{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:35:23Z","timestamp":1790753723888,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: The primary objective of the study was to assess serum 25-hydroxyvitamin D [25(OH)D] values in patients with Cushing\u2019s disease (CD), compared to controls. The secondary objective was to assess the response to a load of 150,000 U of cholecalciferol. Methods: In 50 patients with active CD and 48 controls, we evaluated the anthropometric and biochemical parameters, including insulin sensitivity estimation by the homeostatic model of insulin resistance, Matsuda Index and oral disposition index at baseline and in patients with CD also after 6 weeks of cholecalciferol supplementation. Results: At baseline, patients with CD showed a higher frequency of hypovitaminosis deficiency (p = 0.001) and lower serum 25(OH)D (p &lt; 0.001) than the controls. Six weeks after cholecalciferol treatment, patients with CD had increased serum calcium (p = 0.017), 25(OH)D (p &lt; 0.001), ISI-Matsuda (p = 0.035), oral disposition index (p = 0.045) and decreased serum PTH (p = 0.004) and total cholesterol (p = 0.017) values than at baseline. Multivariate analysis showed that mean urinary free cortisol (mUFC) was independently negatively correlated with serum 25(OH)D in CD. Conclusions: Serum 25(OH)D levels are lower in patients with CD compared to the controls. Vitamin D deficiency is correlated with mUFC and values of mUFC &gt; 240 nmol\/24 h are associated with hypovitaminosis D. Cholecalciferol supplementation had a positive impact on insulin sensitivity and lipids.<\/jats:p>","DOI":"10.3390\/nu14050973","type":"journal-article","created":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T20:48:33Z","timestamp":1645994913000},"page":"973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Vitamin D Deficiency in Cushing\u2019s Disease: Before and After Its Supplementation"],"prefix":"10.3390","volume":"14","author":[{"given":"Valentina","family":"Guarnotta","sequence":"first","affiliation":[{"name":"Department of Health Promotion, Maternal-Infantile Care, Excellence Internal and Specialist Medicine \u201cG. D\u2019Alessandro\u201d [PROMISE], Section of Endocrine Disease and Nutrition, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5910-5750","authenticated-orcid":false,"given":"Francesca","family":"Di Gaudio","sequence":"additional","affiliation":[{"name":"Biochemistry Head CQRC Division (Quality Control and Biochemical Risk), Department of Health Promotion, Maternal-Infantile Care, Excellence Internal and Specialist Medicine \u201cG. D\u2019Alessandro\u201d [PROMISE], University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1731-9395","authenticated-orcid":false,"given":"Carla","family":"Giordano","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Maternal-Infantile Care, Excellence Internal and Specialist Medicine \u201cG. D\u2019Alessandro\u201d [PROMISE], Section of Endocrine Disease and Nutrition, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00204-016-1804-x","article-title":"Vitamin D and chronic diseases: The current state of the art","volume":"91","author":"Muscogiuri","year":"2017","journal-title":"Arch. Toxicol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Marino, R., and Misra, M. (2019). Extra-skeletal effects of Vitamin D. Nutrients, 11.","DOI":"10.3390\/nu11071460"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8829","DOI":"10.1002\/jcb.28185","article-title":"Molecular evidence of role of vitamin D deficiency in various extraskeletal diseases","volume":"120","author":"Zendehdel","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/s41574-019-0312-5","article-title":"New aspects of vitamin D metabolism and action-addressing the skin as source and target","volume":"16","author":"Bikle","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S2213-8587(16)00086-3","article-title":"Complications of Cushing\u2019s syndrome: State of the art","volume":"4","author":"Pivonello","year":"2016","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1007\/s11154-020-09598-x","article-title":"Glucocorticoid excess and COVID-19 disease","volume":"22","author":"Guarnotta","year":"2020","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1530\/EJE-13-0754","article-title":"Is diabetes in Cushing\u2019s syndrome only a consequence of hypercortisolism?","volume":"170","author":"Giordano","year":"2014","journal-title":"Eur. J. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s12020-017-1370-x","article-title":"Cushing\u2032s syndrome: A model for sarcopenic obesity","volume":"57","author":"Drey","year":"2017","journal-title":"Endocrine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.2147\/DMSO.S249090","article-title":"Circulating irisin levels as a marker of osteosarcopenic-obesity in Cushing\u2019s disease","volume":"13","author":"Guarnotta","year":"2020","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101521","DOI":"10.1016\/j.beem.2021.101521","article-title":"Epidemiology and mortality of Cushing\u2032s syndrome","volume":"35","author":"Hakami","year":"2021","journal-title":"Best Pr. Res. Clin. Endocrinol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.ecl.2018.02.005","article-title":"Mortality in patients with endogenous Cushing\u2032s Syndrome","volume":"47","author":"Javanmard","year":"2018","journal-title":"Endocrinol. Metab. Clin. North Am."},{"key":"ref_12","unstructured":"Kufe, D.W., Pollock., R.E., and Weichselbaum, R.R. (2003). Physiologic and pharmacologic effects of corticosteroids. Holland-Frei Cancer Medicine, BC Decker. [6th ed.]."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s11154-016-9391-y","article-title":"Adrenal disorders: Is there any role for Vitamin D?","volume":"18","author":"Tirabassi","year":"2016","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3838","DOI":"10.1210\/jc.2011-1600","article-title":"Association of glucocorticoid use and low 25-Hydroxyvitamin D levels: Results from the National Health and Nutrition Examination Survey (NHANES): 2001\u20132006","volume":"96","author":"Skversky","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1055\/s-0034-1396893","article-title":"Focus on Vitamin D and the Adrenal Gland","volume":"47","author":"Muscogiuri","year":"2015","journal-title":"Horm. Metab. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1210\/jc.2011-2757","article-title":"Clinical review: Do Glucocorticosteroids alter Vitamin D status? A systematic review with meta-analyses of observational studies","volume":"97","author":"Davidson","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.jsbmb.2010.03.081","article-title":"Glucocorticoid regulation of the vitamin D receptor","volume":"121","author":"Hidalgo","year":"2010","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"36228","DOI":"10.1074\/jbc.M111.244061","article-title":"Dexamethasone enhances 1\u03b1,25-Dihydroxyvitamin D3 effects by increasing Vitamin D receptor transcription","volume":"286","author":"Hidalgo","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1172\/JCI107304","article-title":"Effects of cortisone administration on the metabolism and localization of 25-Hydroxycholecalciferol in the rat","volume":"52","author":"Favus","year":"1973","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1507\/endocrj1954.33.345","article-title":"Impaired mineral metabolism in Cushing\u2019s syndrome: Parathyroid function, vitamin D metabolites and osteopenia","volume":"33","author":"Kugai","year":"1986","journal-title":"Endocrinol. Jpn."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1210\/jcem-39-6-981","article-title":"Skeletal metabolism and body composition in Cushing\u2019s Syndrome","volume":"39","author":"Aloia","year":"1974","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1210\/jcem-54-5-1039","article-title":"Vitamin D metabolites and parathyroid hormone in Cushing\u2019s Syndrome: Relationship to calcium and phosphorus homeostasis","volume":"54","author":"Findling","year":"1982","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1172\/JCI109902","article-title":"Production, degradation, and circulating levels of 1,25-dihydroxyvitamin D in health and in chronic glucocorticoid excess","volume":"66","author":"Seeman","year":"1980","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1172\/JCI108762","article-title":"Intestinal calcium absorption in exogenous Hypercortisonism","volume":"60","author":"Klein","year":"1977","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1097\/RHU.0b013e318289bd16","article-title":"Current daily glucocorticoid use and serum creatinine levels are associated with lower 25(OH) Vitamin D levels in Thai patients with systemic lupus erythematosus","volume":"19","author":"Chaiamnuay","year":"2013","journal-title":"JCR J. Clin. Rheumatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/j.1365-2265.1980.tb02706.x","article-title":"Parathyroid hormone and 25-hydroxyvitamin D levels in glucocorticoid-treated patients","volume":"12","author":"Slovik","year":"1980","journal-title":"Clin. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/BF02411246","article-title":"Effect of 1,25-dihydroxyvitamin D3 on osteopenia induced by prednisolone in adult rats","volume":"34","author":"Lindgren","year":"1982","journal-title":"Calcif. Tissue Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.domaniend.2011.09.002","article-title":"Vitamin D status before and after hypophysectomy in dogs with pituitary-dependent hypercortisolism","volume":"42","author":"Corbee","year":"2012","journal-title":"Domest. Anim. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"223","DOI":"10.7570\/jomes.2018.27.4.223","article-title":"Vitamin D and metabolic diseases: Growing roles of Vitamin D","volume":"27","author":"Park","year":"2018","journal-title":"J. Obes. Metab. Syndr."