Multiple endocrine neoplasia type 1
Encyclopedia
Multiple endocrine neoplasia type 1 (MEN-1 syndrome) or Wermer's syndrome is part of a group of disorders that affect the endocrine system
.
ous and noncancerous tumor
s in glands such as the parathyroid, pituitary, and pancreas
. Multiple endocrine neoplasia occurs when tumors are found in at least two of the three main endocrine glands (parathyroid, pituitary, and pancreatico-duodenum). Tumors can also develop in organs and tissues other than endocrine glands. If the tumors become cancerous, some cases can be life-threatening. The disorder affects 1 in 30,000 people.
Although many different types of hormone-producing tumors are associated with multiple endocrine neoplasia, tumors of the parathyroid gland, pituitary gland, and pancreas are most frequent in multiple endocrine neoplasia type 1. Tumors cause an overactivation of these hormone-producing glands, leading to serious health problems such as severe ulcer
s (Due to gastrin hypersecretion, which stimulates secretion of hydrochloric acd). Overactivity of the parathyroid gland (hyperparathyroidism
) is the most common sign of this disorder. Hyperparathyroidism disrupts the normal balance of calcium
in the blood
, which can lead to kidney stones, thinning of bone
s, weakness, and fatigue.
Neoplasia in the pituitary gland can manifest as prolactinoma
s whereby too much prolactin
is secreted, suppressing the release of gonadotropins, causing a decrease in sex hormones such as testosterone
. Pituitary tumor in MEN1 can be large and cause signs by compressing adjacent tissues.
Pancreatic tumors usually form in the islet cells
, which over-secrete insulin
, causing a decrease in blood glucose levels.
Multiple endocrine neoplasia is part of a group of disorders that affect the body's network of hormone-producing glands (the endocrine system). Hormones are chemical messengers that travel through the bloodstream and regulate the function of cells and tissues throughout the body. Multiple endocrine neoplasia involves tumors in at least two endocrine glands; tumors can also develop in other organs and tissues. These growths can be noncancerous (benign) or cancerous (malignant). If the tumors become cancerous, some cases can be life-threatening.
The two major forms of multiple endocrine neoplasia are called type 1 and type 2; they are often confused because of their similar names. Type 1 and type 2 are distinguished by the genes involved, the types of hormones made, and the characteristic signs and symptoms.
Many different types of tumors are associated with multiple endocrine neoplasia. Type 1 frequently involves tumors of the parathyroid gland, pituitary gland, and pancreas. Tumors in these glands lead to the overproduction of hormones. The most common sign of multiple endocrine neoplasia type 1 is overactivity of the parathyroid gland (hyperparathyroidism). Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, thinning of bones, nausea and vomiting, high blood pressure (hypertension), weakness, and fatigue.
The most common sign of multiple endocrine neoplasia type 2 is a form of thyroid cancer called medullary thyroid carcinoma. Some people with this disorder also develop a pheochromocytoma, which is a tumor of the adrenal glands that can cause dangerously high blood pressure. Multiple endocrine neoplasia type 2 is divided into three subtypes: type 2A, type 2B, and familial medullary thyroid carcinoma (FMTC). These subtypes differ in their characteristic signs and symptoms and risk of specific tumors; for example, hyperparathyroidism occurs only in type 2A. The features of this disorder are relatively consistent within any one family.
About 40% of islet cell tumors originate from a β cell, secrete insulin (insulinoma), and can cause fasting hypoglycemia. β-Cell tumors are more common in patients < 40 years of age. About 60% of islet cell tumors originate from non-β-cell elements and tend to occur in patients > 40 years of age. Non-β-cell tumors are somewhat more likely to be malignant.
