Wermer Syndrome

At a glance

Neoplastic disease characterized by tumors or hyperplasia of the parathyroid and pituitary glands and the islands of Langerhans (pancreas), with increased incidence of adrenocortical and thyroid disease. Hyperparathyroidism is present in more than 90% of affected patients. Asymptomatic hypercalcemia is the most common clinical manifestation. It is reported that 25% of patients consult for nephrolithiasis or nephrocalcinosis. Pituitary tumors occur in 15 to 42% of affected individuals. From 25 to 90% are prolactinomas. Pancreatic islet cell tumors occur in 60 to 70% of patients. Tumors are usually multicentric. Adenomas and adenomatous hyperplasia of the thyroid and adrenal glands may occur occasionally. Association with diffuse neuroendocrine tumors in the thymus, bronchi, and duodenopancreas is reported.

Synonyms

Multiple Endocrine Neoplasia Type 1 Syndrome; MEN 1.

History

Genetic disorder first reported by Paul Wermer, American internist in 1954, and in 1955 by Robert Milton Zollinger and Edwin Homer Ellison, American surgeons.

Incidence

Both sexes equally affected. It is rare in childhood. Prevalence in general population ranges between 1:20,000 and 1:40,000.

Genetic inheritance

It is inherited as an autosomal dominant genetic trait. More than 80% of cases are caused by inactivating mutations (including nonsense mutations, deletions, and insertions) of the MEN1 gene, MENIN; localized to chromosome 11q13.

Pathophysiology

Precise role of MENIN is unclear. It is likely to be a tumor-suppressor gene. Mutations lead to hyperplasia of the endocrine organs: pancreatic islet cell adenoma (40% of cases, most commonly gastrinomas and insulinomas), parathyroid adenoma (95% of cases), pituitary adenoma (30% of cases), adrenocortical adenoma, prolactinoma, glucagonoma, insulinoma, and vasointestinal peptide tumor. Lesions of nonendocrine organs may also be present: bronchial carcinoma and carcinoids, thymomas and thymic carcinoid, duodenal carcinoid, malignant schwannoma, ovarian tumors, and lipomas. Adenomas and adenomatous hyperplasia of the thyroid and adrenal glands may occur occasionally. Hormone secretion is rarely altered as a result, and the significance of these abnormalities is uncertain. Carcinoid tumors, particularly those derived from the embryologic foregut, occur in isolated cases. Multiple subcutaneous and visceral lipomas, angiofibromas, and collagenomas may also occur.

Diagnosis

Clinical features and the results of biochemical tests according to the presentation (hypoglycemia, hypercalcemia, hyperphosphatemia, anemia, relevant endocrine abnormalities). Also, the addition of radiological information (delineation and localization of peptic ulcers, pituitary tumor, renal stones, bronchial tumors, etc) is essential.

Clinical aspects

Symptoms and signs associated with the glands involved and the function of adenomas; gastrinoma (intractable peptic ulcer, high incidence of bleeding, perforation and obstruction, ectopic ulcers in esophagus and small intestines, diarrhea, steatorrhea, weight loss); pituitary adenoma (headache, visual field defects; acromegaly; hyperthyroidism; amenorrhea); parathyroid adenoma (hypercalcemia and renal stones); adrenal (Cushing Syndrome); insulinoma (hypoglycemia); glucagonoma ...