Serum pepsinogen I in familial multiple endocrine neoplasia type I

An increased serum pepsinogen I (PG I) concentration has been reported to be a marker of inherited peptic ulcer disease. Since both the Zollinger-Ellison syndrome and hyperparathyroidism, components of the familial multiple endocrine neoplasia type I syndrome (MEN I), are often associated with peptic ulcer, we have studied serum PG I concentrations in members of six well-defined families with MEN I. Serum PG I concentrations in 20 family members with hyperparathyroidism ranged from 35 to 864 ng/ml compared to 21-92 ng/ml in 16 nonaffected MEN I members. However, serum PG I levels were significantly higher (P less than 0.01) in the hyperparathyroid patients with hypergastrinemia (PGI median 192, range 75-864 ng/ml) than in those with normogastrinemia (PGI median 75, range 35-139 ng/ml). In fact, five of seven patients with hyperparathyroidism and hypergastrinemia compared to only one of 13 hyperparathyroid patients without hypergastrinemia had increased serum PG I levels above 130 ng/ml. We conclude that in the MEN I syndrome, increased serum PG I levels are found in patients with Zollinger-Ellison syndrome but not in hyperparathyroid patients with normogastrinemia and not in nonaffected MEN I members. The results indicate that in familial MEN I, hyperpepsinogenemia I is not inherited as a genetic trait but suggest that the elevated serum PG I levels are secondary to chronic hypergastrinemia.