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Guideline Summary
Guideline Title
Medullary thyroid cancer: management guidelines of the American Thyroid Association.
Bibliographic Source(s)
American Thyroid Association Guidelines Task Force, Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H, Moley JF, Pacini F, Ringel MD, Schlumberger M, Wells SA Jr. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009 Jun;19(6):565-612. [398 references] PubMed External Web Site Policy
Guideline Status

This is the current release of the guideline.

Scope

Disease/Condition(s)

Inherited and sporadic medullary thyroid cancer (MTC)

Guideline Category
Counseling
Diagnosis
Evaluation
Management
Risk Assessment
Screening
Treatment
Clinical Specialty
Endocrinology
Medical Genetics
Nuclear Medicine
Oncology
Pediatrics
Radiation Oncology
Radiology
Surgery
Intended Users
Physicians
Guideline Objective(s)
  • To create specific medullary thyroid cancer (MTC) clinical guidelines that would bring together and update the diverse MTC literature and combine it with evidence-based medicine and the knowledge and experience of a panel of expert clinicians
  • To assist in the clinical care of MTC patients and to share what the authors believe is current, rational, and optimal medical practice
Target Population

Patients with inherited and sporadic medullary thyroid cancer (MTC)

Interventions and Practices Considered
  1. Germline (REarranged during Transfection) RET testing
  2. Differential diagnosis
  3. Genetic testing, as applicable
  4. Pre- and post-RET testing genetics counseling, including reproductive options
  5. RET mutation analysis for all first-degree relatives
  6. Testing of exon 10 for activating RET mutations
  7. Sequence and mutation analysis, as applicable
  8. Family member screening
  9. Preoperative testing including basal or stimulated serum calcitonin (Ct), carcinoembryonic antigen (CEA), calcium, RET protooncogene analysis, cervical ultrasound (US), abdominal imaging, magnetic resonance imaging (MRI), computed tomography (CT), biochemical testing, plasma free metanephrines and normetanephrines or 24-hour urine collection for metanephrines and normetanephrines, and albumin-corrected calcium or ionized serum calcium measurements
  10. Consider sources of Ct assay interference
  11. Surgery
    • Prophylactic total thyroidectomy
    • Prophylactic level VI central compartment neck dissection
    • Prophylactic lymph node dissection (not recommended)
    • Resection of just the visibly enlarged glands (with a forearm autograft), subtotal parathyroidectomy leaving one or a piece of one gland in situ (with a forearm autograft), and total parathyroidectomy with forearm autografting (primary hyperparathyroidism [PHPT])
    • Hemithyroidectomy
    • Laparoscopic adrenalectomy
    • Cortical-sparing adrenal surgery
    • Less aggressive neck surgery
  12. Management of normal parathyroid glands resected or devascularized
  13. Medical therapy
  14. Thyrotropin suppression therapy
  15. Postoperative staging
  16. Observation
  17. External beam radiation therapy (EBRT)
  18. Percutaneous interventions
  19. Hepatic embolization
  20. Chemotherapy, as applicable
  21. Somatostatin analogs (Note: considered but not recommended)
  22. Postoperative radioactive iodine (Note: considered but not recommended)
  23. Empiric liver or lung biopsies, hepatic vein sampling, systemic vascular sampling, or hepatic angiography prior to re-operation (Note: not recommended)
  24. Clinical trials
  25. Glucocorticoid therapy for bone metastases
  26. Bisphosphonates (Note: cannot recommend for or against use)
  27. Radio-labeled molecules
  28. Treatment of hormonally active metastases
  29. Long-term follow-up and biochemical monitoring
Major Outcomes Considered
  • Sensitivity and specificity of diagnostic tests
  • Survival rates
  • Cure rates
  • Disease-related morbidity and mortality
  • Recurrence rates

Methodology

Methods Used to Collect/Select the Evidence
Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence

