The Effect of Pituitary Gland Disorders on Glucose Metabolism: From Pathophysiology to Management

Guy I. Sydney; Konstantinos Michalakis; Ilias P. Nikas; Eleftherios Spartalis; Stavroula A. Paschou

doi:10.1055/a-1258-8625

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2021; 53(01): 16-23
DOI: 10.1055/a-1258-8625

Review

The Effect of Pituitary Gland Disorders on Glucose Metabolism: From Pathophysiology to Management

Authors

Guy I. Sydney

¹Center for Pediatric Clinical Effectiveness, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Konstantinos Michalakis

²Imperial College of Medicine, London, UK
Ilias P. Nikas

³School of Medicine, European University Cyprus, Nicosia, Cyprus
Eleftherios Spartalis

⁴2nd Department of Propaedeutic Surgery, National and Kapodistrian University of Athens, Athens, Greece
Stavroula A. Paschou

³School of Medicine, European University Cyprus, Nicosia, Cyprus

⁵School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

Abstract

This review aims to explore, present, and discuss disorders of glucose metabolism implicated in pituitary gland diseases, the appropriate interventions, as well as the therapeutic challenges that may arise. Pituitary pathologies may dysregulate glucose homeostasis, as both the excess and deficiency of various pituitary hormones can affect glucose metabolism. Increased circulating levels of growth hormone, glucocorticoids or prolactin have been shown to mainly provoke hyperglycemic states, while hypopituitarism can be associated with both hyperglycemia and hypoglycemia. Addressing the primary cause of these disorders with the use of surgery, medical treatment or radiotherapy forms the cornerstone of current management strategies. Physicians should bear in mind that some such medications have an unfavorable effect on glucose metabolism too. When unsuccessful, or until the appropriate treatment of the underlying pituitary problem, the addition of established antidiabetic therapies might prove useful. Further studies aiming to discover more accurate and effective drug preparations in combination with optimal lifestyle management models will contribute to achieving a more successful glycemic control in these patients.

Key words

acromegaly - hyperprolactinemia - hypoglycemia - hyperglycemia - pituitary - type 2 diabetes

