Prednisolone ups mortality risk in patients with primary adrenal insufficiency

Use of prednisolone is associated with an increased mortality risk in patients with primary, but not secondary, adrenal insufficiency, reveals a study.

The study is large, but patients treated with prednisolone is small and have greater risk factors. However, the increased mortality associated with prednisolone is consistent despite statistical adjustment, according to the investigators.

This observational study determined the mortality rates with prednisolone vs hydrocortisone. The investigators used data obtained from a UK primary care database (Clinical Practice Research Datalink) to measure the relative mortality of patients with primary and secondary adrenal sufficiency treated with prednisolone or hydrocortisone and control participants who were matched for age, sex, period, and place of follow-up.

Regardless of cause, mortality in adrenal insufficiency was higher, based on 5,478 patients (4,228 on hydrocortisone and 1,250 on prednisolone) and 54,314 controls (41,934 and 12,380, respectively). Overall, the two treatments had similar adjusted hazard ratio: 1.76 (95 percent confidence interval [CI], 1.54–2.01) for prednisolone and 1.69 (95 percent CI, 1.57–1.82) for hydrocortisone (p=0.65). The same was true for secondary adrenal insufficiency.

In primary disease (1,405 on hydrocortisone vs 137 on prednisolone; controls: 13,965 vs 1,347, respectively), users of prednisolone were older, more likely to have a coexisting autoimmune disease and malignancy, and less likely to have mineralocorticoid replacement. After adjustment, however, the HR for prednisolone users was higher than for those on hydrocortisone: 2.92 (95 percent CI, 2.19–3.91) vs 1.90 (95 percent CI, 1.66–2.16; p=0.0020).

Further research is warranted to establish the long-term safety of prednisolone as routine replacement.

“Prednisolone has been recommended rather than hydrocortisone for glucocorticoid replacement in adrenal insufficiency due its longer duration of action and lower cost,” the investigators said.