The influence of hydrocortisone substitution on the quality of life and parameters of bone metabolism in patients with secondary hypocortisolism

OBJECTIVE Hydrocortisone replacement regimes remain rather empirical and pr oduce serum cortisol profiles very different from normal physiology. We hav e analysed the effects of different dosages of hydrocortisone (HC) replacem ent therapy on the health perception and general well-being of patients wit h secondary hypocortisolism. We also evaluated the effects of these regimen s on bone metabolism. DESIGN In a prospective randomized double-blind study, 3 groups of 3 patien ts were treated with 3 different dosages of HC (15, 20 and 30 mg/day), in d ifferent sequences, each sequence for two weeks. PATIENTS Nine adult patients with complete secondary hypocortisolism. MEASUREMENTS Serum cortisol, ACTH, aldosterone, renin, alkaline phosphatase , bone specific alkaline phosphatase, osteocalcin, PTH, C-telopeptides of t ype-I collagen, sodium, potassium, phosphate; urinary free cortisol, pyridi nium cross-links, urine sodium, potassium and phosphate were measured at th e beginning and after each week of the study. For quality of life assessment the patients completed three different quest ionnaires, the Basler Befindlich-keits-Skala (BBS), the Befindlichkeits-Ska la (Bf-S), the Beschwerde-Liste (BL) each week. RESULTS With increasing doses of 15, 20 and 30 mg hydrocortisone a signific ant increase of free urinary cortisol was achieved (298 +/- 26 nmol/day, 45 4 +/- 43, 819 +/- 59, respectively; P<0.01). The mean scores of the psychol ogical questionnaires did not change significantly during the whole study ( BBS 81.8 +/- 3.9; 82.8 +/- 3.9, 83.6 +/- 3.9; Bf-S 15.9 +/- 3.4, 11.3 +/- 2 .6, 12.5 +/- 2.8; BL 15.7 +/- 2.3, 14.4 +/- 2.5, 14.8 +/- 2.6, respectively ). Osteocalcin decreased significantly (2.3 +/- 0.49, 2.1 +/- 0.42, 1.8 +/- 0.38, P<0.01) with increasing HC doses but remained within the normal rang e. The other investigated parameters were within or nearly within the norma l range in all patients at the beginning and did not change during the stud y. CONCLUSION Dosages of 15, 20 or 30 mg hydrocortisone/day have equivalent ef fects on quality of life in patients with secondary hypocortisolism. With 1 5 or 20 mg hydrocortisone/day the patients feel nearly as well and content as normal healthy individuals. Since long-term treatment with a high replac ement dose of glucocorticoids (hydrocortisone 30 mg/day) induces bone loss, this risk can be avoided with a substitution dosage of 20 mg or even 15 mg hydrocortisone/day, without influencing the well-being of the patient.