Impaired subjective health status in chronic adrenal insufficiency: impact of different glucocorticoid replacement regimens

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.

Section: Discussionsupporting

confidence: 93%

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

Ragnarsson

Mattsson

Monson

et al. 2014

“…This is consistent with previous observational studies comparing patients with primary AI and SAI to normative control groups (2,7,8,9). One reason for impaired subjective health may be that common replacement regimens are not able to mimic the physiological diurnal pattern of cortisol secretion (1).…”

Section: Sai Patients (Nz18)supporting

confidence: 91%

“…Previous studies found little differences between standard replacement regimens and their effects on subjective health and quality of life (5,6,7,8,9); however, many of these studies were cross-sectional (7,8,9). Other studies investigated less physiological HC regimes, suggesting an advantage of imitating the circadian rhythm of cortisol secretion (10,11).…”

Section: Introductionmentioning

confidence: 99%

Effects of standard glucocorticoid replacement therapies on subjective well-being: a randomized, double-blind, crossover study in patients with secondary adrenal insufficiency

Benson¹,

Neumann

Unger

et al. 2012

Objective: For secondary adrenal insufficiency (SAI), established biochemical parameters for dosage control are lacking and no optimal substitution dosage and daily distribution have been determined yet. Therefore, in clinical practice, the individual total dose is often adjusted based on patients' subjective well-being. Design: Effects of three standard glucocorticoid replacement regimens on psychological variables were assessed in patients with SAI based on a randomized double-blind study design. Methods: SAI patients (nZ18) were treated with three different established glucocorticoid replacement regimens in a randomized, double-blind, crossover study (treatment A, hydrocortisone 10 mg-placebo-5 mg-placebo; treatment B, hydrocortisone 10 mg-5 mg-placebo-5 mg; and treatment C, prednisone 5 mg-placebo-placebo-placebo). Following each 4-week replacement regimen, quality of life (SF-36) and emotional distress (brief symptom inventory (BSI)) were assessed along with diurnal changes in current well-being (Bf-S) and alertness (Stanford Sleepiness Scale (SSS)) using validated questionnaires, and additionally compared with patient (patients with pituitary disease and adrenal sufficiency) and healthy control groups. Results: SAI patients showed improvements in physical quality of life (i.e. SF-36 physical function, P!0.05; physical role function, P!0.05) and current well-being (at 1800 h, P!0.05) under treatment A (hydrocortisone 10-0-5-0 mg) compared with the other replacement regimens. Quality of life and current well-being were significantly impaired compared with healthy controls but did not differ from patient controls. Conclusions: Although the observed improvements in psychological parameters were comparatively small, our results indicate beneficial effects of a 10-0-5-0 mg hydrocortisone replacement regimen. Nevertheless, treatment effects were insufficient to restore subjective health compared with healthy controls, indicating the need for improved replacement regimens and supportive psychosocial interventions in SAI patients.

“…A subgroup of our patient cohort has previously been described in detail (15,16). All patients with AI currently registered with the outpatient department at the University Hospital Wü rzburg (nZ148) and the University Hospital Charité Berlin (nZ535), and registered members of the German self-help network of patients with pituitary or adrenal diseases suffering from AI (nZ200) were asked to participate in a postal survey.…”

Section: Patientsmentioning

confidence: 99%

Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies

Hahner

Loeffler

Bleicken

et al. 2010

Self Cite

279

303

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.