Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Primer
  • Published:

Hypoparathyroidism

Nature Reviews Disease Primers volume 3, Article number: 17055 (2017) Cite this article

Subjects

A Correction to this article was published on 05 October 2017

Abstract

Hypoparathyroidism is a disease characterized by inadequately low circulating concentrations of parathyroid hormone (PTH) resulting in low calcium levels and increased phosphate levels in the blood. Symptoms of the disease result from increased neuromuscular irritability caused by hypocalcaemia and include tingling, muscle cramps and seizures. The most common cause of the disease is inadvertent removal of, or injury to, the parathyroid glands during neck surgery, followed by genetic, idiopathic and autoimmune aetiologies. Conventional treatment includes activated vitamin D and/or calcium supplements, but this treatment does not fully replace the functions of PTH and can lead to short-term problems (such as hypocalcaemia, hypercalcaemia and increased urinary calcium excretion) and long-term complications (which include nephrocalcinosis, kidney stones and brain calcifications). PTH replacement has emerged as a new treatment option. Clinical trials using human PTH(1–34) and PTH(1–84) showed that this treatment was safe and effective in studies lasting up to 6 years. Recombinant human PTH(1–84) has been approved in the United States and Europe for the management of hypoparathyroidism; however, its effect on long-term complications is still being evaluated. Clinical practice guidelines, which describe the consensus of experts in the field, have been published and recognize the need for more research to optimize care. In this Primer, we summarize current knowledge of the prevalence, pathophysiology, clinical presentation and management of hypoparathyroidism.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Regulation of extracellular calcium homeostasis.
Figure 2: Overview of the regulation of PTH synthesis, secretion and action and associated genetic disorders.
Figure 3: Transcription factors involved in parathyroid gland development and function.
Figure 4: Clinical manifestations of hypoparathyroidism.
Figure 5: Extraskeletal calcifications.

Similar content being viewed by others

References

  1. Bilezikian, J. P. et al. Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research. J. Bone Miner. Res. 26, 2317–2337 (2011).

    Article  CAS  PubMed  Google Scholar 

  2. Shoback, D. Clinical practice. Hypoparathyroidism.N. Engl. J. Med. 359, 391–403 (2008).

    Article  CAS  PubMed  Google Scholar 

  3. Clarke, B. L. et al. Epidemiology and diagnosis of hypoparathyroidism. J. Clin. Endocrinol. Metab. 101, 2284–2299 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Shoback, D. M. et al. Presentation of hypoparathyroidism: etiologies and clinical features. J. Clin. Endocrinol. Metab. 101, 2300–2312 (2016).

    Article  CAS  PubMed  Google Scholar 

  5. Bollerslev, J. et al. European Society of Endocrinology Clinical Guideline: treatment of chronic hypoparathyroidism in adults. Eur. J. Endocrinol. 173, G1–G20 (2015). These are guidelines developed by a panel representing the European Society of Endocrinology.

    Article  CAS  PubMed  Google Scholar 

  6. Brandi, M. L. et al. Management of hypoparathyroidism: summary statement and guidelines. J. Clin. Endocrinol. Metab. 101, 2273–2283 (2016). These are guidelines produced by experts in the field.

    Article  CAS  PubMed  Google Scholar 

  7. Astor, M. C. et al. Epidemiology and health-related quality of life in hypoparathyroidism in Norway. J. Clin. Endocrinol. Metab. 101, 3045–3053 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Underbjerg, L., Sikjaer, T., Mosekilde, L. & Rejnmark, L. The epidemiology of nonsurgical hypoparathyroidism in Denmark: a nationwide case finding study. J. Bone Miner. Res. 30, 1738–1744 (2015).

    Article  CAS  PubMed  Google Scholar 

  9. Underbjerg, L., Sikjaer, T., Mosekilde, L. & Rejnmark, L. Postsurgical hypoparathyroidism — risk of fractures, psychiatric diseases, cancer, cataract, and infections. J. Bone Miner. Res. 29, 2504–2510 (2014).

    Article  PubMed  Google Scholar 

  10. Davies, L. & Welch, H. G. Current thyroid cancer trends in the United States. JAMA Otolaryngol. Head Neck Surg. 140, 317–322 (2014).

    Article  PubMed  Google Scholar 

  11. Powers, J., Joy, K., Ruscio, A. & Lagast, H. Prevalence and incidence of hypoparathyroidism in the United States using a large claims database. J. Bone Miner. Res. 28, 2570–2576 (2013).

    Article  PubMed  Google Scholar 

  12. Clarke, B. L., Leibson, C., Emerson, J., Ransom, J. E. & Lagast, H. Co-morbid-medical conditions associated with prevalent hypoparathyroidism: a population-based study. J. Bone Miner. Res. 26, S182 (2011).

    Article  CAS  Google Scholar 

  13. Underbjerg, L., Sikjaer, T., Mosekilde, L. & Rejnmark, L. Cardiovascular and renal complications to postsurgical hypoparathyroidism: a Danish nationwide controlled historic follow-up study. J. Bone Miner. Res. 28, 2277–2285 (2013). Through analysis of a national patient registry in Denmark, this study confirms that there are increased risks of renal disease and seizures in patients with hypoparathyroidism.

    Article  PubMed  Google Scholar 

  14. Cipriani, C. et al. The Epidemiology of hypoparathyroidism in Italy: an 8-year register-based study. Calcif. Tissue Int. 100, 278–285 (2017).

    Article  CAS  PubMed  Google Scholar 

  15. Hannan, F. M., Babinsky, V. N. & Thakker, R. V. Disorders of the calcium-sensing receptor and partner proteins: insights into the molecular basis of calcium homeostasis. J. Mol. Endocrinol. 57, R127–R142 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Silva, B. C. & Bilezikian, J. P. Parathyroid hormone: anabolic and catabolic actions on the skeleton. Curr. Opin. Pharmacol. 22, 41–50 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bergwitz, C. & Juppner, H. Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23. Annu. Rev. Med. 61, 91–104 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Quarles, L. D. Endocrine functions of bone in mineral metabolism regulation. J. Clin. Invest. 118, 3820–3828 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Thakker, R. V., Bringhurst, F. R. & Jüppner, H. in Endocrinology: Adult and Pediatric 7th edn (eds Jameson, J. L. & De Groot, L. J. ) 1063–1089 (Saunders/Elsevier, 2016).

