Skip to main content
SpringerLink
Log in

Clinical, Laboratory, and Radiological Diagnosis of Hyperparathyroidism

  • Chapter
  • First Online:
Diagnosis and Management of Endocrine Disorders in Interventional Radiology

  • 418 Accesses

Abstract

Primary hyperparathyroidism is the most common cause of hypercalcemia in the outpatient setting. It is characterized by high serum calcium and high or inappropriately normal parathyroid hormone. Most cases are caused by a single parathyroid adenoma, but multiple parathyroid adenomas, parathyroid hyperplasia, and parathyroid carcinoma are also important etiologies. Although most patients present asymptomatically, severe or long-standing hyperparathyroidism can cause symptomatic hypercalcemia, osteoporosis, and nephrolithiasis. A biochemical diagnosis should be confirmed, and alternative diagnoses should be excluded. Ultrasound, SPECT-CT, 4D CT neck, and MRI are useful imaging modalities for identifying an overactive parathyroid gland. Once laboratory and imaging evaluation has confirmed the diagnosis and adverse impact from it, removing the offending parathyroid gland is the most effective treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ziessman H. Endocrine system. Nuclear medicine: the requisites. 4th ed. Philadelphia: Elsevier Mosby; 2015. p. 66–97.

    Google Scholar 

  2. Mettler F, Guiberteau M. Essentials of nuclear medicine and molecular imaging. Elsevier; 2019. p. 85–115.

    Book  Google Scholar 

  3. Kumar V, Abbas AK, Aster JC. Robbins and Cotran pathologic basis of disease. 9th ed. Philadelphia: Elsevier/Saunders; 2015. p 1126–9.

    Google Scholar 

  4. Brewer K, Costa-Guda J, Arnold A. Molecular genetic insights into sporadic primary hyperparathyroidism. Endocr Relat Cancer. 2019;26(2):R53–72.

    Article  CAS  PubMed  Google Scholar 

  5. Arnold A, Staunton CE, Kim HG, Gaz RD, Kronenberg HM. Monoclonality and abnormal parathyroid hormone genes in parathyroid adenomas. N Engl J Med. 1988;318(11):658–62.

    Article  CAS  PubMed  Google Scholar 

  6. Bilezikian JP, Brandi ML, Eastell R, Silverberg SJ, Udelsman R, Marcocci C, et al. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab. 2014;99(10):3561–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Eastell R, Brandi ML, Costa AG, D’Amour P, Shoback DM, Thakker RV. Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab. 2014;99(10):3570–9.

    Article  CAS  PubMed  Google Scholar 

  8. Shepard MM, Smith JW 3rd. Hypercalcemia. Am J Med Sci. 2007;334(5):381–5.

    Article  PubMed  Google Scholar 

  9. Yu N, Donnan PT, Murphy MJ, Leese GP. Epidemiology of primary hyperparathyroidism in Tayside, Scotland, UK. Clin Endocrinol. 2009;71(4):485–93.

    Article  Google Scholar 

  10. Yeh MW, Ituarte PH, Zhou HC, Nishimoto S, Liu IL, Harari A, et al. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J Clin Endocrinol Metab. 2013;98(3):1122–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Silverberg SJ, Shane E, Jacobs TP, Siris E, Bilezikian JP. A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery. N Engl J Med. 1999;341(17):1249–55.

    Article  CAS  PubMed  Google Scholar 

  12. Melmed S, Auchus RJ, Goldfine AB, Koenig RJ, Rosen CJ. Williams textbook of endocrinology. 14th ed. Philadelphia: Elsevier, Inc; 2019. p 1331.

    Google Scholar 

  13. Bandeira FA, Oliveira RI, Griz LH, Caldas G, Bandeira C. Differences in accuracy of 99mTc-sestamibi scanning between severe and mild forms of primary hyperparathyroidism. J Nucl Med Technol. 2008;36(1):30–5.

    Article  CAS  PubMed  Google Scholar 

  14. Abraham D. Ultrasonography of the parathyroid glands. In: Duick D, Levine R, Lupo M, editors. Thyroid and parathyroid ultrasound and ultrasound-guided FNA. Cham: Springer Nature; 2018. p. 263–8.

    Chapter  Google Scholar 

  15. Moore KL, Agur AMR, Dalley AF. Essential clinical anatomy. 4th ed. Baltimore: Lippincott Williams & Wilkins; 2011. p 620–1.

    Google Scholar 

  16. Lappas D, Noussios G, Anagnostis P, Adamidou F, Chatzigeorgiou A, Skandalakis P. Location, number and morphology of parathyroid glands: results from a large anatomical series. Anat Sci Int. 2012;87(3):160–4.

    Article  PubMed  Google Scholar 

  17. Schneider R, Waldmann J, Ramaswamy A, Fernandez ED, Bartsch DK, Schlosser K. Frequency of ectopic and supernumerary intrathymic parathyroid glands in patients with renal hyperparathyroidism: analysis of 461 patients undergoing initial parathyroidectomy with bilateral cervical thymectomy. World J Surg. 2011;35(6):1260–5.

    Article  PubMed  Google Scholar 

  18. Brown EM. Role of the calcium-sensing receptor in extracellular calcium homeostasis. Best Pract Res Clin Endocrinol Metab. 2013;27(3):333–43.

