Description
Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary condition characterised by the development of multiple tumours in endocrine glands. Most commonly, it affects the parathyroid glands, pituitary gland, and pancreas. However, tumours may also occur in other organs.
Pathogenesis
MEN1 results from mutations in the MEN1 gene located on chromosome 11q13, which provides instructions for producing a protein called menin. This protein functions as a tumour suppressor, preventing cells from growing and dividing too rapidly. When the MEN1 gene is mutated, menin is not produced correctly, leading to uncontrolled cell growth and the formation of tumours.
Epidemiology, Risk Factors & Associations
- MEN1 is inherited in an autosomal dominant manner
- The prevalence is estimated to be about 1 in 30,000 people.
- There is no known ethnic, racial, gender, or geographic predisposition.
Clinical Features
Parathyroid Gland Tumours
Parathyroid gland tumours in MEN1 are usually adenomas or hyperplasia involving all four parathyroid glands. They cause primary hyperparathyroidism, leading to an overproduction of parathyroid hormone (PTH) which results in hypercalcaemia. Symptoms of hypercalcaemia can include polyuria, renal stones, osteoporosis, fatigue, and depression.
Pancreatic Gland Tumours
Pancreatic neuroendocrine tumours (NETs) in MEN1 can be non-functioning or functioning. Functioning pancreatic NETs are more common and include:
- Insulinomas: These are the most common functioning pancreatic NETs in MEN1, leading to an overproduction of insulin causing hypoglycaemia.
- Gastrinomas: Overproduction of gastrin leads to excessive gastric acid secretion causing recurrent peptic ulcers, known as Zollinger-Ellison syndrome.
- Glucagonomas, VIPomas, and Somatostatinomas: These are less common functioning pancreatic NETs causing hyperglycaemia, watery diarrhoea syndrome, and steatorrhea, respectively.
Non-functioning pancreatic NETs are less common and usually present as a mass effect or with metastatic disease since they do not produce hormones causing symptoms.
Pituitary Gland Tumours
Pituitary adenomas are the third most common tumour in MEN1. They can be classified based on the type of hormone they overproduce:
- Prolactinomas: The most common pituitary tumour in MEN1, causing an overproduction of prolactin. Symptoms include galactorrhea, infertility, and reduced libido.
- Growth Hormone-Secreting Adenomas: Overproduction of growth hormone causes gigantism in children or acromegaly in adults. Symptoms of acromegaly can include enlarged hands and feet, coarsening of facial features, and joint pain.
- ACTH-Secreting Adenomas: Overproduction of ACTH leads to Cushing’s disease, with symptoms such as weight gain, hypertension, and diabetes.
Non-functioning pituitary adenomas are also common and may present with symptoms of mass effect, such as headaches and visual field defects.
Other Tumours
- Other less common tumours can also occur, such as carcinoid tumours, lipomas, meningiomas, and ependymomas.
- Carcinoid tumours can present with flushing, diarrhoea, and wheezing, while central nervous system tumours may present with neurological symptoms based on their location.
Complications
- Increased risk of malignancy.
- Hypercalcaemia from parathyroid tumours can lead to renal stones and osteoporosis.
- Hypoglycaemia or gastric ulcers from pancreatic tumours.
- Visual field defects or hormonal abnormalities from pituitary tumours.
Pathological Features
- Histopathological: Microscopy often shows adenomatous hyperplasia or adenomas.
- Biochemical: Blood tests often reveal elevated levels of parathyroid hormone (PTH), prolactin, growth hormone (GH), insulin, or gastrin.
Radiological Features
CT
- Pituitary tumours: Hypodense relative to the normal pituitary tissue. Larger tumours may cause expansion of the sella turcica.
- Parathyroid tumours: Typically appear as hypo- to isodense nodules posterior to the thyroid gland. Parathyroid adenomas can sometimes show a faint rim of contrast enhancement.
- Pancreatic tumours: Pancreatic neuroendocrine tumours appear as hypervascular lesions, showing strong enhancement in the arterial phase and washout in the venous phase.
MRI
- Pituitary tumours: T1-weighted images show pituitary adenomas as hypointense and T2-weighted images show them as hyperintense relative to normal pituitary tissue. They enhance homogeneously following contrast administration.
- Parathyroid tumours: Tumours are typically hypointense on T1-weighted images and hyperintense on T2-weighted images.
- Pancreatic tumours: Pancreatic neuroendocrine tumours are typically hypointense on T1-weighted images and hyperintense on T2-weighted images. They show strong enhancement following contrast administration.
US
- Parathyroid tumours: Can be visualised as hypoechoic nodules posterior to the thyroid gland. Larger adenomas may exert a mass effect.
- Pancreatic tumours: Can be difficult to identify due to overlying bowel gas but can sometimes be seen as hypoechoic masses within the pancreas.
NM
- PET FDG: Pituitary and pancreatic neuroendocrine tumours may demonstrate increased FDG uptake, although sensitivity can be low for smaller lesions.
- Octreotide Scan (SRS): Neuroendocrine tumours (including pancreatic and pituitary tumours) may show uptake of radiolabeled octreotide, due to their expression of somatostatin receptors.
Grading and Staging
Staging and grading are typically tumour-specific and depend on the type and location of the tumour.
Differential Diagnosis
- Other types of MEN syndromes (MEN2, MEN4)
- Isolated familial hyperparathyroidism
- Familial isolated pituitary adenomas
- Non-hereditary endocrine tumours
Management
Treatment is individualised based on the type of tumours present and their complications. This could include surgical removal of tumours, medications to manage hormone overproduction, or chemotherapy for malignant tumours. Regular screening for tumour development is crucial for people with MEN1.