eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Multiple Endocrine Neoplasia: Treatment & Medication

Author: Robert J Ferry Jr, MD, Chief, Division of Pediatric Endocrinology and Diabetes, Le Bonheur Children's Medical Center, University of Tennessee Health Science Center at Memphis and St Jude Children's Research Hospital; Lieutenant Colonel (Medical Corps), 162nd Area Support Medical Company, Army National Guard
Coauthor(s): Klaus Radebold, MD, PhD, Research Associate, Department of Surgery, Yale University School of Medicine; Christian A Koch, MD, PhD, FACP, FACE, Professor and Director, Division of Endocrinology, University of Mississippi Medical Center; George P Chrousos, MD, FAAP, MACP, MACE, Professor and Chair, Department of Pediatrics, Athens University Medical School
Contributor Information and Disclosures

Updated: Jun 12, 2008

Treatment

Medical Care

  • Hypercalcemia: For patients with type 1 multiple endocrine neoplasia (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.

Surgical Care

  • Type 1 multiple endocrine neoplasia with hyperparathyroidism: In patients with type 1 multiple endocrine neoplasia (MEN) who have hyperparathyroidism, surgery is the treatment of choice if any of the following conditions are present:
    • Serum albumin–adjusted serum calcium level 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 400 mg
  • Type 1 multiple endocrine neoplasia with ZES
    • In patients with type 1 MEN with ZES, 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 those 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 single large 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 tumors are locally invasive or metastatic, particularly thymic carcinoids.
  • 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. 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.
  • Type 2 multiple endocrine neoplasia
    • 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 those patients with germline mutations in codons 790/791, the age 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 systolic blood pressure is >90 mm Hg while standing/upright).

Medication

Medical therapy is directed toward the specific endocrine syndromes.

Somatostatin analogs

Sandostatin acts similarly to the natural hormone somatostatin by suppressing peptide secretion from gastroenteropancreatic tumors.


Octreotide acetate (Sandostatin)

Primarily acts on somatostatin receptor subtypes II and V. Inhibits GH secretion, and other endocrine and nonendocrine effects, including inhibition of glucagon, VIP, and GI peptides. Controls diarrhea in 80% of patients. Progressive increases in dosage may be necessary.

Adult

50 mcg SC q12h initially; may increase dose to 200-300 μ g/d, based on tolerability and response

Pediatric

200-300 μ g/d SC divided bid/qid during initial 2 wk; individual dosage adjustment prn to control symptoms

Associated with altered nutrient absorption; consider effect on PO drug absorption; may reduce effects of cyclosporine; patients taking insulin, PO hypoglycemics, beta-blockers, and calcium channel blockers may require dosage adjustments

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adverse effects are primarily related to altered GI motility, including nausea, abdominal pain, diarrhea, and increased incidence of gallstones and biliary sludge; because of alteration in counterregulatory hormones (eg, insulin, glucagon, GH), hypoglycemia or hyperglycemia may be observed; bradycardia, cardiac conduction abnormalities, and arrhythmias have been reported; because of inhibition of thyroid-stimulating hormone (TSH) secretion, hypothyroidism may also occur; exercise caution in patients with renal impairment; cholelithiasis may occur; possibility of GH suppression requires monitoring of children's growth

Gastric acid inhibitors

Gastric acid secretion with PPIs is mandatory to prevent complications of gastric acid hypersecretion. PPIs are safe and cause no adverse effects even after long-term use. The goal is to reduce the basal acid output to levels less than 10 mEq/h 1 hour before the next dose in patients without previous acid-reducing gastric surgery and to kess than 5 mEq/h in patients with previous acid-reducing gastric surgery.


Omeprazole (Prilosec)

Substituted benzimidazole that suppresses acid secretion by specifically inhibiting the H+/K+ ATPase at the secretory surface of parietal cell.

Adult

20-60 mg/d PO initially; if >80 mg/d, administer in divided doses

Pediatric

Not established
Suggested dosing: Administer as in adults; dose must be adjusted to the individual BAO

Prolongs elimination of diazepam, warfarin, and phenytoin; theoretically interferes with absorption of drugs for which gastric pH important determinant of bioavailability (eg, ampicillin esters); may decrease effects of itraconazole or ketoconazole

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

ECL cell tumors in stomach observed in rats; long-term data not available; headache, diarrhea, and abdominal pain may occur

Hyperglycemic agents

These agents inhibit insulin release from the tumor.


