Abstract
Hyperprolactinemia has been associated with impaired metabolism, including insulin resistance. However, the metabolic effects of elevated prolactin (PRL) levels are not completely clarified. The aim of this study was to obtain more insights of metabolic consequences in hyperprolactinemia patients. Fourteen consecutive patients, eight women and six men, aged 39.7 (±13.7) years with prolactinomas (median PRL 72 [49–131] μg/L in women and 1,260 [123–9,600] μg/L in men) were included. Anthropometric data and metabolic values were studied before and after 2 and 6 months on DA agonists (Bromocriptine [5.7 (±3.9) mg/day, n = 13] or Cabergoline [0.5 mg/week, n = 1]). Euglycemic hyperinsulinemic clamps were studied in six patients before and after 6 months of treatment. PRL normalized in all patients. Anthropometric data changed only in males with a significant decrease of median body weight (95.6 [80.7–110.1] to 83.4 [77.8–99.1] kg, P = 0.046), waist circumference and fat percentage after 6 months. LDL cholesterol was positively correlated to PRL at diagnosis (r = 0.62, P = 0.025) and decreased within 2 months (3.4 [±0.9] to 2.9 [±0.6] mmol/L, P = 0.003). Insulin, IGFBP-1 and total adiponectin levels did not change. Insulin sensitivity tended to improve after 6 months; M-value from 5.7 (±1.8) to 7.8 (±2.6) mg/kg/min, P = 0.083 and per cent improvement in M-value was correlated to per cent reduction in PRL levels (r = −0.85, P = 0.034). In conclusion, beneficial metabolic changes were seen in prolactinoma patients after treatment with DA agonists, underscoring the importance of an active treatment approach and to consider the metabolic profile in the clinical management of hyperprolactinemia patients.
Similar content being viewed by others
References
Ben-Jonathan N, Mershon JL, Allen DL, Steinmetz RW (1996) Extrapituitary prolactin: distribution, regulation, functions, and clinical aspects. Endocr Rev 17:639–669
Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA (1998) Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev 19:225–268
Ben-Jonathan N, Hugo ER, Brandebourg TD, LaPensee CR (2006) Focus on prolactin as a metabolic hormone. Trends Endocrinol Metab 17:110–116
Landgraf R, Landraf-Leurs MM, Weissmann A, Horl R, von Werder K, Scriba PC (1977) Prolactin: a diabetogenic hormone. Diabetologia 13:99–104
Johnston DG, Alberti KG, Nattrass M, Burrin JM, Blesa-Malpica G, Hall K, Hall R (1980) Hyperinsulinaemia in hyperprolactinaemic women. Clin Endocrinol (Oxf) 13:361–368
Schernthaner G, Prager R, Punzengruber C, Luger A (1985) Severe hyperprolactinemia is associated with decreased insulin binding in vitro and insulin resistance in vivo. Diabetologia 28:138–142
Serri O, Li L, Mamputu JC, Beauchamp MC, Maingrette F, Renier G (2006) The influences of hyperprolactinemia and obesity on cardiovascular risk markers: effects of cabergoline therapy. Clin Endocrinol (Oxf) 64:366–370
Tuzcu A, Bahceci M, Dursun M, Turgut C, Bahceci S (2003) Insulin sensitivity and hyperprolactinemia. J Endocrinol Invest 26:341–346
Yavuz D, Deyneli O, Akpinar I, Yildiz E, Gozu H, Sezgin O, Haklar G, Akalin S (2003) Endothelial function, insulin sensitivity and inflammatory markers in hyperprolactinemic pre-menopausal women. Eur J Endocrinol 149:187–193
Tuzcu A, Yalaki S, Arikan S, Gokalp D, Bahcec M, Tuzcu S (2009) Evaluation of insulin sensitivity in hyperprolactinemic subjects by euglycemic hyperinsulinemic clamp technique. Pituitary 12:330–334
Kamath V, Jones CN, Yip JC, Varasteh BB, Cincotta AH, Reaven GM, Chen YD (1997) 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 20:1697–1701
Cincotta AH, Meier AH, Cincotta M Jr (1999) Bromocriptine improves glycemic control and serum lipid profile in obese Type 2 diabetic subjects: a new approach in the treatment of diabetes. Expert Opin Investig Drugs 8:1683–1707
Pelkonen R, Nikkila EA, Grahne B (1982) Serum lipids, post heparin plasma lipase activities and glucose tolerance in patients with prolactinoma. Clin Endocrinol (Oxf) 16:383–390
Fahy U, Hopton MI, Hartog M, Bolton CH, Hull MG (1999) The lipoprotein profile of women with hyperprolactinemic amenorrhoea. Hum Reprod 14:285–287
Greenman Y, Tordjman K, Stern N (1998) Increased body weight associated with prolactin secreting pituitary adenomas: weight loss with normalization of prolactin levels. Clin Endocrinol (Oxf) 48:547–553