Relevant articles were identified by searching PubMed MEDLINE at Pubmed (NLM) using the following search terms: (medullary carcinoma) OR (medullary thyroid cancer) OR (medullary thyroid carcinoma) OR (RET) OR (calcitonin), which yielded 30,095 articles on March 10, 2007. Limiting the search to include "humans" and "randomized controlled trials" or "meta-analysis" from (medullary carcinoma) OR (medullary thyroid cancer) OR (medullary thyroid carcinoma) yielded 12 articles, of which 8 were relevant and they were reviewed in detail by the Task Force. In addition to these articles, numerous additional relevant articles, book chapters, and other materials were also supplied by Task Force members, including works published after the initial search. Published works were utilized to devise this Guideline as referenced.

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence
Expert Consensus (Committee)
Rating Scheme for the Strength of the Evidence

Not applicable

Methods Used to Analyze the Evidence
Systematic Review
Description of the Methods Used to Analyze the Evidence

Not stated

Methods Used to Formulate the Recommendations
Expert Consensus
Description of Methods Used to Formulate the Recommendations

The American Thyroid Association (ATA) Executive Council selected a Medullary Thyroid Cancer (MTC) Guidelines Task Force chairman using criteria that included MTC clinical experience and the absence of dogmatically held views in areas of recognized controversy. A Task Force was selected based on clinical expertise to include representation of endocrinology, genetics, pediatrics, nuclear medicine, surgery, oncology, and clinical laboratory testing. The Task Force additionally included experts from both North America and Europe.

The Task Force considered how patients with MTC or a genetic predisposition for the disease are encountered, diagnosed, and treated. In this framework, a series of flow diagrams was created and revised, and a list of questions were developed and assigned to individual Task Force members to answer utilizing the published literature and expert opinion when relevant. Based on these documents a preliminary Guideline and a series of Recommendations were made and then critically reviewed and modified by the full Task Force. The level of evidence to support the Recommendations was categorized and reviewed. Finally, the full Task Force again critically reviewed the entire Guideline and Recommendations through several iterations and arrived at a document of consensus. In most cases the consensus was unanimous while in some cases there were disparate views held by a minority of panel members, the most significant of which are noted in this document. The final document is the product of face-to-face meetings in Phoenix, Arizona, October 12, 2006; Columbus, Ohio, November 11, 2006; and Toronto, Ontario, June 2, 2007; and multiple electronic communications and telephone conference calls.

Rating Scheme for the Strength of the Recommendations

Strength of Recommendations Based on Available Evidence

Rating Definition
A Strongly recommends. The recommendation is based on good evidence that the service or intervention can improve important health outcomes. Evidence includes consistent results from well-designed, well-conducted studies in representative populations that directly assess effects on health outcomes.
B Recommends. The recommendation is based on fair evidence that the service or intervention can improve important health outcomes. The evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies; generalizability to routine practice; or indirect nature of the evidence on health outcomes.
C Recommends. The recommendation is based on expert opinion.
D Recommends against. The recommendation is based on expert opinion.
E Recommends against. The recommendation is based on fair evidence that the service or intervention does not improve important health outcomes or that harms outweigh benefits.
F Strongly recommends against. The recommendation is based on good evidence that the service or intervention does not improve important health outcomes or that harms outweigh benefits.
I Recommends neither for nor against. The panel concludes that the evidence is insufficient to recommend for or against providing the service or intervention because evidence is lacking that the service or intervention improves important health outcomes, the evidence is of poor quality, or the evidence is conflicting. As a result, the balance of benefits and harms cannot be determined.

Adapted from the U.S. Preventive Services Task Force, Agency for Healthcare Research and Quality.

