Primary adrenal insufficiency was first described in 1855 by Thomas Addison, demonstrating that the adrenal cortex is essential for life. Life-saving glucocorticoid replacement became widely available only with the clinical introduction of cortisone in 1949. Chronic primary adrenal insufficiency (PAI) has a prevalence of 93140 per million and its incidence is rising due to an increase in autoimmune adrenalitis. In developing countries tuberculosis is still a leading cause of PAI. Despite significant improvements in therapeutic regimens for PAI there is mounting evidence that well-being is not fully restored by current replacement strategies. Impaired well-being has been repeatedly and consistently demonstrated in PAI irrespective of the glucocorticoid used or the distribution of hydrocortisone doses. This may be related to the missing early morning rise in glucocorticoid availability with current replacement regimens. Furthermore, there is now growing evidence that not only quality of life but also life expectancy may be affected by PAI including increased cardiovascular mortality and an increased cancer risk. However, these data have been challenged by a recent investigation from Norway suggesting that increased mortality is restricted to younger age (<40 years) and male sex. In particular, patients with PAI are at risk of life-threatening adrenal crisis. Retrospective analysis in 444 patients with adrenal insufficiency revealed an incidence 5.1 crises per 100 patient years. Major precipitating causes were gastrointestinal infections and fever of any cause. In 8% no specific cause was identified. Patients with PAI and significant non-endocrine comorbidities had a moderately higher risk of crisis (RR 1.24, P=0.057). In secondary adrenal failure female sex and concomitant diabetes insipidus were risk factors for adrenal crisis (RR 1.26 and 1.25, respectively, P<0.05). We currently collect data on adrenal crisis prospectively in a large cohort of patients with adrenal insufficiency to better define the risk factors for this emergency which will be presented. In summary, impaired well-being and altered morbidity and mortality in PAI indicate the need to improve current replacement and surveillance strategies in Addisons disease.
25 - 29 Apr 2009
European Society of Endocrinology