{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T21:49:54Z","timestamp":1779140994238,"version":"3.51.4"},"reference-count":72,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,20]],"date-time":"2020-12-20T00:00:00Z","timestamp":1608422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nickel (Ni) is a ubiquitous metal, the exposure of which is implied in the development of contact dermatitis (nickel allergic contact dermatitis (Ni-ACD)) and Systemic Ni Allergy Syndrome (SNAS), very common among overweight\/obese patients. Preclinical studies have linked Ni exposure to abnormal production\/release of Growth Hormone (GH), and we previously found an association between Ni-ACD\/SNAS and GH-Insulin-like growth factor 1 (IGF1) axis dysregulation in obese individuals, altogether suggesting a role for this metal as a pituitary disruptor. We herein aimed to directly evaluate the pituitary gland in overweight\/obese patients with signs\/symptoms suggestive of Ni allergy, exploring the link with GH secretion; 859 subjects with overweight\/obesity and suspected of Ni allergy underwent Ni patch tests. Among these, 106 were also suspected of GH deficiency (GHD) and underwent dynamic testing as well as magnetic resonance imaging for routine follow up of benign diseases or following GHD diagnosis. We report that subjects with Ni allergies show a greater GH-IGF1 axis impairment, a higher prevalence of Empty Sella (ES), a reduced pituitary volume and a higher normalized T2 pituitary intensity compared to nonallergic ones. We hypothesize that Ni may be detrimental to the pituitary gland, through increased inflammation, thus contributing to GH-IGF1 axis dysregulation.<\/jats:p>","DOI":"10.3390\/ijms21249733","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T01:01:08Z","timestamp":1608512468000},"page":"9733","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Nickel Sensitivity Is Associated with GH-IGF1 Axis Impairment and Pituitary Abnormalities on MRI in Overweight and Obese Subjects"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2905-4398","authenticated-orcid":false,"given":"Renata","family":"Risi","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simonetta","family":"Masieri","sequence":"additional","affiliation":[{"name":"Department of Sensory Organs, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"Poggiogalle","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2225-8814","authenticated-orcid":false,"given":"Mikiko","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Caputi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3358-4204","authenticated-orcid":false,"given":"Rossella","family":"Tozzi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1044-2278","authenticated-orcid":false,"given":"Elena","family":"Gangitano","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Masi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1762-4701","authenticated-orcid":false,"given":"Stefania","family":"Mariani","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucio","family":"Gnessi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Lubrano","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lubrano, C., Saponara, M., Barbaro, G., Specchia, P., Addessi, E., Costantini, D., Tenuta, M., Di Lorenzo, G., Genovesi, G., and Donini, L.M. (2012). Relationships between body fat distribution, epicardial fat and obstructive sleep apnea in obese patients with and without metabolic syndrome. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047059"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e0145811","DOI":"10.1371\/journal.pone.0145811","article-title":"Fatty Liver Index Associates with Relative Sarcopenia and GH\/ IGF- 1 Status in Obese Subjects","volume":"7","author":"Poggiogalle","year":"2016","journal-title":"PLoS ONE"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s11886-020-1273-y","article-title":"Association Between Obesity and Cardiovascular Outcomes: Updated Evidence from Meta-analysis Studies","volume":"22","author":"Dwivedi","year":"2020","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/s41366-018-0076-3","article-title":"Ectopic fat obesity presents the greatest risk for incident type 2 diabetes: A population-based longitudinal study","volume":"43","author":"Okamura","year":"2019","journal-title":"Int. J. Obes. (Lond.)"