Effect of glucocorticoid replacement therapy on glucose tolerance and intermediary metabolites in hypopituitary adults

Excess impaired glucose tolerance and diabetes mellitus have been reported in hypopituitary adults on conventional replacement therapy including glucocorticoids. We investigated the effect of the glucocorticoid component on glucose tolerance and intermediary metabolites in hypopituitary adults.

A 3-hour 75-g oral glucose tolerance test (OGTT) was performed on two study days, at least one week apart. On one study day, the glucocorticoid replacement morning dose was taken 60 minutes before the OGTT, and on the other it was left until after the OGTT. All other pituitary replacement therapies were kept unchanged on the two study days.

Eight hypopituitary adults (3 males and 5 females; aged 46-76 years) on conventional replacement therapy were studied. Their duration of hypopituitarism was mean (range) 15 (5-31) years. Their mean body mass index (BMI) was 28.4 (24.1-35.1) kg/m2. Their total daily cortisol dose was 26 (15-30) mg.

Plasma glucose, insulin, non-esterified fatty acids (NEFA), glycerol and 3-hydroxybutyrate were measured at 30-minute intervals and plasma cortisol levels were measured hourly.

Fasting glucose and insulin concentrations were similar on the glucocorticoid day (GD) and the non-glucocorticoid day (NGD) (glucose (mean +/- SD) 4.9 +/- 0.9 vs 4.4 +/- 0.5 mmol/l; insulin (median (range)) 5 (1-17) vs 2 (1-15) mU/l, respectively). Post-glucose glycaemia was higher on the GD than on the NGD with a significantly higher glucose area under the curve (AUC) (45.0 +/- 8.2 vs 38.9 +/- 11.7 mmol/l h, P < 0.05). Post-glucose insulinaemia was also higher on the GD than on the NGD with significantly higher insulin AUC (270 (47-909) vs 207 (46-687) mU/l h, P < 0.02). Impaired glucose tolerance was found in three patients on the GD, one of whom continued to have impaired glucose tolerance on the NGD. The areas under the curves of NEFA, glycerol and 3-hydroxybutyrate were not significantly different on the two days. On the NGD, plasma cortisol levels were undetectable (< 50 nmol/l) in all patients and on the GD the median (range) peak was 500 (330-740) nmol/l dropping to 125 (60-330) nmol/l at 180 minutes. The difference in glucose AUC between the two days correlated with the maximal plasma cortisol levels (Spearman's p = 0.83, P < 0.01).

Glucocorticoid replacement therapy taken pre-prandially in hypopituitary adults induces mild elevations in circulating glucose and insulin levels even with acceptable plasma cortisol concentrations. Optimal regimens for glucocorticoid replacement require more study.