Most islet cell tumors secrete pancreatic polypeptide, the clinical significance of which is unknown.Gastrin is secreted by many non–β-cell tumors (increased gastrin secretion in MEN 1 also often originates from the duodenum). Increased gastrin secretion increases gastric acid, which may inactivate pancreatic lipase, leading to diarrhea and steatorrhea. Increased gastrin secretion also leads to peptic ulcers in > 50% of MEN 1 patients. Usually the ulcers are multiple or atypical in location, and often bleed, perforate, or become obstructed. Peptic ulcer disease may be intractable and complicated (Zollinger-Ellison syndrome—see Tumors of the GI Tract: Zollinger-Ellison Syndrome). Among patients presenting with Zollinger-Ellison syndrome, 20 to 60% have MEN 1.
A severe secretory diarrhea can develop and cause fluid and electrolyte depletion with non–β-cell tumors. This complex, referred to as the watery diarrhea, hypokalemia, and achlorhydria syndrome (WDHA; pancreatic cholera—see Tumors of the GI Tract: Vipoma), has been ascribed to vasoactive intestinal polypeptide, although other intestinal hormones or secretagogues (including prostaglandins) may contribute. Hypersecretion of glucagon, somatostatin, chromogranin, or calcitonin, ectopic secretion of ACTH (causing Cushing's syndrome), and hypersecretion of growth hormone–releasing hormone (causing acromegaly) sometimes occur in non–β-cell tumors. All of these are rare in MEN 1.
Nonfunctioning pancreatic tumors also occur in patients with MEN 1 and may be the most common type of pancreatoduodenal tumor in MEN 1. The size of the nonfunctioning tumor correlates with risk of metastasis and death.
s. About 25% of pituitary tumors secrete growth hormone or growth hormone and prolactin. Excess prolactin may cause galactorrhea (see Pituitary Disorders: Galactorrhea), and excess growth hormone causes acromegaly clinically indistinguishable from sporadically occurring acromegaly. About 3% of tumors secrete ACTH, producing Cushing's disease. Most of the remainder are nonfunctional. Local tumor expansion may cause visual disturbance, headache, and hypopituitarism. Pituitary tumors in MEN 1 patients appear to be larger and behave more aggressively than sporadic pituitary tumors.
, during diagnosis, one patient gets diagnosed with Wermer's syndrome.
Endocrine system
In physiology, the endocrine system is a system of glands, each of which secretes a type of hormone directly into the bloodstream to regulate the body. The endocrine system is in contrast to the exocrine system, which secretes its chemicals using ducts. It derives from the Greek words "endo"...
.
Explanation
These disorders greatly increase the risk of developing multiple cancerCancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
ous and noncancerous tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
s in glands such as the parathyroid, pituitary, and pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
. Multiple endocrine neoplasia occurs when tumors are found in at least two of the three main endocrine glands (parathyroid, pituitary, and pancreatico-duodenum). Tumors can also develop in organs and tissues other than endocrine glands. If the tumors become cancerous, some cases can be life-threatening. The disorder affects 1 in 30,000 people.
Although many different types of hormone-producing tumors are associated with multiple endocrine neoplasia, tumors of the parathyroid gland, pituitary gland, and pancreas are most frequent in multiple endocrine neoplasia type 1. Tumors cause an overactivation of these hormone-producing glands, leading to serious health problems such as severe ulcer
Peptic ulcer
A peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...
s (Due to gastrin hypersecretion, which stimulates secretion of hydrochloric acd). Overactivity of the parathyroid gland (hyperparathyroidism
Hyperparathyroidism
Hyperparathyroidism is overactivity of the parathyroid glands resulting in excess production of parathyroid hormone . The parathyroid hormone regulates calcium and phosphate levels and helps to maintain these levels...
) is the most common sign of this disorder. Hyperparathyroidism disrupts the normal balance of calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
in the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
, which can lead to kidney stones, thinning of bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
s, weakness, and fatigue.
Neoplasia in the pituitary gland can manifest as prolactinoma
Prolactinoma
A prolactinoma is a benign tumor of the pituitary gland that produces a hormone called prolactin. It is the most common type of pituitary tumor...
s whereby too much prolactin
Prolactin
Prolactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
is secreted, suppressing the release of gonadotropins, causing a decrease in sex hormones such as testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
. Pituitary tumor in MEN1 can be large and cause signs by compressing adjacent tissues.
