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Type 2 Multiple Endocrine Neoplasia Medication

  • Author: Melanie L Richards, MD; Chief Editor: George T Griffing, MD  more...
Updated: Dec 11, 2015

Medication Summary

Patients require hormone replacement following total thyroidectomy and bilateral adrenalectomy or when they have postoperative hypoparathyroidism. In addition, patients who develop postoperative hypoparathyroidism need supplemental calcium and/or vitamin D.

The corticosteroid cortisone and the mineralocorticoid fludrocortisone acetate can be used in combination in patients suffering from adrenocortical insufficiency.

Preoperatively, prepare patients with pheochromocytomas by treating them with an alpha-blocker or a tyrosine hydroxylase inhibitor, such as metyrosine, for 1-2 weeks, after which administration of a beta-blocker can be considered. Many practitioners routinely treat patients with a beta-blocker, while others selectively treat patients based on blood pressure control and tachycardia.

Patients presenting with severe hypercalcemia should first be hydrated, after which they should be treated with furosemide. If they remain severely hypercalcemic, consider treatment with calcitonin, glucocorticoids, or bisphosphonates (such as pamidronate). These patients need urgent parathyroidectomy when calcium levels have been lowered, ideally below 14 mg/dL.


Alpha-Adrenergic Receptor Blockers

Class Summary

At low doses, alpha-adrenergic receptor blockers may be used as monotherapy in the treatment of hypertension. At higher doses, they may cause sodium and fluid to accumulate. As a result, concurrent diuretic therapy may be required to maintain the hypotensive effects of alpha-receptor blockers.

Phenoxybenzamine hydrochloride (Dibenzyline)


This is a long-acting adrenergic alpha-receptor blocker that can produce and maintain a chemical sympathectomy. Phenoxybenzamine hydrochloride lowers supine and upright blood pressure. It does not affect the parasympathetic nervous system.

Doxazosin mesylate (Cardura, Cardura XL)


Doxazosin mesylate is a quinazoline compound that is a selective alpha1-adrenergic antagonist. It inhibits postsynaptic alpha-adrenergic receptors, resulting in the vasodilation of veins and arterioles and a decrease in total peripheral resistance and blood pressure.

Phentolamine mesylate (Oraverse)


This is a nonselective alpha-adrenergic blocking agent. Its drug action is transient and alpha-adrenergic blockade incomplete. Phentolamine mesylate is often used immediately prior to or during adrenalectomy to prevent or control paroxysmal hypertension resulting from anesthesia, stress, or operative manipulation of the tumor. It is an alpha1- and alpha2-adrenergic blocking agent that blocks circulating epinephrine and norepinephrine action, reducing hypertension that results from catecholamine effects on alpha receptors.


Tyrosine Kinase Inhibitors

Class Summary

These agents are used to inhibit catecholamine synthesis in pheochromocytoma.

Metyrosine (Demser)


Metyrosine inhibits tyrosine hydroxylase, the rate-limiting step in catecholamine synthesis. In patients with pheochromocytoma, administration of metyrosine reduces catecholamine biosynthesis by 35-80%, as measured by urinary catecholamine levels. It is indicated in patients with malignant pheochromocytoma or in cases of pheochromocytoma in which surgery is contraindicated. It can be useful in patients who are refractory to phenoxybenzamine therapy, or it can be administered as an adjunct to phenoxybenzamine therapy.


Beta-Adrenergic Receptor Blocking Agents

Class Summary

These agents compete with beta-adrenergic agonists for available beta-receptor sites.

Propranolol hydrochloride (Inderal LA, InnoPran XL)


This is a nonselective beta-adrenergic receptor blocker. After primary treatment with an alpha-receptor blocker, propranolol hydrochloride may be used as adjunctive therapy if control of tachycardia becomes necessary before or during surgery. It may be used to treat excessive beta-receptor stimulation in patients with inoperable metastatic pheochromocytoma. The drug has membrane-stabilizing activity and decreases the automaticity of contractions.

Propranolol hydrochloride is not suitable for the emergency treatment of hypertension; do not administer it intravenously in hypertensive emergencies.

Atenolol (Tenormin)


Atenolol selectively blocks beta1 receptors, with little or no affect on beta2 types.


Diuretics, Loop

Class Summary

Diuretics induce calciuresis. In patients with severe hypercalcemia, the individual typically is volume depleted, which means that volume should be replaced with saline prior to institution of diuretic therapy.

Furosemide (Lasix)


Furosemide inhibits the resorption of sodium and chloride in the loop of Henle and the proximal and distal tubules of the kidney. Its onset of action is rapid after an intravenous dose.


