Primary Hyperparathyroidism in Patients with Gastric Carcinoid Tumors Type 1: An Unusual Coexistence

Abstract

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.

Chronic autoimmune atrophic gastritis associated with primary hyperparathyroidism: a transversal prospective study

“…Primrose et al (12) described the coexistence of hypergastrinemia and achlorhydria, which is suggestive of a diagnosis of CAAG, in 5.2% of 32 patients with PHPT, and Corleto et al (13) demonstrated the presence of CAAG in 7/52 (13.5%) patients with PHPT. On the other hand, Peracchi et al (14) documented the presence of PHPT in 3/52 patients with CAAG (5.8%), whereas Thomas et al (17) did not find PHPT cases in a series of 30 CAAG patients without GC but reported a PHPT prevalence of 15.4% in 26 patients with GC1, suggesting a possible association between GC1 and PHPT rather than between CAAG and PHPT. The coexistence of PHPT and GC1 has been described as a sporadic association in several studies (18,19,20,21,22,23), but the mechanisms (responsible) for this association are still unknown.…”

“…Fujimori et al (26) and Bjorklund et al (27) identified a mutation in exon 3 of the CTNNB1 gene, encoding b-catenin accumulation, both in parathyroid tumours and in carcinoids, but this mutation has not been confirmed in later studies (28,29). An alteration in P21 and P27 has also been suggested (30,31), though their role in ECL and parathyroid oncogenesis remains to be elucidated (17). Overall, further studies are needed to evaluate the possibility of a direct association between GC1 and PHPT.…”

“…There is no evidence that hypergastrinemia could influence PTH secretion in humans (11,17,23), whereas hypercalcaemia and/or elevated PTH levels may stimulate gastrin secretion (32,33,34,35). In our study, gastrin and CgA concentrations did not significantly differ in CAAG patients according to the presence or absence of PHPT.…”

“…In 2005, Peracchi et al (14) reported an increased prevalence of PHPT in patients with CAAG (5.7% compared with a prevalence of 1-3% in the general population (15,16)). Recently, Thomas et al (17) did not confirm this association but rather demonstrated an increased incidence of PHPT (15.4%) in patients with GC1, a condition that actually occurs in patients with CAAG. The association of PHPT with GC1 has been observed sporadically in other studies, and the mechanisms involved remain unknown (18,19,20,21,22,23).…”

Long-term follow-up of a large series of patients with type 1 gastric carcinoid tumors: data from a multicenter study

“…Primary hyperparathyroidism due to a parathyroid adenoma was the commonest neoplasia. Although the exact etiology of this finding is not known, it is plausible to consider that these tumors may develop as a result of the stimulatory effect of gastrin (30). As most patients had autoimmune gastritis, other autoimmune endocrine disorders, such as Hashimoto's thyroiditis, premature ovarian failure, vitiligo, and diabetes mellitus type 1 were also found to be prevalent (31).…”