diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM12436diaendo-12436Research ArticleОбзорыReviewНарушения углеводного обмена и другие метаболические изменения при первичном гиперпаратиреозеImpaired glucose metabolism and other metabolic disorders in patients with primary hyperparathyroidismhttps://orcid.org/0000-0001-5952-5846БибикЕкатерина ЕвгеньевнаBibikEkaterina E.

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117036, Москва, ул. Дм. Ульянова, д. 11

 

MD

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11 Dm. Ulyanova street, 117036 Moscow

 

bibikaterina@mail.ruhttps://orcid.org/0000-0001-6667-062XЕремкинаАнна КонстантиновнаEremkina[Anna K.

Кандидат медицинских наук

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Москва

 

MD, PhD

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Moscow

a.lipatenkova@gmail.comhttps://orcid.org/0000-0001-7963-5022КрупиноваЮлия АлександровнаKrupinovaJulia A.

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Москва

MD

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j.krupinova@gmail.comhttps://orcid.org/0000-0002-2742-372XКлементьеваНаталия ВладимировнаKlementievaNatalia V.

Кандидат биологических наук

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Москва

PhD in Biology

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Moscow

nvklementieva@gmail.comhttps://orcid.org/0000-0002-8916-7346ДобреваЕкатерина АлександровнаDobrevaEkaterina A.

Кандидат медицинских наук

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MD, PhD

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dobrevae@mail.ruhttps://orcid.org/0000-0002-9717-9742МокрышеваНаталья ГеоргиевнаMokryshevaNatalia G.

Доктор медицинских наук, профессор, член-корреспондент РАН

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MD, PhD, Professor

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parathyroid.enc@gmail.comНациональный медицинский исследовательский центр эндокринологииРоссияEndocrinology Research CentreRussian Federation202016122020235459466Copyright © Бибик Е.Е., Еремкина А.К., Крупинова Ю.А., Клементьева Н.В., Добрева Е.А., Мокрышева Н.Г., 20212021Бибик Е.Е., Еремкина А.К., Крупинова Ю.А., Клементьева Н.В., Добрева Е.А., Мокрышева Н.Г.Bibik E.E., Eremkina [.K., Krupinova J.A., Klementieva N.V., Dobreva E.A., Mokrysheva N.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/12436

В клинической картине первичного гиперпаратиреоза (ПГПТ), обусловленного опухолевой трансформацией околощитовидных желез (ОЩЖ), все чаще наблюдаются проявления метаболического синдрома, приводящие к развитию сердечно-сосудистых заболеваний. Согласно клиническим исследованиям, у пациентов с ПГПТ, независимо от формы и степени тяжести основного заболевания, определяется повышенная частота сахарного диабета, инсулинорезистентности, ожирения, дислипидемии, гиперурикемии и других нарушений, значимо влияющих на продолжительность и качество жизни. Фундаментальные научные работы свидетельствуют о неклассических эффектах, которые паратгормон и кальций в повышенных концентрациях могут оказывать на жировую ткань, поджелудочную железу, желудочно-кишечный тракт, почки. Однако патогенетические механизмы формирования нарушений углеводного и других видов обмена при гиперфункции ОЩЖ остаются до конца не ясны ввиду отсутствия адекватных экспериментальных моделей и неоднородности выборок пациентов. Кроме того, неоднозначно влияние хирургического лечения ПГПТ на метаболические изменения. На сегодняшний день необходимо более глубокое изучение данной проблемы, что впоследствии может помочь в разработке оптимальных алгоритмов диагностики и лечения пациентов. В представленной обзорной статье освещены различные аспекты метаболических нарушений на фоне ПГПТ, а также рассмотрены потенциальные ключевые факторы их развития.

The clinical picture of primary hyperparathyroidism (PHPT) which caused by parathyroid neoplasms often includes metabolic syndrome leading to the development of cardiovascular diseases. According to clinical studies, an increased incidence of diabetes mellitus, insulin resistance, obesity, dyslipidemia, hyperuricemia and other disorders that signifi tly affect the life span and quality are observed in patients with PHPT regardless of the form and the severity of the underlying disease. Basic research shows the potential nonclassical effects of high levels of parathyroid hormone and calcium on adipose tissue, pancreas, gastrointestinal tract and kidneys. However, the pathogenetic mechanisms of impaired carbohydrate and other types of metabolism in patients with parathyroid hyperfunction remain unclear because of the lack of relevant experimental models and the heterogeneity of patient groups. Besides, the effect of surgery on metabolic abnormalities is also controversial. Nowadays a deeper understanding of this issue is required, which can subsequently help in the creation of optimal approach to diagnosis and treatment of patients. This review covers different aspects of metabolic disorders in patients with PHPT, as well as potential key factors of their development.

