Approach Considerations
Hyperparathyroidism
Surgery is the definitive treatment for the control of hypercalcemia. Subtotal (3.5 glands) [27] 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. [28]
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. [29]
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. [30] 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. [31, 32] 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. [33] Unresectable tumors can be treated with diazoxide or octreotide. Chemotherapeutic agents or hepatic artery embolization has been used to treat metastatic disease. [3, 15]
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. [33]
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. [34]
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. [3, 15]
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]
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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Multiple endocrine neoplasia type 1 (MEN1). Sagittal (left image) and coronal (right image), T1-weighted magnetic resonance images of the brain in a patient with MEN1 show a pituitary macroadenoma (arrows).
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Multiple endocrine neoplasia type 1 (MEN1). Indium-111 (111In) octreotide scan in a patient with MEN1 demonstrates abnormal activity in the pituitary macroadenoma (curved arrow), parathyroid adenoma (straight arrow), and gastrinoma metastases throughout the abdomen (arrowheads).
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Multiple endocrine neoplasia type 1 (MEN1). Technetium-99m sestamibi scan (99mTc MIBI) in a patient with MEN1 demonstrates persistent abnormal activity of the inferior right parathyroid gland that is consistent with an adenoma.
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Multiple endocrine neoplasia type 1 (MEN1). Computed tomography (CT) scan of the pancreas in a patient with MEN1 and a gastrinoma shows a pancreatic head mass (large, white arrow), as well as a low-attenuating lesion in the liver (small, black arrowhead) that indicates metastases. Note the calcifications of the right renal medullary pyramids (medullary nephrocalcinosis; black arrows) in this nonenhanced CT scan.
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Multiple endocrine neoplasia type 1 (MEN1). Endoscopic ultrasonogram in a patient with an insulinoma. The hypoechoic neoplasm (arrows) is seen in the body of the pancreas anterior to the splenic vein (SV). (From: Rosch T, Lightdale CJ, Botet JF, et al. Localization of pancreatic endocrine tumors by endoscopic ultrasonography. N Engl J Med. Jun 25 1992;326(26):1721-6.)
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Multiple endocrine neoplasia type 1 (MEN1). Computed tomography (CT) scan image with oral and intravenous contrast in a patient with biochemical evidence of insulinoma. The 3-cm contrast-enhancing neoplasm (arrow) is seen in the tail of the pancreas (P) posterior to the stomach (S) (From: Yeo CJ. Islet cell tumors of the pancreas. In: Niederhuber JE, ed. Current Therapy in Oncology. St. Louis, Mo: Mosby-Year Book; 1993: 272.)
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Multiple endocrine neoplasia type 1 (MEN1). Anteroposterior radiographic view of the right hand in a patient with MEN1 and primary hyperparathyroidism shows subperiosteal bone resorption along the radial aspects of the middle phalanges (arrows).
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Multiple endocrine neoplasia type 1 (MEN1). Bilateral, anteroposterior radiographic views of the hands in a patient with MEN1 and primary hyperparathyroidism show subperiosteal bone resorption along the radial aspects of the middle phalanges.
Tables
Tumor |
Age at which to begin screening (yr) |
Blood tests (annual) |
Imaging studies |
Insulinoma |
5 |
Fasting glucose, insulin |
– |
Anterior pituitary |
5 |
Prolactin, IGF-I |
MRI (every 3 yr) |
Parathyroid |
8 |
Calcium, PTH |
– |
Other pancreatic neuroendocrine tumors |
< 10 |
Chromogranin-A; pancreatic polypeptide, glucagon, VIP |
MRI, CT, or EUS (annually) |
Adrenal |
< 10 |
Only in patients with symptoms or signs of a functioning tumor and/or tumor >1 cm identified on an imaging study |
MRI or CT (annually with pancreatic imaging) |
Thymic and bronchial carcinoid |
15 |
None |
CT or MRI (every 1-2 yr) |
Gastrinoma |
20 |
Gastrin (± gastric pH) |
– |
CT = computed tomography; EUS = endoscopic ultrasound; IGF-1 = Insulin-like growth factor 1; ( MRI = magnetic resonance imaging; PTH = parathyroid hormone; VIP = vasoactive intestinal peptide Adapted from Thakker RV, et al. Clinical Practice Guidelines for Multiple Endocrine Neoplasia Type 1 (MEN1). J Clin Endocrinol Metab. 2012 Sep. 97(9):2990-3011. [1] |
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