eMedicine Specialties > Endocrinology > Multiple Endocrine Disease and Miscellaneous Endocrine Disease
Wermer Syndrome (MEN Type 1): Treatment & Medication
Updated: May 14, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Hyperparathyroidism: Surgery is the treatment of choice. In patients who cannot undergo surgery, bisphosphonates may be useful. Calcium-sensing receptor agonists (calcimimetics), a novel class of drugs, have a potential role in the management of hyperparathyroidism associated with MEN 1 by directly reducing PTH release.8
- Gastrinoma: Inhibition of acid hypersecretion is achieved with proton pump inhibitors. Metastatic gastrinoma may be treated with streptozocin and doxorubicin. Octreotide might decrease tumor progression; however, benefit is controversial.
- Insulinoma: No curative long-term medical treatment exists for insulinomas. Surgical tumor removal is the treatment of choice.9 Treat unresectable tumors with diazoxide. Long-acting somatostatin analogs can be useful in controlling hyperinsulinemia.
- Glucagonomas: Surgical extirpation is indicated.
- Vasoactive intestinal polypeptide tumor (VIPoma): Octreotide controls symptoms in 80% of cases, although surgical tumor removal should be attempted.
- Prolactinomas: These are best treated with bromocriptine or other dopamine agonists.
- Patients with symptomatic carcinoid tumors require somatostatin.
Surgical Care
- In general, surgery is indicated to control symptoms that are medically intractable and to prevent metastases of enteropancreatic neoplasms.10
- Surgery is the treatment of choice for hyperparathyroidism in patients with MEN 1, if the following occur:
- Serum albumin-adjusted calcium level is higher than 3 mmol/L (12 mg/dL).
- Kidney stones are found.
- PTH-induced bone disease, including osteoporosis, is present.
- In patients with ZES/MEN 1, parathyroid surgery is favored by some even in milder forms of hypercalcemia because normal serum calcium levels are often associated with lower serum gastrin levels and, consequently, lower gastric acid secretion. However, recently, due to effective pharmacotherapy for ZES, it is not considered to be a significant indication for surgery.
- For parathyroid hyperplasia, the 2 recommended surgical approaches are subtotal parathyroidectomy11 (with removal of 3.5 parathyroid glands) and total parathyroidectomy (with removal of all 4 glands) and immediate autograft of parathyroid tissue into the musculature of the nondominant arm. The current approach seems to be shifting back to removal of 3.5 glands. Hypocalcemia is more frequent with total parathyroidectomy.
- Surgeons should make careful operative notes and mark the residual parathyroid tissue with clips because reoperation is likely in patients with MEN 1. Recurrence is reported in 43% of patients at 10 years of follow-up.
- At the time of parathyroidectomy, thymus might be removed to prevent carcinoid tumor.
- With gastrinoma, the role of surgery in ZES and MEN 1 remains controversial because cure is achieved only occasionally.
- 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. Removal of tumors larger than 2 cm in diameter reduces frequency of liver metastasis, which is an important prognostic factor.
- Gastrinomas are found in the duodenal wall, the pancreas, or the 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. Surgery may also provide symptomatic relief in patients with large, locally metastatic tumors.
- Resection of liver metastases may be beneficial.
- Total pancreatectomy is not indicated because of the deleterious effects of this procedure (ie, pancreatic exocrine insufficiency and diabetes mellitus).
- Insulinomas are most often single large tumors that can be enucleated. Resection may result in cure, although insulinomas in patients with MEN 1 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 insulin secretion.9
- 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 are similar to insulinomas, and resection of single glucagonomas most often results in cure.
- For VIPomas, resection of single and multiple tumors is indicated, which may include a pancreatic tail resection.
- In pituitary tumors, transsphenoidal pituitary surgery is aimed at resection of any pituitary mass, especially in acromegaly, Cushing, or nonfunctional tumors.
- Prolactinomas may be large and multicentric. Patients with prolactinomas should continue treatment with dopamine agonists.
- The recurrence rate after surgical removal is high.
- Transsphenoidal surgery with external radiation therapy (eg, external beam or gamma knife) is indicated in patients in whom long-term dopamine agonist therapy becomes ineffective.
- Carcinoid tumors are removed surgically; half of them are locally invasive or metastatic, particularly thymic carcinoids.3
- For lipomas, local excision is the therapy of choice if troublesome symptoms are present.
- For nonfunctioning pancreatic tumors, surgery might be considered for tumors larger than 2 cm, as tumor size correlates with risk of metastasis and death.
Consultations
This is a process that involves many organ systems, and significant difficulties in diagnosis and management are associated with each system. Multiple consultations are generally necessary, including consultations with an endocrinologist, gastroenterologist, neurosurgeon, general surgeon, and dermatologist.
