Improving glucocorticoid replacement profiles in adrenal insufficiency

Abstract

There is an increased mortality associated with adrenal insufficiency despite glucocorticoid replacement therapy with a standardized mortality ratio greater than two. The cause of the increased mortality is yet to be definitively elucidated, but may be due to excess steroid exposure, or replacement regimens that are uncoupled from the normal physiological cortisol profile. Cortisol secretion follows an ultradian pattern which is not possible to reproduce using oral replacement. With the advent of new pumps, it is now possible to mimic the pulsatility of the adrenal glands. While the cognitive and emotional benefits of reproducing the ultradian rhythm are known, the presence of long‐term benefits is not yet clear. There is a dearth of evidence and high‐quality studies to underline our current understanding of the pathophysiology of adrenal insufficiency and replacement therapy. There is a particular lack of research comparing objective outcomes between patients receiving hydrocortisone replacement (either standard therapy or new sustained release preparations), prednisolone replacement and ultradian pumps. Direct comparative studies are now warranted to understand the optimal approach.

Immunotherapy-induced endocrinopathies: assessment, management and monitoring

“…Thus, clinically stable patients identified with cortisol deficiency may be safely treated with replacement doses of oral glucocorticoids, such as hydrocortisone or low-dose prednisolone. 52…”

Coronary Spastic Angina Induced by Adrenal Insufficiency

“…In patients with adrenal insufficiency, glucocorticoid replacement therapy is mainly administered with hydrocortisone ( 5 ). However, it is very difficult to completely mimic the in vivo circadian rhythm of glucocorticoid levels ( 2 ), and it is challenging to prevent temporary overtreatment or undertreatment ( 6 ). Suboptimal glucocorticoid replacement therapy in adrenal insufficiency patients has been reported to increase the risk of mortality from CVD ( 3 , 4 ).…”

“…Patients with adrenal insufficiency generally receive glucocorticoid replacement therapy. However, mimicking the circadian rhythm of glucocorticoid levels is challenging, and temporary relative adrenal insufficiency sometimes occurs ( 2 ). Although adrenal insufficiency is known to be a risk factor for cardiovascular disease (CVD) ( 3 , 4 ), there are no reports of coronary spastic angina (CSA) associated with adrenal insufficiency.…”

Adrenal insufficiency secondary to chronic use of topical nasal corticosteroids

“…Su incidencia está estimada en Europa entre 6-8/100 pacientes al año. La morbilidad a largo plazo no está bien establecida, el elevado riesgo cardiovascular o la desmineralización ósea, que no son consistentemente reportados, pueden también ser causados (5) por una terapia de reemplazo suprafisiológica . Sin embargo, las alteraciones en la calidad de vida, tanto en la salud mental como física, se han demostrado en varios estudios tanto en insuficiencia (2) suprarrenal primaria como secundaria .…”

“…La insuficiencia suprarrenal tiene una elevada tasa de mortalidad que no está bien establecida, pero se debería a la exposición excesiva a los corticoides o a regímenes de reemplazo desacoplados al perfil fisiológico normal. La secreción de cortisol sigue un ritmo circadiano imposible de reproducir (5) usando reemplazo oral . Los glucocorticoides son secretados en un ritmo circadiano pulsátil, con el pico más alto en la mañana, con niveles más bajos por la tarde, llegando a una meseta alrededor de la medianoche.…”