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      Disorders of Calcium Metabolism: Hypocalcemia and Hypercalcemia

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      Author(s): 1 , 2 ,
      Editor(s): ,
      Publication date (Electronic, pub):
      Publication date (Electronic, collection):
      Journal: Cureus
      Publisher: Cureus
      Keywords: hypocalcemia, hypercalcemia, electrolyte disorders, calcium metabolism, calcium sensing receptor

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          Abstract

          Calcium (Ca +2) is a divalent cation that plays a critical role in numerous body functions such as skeletal mineralization, signal transduction, nerve conduction, muscle contraction, and blood coagulation. Ca +2 metabolism is linked to magnesium (Mg +2) and phosphate metabolism. Ca +2 homeostasis is dependent on intestinal absorption, bone turnover, and renal reabsorption. The hormonal regulators of these processes are the parathyroid hormone (PTH), calcitriol {1,25-dihydroxyvitamin D [1,25(OH) 2D]}, and serum ionized Ca +2. Cloning of the Ca +2-sensing receptor (CaSR) has greatly advanced the understanding of Ca +2 metabolism. Disorders of Ca +2 metabolism are easily recognized because Ca +2 is included in routine chemistry panels. Measurement of ionized Ca +2 is the preferred way to ascertain the diagnosis of hypocalcemia and hypercalcemia.

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          Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects.

          Sylvia Christakos, Puneet Dhawan, Annemieke Verstuyf … (2016)
          1,25-Dihydroxvitamin D3 [1,25(OH)2D3] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH)2D3 action involves the direct binding of the 1,25(OH)2D3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH)2D3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH)2D3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease.
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            Clinical practice. Hypercalcemia associated with cancer.

            Andrew F Stewart (2005)
            Article 0 comments Cited 192 times – based on 0 reviews     Review now
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              Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop.

              John Bilezikian, Maria Brandi, Richard Eastell … (2014)
              Asymptomatic primary hyperparathyroidism (PHPT) is routinely encountered in clinical practices of endocrinology throughout the world. This report distills an update of current information about diagnostics, clinical features, and management of this disease into a set of revised guidelines.
              Article 0 comments Cited 191 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cureus
                Journal ID (iso-abbrev): Cureus
                Journal ID (issn): 2168-8184
                Title: Cureus
                Publisher: Cureus (Palo Alto (CA) )
                ISSN (Electronic): 2168-8184
                Publication date (Electronic, pub): 1 January 2021
                Publication date (Electronic, collection): January 2021
                Volume: 13
                Issue: 1
                Electronic Location Identifier: e12420
                Affiliations
                [1 ] Medicine, Indiana University School of Medicine Northwest-Gary, Gary, USA
                [2 ] Nephrology, Nephrology Specialists, Munster, USA
                Author notes
                Article
                DOI: 10.7759/cureus.12420
                PMC ID: 7849212
                PubMed ID: 33542868
                SO-VID: 8fb09241-3315-48ca-b6ca-0bbb8483d371
                Copyright © Copyright © 2021, Tinawi et al.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date accepted : 1 January 2021
                Categories
                Subject: Endocrinology/Diabetes/Metabolism
                Subject: Internal Medicine
                Subject: Nephrology

                Keywords: hypocalcemia,hypercalcemia,electrolyte disorders,calcium metabolism,calcium sensing receptor
                Data availability:
                Keywords: hypocalcemia, hypercalcemia, electrolyte disorders, calcium metabolism, calcium sensing receptor

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