первичный гиперпаратиреозпаратгормонгиперкальциемиясахарный диабетинсулинорезистентностьожирениедислипидемиягиперурикемияprimary hyperparathyroidismparathyroid hormonehypercalcemiadiabetes mellitusinsulin resistanceobesitydyslipidemiahyperuricemiaИсследование проведено при финансовой поддержке РНФ в рамках проекта 20-75-10141.ReferencesProcopio M, Barale M, Bertaina S, et al. Cardiovascular risk and metabolic syndrome in primary hyperparathyroidism and their correlation to different clinical forms. Endocrine. 2014;47(2):581-589. https://doi.org/10.1007/s12020-013-0091-zProcopio M, Barale M, Bertaina S, et al. Cardiovascular risk and metabolic syndrome in primary hyperparathyroidism and their correlation to different clinical forms. Endocrine. 2014;47(2):581-589. https://doi.org/10.1007/s12020-013-0091-zLjunghall S, Palmer M, Akerstrom G, Wide L. Diabetes mellitus, glucose tolerance and insulin response to glucose in patients with primary hyperparathyroidism before and after parathyroidectomy. Eur J Clin Invest. 1983;13(5):373-377. https://doi.org/10.1111/j.1365-2362.1983.tb00116.xLjunghall S, Palmer M, Akerstrom G, Wide L. Diabetes mellitus, glucose tolerance and insulin response to glucose in patients with primary hyperparathyroidism before and after parathyroidectomy. Eur J Clin Invest. 1983;13(5):373-377. https://doi.org/10.1111/j.1365-2362.1983.tb00116.xМокрышева Н.Г., Добрева Е.А., Мирная С.С., Дедов И.И. Нарушения углеводного и жирового обмена у женщин с первичным гиперпаратиреозом: результаты поперечного исследования // Сахарный диабет. — 2019. — Т. 22. — №1. — С. 8-13. [Mokrysheva NG, Dobreva EA, Mirnaya SS, Dedov II. Carbohydrate and lipid metabolism disorders in women with primary hyperparathyroidism: results of cross-sectional study. Diabetes mellitus. 2019;22(1):8-13. (In Russ.). https://doi.org/10.14341/DM9450Mokrysheva NG, Dobreva EA, Mirnaya SS, Dedov II. Carbohydrate and lipid metabolism disorders in women with primary hyperparathyroidism: results of cross-sectional study. Diabetes mellitus. 2019;22(1):8-13. (In Russ.). https://doi.org/10.14341/DM9450Procopio M, Borretta G. Derangement of glucose metabolism in hyperparathyroidism. J Endocrinol Invest. 2003;26(11):1136-1142. https://doi.org/10.1007/BF03345264Procopio M, Borretta G. Derangement of glucose metabolism in hyperparathyroidism. J Endocrinol Invest. 2003;26(11):1136-1142. https://doi.org/10.1007/BF03345264Tassone F, Maccario M, Gianotti L, et al. Insulin sensitivity in normocalcaemic primary hyperparathyroidism. Endocrine. 2013;44(3):812-814. https://doi.org/10.1007/s12020-013-0059-zTassone F, Maccario M, Gianotti L, et al. Insulin sensitivity in normocalcaemic primary hyperparathyroidism. Endocrine. 2013;44(3):812-814. https://doi.org/10.1007/s12020-013-0059-zTemizkan S, Kocak O, Aydin K, et al. Normocalcemic hyperparathyroidism and insulin resistance. Endocr Pract. 2015;21(1):23-29. https://doi.org/10.4158/EP14195.ORTemizkan S, Kocak O, Aydin K, et al. Normocalcemic hyperparathyroidism and insulin resistance. Endocr Pract. 2015;21(1):23-29. https://doi.org/10.4158/EP14195.ORTassone F, Procopio M, Gianotti L, et al. Insulin resistance is not coupled with defective insulin secretion in primary hyperparathyroidism. Diabet Med. 2009;26(10):968-973. https://doi.org/10.1111/j.1464-5491.2009.02804.xTassone F, Procopio M, Gianotti L, et al. Insulin resistance is not coupled with defective insulin secretion in primary hyperparathyroidism. Diabet Med. 2009;26(10):968-973. https://doi.org/10.1111/j.1464-5491.2009.02804.xKim H, Kalkhoff RK, Costrini NV, et al. Plasma insulin disturbances in primary hyperparathyroidism. J Clin Invest. 1971;50(12):2596-2605. https://doi.org/10.1172/JCI106760Kim H, Kalkhoff RK, Costrini NV, et al. Plasma insulin disturbances in primary hyperparathyroidism. J Clin Invest. 