Cost Analysis

Given that medullary thyroid cancer (MTC) is present in about 0.3% to 1.4% of patients with thyroid nodules, routine serum calcitonin (Ct) measurement in all patients with thyroid nodules has raised concerns of cost-effectiveness, especially when many of the operated patients would not have disease based on the imperfect specificity if a cut-off was chosen that optimized sensitivity. Additionally, the clinical significance and natural history of MTC diagnosed by Ct screening is unknown. However, cost-effectiveness studies in the United States have been favorable, although these models are quite sensitive to multiple important decision analysis variables, including cost of the Ct test, such that assuming a relatively small increase in cost could substantially alter the conclusions. Recent studies utilizing Ct measurement from thyroid nodule fine-needle aspiration (FNA) washings may significantly improve this testing accuracy, although some questions of cost-effectiveness are likely to remain.

Method of Guideline Validation
External Peer Review
Internal Peer Review
Description of Method of Guideline Validation

The final document was approved by the American Thyroid Association (ATA) Board of Directors, and officially endorsed (in alphabetical order) by the American Academy of Otolaryngology—Head and Neck Surgery (AAO-HNS) Endocrine Surgery Committee, American Association of Clinical Endocrinologists (AACE), American Association of Endocrine Surgeons (AAES), American College of Endocrinology (ACE), Asia and Oceanic Thyroid Association (AOTA), British Association of Endocrine and Thyroid Surgeons (BAETS), British Association of Head and Neck Oncologists (BAHNO), Canadian Society of Otolaryngology—Head and Neck Surgery (CSOHNS), The Endocrine Society (ENDO), European Society of Endocrinology (ESE), European Society of Endocrine Surgery (ESES), European Thyroid Association (ETA), International Association of Endocrine Surgeons (IAES), Latin American Thyroid Society (LATS), and the Ukrainian Association of Endocrine Surgeons (UAES).

Recommendations

Major Recommendations

Definitions for the strength of the recommendations (A–F, I) are presented at the end of the "Major Recommendations" field.

Initial Diagnosis and Therapy of Preclinical Disease in Multiple Endocrine Neoplasia Type 2 (MEN 2) Syndromes

Role of Germline RET Testing in Medullary Thyroid Carcinoma (MTC) Patients

R1. All patients with a personal medical history of primary C-cell hyperplasia (CCH), MTC, or MEN 2 should be offered germline REarranged during Transfection (RET) testing. Grade: A Recommendation

R2. The differential diagnosis in patients with intestinal ganglioneuromatosis should include MEN 2B, which together with their history and physical examinations, family history, and ganglioneuromatosis histology may prompt germline RET testing. Grade: B Recommendation

R3. All people with a family history consistent with MEN 2 or familial MTC (FMTC), and at risk for autosomal dominant inheritance of the syndrome, should be offered RET testing. For MEN 2B this should be done shortly after birth. For MEN 2A and FMTC this should be done before 5 years of age (see Table 6 in the original guideline document). Grade: A Recommendation

R4. Lichen planus amyloidosis or pruritus in the central upper back may indicate the presence of a 634 codon mutation and should prompt genetic testing. Grade: C Recommendation

R5. Pre- and post-test genetics counseling by a genetics counselor, or other qualified professional, should be offered to all patients undergoing RET testing. Grade: C Recommendation

Prophylactic Thyroidectomy

R6. Infants with American Thyroid Association level D (ATA-D) mutations (MEN 2B) should undergo prophylactic total thyroidectomy as soon as possible and within the first year of life in an experienced tertiary care setting. Grade: B Recommendation

R7. Children with ATA-C mutations (codon 634) should undergo prophylactic total thyroidectomy before they are 5 years old in an experienced tertiary care setting. Grade: A Recommendation

R8. In patients with ATA-A and ATA-B RET mutations, prophylactic total thyroidectomy may be delayed beyond age 5 years in the setting of a normal annual basal ± stimulated* serum calcitonin (Ct), normal annual neck ultrasound (US), less aggressive MTC family history, and family preference. Surgery is indicated if all of these features are not present. For higher risk mutations (ATA-B), consider treatment before age 5 years in an experienced tertiary care setting, regardless of other factors. Grade: B Recommendation