    Article  CAS  PubMed  Google Scholar 

  19. Wang Q, Palnitkar S, Parfitt AM. The basal rate of cell proliferation in normal human parathyroid tissue: implications for the pathogenesis of hyperparathyroidism. Clin Endocrinol. 1997;46(3):343–9.

    Article  CAS  Google Scholar 

  20. Eastell R, Arnold A, Brandi ML, Brown EM, D’Amour P, Hanley DA, et al. 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 

  21. Friedman PA, Gesek FA. Calcium transport in renal epithelial cells. Am J Phys. 1993;264(2 Pt 2):F181–98.

    CAS  Google Scholar 

  22. Jamal SA, Miller PD. Secondary and tertiary hyperparathyroidism. J Clin Densitom. 2013;16(1):64–8.

    Article  PubMed  Google Scholar 

  23. Albright F, Aub JC, Bauer W. Hyperparathyroidism: a common and polymorphic condition as illustrated by seventeen proved cases from one clinic. JAMA. 1934;102:1276–87.

    Article  Google Scholar 

  24. Bandeira F, Cusano NE, Silva BC, Cassibba S, Almeida CB, Machado VC, et al. Bone disease in primary hyperparathyroidism. Arq Bras Endocrinol Metabol. 2014;58(5):553–61.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Turken SA, Cafferty M, Silverberg SJ, De La Cruz L, Cimino C, Lange DJ, et al. Neuromuscular involvement in mild, asymptomatic primary hyperparathyroidism. Am J Med. 1989;87(5):553–7.

    Article  CAS  PubMed  Google Scholar 

  26. Adami S, Marcocci C, Gatti D. Epidemiology of primary hyperparathyroidism in Europe. J Bone Miner Res. 2002;17(Suppl 2):N18–23.

    PubMed  Google Scholar 

  27. Silverberg SJ. Vitamin D deficiency and primary hyperparathyroidism. J Bone Miner Res. 2007;22(Suppl 2):V100–4.

    Article  CAS  PubMed  Google Scholar 

  28. Bushinsky DA, Monk RD. Electrolyte quintet: calcium. Lancet. 1998;352(9124):306–11.

    Article  CAS  PubMed  Google Scholar 

  29. Sociedade Brasileira de Endocrinologia e M, Bandeira F, Griz L, Chaves N, Carvalho NC, Borges LM, et al. Diagnosis and management of primary hyperparathyroidism--a scientific statement from the Department of Bone Metabolism, the Brazilian Society for Endocrinology and Metabolism. Arq Bras Endocrinol Metabol. 2013;57(6):406–24.

    Article  Google Scholar 

  30. Wermers RA, Khosla S, Atkinson EJ, Hodgson SF, O’Fallon WM, Melton LJ 3rd. The rise and fall of primary hyperparathyroidism: a population-based study in Rochester, Minnesota, 1965-1992. Ann Intern Med. 1997;126(6):433–40.

    Article  CAS  PubMed  Google Scholar 

  31. Silverberg SJ, Clarke BL, Peacock M, Bandeira F, Boutroy S, Cusano NE, et al. Current issues in the presentation of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab. 2014;99(10):3580–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Rubin MR, Bilezikian JP, McMahon DJ, Jacobs T, Shane E, Siris E, et al. The natural history of primary hyperparathyroidism with or without parathyroid surgery after 15 years. J Clin Endocrinol Metab. 2008;93(9):3462–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Khosla S, Melton LJ 3rd, Wermers RA, Crowson CS, O’Fallon W, Riggs B. Primary hyperparathyroidism and the risk of fracture: a population-based study. J Bone Miner Res. 1999;14(10):1700–7.

    Article  CAS  PubMed  Google Scholar 

  34. Walgenbach S, Hommel G, Junginger T. Outcome after surgery for primary hyperparathyroidism: ten-year prospective follow-up study. World J Surg. 2000;24(5):564–9; discussion 9–70

    Article  CAS  PubMed  Google Scholar 

  35. Rao DS, Phillips ER, Divine GW, Talpos GB. Randomized controlled clinical trial of surgery versus no surgery in patients with mild asymptomatic primary hyperparathyroidism. J Clin Endocrinol Metab. 2004;89(11):5415–22.

    Article  CAS  PubMed  Google Scholar 

  36. Ambrogini E, Cetani F, Cianferotti L, Vignali E, Banti C, Viccica G, et al. Surgery or surveillance for mild asymptomatic primary hyperparathyroidism: a prospective, randomized clinical trial. J Clin Endocrinol Metab. 2007;92(8):3114–21.

    Article  CAS  PubMed  Google Scholar 

  37. Bollerslev J, Jansson S, Mollerup CL, Nordenstrom J, Lundgren E, Torring O, et al. Medical observation, compared with parathyroidectomy, for asymptomatic primary hyperparathyroidism: a prospective, randomized trial. J Clin Endocrinol Metab. 2007;92(5):1687–92.

    Article  CAS  PubMed  Google Scholar 

  38. Cheng SP, Lee JJ, Liu TP, Yang PS, Liu SC, Hsu YC, et al. Quality of life after surgery or surveillance for asymptomatic primary hyperparathyroidism: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2015;94(23):e931.

