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Calcium, Phosphate, Vitamin D, Parathyroid Hormone, and Alkaline Phosphatase

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Endocrine Conditions in Pediatrics

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Abstract

Disorders of bone and mineral ion metabolism are rare in pediatrics but may cause substantial morbidity. Key analytes must be interpreted in the context of associated regulatory hormones. In addition, reference ranges for calcium, phosphate, and associated hormones and enzymes often differ from the typical adult range, increasing the risk of misinterpretation. This chapter reviews the measurement and interpretation of circulating calcium, phosphate, vitamin D, parathyroid hormone, and alkaline phosphatase in pediatric patients.

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References

  1. Bringhurst FR, Demay MB, Kronenberg HM. Hormones and disorders of mineral metabolism. In: Melmed S, editor. Williams textbook of endocrinology. 14th ed. Philadelphia: Elsevier, Inc; 2019. p. 1196–255.

    Google Scholar 

  2. Walser M. Ion association. VI. Interactions between calcium, magnesium, inorganic phosphate, citrate and protein in normal human plasma. J Clin Invest. 1961;40:723–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Calvi LM, Bushinsky DA. When is it appropriate to order an ionized calcium? J Am Soc Nephrol. 2008;19(7):1257–60.

    Article  CAS  PubMed  Google Scholar 

  4. David L, Anast CS. Calcium metabolism in newborn infants. The interrelationship of parathyroid function and calcium, magnesium, and phosphorus metabolism in normal, “sick,” and hypocalcemic newborns. J Clin Invest. 1974;54(2):287–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mitchell DM, Juppner H. Regulation of calcium homeostasis and bone metabolism in the fetus and neonate. Curr Opin Endocrinol Diabetes Obes. 2010;17(1):25–30.

    Article  CAS  PubMed  Google Scholar 

  6. Colantonio DA, Kyriakopoulou L, Chan MK, Daly CH, Brinc D, Venner AA, Pasic MD, Armbruster D, Adeli K. Closing the gaps in pediatric laboratory reference intervals: a CALIPER database of 40 biochemical markers in a healthy and multiethnic population of children. Clin Chem. 2012;58(5):854–68.

    Article  CAS  PubMed  Google Scholar 

  7. Mannstadt M, Bilezikian JP, Thakker RV, Hannan FM, Clarke BL, Rejnmark L, Mitchell DM, Vokes TJ, Winer KK, Shoback DM. Hypoparathyroidism. Nat Rev Dis Primers. 2017;3:17080.

    Article  PubMed  Google Scholar 

  8. Carpenter TO, Shaw NJ, Portale AA, Ward LM, Abrams SA, Pettifor JM. Rickets. Nat Rev Dis Primers. 2017;3:17101.

    Article  PubMed  Google Scholar 

  9. Malloy PJ, Feldman D. Genetic disorders and defects in vitamin d action. Endocrinol Metab Clin North Am. 2010;39(2):333–46, table of contents.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Mantovani G, Bastepe M, Monk D, de Sanctis L, Thiele S, Usardi A, Ahmed SF, Bufo R, Choplin T, De Filippo G, Devernois G, Eggermann T, Elli FM, Freson K, Garcia Ramirez A, Germain-Lee EL, Groussin L, Hamdy N, Hanna P, Hiort O, Juppner H, Kamenicky P, Knight N, Kottler ML, Le Norcy E, Lecumberri B, Levine MA, Makitie O, Martin R, Martos-Moreno GA, Minagawa M, Murray P, Pereda A, Pignolo R, Rejnmark L, Rodado R, Rothenbuhler A, Saraff V, Shoemaker AH, Shore EM, Silve C, Turan S, Woods P, Zillikens MC, Perez de Nanclares G, Linglart A. Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement. Nat Rev Endocrinol. 2018;14(8):476–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Stokes VJ, Nielsen MF, Hannan FM, Thakker RV. Hypercalcemic disorders in children. J Bone Miner Res. 2017;32(11):2157–70.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kollars J, Zarroug AE, van Heerden J, Lteif A, Stavlo P, Suarez L, Moir C, Ishitani M, Rodeberg D. Primary hyperparathyroidism in pediatric patients. Pediatrics. 2005;115(4):974–80.

    Article  PubMed  Google Scholar 

  13. Pollak MR, Brown EM, Chou YH, Hebert SC, Marx SJ, Steinmann B, Levi T, Seidman CE, Seidman JG. Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Cell. 1993;75(7):1297–303.

    Article  CAS  PubMed  Google Scholar 

  14. McKnight RF, Adida M, Budge K, Stockton S, Goodwin GM, Geddes JR. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379(9817):721–8.

    Article  CAS  PubMed  Google Scholar 

  15. Schlingmann KP, Kaufmann M, Weber S, Irwin A, Goos C, John U, Misselwitz J, Klaus G, Kuwertz-Broking E, Fehrenbach H, Wingen AM, Guran T, Hoenderop JG, Bindels RJ, Prosser DE, Jones G, Konrad M. Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med. 2011;365(5):410–21.

