Effect of cabergoline on insulin sensitivity, inflammation, and carotid intima media thickness in patients with prolactinoma
- 363 Downloads
- 14 Citations
Abstract
The aim of this study was to evaluate the effect of Cabergoline on insulin sensitivity, inflammatory markers, and carotid intima media thickness in prolactinoma patients. Twenty-one female, newly diagnosed patients with prolactinoma were included in the study. None of the patients were treated previously. Cabergoline was given as treatment, starting with 0.5 mg/day and tapered necessarily. Blood samples were taken for prolactin, highly sensitive C-reactive protein, homocysteine, total cholesterol, low density lipoprotein (LDL) cholesterol, fasting glucose, insulin, and HOMA (homeostasis model assessment of insulin resistance) score was calculated, prior to and 6 months after starting treatment. The body mass index (BMI) was measured and carotid intima media thickness (CIMT) was evaluated for each patient prior to and 6 months after the treatment. The prolactin levels and LDL decreased significantly after cabergoline treatment. Insulin sensitivity improved independently from the decrease in prolactin levels and BMI. The significant decrease in homocysteine and hs-CRP was not related with the decrease in prolactin levels. The significant decrease in CIMT was independent from the decrease in prolactin levels, HOMA score, and BMI. Our data suggest that cabergoline treatment causes an improvement in insulin sensitivity and inflammatory markers and causes a decrease in CIMT independent from the decrease in prolactin, LDL cholesterol, and BMI. We conclude that short term cabergoline treatment can improve endothelial function independently from the changes in metabolic disturbances and inflammatory markers.
Keywords
Prolactinoma Carotid intima media thickness Insulin resistance Inflammation AtherosclerosisNotes
Conflict of interest
Authors declare no conflict of interest.
References
- 1.N.D. Horseman, Prolactin and mammary gland development. J. Mammary Gland Biol. Neoplasia. 4(1), 79–88 (1999)PubMedCrossRefGoogle Scholar
- 2.G. Mazziotti, T. Porcelli, M. Mormando, E. De Menis, A. Bianchi, C. Mejia, T. Mancini, L. De Marinis, A. Giustina, Vertebral fractures in males with prolactinoma. Endocrine 39(3), 288–293 (2011). Epub 2011 Apr 10PubMedCrossRefGoogle Scholar
- 3.G. Mazziotti, T. Mancini, M. Mormando, E. De Menis, A. Bianchi, M. Doga, T. Porcelli, P.P. Vescovi, L. De Marinis, A. Giustina, High prevalence of radiological vertebral fractures in women with prolactin-secreting pituitary adenomas. Pituitary 14(4), 299–306 (2011)PubMedCrossRefGoogle Scholar
- 4.N. Ben-Jonathan, E.R. Hugo, T.D. Brandebourg, C.R. LaPensee, Focus on prolactin as a metabolic hormone. Trends Endocrinol. Metab. 17(3), 110–116 (2006)PubMedCrossRefGoogle Scholar
- 5.F.M. Reis, A.M. Reis, C.C. Coimbra, Effects of hyperprolactinaemia on glucose tolerance and insulin release in male and female rats. J. Endocrinol. 153(3), 423–428 (1997)PubMedCrossRefGoogle Scholar
- 6.M. Matsuda, T. Mori, Effect of estrogen on hyperprolactinemia-induced glucose intolerance in SHN mice. Proc. Soc. Exp. Biol. Med. 212(3), 243–247 (1996)PubMedCrossRefGoogle Scholar
- 7.K. Berinder, T. Nyström, C. Höybye, K. Hall, A.L. Hulting, Insulin sensitivity and lipid profile in prolactinoma patients before and after normalization of prolactin by dopamine agonist therapy. Pituitary 14(3), 199–207 (2011)PubMedCrossRefGoogle Scholar
