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LDL physical properties, lipoprotein and Lp(a) levels in acromegalic patients. Effects of octreotide therapy

      Abstract

      High vascular morbidity and mortality is associated with acromegaly. The aim of the present study was to assess the effects of octreotide therapy on several known cardiovascular risk factors and to correlate them with octreotide-induced hormonal changes. Lipid levels, LDL particle size distribution as evaluated by single vertical spin density gradient ultracentrifugation, apolipoproteins AI and B, lipoprotein (a) [Lp(a)] concentrations and apo(a) phenotypes were evaluated in 20 non-diabetic acromegalic patients (6 M, 14 F), with normal thyroid, adrenal and gonadal function, aged 29–66 years. Normal subjects (20), matched for age, sex and BMI served as control for lipid variables. Acromegalic patients were characterized by lower HDL cholesterol (and apoA-I) and by higher Lp(a) concentrations in comparison to controls. Treatment with octreotide (100 μg t.i.d. for 3 months) led to: an increase in HDL cholesterol (median: +22%), a decrease in LDL cholesterol (−14%) and a decrease of the Lp(a) levels (all phenotypes) (−28%). The expected decreases of IGF-I levels (median: −48%) and 7-h AUC of GH (−50%), insulin (−40%), and glucagon (−20%) were observed. Only Lp(a) modifications showed a correlation with GH modifications. The study of LDL physical properties showed that acromegalic patients had smaller and/or more dense LDL particles, in comparison with normal controls (relative flotation rate, Rf: 0.40±0.03 versus 0.42±0.02 P<0.05), an alteration that might contribute to the high vascular risk of acromegalic patients. However, the LDL subfraction distribution remained unmodified during octreotide therapy (Rf 0.39±0.03). In conclusion, this study shows that in acromegalic patients octreotide treatment is indeed associated with an amelioration of some lipoprotein parameters, i.e. LDL, HDL, and Lp(a) concentrations. However, this treatment has no effect on the small and/or dense LDL particles present in these patients.

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      References

        • Bates A.S.
        • Van’t Hoff W.
        • Jones J.M.
        • Clayton R.N.
        An audit of outcome of treatment in acromegaly.
        Qrt. J. Med. 1993; 86: 293-299
        • Rajasoorya C.
        • Holdaway I.M.
        • Wrightson P.
        • Scott D.J.
        • Ibbertson H.K.
        Determinants of clinical outcome and survival in acromegaly.
        Clin. Endocrinol. 1994; 41: 95-102
        • Arosio M.
        • Macchelli S.
        • Rossi C.M.
        • et al.
        Effects of treatment with octreotide in acromegalic patients-a multicenter Italian study.
        Eur. J. Endocrinol. 1995; 133: 430-439
        • Lamarche B.
        • Tchernof A.
        • Moorjani S.
        • et al.
        Small, dense low-density lipoprotein particles as predictor of the risk of ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study.
        Circulation. 1997; 95: 69-75
        • Nosadini R.
        • Manzato E.
        • Solini A.
        • et al.
        Peripheral, rather than hepatic, insulin resistance and atherogenic lipoprotein phenotype predict cardiovascular complications in NIDDM.
        Eur. J. Clin. Invest. 1994; 24: 258-266
        • Tan K.C.B.
        • Shiu S.W.M.
        • Janus E.D.
        • Lam K.S.L.
        LDL subfractions in acromegaly: relation to growth hormone and insulin-like growth factor-I.
        Atherosclerosis. 1997; 129: 59-65
        • Kostner G.M.
        • Avogaro P.
        • Cazzolato G.
        • Marth E.
        • Bittolo-Bon G.
        • Quinci G.B.
        Lipoprotein Lp(a) and the risk for myocardial infarction.
        Atherosclerosis. 1981; 38: 51-61
        • Rosengren A.
        • Wilhelmsen L.
        • Eriksson E.
        • Risberg B.
        • Wedel H.
        Lipoprotein (a) and coronary heart disease in a general population sample of middle-aged men.
        Brit. Med. J. 1990; 301: 1248-1250
        • Bostom A.G.
        • Cupples L.A.
        • Jenner J.L.
        • et al.
        Elevated plasma lipoprotein (a) and coronary heart disease in men aged 55 years and younger. A prospective study.
        JAMA. 1996; 276: 544-548
        • Lam K.S.L.
        • Pang R.W.C.
        • Janus E.D.
        • Kung A.W.C.
        • Wang C.C.L.
        Serum apolipoprotein(a) correlates with growth hormone levels in Chinese patients with acromegaly.
        Atherosclerosis. 1993; 104: 183-188
        • Mooser V.
        • Hobbs H.H.
        Lipoprotein(a) and growth hormone: is the puzzle solved?.
        Eur. J. Endocrinol. 1997; 137: 450-452
      1. The Expert Committee on the diagnosis and classification of diabetes mellitus. Report of the Expert Committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997;20:1183–1197.

        • Roschlau V.P.
        • Bernt E.
        • Gruber W.
        Enzymatische Bestimmung des Gesamt Cholesterins in Serum.
        Klin. Chem. Klin. Biochem. 1974; 12: 403-407
      2. Lipid Research Clinics Program. Lipid and lipoprotein analysis. In: US Department of Health and Human Service, editor. Manual of Laboratory Operations, 2nd edition, Washington DC, 1982: 63–77.

