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Diagnosis and management of hypocalcemia

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Abstract

The aim of this clinical narrative review is to summarize and critically appraise the literature on the differential diagnosis of hypocalcemia and to provide its correct management. Calcium is essential for muscle contraction and neurotransmitter release, but clinical manifestations of hypocalcaemia (serum calcium level <8 mg/dl; 2.12 mmol/L) may involve almost any organ and system and may range from asymptomatic to life-threating conditions. Disorders causing hypocalcemia can be divided into parathyroid hormone (PTH) and non-PTH mediated. The most frequent cause of hypocalcemia is postsurgical hypoparathyroidism, while a more comprehensive search for other causes is needed for appropriate treatment in the non PTH-mediated forms. Intravenous calcium infusion is essential to raise calcium levels and resolve or minimize symptoms in the setting of acute hypocalcemia. Oral calcium and/or vitamin D supplementation is the most frequently used as treatment of chronic hypocalcemia. In hypoparathyroidism, providing the missing hormone with the use of the recombinant human (rh) PTH(1–84) has been recently approved both by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This new therapy has the advantage of being effective for correcting serum calcium levels and significantly reducing the daily requirements of calcium and active vitamin D supplements. However, due to the high cost, a strict selection of candidates to this therapy is necessary. More challenging is the long-term hypocalcemia treatment, due to its associated complications. The development of long-acting recombinant human PTH will probably modify the management of chronic hypoparathyroidism in the future.

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References

  1. R.B. Payne, A.J. Little, R.B. Williams, J.R. Milner, Interpretation of serum calcium in patients with abnormal serum proteins. Br. Med. J. 4(5893), 643–646 (1973). https://doi.org/10.1136/bmj.4.5893.643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. F.R. Bringhurst, D.M., Kronenberg, Bone and mineral metabolism in health and disease. In: Larry, J. (ed.) Harrison's principles of internal medicine, McGraw-Hill, New York, NY (Harrison's Principles of Internal Medicine, 20 Eds)

  3. F.M. Hannan, R.V. Thakker, Investigating hypocalcaemia. Bmj 346, f2213 (2013). https://doi.org/10.1136/bmj.f2213

    Article  PubMed  Google Scholar 

  4. S. Minisola, J. Pepe, S. Piemonte, C. Cipriani, The diagnosis and management of hypercalcaemia. Bmj 350, h2723 (2015). https://doi.org/10.1136/bmj.h2723

    Article  CAS  PubMed  Google Scholar 

  5. F. Ferrone, J. Pepe, V.C. Danese, V. Fassino, V. Cecchetti, F. De Lucia, F. Biamonte, L. Colangelo, G. Ferrazza, E. Panzini, A. Scillitani, L. Nieddu, F. Blocki, S.D. Rao, S. Minisola, C. Cipriani, The relative influence of serum ionized calcium and 25-hydroxyvitamin D in regulating PTH secretion in healthy subjects. Bone 125, 200–206 (2019). https://doi.org/10.1016/j.bone.2019.05.029

    Article  CAS  PubMed  Google Scholar 

  6. B.L. Clarke, E.M. Brown, M.T. Collins, H. Juppner, P. Lakatos, M.A. Levine, M.M. Mannstadt, J.P. Bilezikian, A.F. Romanischen, R.V. Thakker, Epidemiology and diagnosis of hypoparathyroidism. J. Clin. Endocrinol. Metab. 101(6), 2284–2299 (2016). https://doi.org/10.1210/jc.2015-3908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. C. Cipriani, J. Pepe, F. Biamonte, R. Manai, P. Biondi, L. Nieddu, L. Cianferotti, M.L. Brandi, S. Minisola, The epidemiology of hypoparathyroidism in Italy: an 8-year register-based study. Calcif. tissue Int. 100(3), 278–285 (2017). https://doi.org/10.1007/s00223-016-0222-7

    Article  CAS  PubMed  Google Scholar 

  8. E. Bove-Fenderson, M. Mannstadt, Hypocalcemic disorders. Best practice & research. Clin. Endocrinol. Metab. 32(5), 639–656 (2018). https://doi.org/10.1016/j.beem.2018.05.006