Full Text

References

References
1 Dal J, List EO, Jorgensen JOL. et al. Glucose and fat metabolism in acromegaly: from mice models to patient care. Neuroendocrinology 2016; 103: 96-105
2 Schernthaner G, Prager R, Punzengruber C. et al. Severe hyperprolactinaemia is associated with decreased insulin binding in vitro and insulin resistance in vivo. Diabetologia 1985; 28: 138-142
3 Dogan BA, Berker D, Arduc A. et al. Insulin resistance and androgen levels in eugonadic and hypogonadic women with prolactinoma. Minerva Endocrinol 2016; 41: 175-182
4 Geer EB, Shen W, Strohmayer E. et al. Body composition and cardiovascular risk markers after remission of Cushing’s Disease: A prospective study using whole-body MRI. J Clin Endocrinol Metab 2012; 97: 1702-1711
5 Munir A, Newell-Price J. Management of diabetes mellitus in cushing’s syndrome. Neuroendocrinology 2010; 92: 82-85
6 Geer EB, Islam J, Buettner C. Mechanisms of glucocorticoid-induced insulin resistance. Endocrinol Metab Clin North Am 2014; 43: 75-102
7 Gazzaruso C, Gola M, Karamouzis I. et al. Cardiovascular risk in adult patients with growth hormone (GH) deficiency and following substitution with GH—an update. J Clin Endocrinol Metab 2014; 99: 18-29
8 Barkan AL, Burman P, Clemmons DR. et al. Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant. J Clin Endocrinol Metab 2005; 90: 5684-5691
9 Ben-Shlomo A, Melmed S. Acromegaly. Endocrinol Metab Clin North Am 2008; 37: 101-122
10 Chen Y, Sun D, Krishnamurthy VMR. et al. Endotoxin attenuates growth hormone-induced hepatic insulin-like growth factor I expression by inhibiting JAK2/STAT5 signal transduction and STAT5b DNA binding. Am J Physiol Metab 2007; 292: E1856-E1862
11 Paschou SA, Kanaka-Gantenbein C, Chrousos GP. et al. Growth hormone axis in patients with chronic kidney disease. Hormones 2019; 18: 71-73
12 Clemmons DR. Metabolic actions of insulin-like growth factor-i in normal physiology and diabetes. Endocrinol Metab Clin North Am 2012; 41: 425-443
13 Burks DJ, White MF. IRS proteins and beta-cell function. Diabetes 2001; 50: S140-S145
14 Colao A, Auriemma RS, Galdiero M. et al. Impact of somatostatin analogs versus surgery on glucose metabolism in acromegaly: results of a 5-year observational, open, prospective study. J Clin Endocrinol Metab 2009; 94: 528-537
15 Ronchi CL, Varca V, Beck-Peccoz P. et al. Comparison between six-year therapy with long-acting somatostatin analogs and successful surgery in acromegaly: effects on cardiovascular risk factors. J Clin Endocrinol Metab 2006; 91: 121-128
16 Colao A, Auriemma RS, Savastano S. et al. Glucose tolerance and somatostatin analog treatment in acromegaly: A 12-Month Study. J Clin Endocrinol Metab 2009; 94: 2907-2914
17 Baldelli R, Battista C, Leonetti F. et al. Glucose homeostasis in acromegaly: effects of long-acting somatostatin analogues treatment. Clin Endocrinol (Oxf) 2003; 59: 492-499
18 McKeage K. Pasireotide in acromegaly: a review. Drugs 2015; 75: 1039-1048
19 Henry RR, Ciaraldi TP, Armstrong D. et al. Hyperglycemia associated with pasireotide: results from a mechanistic study in healthy volunteers. J Clin Endocrinol Metab 2013; 98: 3446-3453
20 Ghigo E, Biller BMK, Colao A. et al. Comparison of pegvisomant and long-acting octreotide in patients with acromegaly naïve to radiation and medical therapy. J Endocrinol Invest 2009; 32: 924-933
21 Bajetta E, Procopio G, Catena L. et al. Lanreotide autogel every 6 weeks compared with lanreotide microparticles every 3 weeks in patients with well differentiated neuroendocrine tumors. Cancer 2006; 107: 2474-2481
22 Singh V, Brendel MD, Zacharias S. et al. Characterization of somatostatin receptor subtype-specific regulation of insulin and glucagon secretion: An in vitro study on isolated human pancreatic islets. J Clin Endocrinol Metab 2007; 92: 673-680
23 Bruns C, Lewis I, Briner U. et al. SOM230: A novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol 2002; 707-716
24 Atiya A. Intraislet somatostatin inhibits insulin (via a subtype-2 somatostatin receptor) but not islet amyloid polypeptide secretion in the isolated perfused human pancreas. J Gastrointest Surg 1997; 1: 251-256
25 Schmid HA, Brueggen J. Effects of somatostatin analogs on glucose homeostasis in rats. J Endocrinol 2012; 212: 49-60
26 Ludvigsen E, Stridsberg M, Taylor JE. et al. Regulation of insulin and glucagon secretion from rat pancreatic islets in vitro by somatostatin analogues. Regul Pept 2007; 138: 1-9
27 Tzanela M, Vassiliadi DA, Gavalas N. et al. Glucose homeostasis in patients with acromegaly treated with surgery or somatostatin analogues. Clin Endocrinol (Oxf) 2011; 75: 96-102
28 Baroni MG, Giorgino F, Pezzino V. et al. Italian Society for the study of diabetes (SID)/italian endocrinological society (SIE) guidelines on the treatment of hyperglycemia in cushing’s syndrome and acromegaly. J Endocrinol Invest 2016; 39: 235-255
