Different effects of continuous and intermittent patterns of growth hormone administration on lipoprotein levels in growth hormone-deficient patients

Background: Lipoprotein (a) (Lp(a)) is a risk marker for the development of atherosclerotic coronary heart disease. Growth hormone (GH) administration to GH-deficient (GHD) adults increases serum Lp(a) concentrations, and the levels of Lp(a) and GH are correlated in patients with acromegaly. Studies in rats have demonstrated differential effects of constant and intermitten t GH patterns on levels of certain lipoproteins. The aim of the present stu dies was to describe the impact of intermittent and continuous patterns of GH delivery to GHD patients on serum levels of Lp(a) and other lipoproteins . Methods: In one study (A) 10 GHD patients received in random order a fixe d GH dose intravenously as: (1) continuous infusion; (2) eight bolus inject ions, and (3) a combination of 1 and 2. Each study lasted 36 h and was prec eded by at least 4 weeks without GH. In another study (B) 13 GHD patients r eceived GH in random order as: (1) continuous subcutaneous (s.c.) infusion, and (2) daily s.c. injections in the evening for 1 month each. The patient s were studied during steady-state conditions at the end of each treatment period. Results: In study A Lp(a) levels increased significantly following continuous (p < 0.05) and combined patterns (p < 0.02) of GH administration to GH-deprived GHD patients, whereas the increase after GH bolus injection s alone was not significant (p = 0.14). In study B significantly higher (p < 0.05) serum levels of Lp(a) were obtained after continuous s.c. infusion as compared with daily s.c. injections of GH. Concentrations of the high-de nsity lipoprotein (HDL) cholesterol were significantly lower (p < 0.02) aft er the continuous GH pattern. Similarly, the HDL fraction Apo A-1 tended to be lower with constant GH delivery (p = 0.052). Serum levels of total chol esterol, triglyceride and Apo B were similar on the two occasions. Conclusi on: Short-term GH administration to GH-deprived GHD patients increased seru m Lp(a), but only significantly with continuous delivery. During more prolo nged GH exposure, constant s.c. infusion of GH resulted in slightly raised Lp(a) levels and reduced HDL and Apo Al levels as compared with intermitten tly administered GH. The findings are consistent with the more effective in duction of serum IGF-I levels after continuous patterns of GH delivery prev iously reported in GHD patients. Longer-term data are needed before conclus ions with respect to the impact of the pattern of GH administration on? e.g ., the risk of developing coronary heart disease can be drawn.