Calcium Metabolism Modifiers

Class Summary

Bisphosphonates may be used if the patient remains severely hypercalcemic following the diuretic therapy. These agents are analogues of inorganic pyrophosphate and act by binding to hydroxyapatite in bone matrix, thereby inhibiting the dissolution of crystals. They prevent osteoclast attachment to the bone matrix and osteoclast recruitment and viability.

For maximum gut absorption, all oral bisphosphonates should be taken at least 2 hours before or after meals. The newer bisphosphonates are not completely free of the risk of causing a mineralization defect, but their safe therapeutic window is much wider. They clearly are more potent than etidronate in reducing disease activity and normalizing alkaline phosphatase levels.

Calcitonin analogues may also be used if the patient remains severely hypercalcemic following the diuretic therapy. These agents directly inhibit osteoclastic bone resorption and have a significant analgesic effect on bone. Human calcitonin is no longer available. Salmon calcitonin is more likely than human calcitonin to cause resistant antibodies. As many as 26% of patients treated with salmon calcitonin demonstrated loss of biochemical responsiveness after initial improvement. High titers of salmon calcitonin antibodies produce resistance. All patients resistant to salmon calcitonin responded to human calcitonin.

Pamidronate (Aredia)


The main action of pamidronate is to inhibit the resorption of bone. The mechanism by which this inhibition occurs is not fully known. The drug is adsorbed onto calcium pyrophosphate crystals and may block the dissolution of these crystals, also known as hydroxyapatite, which are an important mineral component of bone. There is also evidence that pamidronate directly inhibits osteoclasts.

Alendronate (Fosamax)


Alendronate is a potent third-generation bisphosphonate that principally acts by inhibiting osteoclastic bone resorption. It is recommended for treatment of Paget disease. Retreatment may be considered after 6-month posttreatment evaluation in patients whose serum alkaline phosphatase level did not normalize.

Risedronate (Actonel, Atelvia)


Risedronate is a potent aminobisphosphonate that principally acts by inhibiting osteoclastic bone resorption. It is recommended for the treatment of Paget disease.

Etidronate (Didronel)


Etidronate was the first bisphosphonate to be studied in humans and approved in the United States (1978) for the treatment of Paget disease. It is the least potent of currently available bisphosphonate drugs.

Tiludronate (Skelid)


Tiludronate is a sulfur-containing bisphosphonate of intermediate potency between etidronate and newer nitrogen-containing bisphosphonates. No food, indomethacin, or calcium should be ingested within 2 hours before and 2 hours after. A 3-month posttreatment evaluation follows.

Zoledronate (Reclast, Zometa)


Zoledronate inhibits bone resorption. It inhibits osteoclastic activity and induces osteoclastic apoptosis.

Salmon calcitonin (Miacalcin, Fortical)


This agent may be used if the patient remains severely hypercalcemic following the diuretic therapy. This agent is a peptide hormone that binds to calcitonin receptors on osteoclasts and rapidly inhibits bone resorption. Osteoclasts do not induce cytotoxic effects in bone cells.

Salmon calcitonin induces reductions in urinary hydroxyproline and serum alkaline phosphatase levels. Serum alkaline phosphatase begins to decline 4 weeks after initiation of treatment. Levels of urinary hydroxyproline may decrease quickly, indicating inhibition of bone resorption. These laboratory markers slowly increase back to pretreatment levels if treatment is stopped. If no response is noted by 3 months, treatment should be discontinued.

Restoration of more normal bone can be seen radiographically, especially after long-term calcitonin treatment. Bone biopsy samples also reflect reduced disease activity because decreased bone cells, marrow fibrosis, and woven bone are present. Reduction in bone pain, cardiac output, and skin temperature over lower limb bones can be observed. Improvement of neurologic deficits and stabilization of hearing have been noted.

Reduction of hemorrhage from orthopedic procedures has been demonstrated with preoperative calcitonin treatment. However, salmon calcitonin only partially suppresses disease while treatment continues.


Thyroid Hormones

Class Summary

These agents are used for supplemental therapy in hypothyroidism.

Levothyroxine sodium (Synthroid, Levoxyl, Levothroid, Tirosint)


The goal of therapy for primary hypothyroidism is to achieve and maintain a clinical and biochemical euthyroid state. In active form, thyroid hormones influence growth and maturation of tissues. These hormones are involved in normal growth, metabolism, and development.


Vitamins, Fat-Soluble

Class Summary

Vitamin D supplements may increase serum calcium levels by improving calcium absorption.

Calcitriol (Rocaltrol, Vectical, Calcijex)


Calcitriol may be required in the management of hypocalcemia and its clinical manifestations in patients with postsurgical hypoparathyroidism. This supplement is important in maintaining calcium balance and in the regulation of PTH. Patients are advised to have a dietary intake of calcium of, at minimum, 1000mg daily.



Class Summary

Corticosteroids cause profound and varied metabolic effects. These agents modify the body's immune response to diverse stimuli.