1971;50(12):2596-2605. https://doi.org/10.1172/JCI106760Sun G, Vasdev S, Martin GR, et al. Altered calcium homeostasis is correlated with abnormalities of fasting serum glucose, insulin resistance, and beta-cell function in the Newfoundland population. Diabetes. 2005;54(11):3336-3339. https://doi.org/10.2337/diabetes.54.11.3336Sun G, Vasdev S, Martin GR, et al. Altered calcium homeostasis is correlated with abnormalities of fasting serum glucose, insulin resistance, and beta-cell function in the Newfoundland population. Diabetes. 2005;54(11):3336-3339. https://doi.org/10.2337/diabetes.54.11.3336Babinsky VN, Hannan FM, Ramracheya RD, et al. Mutant Mice With Calcium-Sensing Receptor Activation Have Hyperglycemia That Is Rectified by Calcilytic Therapy. Endocrinology. 2017;158(8):2486-2502. https://doi.org/10.1210/en.2017-00111Babinsky VN, Hannan FM, Ramracheya RD, et al. Mutant Mice With Calcium-Sensing Receptor Activation Have Hyperglycemia That Is Rectified by Calcilytic Therapy. Endocrinology. 2017;158(8):2486-2502. https://doi.org/10.1210/en.2017-00111Hagstrom E, Hellman P, Lundgren E, et al. Serum calcium is independently associated with insulin sensitivity measured with euglycaemic-hyperinsulinaemic clamp in a community-based cohort. Diabetologia. 2007;50(2):317-324. https://doi.org/10.1007/s00125-006-0532-9Hagstrom E, Hellman P, Lundgren E, et al. Serum calcium is independently associated with insulin sensitivity measured with euglycaemic-hyperinsulinaemic clamp in a community-based cohort. Diabetologia. 2007;50(2):317-324. https://doi.org/10.1007/s00125-006-0532-9Haap M, Heller E, Thamer C, et al. Association of serum phosphate levels with glucose tolerance, insulin sensitivity and insulin secretion in non-diabetic subjects. Eur J Clin Nutr. 2006;60(6):734-739. https://doi.org/10.1038/sj.ejcn.1602375Haap M, Heller E, Thamer C, et al. Association of serum phosphate levels with glucose tolerance, insulin sensitivity and insulin secretion in non-diabetic subjects. Eur J Clin Nutr. 2006;60(6):734-739. https://doi.org/10.1038/sj.ejcn.1602375Harter HR, Santiago J V, Rutherford WE, et al. The relative roles of calcium, phosphorus, and parathyroid hormone in glucoseand tolbutamide-mediated insulin release. J Clin Invest. 1976;58(2):359-367. https://doi.org/10.1172/JCI108480Harter HR, Santiago J V, Rutherford WE, et al. The relative roles of calcium, phosphorus, and parathyroid hormone in glucoseand tolbutamide-mediated insulin release. J Clin Invest. 1976;58(2):359-367. https://doi.org/10.1172/JCI108480Reis JP, Selvin E, Pankow JS, et al. Parathyroid hormone is associated with incident diabetes in white, but not black adults: The Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Metab. 2016;42(3):162-169. https://doi.org/10.1016/j.diabet.2015.12.004Reis JP, Selvin E, Pankow JS, et al. Parathyroid hormone is associated with incident diabetes in white, but not black adults: The Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Metab. 2016;42(3):162-169. https://doi.org/10.1016/j.diabet.2015.12.004Chang E, Donkin SS, Teegarden D. Parathyroid hormone suppresses insulin signaling in adipocytes. Mol Cell Endocrinol. 2009;307(1-2):77-82. https://doi.org/10.1016/j.mce.2009.03.024Chang E, Donkin SS, Teegarden D. Parathyroid hormone suppresses insulin signaling in adipocytes. Mol Cell Endocrinol. 2009;307(1-2):77-82. https://doi.org/10.1016/j.mce.2009.03.024Thomas DM, Rogers SD, Sleeman MW, et al. Modulation of glucose transport by parathyroid hormone and insulin in UMR 106-01, a clonal rat osteogenic sarcoma cell line. J Mol Endocrinol. 1995;14(2):263-275. https://doi.org/10.1677/jme.0.0140263Thomas DM, Rogers SD, Sleeman MW, et al. Modulation of glucose transport by parathyroid hormone and insulin in UMR 106-01, a clonal rat osteogenic sarcoma cell line. J Mol Endocrinol. 1995;14(2):263-275. https://doi.org/10.1677/jme.0.0140263Reusch JE, Begum N, Sussman KE, Draznin B. Regulation of GLUT-4 phosphorylation by intracellular calcium in adipocytes. Endocrinology. 