    Article  CAS  Google Scholar 

  9. J.J. Diez, E. Anda, J. Sastre, B. Perez Corral, C. Alvarez-Escola, L. Manjon, M. Paja, M. Sambo, P. Santiago Fernandez, C. Blanco Carrera, J.C. Galofre, E. Navarro, C. Zafon, E. Sanz, A. Oleaga, O. Bandres, S. Donnay, A. Megia, M. Picallo, C. Sanchez Ragnarsson, G. Baena-Nieto, J.C.F. Garcia, B. Lecumberri, M.S. de la Vega, A.R. Romero-Lluch, P. Iglesias, Prevalence and risk factors for hypoparathyroidism following total thyroidectomy in Spain: a multicentric and nation-wide retrospective analysis. Endocrine 66(2), 405–415 (2019). https://doi.org/10.1007/s12020-019-02014-8

    Article  CAS  PubMed  Google Scholar 

  10. G.L. Canu, F. Medas, A. Longheu, F. Boi, G. Docimo, E. Erdas, P.G. Calo, Correlation between iPTH Levels on the First postoperative day after total thyroidectomy and permanent hypoparathyroidism: our experience. Open Med. 14, 437–442 (2019). https://doi.org/10.1515/med-2019-0047

    Article  CAS  Google Scholar 

  11. L. Underbjerg, T. Sikjaer, L. Mosekilde, L. Rejnmark, Cardiovascular and renal complications to postsurgical hypoparathyroidism: a Danish nationwide controlled historic follow-up study. J. Bone Miner. Res. 28(11), 2277–2285 (2013). https://doi.org/10.1002/jbmr.1979

    Article  PubMed  Google Scholar 

  12. A. Kelly, M.A. Levine, Hypocalcemia in the critically ill patient. J. Inten. Care Med. 28(3), 166–177 (2013). https://doi.org/10.1177/0885066611411543

    Article  Google Scholar 

  13. M.N. Rao, D.M. Shoback, Hypocalcemia. In: K.R. Feingold, B. Anawalt, A. Boyce, G. Chrousos, K. Dungan, A. Grossman, J.M. Hershman, G. Kaltsas, C. Koch, P. Kopp, M. Korbonits, R. McLachlan, J.E. Morley, M. New, L. Perreault, J. Purnell, R. Rebar, F. Singer, D.L. Trence, A. Vinik, D.P. Wilson (eds.) Endotext, South Dartmouth (MA) (2000)

  14. D.M. Shoback, J.P. Bilezikian, A.G. Costa, D. Dempster, H. Dralle, A.A. Khan, M. Peacock, M. Raffaelli, B.C. Silva, R.V. Thakker, T. Vokes, R. Bouillon, Presentation of hypoparathyroidism: etiologies and clinical features. J. Clin. Endocrinol. Metab. 101(6), 2300–2312 (2016). https://doi.org/10.1210/jc.2015-3909

    Article  CAS  PubMed  Google Scholar 

  15. G. Marcucci, L. Cianferotti, M.L. Brandi, Clinical presentation and management of hypoparathyroidism. Best. Pract. Res. Clin. Endocrinol. Metab. 32(6), 927–939 (2018). https://doi.org/10.1016/j.beem.2018.09.007

    Article  CAS  PubMed  Google Scholar 

  16. I.A. Hujoel, The association between serum calcium levels and Chvostek sign: a population-based study. Neurol. Clin. Pract. 6(4), 321–328 (2016). https://doi.org/10.1212/CPJ.0000000000000270

    Article  PubMed  PubMed Central  Google Scholar 

  17. C.P.M. Heemskerk, M. Pereboom, K. van Stralen, F.A. Berger, P. van den Bemt, A.F.M. Kuijper, R.T.M. van der Hoeven, A.K. Mantel-Teeuwisse, M.L. Becker, Risk factors for QTc interval prolongation. Eur. J. Clin. Pharm. 74(2), 183–191 (2018). https://doi.org/10.1007/s00228-017-2381-5

    Article  CAS  Google Scholar 

  18. M. Duval, K. Bach, D. Masson, C. Guimard, P. Le Conte, D. Trewick, Is severe hypocalcemia immediately life-threatening? Endocr. Connect (2018). https://doi.org/10.1530/EC-18-0267

  19. J.C. Jentzer, S. Vallabhajosyula, A.K. Khanna, L.S. Chawla, L.W. Busse, K.B. Kashani, Management of refractory vasodilatory shock. Chest 154(2), 416–426 (2018). https://doi.org/10.1016/j.chest.2017.12.021