    Article  CAS  PubMed  Google Scholar 

  16. Tebben PJ, Singh RJ, Kumar R. Vitamin D-mediated hypercalcemia: mechanisms, diagnosis, and treatment. Endocr Rev. 2016;37(5):521–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Imel EA, Carpenter TO. A practical clinical approach to paediatric phosphate disorders. Endocr Dev. 2015;28:134–61.

    Article  CAS  PubMed  Google Scholar 

  18. Kemp GJ, Blumsohn A, Morris BW. Circadian changes in plasma phosphate concentration, urinary phosphate excretion, and cellular phosphate shifts. Clin Chem. 1992;38(3):400–2.

    Article  CAS  PubMed  Google Scholar 

  19. Bergwitz C, Juppner H. FGF23 and syndromes of abnormal renal phosphate handling. Adv Exp Med Biol. 2012;728:41–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Backstrom MC, Kuusela AL, Maki R. Metabolic bone disease of prematurity. Ann Med. 1996;28(4):275–82.

    Article  CAS  PubMed  Google Scholar 

  21. Topaz O, Shurman DL, Bergman R, Indelman M, Ratajczak P, Mizrachi M, Khamaysi Z, Behar D, Petronius D, Friedman V, Zelikovic I, Raimer S, Metzker A, Richard G, Sprecher E. Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis. Nat Genet. 2004;36(6):579–81.

    Article  CAS  PubMed  Google Scholar 

  22. Mendoza J, Legido J, Rubio S, Gisbert JP. Systematic review: the adverse effects of sodium phosphate enema. Aliment Pharmacol Ther. 2007;26(1):9–20.

    Article  CAS  PubMed  Google Scholar 

  23. Rosen CJ, Adams JS, Bikle DD, Black DM, Demay MB, Manson JE, Murad MH, Kovacs CS. The nonskeletal effects of vitamin D: an Endocrine Society scientific statement. Endocr Rev. 2012;33(3):456–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Fraser DR, Kodicek E. Regulation of 25-hydroxycholecalciferol-1-hydroxylase activity in kidney by parathyroid hormone. Nat New Biol. 1973;241(110):163–6.

    Article  CAS  PubMed  Google Scholar 

  25. Institute of Medicine. Dietary reference intakes for calcium and vitamin D. Washington, DC: National Academies Press; 2011.

    Google Scholar 

  26. Munns CF, Shaw N, Kiely M, Specker BL, Thacher TD, Ozono K, Michigami T, Tiosano D, Mughal MZ, Makitie O, Ramos-Abad L, Ward L, DiMeglio LA, Atapattu N, Cassinelli H, Braegger C, Pettifor JM, Seth A, Idris HW, Bhatia V, Fu J, Goldberg G, Savendahl L, Khadgawat R, Pludowski P, Maddock J, Hypponen E, Oduwole A, Frew E, Aguiar M, Tulchinsky T, Butler G, Hogler W. Global consensus recommendations on prevention and management of nutritional rickets. J Clin Endocrinol Metab. 2016;101(2):394–415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30.

    Article  CAS  PubMed  Google Scholar 

  28. Ward LM, Gaboury I, Ladhani M, Zlotkin S. Vitamin D-deficiency rickets among children in Canada. CMAJ. 2007;177(2):161–6.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Bouillon R, Van Baelen H, De Moor P. 25-hydroxyvitamin D and its binding protein in maternal and cord serum. J Clin Endocrinol Metab. 1977;45(4):679–84.

    Article  CAS  PubMed  Google Scholar 

  30. Gough H, Bissesar A, Goggin T, Higgins D, Baker M, Crowley M, Callaghan N. Factors associated with the biochemical changes in vitamin D and calcium metabolism in institutionalized patients with epilepsy. Ir J Med Sci. 1986;155(6):181–9.

    Article  CAS  PubMed  Google Scholar 

  31. Wang Z, Lin YS, Zheng XE, Senn T, Hashizume T, Scian M, Dickmann LJ, Nelson SD, Baillie TA, Hebert MF, Blough D, Davis CL, Thummel KE. An inducible cytochrome P450 3A4-dependent vitamin D catabolic pathway. Mol Pharmacol. 2012;81(4):498–509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Holick MF, MacLaughlin JA, Doppelt SH. Regulation of cutaneous previtamin D3 photosynthesis in man: skin pigment is not an essential regulator. Science. 1981;211(4482):590–3.

    Article  CAS  PubMed  Google Scholar 

  33. Vogiatzi MG, Jacobson-Dickman E, DeBoer MD, Drugs, Therapeutics Committee of the Pediatric Endocrine Society. Vitamin D supplementation and risk of toxicity in pediatrics: a review of current literature. J Clin Endocrinol Metab. 2014;99(4):1132–41.