- Endocrinologist - Evaluation and treatment of insulinoma, glucagonoma, hyperparathyroidism, Cushing syndrome, and acromegaly
- Dermatologist - Evaluation of rash for specific patterns
- Gastroenterologist - Evaluation and treatment of gastrinoma, VIPoma, PPoma, and carcinoid tumor
- Neurosurgeon - Possible resection of growth hormone–producing macroadenoma; prolactin-producing microadenoma most often can be treated pharmacologically
Medication
Because various syndromes may be expressed in patients with MEN 1, several medications may be indicated.
Somatostatin analogues
These drugs suppress peptide secretion of gastroenteropancreatic tumors or treatment of acromegaly. They have also been reported to relieve pain from spinal metastasis.
Octreotide (Sandostatin)
Acts primarily on somatostatin receptor subtypes II and V. Inhibits GH secretion and has multitude of other endocrine and nonendocrine effects, including inhibition of glucagon, VIP, and GI peptides.
Adult
50 mcg/d SC q12h; dose increase to 200-300 mcg/d is possible based on patient's tolerability and response; long-acting (Sandostatin LR) form also available
Pediatric
Not established
May reduce effects of cyclosporine; patients taking insulin, oral hypoglycemics, beta-blockers, and calcium channel blockers may need dosage adjustments
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adverse effects primarily are related to altered GI motility and include nausea, abdominal pain, diarrhea, and increased incidence of gallstones and biliary sludge; because of alteration in counter-regulatory hormones (eg, insulin, glucagon, GH), hypoglycemia or hyperglycemia may be observed; bradycardia, cardiac conduction abnormalities, and arrhythmias have been reported; due to inhibition of TSH secretion, hypothyroidism also may occur; caution in patients with renal impairment; cholelithiasis may occur
Proton pump inhibitors
Proton pump inhibitors inhibit gastric acid secretion by inhibition of the H+/K+ -ATP-ase enzyme system in the gastric parietal cells. Esomeprazole (Nexium), omeprazole (Prilosec), pantoprazole (Protonix), rabeprazole (Aciphex), and lansoprazole (Prevacid) are available.
Omeprazole (Prilosec)
Proton pump inhibitors effectively block the H+, K+ -ATPase of the parietal cell at the secretory surface and inhibit acid secretion, which is required in MEN 1 associated with gastrinoma. The goal is to reduce the basal acid output to <10 mEq/h 1 h prior to the next dose in patients without previous acid-reducing gastric surgery and to <5 mEq/h in patients with previous acid-reducing gastric surgery.
Adult
20-60 mg PO qd, titrate prn; doses as high as 360 mg/d have been administered (>80 mg/d in divided doses)
Pediatric
Not established
May decrease effects of itraconazole and ketoconazole; may increase toxicity of warfarin, digoxin, and phenytoin; theoretically possible that omeprazole interferes with absorption of drugs where gastric acid pH is an important determinant of their bioavailability (eg, ampicillin esters)
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
GI distress may occur; bioavailability may increase in elderly patients; ECL cell tumors in the stomach have been observed only in rats treated with omeprazole but not in humans with ZES; long-term data are not available
Esomeprazole (Nexium)
S-isomer of omeprazole. Inhibits gastric acid secretion by inhibiting H+/K+ ATPase enzyme system at secretory surface of gastric parietal cells.
Adult
20-40 mg PO qd for 4-8 wk
Pediatric
Not established
None reported
Documented hypersensitivity
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
Symptomatic relief with proton pump inhibitors may mask symptoms of gastric malignancy
Dopamine agonists
Dopamine agonists are the treatment of choice in prolactinoma. In acromegaly, they are usually added to somatostatin analogues if complete remission has not been achieved. They have modest effects if used as a single agent for acromegaly. Bromocriptine (Parlodel) and cabergoline (Dostinex) are available.
Bromocriptine (Parlodel)
Dopamine agonist reduces pituitary production of prolactin and may shrink prolactinoma. May be alternative for treatment of acromegaly, but adverse effects at high dose may limit applicability.
Adult
Prolactinomas: 1.25 mg/d initially; increase slowly by 1.25 mg/d PO q5-7d; maintenance dose is 5-7.5 mg/d
Acromegaly: 1.25 mg PO hs initially for 3-5 d; increase slowly by 1.25 mg/d PO q5-7d; maintenance dose is 20-30 mg/d PO; not to exceed 100 mg/d PO
Pediatric
Not established
Toxicity may increase with ergot alkaloids; amitriptyline, butyrophenones, imipramine, methyldopa, phenothiazines, and reserpine may decrease effects
Documented hypersensitivity; uncontrolled hypertension, toxemia, ischemic heart disease, peripheral vascular disorders
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
Caution in liver or renal disease, myocardial infarct, arrhythmia, or psychiatric disorder
Antihypoglycemic agents
These agents increase blood glucose by inhibiting pancreatic insulin release and possibly through an extrapancreatic effect.
