From the Guidelines
Multiple endocrine neoplasia (MEN) syndromes require prompt and accurate diagnosis to prevent morbidity and mortality, with MEN Type 1 and 2 having distinct clinical features and management strategies. MEN Type 1 is characterized by tumors in the parathyroid glands, pancreas, and pituitary gland, with primary hyperparathyroidism (PHPT) being the most common presenting feature, occurring in 95% of MEN1 patients 1. In contrast, MEN Type 2 primarily affects the thyroid, adrenal glands, and parathyroids, with medullary thyroid carcinoma being the most concerning manifestation, and is further subdivided into MEN2A and MEN2B, with distinct genotype-phenotype correlations and clinical phenotypes 1.
Clinical Features and Diagnosis
MEN1 is diagnosed based on the identification of at least two of the major constituent tumors, including PHPT, pancreatic neuroendocrine tumors, and pituitary neuroendocrine tumors 1. MEN2, on the other hand, is characterized by the presence of medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism, with MEN2A and MEN2B having distinct clinical features and age of onset 1. The age of onset of medullary thyroid carcinoma varies by genotype, occurring in early childhood in those with MEN2B, and adolescence or early adulthood in MEN2A 1.
Management and Treatment
Prophylactic total thyroidectomy is recommended before age 5 for MEN2A and as early as possible for MEN2B to prevent medullary thyroid carcinoma. Pheochromocytomas require alpha-blockade (phenoxybenzamine 10-30 mg twice daily or doxazosin 2-8 mg daily) for 1-2 weeks before surgical removal 1. For MEN1, surgical removal of affected parathyroid glands for hyperparathyroidism is typically recommended, with 3.5 glands removed, and pancreatic tumors require surgical resection if they're over 2 cm or symptomatic 1. Pituitary adenomas are treated with dopamine agonists like cabergoline or surgery depending on the tumor type.
Screening and Genetic Testing
Regular screening is essential for both syndromes, including annual calcium, PTH, prolactin, and IGF-1 measurements for MEN1, and calcitonin and metanephrines for MEN2 1. Genetic testing should be offered to first-degree relatives since these conditions are autosomal dominant with high penetrance. Early diagnosis and treatment are critical to increase the potential for surgical prevention or curative treatment of MEN2B-associated medullary thyroid carcinoma, particularly in the first year of life 1.
From the Research
MEN Type 1
- MEN1 is an autosomal dominant disorder caused by mutations in the tumor suppressor gene MEN1, which encodes a 610-amino acid protein, menin 2.
- The disorder is characterized by the occurrence of parathyroid, pancreatic islet, and anterior pituitary tumors, as well as other tumors such as carcinoid tumors, adrenocortical tumors, meningiomas, facial angiofibromas, collagenomas, and lipomas 2.
- Patients with MEN1 have a decreased life expectancy, and the outcomes of current treatments are not as successful due to multiple tumors, which may be larger, more aggressive, and resistant to treatment, and the concurrence of metastases 2.
- Presymptomatic tumor detection and treatment specific for MEN1 tumors may improve the prognosis for MEN1 patients 2.
MEN Type 2
- MEN2 is a hereditary cancer syndrome with distinct variants, including MEN2A, MEN2B, and familial medullary thyroid cancer (MTC) 3.
- The most distinctive feature of MEN2 is the development of MTC, which can be aggressive and is the primary cause of mortality in MEN2 patients 3.
- Thyroidectomy, preferably during childhood, is the goal in all MEN2 carriers to prevent or cure MTC 3.
- RET testing has replaced calcitonin testing to diagnose the MEN2 carrier state, and the specific RET codon mutation correlates with the MEN2 syndromic variant, age of onset of MTC, and aggressiveness of MTC 3.
Diagnosis and Management
- Diagnosis of MEN1 is done through a combination of clinical evaluation, biochemical tests, and imaging procedures 4.
- Screening for MEN1 in patients with pituitary tumors may be useful to detect MEN1 syndrome, and periodic screening for primary hyperparathyroidism (pHPT) in patients with pituitary tumors is recommended 5.
- Genetic analysis of the MEN1 gene and additional search for related tumors are recommended in patients with MEN1 phenotype 5.
- Management of MEN1 and MEN2 requires a multidisciplinary approach, including skilled surgeons, endocrinologists, and geneticists, and involves tumor monitoring, biochemical tests, imaging procedures, and surgical interventions 2, 4, 3.