Cortisone is the drug of choice for patients with adrenocortical insufficiency. It is used in replacement doses for postsurgical adrenalectomy.

Fludrocortisone acetate (Florinef)


Mineralocorticoids provide a partial replacement therapy for primary and secondary adrenocortical insufficiency. The combination of fludrocortisone acetate tablets with a glucocorticoid, such as hydrocortisone or cortisone, provides substitution therapy approximating normal adrenal activity, with minimal risk of unwanted effects.

Contributor Information and Disclosures

Melanie L Richards, MD MPHE, Professor, Department of Surgery, Mayo Clinic

Melanie L Richards, MD is a member of the following medical societies: American College of Surgeons, International Association of Endocrine Surgeons, Southwestern Surgical Congress, Western Surgical Association, American Association of Endocrine Surgeons

Disclosure: Nothing to disclose.


Suzanne M Carter, MS Senior Genetic Counselor, Associate, Department of Obstetrics and Gynecology, Division of Reproductive Genetics, Montefiore Medical Center, Albert Einstein College of Medicine

Suzanne M Carter, MS is a member of the following medical societies: American Bar Association

Disclosure: Nothing to disclose.

Susan J Gross, MD, FRCSC, FACOG, FACMG Codirector, Division of Reproduction Genetics, Associate Professor, Department of Obstetrics and Gynecology, Albert Einstein College of Medicine

Susan J Gross, MD, FRCSC, FACOG, FACMG is a member of the following medical societies: American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, American Medical Association, American Society of Human Genetics, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.


Ruth Freeman, MD, Director of Menopause Research and Treatment Center, Professor, Departments of Medicine and Obstetrics and Gynecology, Montefiore Medical Center, Albert Einstein College of Medicine

Ruth Freeman, MD is a member of the following medical societies: American College of Clinical Endocrinologists

Disclosure: Nothing to disclose.

Romesh Khardori, MD, PhD Professor and Director, Division of Endocrinology, Metabolism, and Molecular Medicine, Southern Illinois University School of Medicine

Romesh Khardori, MD, PhD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Medical Association, American Society of Andrology, Endocrine Society, and Illinois State Medical Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

  1. Calender A. Genetic testing in multiple endocrine neoplasia and related syndromes. Forum (Genova). 1998 Apr-Jun. 8(2):146-59. [Medline].

  2. Verrienti A, Carbone A, Bellitti P, Fabiano MC, De Rose RF, Maranghi M, et al. A NOVEL DOUBLE MUTATION VAL648ILE AND VAL804LEU OF RET PROTO-ONCOGENE IN MULTIPLE ENDOCRINE NEOPLASIA TYPE 2. Endocr Pract. 2015 Aug 6. [Medline].

  3. Zupan A, Glavač D. The development of rapid and accurate screening test for RET hotspot somatic and germline mutations in MEN2 syndromes. Exp Mol Pathol. 2015 Aug 29. [Medline].

  4. Raue F, Frank-Raue K. Genotype-phenotype relationship in multiple endocrine neoplasia type 2. Implications for clinical management. Hormones (Athens). 2009 Jan-Mar. 8(1):23-8. [Medline]. [Full Text].

  5. Moley JF, Skinner M, Gillanders WE, Lairmore TC, Rowland KJ, Traugott AL, et al. Management of the Parathyroid Glands During Preventive Thyroidectomy in Patients With Multiple Endocrine Neoplasia Type 2. Ann Surg. 2015 Oct. 262 (4):641-6. [Medline].

  6. Kluijfhout WP, van Beek DJ, Verrijn Stuart AA, Lodewijk L, Valk GD, van der Zee DC, et al. Postoperative Complications After Prophylactic Thyroidectomy for Very Young Patients With Multiple Endocrine Neoplasia Type 2: Retrospective Cohort Analysis. Medicine (Baltimore). 2015 Jul. 94 (29):e1108. [Medline].

  7. Lallier M, St-Vil D, Giroux M, et al. Prophylactic thyroidectomy for medullary thyroid carcinoma in gene carriers of MEN2 syndrome. J Pediatr Surg. 1998 Jun. 33(6):846-8. [Medline].

  8. van Heurn LW, Schaap C, Sie G, et al. Predictive DNA testing for multiple endocrine neoplasia 2: a therapeutic challenge of prophylactic thyroidectomy in very young children. J Pediatr Surg. 1999 Apr. 34(4):568-71. [Medline].

  9. de Graaf JS, Lips CJ, Rutter JE, van Vroonhoven TJ. Subtotal adrenalectomy for phaeochromocytoma in multiple endocrine neoplasia type 2A. Eur J Surg. 1999 Jun. 165(6):535-8. [Medline].