Schmid C, Goede DL, Hauser RS, Brandle M (2006) Increased prevalence of high Body Mass Index in patients presenting with pituitary tumours: severe obesity in patients with macroprolactinoma. Swiss Med Wkly 136:254–258
Doknic M, Pekic S, Zarkovic M, Medic-Stojanoska M, Dieguez C, Casanueva F, Popovic V (2002) Dopaminergic tone and obesity: an insight from prolactinomas treated with bromocriptine. Eur J Endocrinol 147:77–84
Delgrange E, Donckier J, Maiter D (1999) Hyperprolactinaemia as a reversible cause of weight gain in male patients? Clin Endocrinol (Oxf) 50:271
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419
Lukaski HC, Johnson PE, Bolonchuk WW, Lykken GI (1985) Assessment of fat-free mass using bioelectrical impedance measurements of the human body. Am J Clin Nutr 41:810–817
DeFronzo RA, Tobin JD, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237:E214–E223
Bang P, Eriksson U, Sara V, Wivall IL, Hall K (1991) Comparison of acid ethanol extraction and acid gel filtration prior to IGF-I and IGF-II radioimmunoassays: improvement of determinations in acid ethanol extracts by the use of truncated IGF-I as radioligand. Acta Endocrinol (Copenh) 124:620–629
Hilding A, Hall K, Wivall-Helleryd IL, Saaf M, Melin AL, Thoren M (1999) Serum levels of insulin-like growth factor I in 152 patients with growth hormone deficiency, aged 19–82 years, in relation to those in healthy subjects. J Clin Endocrinol Metab 84:2013–2019
Povoa G, Roovete A, Hall K (1984) Cross-reaction of serum somatomedin-binding protein in a radioimmunoassay developed for somatomedin-binding protein isolated from human amniotic fluid. Acta Endocrinol (Copenh) 107:563–570
Lewitt MS, Hilding A, Brismar K, Efendic S, Ostenson CG, Hall K (2010) IGF-binding protein 1 and abdominal obesity in the development of type 2 diabetes in women. Eur J Endocrinol 163:233–242
Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502
Erem C, Kocak M, Nuhoglu I, Yilmaz M, Ucuncu O (2009) Blood coagulation, fibrinolysis and lipid profile in patients with prolactinoma. Clin Endocrinol (Oxf) Dec 18. [Epub ahead of print]
Pijl H, Ohashi S, Matsuda M, Miyazaki Y, Mahankali A, Kumar V, Pipek R, Iozzo P, Lancaster JL, Cincotta AH, DeFronzo RA (2000) Bromocriptine: a novel approach to the treatment of type 2 diabetes. Diabetes Care 23:1154–1161
Rudling M, Norstedt G, Olivecrona H, Reihner E, Gustafsson JA, Angelin B (1992) Importance of growth hormone for the induction of hepatic low density lipoprotein receptors. Proc Natl Acad Sci USA 89:6983–6987
Dos Santos Silva CM, Barbosa FR, Lima GA, Warszawski L, Fontes R, Domingues RC, Gadelha MR (2010) BMI and metabolic profile in patients with prolactinoma before and after treatment with dopamine agonists. Obesity (Silver Spring) 17(9):1783–1788
Nilsson L, Binart N, Bohlooly YM, Bramnert M, Egecioglu E, Kindblom J, Kelly PA, Kopchick JJ, Ormandy CJ, Ling C, Billig H (2005) Prolactin and growth hormone regulate adiponectin secretion and receptor expression in adipose tissue. Biochem Biophys Res Commun 331:1120–1126
Brandebourg T, Hugo E, Ben-Jonathan N (2007) Adipocyte prolactin: regulation of release and putative functions. Diabetes Obes Metab 9:464–476
Kotronen A, Lewitt M, Hall K, Brismar K, Yki-Jarvinen H (2008) Insulin-like growth factor binding protein 1 as a novel specific marker of hepatic insulin sensitivity. J Clin Endocrinol Metab 93:4867–4872
Acknowledgments
We gratefully acknowledge RNs Ulrika Sjöstedt, Anette Härström, Agneta Hilding, Christina Häll and Lotta Larsson for taking excellent care of the patients and Inga-Lena Wivall-Helleryd for skilful technical assistance. This work was supported by grants from the Swedish Society of Medicine (2007-19869), Elin Danielsson foundation and Bert von Kantzows foundation.
Conflict of interest
The authors have nothing to declare.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Berinder, K., Nyström, T., Höybye, C. et al. Insulin sensitivity and lipid profile in prolactinoma patients before and after normalization of prolactin by dopamine agonist therapy. Pituitary 14, 199–207 (2011). https://doi.org/10.1007/s11102-010-0277-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11102-010-0277-9