    Article  PubMed  Google Scholar 

  20. S. Minisola, C. Cipriani, L. Colangelo, F. Biamonte, J. Pepe, Serum calcium values and refractory vasodilatory shock. Chest 155(1), 242 (2019). https://doi.org/10.1016/j.chest.2018.08.1066

    Article  PubMed  Google Scholar 

  21. P.V. Jariwala, B. Sudarshan, M.S. Aditya, L. Praveer, K.S. Chandra, Hypoparathyroidism–a cause of reversible dilated cardiomyopathy. J. Assoc. Physicians India 58, 500–502 (2010)

    PubMed  Google Scholar 

  22. D.M. Mitchell, S. Regan, M.R. Cooley, K.B. Lauter, M.C. Vrla, C.B. Becker, S.A. Burnett-Bowie, M. Mannstadt, Long-term follow-up of patients with hypoparathyroidism. J. Clin. Endocrinol. Metab. 97(12), 4507–4514 (2012). https://doi.org/10.1210/jc.2012-1808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. R. Nardone, F. Brigo, E. Trinka, Acute symptomatic seizures caused by electrolyte disturbances. J. Clin. Neurol. 12(1), 21–33 (2016). https://doi.org/10.3988/jcn.2016.12.1.21

    Article  PubMed  Google Scholar 

  24. P. Han, B.J. Trinidad, J. Shi, Hypocalcemia-induced seizure: demystifying the calcium paradox. ASN Neuro. 7(2) (2015). https://doi.org/10.1177/1759091415578050

  25. E. Iacovelli, F. Gilio, M.L. Mascia, A. Scillitani, E. Romagnoli, F. Pichiorri, S. Fucile, S. Minisola, M. Inghilleri, Acute and chronic effects of hypercalcaemia on cortical excitability as studied by 5 Hz repetitive transcranial magnetic stimulation. J. Physiol. 589, 1619–1626 (2011). https://doi.org/10.1113/jphysiol.2010.201111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. C.G. Phillips, M.T. Harnett, W. Chen, S.M. Smith, Calcium-sensing receptor activation depresses synaptic transmission. J. Neurosci. 28(46), 12062–12070 (2008). https://doi.org/10.1523/JNEUROSCI.4134-08.2008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. A.J. Aul, P.R. Fischer, J.S. O'Grady, K.C. Mara, J.A. Maxson, A.M. Meek, T.M. Petterson, T.D. Thacher, Population-based incidence of potentially life-threatening complications of hypocalcemia and the role of vitamin D deficiency. J. Pediatr. 211(98–104), e104 (2019). https://doi.org/10.1016/j.jpeds.2019.02.018

    Article  CAS  Google Scholar 

  28. G.T. Williams, M. Brown, Laryngospasm in hypoparathyroidism. J. Laryngol. Otol. 88(4), 369–373 (1974). https://doi.org/10.1017/s0022215100078804

    Article  CAS  PubMed  Google Scholar 

  29. C.T. Chou, B. Siegel, D. Mehta, Stridor and apnea as the initial presentation of primary hypoparathyroidism. Int. J. Pediatr. Otorhinolaryngol. 80, 30–32 (2016). https://doi.org/10.1016/j.ijporl.2015.11.023

    Article  PubMed  Google Scholar 

  30. N.E. Cusano, J.P. Bilezikian, Signs and symptoms of hypoparathyroidism. Endocrinol. Metab. Clin. North Am. 47(4), 759–770 (2018). https://doi.org/10.1016/j.ecl.2018.07.001

    Article  PubMed  Google Scholar 

  31. R. Fjaer, E. Brodtkorb, A.M. Oye, Y. Sheng, M.D. Vigeland, K.A. Kvistad, P.H. Backe, K.K. Selmer, Generalized epilepsy in a family with basal ganglia calcifications and mutations in SLC20A2 and CHRNB2. Eur. J. Med. Genet. 58(11), 624–628 (2015). https://doi.org/10.1016/j.ejmg.2015.10.005

    Article  PubMed  Google Scholar 

  32. S.K. Bhadada, A. Bhansali, V. Upreti, S. Subbiah, N. Khandelwal, Spectrum of neurological manifestations of idiopathic hypoparathyroidism and pseudohypoparathyroidism. Neurol. India 59(4), 586–589 (2011). https://doi.org/10.4103/0028-3886.84342

