From the Guidelines
Diagnosing Multiple Endocrine Neoplasia (MEN) syndrome requires a comprehensive approach combining clinical evaluation, biochemical testing, and genetic analysis, with the diagnostic criteria for MEN1 including the presence of at least two of the major constituent tumors, such as primary hyperparathyroidism, hormone-secreting or non-secreting pancreatic islet tumors, and anterior pituitary neuroendocrine tumors, as outlined in the study by 1. The diagnostic criteria for MEN syndrome are based on the presence of specific endocrine tumors, and the diagnosis is often suspected in patients with tumors in multiple endocrine glands or with a family history of endocrine tumors.
- The diagnostic criteria for MEN1 include:
- Primary hyperparathyroidism (PHPT) and hypercalcemia resulting from parathyroid adenomas
- Hormone-secreting or non-secreting pancreatic islet tumors
- Anterior pituitary neuroendocrine tumors (PitNETs)
- The study by 1 notes that PHPT is the most common presenting feature of MEN1, occurring in 95% of patients, while pancreatic neuroendocrine tumors occur in 40-75% of patients, and PitNETs are identified in 30-55% of patients.
- Genetic testing is crucial for definitive diagnosis, with analysis of the MEN1 gene for MEN1 syndrome and the RET proto-oncogene for MEN2, as discussed in the study by 1.
- The study by 1 highlights the importance of genotype-phenotype correlations in MEN2, with specific RET variants associated with distinct clinical phenotypes and tumor risks.
- The study by 1 emphasizes the need for pre-symptomatic screening of at-risk patients, which has allowed for earlier detection and intervention, with a resultant decrease in mortality and morbidity associated with these tumors.
- The most recent and highest quality study, 1, provides the basis for the diagnostic criteria for MEN1, and highlights the importance of a comprehensive approach to diagnosis and management.
From the Research
Diagnostic Criteria for Multiple Endocrine Neoplasia (MEN) Syndrome
The diagnostic criteria for MEN syndrome are based on the presence of tumors in multiple endocrine glands. According to 2, the diagnosis of MEN 1 is based on the Gubbio Consensus, which includes:
- Primary hyperparathyroidism
- Gut endocrine tumors
- Pituitary tumors The study also mentions that the most valuable screening tests are:
- Ca++
- PP
- CgA
- Prolactin Endoscopic ultrasound is also considered the most specific method for localizing pancreatic endocrine tumors.
Clinical Features and Diagnosis
3 describes the clinical features and diagnosis of gastrinomas associated with MEN-1 syndrome, including:
- High serum gastrin levels
- Clinical features of Zollinger-Ellison syndrome
- Histopathological confirmation of gastrinoma
- Estimation of other gastrointestinal peptides and Chromogranin-A (CgA)
- Conventional imaging methods (CT, MRI) and OCTREOSCAN or EUS for localizing the primary lesion or metastases
Genetic and Clinical Diagnosis
4 highlights the importance of early genetic and clinical diagnosis of MEN1, which can affect all age groups. The study recommends an intensive surveillance approach for both patients with MEN1 and asymptomatic carriers starting at the age of 5 years. However, there is no clear genotype-phenotype correlation, and individual mutation-dependent surveillance is not possible currently.
Case Reports and Literature Review
5 presents a case report of a MEN1 patient with multiple parathyroid adenomas and transient hypercortisolism, while 6 discusses the genetics, clinical heterogeneity, and modifying genes of childhood MEN syndromes. These studies demonstrate the complexity and variability of MEN syndromes, emphasizing the need for individualized diagnosis and treatment approaches. Key points from these studies include:
- HPT with multiple parathyroid adenomas is an indication of MEN1 gene mutation
- Serum cortisol and its circadian rhythm can be abnormal in the presence of hypercalcemia and high PTH
- Modifying genes and unknown mechanisms may influence the clinical manifestations of MEN syndromes
- A change in scientific focus is needed to understand the factors and genetic variants that control cellular functions and disease gene expression.