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Type 2 Multiple Endocrine Neoplasia Workup

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

Approach Considerations

Perform genetic screening for RET mutations in all index patients. If a mutation is identified, also screen family members who are at risk.

For individuals identified with a mutation or for persons who are at risk, biochemical screening consists of ascertainment of baseline calcitonin levels and of serum calcium and parathyroid hormone (PTH) levels, along with urine collection for catecholamines and metanephrine concentrations. (However, a plasma metanephrine level can be used for screening.)

If a patient's calcitonin level is within reference ranges, a pentagastrin and/or Ca++ stimulation test may be used as a guide to assess the necessity of a central compartment or modified neck dissection.

Patients who have been diagnosed with medullary thyroid carcinoma require serial calcitonin (+/- provocative testing) and carcinoembryonic antigen (CEA) testing to assess for persistent or recurrent disease.

Fine-needle aspiration

Avoid the removal of cells from thyroid masses for cytology in patients with type 2 multiple endocrine neoplasia (MEN 2) who have had their diagnosis previously confirmed by either genetic analysis or elevated calcitonin levels. These patients have an established diagnosis, and a biopsy increases the possibility of tumor spread. A fine-needle aspiration biopsy is primarily used in an index patient who presents with a thyroid nodule when the clinician considers the presence of medullary thyroid carcinoma to be unlikely.

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Screening for Cancer and Hyperparathyroidism

Screening for medullary thyroid carcinoma is done with the pentagastrin stimulation test, with serum calcitonin measured at baseline and at 2, 5, and 10 minutes. False-positive and false-negative results have been reported.

Urinary catecholamines and metanephrines screen for pheochromocytomas. (If these are elevated, imaging studies of the adrenals are recommended.)

Serum calcium level and PTH levels screen for hyperparathyroidism. An inappropriately elevated PTH level in relation to the serum calcium is consistent with primary hyperparathyroidism. If the 24-hour urine calcium level is low, the presence of familial hypocalciuric hypercalcemic syndrome should be considered.

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Imaging Studies

Perform computed tomography (CT) scanning or magnetic resonance imaging (MRI) of the adrenals. A metaiodobenzylguanidine (MIBG) scan is useful for localizing pheochromocytomas.[12, 13, 14]

If calcitonin levels are elevated at either baseline or with provocative testing, evaluate the chest and abdomen for metastatic disease. Available modalities include CT scanning, MRI, octreotide scanning, and, in some instances, laparoscopy.

Radionuclide scanning may reveal the extent of metastasis. OctreoScan provides a whole-body examination and is used to examine the spread of medullary thyroid carcinoma. The somatostatin analogue octreotide, which is used for the treatment of hormone-related symptoms, is labeled with the isotope indium-111 (111 In) and injected intravenously. The next day, the patient is examined with a gamma camera, which can detect the accumulation of radioactivity.

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Histologic Findings

The tumor in medullary thyroid carcinoma is well demarcated, firm, and grayish white. Polygonal cells are uniform, with finely granular eosinophilic cytoplasm with central nuclei. Amyloid formed from calcitonin molecules is often found. Other findings include the following:

  • C-cell hyperplasia - Frequently found; is a precursor in the malignant transformation to medullary thyroid carcinoma.
  • Pheochromocytomas - Benign tumors, often bilateral and multifocal, that arise from diffuse hyperplasia of the adrenal medulla
  • Parathyroid hyperplasia - In this, overgrowth is the most common finding, although adenomatous changes occur in a small percentage of cases
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Staging

TNM classification is used for postoperative staging. (T = the size of the primary lesion, N = the presence or absence of regional lymph node metastatic involvement, and M = the presence or absence of distant metastatic lesions.)

Primary lesions are designated as follows:

  • T1 - Tumor 2cm or less in greatest dimension, limited to the thyroid
  • T2 - Tumor greater than 2 cm but less than or equal to 4 cm; limited to the thyroid
  • T3 - Tumor greater than 4 cm; limited to the thyroid
  • T4a - Tumor of any size that extends extrathyroidally and invades subcutaneous soft tissues
  • T4b - Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

Regional lymph node metastatic involvement is designated as follows:

  • N0 - No evidence of lymph node metastases
  • N1 - Regional lymph node metastasis
  • N1a - Metastasis to level VI (central compartment) cervical lymph node(s)
  • N1b - Metastasis to unilateral or bilateral cervical nodes or to superior mediastinal lymph node(s)

Occurrence of distant metastatic lesions is designated as follows:

  • M0 – No evidence of distant metastases exists
  • M1 – Distant metastatic lesions exist

Postoperative staging is as follows:

  • Stage 1 - T1,N0,M0
  • Stage II - T2,N0,M0
  • Stage III – (T3,N0,M0), (T1,N1a,M0), (T2,N1a,M0), (T3,N1a,M0)
  • Stage IVA - (T4a,N0,M0), (T4a,N1a,M0), (T1,N1b,M0), (T2,N1b,M0), (T3,N1b,M0), (T4a,N1b,M0)
  • Stage IVB - T4b, any N, M0
  • Stage IVC - Any T, any N, and M1
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Contributor Information and Disclosures
Author

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.

Coauthor(s)

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.

Acknowledgements

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

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