    Book  Google Scholar 

  20. Gupta, A., Winer, K., Econs, M. J., Marx, S. J. & Collins, M. T. FGF-23 is elevated by chronic hyperphosphatemia. J. Clin. Endocrinol. Metab. 89, 4489–4492 (2004).

    Article  CAS  PubMed  Google Scholar 

  21. Houillier, P. Mechanisms and regulation of renal magnesium transport. Annu. Rev. Physiol. 76, 411–430 (2014).

    Article  PubMed  Google Scholar 

  22. Quitterer, U., Hoffmann, M., Freichel, M. & Lohse, M. J. Paradoxical block of parathormone secretion is mediated by increased activity of Gα subunits. J. Biol. Chem. 276, 6763–6769 (2001).

    Article  CAS  PubMed  Google Scholar 

  23. Tong, G. M. & Rude, R. K. Magnesium deficiency in critical illness. J. Intensive Care Med. 20, 3–17 (2005).

    Article  PubMed  Google Scholar 

  24. Cholst, I. N. et al. The influence of hypermagnesemia on serum calcium and parathyroid hormone levels in human subjects. N. Engl. J. Med. 310, 1221–1225 (1984).

    Article  CAS  PubMed  Google Scholar 

  25. Quinn, S. J. et al. CaSR-mediated interactions between calcium and magnesium homeostasis in mice. Am. J. Physiol. Endocrinol. Metab. 304, E724–E733 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lorente-Poch, L., Sancho, J. J., Ruiz, S. & Sitges-Serra, A. Importance of in situ preservation of parathyroid glands during total thyroidectomy. Br. J. Surg. 102, 359–367 (2015).

    Article  CAS  PubMed  Google Scholar 

  27. Cho, J. N., Park, W. S. & Min, S. Y. Predictors and risk factors of hypoparathyroidism after total thyroidectomy. Int. J. Surg. 34, 47–52 (2016).

    Article  PubMed  Google Scholar 

  28. Edafe, O., Antakia, R., Laskar, N., Uttley, L. & Balasubramanian, S. P. Systematic review and meta-analysis of predictors of post-thyroidectomy hypocalcaemia. Br. J. Surg. 101, 307–320 (2014).

    Article  CAS  PubMed  Google Scholar 

  29. Halperin, I., Nubiola, A., Vendrell, J. & Vilardell, E. Late-onset hypocalcemia appearing years after thyroid surgery. J. Endocrinol. Invest. 12, 419–420 (1989).

    Article  CAS  PubMed  Google Scholar 

  30. Kim, J. H. et al. Diverse genetic aetiologies and clinical outcomes of paediatric hypoparathyroidism. Clin. Endocrinol. (Oxf.) 83, 790–796 (2015).

    Article  CAS  Google Scholar 

  31. Kobrynski, L. J. & Sullivan, K. E. Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes. Lancet 370, 1443–1452 (2007).

    Article  CAS  PubMed  Google Scholar 

  32. Jerome, L. A. & Papaioannou, V. E. DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1. Nat. Genet. 27, 286–291 (2001).

    Article  CAS  PubMed  Google Scholar 

  33. Yagi, H. et al. Role of TBX1 in human del22q11.2 syndrome. Lancet 362, 1366–1373 (2003).

    Article  CAS  PubMed  Google Scholar 

  34. Villanueva, M. P. et al. Genetic and comparative mapping of genes dysregulated in mouse hearts lacking the Hand2 transcription factor gene. Genomics 80, 593–600 (2002).

    Article  CAS  PubMed  Google Scholar 

  35. Inoue, H. et al. Successful cord blood transplantation for a CHARGE syndrome with CHD7 mutation showing DiGeorge sequence including hypoparathyroidism. Eur. J. Pediatr. 169, 839–844 (2010).

    Article  PubMed  Google Scholar 

  36. Randall, V. et al. Great vessel development requires biallelic expression of Chd7 and Tbx1 in pharyngeal ectoderm in mice. J. Clin. Invest. 119, 3301–3310 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Kisand, K. & Peterson, P. Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. J. Clin. Immunol. 35, 463–478 (2015).

    Article  CAS  PubMed  Google Scholar 

  38. Heino, M. et al. Autoimmune regulator is expressed in the cells regulating immune tolerance in thymus medulla. Biochem. Biophys. Res. Commun. 257, 821–825 (1999).

    Article  CAS  PubMed  Google Scholar 

  39. Anderson, M. S. et al. The cellular mechanism of Aire control of T cell tolerance. Immunity 23, 227–239 (2005).

    Article  CAS  PubMed  Google Scholar 

  40. Ferre E. M. et al. Redefined clinical features and diagnostic criteria in autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy. JCI Insight 1 e88782 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Li, D. et al. Exome sequencing reveals mutations in AIRE as a cause of isolated hypoparathyroidism. J. Clin. Endocrinol. Metab. 102, 1726–1733 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Perheentupa, J. APS-I/APECED: the clinical disease and therapy. Endocrinol. Metab. Clin. North Am. 31, 295–320 (2002).

    Article  PubMed  Google Scholar 

  43. Bensing, S. et al. Increased death risk and altered cancer incidence pattern in patients with isolated or combined autoimmune primary adrenocortical insufficiency. Clin. Endocrinol. (Oxf.) 69, 697–704 (2008).

    Article  Google Scholar 

  44. Ali, A. et al. Functional characterization of GATA3 mutations causing the hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome: insight into mechanisms of DNA binding by the GATA3 transcription factor. Hum. Mol. Genet. 16, 265–275 (2007).

    Article  CAS  PubMed  Google Scholar 

  45. Bilous, R. W. et al. Brief report: autosomal dominant familial hypoparathyroidism, sensorineural deafness, and renal dysplasia. N. Engl. J. Med. 327, 1069–1074 (1992).

    Article  CAS  PubMed  Google Scholar 

  46. Van Esch, H. et al. GATA3 haplo-insufficiency causes human HDR syndrome. Nature 406, 419–422 (2000).

    Article  CAS  PubMed  Google Scholar 

  47. Grigorieva, I. V. et al. Gata3-deficient mice develop parathyroid abnormalities due to dysregulation of the parathyroid-specific transcription factor Gcm2. J. Clin. Invest. 120, 2144–2155 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Grigorieva, I. V. & Thakker, R. V. Transcription factors in parathyroid development: lessons from hypoparathyroid disorders. Ann. NY Acad. Sci. 1237, 24–38 (2011).