    Article  CAS  PubMed  Google Scholar 

  34. Brown EM. Extracellular Ca2+ sensing, regulation of parathyroid cell function, and role of Ca2+ and other ions as extracellular (first) messengers. Physiol Rev. 1991;71(2):371–411.

    Article  CAS  PubMed  Google Scholar 

  35. Segre GV. Advances in techniques for measurement of parathyroid hormone: current applications in clinical medicine and directions for future research. Trends Endocrinol Metab. 1990;1(5):243–7.

    Article  CAS  PubMed  Google Scholar 

  36. Boudou P, Ibrahim F, Cormier C, Chabas A, Sarfati E, Souberbielle JC. Third- or second-generation parathyroid hormone assays: a remaining debate in the diagnosis of primary hyperparathyroidism. J Clin Endocrinol Metab. 2005;90(12):6370–2.

    Article  CAS  PubMed  Google Scholar 

  37. Eastell R, Arnold A, Brandi ML, Brown EM, D’Amour P, Hanley DA, Rao DS, Rubin MR, Goltzman D, Silverberg SJ, Marx SJ, Peacock M, Mosekilde L, Bouillon R, Lewiecki EM. Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab. 2009;94(2):340–50.

    Article  CAS  PubMed  Google Scholar 

  38. Wesseling-Perry K, Salusky IB. Chronic kidney disease: mineral and bone disorder in children. Semin Nephrol. 2013;33(2):169–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Schini M, Jacques RM, Oakes E, Peel NFA, Walsh JS, Eastell R. Normocalcemic hyperparathyroidism: study of its prevalence and natural history. J Clin Endocrinol Metab. 2020;105(4):dgaa084.

    Article  PubMed  Google Scholar 

  40. Deroisy R, Zartarian M, Meurmans L, Nelissenne N, Micheletti MC, Albert A, Reginster JY. Acute changes in serum calcium and parathyroid hormone circulating levels induced by the oral intake of five currently available calcium salts in healthy male volunteers. Clin Rheumatol. 1997;16(3):249–53.

    Article  CAS  PubMed  Google Scholar 

  41. Cusano NE, Maalouf NM, Wang PY, Zhang C, Cremers SC, Haney EM, Bauer DC, Orwoll ES, Bilezikian JP. Normocalcemic hyperparathyroidism and hypoparathyroidism in two community-based nonreferral populations. J Clin Endocrinol Metab. 2013;98(7):2734–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Millan JL, Whyte MP. Alkaline phosphatase and hypophosphatasia. Calcif Tissue Int. 2016;98(4):398–416.

    Article  CAS  PubMed  Google Scholar 

  43. Millan JL. The role of phosphatases in the initiation of skeletal mineralization. Calcif Tissue Int. 2013;93(4):299–306.

    Article  CAS  PubMed  Google Scholar 

  44. Ridefelt P, Gustafsson J, Aldrimer M, Hellberg D. Alkaline phosphatase in healthy children: reference intervals and prevalence of elevated levels. Horm Res Paediatr. 2014;82(6):399–404.

    Article  CAS  PubMed  Google Scholar 

  45. Whyte MP. Hypophosphatasia – aetiology, nosology, pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2016;12(4):233–46.

    Article  CAS  PubMed  Google Scholar 

  46. Shipman KE, Holt AD, Gama R. Interpreting an isolated raised serum alkaline phosphatase level in an asymptomatic patient. BMJ. 2013;346:f976.

    Article  PubMed  Google Scholar 

  47. Huh SY, Feldman HA, Cox JE, Gordon CM. Prevalence of transient hyperphosphatasemia among healthy infants and toddlers. Pediatrics. 2009;124(2):703–9.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Kraut JR, Metrick M, Maxwell NR, Kaplan MM. Isoenzyme studies in transient hyperphosphatasemia of infancy. Ten new cases and a review of the literature. Am J Dis Child. 1985;139(7):736–40.

    Article  CAS  PubMed  Google Scholar 

  49. Gualco G, Lava SA, Garzoni L, Simonetti GD, Bettinelli A, Milani GP, Provero MC, Bianchetti MG. Transient benign hyperphophatasemia. J Pediatr Gastroenterol Nutr. 2013;57(2):167–71.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Deborah M. Mitchell

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  1. Deborah M. Mitchell
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Correspondence to Deborah M. Mitchell .

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Editors and Affiliations

  1. Division of Pediatric Endocrinology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Takara Stanley

  2. Division of Pediatric Endocrinology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Madhusmita Misra

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Mitchell, D.M. (2021). Calcium, Phosphate, Vitamin D, Parathyroid Hormone, and Alkaline Phosphatase. In: Stanley, T., Misra, M. (eds) Endocrine Conditions in Pediatrics. Springer, Cham. https://doi.org/10.1007/978-3-030-52215-5_26

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  • DOI: https://doi.org/10.1007/978-3-030-52215-5_26

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