Pediatric Multiple Endocrine Neoplasia Treatment & Management

Updated: Oct 11, 2017
  • Author: Alicia Diaz-Thomas, MD, MPH; Chief Editor: Robert P Hoffman, MD  more...
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Treatment

Approach Considerations

Treatments for the various conditions associated with multiple endocrine neoplasia (MEN) include the following:

  • Hypercalcemia - For patients with type 1 MEN who have hypercalcemia, surgery is the treatment of choice, including removal of 3.5 parathyroid glands
  • Gastrinoma - The current treatment consists of PPIs to reduce acid hypersecretion
  • Insulinoma - Surgery is the therapy of choice; unresectable tumors are treated with diazoxide
  • Glucagonoma - Glucagonomas are surgically removed
  • VIPoma - Octreotide controls symptoms (diarrhea) in 80% of patients; however, surgical tumor removal should be attempted
  • Prolactinoma - Prolactinomas are treated with dopamine agonists, such as bromocriptine or cabergoline
  • GH-producing pituitary tumor - These tumors are treated by transsphenoidal surgery; in rare instances, medical therapy with a GH receptor antagonist is recommended

Chemotherapy with streptozocin and dacarbazine may reduce the size of nonoperable neuroendocrine tumors.

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Surgery for Type 1 MEN

Type 1 MEN with hyperparathyroidism

In patients with type 1 MEN who have hyperparathyroidism, surgery is the treatment of choice if any of the following conditions are present:

  • Serum albumin–adjusted serum calcium level that is more than 1 mg/dL of the upper limit of the reference range
  • Kidney stones
  • PTH-induced bone disease with a T score of -2.5
  • 24-Hour urinary calcium excretion of more than 400mg

Type 1 MEN with ZES

In patients with type 1 MEN with ZES who have hypercalcemia, perform parathyroidectomy before abdominal tumor resection. In these patients, parathyroid surgery is indicated even in mild forms of hypercalcemia because serum calcium levels in the reference range are often associated with lower serum gastrin levels and consecutively lower gastric acid secretion (high calcium stimulates gastrin in these patients).

Removal of 3.5-4 parathyroid glands controls hypercalcemia. If 4 glands are removed, immediate autograft of parathyroid tissue into the musculature of the nondominant arm is indicated.

Some authors recommend taking careful operative notes and marking the residual parathyroid tissue with clips, because reoperation in patients with type 1 MEN is likely.

Gastrinoma

The role of surgery in ZES and type 1 MEN remains controversial because cure is only occasionally achieved. Most tumors are multicentric, raising the possibility of recurrence. Surgery may be indicated in patients with positive findings on imaging studies and no distant metastases. Gastrinomas are found in the duodenal wall, in the pancreas, or in lymph nodes.

Local tumor excision is preferred, with larger tumors of the pancreatic body or tail removed by distal pancreatectomy. This approach may reduce the risk of subsequent metastatic disease to the liver.

Resection of liver metastases may be beneficial. Total pancreatectomy is not indicated, because of the deleterious effects of this procedure (eg, pancreatic exocrine insufficiency, diabetes mellitus).

Insulinoma

Insulinomas are large, single tumors that can be enucleated. Resection may result in cure, although insulinomas in type 1 MEN may be multicentric.

Some authors recommend subtotal pancreatectomy (≥80% 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.

VIPoma

In VIPoma, resection of single and multiple tumors is indicated, which may include a pancreatic tail resection.

Carcinoid tumors

Carcinoid tumors are removed surgically; half of the tumors, particularly thymic carcinoids, are locally invasive or metastatic. [4]

Pituitary tumors

Transsphenoidal pituitary surgery is aimed at resection of any pituitary mass, particularly in acromegaly. Patients with incomplete resection remain on treatment with dopamine agonists.

Prolactinoma

Prolactinomas may be large and multicentric. The recurrence rate after surgical removal is high, and medical treatment is now the therapy of choice. Transsphenoidal surgery with external radiation therapy (external beam or gamma knife) is indicated in patients in whom long-term bromocriptine therapy is ineffective.

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Surgery or Type 2 MEN

Total thyroidectomy with radical lymph-node dissection is recommended in patients aged 5 years if a RET germline mutation is identified. All regional lymph nodes must be removed, even if they are not macroscopically suspected. Before any surgery, screening for pheochromocytomas must be performed. For patients with germline mutations in codons 790/791, the age at which total thyroidectomy should be performed is controversial.

Pheochromocytomas require surgical excision under alpha-adrenergic blockade, starting 7-10 days before surgery (target blood pressure is 120/80 mm Hg while seated and a systolic blood pressure of >90 mm Hg while standing/upright).

Pheochromocytomas in patients with type 2 MEN may be bilateral. Explore both adrenal glands during surgery.

Patients with a pheochromocytoma and MTC should receive appropriate preparation with alpha-blocker therapy. Then, the pheochromocytoma should be removed first to avoid life-threatening complications (eg, hypertensive crisis, arrhythmias) caused by the adrenal tumor. Laparoscopic adrenalectomy has now become a routine procedure and is most often the management of choice; however, it results in associated Addisonianlike complications and consequent lifelong dependency on steroids. Adrenal-sparing surgery, a highly successful treatment option in experienced centers, may be another option. [17]

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Inpatient Care

After parathyroid surgery, monitor serum ionized calcium and magnesium levels. Transient hypoparathyroidism frequently develops and requires calcium and vitamin D supplementation. In rare cases, hungry-bone syndrome may ensue, with rapid declines in serum calcium and magnesium levels.

Somatostatin therapy is indicated particularly in patients with acromegaly in whom surgery did not achieve complete tumor removal. Tumor shrinkage can be expected in one third of patients, and normalization of IGF-1 levels can be expected in as many as two thirds.

Pregnancy may ensue with treatment that includes cabergoline or bromocriptine in patients with prolactinoma.

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Outpatient Care

In MTC, measure serum calcitonin levels every 6-12 months after surgery. Elevated serum levels in the neck region indicate recurrence that possibly requires further surgery. However, micrometastases often cannot be visualized by using current imaging techniques.

The resection of one endocrine tumor does not exclude a second tumor, even after an interval of several years. Patients need lifelong surveillance, as do their offspring.

Pheochromocytomas are monitored with blood pressure and plasma free metanephrines as well as 24-hour urinary catecholamines, including fractionated metanephrine measurements, to exclude recurrence.

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Complications

A retrospective single-center study by Kluijfhout et al found that patients younger than 3 years had a longer average length of stay (6.9 days) versus the older patient groups (1.7 and 3.5 days) after prophylactic thyroidectomy for MEN 2. [18]

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