GROWTH-HORMONE TREATMENT IN HYPOPITUITARY GH DEFICIENT ADULTS REDUCESCIRCULATING CORTISOL-LEVELS DURING HYDROCORTISONE REPLACEMENT THERAPY

OBJECTIVES Patients with GH deficiency frequently have multiple hormon e deficiencies and require hydrocortisone replacement. We have investi gated whether GH treatment alters circulating cortisol levels in hypop ituitary patients receiving stable replacement therapy. DESIGN Subject s were studied during 6 or 12 months of s.c. GH at a dose of 0.25 IU/k g/week (0.125 IU/kg/week for the first 4 weeks), and after a wash-out period of at least 2 months off GH (range 2-5 months). PATIENTS Fourte en hypopituitary patients (2F:12M) receiving stable hydrocortisone rep lacement and thyroxine, gonadal steroids and bromocriptine therapy as required. MEASUREMENTS Serum cortisol values were measured throughout the day over 10.5 hours. Thyroid hormones and cortisol binding globuli n (CBG) were measured in the baseline sample, Comparisons of the serum cortisol peak after receiving the first dose of hydrocortisone, the t ime when the serum cortisol peak was obtained, the area under the curv e (AUG) for the cortisol values and the levels of unbound cortisol on and off GH therapy were made, The results are expressed as mean +/- SE M, Comparisons were carried out within individuals, using the Wilcoxon signed rank test. A P-value less than 0.05 was considered statistical ly significant. RESULTS During GH therapy, there was a significant red uction in the mean cortisol peak (662.2 +/- 61.1 vs 848.0 +/- 58.6 nmo l/l; P = 0.001), and in the AUC for cortisol (185.3 +/- 18.3 vs 230 +/ - 17.9 nmol/l/10.5 h; P = 0.03), but there was no significant change i n the time of the cortisol peak (55.7 +/- 7.6 vs 57.8 +/- 4.9 minutes; P = NS). During GH therapy there was a significant reduction in CBG l evels (33.4 +/- 1.16 vs 40.86 +/- 1.34 mg/l; P = 0.001); however, no c hanges were found in the levels of calculated unbound cortisol on and off GH (2.87 +/- 0.38 vs 2.90 +/- 0.30 nmol/l; P = NS), During GH ther apy, there was a significant increase in serum triiodothyronine (T3) ( 1.88 +/- 0.15 vs 1.44 +/- 0.11 nmol/l; P = 0.01), and a significant de crease in thyroxine (T4) levels (74.9 +/- 11.1 vs 97.6 +/- 10.9 nmol/l ; P = 0.02) but levels remained within the normal range. No change was observed in serum TSH levels (0.29 +/- 0.13 vs 0.83 +/- 0.71 mU/l; P = NS). CONCLUSIONS These results suggest that GH therapy in GH deficie nt adults produces an alteration in the measured serum cortisol profil e, with a reduction in concentration of total cortisol in blood after orally administered hydrocortisone. These changes in circulating corti sol probably depend primarily on the fall in CBG levels, as no changes were found in the levels of calculated unbound cortisol on and off GH . Our data show that when measuring circulating cortisol levels, the r esults should be interpreted with caution in GH deficient patients on GH replacement, and different criteria may have to be applied to the c irculating cortisol profile of these patients. The results highlight t he importance of ensuring adequate corticosteroid replacement in patie nts starting GH therapy.