Metabolic abnormalities in patients with prolactinoma: response to treatment with cabergoline

Diabetology & Metabolic Syndrome

Rayees A. Dar¹  Raiz A. Misgar²  Bashir A. Laway²  Nazir A. Pala² 

[1] Department of Biostatics, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India;Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India

关键词: Lipids;    Prolactin;    Insulin resistance;    Metabolic syndrome;    Hyperprolactinemia;    Cabergoline;   

Others  :  1234357
DOI  :  10.1186/s13098-015-0094-4

 received in 2015-08-04, accepted in 2015-11-02,  发布年份 2015

【 摘 要 】

Background

Hyperprolactinemia has been associated with changes in body composition and metabolic abnormalities. Normalization of prolactin (PRL) with dopamine agonists has been found to reverse these abnormalities. This study was designed to assess the anthropometric and metabolic alterations associated with prolactinoma and response of these abnormalities to cabergoline treatment.

Methods

In a non-randomised matched prospective design, 19 consecutive patients with prolactinoma (median PRL 118.6 (105.3) μg/L) and 20 controls were studied. The controls were age, gender and body mass index (BMI) matched. Anthropometric data and metabolic variables were studied at baseline, 3 and 6 months after cabergoline treatment.

Results

Patients with prolactinoma had increased level of fasting plasma glucose (P < .001), LDL-cholesterol (P = .001) and triglycerides (TG) (P = .009) as compared to age, gender and BMI matched healthy controls. There was a significant decrease of body weight at 3 months (P = .029), with a further decline at 6 months (P < .001) of cabergoline therapy. In addition, there was a significant decrement of BMI (P < .001), waist circumference (P = .003), waist-hip ratio (P = .03) and total body fat (P = .003) at 6 months of cabergoline treatment. A significant decline in plasma glucose (P < .001), total cholesterol (P = .009), LDL-cholesterol (P < .001) and TG (P < .001) was seen after 6 months of cabergoline treatment.

Conclusions

Patients with prolactinoma have adverse metabolic profile compared with matched controls. Normalization of PRL with cabergoline corrects all the metabolic abnormalities.