RET Testing in Asymptomatic People

R9. Once a germline RET mutation has been identified in a family, RET mutation analysis should be offered to all first-degree relatives of known mutation carriers which should be done before the age of recommended prophylactic thyroidectomy whenever possible. Grade: A Recommendation

R10. Testing of exon 10 for activating RET mutations should be considered in individuals with Hirschsprung disease. Grade: A Recommendation

RET Testing Methodologies

R11. Analysis of the MEN 2–specific exons of RET is the recommended method of initial testing in either a single or multi-tiered approach. Grade: A Recommendation

R12. Sequencing the entire coding region of RET to identify MTC causative mutations is not recommended as the initial testing method (Grade: E Recommendation). However, it should be done when the analysis using the recommended method is negative in the clinical setting of MEN 2 or when there is a discrepancy between the genotype and phenotype. Grade: B Recommendation

R13. Testing of patients with MEN 2B should include analyses to detect the M918T (exon 16) and A883F mutations (exon 15) present in virtually all of these patients. Grade: A Recommendation

R14. In the clinical setting of MEN 2B and negative testing for M918T and A883F mutations, sequencing the entire coding region of RET should be performed. Grade: B Recommendation

R15. Until the phenotype of MEN 2B associated with codon 804 mutations in conjunction with a second variant in RET is clarified, these patients and mutation carriers should be treated similarly to those with the more typical MEN 2B RET-causing mutations. Grade: C Recommendation

Genetic Testing: Privacy vs. Notification of Potentially Affected Family Members

R16. The duty to warn should be fulfilled by notifying a competent patient (or legal guardian) of the risk the inherited RET mutation may pose to family members, ideally in the setting of formal genetic counseling. This notification should include the seriousness of the disease and available forms of treatment and prevention. The highest recommendation should be made that the patient pass this warning to potentially affected family members, and the opportunity for genetic counseling and testing of these individuals should be provided. Conversely, physicians should not disclose confidential genetic or medical information without the patient's permission. When a patient or family refuses to notify relatives of their risk or to provide testing or treatment to legal dependents, the physician may involve the local medical ethics committee and/or legal system. Grade: C Recommendation

Reproductive Options of RET Mutation Carriers

R17. All RET mutation carriers of childbearing age should be considered for counseling about the options of prenatal or preimplantation diagnostic testing. Grade: C Recommendation

Possibility of Inherited Disease in RET Mutation–negative MTC Patients and Families

R18. In a family meeting clinical criteria for MEN 2A or 2B, or FMTC despite negative sequencing of the entire region of the RET oncogene, at-risk relatives should be periodically screened for MTC (neck US, basal ± stimulated* Ct measurement) and associated primary hyperparathyroidism (PHPT) (albumin-corrected calcium or ionized calcium) and/or pheochromocytoma (PHEO) (plasma free metanephrines and normetanephrines, or 24-hour urine metanephrines and normetanephrines) as indicated by the family phenotype. Screening should continue at 1- to 3-year intervals at least until the age of 50 years or 20 years beyond the oldest age of initial diagnosis in the family, whichever is latest. Grade: C Recommendation

Preoperative Testing of Asymptomatic RET Mutation–positive Patients for MTC, Primary Hyperparathyroidism (PHPT), and Pheochromocytoma (PHEO)

R19. Children with MEN 2A or FMTC who are to undergo prophylactic thyroidectomy before 5 years of age may undergo preoperative Ct and cervical US assessment when >3 years old, whereas children older than 5 years require them because of the possibility of metastatic MTC, which would change their clinical management. Caution should be used in interpreting Ct values in children less than 3 years old, and especially in those during the first 6 months of life. Grade: B Recommendation

R20. Children with MEN 2B who are to undergo prophylactic thyroidectomy before age 6 months may undergo preoperative Ct assessment, whereas older children require it. Cervical US should be done in MEN 2B children as soon as possible. These tests are recommended because of the possibilities of metastatic MTC and of test results changing clinical management. Caution should be used in interpreting Ct values in children <3 years old, and especially those in the first 6 months of life. Grade: B Recommendation