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1007\/s12603-015-0638-1","article-title":"Sarcopenic Obesity and Metabolic Syndrome in Adult Caucasian Subjects","volume":"20","author":"Poggiogalle","year":"2016","journal-title":"J. Nutr. Health Aging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1111\/j.1742-1241.2009.02301.x","article-title":"Is obesity protective for osteoporosis? Evaluation of bone mineral density in individuals with high body mass index","volume":"64","author":"Greco","year":"2010","journal-title":"Int. J. Clin. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1007\/s12020-016-0857-1","article-title":"Lenzi A Assessment of trabecular bone score (TBS) in overweight\/obese men: Effect of metabolic and anthropometric factors","volume":"54","author":"Romagnoli","year":"2016","journal-title":"Endocrine"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"NCD Risk Factor Collaboration (NCD-RisC) (2016). Trends in adult body-mass index in 200 countries from 1975 to 2014: A pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet, 387, 1377\u20131396.","DOI":"10.1016\/S0140-6736(16)30054-X"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Watanabe, M., Risi, R., De Giorgi, F., Tuccinardi, D., Mariani, S., Basciani, S., Lubrano, C., Lenzi, A., and Gnessi, L. (2020). Obesity treatment within the tertiary Italian national healthcare system: What can we learn from it?. Eat. Weight Disord.","DOI":"10.1007\/s40519-020-00936-1"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.amjmed.2014.10.014","article-title":"The Mediterranean diet, its components, and cardiovascular disease","volume":"128","author":"Widmer","year":"2015","journal-title":"Am. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1038\/sj.ijo.0802782","article-title":"Reduction of risk factors for cardiovascular diseases in morbid-obese patients following biliary-intestinal bypass: 3 years\u2019 follow-up","volume":"28","author":"Lubrano","year":"2004","journal-title":"Int. J. Obes. Relat. Metab. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Watanabe, M., Gangitano, E., Francomano, D., Addessi, E., Toscano, R., Costantini, D., Tuccinardi, D., Mariani, S., Basciani, S., and Spera, G. (2018). Mangosteen extract shows a potent insulin sensitizing effect in obese female patients: A prospective randomized controlled pilot study. Nutrients, 10.","DOI":"10.20944\/preprints201804.0049.v1"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Watanabe, M., Tozzi, R., Risi, R., Tuccinardi, D., Mariani, S., Basciani, S., Spera, G., Lubrano, C., and Gnessi, L. (2020). Beneficial effects of the ketogenic diet on nonalcoholic fatty liver disease: A comprehensive review of the literature. Obes. Rev., 1\u201311.","DOI":"10.1111\/obr.13024"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1007\/s40618-019-01061-2","article-title":"Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: Systematic review and consensus statement from the Italian Society of Endocrinology (SIE)","volume":"42","author":"Caprio","year":"2019","journal-title":"J. Endocrinol. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Basciani, S., Camajani, E., Contini, S., Persichetti, A., Risi, R., Bertoldi, L., Strigari, L., Prossomariti, G., Watanabe, M., and Mariani, S. (2020). Very-Low-Calorie Ketogenic Diets with Whey, Vegetable or Animal Protein in Patients with Obesity: A Randomized Pilot Study. J. Clin. Endocrinol. Metab.","DOI":"10.1210\/clinem\/dgaa336"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bruci, A., Tuccinardi, D., Tozzi, R., Balena, A., Santucci, S., Frontani, R., Mariani, S., Basciani, S., Spera, G., and Gnessi, L. (2020). Very Low-Calorie Ketogenic Diet: A Safe and Effective Tool for Weight Loss in Patients with Obesity and Mild Kidney Failure. Nutrients, 12.","DOI":"10.3390\/nu12020333"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Watanabe, M., Risi, R., Camajani, E., Contini, S., Persichetti, A., Tuccinardi, D., Ernesti, I., Mariani, S., Lubrano, C., and Genco, A. (2020). Baseline HOMA IR and Circulating FGF21 Levels Predict NAFLD Improvement in Patients Undergoing a Low Carbohydrate Dietary Intervention for Weight Loss: A Prospective Observational Pilot Study. Nutrients, 12.","DOI":"10.3390\/nu12072141"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s12020-014-0355-2","article-title":"Safety and efficacy of a multiphase dietetic protocol with meal replacements including a step with very low calorie diet","volume":"48","author":"Basciani","year":"2015","journal-title":"Endocrine"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Watanabe, M., Risi, R., Masi, D., Caputi, A., Balena, A., Rossini, G., Tuccinardi, D., Mariani, S., Basciani, S., and Manfrini, S. (2020). Current Evidence to Propose Different Food Supplements for Weight Loss: A Comprehensive Review. Nutrients, 12.","DOI":"10.3390\/nu12092873"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1210\/er.2017-00111","article-title":"Obesity Pathogenesis: An Endocrine Society Scientific Statement","volume":"38","author":"Schwartz","year":"2017","journal-title":"Endocr. