Quality of Life in European Patients with Addison's Disease: Validity of the Disease-Specific Questionnaire AddiQoL

Objective: Individuals with primary adrenal insufficiency (PAI) or congenital adrenal hyperplasia (CAH) receive life-long glucocorticoid (GC) replacement therapy. Current daily GC doses are still higher than the reported adrenal cortisol production rate. This GC excess could result in long-term morbidities such as osteoporosis. No prospective trials have investigated the long-term effect of GC dose changes in PAI and CAH patients. Methods: This is a prospective and longitudinal study including 57 subjects with PAI (42 women) and 33 with CAH (21 women). Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry at baseline and after 2 years. Subjects were divided into three groups (similar baseline characteristics) depending on changes in daily hydrocortisone equivalent dose (group 1: unchanged 25.2G8.2 mg (meanGS.D., nZ50); group 2: increased 18.7G10.3 to 25.9G12.0 mg (nZ13); group 3: decreased 30.8G8.5 to 21.4G7.2 mg (nZ27)). Results: Subjects in group 1 showed normal lumbar and femoral Z-scores which were unchanged over time. Group 2 subjects showed a significant decrease in femoral neck Z-scores over time (K0.15G1.1 to K0.37G1.0 (P!0.05)), whereas group 3 subjects showed a significant increase in lumbar spine and hip Z-scores (L1-L4: K0.93G1.2 to -0.65G1.5 (P!0.05); total hip: K0.40G1.0 to K0.28G1.0 (P!0.05)). No changes in BMI over time were seen within any group. Reduction in GC dose did not increase the risk of adrenal crisis. Conclusion: This study demonstrates for the first time that cautious reduction in hydrocortisone equivalent doses leads to increases in BMD, whereas dose increments reduced BMD. These data emphasize the need for the lowest possible GC replacement dose in AI patients to maintain health and avoid long-term adverse effects.

Section: Measurementsmentioning

confidence: 99%

Section: Measurementsmentioning

confidence: 99%

Reduction in daily hydrocortisone dose improves bone health in primary adrenal insufficiency

Schulz

Frey

Cooper

et al. 2016

“…Therefore, it is likely that certain important aspects of QoL impairment in patients with an excess of GCs are not being captured by the QoL-AGHDA. Recently, a diseasespecific questionnaire has been developed for patients with primary AI (39). It is possible that such a questionnaire would have been more appropriate than the one we used, although its properties lack the specificity to capture GHD-related problems.…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

The relationship between glucocorticoid replacement and quality of life in 2737 hypopituitary patients

Ragnarsson

Mattsson

Monson

et al. 2014

Objective: Quality of life (QoL) is impaired in hypopituitary patients and patients with primary adrenal insufficiency. The aim of this study was to analyse the impact of glucocorticoid (GC) replacement on QoL. The main hypothesis was that ACTHinsufficient patients experience a dose-dependent deterioration in QoL. Design, patients and methods: This was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database). Data from 2737 adult GH-deficient (GHD) hypopituitary patients were eligible for analysis. Thirty-six per cent were ACTH sufficient and 64% ACTH insufficient receiving a meanGS.D. hydrocortisone equivalent (HCeq) dose of 22.3G8.7 mg (median 20.0). QoL at baseline and 1 year after commencement of GH replacement was assessed by the QoL-assessment of GHD in adults. Results: At baseline, no significant difference in QoL was observed between ACTH-sufficient and -insufficient patients. Increasing HCeq dose was associated with worse QoL. Patients on HCeq %10 mg had the best and patients receiving R25 mg demonstrated the poorest QoL. At 1 year of GH replacement, the improvement in QoL did not differ between ACTH-sufficient and -insufficient patients, and no association was observed between HCeq dose and QoL improvement. Conclusion: Adult hypopituitary patients with untreated GHD receiving GC replacement have similar QoL as ACTH-sufficient patients. Among ACTH-insufficient patients, there is a dose-dependent association between increasing dose and impaired QoL. This association may be explained by supraphysiological GC exposure although it remains plausible that clinicians may have increased GC doses in order to address otherwise unexplained QoL deficits.

“…This initial tremendous improvement in well-being has deceived expert physicians for some decades and led them to believe that treated patients with adrenal insufficiency lead a largely normal life with a normal life expectancy (1,2,3). Only in recent years, it became evident that restoration of well-being remains incomplete (4,5,6,7,8,9). The reasons for this incomplete recovery of well-being with current replacement regimens are still not fully understood and comprise among others a non-physiological glucocorticoid replacement with an altered diurnal rhythm of cortisol availability (10,11,12,13,14), lack of DHEA (15,16,17) and reduced adrenaline secretion from the adrenal medulla (18,19).…”

Section: Introductionmentioning

confidence: 99%

EXTENSIVE EXPERTISE IN ENDOCRINOLOGY: Adrenal crisis

Allolio

2015

191

230

Adrenal crisis is a life-threatening emergency contributing to the excess mortality of patients with adrenal insufficiency. Studies in patients on chronic replacement therapy for adrenal insufficiency have revealed an incidence of 5-10 adrenal crises/100 patient years and suggested a mortality rate from adrenal crisis of 0.5/100 patient years. Patients with adrenal crisis typically present with profoundly impaired well-being, hypotension, nausea and vomiting, and fever responding well to parenteral hydrocortisone administration. Infections are the major precipitating causes of adrenal crisis. Lack of increased cortisol concentrations during infection enhances pro-inflammatory cytokine release and sensitivity to the toxic effects of these cytokines (e.g. tumour necrosis factor alpha). Furthermore, pro-inflammatory cytokines may impair glucocorticoid receptor function aggravating glucocorticoid deficiency. Treatment of adrenal crisis is simple and highly effective consisting of i.v. hydrocortisone (initial bolus of 100 mg followed by 200 mg over 24 h as continuous infusion) and 0.9% saline (1000 ml within the first hour). Prevention of adrenal crisis requires appropriate hydrocortisone dose adjustments to stressful medical procedures (e.g. major surgery) and other stressful events (e.g. infection). Patient education is a key for such dose adjustments but current education concepts are not sufficiently effective. Thus, improved education strategies are needed. Every patient should carry an emergency card and should be provided with an emergency kit for parenteral hydrocortisone self-administration. A hydrocortisone pen would hold a great potential to lower the current barriers to hydrocortisone self-injection. Improved patient education and measures to facilitate parenteral hydrocortisone self-administration in impending crisis are expected to significantly reduce morbidity and mortality from adrenal crisis.