1991;129(6):3269-3273. https://doi.org/10.1210/endo-129-6-3269Reusch JE, Begum N, Sussman KE, Draznin B. Regulation of GLUT-4 phosphorylation by intracellular calcium in adipocytes. Endocrinology. 1991;129(6):3269-3273. https://doi.org/10.1210/endo-129-6-3269Kanazawa I. Interaction between bone and glucose metabolism [Review]. Endocr J. 2017;64(11):1043-1053. https://doi.org/10.1507/endocrj.EJ17-0323Kanazawa I. Interaction between bone and glucose metabolism [Review]. Endocr J. 2017;64(11):1043-1053. https://doi.org/10.1507/endocrj.EJ17-0323Bao Y, Ma X, Yang R, et al. Inverse relationship between serum osteocalcin levels and visceral fat area in Chinese men. J Clin Endocrinol Metab. 2013;98(1):345-351. https://doi.org/10.1210/jc.2012-2906Bao Y, Ma X, Yang R, et al. Inverse relationship between serum osteocalcin levels and visceral fat area in Chinese men. J Clin Endocrinol Metab. 2013;98(1):345-351. https://doi.org/10.1210/jc.2012-2906Gianotti L, Piovesan A, Croce CG, et al. Interplay between serum osteocalcin and insulin sensitivity in primary hyperparathyroidism. Calcif Tissue Int. 2011;88(3):231-237. https://doi.org/10.1007/s00223-010-9453-1Gianotti L, Piovesan A, Croce CG, et al. Interplay between serum osteocalcin and insulin sensitivity in primary hyperparathyroidism. Calcif Tissue Int. 2011;88(3):231-237. https://doi.org/10.1007/s00223-010-9453-1Mendonca ML, Batista SL, Nogueira-Barbosa MH, et al. Primary Hyperparathyroidism: The Influence of Bone Marrow Adipose Tissue on Bone Loss and of Osteocalcin on Insulin Resistance. Clinics (Sao Paulo). 2016;71(8):464-469. https://doi.org/10.6061/clinics/2016(08)09Mendonca ML, Batista SL, Nogueira-Barbosa MH, et al. Primary Hyperparathyroidism: The Influence of Bone Marrow Adipose Tissue on Bone Loss and of Osteocalcin on Insulin Resistance. Clinics (Sao Paulo). 2016;71(8):464-469. https://doi.org/10.6061/clinics/2016(08)09Putnam R, Dhibar DP, Varshney S, et al. Effect of curative parathyroidectomy on insulin resistance. Indian J Endocrinol Metab. 2016;20(6):784-789. https://doi.org/10.4103/2230-8210.192916Putnam R, Dhibar DP, Varshney S, et al. Effect of curative parathyroidectomy on insulin resistance. Indian J Endocrinol Metab. 2016;20(6):784-789. https://doi.org/10.4103/2230-8210.192916Bhadada SK, Bhansali A, Shah VN, Rao DS. Changes in serum leptin and adiponectin concentrations and insulin resistance after curative parathyroidectomy in moderate to severe primary hyperparathyroidism. Singapore Med J. 2011;52(12):890-893.Bhadada SK, Bhansali A, Shah VN, Rao DS. Changes in serum leptin and adiponectin concentrations and insulin resistance after curative parathyroidectomy in moderate to severe primary hyperparathyroidism. Singapore Med J. 2011;52(12):890-893.Bergenfelz A, Bladstrom A, Their M, et al. Serum levels of uric acid and diabetes mellitus influence survival after surgery for primary hyperparathyroidism: a prospective cohort study. World J Surg. 2007;31(7):1392-1393. https://doi.org/10.1007/s00268-007-9091-6Bergenfelz A, Bladstrom A, Their M, et al. Serum levels of uric acid and diabetes mellitus influence survival after surgery for primary hyperparathyroidism: a prospective cohort study. World J Surg. 2007;31(7):1392-1393. https://doi.org/10.1007/s00268-007-9091-6Kautzky-Willer A, Pacini G, Niederle B, et al. Insulin secretion, insulin sensitivity and hepatic insulin extraction in primary hyperparathyroidism before and after surgery. Clin Endocrinol (Oxf). 1992;37(2):147-155. https://doi.org/10.1111/j.1365-2265.1992.tb02299.xKautzky-Willer A, Pacini G, Niederle B, et al. Insulin secretion, insulin sensitivity and hepatic insulin extraction in primary hyperparathyroidism before and after surgery. Clin Endocrinol (Oxf). 1992;37(2):147-155. https://doi.org/10.1111/j.1365-2265.1992.tb02299.xCvijovic G, Micic D, Kendereski A, et al. The effect of parathyroidectomy on insulin sensitivity in patients with primary hyperparathyroidism — an never ending story? Exp Clin Endocrinol Diabetes. 