Long‐term follow‐up of bone mineral density in Addison's disease

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: Introductionmentioning

confidence: 87%

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

Schulz

Frey

Cooper

et al. 2016

“…Limited data are available regarding long-term side effects of glucocorticoid replacement therapy (13). The currently available studies might suggest that bone loss is not influenced by the duration or type of steroid treatment (14,15), but rather by the glucocorticoid dose used for chronic replacement (16). However, none of the studies had included large enough numbers to address this properly.…”

Section: Introductionmentioning

confidence: 99%

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

Bleicken

Hahner

Loeffler

et al. 2008

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

“…The majority of available studies have been carried out in subjects with primary adrenal failure, with some studies finding a reduced bone mineral density (BMD) in men with increasing hydrocortisone (HC) equivalent doses (7,8) and a lower femoral neck BMD correlated with weight-adjusted GC dose (9), while others have found no difference in BMD compared with that of the control population (10,11), except in subjects on prednisolone, in whom a significant decrease in BMD was observed (12).…”

Section: Introductionmentioning

confidence: 99%

Low-dose hydrocortisone replacement therapy is associated with improved bone remodelling balance in hypopituitary male patients

Behan

Kelleher²,

Hannon³

et al. 2014

Objective: Glucocorticoid (GC) therapy is associated with adverse effects on bone metabolism, yet the effects of different GC physiological replacement regimens in hypopituitarism are not well characterised. We aimed to assess the effect of three hydrocortisone (HC) replacement dose regimens on bone turnover. Study design: An open cross-over study randomising ten hypopituitary men with severe ACTH deficiency to three commonly used HC dose regimens: dose A (20 mg mane and 10 mg tarde), dose B (10 mg mane and 10 mg tarde) and dose C (10 mg mane and 5 mg tarde). Methods: Following 6 weeks of each regimen, the participants underwent 24-h serum cortisol sampling and measurement of bone turnover markers: bone-specific alkaline phosphatase, procollagen type I N-propeptide (PINP), intact osteocalcin (OC(1-49)), C-terminal cross-linking telopeptide (CTX-I) and tartrate-resistant acid phosphatase 5b (TRACP5b). Bone remodelling balance was estimated as an absolute ratio (PINP:CTX-I) and as an index using standardised scores derived from the matched controls. Results: There were significant increases in the concentrations of the formation markers PINP (PZ0.045) and OC(1-49) (PZ0.006) and in the PINP:CTX-I ratio (PZ0.015), and a more positive bone remodelling balance index (PZ0.03) was observed in patients on the lowest dose C than in those on the highest dose A. Mean 24-h cortisol concentrations correlated negatively with CTX-I (rZK0.66 and PZ0.04) and TRACP5b (rZK0.74 and PZ0.01) in patients on dose B and with OC(1-49) (rZK0.66 and PZ0.04) and CTX-I (rZK0.81 and P!0.01) in patients on dose C. In patients receiving the lower-dose regimen, trough cortisol concentrations correlated with increased bone formation and resorption. Conclusion: Low-dose HC replacement (10 mg mane and 5 mg tarde) is associated with increased bone formation and a positive bone remodelling balance. This may have a long-term beneficial effect on bone health.