Pancreatic tumors usually form in the islet cells
Islets of Langerhans
The islets of Langerhans are the regions of the pancreas that contain its endocrine cells. Discovered in 1869 by German pathological anatomist Paul Langerhans at the age of 22, the islets of Langerhans constitute approximately 1 to 2% of the mass of the pancreas...
, which over-secrete insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
, causing a decrease in blood glucose levels.
Multiple endocrine neoplasia is part of a group of disorders that affect the body's network of hormone-producing glands (the endocrine system). Hormones are chemical messengers that travel through the bloodstream and regulate the function of cells and tissues throughout the body. Multiple endocrine neoplasia involves tumors in at least two endocrine glands; tumors can also develop in other organs and tissues. These growths can be noncancerous (benign) or cancerous (malignant). If the tumors become cancerous, some cases can be life-threatening.
The two major forms of multiple endocrine neoplasia are called type 1 and type 2; they are often confused because of their similar names. Type 1 and type 2 are distinguished by the genes involved, the types of hormones made, and the characteristic signs and symptoms.
Many different types of tumors are associated with multiple endocrine neoplasia. Type 1 frequently involves tumors of the parathyroid gland, pituitary gland, and pancreas. Tumors in these glands lead to the overproduction of hormones. The most common sign of multiple endocrine neoplasia type 1 is overactivity of the parathyroid gland (hyperparathyroidism). Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, thinning of bones, nausea and vomiting, high blood pressure (hypertension), weakness, and fatigue.
The most common sign of multiple endocrine neoplasia type 2 is a form of thyroid cancer called medullary thyroid carcinoma. Some people with this disorder also develop a pheochromocytoma, which is a tumor of the adrenal glands that can cause dangerously high blood pressure. Multiple endocrine neoplasia type 2 is divided into three subtypes: type 2A, type 2B, and familial medullary thyroid carcinoma (FMTC). These subtypes differ in their characteristic signs and symptoms and risk of specific tumors; for example, hyperparathyroidism occurs only in type 2A. The features of this disorder are relatively consistent within any one family.
Genetic effects
People with multiple endocrine neoplasia type 1 are born with one mutated copy of the MEN1 gene in each cell. Then, during their lifetime, the other copy of the gene is mutated in a small number of cells. These genetic changes result in no functional copies of the MEN1 gene in selected cells, allowing the cells to divide with little control and form tumors.Parathyroid
Hyperparathyroidism is present in ≥ 90% of patients. Asymptomatic hypercalcemia is the most common manifestation: about 25% of patients have evidence of nephrolithiasis or nephrocalcinosis. In contrast to sporadic cases of hyperparathyroidism, diffuse hyperplasia or multiple adenomas are more common than solitary adenomas.Pancreas
Pancreatic islet cell tumors occur in 60 to 70% of patients. Tumors are usually multicentric. Multiple adenomas or diffuse islet cell hyperplasia commonly occurs; such tumors may arise from the small bowel rather than the pancreas. About 30% of tumors are malignant and have local or distant metastases. Malignant islet cell tumors due to MEN 1 syndrome often have a more benign course than do sporadically occurring malignant islet cell tumors.About 40% of islet cell tumors originate from a β cell, secrete insulin (insulinoma), and can cause fasting hypoglycemia. β-Cell tumors are more common in patients < 40 years of age. About 60% of islet cell tumors originate from non-β-cell elements and tend to occur in patients > 40 years of age. Non-β-cell tumors are somewhat more likely to be malignant.
