What is the treatment approach for multiple endocrine neoplasia (MEN)?

Treatment Approach for Multiple Endocrine Neoplasia (MEN)

The treatment of multiple endocrine neoplasia requires a multidisciplinary approach at specialized centers, with interventions tailored to the specific MEN subtype and guided by genetic testing to prevent morbidity and mortality through early detection and prophylactic management of associated tumors. 1

General Treatment Principles

• Treatment should be provided by multidisciplinary teams at specialized referral centers with expertise in MEN syndromes, including endocrinologists, surgeons, radiologists, nuclear medicine specialists, histopathologists, and clinical nurse specialists 1
• Genetic testing should be performed early to confirm diagnosis and guide management, with subsequent screening of family members due to the 50% risk of inheritance 1, 2
• The primary aim of treatment is curative when possible, with a focus on maintaining disease-free status and quality of life for as long as possible 1
• Treatment decisions should be based on the extent of disease, histological grade, secretory profile, and specific MEN subtype 1, 2

MEN Type 1 (MEN1) Management

Primary Hyperparathyroidism (PHPT)

• Surgical intervention is the mainstay of treatment for PHPT in MEN1 3
• Subtotal parathyroidectomy (removal of 3.5 glands) or total parathyroidectomy with autotransplantation is recommended due to the multigland involvement and high recurrence risk 4, 5
• Preoperative localization includes ultrasound and/or 99mTc-sestamibi scintigraphy with SPECT/CT 1

Pancreatic Neuroendocrine Tumors (pNETs)

• Regular surveillance should begin at age 5 with biochemical screening and imaging starting at age 15 1
• Surgical approach depends on tumor size, functionality, and location:
  • Small tumors (<3 cm): Surveillance may be appropriate 1
  • Larger tumors (>3 cm): Surgical intervention is indicated 1
  • Selective tumor enucleation is not recommended; instead, procedures like distal pancreatectomy with lymphadenectomy should be considered 3, 4
• For non-resectable disease, options include somatostatin analogs, targeted radionuclide therapy, locoregional treatments, and chemotherapy 1

Pituitary Tumors

• Management includes watchful waiting and medical therapy more often than in other MEN1 manifestations 3
• Treatment is similar to sporadic pituitary tumors but with awareness of potential multiple or more aggressive tumors 2

MEN Type 2 (MEN2) Management

Medullary Thyroid Carcinoma (MTC)

• Prophylactic thyroidectomy is the cornerstone of MEN2 management, with timing based on specific RET mutation 1
  • High-risk mutations (codons 883,918,922): Thyroidectomy during the first year of life 1
  • Intermediate-risk mutations (codons 609,611,620,630,634,804,891): Thyroidectomy before age 6 1
  • Lower-risk mutations (codons 768,790,791): Thyroidectomy after abnormal C-cell stimulation test 1
• Surgery should be performed by experienced surgeons to minimize complications 1

Pheochromocytoma

• Preoperative screening is essential before any surgical intervention in MEN2 patients 1
• Adrenalectomy is the treatment of choice when pheochromocytoma is detected 2

MEN Type 4 (MEN4) Management

• Limited data exists due to the rarity of this condition 1
• Treatment focuses on PHPT (present in 100% of cases) and pituitary neuroendocrine tumors 1
• No specific surveillance guidelines have been established, but clinical monitoring should begin by age 30 1

Surveillance and Follow-up

• A "virtual outpatient department" approach is recommended to coordinate multiple specialist appointments on the same day 1
• Regular biochemical and imaging surveillance should follow established protocols based on MEN subtype 1
• For MEN1:
  • Biochemical screening from age 5
  • Imaging studies from age 15
  • Biannual evaluations 1
• For MEN2:
  • Annual calcitonin measurements post-thyroidectomy
  • Regular screening for pheochromocytoma 1

Special Considerations

• Surgical cure rates are significantly higher for presymptomatic patients (89%) compared to symptomatic patients (25%), emphasizing the importance of early detection 1
• External beam radiotherapy may be beneficial for bone metastases 1
• Chemotherapy is indicated for inoperable or metastatic pancreatic NETs and poorly differentiated NETs 1
• Targeted therapies like sunitinib or everolimus may be considered for progressive disease 1

Common Pitfalls to Avoid

• Treating MEN-related tumors as if they were sporadic counterparts can lead to suboptimal outcomes 3, 2
• Delaying prophylactic surgery in MEN2 increases the risk of incurable metastatic disease 1
• Performing selective tumor enucleation for MEN1-related pNETs is inadequate 3
• Failing to coordinate care among multiple specialists can lead to fragmented treatment and patient burden 1
• Underestimating the importance of lifelong surveillance due to the risk of metachronous tumors 5