29 Auriemma RS, De Alcubierre D, Pirchio R. et al. Glucose abnormalities associated to prolactin secreting pituitary adenomas. Front Endocrinol (Lausanne) 2019; 10: 327
30 Nilsson L, Binart N, Bohlooly-Y M. et al. Prolactin and growth hormone regulate adiponectin secretion and receptor expression in adipose tissue. Biochem Biophys Res Commun 2005; 331: 1120-1126
31 Brandebourg T, Hugo E, Ben-Jonathan N. Adipocyte prolactin: regulation of release and putative functions. Diabetes, Obes Metab 2007; 9: 464-476
32 Ling C, Svensson L, Oden B. 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
33 Hogan JC, Stephens JM. The regulation of fatty acid synthase by STAT5A. Diabetes 2005; 54: 1968-1975
34 Combs TP, Berg AH, Rajala MW. et al. Sexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin. Diabetes 2003; 52: 268-276
35 Weinhaus AJ, Stout LE, Bhagroo NV. et al. Regulation of glucokinase in pancreatic islets by prolactin: a mechanism for increasing glucose-stimulated insulin secretion during pregnancy. J Endocrinol 2007; 193: 367-381
36 Sorenson R, Brelje T. Adaptation of islets of langerhans to pregnancy: b-cell growth, enhanced insulin secretion and the role of lactogenic hormones. Horm Metab Res 1997; 29: 301-307
37 Labriola L, Montor WR, Krogh K. et al. Beneficial effects of prolactin and laminin on human pancreatic islet-cell cultures. Mol Cell Endocrinol 2007; 263: 120-133
38 Fleenor DE, Freemark M. Prolactin induction of insulin gene transcription: roles of glucose and signal transducer and activator of transcription 5*. Endocrinology 2001; 142: 2805-2810
39 Cejkova P, Fojtikova M, Cerna M. Immunomodulatory role of prolactin in diabetes development. Autoimmun Rev 2009; 9: 23-27
40 Landgraf R, Landgraf-Leurs MMC, Weissmann A. et al. Prolactin: a diabetogenic hormone. Diabetologia 1977; 13: 99-104
41 Tuzcu A, Yalaki S, Arikan S. et al. Evaluation of insulin sensitivity in hyperprolactinemic subjects by euglycemic hyperinsulinemic clamp technique. Pituitary 2009; 12: 330-334
42 Park S, Kim DS, Daily JW. et al. Serum prolactin concentrations determine whether they improve or impair β-cell function and insulin sensitivity in diabetic rats. Diabetes Metab Res Rev 2011; 27: 564-574
43 Park S, Kang S, Lee H-W. et al. Central prolactin modulates insulin sensitivity and insulin secretion in diabetic rats. Neuroendocrinology 2012; 95: 332-343
44 Doknic M, Pekic S, Zarkovic M. et al. Dopaminergic tone and obesity: An insight from prolactinomas treated with bromocriptine. Eur J Endocrinol 2002; 77-84
45 Lyons DJ, Hellysaz A, Broberger C. Prolactin regulates tuberoinfundibular dopamine neuron discharge pattern: novel feedback control mechanisms in the lactotrophic axis. J Neurosci 2012; 32: 8074-8083
46 Berinder K, Nystrom T, Hoybye C. et al. Insulin sensitivity and lipid profile in prolactinoma patients before and after normalization of prolactin by dopamine agonist therapy. Pituitary 2011; 14: 199-207
47 DeFronzo RA. Bromocriptine: A Sympatholytic, D2-Dopamine agonist for the treatment of type 2 diabetes. Diabetes Care 2011; 34: 789-794
48 Cincotta AH. Hypothalamic role in the insulin resistance syndrome In: insulin resistance syndrome. Hansen B, Shaffrir E, eds London: Taylor and Francis; 2002
49 Cincotta AH, Meier AH, Cincotta M. 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 1999; 8: 1683-1707
50 Pijl H, Ohashi S, Matsuda M. et al. Bromocriptine: a novel approach to the treatment of type 2 diabetes. Diabetes Care 2000; 23: 1154-1161
51 Gaziano JM, Cincotta AH, OConnor CM. et al. Randomized clinical trial of quick-release bromocriptine among patients with type 2 diabetes on overall safety and cardiovascular outcomes. Diabetes Care 2010; 33: 1503-1508
52 Pala NA, Laway BA, Misgar RA. et al. Metabolic abnormalities in patients with prolactinoma: response to treatment with cabergoline. Diabetol Metab Syndr 2015; 7: 99
53 Ruiz-Herrera X, de los Rios EA, Diosaz JM. et al. Prolactin promotes adipose tissue fitness and insulin sensitivity in obese males. Endocrinology 2016; 2016-1444
54 Wagner R, Heni M, Linder K. et al. Age-dependent association of serum prolactin with glycaemia and insulin sensitivity in humans. Acta Diabetol 2014; 51: 71-78
55 Balbach L, Wallaschofski H, Volzke H. et al. Serum prolactin concentrations as risk factor of metabolic syndrome or type 2 diabetes?. BMC Endocr Disord 2013; 13: 12
56 Li J, Rice MS, Huang T. et al. Circulating prolactin concentrations and risk of type 2 diabetes in US women. Diabetologia 2018; 61: 2549-2560
57 Fasshauer M, Klein J, Neumann S. et al. Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun 2002; 290: 1084-1089
58 Feelders RA, Pulgar SJ, Kempel A. et al. Management of endocrine disease: the burden of cushing’s disease: clinical and health-related quality of life aspects. Eur J Endocrinol 2012; 167: 311-326
59 Mazziotti G, Gazzaruso C, Giustina A. Diabetes in Cushing syndrome: basic and clinical aspects. Trends Endocrinol Metab 2011; 22: 499-506