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lubrano, C., Genovesi, G., Specchia, P., Costantini, D., Mariani, S., Petrangeli, E., Lenzi, A., and Gnessi, L. (2013). Obesity and metabolic comorbidities: Environmental diseases?. Oxid. Med. Cell. Longev.","DOI":"10.1155\/2013\/640673"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Saito, M., Arakaki, R., Yamada, A., Tsunematsu, T., Kudo, Y., and Ishimaru, N. (2016). Molecular mechanisms of nickel allergy. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17020202"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/cod.12846","article-title":"Prevalence of nickel allergy in Europe following the EU Nickel Directive\u2014A review","volume":"77","author":"Thyssen","year":"2017","journal-title":"Contact Dermat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2","DOI":"10.4103\/ijpvm.IJPVM_48_19","article-title":"Trace Elements in Human Nutrition (II)\u2014An Update","volume":"11","author":"Mehri","year":"2020","journal-title":"Int. J. Prev. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/cod.13327","article-title":"Nickel allergy and allergic contact dermatitis: A clinical review of immunology, epidemiology, exposure, and treatment","volume":"81","author":"Thyssen","year":"2019","journal-title":"Contact Dermat."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e20200628","DOI":"10.1542\/peds.2020-0628","article-title":"Nickel Allergic Contact Dermatitis: Identification, Treatment, and Prevention","volume":"145","author":"Silverberg","year":"2020","journal-title":"Pediatrics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1177\/039463201402700118","article-title":"Systemic nickel allergy Syndrome: Epidemiological data from four Italian allergy units","volume":"27","author":"Ricciardi","year":"2014","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.envres.2010.11.006","article-title":"Prevalence of nickel sensitization and urinary nickel content of children are increased by nickel in ambient air","volume":"111","author":"Sugiri","year":"2011","journal-title":"Environ. Res."},{"key":"ref_29","first-page":"1","article-title":"Scientific Opinion on the risks to public health related to the presence of nickel in food and drinking water","volume":"13","author":"Panel","year":"2015","journal-title":"EFSA J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"56","DOI":"10.2500\/ar.2015.6.0109","article-title":"Nickel sensitization and dietary nickel are a substantial cause of symptoms provocation in patients with chronic allergic-like dermatitis syndromes","volume":"6","author":"Antico","year":"2015","journal-title":"Allergy Rhinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1177\/039463201302600314","article-title":"Systemic nickel allergy syndrome: Nosologic framework and usefulness of diet regimen for diagnosis","volume":"26","author":"Sugiri","year":"2013","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1093\/ajcn\/66.3.616","article-title":"Nickel metabolism in humans investigated with an oral stable isotope","volume":"66","author":"Patriarca","year":"1997","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Freire, C., Vrhovnik, P., Fiket, \u017d., Salcedo-Bellido, I., Echeverr\u00eda, R., Mart\u00edn-Olmedo, P., Kniewald, G., Fern\u00e1ndez, M.F., and Arrebola, J.P. (2020). Adipose tissue concentrations of arsenic, nickel, lead, tin, and titanium in adults from GraMo cohort in Southern Spain: An exploratory study. Sci. Total Environ., 719.","DOI":"10.1016\/j.scitotenv.2020.137458"},{"key":"ref_34","unstructured":"WHO Regional Office for Europe (2000). Nickel Air Quality Guidelines, Chapter 6.10."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e0123265","DOI":"10.1371\/journal.pone.0123265","article-title":"High prevalence of nickel allergy in an overweight female population: A pilot observational analysis","volume":"10","author":"Lusi","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e0202683","DOI":"10.1371\/journal.pone.0202683","article-title":"Overweight and obese patients with nickel allergy have a worse metabolic profile compared to weight matched non-allergic individuals","volume":"13","author":"Watanabe","year":"2018","journal-title":"PLoS ONE"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.det.2009.05.005","article-title":"Systemic Contact Dermatitis","volume":"27","author":"Nijhawan","year":"2009","journal-title":"Dermatol. Clin."