- 8.R. Landgraf, M.M. Nyström Landraf-Leurs, A. Weissmann, R. Hörl, K. von Werder, P.C. Scriba, Prolactin: a diabetogenic hormone. Diabetologia 13(2), 99–104 (1977)PubMedCrossRefGoogle Scholar
- 9.D.E. Fleenor, M. Freemark, Prolactin induction of insulin gene transcription: roles of glucose and signal transducer and activator of transcription 5. Endocrinology 142(7), 2805–2810 (2001)PubMedCrossRefGoogle Scholar
- 10.M. Doknic, S. Pekic, M. Zarkovic, M. Medic-Stojanoska, C. Dieguez, F. Casanueva, V. Popovic, Dopaminergic tone and obesity: an insight from prolactinomas treated with bromocriptine. Eur. J. Endocrinol. 147(1), 77–84 (2002)PubMedCrossRefGoogle Scholar
- 11.O. Serri, L. Li, J.C. Mamputu, M.C. Beauchamp, F. Maingrette, G. Renier, The influences of hyperprolactinemia and obesity on cardiovascular risk markers: effects of cabergoline therapy. Clin. Endocrinol. (Oxf) 64(4), 366–370 (2006)Google Scholar
- 12.E.C. Naliato, A.H. Violante, D. Caldas, A. Lamounier Filho, C.R. Loureiro, R. Fontes, Y. Schrank, R.G. Souza, P.L. Costa, A. Colao, Body fat in nonobese women with prolactinoma treated with dopamine agonists. Clin. Endocrinol. (Oxf). 67(6), 845–852 (2007). Epub 2007 Jul 20PubMedCrossRefGoogle Scholar
- 13.C.M. dos Santos Silva, F.R. Barbosa, G.A. Lima, L. Warszawski, R. Fontes, R.C. Domingues, M.R. Gadelha, BMI and metabolic profile in patients with prolactinoma before and after treatment with dopamine agonists. Obesity (Silver Spring) 19(4), 800–805 (2011)CrossRefGoogle Scholar
- 14.K. Dorshkind, N.D. Horseman, The roles of prolactin, growth hormone, insulin-like growth factor-I, and thyroid hormones in lymphocyte development and function: insights from genetic models of hormone and hormone receptor deficiency. Endocr. Rev. 21(3), 292–312 (2000)PubMedCrossRefGoogle Scholar
- 15.A.Q. Reuwer, M. van Eijk, F.M. Houttuijn-Bloemendaal, C.M. van der Loos, N. Claessen, P. Teeling, J.J. Kastelein, J. Hamann, V. Goffin, J.H. von der Thüsen, M.T. Twickler, J. Aten, The prolactin receptor is expressed in macrophages within human carotid atherosclerotic plaques: a role for prolactin in atherogenesis? J. Endocrinol. 208(2), 107–117 (2011)PubMedCrossRefGoogle Scholar
- 16.M.L. Bots, A.W. Hoes, P.J. Koudstaal, A. Hofman, D.E. Grobbee, Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation 96(5), 1432–1437 (1997)PubMedCrossRefGoogle Scholar
- 17.G.A. Georgiopoulos, K.S. Stamatelopoulos, I. Lambrinoudaki, M. Lykka, K. Kyrkou, D. Rizos, M. Creatsa, G. Christodoulakos, M. Alevizaki, P.P. Sfikakis, C. Papamichael, Prolactin and preclinical atherosclerosis in menopausal women with cardiovascular risk factors. Hypertension 54(1), 98–105 (2009). Epub 2009 May 18PubMedCrossRefGoogle Scholar
- 18.D.R. Matthews, J.P. Hosker, A.S. Rudenski, B.A. Naylor, D.F. Treacher, R.C. Turner, Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7), 412–419 (1985)PubMedCrossRefGoogle Scholar
- 19.A. Tuzcu, S. Yalaki, S. Arikan, D. Gokalp, M. Bahcec, S. Tuzcu, Evaluation of insulin sensitivity in hyperprolactinemic subjects by euglycemic hyperinsulinemic clamp technique. Pituitary 12(4), 330–334 (2009)PubMedCrossRefGoogle Scholar
- 20.A. Tuzcu, M. Bahceci, M. Dursun, C. Turgut, S. Bahceci, Insulin sensitivity and hyperprolactinemia. J. Endocrinol. Invest. 26(4), 341–346 (2003)PubMedGoogle Scholar
