Growth hormone treatment in hypopituitary GH deficient adults reduces circulating cortisol levels during...

Patients with GH deficiency frequently have multiple hormone deficiencies and require hydrocortisone replacement. We have investigated whether GH treatment alters circulating cortisol levels in hypopituitary patients receiving stable replacement therapy.

Subjects were studied during 6 or 12 months of s.c. GH at a dose of 0.25 IU/kg/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).

Fourteen hypopituitary patients (2F:12M) receiving stable hydrocortisone replacement and thyroxine, gonadal steroids and bromocriptine therapy as required.

Serum cortisol values were measured throughout the day over 10.5 hours. Thyroid hormones and cortisol binding globulin (CBG) were measured in the baseline sample. Comparisons of the serum cortisol peak after receiving the first dose of hydrocortisone, the time when the serum cortisol peak was obtained, the area under the curve (AUC) for the cortisol values and the levels of unbound cortisol on and off GH therapy were made. The results are expressed as mean +/- SEM. Comparisons were carried out within individuals, using the Wilcoxon signed rank test. A P-value less than 0.05 was considered statistically significant.

During GH therapy, there was a significant reduction in the mean cortisol peak (662.2 +/- 61.1 vs 848.0 +/- 58.6 nmol/l; P = 0.001), and in the AUC for cortisol (185.3 +/- 18.3 vs 230 +/- 17.9 nmol/l/10.5h; P = 0.03), but there was no significant change in 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 levels (33.64 +/- 1.16 vs 40.86 +/- 1.34 mg/l; P = 0.001); however, no changes 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 therapy, 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 decrease 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).

These results suggest that GH therapy in GH deficient adults produces an alteration in the measured serum cortisol profile, with a reduction in concentration of total cortisol in blood after orally administered hydrocortisone. These changes in circulating cortisol 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 results should be interpreted with caution in GH deficient patients on GH replacement, and different criteria may have to be applied to the circulating cortisol profile of these patients. The results highlight the importance of ensuring adequate corticosteroid replacement in patients starting GH therapy.