    Article  CAS  PubMed  Google Scholar 

  49. Han, S. I., Tsunekage, Y. & Kataoka, K. Gata3 cooperates with Gcm2 and MafB to activate parathyroid hormone gene expression by interacting with SP1. Mol. Cell Endocrinol. 411, 113–120 (2015).

    Article  CAS  PubMed  Google Scholar 

  50. Kamitani-Kawamoto, A. et al. MafB interacts with Gcm2 and regulates parathyroid hormone expression and parathyroid development. J. Bone Miner. Res. 26, 2463–2472 (2011).

    Article  CAS  PubMed  Google Scholar 

  51. El-Hattab, A. W., Adesina, A. M., Jones, J. & Scaglia, F. MELAS syndrome: clinical manifestations, pathogenesis, and treatment options. Mol. Genet. Metab. 116, 4–12 (2015).

    Article  CAS  PubMed  Google Scholar 

  52. Harvey, J. N. & Barnett, D. Endocrine dysfunction in Kearns–Sayre syndrome. Clin. Endocrinol. (Oxf.) 37, 97–103 (1992).

    Article  CAS  Google Scholar 

  53. Naiki, M. et al. Mutations in HADHB, which encodes the beta-subunit of mitochondrial trifunctional protein, cause infantile onset hypoparathyroidism and peripheral polyneuropathy. Am. J. Med. Genet. A 164A, 1180–1187 (2014).

    Article  PubMed  CAS  Google Scholar 

  54. Naguib, K. K. et al. Sanjad–Sakati syndrome/Kenny–Caffey syndrome type 1: a study of 21 cases in Kuwait. East Mediterr. Health J. 15, 345–352 (2009).

    Article  CAS  PubMed  Google Scholar 

  55. Parvari, R. et al. Mutation of TBCE causes hypoparathyroidism–retardation–dysmorphism and autosomal recessive Kenny–Caffey syndrome. Nat. Genet. 32, 448–452 (2002).

    Article  CAS  PubMed  Google Scholar 

  56. Parvari, R., Diaz, G. A. & Hershkovitz, E. Parathyroid development and the role of tubulin chaperone E. Horm. Res. 67, 12–21 (2007).

    CAS  PubMed  Google Scholar 

  57. Alabert, C. et al. Nascent chromatin capture proteomics determines chromatin dynamics during DNA replication and identifies unknown fork components. Nat. Cell Biol. 16, 281–293 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Unger, S. et al. FAM111A mutations result in hypoparathyroidism and impaired skeletal development. Am. J. Hum. Genet. 92, 990–995 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Nesbit, M. A. et al. Mutations affecting G-protein subunit α11 in hypercalcemia and hypocalcemia. N. Engl. J. Med. 368, 2476–2486 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Pearce, S. H. et al. A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor. N. Engl. J. Med. 335, 1115–1122 (1996). Building on previous case reports, this paper reports activating mutations of CASR in five out of six kindreds with autosomal dominant hypocalcaemia.

    Article  CAS  PubMed  Google Scholar 

  61. Winer, K. K., Fulton, K. A., Albert, P. S. & Cutler, G. B. Jr. Effects of pump versus twice-daily injection delivery of synthetic parathyroid hormone 1–34 in children with severe congenital hypoparathyroidism. J. Pediatr. 165, 556–563.e1 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Winer, K. K., Yanovski, J. A., Sarani, B. & Cutler, G. B. Jr. A randomized, cross-over trial of once-daily versus twice-daily parathyroid hormone 1–34 in treatment of hypoparathyroidism. J. Clin. Endocrinol. Metab. 83, 3480–3486 (1998).

    CAS  PubMed  Google Scholar 

  63. Raue, F. et al. Activating mutations in the calcium-sensing receptor: genetic and clinical spectrum in 25 patients with autosomal dominant hypocalcaemia — a German survey. Clin. Endocrinol. (Oxf.) 75, 760–765 (2011).

    Article  CAS  Google Scholar 

  64. Watanabe, S. et al. Association between activating mutations of calcium-sensing receptor and Bartter's syndrome. Lancet 360, 692–694 (2002).

    Article  CAS  PubMed  Google Scholar 

  65. Mannstadt, M. et al. Germline mutations affecting Gα11 in hypoparathyroidism. N. Engl. J. Med. 368, 2532–2534 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Piret, S. E. et al. Identification of a G-protein subunit-α11 gain-of-function mutation, Val340Met, in a family with autosomal dominant hypocalcemia type 2 (ADH2). J. Bone Miner. Res. 31, 1207–1214 (2016).

    Article  CAS  PubMed  Google Scholar 

  67. Li, D. et al. Autosomal dominant hypoparathyroidism caused by germline mutation in GNA11: phenotypic and molecular characterization. J. Clin. Endocrinol. Metab. 99, E1774–E1783 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Tenhola, S. et al. Impaired growth and intracranial calcifications in autosomal dominant hypocalcemia caused by a GNA11 mutation. Eur. J. Endocrinol. 175, 211–218 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Günther, T. et al. Genetic ablation of parathyroid glands reveals another source of parathyroid hormone. Nature 406, 199–203 (2000).

    Article  PubMed  Google Scholar 

  70. Bowl, M. R. et al. Identification and characterization of novel parathyroid-specific transcription factor glial cells missing homolog B (GCMB) mutations in eight families with autosomal recessive hypoparathyroidism. Hum. Mol. Genet. 19, 2028–2038 (2010).

    Article  CAS  PubMed  Google Scholar 

  71. Mannstadt, M. et al. Dominant-negative GCMB mutations cause an autosomal dominant form of hypoparathyroidism. J. Clin. Endocrinol. Metab. 93, 3568–3576 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Mirczuk, S. M. et al. A missense glial cells missing homolog B (GCMB) mutation, Asn502His, causes autosomal dominant hypoparathyroidism. J. Clin. Endocrinol. Metab. 95, 3512–3516 (2010).

