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

Context: Individuals with primary adrenal insufficiency (PAI) or congenital adrenal hyperplasia (CAH) receive life-long glucocorticoid (GC) replacement therapy. GC doses used for replacement therapy in these diseases are much lower than GC doses used for immunosuppressive therapy. However, 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. So far, all studies on bone mineral density (BMD) in PAI and CAH patients had a cross sectional design, small patient numbers and showed inconsistent findings. Objective: The aim of this study was to prospectively investigate the effect of decreasing or increasing GC doses on BMD in those patients over a two-year period. Methods: We conducted a prospective, longitudinal study including 57 subjects with PAI and 33 with CAH. BMD was measured by DXA at baseline and after two years. At the end of the study period subjects were divided into three groups depending on changes in daily hydrocortisone equivalent dose: group1 with unchanged daily hydrocortisone equivalent dose (25·2±8·2mg (mean+SD; n=50)); group2 with increased daily hydrocortisone equivalent dose (18·7±10·3 to 25·9±12·0mg (n=13)) and group3 with decreased daily hydrocortisone equivalent dose (30·8±8·5 to 21·4±7·2mg (n=27)) during the study period. To assess the safety and the effects of changing GC doses on patient’s quality of life, all adrenal crises that occurred during the study time were documented and patients were asked to complete an Addison’s disease- specific questionnaire (AddiQoL). Results: Subjects in group1 showed normal lumbar and femoral Z-scores which were unchanged over time. Group2 subjects showed a significant decrease in femoral neck Z-scores over time (-0·15±1·1 to -0·37±1·0 (p<0·05)), whereas group3 subjects showed a significant increase in lumbar spine and hip Z-scores (L1-L4: -0·93±1·2 to -0·65±1·5 (p<0·05); total hip: -0·40±1·0 to -0·28±1·0 (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. Furthermore, there were no statistically significant changes in AddiQoL scores over time. Conclusions: This study demonstrated for the first time that cautious reduction in hydrocortisone equivalent doses leads to increases in BMD, whereas dose increments reduced BMD. Additionally, cautious GC reduction did not result in an increased frequency of adrenal crises or decreased quality of life. Therefore, these data emphasize the need for the lowest possible GC replacement dose in patients with adrenal insufficiency to maintain health and avoid long-term adverse effects.

Author dc:creator

• Schulz, Julia

• adrenal insufficiency
• bone mineral density
• glucocorticoid replacement therapy

Licence dc:rights.uri

• http://www.fu-berlin.de/sites/refubium/rechtliches/Nutzungsbedingungen

Language dc:language

ger

Identifier URI

http://dx.doi.org/10.17169/refubium-14163

OAI record oai:identifier

https://refubium.fu-berlin.de/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Arefubium.fu-berlin.de%3Afub188%2F9965