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DOI: 10.1055/s-2001-16944
Primary Hyperparathyroidism in Patients with Multiple Endocrine Neoplasia Type 1: Comparison with Sporadic Parathyroid Adenomas
Publication History
Publication Date:
04 September 2001 (online)
A prospective study on the natural course of primary hyperparathyroidism has recently been reported. Since hyperparathyroidism in multiple endocrine neoplasia type 1 (MEN 1) is genetically distinct from most forms of sporadic hyperparathyroidism, it is important to know the natural course of hyperparathyroidism in MEN 1 for better clinical management. For this purpose, we retrospectively reviewed clinical parameters of patients with MEN 1 when they were diagnosed as having hyperparathyroidism, and compared them with those of patients with sporadic primary hyperparathyroidism. In patients with MEN 1: 1) levels of intact PTH (i-PTH) gradually increased with age, which accelerated over 40 years; 2) compared to the steep rise in i-PTH levels in aged patients, increase in serum calcium or decrease of serum inorganic phosphate concentration was relatively mild, and 3) the high concentrations of i-PTH in aged patients were not due to renal insufficiency. These features were not observed in patients with sporadic primary parathyroid adenomas. Clinical features of untreated hyperparathyroidism in MEN 1 may be significantly affected by the age of the patient. The effect, if any, of age-dependent deterioration on recurrence rate after subtotal or total parathyroidectomy requires further elucidation.
Key words:
MEN1 Gene - Mutation - Parathyroid Hormone - Renal Function
References
- 1 Thakker R V. Multiple endocrine neoplasia - syndromes of the twentieth century. J Clin Endocrinol Metab . 1998; 83 2617-2620
- 2 van Heerden J A, Kent R B, Sizemore G W, Grant C S, ReMine W H. Primary hyperparathyroidism in patients with multiple endocrine neoplasia syndromes. Arch Surg. 1983; 118 533-536
- 3 Thompson N W. The surgical management of hyperparathyroidism and endocrine disease of the pancreas in the multiple endocrine neoplasia type 1. J Intern Med. 1995; 238 269-280
- 4 Rizzoli R, Green J III, Marx S J. Primary hyperparathyroidism in familial multiple endocrine neoplasia type 1. Long-term follow-up of serum calcium levels after parathyroidectomy. Am J Med. 1985; 78 467-474
- 5 Hellman P, Skogseid B, Öberg K, Juhlin C, Akerström G, Rastad J. Primary and reoperative parathyroid operations in hyperparathyroidism of multiple endocrine neoplasia type 1. Surgery. 1998; 124 993-999
- 6 Burgess J R, David R, Parameswaran V, Greenaway T M, Shepherd J J. The outcome of subtotal parathyroidectomy for the treatment of hyperparathyroidism in multiple endocrine neoplasia type 1. Arch Surg. 1998; 133 126-129
- 7 Chandrasekharappa S C, Guru S C, Manickam P, Olufemi S -E, Collins F S, Emmert-Buck M R, Debelenko L V, Zhuang Z, Lubensky I A, Liotta L A, Crabtree J S, Wang Y, Roe B A, Weisemann J, Boguski M S, Agarwal S K, Kester M B, Kim Y S, Heppner C, Dong Q, Spiegel A M, Burns AL and Marx S J. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science. 1997; 276 404-407
- 8 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. 1999; 341 1249-1255
- 9 Katai M, Sakurai A, Itakura Y, Ikeo Y, Nakajima K, Hara M, Iijima S, Kaneko T, Kobayashi M, Ichikawa K, Aizawa T, Hashizume K. Multiple endocrine neoplasia type 1 is not rare in Japan. Endocr J. 1997; 44 841-845
- 10 Sakurai A, Shirahama S, Fujimori M, Katai M, Itakura Y, Kobayashi S, Amano J, Fukushima Y, Hashizume K. Novel MEN1 gene mutations in familial multiple endocrine neoplasia type 1. J Hum Genet. 1998; 43 199-201
- 11 Orwoll E S, Meier D E. Alterations in calcium, vitamin D, and parathyroid hormone physiology in normal men with aging: relationship to the development of senile osteopenia. J Clin Endocrinol Metab. 1986; 63 1262-1269
