal hypertension. However, an increasing proportion of phaeochromocytoma seems to be discovered incidentally upon abdominal imaging. Objective: To specify the exact circumstances of discovery of adrenal and extra-adrenal phaeochromocytoma. Design and patients: Four German endocrine centres participated in this retrospective study. Medical records of 201 patients with adrenal and extra-adrenal phaeochromocytoma who were diagnosed between 1973 and 2007 were analyzed. Results: The typical triad of symptoms was found only in 10% of cases. Ten percent of patients presented were without clinical symptoms and 6.1% were normotensive. Documented blood pressure peaks occurred in 44.1% of cases. In 24 patients (12.2%), phaeochromocytoma was malignant. Before 1985, !10% of cases were incidentally discovered, whereas thereafter the frequency was O25% (29.4% of the total study population). Patients with incidentally detected phaeochromocytoma were significantly older (53.1G1.9 vs 47.0G1.3 years; P!0.05) and often had less blood pressure peaks (37.0 vs 70.7%; P!0.001) than patients in whom the diagnosis was suspected on clinical grounds. Of phaeochromocytomas 94.4% were intra-adrenal tumours, of which 12.9% were bilateral. Bilateral tumours were significantly smaller than unilateral tumours (36.6G14.7 vs 52.5G34.3 mm; P!0.05), whereas extra-adrenal tumours had a mean diameter of 52.6G28.7 mm. Conclusions: Owing to better availability and accessibility of imaging procedures, the number of incidentally discovered phaeochromocytoma is increasing and reaches nearly 30% in our study population. Every adrenal incidentaloma should be investigated for the presence of phaeochromocytoma.

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.

Objective: Patients with adrenal insufficiency (AI) have impaired health-related quality of life (HRQoL), which is thought to be in part due to unphysiological glucocorticoid replacement therapy. The aim was to compare once-daily hydrocortisone (HC) dual-release tablet (modified-release) with conventional HC therapy regarding clinical data and HRQoL. Design and methods:We conducted an open, prospective trial at one endocrine center. There were 15 of 26 patients with primary AI, nine of 18 patients with secondary AI, and six congenital adrenal hyperplasia patients switched to modifiedrelease HC therapy by their own decision. We evaluated clinical outcome and disease-specific HRQoL by using AddiQoL questionnaire at baseline and at follow-up (median 202 days (85-498)). Results: Patients on modified-release HC (nZ30) showed significant decreases in BMI (26.0G0.75-25.6G0.71, P for changeZ0.006) and HbA1c (6.04G0.29-5.86G0.28, P for changeZ0.005), whereas patients remaining on conventional HC (nZ20) showed no change in these parameters (P for interactionZ0.029 and 0.017 respectively). No significant change in AddiQoL score were found in the modified-release HC group (83.8 baseline and 84.9 at follow-up; P for changeZ0.629). In the conventional HC group, there was a significant decrease in scores (84.0 baseline and 80.9 at follow-up; P for changeZ0.016), with a between-treatment P for interaction of 0.066. The fatigue subscore of AddiQoL showed the same pattern with a significant decrease (P for changeZ0.024) in patients on conventional HC therapy (P for interactionZ0.116). Conclusions: Modified-release HC decreases BMI and HbA1c compared with conventional HC treatment. In addition, it seems to stabilize HRQoL over time.

Adult PAI and CAH patients on low glucocorticoid doses showed normal BMD within the normal reference range. The use of longer acting prednisolone resulted in significantly lower BMD in PAI. In addition, DHEA treatment may have a beneficial effect on bone in Addison's women.

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.