    Article  PubMed  Google Scholar 

  33. L.S. Basser, F.C. Neale, A.W. Ireland, S. Posen, Epilepsy and electroencephalographic abnormalities in chronic surgical hypoparathyroidism. Ann. Intern Med 71(3), 507–515 (1969). https://doi.org/10.7326/0003-4819-71-3-507

    Article  CAS  PubMed  Google Scholar 

  34. A. Maiti, S. Chatterjee, Neuropsychiatric manifestations and their outcomes in chronic hypocalcaemia. J. Indian Med Assoc. 111(3), 174–177 (2013)

    PubMed  Google Scholar 

  35. S.I. Rosenfeld, J.C. Bobrow, et al. Lens and cataracts. In: T.J. Leisenberg, G.L. Skuta, L.B. Couter (eds), Basic and Clinical Science Course. American Academy of Opthamology, Section 1, 45–69 (2004)

  36. L. Underbjerg, T. Sikjaer, L. Rejnmark, Long-term complications in patients with hypoparathyroidism evaluated by biochemical findings: a case-control study. J. Bone Miner. Res. 33(5), 822–831 (2018). https://doi.org/10.1002/jbmr.3368

    Article  CAS  PubMed  Google Scholar 

  37. G. Tabacco, A.M. Naciu, D. Maggi, A. Santonati, C. Pedone, R. Cesareo, D. Bosco, G. Gaspa, N. Napoli, P. Pozzilli, S. Manfrini, A. Palermo, Cardiovascular autonomic neuropathy as a new complication of postsurgical chronic hypoparathyroidism. J. Bone Min. Res 34(3), 475–481 (2019). https://doi.org/10.1002/jbmr.3623

    Article  CAS  Google Scholar 

  38. S. Velayuthan, N. Gungor, R. McVie, Hypocalcemic cardiomyopathy as initial presentation of primary hypoparathyroidism. Pediatrics Int. 56(4), e23–25 (2014). https://doi.org/10.1111/ped.12378

    Article  Google Scholar 

  39. A. Avsar, A. Dogan, T. Tavli, A rare cause of reversible dilated cardiomyopathy: hypocalcemia. Echocardiography 21(7), 609–612 (2004). https://doi.org/10.1111/j.0742-2822.2004.03149.x

    Article  PubMed  Google Scholar 

  40. D.B. Newman, S.S. Fidahussein, D.T. Kashiwagi, K.A. Kennel, K.B. Kashani, Z. Wang, O. Altayar, M.H. Murad, Reversible cardiac dysfunction associated with hypocalcemia: a systematic review and meta-analysis of individual patient data. Heart Fail. Rev. 19(2), 199–205 (2014). https://doi.org/10.1007/s10741-013-9371-1

    Article  CAS  PubMed  Google Scholar 

  41. G. Tabacco, Y.D. Tay, N.E. Cusano, J. Williams, B. Omeragic, R. Majeed, M.G. Almonte, M.R. Rubin, J.P. Bilezikian, Quality of life in hypoparathyroidism improves with rhPTH(1-84) throughout 8 years of therapy. J. Clin. Endocrinol. Metab. 104(7), 2748–2756 (2019). https://doi.org/10.1210/jc.2018-02430

    Article  PubMed  PubMed Central  Google Scholar 

  42. KDIGO, KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease–mineral and bone disorder (CKD-MBD). Kidney Int. 7(Suppl.), 1–59 (2017).

    Google Scholar 

  43. P.C. Pham, P.A. Pham, S.V. Pham, P.T. Pham, P.M. Pham, P.T. Pham, Hypomagnesemia: a clinical perspective. Int. J. Nephrol. Renovascular Dis. 7, 219–230 (2014). https://doi.org/10.2147/IJNRD.S42054

    Article  CAS  Google Scholar 

  44. E. Tsourdi, B. Langdahl, M. Cohen-Solal, B. Aubry-Rozier, E.F. Eriksen, N. Guanabens, B. Obermayer-Pietsch, S.H. Ralston, R. Eastell, M.C. Zillikens, Discontinuation of denosumab therapy for osteoporosis: a systematic review and position statement by ECTS. Bone 105, 11–17 (2017). https://doi.org/10.1016/j.bone.2017.08.003