Diazoxide (Proglycem)

Binds sulfonylurea receptor (SUR1) of the pancreatic beta cell, inhibiting insulin secretion. PO form opens K ATP channels and inhibits insulin secretion. Increases blood glucose level within 1 h by inhibiting insulin release from insulinoma. Unlike rapid IV administration, PO not antihypertensive.

Adult

3-8 mg/kg/d PO divided tid q8h

Pediatric

5-15 mg/kg/d PO divided tid q8h

May decrease serum hydantoin levels, possibly decreasing anticonvulsant effects; thiazide diuretics may potentiate hyperuricemic and hypoglycemic effects

Documented hypersensitivity; functional hypoglycemia

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Start only under close clinical supervision; prolonged treatment requires regular monitoring of urine for sugar and ketones; blood sugar levels should be monitored for dose adjustments; plasma half-life prolonged in impaired renal function; lanugo-type thick hair growth occurs in children in frontotemporal areas, extremities, and back; may cause sodium retention with edema

More on Multiple Endocrine Neoplasia

Overview: Multiple Endocrine Neoplasia
Differential Diagnoses & Workup: Multiple Endocrine Neoplasia
Treatment & Medication: Multiple Endocrine Neoplasia
Follow-up: Multiple Endocrine Neoplasia
References
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Further Reading

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Keywords

multiple endocrine neoplasia, MEN syndrome, MEN 1, MEN 2A, MEN 2B, Wermer syndrome, Wermer's syndrome, Sipple syndrome, Sipple's syndrome, multiple endocrine adenopathy, MEA, pluriglandular syndrome, Carney complex, vasoactive intestinal peptide tumor, VIPoma, pancreatic polypeptide–producing tumor, PPoma, medullary thyroid carcinoma, MTC, gastrinoma, insulinoma, glucagonoma, prolactinoma, somatotropinoma, corticotropinoma, nonfunctioning tumors, lipomas, angiofibromas, pheochromocytoma, hyperparathyroidism, parathyroid gland hyperplasia, thyroid cancer, mucosal neuroma, medullated corneal nerve fibers, marfanoid habitus, peptic ulcer disease, coronary heart disease, hypercalcemia, stroke, heart failure, Zollinger-Ellison syndrome, ZES, Hirschsprung disease

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Contributor Information and Disclosures

Author

Robert J Ferry Jr, MD, Chief, Division of Pediatric Endocrinology and Diabetes, Le Bonheur Children's Medical Center, University of Tennessee Health Science Center at Memphis and St Jude Children's Research Hospital; Lieutenant Colonel (Medical Corps), 162nd Area Support Medical Company, Army National Guard
Robert J Ferry Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society
Disclosure: Nutropin Speakers Bureau Honoraria Speaking and teaching

Coauthor(s)

Klaus Radebold, MD, PhD, Research Associate, Department of Surgery, Yale University School of Medicine
Klaus Radebold, MD, PhD is a member of the following medical societies: American Gastroenterological Association and New York Academy of Sciences
Disclosure: Nothing to disclose.

Christian A Koch, MD, PhD, FACP, FACE, Professor and Director, Division of Endocrinology, University of Mississippi Medical Center
Christian A Koch, MD, PhD, FACP, FACE is a member of the following medical societies: American Academy of Neurology, American Association of Clinical Endocrinologists, American College of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Society for Clinical Pharmacology and Therapeutics, American Society for Dermatologic Surgery, Endocrine Society, and German Diabetes Society
Disclosure: Nothing to disclose.

George P Chrousos, MD, FAAP, MACP, MACE, Professor and Chair, Department of Pediatrics, Athens University Medical School
George P Chrousos, MD, FAAP, MACP, MACE is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Arlan L Rosenbloom, MD, Adjunct Distinguished Service Professor Emeritus of Pediatrics, University of Florida; Fellow of the American Academy of Pediatrics; Fellow of the American College of Epidemiology
Arlan L Rosenbloom, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Epidemiology, American Pediatric Society, Endocrine Society, Florida Pediatric Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Lynne Lipton Levitsky, MD, Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor, Department of Pediatrics, Harvard University Medical School
Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD, Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas and Arkansas Children's Hospital
Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research
Disclosure: Genentech, Inc. Honoraria Speaking and teaching; Pfiser, Inc. Honoraria Consulting

 
 
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