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Optimizing glucocorticoid replacement therapy in severely adrenocorticotropin‐deficient hypopituitary male patients
Author(s) -
Behan LucyAnn,
Rogers Bairbre,
Han Mark J.,
O’Kelly Patrick,
Tormey William,
Smith Diarmuid,
Thompson Christopher J.,
Agha Amar
Publication year - 2011
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2011.04074.x
Subject(s) - regimen , medicine , nottingham health profile , hydrocortisone , endocrinology , glucocorticoid , basal (medicine) , transcortin , crossover study , corticosteroid , globulin , placebo , pathology , insulin , alternative medicine
Summary Background The optimal replacement regimen of hydrocortisone in adults with severe ACTH deficiency remains unknown. Management strategies vary from treatment with 15–30 mg or higher in daily divided doses, reflecting the paucity of prospective data on the adequacy of different glucocorticoid regimens. Objective Primarily to define the hydrocortisone regimen which results in a 24 h cortisol profile that most closely resembles that of healthy controls and secondarily to assess the impact on quality of life (QoL). Design Ten male hypopituitary patients with severe ACTH deficiency (basal cortisol <100 n m and peak response to stimulation <400 n m ) were enrolled in a prospective, randomized, crossover study of 3 hydrocortisone dose regimens. Following 6 weeks of each regimen patients underwent 24 h serum cortisol sampling and QoL assessment with the Short Form 36 (SF36) and the Nottingham Health Profile (NHP) questionnaires. Free cortisol was calculated using Coolen’s equation. All results were compared to those of healthy, matched controls. Results Corticosteroid binding globulin (CBG) was significantly lower across all dose regimens compared to controls ( P < 0·05). The lower dose regimen C (10 mg mane/5 mg tarde) produced a 24 h free cortisol profile (FCP) which most closely resembled that of controls. Both regimen A(20 mg mane/10 mg tarde) and B(10 mg mane/10 mg tarde) produced supraphysiological post‐absorption peaks. There was no significant difference in QoL in patients between the three regimens, however energy level was significantly lower across all dose regimens compared to controls ( P < 0·001). Conclusions The lower dose of hydrocortisone (10 mg/5 mg) produces a more physiological cortisol profile, without compromising QoL, compared to higher doses still used in clinical practice. This may have important implications in these patients, known to have excess cardiovascular mortality.