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature05485","article-title":"Inflammation and metabolic disorders","volume":"444","author":"Hotamisligil","year":"2006","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"109541","DOI":"10.1016\/j.envres.2020.109541","article-title":"Metals, autoimmunity, and neuroendocrinology: Is there a connection?","volume":"187","author":"Dadar","year":"2020","journal-title":"Environ. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1743-8977-9-40","article-title":"Effect of co-exposure to nickel and particulate matter on insulin resistance and mitochondrial dysfunction in a mouse model","volume":"9","author":"Xu","year":"2012","journal-title":"Part. Fibre Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e014215","DOI":"10.1136\/bmjopen-2016-014215","article-title":"Association between soil heavy metals and fatty liver disease in men in Taiwan: A cross sectional study","volume":"7","author":"Lin","year":"2017","journal-title":"BMJ Open"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1006\/niox.2000.0278","article-title":"Involvement of nitric oxide in nickel-induced hyperglycemia in rats","volume":"4","author":"Gupta","year":"2000","journal-title":"Nitric Oxide"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s10517-016-3575-z","article-title":"Oxidative stress and biochemical markers of endothelial dysfunction and organ damage under conditions of experimental nonferrous metal intoxication","volume":"162","author":"Dzugkoeva","year":"2016","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_44","first-page":"412","article-title":"Nickel, its adverse health effects & oxidative stress","volume":"128","author":"Das","year":"2008","journal-title":"Indian J. Med. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"169","DOI":"10.4161\/isl.1.3.9262","article-title":"Heavy metals, islet function and diabetes development","volume":"1","author":"Chen","year":"2009","journal-title":"Islets"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8618","DOI":"10.1016\/S0021-9258(18)32101-X","article-title":"Divalent Cation Inhibition of Hormone Release from Isolated Adenohypophysial Secretory Granules","volume":"258","author":"Lorenson","year":"1983","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1016\/0024-3205(84)90271-6","article-title":"Inhibition of prolactin and growth hormone secretion by nickel","volume":"35","author":"Carlson","year":"1984","journal-title":"Life Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1042\/bj1400135","article-title":"The effect of nickel on secretory systems. Studies on the release of amylase, insulin and growth hormone","volume":"140","author":"Dormer","year":"1974","journal-title":"Biochem. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/245330a0","article-title":"Prolactin Secretion is Specifically Inhibited by Nickel","volume":"245","author":"Dular","year":"1973","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1172\/JCI59660","article-title":"Obesity is associated with hypothalamic injury in rodents and humans","volume":"122","author":"Thaler","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"R275","DOI":"10.1530\/EJE-17-0505","article-title":"Diagnosis of endocrine disease: Primary empty sella: A comprehensive review","volume":"177","author":"Chiloiro","year":"2017","journal-title":"Eur. J. Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.mce.2009.08.017","article-title":"Obesity, growth hormone and weight loss","volume":"316","author":"Rasmussen","year":"2010","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1007\/s00247-018-4070-7","article-title":"Pituitary height at magnetic resonance imaging in pediatric isolated growth hormone deficiency","volume":"48","author":"Dumrongpisutikul","year":"2018","journal-title":"Pediatr. Radiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9473","DOI":"10.12659\/MSM.911977","article-title":"Relevance of pituitary gland magnetic resonance imaging results with clinical and laboratory findings in growth hormone deficiency","volume":"24","author":"Kara","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1515\/jpem-2015-0404","article-title":"Pituitary volume in children with growth hormone deficiency, idiopathic short stature and