    Article  CAS  PubMed  Google Scholar 

  73. Ertl, D. A., Stary, S., Streubel, B., Raimann, A. & Haeusler, G. A novel homozygous mutation in the parathyroid hormone gene (PTH) in a girl with isolated hypoparathyroidism. Bone 51, 629–632 (2012).

    Article  CAS  PubMed  Google Scholar 

  74. Parkinson, D. B. & Thakker, R. V. A donor splice site mutation in the parathyroid hormone gene is associated with autosomal recessive hypoparathyroidism. Nat. Genet. 1, 149–152 (1992).

    Article  CAS  PubMed  Google Scholar 

  75. Lee, S. et al. A homozygous [Cys25]PTH(1–84) mutation that impairs PTH/PTHrP receptor activation defines a novel form of hypoparathyroidism. J. Bone Miner. Res. 30, 1803–1813 (2015).

    Article  CAS  PubMed  Google Scholar 

  76. Mumm, S., Whyte, M. P., Thakker, R. V., Buetow, K. H. & Schlessinger, D. mtDNA analysis shows common ancestry in two kindreds with X-linked recessive hypoparathyroidism and reveals a heteroplasmic silent mutation. Am. J. Hum. Genet. 60, 153–159 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Bowl, M. R. et al. An interstitial deletion-insertion involving chromosomes 2p25.3 and Xq27.1, near SOX3, causes X-linked recessive hypoparathyroidism. J. Clin. Invest. 115, 2822–2831 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Taylor, J. C. et al. Factors influencing success of clinical genome sequencing across a broad spectrum of disorders. Nat. Genet. 47, 717–726 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Nair, K. S., Holdaway, I. M., Evans, M. C. & Cameron, A. D. Influence of magnesium on the secretion and action of parathyroid hormone. J. Endocrinol. Invest. 2, 267–270 (1979).

    Article  CAS  PubMed  Google Scholar 

  80. Saggese, G., Federico, G., Bertelloni, S., Baroncelli, G. I. & Calisti, L. Hypomagnesemia and the parathyroid hormone-vitamin D endocrine system in children with insulin-dependent diabetes mellitus: effects of magnesium administration. J. Pediatr. 118, 220–225 (1991).

    Article  CAS  PubMed  Google Scholar 

  81. Frankenhaeuser, B. & Hodgkin, A. L. The action of calcium on the electrical properties of squid axons. J. Physiol. 137, 218–244 (1957).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Williams, G. T. & Brown, M. Laryngospasm in hypoparathyroidism. J. Laryngol. Otol. 88, 369–373 (1974).

    Article  CAS  PubMed  Google Scholar 

  83. Chou, C. T., Siegel, B. & Mehta, D. Stridor and apnea as the initial presentation of primary hypoparathyroidism. Int. J. Pediatr. Otorhinolaryngol. 80, 30–32 (2016).

    Article  PubMed  Google Scholar 

  84. Jesus, J. E. & Landry, A. Images in clinical medicine. Chvostek's and Trousseau's signs. N. Engl. J. Med. 367, e15 (2012).

    Article  PubMed  Google Scholar 

  85. Mitchell, D. M. et al. Long-term follow-up of patients with hypoparathyroidism. J. Clin. Endocrinol. Metab. 97, 4507–4514 (2012). This paper describes the first large long-term follow-up study of patients with hypoparathyroidism, which revealed that rates of complications including renal disease are high.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Goswami, R. et al. Prevalence and progression of basal ganglia calcification and its pathogenic mechanism in patients with idiopathic hypoparathyroidism. Clin. Endocrinol. (Oxf.) 77, 200–206 (2012). This study of a large Indian cohort of patients with idiopathic hypoparathyroidism reports a high prevalence of basal ganglia calcifications (73.8%) and shows that the risk of progression over time was associated with a lower serum calcium–phosphate ratio.

    Article  CAS  Google Scholar 

  87. Legati, A. et al. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. Nat. Genet. 47, 579–581 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Wang, C. et al. Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis. Nat. Genet. 44, 254–256 (2012).

    Article  CAS  PubMed  Google Scholar 

  89. Abe, S. et al. A rare case of idiopathic hypoparathyroidism with varied neurological manifestations. Intern. Med. 35, 129–134 (1996).

    Article  CAS  PubMed  Google Scholar 

  90. Kowdley, K. V., Coull, B. M. & Orwoll, E. S. Cognitive impairment and intracranial calcification in chronic hypoparathyroidism. Am. J. Med. Sci. 317, 273–277 (1999).

    Article  CAS  PubMed  Google Scholar 

  91. Aggarwal, S. et al. Neuropsychological dysfunction in idiopathic hypoparathyroidism and its relationship with intracranial calcification and serum total calcium. Eur. J. Endocrinol. 168, 895–903 (2013).

    Article  CAS  PubMed  Google Scholar 

  92. Vered, I., Vered, Z., Perez, J. E., Jaffe, A. S. & Whyte, M. P. Normal left ventricular performance documented by Doppler echocardiography in patients with long-standing hypocalcemia. Am. J. Med. 86, 413–416 (1989).

    Article  CAS  PubMed  Google Scholar 

  93. Newman, D. B. et al. Reversible cardiac dysfunction associated with hypocalcemia: a systematic review and meta-analysis of individual patient data. Heart Fail. Rev. 19, 199–205 (2014).

    Article  CAS  PubMed  Google Scholar 

  94. Velayuthan, S., Gungor, N. & McVie, R. Hypocalcemic cardiomyopathy as initial presentation of primary hypoparathyroidism. Pediatr. Int. 56, e23–e25 (2014).

    Article  PubMed  Google Scholar 

  95. Yamamoto, M., Akatsu, T., Nagase, T. & Ogata, E. Comparison of hypocalcemic hypercalciuria between patients with idiopathic hypoparathyroidism and those with gain-of-function mutations in the calcium-sensing receptor: is it possible to differentiate the two disorders? J. Clin. Endocrinol. Metab. 85, 4583–4591 (2000).

    Article  CAS  PubMed  Google Scholar 

  96. Lienhardt, A. et al. Activating mutations of the calcium-sensing receptor: management of hypocalcemia. J. Clin. Endocrinol. Metab. 86, 5313–5323 (2001).

