Overview
Polyendocrine endocrinopathy type I, also known as multiple endocrine neoplasia syndrome type I and Weber syndrome, is characterized by tumors of the parathyroid glands, pancreatic islet cells, and pituitary glands. It is an autosomal dominant disease with equal prevalence in men and women, and 80% of patients develop the disease before the age of 50. The prevalence in the general population is 2-20 per 100,000 people. From randomly selected autopsy cases, the prevalence of polyendocrinopathy type I type was found to be 0.25%, whereas the prevalence of polyendocrinopathy type I was found to be 18% in patients with primary hyperparathyroidism.
Etiology
The gene responsible for the development of polyendocrinopathy type I is on chromosome 11 and appears to be a tumor suppressor gene.
Symptoms
Polyendocrinopathy type I can have a variety of clinical manifestations, depending primarily on the type of tumor that involves the patient.
1. Hyperparathyroidism
It is the most common and earliest presenting lesion in polyendocrine endocrinopathy type I. Compared with cases of sporadic hyperparathyroidism due to adenomas, it has an earlier onset (in the mid-20s), a similar incidence in both sexes, and pathologically consists of multiple parathyroid hyperplasia, which may be heterogeneous in size. Hypercalcemia due to hyperparathyroidism may exacerbate the symptoms and elevated blood gastrin levels in patients with coexisting gastrinomas.
2. Enteropancreatic endocrine tumors
They may be functional or nonfunctional and include gastrinomas and insulinomas.
(1) Gastrinoma: It is often accompanied by Zollinger-Ellison syndrome and accounts for 50% to 60% of enteropancreatic tumors in multiple endocrine gland disease type I. The tumor can be functional or nonfunctional, including gastrinoma and insulinoma. This kind of gastrinoma is characterized by small size, multicentricity, and can be ectopic, not located in the pancreas, but in the duodenal submucosa, often malignant, but its invasiveness is not as serious as sporadic.
(2) Insulinoma: The incidence of insulinoma in multiple endocrine gland disease type I accounts for about 20% of tumors originating from the pancreatic islets, and the rest are pancreatic glucagon tumors, schwannomas, and non-functioning tumors.
3. Pituitary tumor
Pituitary tumors occur in about 25% of cases, most of which are prolactinomas with or without increased secretion of growth hormone, followed by growth hormone tumors, anaplastic tumors, and adrenocorticotropic hormone tumors with Cushing’s syndrome. Pituitary tumors in polyendocrinopathy type I are rarely malignant, and their diagnosis and treatment are the same as in sporadic cases.
4. Adrenal adenoma and other lesions
Adrenal adenomas, including cortisol-secreting adenomas, are seen in PEGANOPATHY I. The diagnosis and treatment are the same as in sporadic cases. There are three possibilities for Cushing’s syndrome in polyendocrine endocrinopathy type I: (1) adrenal adenoma; (2) pituitary adrenocorticotropic hormone tumor; and (3) carcinoid tumor with ectopic adrenocorticotropic hormone syndrome. Pituitary tumors are more common. Thyroid adenomas and other thyroid disorders are also more common in polyendocrine gland disease type I. Subcutaneous lipomas, cutaneous collagenomas, and multiple angiofibromas of the face occur in 30% to 90% of family members with polyendocrinopathy type I. Such manifestations may be useful in screening these individuals to identify carriers of the gene for the polyendocrinopathy type I defect.
5. Other
Less commonly, multiple endocrinopathy type I syndromes include adenomas and adenomatous hyperplasia of the thyroid and adrenal glands, as well as carcinoid tumors. Multiple subcutaneous and visceral lipomas are also seen.
Examination
Due to the small size of gastrinomas in multiple endocrine glands, their localization is difficult. CT and magnetic resonance can detect liver metastatic lesions, but it is often difficult to confirm the diagnosis of gastrinomas, and further localization methods include endoscopic ultrasound, hepatic vein blood sampling for gastrin measurement after selective arterial injection of pancreatin, and radionuclide-labeled oxytocin scanning. If necessary, a secretin excitation test may be performed, and plasma gastrin is elevated in patients with gastrinomas.
Insulinomas in polyendocrine gland disease type I are also often multicentric and difficult to localize. Endoscopic ultrasonography and hepatic vein blood sampling for insulin measurement after selective calcium drip can help to localize the tumor.
In some families, it is now possible to identify genetic carriers by genetic screening with DNA restriction segment length polymorphism analysis, which is 99.5% correct. Regular annual screening for genetic carriers starting at age 15 years includes a history of patients with suggestive symptoms; peptic ulcer, diarrhea, kidney stones, hypoglycemia, and hypopituitarism as well as screening for visual field defects, acromegaly, and subcutaneous lipomas; and measurement of serum calcium, intact parathyroid hormone, gastrin, and prolactin. If necessary, additional laboratory and diagnostic tests, CT or MRI of the pituitary gland should be performed.
Diagnosis
Parathyroid, pancreatic and pituitary tumors are present in about 40% of cases. A relative of the patient who exhibits any of the typical symptoms of the syndrome is at risk of developing other concomitant tumors.
The diagnosis of insulin-secreting beta-cell tumors of the pancreas is established by demonstrating fasting hypoglycemia with hyperinsulinemia. Gastrin-secreting non-beta-cell tumors may be diagnosed by high basal gastrin levels, demonstrated hyperresponsiveness to calcium titration, and paradoxical elevation of gastrin after instillation of pancreatin. High basal pancreatic polypeptide or gastrin or an overreaction to a standard meal of this hormone may be an early symptom of pancreatic involvement in polyendocrine gland disease type I syndrome. Increased growth hormone, which cannot be suppressed by glucose and high levels of interleukin-C (insulin-like growth factor-1 or IGF-1), establishes the diagnosis of acromegaly.
The diagnosis of gastrinoma is based on the coexistence of hypergastrinemia and high gastric acid secretion, whereby it can be differentiated from the common gastric acid deficiency with hypergastrinemia.
Treatment
Parathyroid and pituitary diseases are mainly treated surgically. Islet cell tumors are more difficult to manage because the lesions are small and difficult to find, and multiple lesions are common. If a single tumor cannot be found, total pancreatectomy is required for adequate control of hyperinsulinemia. Diazoxide can be used as an adjunct in the management of hypoglycemia, while streptozotocin and other cytotoxic agents may improve symptoms by shrinking the tumor.
Treatment of gastrin-secreting nonbeta-cell tumors is complex. Locate and resect the tumor in all patients if possible. If this is not possible, oxytocin is used, and neutron pump blockers often achieve relief of peptic ulcer symptoms.H2 blockers are also available but are less effective. Gastrectomy is rarely required for the treatment of recalcitrant ulcers.