- 12 Sherman S S, Hollis B W, Tobin J D. Vitamin D status and related parameters in a healthy population: the effects of age, sex and season. J Clin Endocrinol Metab. 1990; 71 405-413
- 13 Prince R L, Dick I, Devine A, Price R I, Gutteridge D H, Kerr D, Criddle A, Garcia-Webb P, St John A. The effects of menopause and age on calcitropic hormones: a cross-sectional study of 655 healthy women aged 35 to 90. J Bone Miner Res. 1995; 10 835-842
- 14 Bassett J HD, Forbes S A, Pannett A AJ, Lloyd S E, Christie P T, Wooding C, Harding B, Besser G M, Edwards C R, Monson J P, Sampson J, Wass J AH, Wheeler M H, Thakker R V. Characterization of mutations in patients with multiple endocrine neoplasia type 1.<./TI>. Am J Hum Genet. 1998; 62 232-244
- 15 Smogorzewski M, Tian J, Massry S G. Down-regulation of PTH-PTHrP receptor of heart in CRF: role of [Ca2+]i. Kidney Int. 1995; 47 1182-1186
- 16 Morieux Y J, Denne M A, Bouizar Z, Urena P, de Vernejoul M C. Paridronate corrects the down-regulation of the renal parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor mRNA in rats bearing Walker tumors. Horm Metab Res. 1998; 30 249-255
- 17 Carling T, Rastad J, Ridefelt P, Gobl A, Hellman P, Öberg K, Rask L, Larsson C, Juhlin C, Åkerström G, Skogseid B. Hyperparathyroidism of multiple endocrine neoplasia type 1: candidate gene and parathyroid calcium sensing protein expression. Surgery. 1995; 118 924-931
- 18 D’Amour P, Palardy J, Bahsali G, Mallette L E, DeLéan A, Lepage R. The modulation of circulating parathyroid hormone immunoheterogeneity in man by ionized calcium concentration. J Clin Endocrinol Metab. 1992; 74 525-532
- 19 Heppner C, Kester M B, Agarwal S K, Debelenko L V, Emmert-Buck M R, Guru S C, Manickam P, Olufemi S -E, Skarulis M C, Doppman J L, Alexander R H, Kim Y S, Saggar S K, Lubensky I A, Zhuang Z, Liotta L A, Chandrasekharappa S C, Collins F S, Spiegel A M, Burns A L, Marx S J. Somatic mutation of the MEN1 gene in parathyroid tumors. Nat Genet. 1997; 16 375-378
- 20 Farnebo F, The B T, Kytyölä S, Svensson A, Phelan C, Sandelin K, Thompson N W, Höög A, Weber G, Farnebo L -O, Larsson C. Alterations of the MEN1 gene in sporadic parathyroid tumors. J Clin Endocrinol Metab. 1998; 83 2627-2630
- 21 Carling T, Correa P, Hessman O, Hedberg J, Skogseid B, Lindberg D, Rastad J, Westin G, Åkerström G. Parathyroid MEN 1 gene mutations in relation to clinical characteristics of nonfamilial primary hyperparathyroidism. J Clin Endocrinol Metab. 1998; 83 2960-2963
- 22 Arnold A, Kim H G, Gaz R D, Eddy R L, Fukushima Y, Byers MG Shows T B, Kronenberg H M. Molecular cloning and chromosomal mapping of DNA rearranged with the parathyroid hormone gene in a parathyroid adenoma. J Clin Invest. 1989; 83 2034-2040
- 23 Cryns V, Yi S M, Tahara E, Gaz R D, Arnold A. Frequent loss of chromosome arm 1p in parathyroid adenomas. Genes Chromosome Cancer. 1995; 13 9-17
- 24 Tahara H, Smith A P, Gas R D, Cryns V L, Arnold A. Genomic localization of novel candidate tumor suppressor gene loci in human parathyroid adenomas. Cancer Res. 1996; 56 599-605
- 25 Teh B T, Farnebo F, Kristoffersson U, Sundelin B, Cardinal J, Axelson R, Yap A, Epstein M, Heath H III, Cameron D, Larsson C. Autosomal dominant primary hyperparathyroidism and jaw tumor syndrome associated with renal hamartomas and cystic kidney disease: linkage to 1q21-q32 and loss of the wild type allele in renal hamartomas. J Clin Endocrinol Metab. 1996; 81 4204-4211
A. Sakurai, M.D., Ph.D.
Department of Aging Medicine and Geriatrics
Shinshu University School of Medicine
3-1-1 Asahi
Matsumoto, 390-8621
Japan
Phone: + 81 (263) 37-2686
Fax: + 81 (263) 37-2710
Email: bakabon@hsp.md.shinshu-u.ac.jp