    Article  CAS  PubMed  Google Scholar 

  97. Levy, I., Licht, C., Daneman, A., Sochett, E. & Harrington, J. The impact of hypoparathyroidism treatment on the kidney in children: long-term retrospective follow-up study. J. Clin. Endocrinol. Metab. 100, 4106–4113 (2015).

    Article  CAS  PubMed  Google Scholar 

  98. Clarke, B. L. Bone disease in hypoparathyroidism. Arq. Bras. Endocrinol. Metabol. 58, 545–552 (2014).

    Article  PubMed  Google Scholar 

  99. Silva, B. C., Rubin, M. R., Cusano, N. E. & Bilezikian, J. P. Bone imaging in hypoparathyroidism. Osteoporosis Int. 28, 463–471 (2017).

    Article  CAS  Google Scholar 

  100. Dempster, D. in Hypoparathyroidism (eds Brandi, M. L. & Brown, E. M. ) 287–296 (Springer, 2015).

    Book  Google Scholar 

  101. Rubin, M. R. et al. PTH(1–84) administration reverses abnormal bone-remodeling dynamics and structure in hypoparathyroidism. J. Bone Miner. Res. 26, 2727–2736 (2011).

    Article  CAS  PubMed  Google Scholar 

  102. Rubin, M. R. et al. Dynamic and structural properties of the skeleton in hypoparathyroidism. J. Bone Miner. Res. 23, 2018–2024 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Rubin, M. R. et al. Three dimensional cancellous bone structure in hypoparathyroidism. Bone 46, 190–195 (2010).

    Article  PubMed  Google Scholar 

  104. Sikjaer, T. et al. Changes in 3-dimensional bone structure indices in hypoparathyroid patients treated with PTH(1–84): a randomized controlled study. J. Bone Miner. Res. 27, 781–788 (2012).

    Article  CAS  PubMed  Google Scholar 

  105. Jensen, S. B., Illum, F. & Dupont, E. Nature and frequency of dental changes in idiopathic hypoparathyroidism and pseudohypoparathyroidism. Scand. J. Dental Res. 89, 26–37 (1981).

    CAS  Google Scholar 

  106. Srirangarajan, S., Satyanarayan, A., Ravindra, S. & Thakur, S. Dental manifestation of primary idiopathic hypoparathyroidism. J. Indian Soc. Periodontol. 18, 524–526 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  107. Jakkani, R. K., Sureka, J. & Mathew, J. Spondyloarthropathy occurring in long-standing idiopathic hypoparathyroidism. Radiol. Case Rep. 6, 545 (2011).

    Article  PubMed  Google Scholar 

  108. Goswami, R. et al. Presence of spondyloarthropathy and its clinical profile in patients with hypoparathyroidism. Clin. Endocrinol. (Oxf.) 68, 258–263 (2008).

    CAS  Google Scholar 

  109. Policepatil, S. M., Caplan, R. H. & Dolan, M. Hypocalcemic myopathy secondary to hypoparathyroidism. WMJ 111, 173–175 (2012).

    PubMed  Google Scholar 

  110. Dai, C. L., Sun, Z. J., Zhang, X. & Qiu, M. C. Elevated muscle enzymes and muscle biopsy in idiopathic hypoparathyroidism patients. J. Endocrinol. Invest. 35, 286–289 (2012).

    CAS  PubMed  Google Scholar 

  111. Sikjaer, T. et al. Concurrent hypoparathyroidism is associated with impaired physical function and quality of life in hypothyroidism. J. Bone Miner. Res. 31, 1440–1448 (2016).

    Article  PubMed  Google Scholar 

  112. Steinberg, H. & Waldron, B. R. Idiopathic hypoparathyroidism; an analysis of fifty-two cases, including the report of a new case. Medicine 31, 133–154 (1952).

    Article  CAS  PubMed  Google Scholar 

  113. Arlt, W. et al. Well-being, mood and calcium homeostasis in patients with hypoparathyroidism receiving standard treatment with calcium and vitamin D. Eur. J. Endocrinol. 146, 215–222 (2002). This study describes an investigation into the mood and well-being of 25 women with post-surgical hypoparathyroidism compared with that of a control group of women with a history of thyroid surgery alone that found decreased well-being, with specific increases in anxiety, in the women with hypoparathyroidism despite them having generally good control of serum calcium levels.

    Article  CAS  PubMed  Google Scholar 

  114. Saha, S. et al. Long-term outcome of cataract surgery in patients with idiopathic hypoparathyroidism and its relationship with their calcemic status. J. Bone Miner. Metab. 35, 405–411 (2017).

    Article  PubMed  Google Scholar 

  115. Bunce, G. E., Kinoshita, J. & Horwitz, J. Nutritional factors in cataract. Annu. Rev. Nutr. 10, 233–254 (1990).

    Article  CAS  PubMed  Google Scholar 

  116. Ayuk, J., Matthews, T., Tayebjee, M. & Gittoes, N. J. A blind panic. Lancet 357, 1262 (2001).

    Article  CAS  PubMed  Google Scholar 

  117. Sarkar, S., Mondal, M., Das, K. & Shrimal, A. Mucocutaneous manifestations of acquired hypoparathyroidism: an observational study. Indian J. Endocrinol. Metab. 16, 819–820 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  118. Lee, Y., Nam, Y. H., Lee, J. H., Park, J. K. & Seo, Y. J. Hypocalcaemia-induced pustular psoriasis-like skin eruption. Br. J. Dermatol. 152, 591–593 (2005).

    Article  CAS  PubMed  Google Scholar 

  119. Guerreiro de Moura, C. A. et al. A case of acute generalized pustular psoriasis of von Zumbusch triggered by hypocalcemia. Case Rep. Dermatol. 7, 345–351 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  120. Hadker, N., Egan, J., Sanders, J., Lagast, H. & Clarke, B. L. Understanding the burden of illness associated with hypoparathyroidism reported among patients in the paradox study. Endocr. Pract. 20, 671–679 (2014).

    Article  PubMed  Google Scholar 

  121. O'Neill, W. C. The fallacy of the calcium-phosphorus product. Kidney Int. 72, 792–796 (2007).

    Article  CAS  PubMed  Google Scholar 

  122. Uhlig, K. et al. KDOQI US commentary on the 2009 KDIGO Clinical Practice Guideline for the diagnosis, evaluation, and treatment of CKD-mineral and bone disorder (CKD-MBD). Am. J. Kidney Dis. 55, 773–799 (2010).