2015;123(6):336-341. https://doi.org/10.1055/s-0035-1549906Cvijovic G, Micic D, Kendereski A, et al. The effect of parathyroidectomy on insulin sensitivity in patients with primary hyperparathyroidism — an never ending story? Exp Clin Endocrinol Diabetes. 2015;123(6):336-341. https://doi.org/10.1055/s-0035-1549906Prager R, Schernthaner G, Niederle B, Roka R. Evaluation of glucose tolerance, insulin secretion, and insulin action in patients with primary hyperparathyroidism before and after surgery. Calcif Tissue Int. 1990;46(1):1-4. https://doi.org/10.1007/bf02555816Prager R, Schernthaner G, Niederle B, Roka R. Evaluation of glucose tolerance, insulin secretion, and insulin action in patients with primary hyperparathyroidism before and after surgery. Calcif Tissue Int. 1990;46(1):1-4. https://doi.org/10.1007/bf02555816Antonopoulou V, Karras SN, Koufakis T, et al. Rising Glucagon-Like Peptide 1 Concentrations After Parathyroidectomy in Patients With Primary Hyperparathyroidism. J Surg Res. 2020;245:22-30. https://doi.org/10.1016/j.jss.2019.07.019Antonopoulou V, Karras SN, Koufakis T, et al. Rising Glucagon-Like Peptide 1 Concentrations After Parathyroidectomy in Patients With Primary Hyperparathyroidism. J Surg Res. 2020;245:22-30. https://doi.org/10.1016/j.jss.2019.07.019McCallum RW, Parameswaran V, Burgess JR. Multiple endocrine neoplasia type 1 (MEN 1) is associated with an increased prevalence of diabetes mellitus and impaired fasting glucose. Clin Endocrinol (Oxf). 2006;65(2):163-168. https://doi.org/10.1111/j.1365-2265.2006.02563.xMcCallum RW, Parameswaran V, Burgess JR. Multiple endocrine neoplasia type 1 (MEN 1) is associated with an increased prevalence of diabetes mellitus and impaired fasting glucose. Clin Endocrinol (Oxf). 2006;65(2):163-168. https://doi.org/10.1111/j.1365-2265.2006.02563.xvan Wijk JPH, Dreijerink KMA, Pieterman CRC, et al. Increased prevalence of impaired fasting glucose in MEN1 gene mutation carriers. Clin Endocrinol (Oxf). 2012;76(1):67-71. https://doi.org/10.1111/j.1365-2265.2011.04166.xvan Wijk JPH, Dreijerink KMA, Pieterman CRC, et al. Increased prevalence of impaired fasting glucose in MEN1 gene mutation carriers. Clin Endocrinol (Oxf). 2012;76(1):67-71. https://doi.org/10.1111/j.1365-2265.2011.04166.xGrey AB, Evans MC, Stapleton JP, Reid IR. Body weight and bone mineral density in postmenopausal women with primary hyperparathyroidism. Ann Intern Med. 1994;121(10):745-749. https://doi.org/10.7326/0003-4819-121-10-199411150-00003Grey AB, Evans MC, Stapleton JP, Reid IR. Body weight and bone mineral density in postmenopausal women with primary hyperparathyroidism. Ann Intern Med. 1994;121(10):745-749. https://doi.org/10.7326/0003-4819-121-10-199411150-00003Bolland MJ, Grey AB, Gamble GD, Reid IR. Association between primary hyperparathyroidism and increased body weight: a meta-analysis. J Clin Endocrinol Metab. 2005;90(3):1525-1530. https://doi.org/10.1210/jc.2004-1891Bolland MJ, Grey AB, Gamble GD, Reid IR. Association between primary hyperparathyroidism and increased body weight: a meta-analysis. J Clin Endocrinol Metab. 2005;90(3):1525-1530. https://doi.org/10.1210/jc.2004-1891Мокрышева Н.Г. Первичный гиперпаратиреоз. Эпидемиология, клиника, современные принципы диагностики и лечения: Дис. ... док. мед. наук. — М., 2011. Доступно по: https://dlib.rsl.ru/01005084680Mokrysheva NG. Pervichnyi giperparatireoz. Epidemiologgiya, klinika, sovremennye princypy diagnostiki i lecheniya. [dissertation]. M., 2011. (In Russ.). Доступно по: https://dlib.rsl.ru/01005084680McCarty MF, Thomas CA. PTH excess may promote weight gain by impeding catecholamine-induced lipolysisimplications for the impact of calcium, vitamin D, and alcohol on body weight. Med Hypotheses. 