Diazoxide (Hyperstat, Proglycem)
Inhibitory effect of diazoxide in insulinoma may be effective in 90% of patients, the remaining 10% may not respond or tolerate drug. Treat adverse effects with hydrochlorothiazide. Hyperglycemic effect starts within 1 h and usually lasts a maximum of 8 h with normal renal function. In patients not responsive to diazoxide, somatostatin may be indicated.
Adult
3-8 mg/kg/d IV divided bid/tid q8-12h
Refractory hypoglycemia may require higher dose
Pediatric
Newborns and infants: 8-15 mg/kg/d IV divided bid/tid q8-12h
Children: Administer as in adults
May decrease serum hydantoins, possibly resulting in decreased anticonvulsant effects; thiazide diuretics may potentiate hyperuricemic and antihypertensive effects of diazoxide
Documented hypersensitivity, aortic coarctation, pheochromocytoma, arteriovenous shunts, aortic aneurysm, 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
Patients with diabetes mellitus may require treatment for hyperglycemia; when administered prior to delivery, may produce fetal or neonatal hyperbilirubinemia, thrombocytopenia, altered carbohydrate metabolism, and other adverse reactions; may precipitate CHF
Ergot Alkaloid And Derivative
Dopaminergic activity of some of these agents may reduce prolactin secretion.
Cabergoline (Dostinex)
Long-acting dopamine receptor agonist with high affinity for D2 receptors. Low affinity for D1 receptors. Inhibits prolactin secretion. Prolactin secretion by anterior pituitary predominates under hypothalamic inhibitory control exerted through dopamine.
Adult
0.25 mg PO twice weekly initially; dose may be increased (no more rapidly than q4wk) by 0.25 mg twice weekly to maximum of 1 mg twice weekly according to patient's serum prolactin level
Pediatric
Not established
May increase effects of antihypertensive medications (adjust dose accordingly); dopamine agonists may reduce effects of cabergoline
Use of serotonin agonists or sibutramine with cabergoline may increase risk of serotonin syndrome
Antipsychotics and metoclopramide may diminish effects of cabergoline
Documented hypersensitivity to cabergoline, protease inhibitors, azole antifungals, and some macrolide antibiotics; uncontrolled hypertension
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May cause headache, dizziness, nausea, hypotension, syncope
More on Wermer Syndrome (MEN Type 1) |
| Overview: Wermer Syndrome (MEN Type 1) |
| Differential Diagnoses & Workup: Wermer Syndrome (MEN Type 1) |
 Treatment & Medication: Wermer Syndrome (MEN Type 1) |
| Follow-up: Wermer Syndrome (MEN Type 1) |
| Multimedia: Wermer Syndrome (MEN Type 1) |
| References |
| Further Reading |
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Further Reading
Related eMedicine topics:
Gastrinoma
Glucagonoma
Hyperparathyroidism [Emergency Medicine]
Hyperparathyroidism [Endocrinology]
Hyperparathyroidism [Otolaryngology and Facial Plastic Surgery]
Hyperparathyroidism [Pediatrics: General Medicine]
Hyperparathyroidism, Primary
Insulinoma
Multiple Endocrine Neoplasia
Multiple Endocrine Neoplasia Type 1
Multiple Endocrine Neoplasia, Type 2
Neoplasms of the Endocrine Pancreas
Pancreas, Islet Cell Tumors
Prolactinoma
Zollinger-Ellison Syndrome [Gastroenterology]
Zollinger-Ellison Syndrome [Pediatrics: General Medicine]
Zollinger-Ellison Syndrome [Radiology]
Clinical guidelines:
Intraoperative parathyroid hormone. Laboratory medicine practice guidelines: evidence-based practice for point-of-care testing. National Academy of Clinical Biochemistry - Professional Association. 2006. 15 pages. NGC:005645
Procedure guideline for parathyroid scintigraphy. Society of Nuclear Medicine, Inc - Medical Specialty Society. 1999 Feb (revised 2004 Jun). 6 pages. NGC:004256
Clinical studies:
Studies of Inherited Diseases of Metabolism
Treatment of Zollinger-Ellison Syndrome With Prevacid
Keywords
multiple endocrine neoplasia type 1, MEN 1, parathyroid, hyperparathyroidism, pituitary tumor, MEN 1 syndrome, MEN 2 syndrome, MEN 2a, MEN 2b, prolactinoma, insulinoma, pituitary tumors, pancreatic tumor, pancreatic tumors, endocrine disorder, endocrine disease, endocrine diseases, glucagonoma, islet cell tumor, pluriglandular syndrome, multiple endocrine adenopathy, MEA, Wermer's syndrome, parathyroid tumor, pancreatic islet cell tumor, pituitary hyperplasia, pituitary tumor formation, pancreas tumor, pancreatic polypeptide tumors, PPomas, gastrinomas, VIPoma, vasoactive intestinal polypeptide tumor, Zollinger-Ellison syndrome, ZES, Cushing syndrome, Cushing’s syndrome, Sipple syndrome