    Article  PubMed  Google Scholar 

  123. Bilezikian, J. P. et al. Management of hypoparathyroidism: present and future. J. Clin. Endocrinol. Metab. 101, 2313–2324 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Boyce, A. M. et al. Ultrasound is superior to computed tomography for assessment of medullary nephrocalcinosis in hypoparathyroidism. J. Clin. Endocrinol. Metab. 98, 989–994 (2013). This paper demonstrates that ultrasound has substantially higher sensitivity than CT for detecting nephrocalcinosis, particularly mild-to-moderate disease, among patients with hypoparathyroidism.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Kirpalani, D. A. et al. An interesting case of primary hypoparathyroidism. Indian J. Nephrol. 24, 175–177 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Streeten, E. A., Mohtasebi, Y., Konig, M., Davidoff, L. & Ryan, K. Hypoparathyroidism: less severe hypocalcemia with treatment with vitamin D2 compared with calcitriol. J. Clin. Endocrinol. Metab. 102, 1505–1510 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  127. Stamp, T. C. Calcitriol dosage in osteomalacia, hypoparathyroidism and attempted treatment of myositis ossificans progressiva. Curr. Med. Res. Opin. 7, 316–336 (1981).

    Article  CAS  PubMed  Google Scholar 

  128. Shaw, N. J. A practical approach to hypocalcaemia in children. Endocr. Dev. 28, 84–100 (2015).

    Article  PubMed  CAS  Google Scholar 

  129. Winer, K. K. et al. Long-term treatment of hypoparathyroidism: a randomized controlled study comparing parathyroid hormone-(1–34) versus calcitriol and calcium. J. Clin. Endocrinol. Metab. 88, 4214–4220 (2003).

    Article  CAS  PubMed  Google Scholar 

  130. Winer, K. K., Sinaii, N., Peterson, D., Sainz, B. Jr & Cutler, G. B. Jr. Effects of once versus twice-daily parathyroid hormone 1–34 therapy in children with hypoparathyroidism. J. Clin. Endocrinol. Metab. 93, 3389–3395 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Winer, K. K. et al. Long-term treatment of 12 children with chronic hypoparathyroidism: a randomized trial comparing synthetic human parathyroid hormone 1–34 versus calcitriol and calcium. J. Clin. Endocrinol. Metab. 95, 2680–2688 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Winer, K. K., Yanovski, J. A. & Cutler, G. B. Jr. Synthetic human parathyroid hormone 1–34 versus calcitriol and calcium in the treatment of hypoparathyroidism. JAMA 276, 631–636 (1996). This paper details the first controlled study in patients with hypoparathyroidism using a PTH analogue and demonstrates that it is a safe and effective treatment.

    Article  CAS  PubMed  Google Scholar 

  133. Winer, K. K. et al. Synthetic human parathyroid hormone 1–34 replacement therapy: a randomized crossover trial comparing pump versus injections in the treatment of chronic hypoparathyroidism. J. Clin. Endocrinol. Metab. 97, 391–399 (2012). In a trial of adults with post-surgical hypoparathyroidism, this study shows that continuous subcutaneous infusion, when compared with twice-daily injection, of a PTH analogue results in less fluctuation in serum calcium levels, normalized urinary calcium excretion, normalized levels of bone turnover markers and a decreased overall medication dose.

    CAS  PubMed  Google Scholar 

  134. Linglart, A. et al. Long-term results of continuous subcutaneous recombinant PTH (1–34) infusion in children with refractory hypoparathyroidism. J. Clin. Endocrinol. Metab. 96, 3308–3312 (2011).

    Article  CAS  PubMed  Google Scholar 

  135. Gafni, R. I. et al. Transient increased calcium and calcitriol requirements after discontinuation of human synthetic parathyroid hormone 1–34 (hPTH 1–34) replacement therapy in hypoparathyroidism. J. Bone Miner. Res. 30, 2112–2118 (2015).

    Article  CAS  PubMed  Google Scholar 

  136. Fox, J., Garceau, R. & Lagast, H. SC injection of recombinant human parathyroid hormone rhPTH(1–84) in thigh provides a more prolonged pharmacokinetic profile and a greater calcemic response when compared with injection in abdomen. Bone Abstr. 3, 73 (2014).

    Google Scholar 

  137. Rubin, M. R. et al. Therapy of hypoparathyroidism with PTH(1–84): a prospective six year investigation of efficacy and safety. J. Clin. Endocrinol. Metab. 101, 2742–2750 (2016). This study describes a cohort of 33 patients treated with rhPTH(1–84) demonstrating persistent efficacy and apparent safety of this treatment regimen over a relatively long time.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Sikjaer, T. et al. The effect of adding PTH(1–84) to conventional treatment of hypoparathyroidism: a randomized, placebo-controlled study. J. Bone Miner. Res. 26, 2358–2370 (2011).

    Article  CAS  PubMed  Google Scholar 

  139. Clarke, B. L. et al. Effects of parathyroid hormone rhPTH(1–84) on phosphate homeostasis and vitamin D metabolism in hypoparathyroidism: REPLACE phase 3 study. Endocrine 55, 273–282 (2017).

    Article  CAS  PubMed  Google Scholar 

  140. Mannstadt, M. et al. Efficacy and safety of recombinant human parathyroid hormone (1–84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study. Lancet Diabetes Endocrinol. 1, 275–283 (2013). This paper describes a phase III randomized controlled trial using flexible dosing of rhPTH(1–84) in hypoparathyroidism that demonstrated efficacy in reducing calcitriol and calcium needs and served as the basis for drug approval in the United States.

    Article  CAS  PubMed  Google Scholar 

  141. Middler, S., Pak, C. Y., Murad, F. & Bartter, F. C. Thiazide diuretics and calcium metabolism. Metabolism 22, 139–146 (1973).

    Article  CAS  PubMed  Google Scholar 

  142. Parfitt, A. M. The interactions of thiazide diuretics with parathyroid hormone and vitamin D. Studies in patients with hypoparathyroidism. J. Clin. Invest. 51, 1879–1888 (1972).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. McCormick, J. A. & Ellison, D. H. Distal convoluted tubule. Compr. Physiol. 5, 45–98 (2015).