2003;61(5-6):535-542. https://doi.org/10.1016/s0306-9877(03)00227-5McCarty MF, Thomas CA. PTH excess may promote weight gain by impeding catecholamine-induced lipolysisimplications for the impact of calcium, vitamin D, and alcohol on body weight. Med Hypotheses. 2003;61(5-6):535-542. https://doi.org/10.1016/s0306-9877(03)00227-5Fan Y, Hanai J-I, Le PT, et al. Parathyroid Hormone Directs Bone Marrow Mesenchymal Cell Fate. Cell Metab. 2017;25(3):661-672. https://doi.org/10.1016/j.cmet.2017.01.001Fan Y, Hanai J-I, Le PT, et al. Parathyroid Hormone Directs Bone Marrow Mesenchymal Cell Fate. Cell Metab. 2017;25(3):661-672. https://doi.org/10.1016/j.cmet.2017.01.001Bravo-Sagua R, Mattar P, Díaz X, et al. Calcium Sensing Receptor as a Novel Mediator of Adipose Tissue Dysfunction: Mechanisms and Potential Clinical Implications. Front Physiol. 2016;7:395. https://doi.org/10.3389/fphys.2016.00395Bravo-Sagua R, Mattar P, Díaz X, et al. Calcium Sensing Receptor as a Novel Mediator of Adipose Tissue Dysfunction: Mechanisms and Potential Clinical Implications. Front Physiol. 2016;7:395. https://doi.org/10.3389/fphys.2016.00395Christensen MHE, Dankel SN, Nordbø Y, et al. Primary Hyperparathyroidism Influences the Expression of Inflammatory and Metabolic Genes in Adipose Tissue. Oresic M, ed. PLoS One. 2011;6(6):e20481. https://doi.org/10.1371/journal.pone.0020481Christensen MHE, Dankel SN, Nordbø Y, et al. Primary Hyperparathyroidism Influences the Expression of Inflammatory and Metabolic Genes in Adipose Tissue. Oresic M, ed. PLoS One. 2011;6(6):e20481. https://doi.org/10.1371/journal.pone.0020481Delfi E, Petramala L, Caliumi C, et al. Circulating leptin and adiponectin levels in patients with primary hyperparathyroidism. Metabolism. 2007;56(1):30-36. https://doi.org/10.1016/j.metabol.2006.08.019Delfi E, Petramala L, Caliumi C, et al. Circulating leptin and adiponectin levels in patients with primary hyperparathyroidism. Metabolism. 2007;56(1):30-36. https://doi.org/10.1016/j.metabol.2006.08.019Matsunuma A, Horiuchi N. Leptin attenuates gene expression for renal 25-hydroxyvitamin D3-1alpha-hydroxylase in mice via the long form of the leptin receptor. Arch Biochem Biophys. 2007;463(1):118-127. https://doi.org/10.1016/j.abb.2007.02.031Matsunuma A, Horiuchi N. Leptin attenuates gene expression for renal 25-hydroxyvitamin D3-1alpha-hydroxylase in mice via the long form of the leptin receptor. Arch Biochem Biophys. 2007;463(1):118-127. https://doi.org/10.1016/j.abb.2007.02.031Grethen E, Hill KM, Jones R, et al. Serum leptin, parathyroid hormone, 1,25-dihydroxyvitamin D, fi oblast growth factor 23, bone alkaline phosphatase, and sclerostin relationships in obesity. J Clin Endocrinol Metab. 2012;97(5):1655-1662. https://doi.org/10.1210/jc.2011-2280Grethen E, Hill KM, Jones R, et al. Serum leptin, parathyroid hormone, 1,25-dihydroxyvitamin D, fi oblast growth factor 23, bone alkaline phosphatase, and sclerostin relationships in obesity. J Clin Endocrinol Metab. 2012;97(5):1655-1662. https://doi.org/10.1210/jc.2011-2280Hoang D, Broer N, Sosa JA, et al. Leptin Is Produced by Parathyroid Glands and Stimulates Parathyroid Hormone Secretion. Ann Surg. 2017;266(6):1075-1083. https://doi.org/10.1097/SLA.0000000000002004Hoang D, Broer N, Sosa JA, et al. Leptin Is Produced by Parathyroid Glands and Stimulates Parathyroid Hormone Secretion. Ann Surg. 2017;266(6):1075-1083. https://doi.org/10.1097/SLA.0000000000002004Raghay K, García-Caballero T, Nogueiras R, et al. Ghrelin localization in rat and human thyroid and parathyroid glands and tumours. Histochem Cell Biol. 2006;125(3):239-246. https://doi.org/10.1007/s00418-005-0044-6Raghay K, García-Caballero T, Nogueiras R, et al. Ghrelin localization in rat and human thyroid and parathyroid glands and tumours. Histochem Cell Biol. 2006;125(3):239-246. https://doi.org/10.1007/s00418-005-0044-6Yamamoto K, Isogai Y, Ishida T, Hagihara K. Enhancement of ghrelin-signaling system by Rikkunshi-To attenuates teriparatideinduced pica in rats. J Pharmacol Sci. 2018;137(2):137-145. https://doi.org/10.1016/j.jphs.2018.05.003Yamamoto K, Isogai Y, Ishida T, Hagihara K. Enhancement of ghrelin-signaling system by Rikkunshi-To attenuates teriparatideinduced pica in rats. J Pharmacol Sci. 2018;137(2):137-145. https://doi.org/10.1016/j.jphs.2018.05.003Adam MA, Untch BR, Danko ME, et al. Severe obesity is associated with symptomatic presentation, higher parathyroid hormone levels, and increased gland weight in primary hyperparathyroidism. J Clin Endocrinol Metab. 