Bone density and turnover in Addison's disease: effect of glucocorticoid treatment

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

Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

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

Bleicken

Hahner

Loeffler

et al. 2008

“…Therefore, small changes in cortisol replacement therapy may have effects on bone turnover with higher doses more likely to have an adverse effect on bone formation (36). Despite this, no specific changes have been observed in circulating bone alkaline phosphatase, another marker of bone formation, in those on glucocorticoid replacement therapy (37).…”

Section: Defects In Bone Metabolismmentioning

confidence: 99%

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

Debono

Ross²,

Newell‐Price

2009

116

Patients with adrenal insufficiency need lifelong glucocorticoid replacement, but many suffer from poor quality of life, and overall there is increased mortality. Moreover, it appears that use of glucocorticoids at the higher end of the replacement dose range is associated with increased risk for cardiovascular and metabolic bone disease. These data highlight some of the inadequacies of current regimes.The cortisol production rate is estimated to be equivalent to 5.7-7.4 mg/m 2 per day, and a major difficulty for replacement regimes is the inability to match the distinct circadian rhythm of circulating cortisol levels, which are low at the time of sleep onset, rise between 0200 and 0400 h, peaking just after waking and then fall during the day. Another issue is that current dose equivalents of glucocorticoids used for replacement are based on anti-inflammatory potency, and few data exist as to doses needed for equivalent cardiovascular and bone effects. Weight-adjusted, thrice-daily dosing using hydrocortisone (HC) reduces glucocorticoid overexposure and represents the most refined regime for current oral therapy, but does not replicate the normal cortisol rhythm. Recently, proof-of-concept studies have shown that more physiological circadian glucocorticoid therapy using HC infusions and newly developed oral formulations of HC have the potential for better biochemical control in patients with adrenal insufficiency. Whether such physiological replacement will have an impact on the complications seen in patients with adrenal insufficiency will need to be analysed in future clinical trials.

“…These studies have shown inconsistent findings relating to BMD, disease duration, GC type and daily dose. Some studies reported reduced BMD in all PAI patients (2,3), some only in postmenopausal women (4,5) or only in men (6,7), whereas other studies found no significant differences in BMD in either gender (8,9,10). In CAH patients some studies reported no significant differences in BMD between patients with CAH and controls (10,11,12,13,14,15,16), whereas others found reduced BMD in all or some subpopulations of CAH patients (17,18,19,20,21,22,23,24).…”

Section: Introductionmentioning

confidence: 98%

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

Schulz

Frey

Cooper

et al. 2016

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.