    Article  PubMed  Google Scholar 

  45. J. Everts-Graber, S. Reichenbach, H.R. Ziswiler, U. Studer, T. Lehmann, A single infusion of zoledronate in postmenopausal women following denosumab discontinuation results in partial conservation of bone mass gains. J. Bone Min. Res. (2020). https://doi.org/10.1002/jbmr.3962

  46. V. Kreutle, C. Blum, C. Meier, M. Past, B. Muller, P. Schutz, K. Borm, Bisphosphonate induced hypocalcaemia - report of six cases and review of the literature. Swiss Med. Wkly. 144, w13979 (2014). https://doi.org/10.4414/smw.2014.13979

    Article  CAS  PubMed  Google Scholar 

  47. C. Thongprayoon, P. Acharya, N.R. Aeddula, A. Torres-Ortiz, T. Bathini, K. Sharma, P. Ungprasert, K. Watthanasuntorn, M.L.G. Suarez, S.A. Salim, W. Kaewput, J. Chenbhanich, M.A. Mao, W. Cheungpasitporn, Effects of denosumab on bone metabolism and bone mineral density in kidney transplant patients: a systematic review and meta-analysis. Arch. Osteoporos. 14(1), 35 (2019). https://doi.org/10.1007/s11657-019-0587-0

    Article  PubMed  Google Scholar 

  48. D.M. McDonald-McGinn, K.E. Sullivan, B. Marino, N. Philip, A. Swillen, J.A. Vorstman, E.H. Zackai, B.S. Emanuel, J.R. Vermeesch, B.E. Morrow, P.J. Scambler, A.S. Bassett, 22q11.2 deletion syndrome. Nature reviews. Dis. Prim. 1, 15071 (2015). https://doi.org/10.1038/nrdp.2015.71

    Article  Google Scholar 

  49. A. Linglart, M.A. Levine, H. Juppner, Pseudohypoparathyroidism. Endocrinol. Metab. Clin. North Am. 47(4), 865–888 (2018). https://doi.org/10.1016/j.ecl.2018.07.011

    Article  PubMed  PubMed Central  Google Scholar 

  50. P.J. Malloy, D. Feldman, Genetic disorders and defects in vitamin d action. Endocrinol. Metab. Clin. North Am. 39(2), 333–346 (2010). https://doi.org/10.1016/j.ecl.2010.02.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. P.J. Malloy, D. Feldman, Genetic disorders and defects in vitamin D action. Rheum. Dis. Clin. North Am. 38(1), 93–106 (2012). https://doi.org/10.1016/j.rdc.2012.03.009

    Article  PubMed  Google Scholar 

  52. J. Fong, A. Khan, Hypocalcemia: updates in diagnosis and management for primary care. Can. Fam. Phys. Med. de. famille canadien 58(2), 158–162 (2012)

    Google Scholar 

  53. Hammond, D.A., Stojakovic, J., Kathe, N., Tran, J., Clem, O.A., Erbach, K., King, J.: Effectiveness and Safety of Magnesium Replacement in Critically Ill Patients Admitted to the Medical Intensive Care Unit in an Academic Medical Center: A Retrospective, Cohort Study. J. Inten. Care Med. 885066617720631 (2017). https://doi.org/10.1177/0885066617720631

  54. S. Minisola, J. Pepe, P. Donato, E. Vigna, M. Occhiuto, F. Ferrone, F. Biamonte, V. Cecchetti, V.C. Danese, C. Sonato, B.I. P, L. Colangelo, C. Cipriani, Replenishment of vitamin D status: theoretical and practical considerations. Hormones 18(1), 3–5 (2019). https://doi.org/10.1007/s42000-018-0040-6

    Article  PubMed  Google Scholar 

  55. W.T. Clusin, Calcium and cardiac arrhythmias: DADs, EADs, and alternans. Crit. Rev. Clin. Lab. Sci. 40(3), 337–375 (2003). https://doi.org/10.1080/713609356

    Article  CAS  PubMed  Google Scholar 

  56. A. Sanabria, A. Rojas, J. Arevalo, Meta-analysis of routine calcium/vitamin D3 supplementation versus serum calcium level-based strategy to prevent postoperative hypocalcaemia after thyroidectomy. Br. J. Surg. 106(9), 1126–1137 (2019). https://doi.org/10.1002/bjs.11216