2010;95(11):4917-4924. https://doi.org/10.1210/jc.2010-0666Adam MA, Untch BR, Danko ME, et al. Severe obesity is associated with symptomatic presentation, higher parathyroid hormone levels, and increased gland weight in primary hyperparathyroidism. J Clin Endocrinol Metab. 2010;95(11):4917-4924. https://doi.org/10.1210/jc.2010-0666Kuo LE, Wachtel H, Fraker D, Kelz R. Reoperative parathyroidectomy: who is at risk and what is the risk? J Surg Res. 2014;191(2):256-261. https://doi.org/10.1016/j.jss.2014.05.073Kuo LE, Wachtel H, Fraker D, Kelz R. Reoperative parathyroidectomy: who is at risk and what is the risk? J Surg Res. 2014;191(2):256-261. https://doi.org/10.1016/j.jss.2014.05.073Hedesan OC, Fenzl A, Digruber A, et al. Parathyroid hormone induces a browning program in human white adipocytes. Int J Obes (Lond). 2019;43(6):1319-1324. https://doi.org/10.1038/s41366-018-0266-zHedesan OC, Fenzl A, Digruber A, et al. Parathyroid hormone induces a browning program in human white adipocytes. Int J Obes (Lond). 2019;43(6):1319-1324. https://doi.org/10.1038/s41366-018-0266-zHe Y, Liu R-X, Zhu M-T, et al. The browning of white adipose tissue and body weight loss in primary hyperparathyroidism. EBioMedicine. 2019;40:56-66. https://doi.org/10.1016/j.ebiom.2018.11.057He Y, Liu R-X, Zhu M-T, et al. The browning of white adipose tissue and body weight loss in primary hyperparathyroidism. EBioMedicine. 2019;40:56-66. https://doi.org/10.1016/j.ebiom.2018.11.057Wannamethee SG, Welsh P, Papacosta O, et al. Elevated parathyroid hormone, but not vitamin D deficiency, is associated with increased risk of heart failure in older men with and without cardiovascular disease. Circ Heart Fail. 2014;7(5):732-739 https://doi.org/10.1161/CIRCHEARTFAILURE.114.001272Wannamethee SG, Welsh P, Papacosta O, et al. Elevated parathyroid hormone, but not vitamin D deficiency, is associated with increased risk of heart failure in older men with and without cardiovascular disease. Circ Heart Fail. 2014;7(5):732-739 https://doi.org/10.1161/CIRCHEARTFAILURE.114.001272Querfeld U, Hoffmann MM, Klaus G, et al. Antagonistic effects of vitamin D and parathyroid hormone on lipoprotein lipase in cultured adipocytes. J Am Soc Nephrol. 1999;10(10):2158-2164.Querfeld U, Hoffmann MM, Klaus G, et al. Antagonistic effects of vitamin D and parathyroid hormone on lipoprotein lipase in cultured adipocytes. J Am Soc Nephrol. 1999;10(10):2158-2164.Hagstrom E, Lundgren E, Lithell H, et al. Normalized dyslipidaemia after parathyroidectomy in mild primary hyperparathyroidism: population-based study over five years. Clin Endocrinol (Oxf). 2002;56(2):253-260. https://doi.org/10.1046/j.0300-0664.2001.01468.xHagstrom E, Lundgren E, Lithell H, et al. Normalized dyslipidaemia after parathyroidectomy in mild primary hyperparathyroidism: population-based study over five years. Clin Endocrinol (Oxf). 2002;56(2):253-260. https://doi.org/10.1046/j.0300-0664.2001.01468.xHagstrom E, Lundgren E, Rastad J, Hellman P. Metabolic abnormalities in patients with normocalcemic hyperparathyroidism detected at a population-based screening. Eur J Endocrinol. 2006;155(1):33-39. https://doi.org/10.1530/eje.1.02173Hagstrom E, Lundgren E, Rastad J, Hellman P. Metabolic abnormalities in patients with normocalcemic hyperparathyroidism detected at a population-based screening. Eur J Endocrinol. 