Most islet cell tumors secrete pancreatic polypeptide, the clinical significance of which is unknown.Gastrin is secreted by many non–β-cell tumors (increased gastrin secretion in MEN 1 also often originates from the duodenum). Increased gastrin secretion increases gastric acid, which may inactivate pancreatic lipase, leading to diarrhea and steatorrhea. Increased gastrin secretion also leads to peptic ulcers in > 50% of MEN 1 patients. Usually the ulcers are multiple or atypical in location, and often bleed, perforate, or become obstructed. Peptic ulcer disease may be intractable and complicated (Zollinger-Ellison syndrome—see Tumors of the GI Tract: Zollinger-Ellison Syndrome). Among patients presenting with Zollinger-Ellison syndrome, 20 to 60% have MEN 1.
A severe secretory diarrhea can develop and cause fluid and electrolyte depletion with non–β-cell tumors. This complex, referred to as the watery diarrhea, hypokalemia, and achlorhydria syndrome (WDHA; pancreatic cholera—see Tumors of the GI Tract: Vipoma), has been ascribed to vasoactive intestinal polypeptide, although other intestinal hormones or secretagogues (including prostaglandins) may contribute. Hypersecretion of glucagon, somatostatin, chromogranin, or calcitonin, ectopic secretion of ACTH (causing Cushing's syndrome), and hypersecretion of growth hormone–releasing hormone (causing acromegaly) sometimes occur in non–β-cell tumors. All of these are rare in MEN 1.
Nonfunctioning pancreatic tumors also occur in patients with MEN 1 and may be the most common type of pancreatoduodenal tumor in MEN 1. The size of the nonfunctioning tumor correlates with risk of metastasis and death.
Pituitary
Pituitary tumors occur in 15 to 42% of MEN 1 patients. From 25 to 90% are prolactinomaProlactinoma
A prolactinoma is a benign tumor of the pituitary gland that produces a hormone called prolactin. It is the most common type of pituitary tumor...
s. About 25% of pituitary tumors secrete growth hormone or growth hormone and prolactin. Excess prolactin may cause galactorrhea (see Pituitary Disorders: Galactorrhea), and excess growth hormone causes acromegaly clinically indistinguishable from sporadically occurring acromegaly. About 3% of tumors secrete ACTH, producing Cushing's disease. Most of the remainder are nonfunctional. Local tumor expansion may cause visual disturbance, headache, and hypopituitarism. Pituitary tumors in MEN 1 patients appear to be larger and behave more aggressively than sporadic pituitary tumors.
Other manifestations
Adenomas and adenomatous hyperplasia of the thyroid and adrenal glands occurs occasionally in MEN 1 patients. 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.Diagnostic workup
Individuals with a combination of endocrine neoplasias suggestive of the MEN1 syndrome are recommended to have a mutational analysis of the MEN1 gene if additional diagnostic criteria are sufficiently met, mainly including:- age <40 years
- positive family history
- multifocal or recurrent neoplasia
- two or more organ systems affected
Disease Database
MEN1 gene variant databasePopular Culture
In the video game, Trauma TeamTrauma Team
Trauma Team, known in Japan as is a video game for the Wii console. The game is part of the Trauma Center series by Atlus. The game was released on May 18, 2010 in North America....
, during diagnosis, one patient gets diagnosed with Wermer's syndrome.
See also
- Multiple endocrine neoplasiaMultiple endocrine neoplasiaThe term multiple endocrine neoplasia encompasses several distinct syndromes featuring tumors of endocrine glands, each with its own characteristic pattern. In some cases, the tumors are malignant, in others, benign...
- Multiple endocrine neoplasia type 2a
- Multiple endocrine neoplasia type 2bMultiple endocrine neoplasia type 2bMultiple endocrine neoplasia type 3 is a genetic disease that causes multiple tumors on the mouth, eyes, and endocrine glands...
- AcromegalyAcromegalyAcromegaly is a syndrome that results when the anterior pituitary gland produces excess growth hormone after epiphyseal plate closure at puberty...
- ProlactinomaProlactinomaA prolactinoma is a benign tumor of the pituitary gland that produces a hormone called prolactin. It is the most common type of pituitary tumor...
- Werner syndromeWerner syndromeWerner syndrome is a very rare, autosomal recessive disorder characterized by the appearance of premature aging....