Primary Hyperparathyroidism is the Most Common Feature of Multiple Endocrine Neoplasia Type 1
In multiple endocrine neoplasia type 1 (MEN1), almost all patients (95%) have parathyroid hyperplasia/primary hyperparathyroidism, making option (a) the correct answer. 1, 2
Prevalence of Major MEN1 Manifestations
MEN1 is characterized by three main tumor types, but they occur with different frequencies:
- Primary hyperparathyroidism (PHPT): Occurs in 95% of MEN1 patients, making it the most common manifestation 1, 2, 3
- Pancreatic neuroendocrine tumors: Occur in 40-75% of MEN1 patients 1, 2
- Pituitary adenomas: Occur in 30-55% of MEN1 patients 1
Clinical Diagnosis and Disease Penetrance
- Clinical diagnosis of MEN1 requires identification of at least two of the major constituent tumors 1, 2
- Disease penetrance increases with age: 45% by age 30,82% by age 50, and 96% by age 70 1, 2
- While penetrance is high with age, not all patients develop all three major manifestations 1, 3
Genetics and Pathophysiology
- MEN1 is caused by pathogenic variants in the MEN1 tumor-suppressor gene on chromosome 11q13 1, 2
- The gene encodes menin, a scaffold protein involved in cell-cycle control, transcriptional regulation, and genomic stability 1
- Pathogenic germline variants are identified in 80-95% of familial cases and 65-70% of sporadic cases 1
Clinical Implications and Management
- Early detection through surveillance is critical as delays in diagnosis are associated with increased morbidity and mortality 2, 4
- Despite advances in diagnosis and treatment, MEN1 patients continue to have decreased life expectancy primarily due to malignant neuroendocrine tumors 5
- Optimal treatment often requires specialized interdisciplinary centers due to the complex nature of the disease 6
Important Considerations
- MEN1 was previously thought to be primarily an adult-onset disorder, but 17% of MEN1-associated tumors are diagnosed before age 21 1, 5
- Recent data suggest that 42% of MEN1 patients in their teens may have clinically occult (non-functioning) pancreatic NETs 1
- The disease cannot be viewed as coinciding sporadic tumors; MEN1-related tumors differ from their sporadic counterparts in epidemiology and pathology 7
Common Pitfalls to Avoid
- Failing to screen for other MEN1-associated tumors when one component is identified 2
- Assuming all patients with MEN1 will develop all three major manifestations (parathyroid, pancreatic, and pituitary tumors) 1, 3
- Delaying genetic testing in at-risk individuals, as early identification allows for timely intervention 4, 5