Multiple endocrine neoplasia type 2 medical therapy

Multiple endocrine neoplasia type 2 Microchapters
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Medical Therapy

Medical management of multiple endocrine neoplasia type 2 depends on the type of tumor involved.

Medullary Thyroid Cancer

Pregnancy Management

• Patients should be tested for pheochromocytoma prior to a planned pregnancy. If it is a case of unplanned pregnancy, the patient should be tested for pheochromocytoma as early as possible.

Conventional Therapy

• The treatment of choice for primary MTC, both sporadic or hereditary, is total thyroidectomy with systematic dissection of all lymph nodes of the central compartment. Total thyroidectomy is necessary as MTC is multicentric in 65–90% of patients in MEN 2 and extensive central lymph node dissection has been reported to improve survival and recurrence rates compared to less aggressive procedures. Lymph node dissection of laterocervical compartments is not performed on principle but only when the neck ultrasound suggests the presence of metastatic nodes.
• Endoscopic adrenal-sparing surgery has become the method of choice for the surgical therapy of PHEO. In cases with an asynchronous development of PHEO, the adrenal gland without PHEO can be preserved, but the patient must be aware that the probability to repeat the surgical treatment in the near future is very high. The advantage of a monolateral adrenal surgery is the possibility to avoid substitutive therapy until the second surgery will be performed.
• The parathyroid glands are frequently found to be enlarged at the time of the thyroidectomy for MTC and should, therefore, be carefully evaluated. The goal in MEN 2 patients with PHPT is to excise the enlarged glands and to leave at least one apparently normal parathyroid gland intact. If all glands are enlarged, a subtotal parathyroidectomy or total parathyroidectomy with autotransplantation should be performed. In patients with persistent or recurrent PHPT, the long-term oral administration of calcimimetic drugs as cinacalcet to achieve long-term reductions in serum calcium and PTH concentration should be considered.

Target Therapy for Persistent MTC

• Thirty percent of MTC patients, especially in MEN 2B and 2A, are not cured by surgery. They remain affected and can develop, if not already present at the time of the diagnosis, distant metastasis in the lungs, liver, bone and, more rarely, brain. Several studies demonstrated that conventional therapies, such as chemotherapy and radiotherapy, did not determine any clinical benefit. Until few years ago, patients with advanced and progressive MTC were “orphan” of drugs. Recently, developed molecular therapeutics that target the RETpathway have shown very promising activity in clinical trials of patients with advanced MTC. In the majority of cases, the drug is a multityrosine kinase inhibitor (TKI) with the ability to block not only retbutalsoone or more of the vascular endothelial growth factor receptors (VEGF-R) as well as C-MET and/or C-KIT or FLT3 and/or other kinases. Vandetanib has been recently approved both by FDA (Food and Drug Administration) and EMA (European Medical Agency) for the treatment of advanced and progressive MTC. Other TKIs, such as sorafenib, sunitinib, motesanib, lenvatinib, AND cabozantinib, are still under investigation either in official phase II/III clinical trials or in “off-label” studies [99]. Although very promising, further studies and longer followup are needed to better evaluate the clinical benefits in terms of progression-free survival and overall survival as compared to the discomfort determined by the side effects which is not negligible. Among several, the most severe and intolerable side effects are anorexia, weight loss, and fatigue, which are difficult to be controlled. Others, such as hypertension or skin lesions can be managed with standard care procedures.
• Vandetanib has been recommended for the treatment of advanced metastatic medullary thyroid cancer.

Radiation Therapy

• External beam radiation therapy
• Intensity modulated radiation therapy

Contraindicated Medications

• Dopamine D2 receptor antagonists
• Beta adrenergic receptor antagonists