Multiple Endocrine Neoplasia Type 1 (MEN1) Treatment & Management

Updated: Oct 31, 2017
  • Author: Catherine Anastasopoulou, MD, PhD, FACE; Chief Editor: George T Griffing, MD  more...
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Treatment

Approach Considerations

Hyperparathyroidism

Surgery is the definitive treatment for the control of hypercalcemia. Subtotal (3.5 glands) [22] or total parathyroidectomy with forearm autotransplantation is performed with an open bilateral neck exploration. The recommended timing and type of surgery is controversial. Recurrent hypercalcemia is common. Reimplantation after total parathyroidectomy has a high incidence of graft failure and subsequent permanent hypoparathyrodism.

Surgery is fundamental in patients with hypercalcemia due to primary hyperparathyroidism with Zollinger-Ellison syndrome (ZES), since restoring a normal calcium level contributes to reducing gastric acid output and the consequent risk of peptic ulcers. Transcervical thymectomy may need to be performed at the same time, owing to the mortality associated with malignant carcinoid tumors of the thymus. Minimally invasive parathyroidectomy is usually not recommended because multiple glands are typically affected. [1]

Re-operation to cure recurrent and/or persistent primary hyperparathyroidism is often difficult and associated with increased morbidity. Multiple percutaneous parathyroid ethanol ablation (PEA) treatment has been shown to safely and effectively control hyperparathyroidsim with a low rate of hypocalcemia and permanent complications, when performed by an experienced radiologist. [23]

PEA is not a definitive therapy and cannot replace primary surgical therapy. However, it can be considered as an alternative approach who requires re-operation.

Calcimimetics (eg, cinacalcet), a class of calcium-sensing receptor agonists, can be used to reduce parathyroid hormone release by parathyroid cells and to control cell growth. Cinacalcet normalizes serum calcium in 70-80% of patients with primary hyperparathyroidism and can maintain the effect over 5 years. Cinacalcet neither impacts bone mineral density nor lowers biochemical markers of bone turnover. Cinacalcet is not recommended as a first line therapy.

Gastrinoma

Inhibition of acid hypersecretion is achieved with proton pump inhibitors (eg, omeprazole, lansoprazole, pantoprazole). Histamine receptor antagonists (eg, cimetidine, ranitidine, famotidine) may be added.

Nonmetastatic gastrinomas located in the pancreas are rare but can be surgically excised. Removal of tumors larger than 2 cm in diameter reduces the frequency of liver metastasis, which is an important prognostic factor. [1]

Surgical cure of multiple duodenal gastrinomas is difficult and is not associated with a high disease-free state. [24] More extensive gastrointestinal surgery, such as Whipple pancreaticoduodenectomy, can be associated with a higher cure rate at the expense of a higher operative mortality risk. Other novel approaches, such as chemotherapeutic agents or hormonal therapy with somatostatin analogs, can be considered for treatment of disseminated gastrinomas.

Insulinoma

No curative long-term medical treatment exists for insulinomas. Surgical removal of the tumor is the treatment of choice. [25] Unresectable tumors can be treated with diazoxide or octreotide. Chemotherapeutic agents or hepatic artery embolization has been used to treat metastatic disease. [2, 13]

Insulinomas are most often single, large tumors that can be enucleated. Resection may result in cure, although insulinomas in patients with multiple endocrine neoplasia type 1 (MEN1) may be multicentric and small. A problem in these familial cases is that the lesion detected radiologically may not be the one causing hypoglycemia. Insulin measurements in the portal or hepatic veins may be required to localize the source of excess insulin secretion. [25]

Some authors recommend subtotal pancreatectomy (80% or more of the pancreas) in patients with multiple tumors or when the tumor is not localized. Surgical debulking in metastatic disease may reduce hypoglycemia to a certain extent. Intraoperative ultrasonography facilitates tumor identification. Other methods include intraoperative monitoring of plasma glucose and insulin levels.

Glucagonomas

Surgical removal of the tumor is the treatment of choice. Usually, this involves excision of the tail of the pancreas. However, in many cases metastases have already occurred at the time of diagnosis. Somatostatin analogs (lanreotide or octreotide), chemotherapeutic agents, and hepatic artery embolization have also been used. [2, 13]

Vasoactive intestinal polypeptide tumor (VIPoma)

Somatostatin analogs control symptoms in 80% of cases. Nevertheless, surgical cure should be attempted.

Asymptomatic nonfunctioning pancreatic neuroendocrine tumors

A consensus regarding surgical indications has not been established. The goal is to reduce mortality and morbidity associated with metastatic disease while preserving pancreatic tissue. Conflicting expert opinion suggests surgical removal of tumors greater than 1 cm versus 2 cm.

Pituitary tumors

Treatment is similar to non-MEN1–associated pituitary tumors.  Prolactinomas are treated with dopamine agonists (bromocriptine or cabergoline); trans-sphenoidal surgery and radiotherapy are usually reserved for drug-resistant tumors and for macroadenomas that are compressing adjacent structures. 

Somatostatin analogs (octreotide or lanreotide) is used to control growth hormone over-secretion, and is reserved for second line therapy or for patients not eligible for surgery.

Carcinoid tumors

If resectable, surgery is the treatment of choice. For unresectable tumors, treatment with radiotherapy or chemotherapeutic agents can be used. Somatostatin analogs can help with symptoms and may shrink some tumors.

Cutaneous manifestations of MEN1

Management is conservative for lipomas, facial angiofibromas, and collagenomas. Local excision can be performed if desired.

Adrenal tumors

Surgery is indicated for functioning tumors (eg. primary hyperaldosteronism or hypercortisolism), and nonfunctioning tumors with atypical features, size greater than 4 cm, or significant growth over a 6-month interval. [1]

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Consultations

Multiple endocrine neoplasia type 1 (MEN1) involves many organ systems, and significant difficulties in diagnosis and management are associated with each system. Centers with expertise in MEN1 diagnosis and treatment are recommended for patients. Multiple consultations are generally necessary, including evaluation by specialists in endocrinology, gastroenterology, neurosurgery, general surgery, and dermatology.

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