{Reference Type}: Journal Article
{Title}: Improved Urinary Cortisol Metabolome in Addison Disease: A Prospective Trial of Dual-Release Hydrocortisone.
{Author}: Espiard S;McQueen J;Sherlock M;Ragnarsson O;Bergthorsdottir R;Burman P;Dahlqvist P;Ekman B;Engström BE;Skrtic S;Wahlberg J;Stewart PM;Johannsson G;
{Journal}: J Clin Endocrinol Metab
{Volume}: 106
{Issue}: 3
{Year}: 03 2021 8
{Factor}: 6.134
{DOI}: 10.1210/clinem/dgaa862
{Abstract}: Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy has demonstrated an improved metabolic profile compared to conventional 3-times-daily (TID-HC) therapy among patients with primary adrenal insufficiency. This effect might be related to a more physiological cortisol profile, but also to a modified pattern of cortisol metabolism.<BR>This work aimed to study cortisol metabolism during DR-HC and TID-HC.<BR>A randomized, 12-week, crossover study was conducted.<BR>DC-HC and same daily dose of TID-HC were administered to patients with primary adrenal insufficiency (n = 50) vs healthy individuals (n = 124) as controls.<BR>Urinary corticosteroid metabolites were measured by gas chromatography/mass spectrometry at 24-hour urinary collections.<BR>Total cortisol metabolites decreased during DR-HC compared to TID-HC (P < .001) and reached control values (P = .089). During DR-HC, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity measured by tetrahydrocortisol + 5α-tetrahydrocortisol/tetrahydrocortisone ratio was reduced compared to TID-HC (P < .05), but remained increased vs controls (P < .001). 11β-HSD2 activity measured by urinary free cortisone/free cortisol ratio was decreased with TID-HC vs controls (P < .01) but normalized with DR-HC (P = .358). 5α- and 5β-reduced metabolites were decreased with DR-HC compared to TID-HC. Tetrahydrocortisol/5α-tetrahydrocortisol ratio was increased during both treatments, suggesting increased 5β-reductase activity.<BR>The urinary cortisol metabolome shows striking abnormalities in patients receiving conventional TID-HC replacement therapy, with increased 11β-HSD1 activity that may account for the unfavorable metabolic phenotype in primary adrenal insufficiency. Its change toward normalization with DR-HC may mediate beneficial metabolic effects. The urinary cortisol metabolome may serve as a tool to assess optimal cortisol replacement therapy.