【 授权许可】

   
2015 Pala et al.

【 参考文献 】

• [1]Knudtzon J, Johansen PW, Haug E, Gautvik K: Effects of hypersecretion of growth hormone and prolactin on plasma levels of glucagon and insulin in GH3-cell tumor-bearing rats, and the influence of bromocriptine treatment. Life Sci 1986, 39:617-621.
• [2]Byatt JC, Staten NR, Salsgiver WJ, Kostelc JG, Collier RJ: Stimulation of food intake and weight gain in mature female rats by bovine prolactin and bovine growth hormone. Am J Physiol 1993, 264:E986-E992.
• [3]Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA: Prolactin and its receptor: actions signal transduction pathways and phenotypes observed in prolactin receptor knockout mice. Endocr Rev 1998, 19:225-268.
• [4]Ben-Jonathan N, Hugo ER, Brandebourg TD, LaPensee CR: Focus on prolactin as a metabolic hormone. Trends Endocrinol Metab 2006, 17:110-116.
• [5]Moore BJ, Gerardo-Gettens T, Horvitz BA, Stern JS: Hyperprolactinemia stimulates food intake in the female rat. Brain Res Bull 1986, 17:563-569.
• [6]Shibli-Rahhal A, Schlechte J: The effects of hyperprolactinemia on bone and fat. Pituitary. 2009, 12:96-104.
• [7]Doknic M, Pekic S, Zarkovic M, Medic-Stojanoska M, Dieguez C, Casanueva F, et al.: Dopaminergic tone and obesity: an insight from prolactinoma treated with bromocriptine. Eur J Endocrinol 2002, 147:77-84.
• [8]Gualillo O, Lago F, García M, Menéndez C, Señarís R, Casanueva FF, et al.: Prolactin stimulates leptin secretion by rat white adipose tissue. Endocrinology 1999, 140:5149-5153.
• [9]Nilsson L, Binart N, Bohlooly-Y M, Bramnert M, Egecioglu E, Kindblom J, et al.: Prolactin and growth hormone regulate adiponectin secretion and receptor expression in adipose tissue. Biochem Biophys Res Commun. 2005, 331:1120-1126.
• [10]Schmid C, Goede DL, Hauser RS, Brändle M: Increased prevalence of high body mass index in patients presenting with pituitary tumours: severe obesity in patients with macroprolactinoma. Swiss Med Wkly. 2006, 136:254-258.
• [11]Serri O, Beauregard H, Rasio E, Hardy J: Decreased sensitivity to insulin in women with microprolactinomas. Fertil Steril 1986, 45:572-574.
• [12]Maccario M, Grottoli S, Razzore P, Procopio M, Oleandri SE, Ciccarelli E, et al.: Effects of glucose load and/or arginine on insulin and growth hormone secretion in hyperprolactinemia and obesity. Eur J Endocrinol 1996, 135:205-210.
• [13]Ling C, Svensson L, Odén B, Weijdegård B, Edén B, Edén S, et al.: Identification of functional prolactin (PRL) receptor gene expression: PRL inhibits lipoprotein lipase activity in human white adipose tissue. J Clin Endocrinol Metab 2003, 88:1804-1808.
• [14]Creemers LB, Zelissen PM, van`t Verlaat JW, Koppeschaar HP: Prolactinoma and body weight: a retrospective study. Acta Endocrinol 1991, 125:392-396.
• [15]Galluzzi F, Salti R, Stagi S, La Cauza F, Chiarelli F: Reversible weight gain and prolactin levels—long-term follow-up in childhood. J Pediatr Endocrinol Metab 2005, 18:921-924.
• [16]LaPensee CR, Horseman ND, Tso P, Brandebourg TD, Hugo ER, Ben-Jonathan N: The prolactin-deficient mouse has an unaltered metabolic phenotype. Endocrinology 2006, 147:4638-4645.
• [17]Masao K, Nobuo Y, Toshimasa O, Yoshio N, Paul Z, Shuji I: Criteria and classification of obesity in Japan and Asia-Oceania. Asia Pacific J Clin Nutr. 2002, 11:S732-S737.
• [18]Naliato EC, Violante AH, Caldas D, Lamounier Filho A, Loureiro CR, Fontes R, et al.: Body fat in nonobese women with prolactinoma treated with dopamine agonists. Clin Endocrinol. 2007, 67:845-852.
• [19]Berinder K, Nystrom T, Hoybye C, Hall K, Hulting AL: Insulin sensitivity and lipid profile in prolactinoma patients before and after normalization of prolactin by dopamine agonist therapy. Pituitary 2011, 14:199-207.
• [20]Landgraf R, Landraf-Leurs MM, Weissmann A, Hörl R, von Werder K, Scriba PC: Prolactin: a diabetogenic hormone. Diabetologia 1977, 13:99-104.
• [21]Tuzcu A, Bahceci M, Dursun M, Turgut C, Bahceci S: Insulin sensitivity and hyperprolactinemia. J Endocrinol Invest 2003, 26:341-346.
• [22]Bahceci M, Tuzcu A, Bahceci S, Tuzcu S: Is hyperprolactinemia associated with insulin resistance in non-obese patients with polycystic ovary syndrome? J Endocrinol Invest 2003, 26:655-659.
• [23]Yavuz D, Deyneli O, Akpinar I, Yildiz E, Gözü H, Sezgin O, et al.: Endothelial function, insulin sensitivity and inflammatory markers in hyperprolactinemic pre-menopausal women. Eur J Endocrinol 2003, 149:187-193.
• [24]Greenman Y, Tordjman K, Stern N: Increased body weight associated with prolactin-secreting pituitary adenomas: weight loss with normalization of prolactin levels. Clin Endocrinol 1998, 48:547-553.
• [25]Pelkonen R, Nikkilä EA, Grahne B: Serum lipids, postheparin plasma lipase activities and glucose tolerance in patients with prolactinoma. Clin Endocrinol 1982, 16:383-390.
• [26]Heshmati HM, Turpin G, de Gennes JL: Chronic hyperprolactinemia and plasma lipids in women. Klin Wochenschr. 1987, 65:516-519.
• [27]Fahy U, Hopton MI, Hartog M, Bolton CH, Hull MG: The lipoprotein profile of women with hyperprolactinaemic amenorrhoea. Hum Reprod 1999, 14:285-287.
• [28]Kok P, Roelfsema F, Frölich M, Frölich M, van Pelt J, Stokkel MP, et al.: Activation of dopamine D2 receptors simultaneously ameliorates various metabolic features of obese women. Am J Physiol Endocrinol Metab. 2006, 291:E1038-E1043.
• [29]Lachelin GC, Abu-fadil S, Yen SS: Functional delineation of hyperprolactinemic-amenorrhea. J Clin Endocrinol Metab 1977, 44:1163-1174.
• [30]Nunes MC, Sobrinho LG, Calhaz-Jorge C, Santos MA, Mauricio JC, Sousa MF: Psychosomatic factors in patients with hyperprolactinemia and/or galactorrhea. Obstet Gynecol 1980, 55:591-595.
• [31]Auriemma RS, Granieri L, Galdiero M, Simeoli C, Perone Y, Vitale P, et al.: Effect of cabergoline on metabolism in prolactinomas. Neuroendocrinology 2013, 98:299-310.
• [32]Brandebourg T, Hugo E, Ben-Jonathan N: Adipocyte prolactin: regulation of release and putative functions. Diabetes Obes Metab 2007, 9:464-476.
• [33]Serri O, Li L, Mamputu JC, Beauchamp MC, Maingrette F, Renier G: The influences of hyperprolactinemia and obesity on cardiovascular risk markers: effects of cabergoline therapy. Clin Endocrinol 2006, 64:366-370.
• [34]dos Santos Silva CM, Barbosa FR, Lima GA, Warszawski L, Fontes R, Domingues RC, et al.: BMI and metabolic profile in patients with prolactinoma before and after treatment with dopamine agonists. Obesity (Silver Spring). 2011, 19:800-805.
• [35]Inancli SS, Usluogullari A, Ustu Y, Caner S, Tam AA, Ersoy R, et al.: Effect of Cabergolin on insulin sensitivity, inflammation and carotid intimal thickness in patients with prolactinoma. Endocrine 2013, 44:193-199.
• [36]Gibson CD, Karmally W, McMahon DJ, Wardlaw SL, Korner J: Randomized pilot study of cabergoline, a dopamine receptor agonist: effects on body weight and glucose tolerance in obese adults. Diabetes Obe Metab. 2012, 14:335-340.
• [37]Kamath V, Jones CN, Yip JC, Varasteh BB, Cincotta AH, Reaven GM, et al.: 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 1997, 20:1697-1701.
• [38]Ciresi A, Amato MC, Guarnotta V, Lo Castro F, Giordano C: Higher doses of cabergoline further improve metabolic parameters in patients with prolactinoma regardless of the degree of reduction in prolactin levels. Clin Endocrinol. 2013, 79:845-852.