    Article  CAS  PubMed  Google Scholar 

  57. O. Edafe, C.E. Mech, S.P. Balasubramanian, Calcium, vitamin D or recombinant parathyroid hormone for managing post-thyroidectomy hypoparathyroidism. Cochrane Database Syst. Rev. 5, CD012845 (2019). https://doi.org/10.1002/14651858.CD012845.pub2

    Article  PubMed  Google Scholar 

  58. J. Bollerslev, L. Rejnmark, C. Marcocci, D.M. Shoback, A. Sitges-Serra, W. van Biesen, O.M. Dekkers, European Society of Endocrinology Clinical Guideline: Treatment of chronic hypoparathyroidism in adults. Eur. J. Endocrinol. 173(2), G1–20 (2015). https://doi.org/10.1530/EJE-15-0628

    Article  CAS  PubMed  Google Scholar 

  59. M.L. Brandi, J.P. Bilezikian, D. Shoback, R. Bouillon, B.L. Clarke, R.V. Thakker, A.A. Khan, J.T. Potts Jr, Management of hypoparathyroidism: summary statement and guidelines. J. Clin. Endocrinol. Metab. 101(6), 2273–2283 (2016). https://doi.org/10.1210/jc.2015-3907

    Article  CAS  PubMed  Google Scholar 

  60. L.A. Orloff, S.M. Wiseman, V.J. Bernet, T.J. Fahey III, A.R. Shaha, M.L. Shindo, S.K. Snyder, B.C. Stack Jr, J.B. Sunwoo, M.B: Wang, American thyroid association staement on postoperative hypoparathyroidism: diagnosis, prevention, and management in adults. Thyroid. 28(7), 830–841 (2018). https://doi.org/10.1089/thy.2017.0309

    Article  PubMed  Google Scholar 

  61. E. Coudenys, T. Van Meerhaeghe, D. Unuane, R. Buyl, B. Bravenboer, Long-term treatment with calcitriol in postsurgical hypoparathyroidism leads to renal function decline. Horm. Metab. Res. 51(6), 362–366 (2019). https://doi.org/10.1055/a-0902-8476

    Article  CAS  PubMed  Google Scholar 

  62. M. Mannstadt, B.L. Clarke, T. Vokes, M.L. Brandi, L. Ranganath, W.D. Fraser, P. Lakatos, L. Bajnok, R. Garceau, L. Mosekilde, H. Lagast, D. Shoback, J.P. Bilezikian, 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(4), 275–283 (2013). https://doi.org/10.1016/S2213-8587(13)70106-2

    Article  CAS  PubMed  Google Scholar 

  63. K.K. Winer, C.W. Ko, J.C. Reynolds, K. Dowdy, M. Keil, D. Peterson, L.H. Gerber, C. McGarvey, G.B. Cutler Jr, Long-term treatment of hypoparathyroidism: a randomized controlled study comparing parathyroid hormone-(1-34) versus calcitriol and calcium. J. Clin. Endocrinol. Metab. 88(9), 4214–4220 (2003). https://doi.org/10.1210/jc.2002-021736

    Article  CAS  PubMed  Google Scholar 

  64. K.K. Winer, N. Sinaii, J. Reynolds, D. Peterson, K. Dowdy, G.B. Cutler Jr, 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(6), 2680–2688 (2010). https://doi.org/10.1210/jc.2009-2464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. A. Palermo, A. Santonati, G. Tabacco, D. Bosco, A. Spada, C. Pedone, B. Raggiunti, T. Doris, D. Maggi, F. Grimaldi, S. Manfrini, F. Vescini, PTH(1-34) for surgical hypoparathyroidism: a 2-year prospective, open-label investigation of efficacy and quality of life. J. Clin. Endocrinol. Metab. 103(1), 271–280 (2018). https://doi.org/10.1210/jc.2017-01555

    Article  PubMed  Google Scholar 

  66. S. Minisola, C. Cipriani, G.D. Grotta, L. Colangelo, M. Occhiuto, P. Biondi, C. Sonato, E. Vigna, M. Cilli, J. Pepe, Update on the safety and efficacy of teriparatide in the treatment of osteoporosis. Therapeutic Adv. Musculoskelet. Dis. 11, 1759720X19877994 (2019). https://doi.org/10.1177/1759720X19877994