controls","volume":"29","author":"Kessler","year":"2016","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s12020-015-0530-0","article-title":"Severe growth hormone deficiency and empty sella in obesity: A cross-sectional study","volume":"49","author":"Lubrano","year":"2015","journal-title":"Endocrine"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1007\/s11604-016-0532-8","article-title":"Contribution of metals to brain MR signal intensity: Review articles","volume":"34","author":"Kanda","year":"2016","journal-title":"Jpn. J. Radiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ejrad.2006.11.016","article-title":"MRI for the determination of pituitary iron overload in children and young adults with \u03b2-thalassaemia major","volume":"62","author":"Christoforidis","year":"2007","journal-title":"Eur. J. Radiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3109\/07435800.2015.1068796","article-title":"Iron overload detection using pituitary and hepatic MRI in thalassemic patients having short stature and hypogonadism","volume":"41","author":"Mousa","year":"2016","journal-title":"Endocr. Res."},{"key":"ref_60","first-page":"2","article-title":"The National Cholesterol Education Program Adult Treatment Panel III guidelines","volume":"9","author":"Lipsy","year":"2003","journal-title":"J. Manag. Care Pharm."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4158\/EP.15.S2.1","article-title":"American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in growth hormone-deficient adults and transition patients\u20142009 update","volume":"15","author":"Cook","year":"2009","journal-title":"Endocr. Pract."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.taap.2013.09.014","article-title":"Crucial role of Toll-like receptors in the zinc\/nickel-induced inflammatory response in vascular endothelial cells","volume":"273","author":"Tsou","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.1016\/j.yexcr.2013.08.012","article-title":"Functional Toll-like receptor 4 expressed in lactotrophs mediates LPS-induced proliferation in experimental pituitary hyperplasia","volume":"319","author":"Sabatino","year":"2013","journal-title":"Exp. Cell Res."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Tomaszewska-Zaremba, D., Haziak, K., Tomczyk, M., and Herman, A.P. (2018). Inflammation and LPS-binding protein enable the stimulatory effect of endotoxin on prolactin secretion in the ovine anterior pituitary: Ex vivo study. Mediat. Inflamm., 2018.","DOI":"10.1155\/2018\/5427089"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4190","DOI":"10.1210\/en.2011-1004","article-title":"From pituitary expansion to empty sella: Disease progression in a mouse model of autoimmune hypophysitis","volume":"152","author":"Lupi","year":"2011","journal-title":"Endocrinology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1177\/14034948020300010701","article-title":"Prevalence of subjective health complaints (SHC) in Norway","volume":"30","author":"Ihlebaek","year":"2002","journal-title":"Scand. J. Public Health"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Bunt, S.N.W., Merelle, S.Y.M., Steenhuis, I.H.M., and Kroeze, W. (2017). Predictors of need for help with weight loss among overweight and obese men and women in the Netherlands: A cross-sectional study. BMC Health Serv. Res., 17.","DOI":"10.1186\/s12913-017-2759-1"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Lachapelle, J.-M., and Maibach, H.I. (2012). Patch Testing and Prick Testing: A Practical Guide Official Publication of the ICDRG, Springer Science & Business Media.","DOI":"10.1007\/978-3-642-25492-5"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1210\/jc.2011-0179","article-title":"Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline","volume":"96","author":"Molitch","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1530\/EJE-07-0631","article-title":"Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: A statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia","volume":"157","author":"Ho","year":"2020","journal-title":"Eur. J. Endocrinol."},{"key":"ref_71","first-page":"64","article-title":"Pituitary dimensions and volume measurements in pregnancy and post-partum: MR assessment","volume":"39","author":"Esen","year":"1998","journal-title":"Acta Radiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1210\/jcem-71-2-505","article-title":"In vivo assessment of pituitary gland volume with magnetic resonance imaging: The effect of age","volume":"71","author":"Lurie","year":"1990","journal-title":"J. Clin. Endocrinol. 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