60 Mazziotti G, Formenti AM, Frara S. et al. Diabetes in cushing disease. Curr Diab Rep 2017; 17: 32
61 Scaroni C, Zilio M, Foti M. et al. Glucose metabolism abnormalities in cushing syndrome: from molecular basis to clinical management. Endocr Rev 2017; 38: 189-219
62 Hofland LJ, Lamberts SWJ. The pathophysiological consequences of somatostatin receptor internalization and resistance. Endocr Rev 2003; 24: 28-47
63 Colao A, Petersenn S, Newell-Price J. et al. A 12-month phase 3 study of pasireotide in Cushing’s Disease. N Engl J Med 2012; 366: 914-924
64 MacKenzie Feder J, Bourdeau I, Vallette S. et al. Pasireotide monotherapy in cushing’s disease: a single-centre experience with 5-year extension of phase III trial. Pituitary 2014; 17: 519-529
65 Boscaro M, Bertherat J, Findling J. et al. Extended treatment of cushing’s disease with pasireotide: results from a 2-year, phase II study. Pituitary 2014; 17: 320-326
66 Davies MJ, DAlessio DA, Fradkin J. et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the american diabetes association (ADA) and the european association for the study of diabetes (EASD). Diabetes Care 2018; 41: 2669-2701
67 Ferrau F, Korbonits M. Metabolic comorbidities in cushing’s syndrome. Eur J Endocrinol 2015; 173: M133-M157
68 Upadhyay J, Polyzos SA, Perakakis N. et al. Pharmacotherapy of type 2 diabetes: an update. Metabolism 2018; 78: 13-42
69 Ambrosi B, DallAsta C, Cannavo S. et al. Effects of chronic administration of PPAR-gamma ligand rosiglitazone in cushing’s disease. Eur J Endocrinol 2004; 173-178
70 Cannavo S, Ambrosi B, Chiodini I. et al. Baseline and CRH-stimulated ACTH and cortisol levels after administration of the peroxisome proliferator-activated receptor-gamma ligand, rosiglitazone, in cushing’s disease. J Endocrinol Invest 2004; 27: RC8-RC11
71 Suri D, Weiss RE. Effect of pioglitazone on adrenocorticotropic hormone and cortisol secretion in cushing’s disease. J Clin Endocrinol Metab 2005; 90: 1340-1346
72 Nauck M, Stockmann F, Ebert R. et al. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 1986; 29: 46-52
73 van Raalte DH, van Genugten RE, Linssen MML. et al. Glucagon-like peptide-1 receptor agonist treatment prevents glucocorticoid-induced Glucose intolerance and islet-cell dysfunction in humans. Diabetes Care 2011; 34: 412-417
74 Conrado DJ, Krishnaswami S, Shoji S. et al. Predicting the probability of successful efficacy of a dissociated agonist of the glucocorticoid receptor from dose–response analysis. J Pharmacokinet Pharmacodyn 2016; 43: 325-341
75 Anderson A, Walker BR. 11b-HSD1 Inhibitors for the treatment of type 2 diabetes and cardiovascular disease. Drugs 2013; 73: 1385-1393
76 Lee NK, Sowa H, Hinoi E. et al. Endocrine regulation of energy metabolism by the skeleton. Cell 2007; 130: 456-469
77 Ioakim KJ, Sydney GI, Paschou SA. Glucose metabolism disorders in patients with adrenal gland disorders: pathophysiology and management. Hormones 2020; 19: 135-143
78 Hwang Y-C, Jeong I-K, Ahn KJ. et al. The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced b-cell function in middle-aged male subjects. Diabetes Metab Res Rev 2009; 25: 768-772
79 Winhofer Y, Handisurya A, Tura A. et al. Osteocalcin is related to enhanced insulin secretion in gestational diabetes mellitus. Diabetes Care 2010; 33: 139-143
80 Herrmann BL, Saller B, Stratmann M. et al. Effects of a combination of rhGH and metformin on adiponectin levels in patients with metabolic syndrome. Horm Metab Res 2005; 37: 49-52
81 Twickler TB, Cramer MJM, Dallinga-Thie GM. et al. Adult-onset growth hormone deficiency: relation of postprandial dyslipidemia to premature atherosclerosis. J Clin Endocrinol Metab 2003; 88: 2479-2488
82 Clemmons DR. The relative roles of growth hormone and IGF-1 in controlling insulin sensitivity. J Clin Invest 2004; 113: 25-27
83 Liu J-L, Coschigano KT, Robertson K. et al. Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice. Am J Physiol Metab 2004; 287: E405-E413
84 Guo Y, Lu Y, Houle D. et al. Pancreatic islet-specific expression of an insulin-like growth factor-i transgene compensates islet cell growth in growth hormone receptor gene-deficient mice. Endocrinology 2005; 146: 2602-2609
85 Gola M, Bonadonna S, Doga M. et al. Growth hormone and cardiovascular risk factors. J Clin Endocrinol Metab 2005; 90: 1864-1870
86 Miller KK, Biller BMK, Lipman JG. et al. Truncal adiposity, relative growth hormone deficiency, and cardiovascular risk. J Clin Endocrinol Metab 2005; 90: 768-774
87 Yuen KCJ, Frystyk J, White DK. et al. Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency. Clin Endocrinol (Oxf) 2005; 63: 428-436
88 Kim SY. Diagnosis and treatment of hypopituitarism. Endocrinol Metab 2015; 30: 443
89 Paschou SA, Vryonidou A, Goulis DG. Pituitary incidentalomas: a guide to assessment, treatment and follow-up. Maturitas 2016; 92: 143-149