Objective: Although a number of familiar syndromes are associated with primary hyperparathyroidism (PHP), there is no information regarding the prevalence of PHP in other sporadic neuroendocrine diseases. The aim of this study is to investigate the prevalence of PHP in our group of patients with gastric carcinoid (GC) type 1 tumors. Methods: Twenty-six patients with biopsy-proven GC type 1 tumors were retrospectively studied. The diagnosis of PHP was suspected following elevated or high-normal serum calcium levels and elevated or inappropriate normal parathyroid hormone levels. Further tests for the localization of the hyperfunctioning parathyroid glands included neck ultrasound, 99mTc-SESTAMIBI scanning, and cervical or upper mediastinal MR imaging studies. Four control groups were also studied: two age- and sex-matched groups of individuals with (n = 49) and without (n = 34) thyroid autoimmunity and normal endoscopy of the stomach, a third group with nongastric neuroendocrine tumors (n = 68), and a fourth group with atrophic gastritis and hypergastrinemia, without gastric endocrine tumors (n = 30). Results: PHP was diagnosed in 4 (15.38%) patients with GC type 1 tumors compared to none of the 4 control groups. Three of the 4 patients with PHP were operated and proved to have a parathyroid adenoma. No statistically significant differences were observed between patients with or without PHP in mean gastrin and chromogranin A levels, number of lesions, ki-67 labeling index expression, and maximum GC type 1 tumor diameter. Conclusion: PHP seems to be relatively common, approximately 15% in the present cohort, in patients with GC type 1 tumors. PHP should be actively looked for in such patients and treated accordingly.

Keywords:
Gastric carcinoid tumors type 1, Primary hyperparathyroidism
1.
Modlin IM, Lye KD, Kidd M: A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003;6:203–209.
2.
Rindi G, Luinetti O, Cornaggia M, Capella C, Solcia E: Three subtypes of gastric argyrophil carcinoid and the gastric neuroendocrine carcinoma: a clinicopathologic study. Gastroenterology 1993;104:994–1006.
3.
Centanni M, Marignani M, Gargano L, Corleto VD, Casini A, Delle Fave G, Andreoli M, Annibale B: Atrophic body gastritis in patients with autoimmune thyroid disease: an underdiagnosed association. Arch Intern Med 1999;159:1726–1730.
4.
Modlin IM, Lye KD, Kidd M: A 50 year analysis of gastric carcinoids: small tumor or larger problem? Am J Gastroenterol 2004;99:23–32.
5.
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;126:433–440.
6.
Vierimaa O, Villablanca A, Alimov A, Georgitsi M, Raitila A, Vahteristo P, Larsson C, Ruokonen A, Eloranta E, Ebeling TM, Ignatius J, Aoltonen LA, Leisti J, Salmela PI: Mutation analysis of MEN1, HRPT2, CASR, CDKN1B and AIP genes in primary hyperparathyroidism patients with features of genetic predisposition. J Endocrinol Invest 2009;32:512–518.
7.
Cetani F, Pardi E, Borsari S, Viacava P, Dipollina G, Cianferotti L, Ambrogini E, Gazzerro E, Colussi G, Berti P, Miccoli P, Pinchera A, Marcocci C: Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors. J Clin Endocrinol Metab 2004;89:5583–5591.
8.
Marx SJ, Simonds WF, Aqarval SK, Burns AL, Weinstein LS, Cohran C, Skarulis MC, Spiegel AM, Libutti SK, Alexander HR Jr, Chen CC, Chang R, Chandrasekharappa SC, Collins FS: Hyperparathyroidism in hereditary syndromes: special expressions and special managements. J Bone Miner Res 2002;17:37–43.
9.
Rindi G, Klöppel G, Alhman H, Caplin M, Couvelard A, de Herder WW, Eriksson B, Falchetti A, Falconi M, Komminoth P, Körner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B, Frascati Consensus Conference Participants: TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a staging system. Virchows Arch 2006;449:395–401.
10.
Bilezikian JP, Potts JT Jr, Fuleihan GH, Kleerekoper M, Neer R, Peacock M, Rastad J, Silverberg SJ, Udelsman R, Wells SA: Summary statement from a workshop on asymptomatic primary hyperparathyroidism: a perspective for the 21st century. J Clin Endocrinol Metab 2002;87:5353–5361.
11.
Alberti-Flor JJ, Halter S, Dunn GD: Multiple gastric carcinoids in a patient with a history of primary hyperparathyroidism. Am J Gastroenterol 1985;80:531–534.
12.