    Article  Google Scholar 

  39. Cusano NE, Silverberg SJ, Bilezikian JP. Normocalcemic primary hyperparathyroidism. J Clin Densitom. 2013;16(1):33–9.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Lowe H, McMahon DJ, Rubin MR, Bilezikian JP, Silverberg SJ. Normocalcemic primary hyperparathyroidism: further characterization of a new clinical phenotype. J Clin Endocrinol Metab. 2007;92(8):3001–5.

    Article  CAS  PubMed  Google Scholar 

  41. Bilezikian JP, Bandeira L, Khan A, Cusano NE. Hyperparathyroidism. Lancet. 2018;391(10116):168–78.

    Article  CAS  PubMed  Google Scholar 

  42. Tee MC, Holmes DT, Wiseman SM. Ionized vs serum calcium in the diagnosis and management of primary hyperparathyroidism: which is superior? Am J Surg. 2013;205(5):591–6; discussion 6

    Article  CAS  PubMed  Google Scholar 

  43. Ong GS, Walsh JP, Stuckey BG, Brown SJ, Rossi E, Ng JL, et al. The importance of measuring ionized calcium in characterizing calcium status and diagnosing primary hyperparathyroidism. J Clin Endocrinol Metab. 2012;97(9):3138–45.

    Article  CAS  PubMed  Google Scholar 

  44. 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 

  45. Berson SA, Yalow RS, Aurbach GD, Potts JT. Immunoassay of bovine and human parathyroid hormone. Proc Natl Acad Sci U S A. 1963;49(5):613–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Gao P, D’Amour P. Evolution of the parathyroid hormone (PTH) assay--importance of circulating PTH immunoheterogeneity and of its regulation. Clin Lab. 2005;51(1–2):21–9.

    CAS  PubMed  Google Scholar 

  47. Ekins R. More sensitive immunoassays. Nature. 1980;284(5751):14–5.

    Article  CAS  PubMed  Google Scholar 

  48. Aloia JF, Feuerman M, Yeh JK. Reference range for serum parathyroid hormone. Endocr Pract. 2006;12(2):137–44.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53–8.

    Article  CAS  PubMed  Google Scholar 

  50. Medicine Io. Dietary reference intakes for calcium and vitamin D. Washington, DC: The National Academies Press; 2011.

    Google Scholar 

  51. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. 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 

  52. Wallace LB, Parikh RT, Ross LV, Mazzaglia PJ, Foley C, Shin JJ, et al. The phenotype of primary hyperparathyroidism with normal parathyroid hormone levels: how low can parathyroid hormone go? Surgery. 2011;150(6):1102–12.

    Article  PubMed  Google Scholar 

  53. Al-Azem H, Khan A. Primary hyperparathyroidism. CMAJ. 2011;183(10):E685–9.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Priya G, Jyotsna VP, Gupta N, Chumber S, Bal CS, Karak AK, et al. Clinical and laboratory profile of primary hyperparathyroidism in India. Postgrad Med J. 2008;84(987):34–9.

    Article  CAS  PubMed  Google Scholar 

  55. Boudou P, Ibrahim F, Cormier C, Sarfati E, Souberbielle JC. A very high incidence of low 25 hydroxy-vitamin D serum concentration in a French population of patients with primary hyperparathyroidism. J Endocrinol Investig. 2006;29(6):511–5.

    Article  CAS  Google Scholar 

  56. Bollerslev J, Marcocci C, Sosa M, Nordenstrom J, Bouillon R, Mosekilde L. Current evidence for recommendation of surgery, medical treatment and vitamin D repletion in mild primary hyperparathyroidism. Eur J Endocrinol. 2011;165(6):851–64.

    Article  CAS  PubMed  Google Scholar 

  57. Amstrup AK, Rejnmark L, Vestergaard P, Sikjaer T, Rolighed L, Heickendorff L, et al. Vitamin D status, physical performance and body mass in patients surgically cured for primary hyperparathyroidism compared with healthy controls - a cross-sectional study. Clin Endocrinol. 2011;74(1):130–6.

    Article  CAS  Google Scholar 

  58. Kandil E, Tufaro AP, Carson KA, Lin F, Somervell H, Farrag T, et al. Correlation of plasma 25-hydroxyvitamin D levels with severity of primary hyperparathyroidism and likelihood of parathyroid adenoma localization on sestamibi scan. Arch Otolaryngol Head Neck Surg. 2008;134(10):1071–5.

    Article  PubMed  Google Scholar 

  59. Grey A, Lucas J, Horne A, Gamble G, Davidson JS, Reid IR. Vitamin D repletion in patients with primary hyperparathyroidism and coexistent vitamin D insufficiency. J Clin Endocrinol Metab. 2005;90(4):2122–6.

    Article  CAS  PubMed  Google Scholar 

  60. Walker MD, Cong E, Lee JA, Kepley A, Zhang C, McMahon DJ, et al. Vitamin D in primary hyperparathyroidism: effects on clinical, biochemical, and densitometric presentation. J Clin Endocrinol Metab. 2015;100(9):3443–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Fillee C, Keller T, Mourad M, Brinkmann T, Ketelslegers JM. Impact of vitamin D-related serum PTH reference values on the diagnosis of mild primary hyperparathyroidism, using bivariate calcium/PTH reference regions. Clin Endocrinol. 2012;76(6):785–9.

    Article  CAS  Google Scholar 

  62. Brasier AR, Nussbaum SR. Hungry bone syndrome: clinical and biochemical predictors of its occurrence after parathyroid surgery. Am J Med. 1988;84(4):654–60.

    Article  CAS  PubMed  Google Scholar 

  63. Corder CJ, Leslie SW. 24-hour urine collection. Treasure Island: StatPearls; 2020.

    Google Scholar 

  64. Corbetta S, Baccarelli A, Aroldi A, Vicentini L, Fogazzi GB, Eller-Vainicher C, et al. Risk factors associated to kidney stones in primary hyperparathyroidism. J Endocrinol Investig. 2005;28(2):122–8.

    Article  CAS  Google Scholar 

  65. Franca TC, Griz L, Pinho J, Diniz ET, Andrade LD, Lucena CS, et al. Bisphosphonates can reduce bone hunger after parathyroidectomy in patients with primary hyperparathyroidism and osteitis fibrosa cystica. Rev Bras Reumatol. 2011;51(2):131–7.

    Article  PubMed  Google Scholar 

  66. Costa AG, Bilezikian JP. Bone turnover markers in primary hyperparathyroidism. J Clin Densitom. 2013;16(1):22–7.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Moosgaard B, Christensen SE, Vestergaard P, Heickendorff L, Christiansen P, Mosekilde L. Vitamin D metabolites and skeletal consequences in primary hyperparathyroidism. Clin Endocrinol. 2008;68(5):707–15.

    Article  CAS  Google Scholar 

  68. Coe FL, Canterbury JM, Firpo JJ, Reiss E. Evidence for secondary hyperparathyroidism in idiopathic hypercalciuria. J Clin Invest. 1973;52(1):134–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Balsa JA, Botella-Carretero JI, Peromingo R, Zamarron I, Arrieta F, Munoz-Malo T, et al. Role of calcium malabsorption in the development of secondary hyperparathyroidism after biliopancreatic diversion. J Endocrinol Investig. 2008;31(10):845–50.

    Article  CAS  Google Scholar 

  70. Selby PL, Davies M, Adams JE, Mawer EB. Bone loss in celiac disease is related to secondary hyperparathyroidism. J Bone Miner Res. 1999;14(4):652–7.

    Article  CAS  PubMed  Google Scholar 

  71. Vasikaran SD. Bisphosphonates: an overview with special reference to alendronate. Ann Clin Biochem. 2001;38(Pt 6):608–23.

    Article  CAS  PubMed  Google Scholar 

  72. Makras P, Polyzos SA, Papatheodorou A, Kokkoris P, Chatzifotiadis D, Anastasilakis AD. Parathyroid hormone changes following denosumab treatment in postmenopausal osteoporosis. Clin Endocrinol. 2013;79(4):499–503.

    Article  CAS  Google Scholar 

  73. Mallette LE, Eichhorn E. Effects of lithium carbonate on human calcium metabolism. Arch Intern Med. 1986;146(4):770–6.

    Article  CAS  PubMed  Google Scholar 

  74. Grieff M, Bushinsky DA. Diuretics and disorders of calcium homeostasis. Semin Nephrol. 2011;31(6):535–41.

    Article  CAS  PubMed  Google Scholar 

  75. Griebeler ML, Kearns AE, Ryu E, Thapa P, Hathcock MA, Melton LJ 3rd, et al. Thiazide-associated hypercalcemia: incidence and association with primary hyperparathyroidism over two decades. J Clin Endocrinol Metab. 2016;101(3):1166–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Brown EM, Hebert SC. A cloned Ca(2+)-sensing receptor: a mediator of direct effects of extracellular Ca2+ on renal function? J Am Soc Nephrol. 1995;6(6):1530–40.

    Article  CAS  PubMed  Google Scholar 

  77. Sato K, Obara T, Yamazaki K, Kanbe M, Nakajima K, Yamada A, et al. Somatic mutations of the MEN1 gene and microsatellite instability in a case of tertiary hyperparathyroidism occurring during high phosphate therapy for acquired, hypophosphatemic osteomalacia. J Clin Endocrinol Metab. 2001;86(11):5564–71.

    Article  CAS  PubMed  Google Scholar 

  78. Rivkees SA, el-Hajj-Fuleihan G, Brown EM, Crawford JD. Tertiary hyperparathyroidism during high phosphate therapy of familial hypophosphatemic rickets. J Clin Endocrinol Metab. 1992;75(6):1514–8.

    CAS  PubMed  Google Scholar 

  79. Knudtzon J, Halse J, Monn E, Nesland A, Nordal KP, Paus P, et al. Autonomous hyperparathyroidism in X-linked hypophosphataemia. Clin Endocrinol. 1995;42(2):199–203.

    Article  CAS  Google Scholar 

  80. Makitie O, Kooh SW, Sochett E. Prolonged high-dose phosphate treatment: a risk factor for tertiary hyperparathyroidism in X-linked hypophosphatemic rickets. Clin Endocrinol. 2003;58(2):163–8.

    Article  CAS  Google Scholar 

  81. Huang QL, Feig DS, Blackstein ME. Development of tertiary hyperparathyroidism after phosphate supplementation in oncogenic osteomalacia. J Endocrinol Investig. 2000;23(4):263–7.

    Article  CAS  Google Scholar 

  82. Gilat H, Feinmesser R, Vinkler Y, Morgenstern S, Shvero J, Bachar G, et al. Clinical and operative management of persistent hyperparathyroidism after renal transplantation: a single-center experience. Head Neck. 2007;29(11):996–1001.

    Article  PubMed  Google Scholar 

  83. Hsieh TM, Sun CK, Chen YT, Chou FF. Total parathyroidectomy versus subtotal parathyroidectomy in the treatment of tertiary hyperparathyroidism. Am Surg. 2012;78(5):600–6.

    Article  PubMed  Google Scholar 

  84. Eldeiry LS, Ruan DT, Brown EM, Gaglia JL, Garber JR. Primary hyperparathyroidism and familial hypocalciuric hypercalcemia: relationships and clinical implications. Endocr Pract. 2012;18(3):412–7.

    Article  PubMed  Google Scholar 

  85. Jayasena CN, Mahmud M, Palazzo F, Donaldson M, Meeran K, Dhillo WS. Utility of the urine calcium-to-creatinine ratio to diagnose primary hyperparathyroidism in asymptomatic hypercalcaemic patients with vitamin D deficiency. Ann Clin Biochem. 2011;48(Pt 2):126–9.

    Article  CAS  PubMed  Google Scholar 

  86. Taha W, Singh N, Flack JM, Abou-Samra AB. Low urine calcium excretion in African American patients with primary hyperparathyroidism. Endocr Pract. 2011;17(6):867–72.

    Article  PubMed  Google Scholar 

  87. Nesbit MA, Hannan FM, Howles SA, Babinsky VN, Head RA, Cranston T, et al. Mutations affecting G-protein subunit alpha11 in hypercalcemia and hypocalcemia. N Engl J Med. 2013;368(26):2476–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hannan FM, Nesbit MA, Zhang C, Cranston T, Curley AJ, Harding B, et al. Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites. Hum Mol Genet. 2012;21(12):2768–78.

    Article  CAS  PubMed  Google Scholar 

  89. Nesbit MA, Hannan FM, Howles SA, Reed AA, Cranston T, Thakker CE, et al. Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3. Nat Genet. 2013;45(1):93–7.

    Article  CAS  PubMed  Google Scholar 

  90. Christensen SE, Nissen PH, Vestergaard P, Heickendorff L, Brixen K, Mosekilde L. Discriminative power of three indices of renal calcium excretion for the distinction between familial hypocalciuric hypercalcaemia and primary hyperparathyroidism: a follow-up study on methods. Clin Endocrinol. 2008;69(5):713–20.

    Article  CAS  Google Scholar 

  91. Serra AL, Schwarz AA, Wick FH, Marti HP, Wuthrich RP. Successful treatment of hypercalcemia with cinacalcet in renal transplant recipients with persistent hyperparathyroidism. Nephrol Dial Transplant. 2005;20(7):1315–9.

    Article  CAS  PubMed  Google Scholar 

  92. Serra AL, Savoca R, Huber AR, Hepp U, Delsignore A, Hersberger M, et al. Effective control of persistent hyperparathyroidism with cinacalcet in renal allograft recipients. Nephrol Dial Transplant. 2007;22(2):577–83.

    Article  CAS  PubMed  Google Scholar 

  93. Kruse AE, Eisenberger U, Frey FJ, Mohaupt MG. The calcimimetic cinacalcet normalizes serum calcium in renal transplant patients with persistent hyperparathyroidism. Nephrol Dial Transplant. 2005;20(7):1311–4.

    Article  CAS  PubMed  Google Scholar 

  94. Pallais JC, Kemp EH, Bergwitz C, Kantham L, Slovik DM, Weetman AP, et al. Autoimmune hypocalciuric hypercalcemia unresponsive to glucocorticoid therapy in a patient with blocking autoantibodies against the calcium-sensing receptor. J Clin Endocrinol Metab. 2011;96(3):672–80.

    Article  CAS  PubMed  Google Scholar 

  95. Pallais JC, Kifor O, Chen YB, Slovik D, Brown EM. Acquired hypocalciuric hypercalcemia due to autoantibodies against the calcium-sensing receptor. N Engl J Med. 2004;351(4):362–9.

    Article  CAS  PubMed  Google Scholar 

  96. Kifor O, Moore FD Jr, Delaney M, Garber J, Hendy GN, Butters R, et al. A syndrome of hypocalciuric hypercalcemia caused by autoantibodies directed at the calcium-sensing receptor. J Clin Endocrinol Metab. 2003;88(1):60–72.

    Article  CAS  PubMed  Google Scholar 

  97. Mantovani G. Clinical review: Pseudohypoparathyroidism: diagnosis and treatment. J Clin Endocrinol Metab. 2011;96(10):3020–30.

    Article  CAS  PubMed  Google Scholar 

  98. Neary NM, El-Maouche D, Hopkins R, Libutti SK, Moses AM, Weinstein LS. Development and treatment of tertiary hyperparathyroidism in patients with pseudohypoparathyroidism type 1B. J Clin Endocrinol Metab. 2012;97(9):3025–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012;97(9):2990–3011.

    Article  CAS  PubMed  Google Scholar 

  100. Eller-Vainicher C, Chiodini I, Battista C, Viti R, Mascia ML, Massironi S, et al. Sporadic and MEN1-related primary hyperparathyroidism: differences in clinical expression and severity. J Bone Miner Res. 2009;24(8):1404–10.

    Article  PubMed  Google Scholar 

  101. Machens A, Schaaf L, Karges W, Frank-Raue K, Bartsch DK, Rothmund M, et al. Age-related penetrance of endocrine tumours in multiple endocrine neoplasia type 1 (MEN1): a multicentre study of 258 gene carriers. Clin Endocrinol. 2007;67(4):613–22.

    Google Scholar 

  102. El Lakis M, Nockel P, Gaitanidis A, Guan B, Agarwal S, Welch J, et al. Probability of positive genetic testing results in patients with family history of primary hyperparathyroidism. J Am Coll Surg. 2018;226(5):933–8.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Newey PJ, Nesbit MA, Rimmer AJ, Attar M, Head RT, Christie PT, et al. Whole-exome sequencing studies of nonhereditary (sporadic) parathyroid adenomas. J Clin Endocrinol Metab. 2012;97(10):E1995–2005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Licata AA, Williams SE. A DXA primer for the practicing clinician: a case-based manual for understanding and interpreting bone densitometry. New York: Springer; 2014. xix, 167 pages p.

    Book  Google Scholar 

  105. El Maghraoui A, Roux C. DXA scanning in clinical practice. QJM. 2008;101(8):605–17.

    Article  PubMed  Google Scholar 

  106. Lorente-Ramos R, Azpeitia-Arman J, Munoz-Hernandez A, Garcia-Gomez JM, Diez-Martinez P, Grande-Barez M. Dual-energy x-ray absorptiometry in the diagnosis of osteoporosis: a practical guide. AJR Am J Roentgenol. 2011;196(4):897–904.

    Article  PubMed  Google Scholar 

  107. Shuhart CR, Yeap SS, Anderson PA, Jankowski LG, Lewiecki EM, Morse LR, et al. Executive summary of the 2019 ISCD position development conference on monitoring treatment, DXA cross-calibration and least significant change, spinal cord injury, peri-prosthetic and orthopedic bone health, transgender medicine, and pediatrics. J Clin Densitom. 2019;22(4):453–71.

    Article  PubMed  Google Scholar 

  108. Silverberg SJ, Shane E, de la Cruz L, Dempster DW, Feldman F, Seldin D, et al. Skeletal disease in primary hyperparathyroidism. J Bone Miner Res. 1989;4(3):283–91.

    Article  CAS  PubMed  Google Scholar 

  109. Laster A. A basic primer on vertebral fracture assessment (VFA): the International Society for Clinical Densitometry; 2012. Available from: https://www.iscd.org/publications/osteoflash/a-basic-primer-on-vertebral-fracture-assessment-vfa/.

    Google Scholar 

  110. Lewiecki EM, Laster AJ. Clinical review: clinical applications of vertebral fracture assessment by dual-energy x-ray absorptiometry. J Clin Endocrinol Metab. 2006;91(11):4215–22.

    Article  CAS  PubMed  Google Scholar 

  111. Kaptoge S, Armbrecht G, Felsenberg D, Lunt M, O’Neill TW, Silman AJ, et al. When should the doctor order a spine X-ray? Identifying vertebral fractures for osteoporosis care: results from the European Prospective Osteoporosis Study (EPOS). J Bone Miner Res. 2004;19(12):1982–93.

    Article  PubMed  Google Scholar 

  112. Lee JH, Lee YK, Oh SH, Ahn J, Lee YE, Pyo JH, et al. A systematic review of diagnostic accuracy of vertebral fracture assessment (VFA) in postmenopausal women and elderly men. Osteoporos Int. 2016;27(5):1691–9.

    Article  PubMed  Google Scholar 

  113. Silva BC, Leslie WD, Resch H, Lamy O, Lesnyak O, Binkley N, et al. Trabecular bone score: a noninvasive analytical method based upon the DXA image. J Bone Miner Res. 2014;29(3):518–30.

    Article  PubMed  Google Scholar 

  114. Dufour R, Winzenrieth R, Heraud A, Hans D, Mehsen N. Generation and validation of a normative, age-specific reference curve for lumbar spine trabecular bone score (TBS) in French women. Osteoporos Int. 2013;24(11):2837–46.

    Article  CAS  PubMed  Google Scholar 

  115. Silva BC, Boutroy S, Zhang C, McMahon DJ, Zhou B, Wang J, et al. Trabecular bone score (TBS)--a novel method to evaluate bone microarchitectural texture in patients with primary hyperparathyroidism. J Clin Endocrinol Metab. 2013;98(5):1963–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Cheung AM, Adachi JD, Hanley DA, Kendler DL, Davison KS, Josse R, et al. High-resolution peripheral quantitative computed tomography for the assessment of bone strength and structure: a review by the Canadian Bone Strength Working Group. Curr Osteoporos Rep. 2013;11(2):136–46.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Burghardt AJ, Pialat JB, Kazakia GJ, Boutroy S, Engelke K, Patsch JM, et al. Multicenter precision of cortical and trabecular bone quality measures assessed by high-resolution peripheral quantitative computed tomography. J Bone Miner Res. 2013;28(3):524–36.

