Sustained reduction in circulating cholesterol in adult hypopituitary patients given low dose titrated growth hormone replacement therapy: a two year study
Authors: Florakis Dimos , Hung Victor , Kaltsas Gregory , Coyte Donna , Jenkins Paul J. , Chew Shern L. , Grossman Ashley B. , Besser G. Michael , Monson John P. 
Published: March 2003

OBJECTIVE

To study the effects of short (6 months) and longer‐term (up to 24 months) growth hormone (GH) replacement therapy using a dose titration regimen, on lipid and glucose metabolism in GH‐deficient, hypopituitary adults.

DESIGN

On‐going open study of GH treatment up to 24 months. Measurements were performed at baseline and at 6, 12, 18 months and 2 years during therapy (data shown at 6 months and 2 years only). Using a dose titration regimen the median GH dose used to achieve and maintain IGF‐I levels above the median, but below the upper limit of the age‐related reference range (median IGF‐I 202.5 μg/l, range 76–397 μg/l), was 1.2 IU daily (range 0.4–3 IU) [0.8 IU/day, males; 1.6 IU/day, females].

PATIENTS

Ninety GH‐deficient hypopituitary adults (54 female, median age 48 years, range 19–79 years) entered the study and 24 (14 female, median age 45 years, range 32–79 years) have concluded the 2 year period of assessment.

MEASUREMENTS

Body mass index (BMI), waist and hip circumference ratio (WHR), fasting lipids, glucose and glycated haemoglobin (HbA1c) levels were measured at 6 month intervals during GH therapy.

RESULTS

Using the dose titration regimen, compared to pretreatment values, total and low density lipoprotein (LDL)‐cholesterol levels were significantly lower at 6 months (mean ± SEM, 5.61 ± 0.1 vs. 5.25 ± 0.1, and 3.85 ± 0.19 vs. 3.43 ± 0.26, respectively, P < 0.05), and were maintained throughout the study. Male patients had significantly lower pretreatment total and LDL cholesterol levels than females (mean ± SEM, 5.33 ± 0.16 mmol/l vs. 5.7 ± 0.12 mmol/l and 3.8 ± 0.23 mmol/l vs. 3.92 ± 0.29 mmol/l, respectively, P < 0.05). A decrease in total cholesterol was confined to patients with pretreatment total cholesterol levels above 5.8 mmol/l; patients with the highest pretreatment cholesterol levels (> 6.4 mmol/l) obtained the greatest cholesterol reduction (mean ± SEM, 7.13 ± 0.14 mmol/l vs. 5.76 ± 0.31 mmol/l, P < 0.05). A cholesterol‐lowering effect of GH therapy was evident in patients who had elevated pre‐GH total cholesterol levels even if they were already receiving and continuing lipid lowering medication (mean ± SEM, 5.62 ± 0.22 vs. 5.03 ± 0.285, P < 0.05). A modest increment in high density lipoprotein (HDL)‐cholesterol was evident at 18 months but there was no significant change in triglycerides at any time point. Fasting plasma glucose increased significantly at 6 months but remained within the reference range. Glycated haemoglobin increased significantly at 6 months and was maintained throughout the study; one patient developed frank diabetes mellitus while receiving treatment. There was a weak but significant correlation between the increment in glycated haemoglobin and pretreatment BMI (r = + 0.215, P < 0.05).

CONCLUSION

The effect of GH on lowering total and low density lipoprotein‐cholesterol is more prominent in patients with higher pretreatment cholesterol levels and is evident even in patients receiving other lipid‐lowering medication. A modest increment in mean fasting glucose (within the reference range) and mean glycated haemoglobin persisted throughout the study. One patient developed diabetes mellitus. A GH replacement regimen using low dose and careful titration to avoid elevated IGF‐I levels and adverse effects is associated with sustained beneficial effects on circulating lipids.