    PubMed  PubMed Central  Google Scholar 

  144. Nijenhuis, T. et al. Enhanced passive Ca2+ reabsorption and reduced Mg2+ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia. J. Clin. Invest. 115, 1651–1658 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Eknoyan, G., Suki, W. N. & Martinez-Maldonado, M. Effect of diuretics on urinary excretion of phosphate, calcium, and magnesium in thyroparathyroidectomized dogs. J. Lab. Clin. Med. 76, 257–266 (1970).

    CAS  PubMed  Google Scholar 

  146. Porter, R. H. et al. Treatment of hypoparathyroid patients with chlorthalidone. N. Engl. J. Med. 298, 577–581 (1978).

    Article  CAS  PubMed  Google Scholar 

  147. Sato, K. et al. Hydrochlorothiazide effectively reduces urinary calcium excretion in two Japanese patients with gain-of-function mutations of the calcium-sensing receptor gene. J. Clin. Endocrinol. Metab. 87, 3068–3073 (2002).

    Article  CAS  PubMed  Google Scholar 

  148. Breslau, N. A., McGuire, J. L., Zerwekh, J. E. & Pak, C. Y. The role of dietary sodium on renal excretion and intestinal absorption of calcium and on vitamin D metabolism. J. Clin. Endocrinol. Metab. 55, 369–373 (1982).

    Article  CAS  PubMed  Google Scholar 

  149. Vahle, J. L. et al. Bone neoplasms in F344 rats given teriparatide [rhPTH(1–34)] are dependent on duration of treatment and dose. Toxicol. Pathol. 32, 426–438 (2004).

    Article  CAS  PubMed  Google Scholar 

  150. Vahle, J. L., Sato, M. & Long, G. G. Variations in animal populations over time and differences in diagnostic thresholds used can impact tumor incidence data. Toxicol. Pathol. 35, 1045–1046 (2007).

    Article  PubMed  Google Scholar 

  151. Vahle, J. L. et al. Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1–34) for 2 years and relevance to human safety. Toxicol. Pathol. 30, 312–321 (2002).

    Article  CAS  PubMed  Google Scholar 

  152. Tashjian, A. H. Jr & Goltzman, D. On the interpretation of rat carcinogenicity studies for human PTH(1–34) and human PTH(1–84). J. Bone Miner. Res. 23, 803–811 (2008).

    Article  CAS  PubMed  Google Scholar 

  153. Vahle, J. L. et al. Lack of bone neoplasms and persistence of bone efficacy in cynomolgus macaques after long-term treatment with teriparatide [rhPTH(1–34)]. J. Bone Miner. Res. 23, 2033–2039 (2008).

    Article  CAS  PubMed  Google Scholar 

  154. Silverberg, S. J., Shane, E., Jacobs, T. P., Siris, E. & Bilezikian, J. P. A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery. N. Engl. J. Med. 341, 1249–1255 (1999).

    Article  CAS  PubMed  Google Scholar 

  155. Andrews, E. B. et al. The US postmarketing surveillance study of adult osteosarcoma and teriparatide: study design and findings from the first 7 years. J. Bone Miner. Res. 27, 2429–2437 (2012).

    Article  CAS  PubMed  Google Scholar 

  156. Cipriani, C., Irani, D. & Bilezikian, J. P. Safety of osteoanabolic therapy: a decade of experience. J. Bone Miner. Res. 27, 2419–2428 (2012).

    Article  PubMed  CAS  Google Scholar 

  157. Cho, N. L. et al. Surgeons and patients disagree on the potential consequences from hypoparathyroidism. Endocr. Pract. 20, 427–446 (2014).

    Article  PubMed  Google Scholar 

  158. Cusano, N. E. et al. The effect of PTH(1–84) on quality of life in hypoparathyroidism. J. Clin. Endocrinol. Metab. 98, 2356–2361 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Cusano, N. E. et al. PTH(1–84) is associated with improved quality of life in hypoparathyroidism through 5 years of therapy. J. Clin. Endocrinol. Metab. 99, 3694–3699 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Santonati, A. et al. PTH(1–34) for surgical hypoparathyroidism: a prospective, open-label investigation of efficacy and quality of life. J. Clin. Endocrinol. Metab. 100, 3590–3597 (2015).

    Article  CAS  PubMed  Google Scholar 

  161. Sikjaer, T. et al. Effects of PTH(1–84) therapy on muscle function and quality of life in hypoparathyroidism: results from a randomized controlled trial. Osteoporosis Int. 25, 1717–1726 (2014).

    Article  CAS  Google Scholar 

  162. Vokes, T. et al. Recombinant human parathyroid hormone (rhPTH [1–84]) therapy in hypoparathyroidism and improvement in quality of life. J. Bone Miner. Res. 30, S200 (2015).

    Google Scholar 

  163. Niall, H. D. et al. The amino acid sequence of bovine parathyroid hormone I. Hoppe Seylers Z. Physiol. Chem. 351, 1586–1588 (1970).

    CAS  PubMed  Google Scholar 

  164. Nussbaum, S. R. et al. Highly sensitive two-site immunoradiometric assay of parathyrin, and its clinical utility in evaluating patients with hypercalcemia. Clin. Chem. 33, 1364–1367 (1987).

    Article  CAS  PubMed  Google Scholar 

  165. Bi, R. et al. Diphtheria toxin- and GFP-based mouse models of acquired hypoparathyroidism and treatment with a long-acting parathyroid hormone analog. J. Bone Miner. Res. 31, 975–984 (2016).

    Article  CAS  PubMed  Google Scholar 

  166. Tamura, T. et al. Identification of an orally active small-molecule PTHR1 agonist for the treatment of hypoparathyroidism. Nat. Commun. 7, 13384 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Lemos, M. C. & Thakker, R. V. GNAS mutations in pseudohypoparathyroidism type 1a and related disorders. Hum. Mutat. 36, 11–19 (2015).