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Medrano, M., Carrillo-Cruz, E., Montero, I., and Perez-Simon, J.A. (2018). Vitamin D: Effect on Haematopoiesis and immune system and clinical applications. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092663"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/S2213-8587(21)00235-7","article-title":"Consensus on diagnosis and management of Cushing\u2019s disease: A guideline update","volume":"9","author":"Fleseriu","year":"2021","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1210\/jc.2008-0125","article-title":"The diagnosis of Cushing\u2019s Syndrome: An endocrine society clinical practice guideline","volume":"93","author":"Nieman","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Expert Panel on Detection, Evaluation, Treatment of High Blood Cholesterol in Adults (2001). Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA, 285, 2486\u20132497.","DOI":"10.1001\/jama.285.19.2486"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2021). Classification and diagnosis of diabetes: Standards of medical care in diabetes\u20142021. Diabetes Care, 44, S15\u2013S33.","DOI":"10.2337\/dc21-S002"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1007\/s12020-016-0914-9","article-title":"The degree of urinary hypercortisolism is not correlated with the severity of cushing\u2019s syndrome","volume":"55","author":"Guarnotta","year":"2016","journal-title":"Endocrine"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1210\/jc.2011-0385","article-title":"Endocrine Society. Evaluation, treatment, and prevention of Vitamin D deficiency: An endocrine society clinical practice guideline","volume":"96","author":"Holick","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1111\/j.1365-2036.2010.04479.x","article-title":"Deficiencies in fat-soluble vitamins in long-term users of somatostatin analogue","volume":"32","author":"Fiebrich","year":"2010","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and \u03b2-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.2337\/diacare.22.9.1462","article-title":"Insulin sensitivity indices obtained from oral glucose tolerance testing: Comparison with the euglycemic insulin clamp","volume":"22","author":"Matsuda","year":"1999","journal-title":"Diabetes Care"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"335","DOI":"10.2337\/dc08-1478","article-title":"Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels","volume":"32","author":"Utzschneider","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/jbmr.524","article-title":"Effects of three-monthly oral 150,000 IU cholecalciferol supplementation on falls, mobility, and muscle strength in older postmenopausal women: A randomized controlled trial","volume":"27","author":"Glendenning","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"341","DOI":"10.4158\/EP13265.RA","article-title":"Large, single-dose, oral Vitamin D supplementation in adult populations: A systematic review","volume":"20","author":"Kearns","year":"2014","journal-title":"Endocr. Pract."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/j.bbalip.2010.04.009","article-title":"1\u03b1,25-Dihydroxyvitamin D3 affects hormone production and expression of steroidogenic enzymes in human adrenocortical NCI-H295R cells","volume":"1801","author":"Lundqvist","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1530\/EJE-19-0156","article-title":"Effects of 6-month vitamin D supplementation on insulin sensitivity and secretion: A randomised, placebo-controlled trial","volume":"181","author":"Lemieux","year":"2019","journal-title":"Eur. J. Endocrinol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"21536","DOI":"10.1038\/s41598-021-01064-1","article-title":"Association of changes in lipid levels with changes in vitamin D levels in a real-world setting","volume":"11","author":"Li","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1093\/nutrit\/nuz037","article-title":"Effect of vitamin D supplementation on serum lipid profiles: A systematic review and meta-analysis","volume":"77","author":"Dibaba","year":"2019","journal-title":"Nutr. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Povaliaeva, A., Bogdanov, V., Pigarova, E., Zhukov, A., Dzeranova, L., Belaya, Z., Rozhinskaya, L., Mel\u2019Nichenko, G., and Mokrysheva, N. (2021). Assessment of Vitamin D metabolism in patients with Cushing\u2019s disease in response to 150,000 IU cholecalciferol treatment. Nutrients, 13.","DOI":"10.3390\/nu13124329"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/5\/973\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:27:16Z","timestamp":1760135236000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/5\/973"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,25]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["nu14050973"],"URL":"https:\/\/doi.org\/10.3390\/nu14050973","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,25]]}}}