Rode J, Dhillon AP, Cotton PB, Woolf A, O’Rhiordan JLH: Carcinoid tumor of the stomach and primary hyperparathyroidism: a new association. J Clin Pathol 1987;40:546–551.
13.
Nores JM, Dalayeun JF, Remy JM, Nenna AD: Gastric carcinoid tumor and parathyroid adenoma. Gut 1988;29:689–690.
14.
Corleto VD, Goebel SU, Panzuto F, Jensen RT, Delle Fave G, Annibale G: Co-existence of hyperparathyroidism, hypergastrinemia and multiple gastric carcinoids is not always due to incomplete expression of the MEN-1 syndrome. Dig Liver Dis 2003;35:585–589.
15.
Christopoulos C, Balatsos V, Rotas E, Karoumpalis I, Papavasileiou D, Kontogeorgos G, Dupasquier S, Calender A, Skandalis N, Economopoulos P: The syndrome of gastric carcinoid and hyperparathyroidism: a family study and literature review. Eur J Endocrinol 2009;160:689–694.
16.
Fujimori M, Ikeda S, Shimizu Y, Okajima M, Asahara T: Accumulation of beta-catenin protein and mutations in exon 3 of beta-catenin gene in gastrointestinal carcinoid tumor. Cancer Res 2001;61:6656–6659.
17.
Bjorklund P, Linddberg D, Akerstrom G, Westin G: Stabilizing mutation of CTNNB1/beta-catenin and protein accumulation analyzed in a large series of parathyroid tumors of Swedish patients. Mol Cancer 2008;7:53.
18.
Erickson LA, Jin L, Wollan P, Thompson GB, van Heerden JA, Lloyd RV: Parathyroid hyperplasia, adenomas, and carcinomas: differential expression of p27Kip1 protein. Am J Surg Pathol 1999;23:288–295.
19.
Doganavsargil B, Sarsik B, Kirdok FS, Musoglu A, Tuncyurek M: p21 and p27 immunoexpression in gastric well-differentiated endocrine tumors (ECL-cell carcinoids). World J Gastroenterol 2006;12:6280–6284.
20.
Sorensen OH, Hindberg I, Madsen SN: Secondary hyperparathyroidism in young rats given prolonged treatment with calcitonin. Acta Endocrinol 1972;71:313–320.
21.
Erdogan MF, Gursoy A, Kulaksizoglu M: Long-term effects of elevated gastrin levels on calcitonin secretion. J Endocrinol Invest 2006;29:771–775.
22.
Selking O, Borch K, Johanson H, Ljunghall S, Wide L: Evaluation of parathyroid function in patients with hypergastrinemia and pernicious anemia. Upsala J Med Sci 1982;87:215–222.
23.
Dufresne M, Seva C, Fourmy D: Cholecystokinine and gastrin receptors. Physiol Rev 2006;86:805–847.
24.
Reubi JC, Schaer JC Waser B: Cholecystokinine (CCK)-A and CCK-B/gastrin receptors in human tumors. Cancer Res 1997;57:1377–1386.
25.
Gagnemo-Persson R, Samuelsson A, Hakanson R, Persson P: Chicken parathyroid hormone gene expression in response to gastrin, omeprazole, ergocalciferol, and restricted food intake. Calcified Tissue Int 1997;61:210–215.
26.
Polak JM, Bussolati G, Pearse AGE: Cytochemical, immunofluorescence and ultrastructural investigation on the antral G cells in hyperparathyroidism. Virchows Arch 1971;9:187–197.
27.
Creutzfeld W, Arnold R, Creutzfeld C, Feurle G, Ketterer H: Gastrin and G cells in the antral mucosa of patients with pernicious anaemia, acromegaly and hyperparathyroidism and in Zollinger-Ellison tumor of the pancreas. Eur J Clin Invest 1971;1:461–479.
28.
Buchan AM, Squires P, Ring M, Meloche RM: Mechanism of action of the calcium-sensing receptor in human antral gastrin cells. Gastroenterolgy 2001;120:1279–1281.
29.
Corleto VD, Minisola S, Moretti A, Damiani C, Grossi C, Ciardi S, D’Ambra G, Bordi C, Strom R, Spagna G, Delle Fave G, Annibale B: Prevalence and causes of hypergastrinemia in primary hyperparathyroidism: a prospective study. J Clin Endocrinol Metab 1999;84:4554–4558.
30.
Kagawa J, Honda S, Kodama M, Sato R, Murakami K, Fujioka T: Enterochromaffin-like cell tumor induced by Helicobacter pylori infection in Mongolian gerbils. Helicobacter 2002;7:390–397.
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2010
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