Regarding MEN 2 syndromes, all of the following are true EXCEPT:

Explanation

## MEN 2 Syndromes: RET-Driven Neoplasia **Key Point:** MEN 2A and MEN 2B are autosomal dominant disorders caused by **activating mutations in the RET proto-oncogene**. Both feature **medullary thyroid carcinoma (MTC)** as the hallmark, but differ in associated tumors. ### Comparison of MEN 2A vs MEN 2B | Feature | MEN 2A | MEN 2B | |---------|--------|--------| | **RET mutation** | Yes (exons 5, 8, 11, 13–16) | Yes (exon 16, codon 918) | | **Medullary thyroid carcinoma** | ~100% (mandatory) | ~100% (mandatory) | | **Pheochromocytoma** | ~50% | ~50% | | **Primary hyperparathyroidism** | ~20–30% | **Absent/Rare** | | **Mucosal neuromas** | Absent | ~100% (present) | | **Marfanoid habitus** | Absent | ~100% (present) | | **Intestinal ganglioneuromatosis** | Absent | ~100% (present) | | **Corneal nerve thickening** | Absent | ~100% (present) | ### Why Primary Hyperparathyroidism is NOT Mandatory in Both **High-Yield:** Primary hyperparathyroidism occurs in **~20–30% of MEN 2A** patients but is **essentially absent in MEN 2B**. Therefore, it is NOT a universal feature of "both MEN 2A and MEN 2B." **Clinical Pearl:** MEN 2B is distinguished by **mucosal and cutaneous manifestations** (neuromas, marfanoid features, intestinal ganglioneuromatosis) rather than endocrine hyperfunction. The absence of hyperparathyroidism in MEN 2B is a key differentiator from MEN 2A. ### MEN 2 Diagnostic Algorithm ```mermaid flowchart TD A[RET mutation positive]:::outcome --> B{Clinical phenotype?}:::decision B -->|MTC + Pheo + HPT| C[MEN 2A]:::outcome B -->|MTC + Pheo + Neuromas + Marfanoid| D[MEN 2B]:::outcome B -->|MTC only| E[Familial MTC]:::outcome C --> F[Screen for HPT in 20-30%]:::action D --> G[HPT screening NOT indicated]:::action ``` **Mnemonic:** **MEN 2A = "A" for Adrenal (pheo) + parathyroid (HPT)**; **MEN 2B = "B" for Bumpy (neuromas) + Bone (marfanoid)**.