Endocrine Abstracts

Before the availability of glucocorticoids as drugs, the majority of patients with primary adrenal insufficiency (AI) died within 2 years of diagnosis. Today patients with AI receive life-long replacement therapy with glucocorticoids with the assumption that life expectancy is normal. Recent studies have, however, shown excess mortality in patients with both primary and secondary AI mainly due to cardiovascular diseases and infections. Patients with AI also have increased rate of diabetes, hypertension and hospital admission rates due to infections. It is likely that non-physiological exposure of glucocorticoids both in term of dose and time exposure profile contributes to this poor outcome together with inadequate intercurrent illness rescue therapy. Modified release hydrocortisone has been developed to improve outcome among patients with AI, by improving the circadian exposure of hydrocortisone. Prospective trials have shown indications that the metabolic outcome is improved and frequency of infections may be reduced in comparison with the same daily dose of conventional hydrocortisone. Treatment with modified release hydrocortisone may also improve and normalise immune function and peripheral expression of clock genes. Limited data exist on the long-term safety of these new treatments from prospective studies. Available data from a 5 year prospective study suggest a good safety profile, but the question remains whether long-term outcome is improved in comparison with conventional glucocorticoid replacement therapy. New options have emerged for the treatment of glucocorticoid deficiency in AI. Outcome from prospective short-term studies has shown promising results. Limited data on long-term treatment outcome with modified hydrocortisone support their safety.