    Article  CAS  PubMed  Google Scholar 

  168. Linglart, A., Gensure, R. C., Olney, R. C., Jüppner, H. & Bastepe, M. A novel STX16 deletion in autosomal dominant pseudohypoparathyroidism type Ib redefines the boundaries of a cis-acting imprinting control element of GNAS. Am. J. Hum. Genet. 76, 804–814 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Richard, N. et al. A new deletion ablating NESP55 causes loss of maternal imprint of A/B GNAS and autosomal dominant pseudohypoparathyroidism type Ib. J. Clin. Endocrinol. Metab. 97, E863–E867 (2012).

    Article  CAS  PubMed  Google Scholar 

  170. Brix, B. et al. Different pattern of epigenetic changes of the GNAS gene locus in patients with pseudohypoparathyroidism type Ic confirm the heterogeneity of underlying pathomechanisms in this subgroup of pseudohypoparathyroidism and the demand for a new classification of GNAS-related disorders. J. Clin. Endocrinol. Metab. 99, E1564–E1570 (2014).

    Article  CAS  PubMed  Google Scholar 

  171. Srivastava, T. & Alon, U. S. Stage I vitamin D-deficiency rickets mimicking pseudohypoparathyroidism type II. Clin. Pediatr. (Phila) 41, 263–268 (2002).

    Article  Google Scholar 

  172. Segre, B. V., D'Amour, P. & Potts, J. T. Metabolism of radioiodinated bovine parathyroid hormone in the rat. Endocrinology 99, 1645–1652 (1976).

    Article  CAS  PubMed  Google Scholar 

  173. Zhang, C. X., Weber, B. V., Thammavong, J., Grover, T. A. & Wells, D. S. Identification of carboxyl-terminal peptide fragments of parathyroid hormone in human plasma at low-picomolar levels by mass spectrometry. Anal. Chem. 78, 1636–1643 (2006).

    Article  CAS  PubMed  Google Scholar 

  174. D'Amour, P. Acute and chronic regulation of circulating PTH: significance in health and in disease. Clin. Biochem. 45, 964–969 (2012).

    Article  CAS  PubMed  Google Scholar 

  175. Berson, S. A., Yalow, R. S., Aurbach, G. D. & Potts, J. T. Immunoassay of bovine and human parathyroid hormone. Proc. Natl Acad. Sci. USA 49, 613–617 (1963).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. John, M. R. et al. A novel immunoradiometric assay detects full-length human PTH but not amino-terminally truncated fragments: implications for PTH measurements in renal failure. J. Clin. Endocrinol. Metab. 84, 4287–4290 (1999).

    Article  CAS  PubMed  Google Scholar 

  177. Inaba, M. et al. Technical and clinical characterization of the bio-PTH (1–84) immunochemiluminometric assay and comparison with a second-generation assay for parathyroid hormone. Clin. Chem. 50, 385–390 (2004).

    Article  CAS  PubMed  Google Scholar 

  178. D'Amour, P. et al. Evidence that the amino-terminal composition of non-(1–84) parathyroid hormone fragments starts before position 19. Clin. Chem. 51, 169–176 (2005).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank J. Warshauer (Division of Endocrinology, Metabolism, and Diabetes, University of California, San Francisco, USA) for providing Figure 5a,b, and H. Jüppner (Endocrine Unit and Pediatric Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA) for comments.

Author information

Authors and Affiliations

  1. Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, 50 Blossom St., Boston, 02114, Massachusetts, USA

    Michael Mannstadt & Deborah M. Mitchell

  2. Division of Endocrinology, College of Physicians and Surgeons, Columbia University Medical Center, New York, New York, USA

    John P. Bilezikian

  3. Radcliffe Department of Medicine, Academic Endocrine Unit, University of Oxford, Oxford, UK

    Rajesh V. Thakker & Fadil M. Hannan

  4. Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, Faculty of Health & Life Sciences, University of Liverpool, Liverpool, UK

    Fadil M. Hannan

  5. Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA

    Bart L. Clarke

  6. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

    Lars Rejnmark

  7. Section of Endocrinology, University of Chicago Medicine, Chicago, Illinois, USA

    Tamara J. Vokes

  8. Pediatric Growth and Nutrition Branch, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA

    Karen K. Winer

  9. San Francisco Department of Veterans Affairs Medical Center, Endocrine Research Unit, University of California, San Francisco, California, USA

    Dolores M. Shoback

Authors
  1. Michael Mannstadt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John P. Bilezikian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rajesh V. Thakker
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fadil M. Hannan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bart L. Clarke
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lars Rejnmark
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Deborah M. Mitchell
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tamara J. Vokes
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Karen K. Winer
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Dolores M. Shoback
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Introduction (M.M.); Epidemiology (B.L.C.); Mechanisms/pathophysiology (R.V.T. and F.M.H.); Diagnosis, screening and prevention (D.M.M., M.M. and L.R.); Management (K.K.W. and D.M.S.); Quality of life (T.J.V.); Outlook (J.P.B.); Overview of Primer (M.M.).

Corresponding author

Correspondence to Michael Mannstadt.

Ethics declarations

Competing interests

M.M. has received consulting fees and a research grant from Shire Pharmaceuticals. J.P.B. is a consultant for Shire Pharmaceuticals. R.V.T. has received grant funding from NPS/Shire Pharmaceuticals, GlaxoSmithKline, Novartis Pharma AG and the Marshall Smith Syndrome Foundation, and he is a medical adviser for the patient charity HypoPara UK. F.M.H. has received grant funding from NPS/Shire Pharmaceuticals and GlaxoSmithKline. B.L.C. has received research grants from Shire Pharmaceuticals and has received honoraria from Amgen. L.R. has received honoraria and speaker fees from Amgen, Eli Lilly, Novo Nordic, Takeda Pharmaceuticals, NPS Pharmaceuticals, Shire, Bristol-Myers Squibb, Abbott, and Boehringer Ingelheim Denmark. T.J.V. is a consultant and investigator for Shire Pharmaceuticals. D.M.S. is a consultant for Shire Pharmaceuticals and Ascendis Pharmaceuticals. D.M.M. and K.K.W. declare no competing interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mannstadt, M., Bilezikian, J., Thakker, R. et al. Hypoparathyroidism. Nat Rev Dis Primers 3, 17055 (2017). https://doi.org/10.1038/nrdp.2017.55

Download citation

  • Published:

  • DOI: https://doi.org/10.1038/nrdp.2017.55

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing