Abstract
Primary hyperparathyroidism (HPTH) occurs sporadically in the vast majority of cases. However, it may also be part of a group of familial disorders with a high degree of disease penetrance, including multiple endocrine neoplasia type 1 (MEN1), MEN2A, the HPTH-jaw tumor syndrome (HPTH-JT), familial isolated hyperparathyroidism (FIHPTH), autosomal dominant mild hyperparathyroidism (ADMH), and neonatal severe HPTH (NSHPTH). The underlying genetic abnormalities causing the various syndromes have largely been unveiled over the past decade and are summarized in Table 36.1. Molecular genetic studies have also provided the basis for the diagnosis of familial HPTH, which now is largely based on genetic testing. This chapter summarizes the diagnosis and surgical management of familial HPTH.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Carling T, Udelsman R (2003) Parathyroid tumors. Curr Treat Options Oncol 4(4):319–328
Carling T (2005) Multiple endocrine neoplasia syndrome: genetic basis for clinical management. Curr Opin Oncol 17(1):7–12
Brandi ML, Gagel RF, Angeli A et al (2001) Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 86(12):5658–5671
Georgitsi M, Raitila A, Karhu A et al (2007) Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia. J Clin Endocrinol Metab 92(8):3321–3325
Pellegata NS, Quintanilla-Martinez L, Siggelkow H et al (2006) Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Natl Acad Sci USA 103(42):15558–15563
Skogseid B, Rastad J, Oberg K (1994) Multiple endocrine neoplasia type 1. Clinical features and screening. Endocrinol Metab Clin North Am 23(1):1–18
Carling T (2001) Molecular pathology of parathyroid tumors. Trends Endocrinol Metab 12(2):53–58
Hellman P, Skogseid B, Oberg K et al (1998) Primary and reoperative parathyroid operations in hyperparathyroidism of multiple endocrine neoplasia type 1. Surgery 124(6):993–999
Burgess JR, David R, Greenaway TM et al (1999) Osteoporosis in multiple endocrine neoplasia type 1: severity, clinical significance, relationship to primary hyperparathyroidism, and response to parathyroidectomy. Arch Surg 134(10):1119–1123
Norton JA, Cornelius MJ, Doppman JL et al (1987) Effect of parathyroidectomy in patients with hyperparathyroidism, Zollinger-Ellison syndrome, and multiple endocrine neoplasia type I: a prospective study. Surgery 102(6):958–966
Norton JA, Venzon DJ, Berna MJ et al (2008) Prospective study of surgery for primary hyperparathyroidism (HPTH) in multiple endocrine neoplasia-type 1 and Zollinger-Ellison syndrome: long-term outcome of a more virulent form of HPTH. Ann Surg 247(3):501–510
Stålberg P, Carling T (2009) Familial parathyroid tumors: diagnosis and management. World J Surg 33:2234–2243
Wells SA Jr, Ellis GJ, Gunnells JC et al (1976) Parathyroid autotransplantation in primary parathyroid hyperplasia. N Engl J Med 295(2):57–62
Akerstrom G, Malmaeus J, Bergstrom R (1984) Surgical anatomy of human parathyroid glands. Surgery 95(1):14–21
Hellman P, Skogseid B, Juhlin C et al (1992) Findings and long-term results of parathyroid surgery in multiple endocrine neoplasia type 1. World J Surg 16(4):718–722; discussion 722–723
Kraimps JL, Duh QY, Demeure M, Clark OH (1992) Hyperparathyroidism in multiple endocrine neoplasia syndrome. Surgery 112(6):1080–1086; discussion 1086–1088
O’Riordain DS, O’Brien T, Grant CS et al (1993) Surgical management of primary hyperparathyroidism in multiple endocrine neoplasia types 1 and 2. Surgery 114(6):1031–1037; discussion 1037–1039
Goudet P, Cougard P, Verges B et al (2001) Hyperparathyroidism in multiple endocrine neoplasia type I: surgical trends and results of a 256-patient series from groupe D’etude des neoplasies endocriniennes multiples study group. World J Surg 25(7):886–890
Dotzenrath C, Cupisti K, Goretzki PE et al (2001) Long-term biochemical results after operative treatment of primary hyperparathyroidism associated with multiple endocrine neoplasia types I and IIa: is a more or less extended operation essential? Eur J Surg 167(3):173–178
Elaraj DM, Skarulis MC, Libutti SK et al (2003) Results of initial operation for hyperparathyroidism in patients with multiple endocrine neoplasia type 1. Surgery 134(6):858–864; discussion 864–865
Edis AJ, van Heerden JA, Scholz DA (1979) Results of subtotal parathyroidectomy for primary chief cell hyperplasia. Surgery 86(3):462–469
Prinz RA, Gamvros OI, Sellu D, Lynn JA (1981) Subtotal parathyroidectomy for primary chief cell hyperplasia of the multiple endocrine neoplasia type I syndrome. Ann Surg 193(1):26–29
Van Heerden JA, Kent RB 3rd, Sizemore GW et al (1983) Primary hyperparathyroidism in patients with multiple endocrine neoplasia syndromes. Surgical experience. Arch Surg 118(5):533–536
Goretzki PE, Dotzenrath C, Roeher HD (1991) Management of primary hyperparathyroidism caused by multiple gland disease. World J Surg 15(6):693–697
Arnalsteen LC, Alesina PF, Quiereux JL et al (2002) Long-term results of less than total parathyroidectomy for hyperparathyroidism in multiple endocrine neoplasia type 1. Surgery 132(6):1119–1124; discussion 1124–1125
Hubbard JG, Sebag F, Maweja S, Henry JF (2006) Subtotal parathyroidectomy as an adequate treatment for primary hyperparathyroidism in multiple endocrine neoplasia type 1. Arch Surg 141(3):235–239
Wells SA Jr, Farndon JR, Dale JK et al (1980) Long-term evaluation of patients with primary parathyroid hyperplasia managed by total parathyroidectomy and heterotopic autotransplantation. Ann Surg 192(4):451–458
Malmaeus J, Benson L, Johansson H et al (1986) Parathyroid surgery in the multiple endocrine neoplasia type I syndrome: choice of surgical procedure. World J Surg 10(4):668–672
Burgess JR, David R, Parameswaran V et al (1998) The outcome of subtotal parathyroidectomy for the treatment of hyperparathyroidism in multiple endocrine neoplasia type 1. Arch Surg 133(2):126–129
Thompson NW (1995) The surgical management of hyperparathyroidism and endocrine disease of the pancreas in the multiple endocrine neoplasia type 1 patient. J Intern Med 238(3):269–280
Kraimps JL, Denizot A, Carnaille B et al (1996) Primary hyperparathyroidism in multiple endocrine neoplasia type IIa: retrospective French multicentric study. Groupe d’Etude des Tumeurs a Calcitonine (GETC, French Calcitonin Tumors Study Group), French Association of Endocrine Surgeons. World J Surg 20(7):808–812; discussion 812–813
Wells SA Jr, Debenedetti MK, Doherty GM (2002) Recurrent or persistent hyperparathyroidism. J Bone Miner Res 17(Suppl 2):N158–N162
Alexander HR Jr, Chen CC, Shawker T et al (2002) Role of preoperative localization and intraoperative localization maneuvers including intraoperative PTH assay determination for patients with persistent or recurrent hyperparathyroidism. J Bone Miner Res 17(Suppl 2):N133–N140
Udelsman R, Aruny JE, Donovan PI et al (2003) Rapid parathyroid hormone analysis during venous localization. Ann Surg 237(5):714–719; discussion 719–721
Udelsman R (1996) Parathyroid imaging: the myth and the reality. Radiology 201(2):317–318
Civelek AC, Ozalp E, Donovan P, Udelsman R (2002) Prospective evaluation of delayed technetium-99m sestamibi SPECT scintigraphy for preoperative localization of primary hyperparathyroidism. Surgery 131(2):149–157
Casanova D, Sarfati E, De Francisco A et al (1991) Secondary hyperparathyroidism: diagnosis of site of recurrence. World J Surg 15(4):546–549; discussion 549–550
Knudsen L, Brandi L, Daugaard H et al (1996) Five to 10 years follow-up after total parathyroidectomy and autotransplantation of parathyroid tissue: evaluation of parathyroid function by use of ischaemic blockade manoeuvre. Scand J Clin Lab Invest 56(1):47–51
Kivlen MH, Bartlett DL, Libutti SK et al (2001) Reoperation for hyperparathyroidism in multiple endocrine neoplasia type 1. Surgery 130(6):991–998
Mulligan LM, Ponder BA (1995) Genetic basis of endocrine disease: multiple endocrine neoplasia type 2. J Clin Endocrinol Metab 80(7):1989–1995
Eng C (1999) RET proto-oncogene in the development of human cancer. J Clin Oncol 17(1):380–393
Eng C, Clayton D, Schuffenecker I et al (1996) The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA 276(19):1575–1579
Milos IN, Frank-Raue K, Wohllk N et al (2008) Age-related neoplastic risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germ line RET Cys634Trp (TGC > TGG) mutation. Endocr Relat Cancer 15(4):1035–1041
Raue F, Kraimps JL, Dralle H et al (1995) Primary hyperparathyroidism in multiple endocrine neoplasia type 2A. J Intern Med 238(4):369–373
Herfarth KK, Bartsch D, Doherty GM et al (1996) Surgical management of hyperparathyroidism in patients with multiple endocrine neoplasia type 2A. Surgery 120(6):966–973; discussion 973–974
Skinner MA, Norton JA, Moley JF et al (1997) Heterotopic autotransplantation of parathyroid tissue in children undergoing total thyroidectomy. J Pediatr Surg 32(3):510–513
Carpten JD, Robbins CM, Villablanca A et al (2002) HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet 32(4):676–680
Wassif WS, Moniz CF, Friedman E et al (1993) Familial isolated hyperparathyroidism: a distinct genetic entity with an increased risk of parathyroid cancer. J Clin Endocrinol Metab 77(6):1485–1489
Szabo J, Heath B, Hill VM et al (1995) Hereditary hyperparathyroidism-jaw tumor syndrome: the endocrine tumor gene HRPT2 maps to chromosome 1q21–q31. Am J Hum Genet 56(4):944–950
Haven CJ, Wong FK, Van Dam EW et al (2000) A genotypic and histopathological study of a large Dutch kindred with hyperparathyroidism-jaw tumor syndrome. J Clin Endocrinol Metab 85(4):1449–1454
Simonds WF, James-Newton LA, Agarwal SK et al (2002) Familial isolated hyperparathyroidism: clinical and genetic characteristics of 36 kindreds. Medicine (Baltimore) 81(1):1–26
Winer KK, Ko CW, Reynolds JC et al (2003) 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
Iacobone M, Barzon L, Porzionato A et al (2007) Parafibromin expression, single-gland involvement, and limited parathyroidectomy in familial isolated hyperparathyroidism. Surgery 142(6):984–991; discussion 984–991
Carling T, Udelsman R (2003) Advancements in the surgical treatment of primary hyperparathyroidism. Probl Gen Surg 20(3):31–37
Scillatini A, Muscarella L, Guarnieri V et al (2004) Preclinical diagnosis of parathyroid carcinoma in a subject with a germline mutation of the parafibromin gene. J Intern Med 255:716
Gunn IR, Gaffney D (2004) Clinical and laboratory features of calcium-sensing receptor disorders: a systematic review. Ann Clin Biochem 41(Pt 6):441–458
Thorgeirsson U, Costa J, Marx SJ (1981) The parathyroid glands in familial hypocalciuric hypercalcemia. Hum Pathol 12(3):229–237
Marx SJ (1980) Familial hypocalciuric hypercalcemia. N Engl J Med 303(14):810–811
Cole DE, Janicic N, Salisbury SR, Hendy GN (1997) Neonatal severe hyperparathyroidism, secondary hyperparathyroidism, and familial hypocalciuric hypercalcemia: multiple different phenotypes associated with an inactivating Alu insertion mutation of the calcium-sensing receptor gene. Am J Med Genet 71(2):202–210
Carling T, Szabo E, Bai M et al (2000) Familial hypercalcemia and hypercalciuria caused by a novel mutation in the cytoplasmic tail of the calcium receptor. J Clin Endocrinol Metab 85(5):2042–2047
Szabo E, Carling T, Hessman O, Rastad J (2002) Loss of heterozygosity in parathyroid glands of familial hypercalcemia with hypercalciuria and point mutation in calcium receptor. J Clin Endocrinol Metab 87(8):3961–3965
Warner J, Epstein M, Sweet A et al (2004) Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications. J Med Genet 41(3):155–160
Carling T, Udelsman R (2008) Focused approach to parathyroidectomy. World J Surg 32(7):1512–1517
Carneiro DM, Solorzano CC, Nader MC et al (2003) Comparison of intraoperative iPTH assay (QPTH) criteria in guiding parathyroidectomy: which criterion is the most accurate? Surgery 134(6):973–979; discussion 979–981
Sokoll LJ, Drew H, Udelsman R (2000) Intraoperative parathyroid hormone analysis: a study of 200 consecutive cases. Clin Chem 46(10):1662–1668
Di Stasio E, Carrozza C, Pio Lombardi C et al (2007) Parathyroidectomy monitored by intra-operative PTH: the relevance of the 20 min end-point. Clin Biochem 40(9–10):595–603
Clerici T, Brandle M, Lange J et al (2004) Impact of intraoperative parathyroid hormone monitoring on the prediction of multiglandular parathyroid disease. World J Surg 28(2):187–192
Jaskowiak NT, Sugg SL, Helke J et al (2002) Pitfalls of intraoperative quick parathyroid hormone monitoring and gamma probe localization in surgery for primary hyperparathyroidism. Arch Surg 137(6):659–668; discussion 668–669
Tonelli F, Spini S, Tommasi M et al (2000) Intraoperative parathormone measurement in patients with multiple endocrine neoplasia type I syndrome and hyperparathyroidism. World J Surg 24(5):556–562; discussion 562–563
Weber CJ, Ritchie JC (1999) Retrospective analysis of sequential changes in serum intact parathyroid hormone levels during conventional parathyroid exploration. Surgery 126(6):1139–1143; discussion 1143–1144
Dackiw AP, Sussman JJ, Fritsche HA Jr et al (2000) Relative contributions of technetium Tc 99m sestamibi scintigraphy, intraoperative gamma probe detection, and the rapid parathyroid hormone assay to the surgical management of hyperparathyroidism. Arch Surg 135(5):550–555; discussion 555–557
Lal A, Bianco J, Chen H (2007) Radioguided parathyroidectomy in patients with familial hyperparathyroidism. Ann Surg Oncol 14(2):739–743
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Starker, L.F., Carling, T. (2012). Familial Syndromes Associated with Primary Hyperparathyroidism. In: Oertli, D., Udelsman, R. (eds) Surgery of the Thyroid and Parathyroid Glands. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-23459-0_36
Download citation
DOI: https://doi.org/10.1007/978-3-642-23459-0_36
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-23458-3
Online ISBN: 978-3-642-23459-0
eBook Packages: MedicineMedicine (R0)