ORIGINAL ARTICLE Postprandial triglyceride profile after a standardized oral fat load is altered in growth hormone (GH)-deficient adult patients and is not improved after short-term GH replacement therapy Mario Perotti*, Andrea Caumo†, Amelia Brunani‡, Nadia Cambiaghi§, Marco Casati§, Massimo Scacchi¶ , **, Silvia Perra*, Cristina Rocco††, Giuseppe Mancia*, Guido Grassi+++, Francesco Cavagnini‡‡ and Angela Ida Pincelli * *Clinica Medica, Ospedale San Gerardo, Universita` Milano-Bicocca, Monza, †Nutrition Unit, Department of Medicine, Istituto Scientifico San Raffaele, Universita` Vita-Salute, Milan, ‡Istituto Auxologico Italiano Piancavallo, Verbania, §Laboratory of Chemical and Clinical Analyses, Ospedale San Gerardo, Monza, ¶Cattedra di Endocrinologia, Universita` di Milano, **Ospedale San Luca, Istituto Auxologico Italiano IRCCS, Milan, ††Centro per la Cura dei Disturbi del Comportamento e della Alimentazione, Ospedale San Gerardo, Monza, ‡‡Neuroendocrine Research Laboratory, Istituto Auxologico Italiano, and +++Istituto Scientifico IRCSS Multimedica, Sesto San Giovanni, Milan, Italy Summary Objective Adult growth hormone deficiency (GHD) has detri- mental effects on metabolic profile, leading to an increased car- diovascular mortality and morbidity. Above all, disturbance in postprandial triglyceride metabolism is of major concern because of the crucial role of triglyceride-rich lipoproteins in atherogene- sis. The majority of previous studies on GH replacement have shown favourable changes in the fasting lipid profile. Aim of this study is to investigate whether this beneficial effect is exerted also on postprandial triglyceride (TG) metabolism. Patients and methods We challenged nine GHD patients with a standardized fat loading meal at baseline and after 6 months of GH replacement therapy. Nine healthy control subjects were similarly tested under baseline conditions. Blood samples were obtained before and up to 8 h after fat loading for serum lipid analysis. Results We found that GHD patients with fasting TG level in the normal range (1·29 ± 0·31 mM) had a delayed postprandial TG clearance compared to healthy controls (triglyceride level at 8 h, 3·82 ± 0·83 vs 1 ± 0·06 mM P < 0·01), and the postprandial hypertriglyceridaemia was not corrected by 6 months of GH therapy. Conclusions This study has shown for the first time that GHD adult patients have a higher postprandial triglyceridaemia com- pared to healthy controls when challenged by a standardized fat load and that this atherogenic feature is not normalized by short-term GH treatment despite a decrease in visceral fat mass described during the replacement therapy. (Received 23 January 2012; returned for revision 18 February 2012; finally revised 31 March 2012; accepted 12 April 2012) Introduction Hypopituitary GH-deficient patients have been shown to have a higher risk of atherosclerosis, resulting in increased cardiovascu- lar mortality and morbidity. 1 It is widely recognized that adult GH deficiency (GHD) syndrome is characterized by central fat accumulation, reduced insulin sensitivity and dyslipidaemic pro- file with increased triglycerides, preponderance of small dense LDL and decreased HDL-cholesterol, representing a cluster of abnormalities described in the metabolic syndrome that identi- fies people at high risk of cardiovascular disease. 2,3 The majority of studies of GH replacement therapy have shown favourable changes in fasting lipid profile in terms of reduction in total- and LDL-cholesterol. 4,5 Although it is widely accepted that total- cholesterol, LDL-cholesterol and HDL-cholesterol represent independent risk factors for cardiovascular disease, 6 postprandial triglyceride levels have received more attention. 7,8 Indeed, postprandial triglyceride-rich remnant lipoproteins, derived from lipolysis of triglycerides within chylomicrons, are able to reach the endothelial cell layer and promote the genesis of foam cells, an early step of the atherogenic process. Therefore, impaired postprandial metabolism of triglycerides in terms of a higher peak or delayed clearance may provide an accumula- tion of these atherogenic particles. Considering that non-fast- ing state represents the preponderant part of a day and that triglyceride clearance after a meal may take up to 12 h, triglyceride measurement in non-fasting samples may provide a powerful tool to predict the risk of cardiovascular events. 9 In contrast to the abundant literature on the effect of GH replacement therapy on fasting lipid metabolism, 4,5,10–12 only Correspondence: Angela Ida Pincelli, Clinica Medica, Ospedale San Gerardo dei Tintori, Universita` Milano-Bicocca, Via Pergolesi 33, 20900 Monza, Italy. Tel.: +390392339790; Fax: +390392333349; E-mail: angelaida.pincelli@noesim.it © 2012 Blackwell Publishing Ltd 721 Clinical Endocrinology (2012) 77, 721–727 doi: 10.1111/j.1365-2265.2012.04416.x