- 21.O. Serri, H. Beauregard, E. Rasio, J. Hardy, Decreased sensitivity to insulin in women with microprolactinomas. Fertil. Steril. 45(4), 572–574 (1986)PubMedGoogle Scholar
- 22.A.B. Gustafson, M.F. Banasiak, R.K. Kalkhoff, T.C. Hagen, H.J. Kim, Correlation of hyperprolactinemia with altered plasma insulin and glucagon: similarity to effects of late human pregnancy. J. Clin. Endocrinol. Metab. 51(2), 242–246 (1980)PubMedCrossRefGoogle Scholar
- 23.G. Schernthaner, R. Prager, C. Punzengruber, A. Luger, Severe hyperprolactinaemia is associated with decreased insulin binding in vitro and insulin resistance in vivo. Diabetologia 28(3), 138–142 (1985)PubMedGoogle Scholar
- 24.D. Yavuz, O. Deyneli, I. Akpinar, E. Yildiz, H. Gözü, O. Sezgin, G. Haklar, Endothelial function, insulin sensitivity and inflammatory markers in hyperprolactinemic pre-menopausal women. Eur. J. Endocrinol. 149(3), 187–193 (2003)PubMedCrossRefGoogle Scholar
- 25.C. Schmid, D.L. Goede, R.S. Hauser, M. Brändle, Increased prevalence of high body mass index in patients presenting with pituitary tumours: severe obesity in patients with macroprolactinoma. Swiss. Med. Wkly. 136(15–16), 254–258 (2006)PubMedGoogle Scholar
- 26.Y. Greenman, K. Tordjman, N. Stern, Increased body weight associated with prolactin secreting pituitary adenomas: weight loss with normalization of prolactin levels. Clin. Endocrinol. (Oxf). 48(5), 547–553 (1998)PubMedCrossRefGoogle Scholar
- 27.E. Delgrange, J. Donckier, D. Maiter, Hyperprolactinaemia as a reversible cause of weight gain in male patients? Clin. Endocrinol. (Oxf). 50(2), 271 (1999)PubMedCrossRefGoogle Scholar
- 28.R. Pelkonen, E.A. Nikkilä, B. Grahne, Serum lipids, postheparin plasma lipase activities and glucose tolerance in patients with prolactinoma. Clin. Endocrinol. (Oxf). 16(4), 383–390 (1982)PubMedCrossRefGoogle Scholar
- 29.U. Fahy, M.I. Hopton, M. Hartog, C.H. Bolton, M.G. Hull, The lipoprotein profile of women with hyperprolactinaemic amenorrhoea. Hum. Reprod. 14(2), 285–287 (1999)PubMedCrossRefGoogle Scholar
- 30.V. Kamath, C.N. Jones, J.C. Yip, B.B. Varasteh, A.H. Cincotta, G.M. Reaven, Y.D. Chen, Effects of a quick-release form of bromocriptine (Ergoset) on fasting and postprandial plasma glucose, insulin, lipid, and lipoprotein concentrations in obese nondiabetic hyperinsulinemic women. Diabetes Care 20(11), 1697–1701 (1997)PubMedCrossRefGoogle Scholar
- 31.A.H. Cincotta, A.H. Meier, M. Cincotta Jr, Bromocriptine improves glycaemic control and serum lipid profile in obese Type 2 diabetic subjects: a new approach in the treatment of diabetes. Expert Opin. Investig. Drugs 8(10), 1683–1707 (1999)PubMedCrossRefGoogle Scholar
- 32.H. Wallaschofski, A. Kobsar, O. Sokolova, M. Eigenthaler, T. Lohmann, Co-activation of platelets by prolactin or leptin—pathophysiological findings and clinical implications. Hormone Metab. Res. 36(1–6), 99 (2004)Google Scholar
- 33.H. Wallaschofski, M. Donne, M. Eigenthaler, B. Hentschel, R. Faber, H. Stepan, M. Koksch, T. Lohmann, PRL as a novel potent cofactor for platelet aggregation. J. Clin. Endocrinol. Metab. 86, 5912–5919 (2001)PubMedCrossRefGoogle Scholar
- 34.M. Franchini, G. Lippi, F. Manzato, P.P. Vescovi, G. Targher, Hemostatic abnormalities in endocrine and metabolic disorders. Eur. J. Endocrinol. 162(3), 439–451 (2010). Epub 2009 Nov 24PubMedCrossRefGoogle Scholar