    Article  Google Scholar 

  67. Y. Ramakrishnan, H.C. Cocks, Impact of recombinant PTH on management of hypoparathyroidism: a systematic review. Eur. Arch. Oto-Rhino-laryngol 273(4), 827–835 (2016). https://doi.org/10.1007/s00405-014-3484-6

    Article  CAS  Google Scholar 

  68. Tuli, G., Buganza, R., Tessaris, D., Einaudi, S., Matarazzo, P., de Sanctis, L.: Teriparatide (rhPTH 1-34) treatment in the pediatric age: long-term efficacy and safety data in a cohort with genetic hypoparathyroidism. Endocrine (2019). https://doi.org/10.1007/s12020-019-02128-z

  69. R.I. Gafni, L.C. Guthrie, M.H. Kelly, B.A. Brillante, C.M. Christie, J.C. Reynolds, N.A. Yovetich, R. James, M.T. Collins, 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(11), 2112–2118 (2015). https://doi.org/10.1002/jbmr.2555

    Article  CAS  PubMed  Google Scholar 

  70. Y.D. Tay, G. Tabacco, N.E. Cusano, J. Williams, B. Omeragic, R. Majeed, M. Gomez Almonte, J.P. Bilezikian, M.R. Rubin, Therapy of hypoparathyroidism with rhPTH(1-84): a prospective, 8-year investigation of efficacy and safety. J. Clin. Endocrinol. Metab. 104(11), 5601–5610 (2019). https://doi.org/10.1210/jc.2019-00893

    Article  PubMed  PubMed Central  Google Scholar 

  71. R.I. Gafni, C.B. Langman, L.C. Guthrie, B.A. Brillante, R. James, N.A. Yovetich, A.M. Boyce, M.T. Collins, Hypocitraturia is an untoward side effect of synthetic human parathyroid hormone (hpth) 1-34 therapy in hypoparathyroidism that may increase renal morbidity. J. Bone Min. Res 33(10), 1741–1747 (2018). https://doi.org/10.1002/jbmr.3480

    Article  CAS  Google Scholar 

  72. K.K. Winer, B. Zhang, J.A. Shrader, D. Peterson, M. Smith, P.S. Albert, G.B. Cutler Jr, 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(2), 391–399 (2012). https://doi.org/10.1210/jc.2011-1908

    Article  CAS  PubMed  Google Scholar 

  73. L. Holten-Andersen, S. Pihl, C.E. Rasmussen, J. Zettler, G. Maitro, J. Baron, S. Heinig, E. Hoffmann, T. Wegge, M. Krusch, F. Faltinger, S. Killian, K. Sprogoe, D.B. Karpf, V.M. Breinholt, F. Cleemann, Design and preclinical development of transcon pth, an investigational sustained-release pth replacement therapy for hypoparathyroidism. J. Bone Miner. Res.: Off. J. Am. Soc. Bone Miner. Res. 34(11), 2075–2086 (2019). https://doi.org/10.1002/jbmr.3824

    Article  CAS  Google Scholar 

  74. G. Marcucci, M.L. Brandi, A new era for chronic management of hypoparathyroidism: parathyroid hormone peptides. Front. Horm. Res. 51, 165–171 (2019). https://doi.org/10.1159/000491047

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University, Rome, Italy

    Jessica Pepe, Luciano Colangelo, Federica Biamonte, Chiara Sonato, Vittoria Carmela Danese, Veronica Cecchetti, Marco Occhiuto, Valentina Piazzolla, Viviana De Martino, Federica Ferrone, Salvatore Minisola & Cristiana Cipriani

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  1. Jessica Pepe
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  2. Luciano Colangelo
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Correspondence to Luciano Colangelo.

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S.M. served as speaker for Abiogen, Amgen, Bruno Farmaceutici, Diasorin, Eli Lilly, Shire, Sandoz, Takeda. He also served in advisory board of Abiogen, Kyowa Kirin, Pfizer, UCB. All other authors declare no competing interests.

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Pepe, J., Colangelo, L., Biamonte, F. et al. Diagnosis and management of hypocalcemia. Endocrine 69, 485–495 (2020). https://doi.org/10.1007/s12020-020-02324-2

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