    Article  PubMed  Google Scholar 

  118. Tjong W, Kazakia GJ, Burghardt AJ, Majumdar S. The effect of voxel size on high-resolution peripheral computed tomography measurements of trabecular and cortical bone microstructure. Med Phys. 2012;39(4):1893–903.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Whittier DE, Boyd SK, Burghardt AJ, Paccou J, Ghasem-Zadeh A, Chapurlat R, et al. Guidelines for the assessment of bone density and microarchitecture in vivo using high-resolution peripheral quantitative computed tomography. Osteoporos Int. 2020;31(9):1607–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Krug R, Burghardt AJ, Majumdar S, Link TM. High-resolution imaging techniques for the assessment of osteoporosis. Radiol Clin N Am. 2010;48(3):601–21.

    Article  PubMed  Google Scholar 

  121. Liu XS, Zhang XH, Sekhon KK, Adams MF, McMahon DJ, Bilezikian JP, et al. High-resolution peripheral quantitative computed tomography can assess microstructural and mechanical properties of human distal tibial bone. J Bone Miner Res. 2010;25(4):746–56.

    CAS  PubMed  Google Scholar 

  122. Burghardt AJ, Kazakia GJ, Majumdar S. A local adaptive threshold strategy for high resolution peripheral quantitative computed tomography of trabecular bone. Ann Biomed Eng. 2007;35(10):1678–86.

    Article  PubMed  Google Scholar 

  123. MacNeil JA, Boyd SK. Accuracy of high-resolution peripheral quantitative computed tomography for measurement of bone quality. Med Eng Phys. 2007;29(10):1096–105.

    Article  PubMed  Google Scholar 

  124. Stein EM, Silva BC, Boutroy S, Zhou B, Wang J, Udesky J, et al. Primary hyperparathyroidism is associated with abnormal cortical and trabecular microstructure and reduced bone stiffness in postmenopausal women. J Bone Miner Res. 2013;28(5):1029–40.

    Article  PubMed  Google Scholar 

  125. Hansen S, Beck Jensen JE, Rasmussen L, Hauge EM, Brixen K. Effects on bone geometry, density, and microarchitecture in the distal radius but not the tibia in women with primary hyperparathyroidism: a case-control study using HR-pQCT. J Bone Miner Res. 2010;25(9):1941–7.

    Article  PubMed  Google Scholar 

  126. Hansen S, Hauge EM, Rasmussen L, Jensen JE, Brixen K. Parathyroidectomy improves bone geometry and microarchitecture in female patients with primary hyperparathyroidism: a one-year prospective controlled study using high-resolution peripheral quantitative computed tomography. J Bone Miner Res. 2012;27(5):1150–8.

    Article  PubMed  Google Scholar 

  127. Pialat JB, Burghardt AJ, Sode M, Link TM, Majumdar S. Visual grading of motion induced image degradation in high resolution peripheral computed tomography: impact of image quality on measures of bone density and micro-architecture. Bone. 2012;50(1):111–8.

    Article  CAS  PubMed  Google Scholar 

  128. Kebebew E, Clark OH. Parathyroid adenoma, hyperplasia, and carcinoma: localization, technical details of primary neck exploration, and treatment of hypercalcemic crisis. Surg Oncol Clin N Am. 1998;7(4):721–48.

    Article  CAS  PubMed  Google Scholar 

  129. Kamaya A, Quon A, Jeffrey RB. Sonography of the abnormal parathyroid gland. Ultrasound Q. 2006;22(4):253–62.

    Article  PubMed  Google Scholar 

  130. Alveryd A. Parathyroid glands in thyroid surgery. I. Anatomy of parathyroid glands. II. Postoperative hypoparathyroidism--identification and autotransplantation of parathyroid glands. Acta Chir Scand. 1968;389:1–120.

    CAS  PubMed  Google Scholar 

  131. Andre V, Andre M, Le Dreff P, Granier H, Forlodou P, Garcia JF. [Intrathyroid parathyroid adenoma]. J Radiol. 1999;80(6):591–2.

    Google Scholar 

  132. McIntyre RC Jr, Eisenach JH, Pearlman NW, Ridgeway CE, Liechty RD. Intrathyroidal parathyroid glands can be a cause of failed cervical exploration for hyperparathyroidism. Am J Surg. 1997;174(6):750–3; discussion 3–4

    Article  PubMed  Google Scholar 

  133. Lane MJ, Desser TS, Weigel RJ, Jeffrey RB Jr. Use of color and power Doppler sonography to identify feeding arteries associated with parathyroid adenomas. AJR Am J Roentgenol. 1998;171(3):819–23.

    Article  CAS  PubMed  Google Scholar 

  134. Wolf RJ, Cronan JJ, Monchik JM. Color Doppler sonography: an adjunctive technique in assessment of parathyroid adenomas. J Ultrasound Med. 1994;13(4):303–8.

    Article  CAS  PubMed  Google Scholar 

  135. Purcell GP, Dirbas FM, Jeffrey RB, Lane MJ, Desser T, McDougall IR, et al. Parathyroid localization with high-resolution ultrasound and technetium Tc 99m sestamibi. Arch Surg. 1999;134(8):824–8; discussion 8–30

    Article  CAS  PubMed  Google Scholar 

  136. Cheung K, Wang TS, Farrokhyar F, Roman SA, Sosa JA. A meta-analysis of preoperative localization techniques for patients with primary hyperparathyroidism. Ann Surg Oncol. 2012;19(2):577–83.

    Article  PubMed  Google Scholar 

  137. Udelsman R, Donovan PI. Open minimally invasive parathyroid surgery. World J Surg. 2004;28(12):1224–6.

    Article  PubMed  Google Scholar 

  138. Nafisi Moghadam R, Amlelshahbaz AP, Namiranian N, Sobhan-Ardekani M, Emami-Meybodi M, Dehghan A, et al. Comparative diagnostic performance of ultrasonography and 99mTc-Sestamibi scintigraphy for parathyroid adenoma in primary hyperparathyroidism; systematic review and meta-analysis. Asian Pac J Cancer Prev. 2017;18(12):3195–200.

    PubMed  Google Scholar 

  139. Frank E, Ale-Salvo D, Park J, Liu Y, Simental A Jr, Inman JC. Preoperative imaging for parathyroid localization in patients with concurrent thyroid disease: a systematic review. Head Neck. 2018;40(7):1577–87.

    Article  PubMed  Google Scholar 

  140. Harari A, Mitmaker E, Grogan RH, Lee J, Shen W, Gosnell J, et al. Primary hyperparathyroidism patients with positive preoperative sestamibi scan and negative ultrasound are more likely to have posteriorly located upper gland adenomas (PLUGs). Ann Surg Oncol. 2011;18(6):1717–22.

    Article  PubMed  PubMed Central  Google Scholar 

  141. Treglia G, Piccardo A, Imperiale A, Strobel K, Kaufmann PA, Prior JO, et al. Diagnostic performance of choline PET for detection of hyperfunctioning parathyroid glands in hyperparathyroidism: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2019;46(3):751–65.

    Article  CAS  PubMed  Google Scholar 

  142. Broos WAM, van der Zant FM, Knol RJJ, Wondergem M. Choline PET/CT in parathyroid imaging: a systematic review. Nucl Med Commun. 2019;40(2):96–105.

    Article  PubMed  Google Scholar 

  143. Hoang JK, Sung WK, Bahl M, Phillips CD. How to perform parathyroid 4D CT: tips and traps for technique and interpretation. Radiology. 2014;270(1):15–24.

    Article  PubMed  Google Scholar 

  144. Yeh R, Tay YD, Tabacco G, Dercle L, Kuo JH, Bandeira L, et al. Diagnostic performance of 4D CT and Sestamibi SPECT/CT in localizing parathyroid adenomas in primary hyperparathyroidism. Radiology. 2019;291(2):469–76.

    Article  PubMed  Google Scholar 

  145. Bahl M, Sepahdari AR, Sosa JA, Hoang JK. Parathyroid adenomas and hyperplasia on four-dimensional CT scans: three patterns of enhancement relative to the thyroid gland justify a three-phase protocol. Radiology. 2015;277(2):454–62.

    Article  PubMed  Google Scholar 

  146. Bahl M, Muzaffar M, Vij G, Sosa JA, Choudhury KR, Hoang JK. Prevalence of the polar vessel sign in parathyroid adenomas on the arterial phase of 4D CT. AJNR Am J Neuroradiol. 2014;35(3):578–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Gotway MB, Reddy GP, Webb WR, Morita ET, Clark OH, Higgins CB. Comparison between MR imaging and 99mTc MIBI scintigraphy in the evaluation of recurrent of persistent hyperparathyroidism. Radiology. 2001;218(3):783–90.

    Article  CAS  PubMed  Google Scholar 

  148. Grayev AM, Gentry LR, Hartman MJ, Chen H, Perlman SB, Reeder SB. Presurgical localization of parathyroid adenomas with magnetic resonance imaging at 3.0 T: an adjunct method to supplement traditional imaging. Ann Surg Oncol. 2012;19(3):981–9.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Paul Guido, MD – Division of Endocrinology and Metabolism, Department of Internal Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Nitya Kumar, MD – Division of Endocrinology and Metabolism, Department of Internal Medicine, Duke University, Durham, North Carolina, USA.

Author information

Authors and Affiliations

  1. Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH, USA

    Jennifer D. Merrill

  2. Division of Neuroradiology, Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Carlos A. Zamora

  3. Division of Molecular Imaging and Therapeutics, Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC, USA

    Jorge D. Oldan

Authors
  1. Jennifer D. Merrill
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carlos A. Zamora
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jorge D. Oldan
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Vascular and Interventional RadiologyDepartment of Radiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA

    Hyeon Yu

  2. Division of Vascular and Interventional RadiologyDepartment of Radiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA

    Charles T. Burke

  3. Division of Vascular and Interventional RadiologyDepartment of Radiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA

    Clayton W. Commander

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Merrill, J.D., Zamora, C.A., Oldan, J.D. (2022). Clinical, Laboratory, and Radiological Diagnosis of Hyperparathyroidism. In: Yu, H., Burke, C.T., Commander, C.W. (eds) Diagnosis and Management of Endocrine Disorders in Interventional Radiology. Springer, Cham. https://doi.org/10.1007/978-3-030-87189-5_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-87189-5_2

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-87188-8

  • Online ISBN: 978-3-030-87189-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation