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Continuation of Growth Hormone (GH) Substitution during Fasting in GH-Deficient Patients Decreases Urea Excretion and Conserves Protein Synthesis¹

Medical Department M (Endocrinology and Diabetes) (H.N., N.M., J.S.C., J.O.L.J.), Aarhus Kommunehospital, Aarhus DK-8000, Denmark; and Endocrinology Division (K.S.N.), Mayo Clinic, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Helene Nørrelund, Medical Department M, Aarhus Kommunehospital, 8000 Aarhus C, Denmark. E-mail: helenenorrelund{at}dadlnet.dk

Abstract

The consequences of GH deficiency during conditions in which endogenous GH release is acutely stimulated are largely unknown. Short-term fasting constitutes a robust GH stimulus, but the metabolic significance of GH during fasting is uncertain.

To address both of these issues, we therefore evaluated the effect of GH on substrate metabolism during fasting in adults with GH deficiency. Seven hypopituitary GH-deficient patients were each studied twice during a 40-h fast: once with GH replacement continued and once with GH discontinued during the fast. After 40 h of fasting, protein synthesis and turnover were higher with than without GH replacement [phenylalanine incorporation (µmol/kg fat free mass/h): 36.6 ± 1.2 (GH) vs. 32.8 ± 1.4, P < 0.05; phenylalanine flux (µmol/kg fat free mass/h): 41.3 ± 1.0 (GH) vs. 38.0 ± 1.8, P < 0.05]. During continued GH replacement, urea excretion decreased during nighttime [urea excretion (mmol/24 h): 269 ± 51 (GH) vs. 390 ± 69, P < 0.05], and a significant decline in urea-N synthesis rate was found [urea-N synthesis rate (mmol/h): 14.7 ± 1.6 (GH) vs. 21.1 ± 2.2, P < 0.01]. GH replacement was associated with increased lipid oxidation [lipid oxidation (mg/kg per min): 0.91 ± 0.07 (GH) vs. 0.70 ± 0.03, P < 0.05]. Finally, continuation of GH induced moderate elevations in plasma glucose levels without significant changes in total glucose turnover or oxidation.

In summary, continued GH substitution during fasting conserves nitrogen, which involves stimulation or maintenance of protein synthesis. Our data support the importance of GH replacement in hypopituitary adults.

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