2006;155(1):33-39. https://doi.org/10.1530/eje.1.02173Beysel S, Caliskan M, Kizilgul M, et al. Parathyroidectomy improves cardiovascular risk factors in normocalcemic and hypercalcemic primary hyperparathyroidism. BMC Cardiovasc Disord. 2019;19(1):106. https://doi.org/10.1186/s12872-019-1093-4Beysel S, Caliskan M, Kizilgul M, et al. Parathyroidectomy improves cardiovascular risk factors in normocalcemic and hypercalcemic primary hyperparathyroidism. BMC Cardiovasc Disord. 2019;19(1):106. https://doi.org/10.1186/s12872-019-1093-4Godang K, Lundstam K, Mollerup C, et al. The effect of surgery on fat mass, lipid and glucose metabolism in mild primary hyperparathyroidism. Endocr Connect. 2018;7(8):941-948. https://doi.org/10.1530/EC-18-0259Godang K, Lundstam K, Mollerup C, et al. The effect of surgery on fat mass, lipid and glucose metabolism in mild primary hyperparathyroidism. Endocr Connect. 2018;7(8):941-948. https://doi.org/10.1530/EC-18-0259Ponvilawan B, Charoenngam N, Ungprasert P. Primary hyperparathyroidism is associated with a higher level of serum uric acid: A systematic review and meta-analysis. Int J Rheum Dis. 2020;23(2):174-180. https://doi.org/10.1111/1756-185X.13740Ponvilawan B, Charoenngam N, Ungprasert P. Primary hyperparathyroidism is associated with a higher level of serum uric acid: A systematic review and meta-analysis. Int J Rheum Dis. 2020;23(2):174-180. https://doi.org/10.1111/1756-185X.13740Paik JM, Farwell WR, Taylor EN. Demographic, dietary, and serum factors and parathyroid hormone in the National Health and Nutrition Examination Survey. Osteoporos Int. 2012;23(6):1727-1736. https://doi.org/10.1007/s00198-011-1776-xPaik JM, Farwell WR, Taylor EN. Demographic, dietary, and serum factors and parathyroid hormone in the National Health and Nutrition Examination Survey. Osteoporos Int. 2012;23(6):1727-1736. https://doi.org/10.1007/s00198-011-1776-xSugimoto R, Watanabe H, Ikegami K, et al. Downregulation of ABCG2, a urate exporter, by parathyroid hormone enhances urate accumulation in secondary hyperparathyroidism. Kidney Int. 2017;91(3):658-670. https://doi.org/10.1016/j.kint.2016.09.041Sugimoto R, Watanabe H, Ikegami K, et al. Downregulation of ABCG2, a urate exporter, by parathyroid hormone enhances urate accumulation in secondary hyperparathyroidism. Kidney Int. 2017;91(3):658-670. https://doi.org/10.1016/j.kint.2016.09.041Girardi AC, Titan SM, Malnic G, Reboucas NA. Chronic effect of parathyroid hormone on NHE3 expression in rat renal proximal tubules. Kidney Int. 2000;58(4):1623-1631. https://doi.org/10.1046/j.1523-1755.2000.00323.xGirardi AC, Titan SM, Malnic G, Reboucas NA. Chronic effect of parathyroid hormone on NHE3 expression in rat renal proximal tubules. Kidney Int. 2000;58(4):1623-1631. https://doi.org/10.1046/j.1523-1755.2000.00323.xCarroll R, Matfin G. Endocrine and metabolic emergencies:hypercalcaemia. Ther Adv Endocrinol Metab. 2010;1(5):225-234. https://doi.org/10.1177/2042018810390260Carroll R, Matfin G. Endocrine and metabolic emergencies:hypercalcaemia. Ther Adv Endocrinol Metab. 2010;1(5):225-234. https://doi.org/10.1177/2042018810390260Christensson T. Serum urate in subjects with hypercalcaemic hyperparathyroidism. Clin Chim Acta. 1977;80(3):529-533. https://doi.org/10.1016/0009-8981(77)90147-4Christensson T. Serum urate in subjects with hypercalcaemic hyperparathyroidism. Clin Chim Acta. 1977;80(3):529-533. https://doi.org/10.1016/0009-8981(77)90147-4Yoneda M, Takatsuki K, Tomita A. [Parathyroid function and uric acid metabolism]. Nihon Naibunpi Gakkai Zasshi. 1983;59(11):1738-1751. https://doi.org/10.1507/endocrine1927.59.11_1738Yoneda M, Takatsuki K, Tomita A. [Parathyroid function and uric acid metabolism]. Nihon Naibunpi Gakkai Zasshi. 1983;59(11):1738-1751. https://doi.org/10.1507/endocrine1927.59.11_1738

The authors declare that there are no conflicts of interest present.