        • Wahlefeld A.W.
        Triglycerides determination after enzymatic hydrolysis.
        in: Bergmeyer H.U. Methods of Enzymatic Analysis. Academic Press, 1976, New York1976: 1831-1835
        • Friedewald W.T.
        • Levy R.I.
        • Fredrickson D.S.
        Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.
        Clin. Chem. 1972; 18: 499-502
        • Chung B.H.
        • Wilkinson T.
        • Geer J.C.
        • Segrest J.P.
        Preparative and quantitative isolation of plasma lipoproteins: rapid, single discontinuous density gradient ultracentrifugation in a vertical rotor.
        J. Lipid. Res. 1980; 21: 284-291
        • Chung B.H.
        • Segrest J.P.
        • Ray M.J.
        • et al.
        Single vertical spin density gradient ultracentrifugation.
        in: Segrest J.P. Albers J.J. Methods in Enzymology, vol 128. Plasma Lipoproteins: Preparation, Structure and Molecular Biology. Academic Press, Orlando, FL1986: 181-209
        • Utermann G.
        • Menzel H.J.
        • Kraft H.G.
        • Duba H.C.
        • Kemmier H.G.
        • Seitz C.
        Lp(a) glycoprotein phenotypes. Inheritance and relation to Lp(a)-lipoprotein concentrations in plasma.
        J. Clin. Invest. 1987; 80: 458-465
        • Barreca A.
        • Ciccarelli E.
        • Minuto F.
        • Bruzzi P.
        • Giordano G.
        • Camanni F.
        Insulin-like growth factor I and daily growth hormone profile in the assessment of active acromegaly.
        Acta. Endocrinol. 1989; 120: 635-639
        • James R.A.
        • Møller N.
        • Chatterjee S.
        • White M.
        • Kendall-Taylor P.
        Carbohydrate tolerance and serum lipids in acromegaly before and during treatment with high dose octreotide.
        Diabetic Med. 1991; 8: 517-523
        • Sassolas G.
        • Harris A.G.
        • James-Deidier A.
        Long term effect of incremental doses of the somatostatin analog SMS 201-995 in 58 acromegalic patients.
        J. Clin. Endocrinol. Metab. 1990; 71: 391-397
        • Cohen R.
        • Chanson P.
        • Bruckert E.
        • et al.
        Effects of octreotide on lipid metabolism in acromegaly.
        Horm. Metab. Res. 1992; 24: 397-400
        • Simsolo R.B.
        • Ezzat S.
        • Ong J.M.
        • Saghizadeh M.
        • Kern P.A.
        Effects of acromegaly treatment and growth hormone on adipose tissue lipoprotein lipase.
        J. Clin. Endocrinol. Metab. 1995; 80: 3233-3238
        • Wildbrett J.
        • Hanefeld M.
        • Fucker K.
        • et al.
        Anomalies of lipoprotein pattern and fibrinolysis in acromegalic patients: relation to growth hormone levels and insulin-like growth factor I.
        Exp. Clin. Endocrinol. Diabetes. 1997; 105: 331-335
        • Rudling M.
        • Norstedt G.
        • Olivecrona H.
        • Reihnér E.
        • Gustafsson J.-Å.
        • Angelin B.
        Importance of growth hormone for the induction of hepatic low density lipoprotein receptors.
        Proc. Natl. Acad. Sci. USA. 1992; 89: 6983-6987
        • Murase T.
        • Yamada N.
        • Ohsawa N.
        • Kosaka K.
        • Morita S.
        • Yoshida S.
        Decline of postheparin plasma lipoprotein lipase in acromegalic patients.
        Metabolism. 1980; 29: 666-672
        • Fineberg S.E.
        • Merimee T.J.
        • Rabinowitz D.
        • Edgar P.J.
        Insulin secretion in acromegaly.
        J. Clin. Endocrinol. Metab. 1970; 30: 288-292
        • Hansen I.
        • Tsalikian E.
        • Beaufrere B.
        • Gerich J.
        • Haymond M.
        • Rizza R.
        Insulin resistance in acromegaly: defects in both hepatic and extra-hepatic insulin action.
        Am. J. Physiol. 1986; 250: 269-273
        • Zambon S.
        • Manzato E.
        • Solini A.
        • et al.
        Lipoprotein abnormalities in non-insulin-dependent diabetic patients with impaired extrahepatic insulin sensitivity, hypertension, and microalbuminuria.
        Arterioscler. Thromb. 1994; 14: 911-917
        • Zambon A.
        • Austin M.A.
        • Brown B.G.
        • Hokanson J.E.
        • Brunzell J.D.
        Effect of hepatic lipase on LDL in normal men and those with coronary artery disease.
        Arterioscler. Thromb. 1993; 13: 147-152
        • Ho K.K.
        • Jenkins A.B.
        • Furler S.M.
        • Borkman M.
        • Chisholm D.J.
        Impact of octreotide, a long-acting somatostatin analogue, on glucose tolerance and insulin sensitivity in acromegaly.
        Clin. Endocrinol. 1992; 36: 271-279
        • Sato K.
        • Takamatsu K.
        • Hashimoto K.
        Short-term effects of octreotide on glucose tolerance in patients with acromegaly.
        Endocrinol. J. 1995; 42: 739-745
        • Laron Z.
        • Wang X.L.
        • Klinger B.
        • Silbergeld A.
        • Wilcken D.E.L.
        Insulin-like growth factor-I decreases serum lipoprotein (a) during long-term treatment of patients with Laron syndrome.
        Metabolism. 1996; 45: 1263-1266