Torben Laursen

Background: Diurnal variation in serum growth hormone (s-GH) levels after exogenous GH delivery has previously been repotted in patients with no endogenous GH secretion. Changes in postural position or physical activity, leading to changes in blood flow and/or lymphatic drainage may be underlying explanations.

Primary objectives: The primary aim of this study is to study a possible impact of exercise and supine rest on pharmacokinetics (PK) and day-to-day variation of subcutaneously (sc) administered GH in adult GH deficient (AGHD) patients.

Secondary objective: The secondary aim of this study is to compare s-IGF-I, s-insulin, and plasma (p)-glucose profiles after a carbohydrate rich breakfast following sc GM injection vs. continuous infusion.

Design and methods: During supine rest eight AGHD males (59.8 +/- 8 years, BMI 29.7 +/- 4.9 kg/m(2)) were treated with one daily sc GM injections of 3 mg/24 h for 48 h (treatment sessions A, B) or a continuous sc GM infusion of 3 mg/24 h for 60 h (treatment sessions C, D). Exercise comprised 1 h bicycling with 50 W load on two consecutive days during treatment sessions B and D.

Results: Administration of GM as a bolus injection, but not as a continuous GH infusion, resulted in about 32% higher s-GM levels during exercise (60 min) as well as 30 min after (s-GH logAUC((B-A)) difference was 0.28; 95% CI: 0.14-.0.4; p <0.001). However, the total s-GH(AUC) (0-24 h) (p = 0.75) and s-IGF-I-AUC (0-48 h) levels (p = 0.51) remained unchanged between the two occasions. P-glucose and insulin profiles were significantly higher after carbohydrate rich breakfast before first and second dosing both following sc GM injection and continuous infusion (p <0.05).

Conclusions: Moderate exercise intermittently increased s-GH levels. These changes seem to have no clinical short-term relevance, since total s-GH(24 h) and s-IGF-I-48 h levels were unaffected. (C) 2014 Elsevier Ltd. All rights reserved.