Objective: To determine the clinical features, natural history, and role of surgery for gastrointestinal manifestations of the multiple endocrine neoplasia type 2 (MEN 2) syndromes.
Summary background data: The MEN 2 syndromes are characterized by medullary thyroid carcinoma and other endocrinopathies. In addition, some patients with MEN 2A develop Hirschsprung's disease (HD), and all patients with MEN 2B have intestinal neuromas and megacolon that can cause significant gastrointestinal problems.
Methods: From 83 families with MEN 2A, eight patients with HD were identified (MEN 2A-HD). These and all patients with MEN 2B followed at the authors' institution (n = 53) were sent questionnaires to describe the onset and type of gastrointestinal symptoms and treatment they had before the diagnosis of MEN 2. Records of all patients responding were reviewed, including radiographic imaging, histology, surgical records, and genetic testing.
Results: Thirty-six of the 61 patients (59%) responded (MEN 2A = 8, MEN 2B = 28) to the questionnaires. All patients with MEN 2A-HD were operated on for HD 2 to 63 years before being diagnosed with MEN 2. All patients responding were underweight as infants and had symptoms of abdominal pain, distention, and constipation. Eighty-eight percent had hematochezia, 63% had emesis, and 33% had intermittent diarrhea before surgery. All patients with MEN 2A-HD had rectal biopsies with a diverting colostomy as the initial surgical procedure. This was followed by a colostomy takedown and pull-through procedure at a later interval. Ninety-three percent of patients with MEN 2B had gastrointestinal symptoms 1 to 24 years before the diagnosis of MEN 2. Symptoms included flatulence (86%), abdominal distention or being underweight as a child (64%), abdominal pain (54%), constipation or diarrhea (43%), difficulty swallowing (39%), and vomiting (14%). Seventy-one percent of patients with MEN-2B with gastrointestinal symptoms had radiographic imaging, 32% were admitted to the hospital, and 29% underwent surgery.
Conclusions: Patients with MEN 2A-HD had a typical HD presentation and always required surgery. Patients with MEN 2B have significant gastrointestinal symptoms, but less than a third had surgical intervention. Understanding the clinical course and differences in these patients will improve clinical management.