  10. Edstrom E, Grondal S, Norstrom F, et al. Long term experience after subtotal adrenalectomy for multiple endocrine neoplasia type IIa. Eur J Surg. 1999 May. 165(5):431-5. [Medline].

  11. Gagel RF, Levy ML, Donovan DT, et al. Multiple endocrine neoplasia type 2a associated with cutaneous lichen amyloidosis. Ann Intern Med. 1989 Nov 15. 111(10):802-6. [Medline].

  12. Ilias I, Pacak K. Diagnosis, localization and treatment of pheochromocytoma in MEN 2 syndrome. Endocr Regul. 2009 Apr. 43(2):89-93. [Medline].

  13. Pacak K, Eisenhofer G, Ilias I. Diagnosis of pheochromocytoma with special emphasis on MEN2 syndrome. Hormones (Athens). 2009 Apr-Jun. 8(2):111-6. [Medline]. [Full Text].

  14. Taïeb D, Sebag F, Barlier A, et al. 18F-FDG avidity of pheochromocytomas and paragangliomas: a new molecular imaging signature?. J Nucl Med. 2009 May. 50(5):711-7. [Medline].

  15. Yoshida S, Imai T, Kikumori T, et al. Long term parathyroid function following total parathyroidectomy with autotransplantation in adult patients with MEN2A. Endocr J. 2009 Aug. 56(4):545-51. [Medline].

  16. Calmettes C, Ponder BA, Fischer JA, Raue F. Early diagnosis of the multiple endocrine neoplasia type 2 syndrome: consensus statement. European Community Concerted Action: Medullary Thyroid Carcinoma. Eur J Clin Invest. 1992 Nov. 22(11):755-60. [Medline].

  17. Carling T. Multiple endocrine neoplasia syndrome: genetic basis for clinical management. Curr Opin Oncol. 2005 Jan. 17(1):7-12. [Medline].

  18. Chi DD, Moley JF. Medullary thyroid carcinoma: genetic advances, treatment recommendations, and the approach to the patient with persistent hypercalcitoninemia. Surg Oncol Clin N Am. 1998 Oct. 7(4):681-706. [Medline].

  19. Evans DB, Fleming JB, Lee JE, et al. The surgical treatment of medullary thyroid carcinoma. Semin Surg Oncol. 1999 Jan-Feb. 16(1):50-63. [Medline].

  20. Frank-Raue K, Rondot S, Hoeppner W, Goretzki P, Raue F, Meng W. Coincidence of multiple endocrine neoplasia types 1 and 2: mutations in the RET protooncogene and MEN1 tumor suppressor gene in a family presenting with recurrent primary hyperparathyroidism. J Clin Endocrinol Metab. 2005 Jul. 90(7):4063-7. [Medline].

  21. Gagel RF, Tashjian AH Jr, Cummings T, et al. The clinical outcome of prospective screening for multiple endocrine neoplasia type 2a. An 18-year experience. N Engl J Med. 1988 Feb 25. 318(8):478-84. [Medline].

  22. Goretzki PE, Hoppner W, Dotzenrath C, et al. Genetic and biochemical screening for endocrine disease. World J Surg. 1998 Dec. 22(12):1202-7. [Medline].

  23. Iler MA, King DR, Ginn-Pease ME, et al. Multiple endocrine neoplasia type 2A: a 25-year review. J Pediatr Surg. 1999 Jan. 34(1):92-6; discussion 96-7. [Medline].

  24. Johnston LB, Chew SL, Trainer PJ, et al. Screening children at risk of developing inherited endocrine neoplasia syndromes. Clin Endocrinol (Oxf). 2000 Feb. 52(2):127-36. [Medline].

  25. Koch CA. Molecular pathogenesis of MEN2-associated tumors. Fam Cancer. 2005. 4(1):3-7. [Medline].

  26. Lips CJ. Clinical management of the multiple endocrine neoplasia syndromes: results of a computerized opinion poll at the Sixth International Workshop on Multiple Endocrine Neoplasia and von Hippel-Lindau disease. J Intern Med. 1998 Jun. 243(6):589-94. [Medline].

  27. Moore SW, Appfelstaedt J, Zaahl MG. Familial medullary carcinoma prevention, risk evaluation, and RET in children of families with MEN2. J Pediatr Surg. Feb. 42:326-32. [Medline].

  28. Neumann HP, Bausch B, McWhinney SR. Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med. 2002 May 9. 346(19):1459-66. [Medline].

  29. Romeo G, Ceccherini I, Celli J, et al. Association of multiple endocrine neoplasia type 2 and Hirschsprung disease. J Intern Med. 1998 Jun. 243(6):515-20. [Medline].

  30. Wick MJ. Clinical and molecular aspects of multiple endocrine neoplasia. Clin Lab Med. 1997 Mar. 17(1):39-57. [Medline].

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