R21. When it is decided to delay prophylactic thyroidectomy beyond the first 5 years of life in children with MEN 2A/FMTC:

  1. Basal serum Ct testing and cervical US should be performed annually starting by 5 years of age. Grade: B Recommendation
  2. The role of annual Ct stimulation* testing in these patients is less certain but may be performed. Grade: C Recommendation

R22. Screening abdominal imaging for PHEO is not recommended in the absence of symptoms or biochemical data suggesting the tumor, except for the rare urgent need to exclude PHEO. Grade: D Recommendation

R23. Symptoms or signs consistent with catecholamine excess, or an adrenal mass, should prompt biochemical testing for a PHEO. Grade: B Recommendation

R24. In the absence of symptoms or an adrenal mass to suggest the possibility of PHEO, surveillance (including preoperative testing) should include annual plasma free metanephrines and normetanephrines, or 24-hour urine collection for metanephrines and normetanephrines beginning by age 8 years in carriers of RET mutations associated with MEN 2B and in codons 630 and 634, and by age 20 years in carriers of other MEN 2A RET mutations. Patients with RET mutations associated only with FMTC (see Table 5 in the original guideline document) should be screened at least periodically from the age of 20 years. Grades: B Recommendation for genotype–phenotype distinctions, and C Recommendation for the frequency of testing.

R25. Because of the high risk to the fetus and mother, women with a RET mutation associated with MEN 2 should be biochemically screened for PHEO prior to a planned pregnancy or as soon as possible during an unplanned pregnancy. Grade: B Recommendation

R26. Surveillance for PHPT should include annual albumin-corrected calcium or ionized serum calcium measurements (with or without serum intact–parathyroid hormone [PTH]) beginning by age 8 years in carriers of RET mutations in codons 630 and 634, and by age 20 years in carriers of other MEN 2A RET mutations, and periodically with RET mutations associated only with FMTC (see Table 5 in the original guideline document) starting from age 20 years. Grades: B Recommendation for genotype–phenotype distinctions, and C Recommendation for the frequency of testing.

Sources of Ct Assay Interference

R27. It should be recognized that minimal or mild elevations in serum Ct may be seen in multiple clinical settings including CCH, renal failure, and autoimmune thyroiditis. Elevated Ct levels may occur from nonthyroidal neuroendocrine neoplasms and heterophilic antibodies. Falsely low Ct levels may occur in the setting of heterophilic antibodies and the "hook effect." Grade: B Recommendation

Effects of Age or Sex on the Normal Ct Range

R28. Optimally, an individual should be followed using the same Ct assay over time. Whenever possible, a blood sample should be measured using both assays to reestablish the baseline when it is necessary to change the assay. Grade: C Recommendation

R29. Laboratories should report the Ct assay being used, and notify clinicians of changes in methodology when they occur. Grade: C Recommendation

R30. In the setting of an intact thyroid gland, Ct values should be interpreted in the setting of sex-specific reference ranges, at least in adults. Grade: B Recommendation

R31. Due to the limited data available on the normal range for serum Ct in children <3 years of age and the probability that it may be higher than in adults, caution should be used in interpreting these values in young children. Grade: B Recommendation

Surgery for the Youngest MEN 2B Patients

R32. MEN 2B patients undergoing prophylactic thyroidectomy within the first 1 year of life should have this procedure performed in an experienced tertiary care setting, and preservation of parathyroid function should be given a high priority. Grade: C Recommendation

R33. Prophylactic level VI central compartment neck dissection may not be necessary in MEN 2B patients who undergo prophylactic thyroidectomy within the first year of life unless there is clinical or radiological evidence of lymph node metastases or thyroid nodules >5 mm in size (at any age), or a serum basal serum Ct >40 pg/mL in a child >6 months old; all of which suggests the possibility of more extensive disease that requires further evaluation and treatment (see Figure 1 in the original guideline document). Grade: E Recommendation

Surgery for the Youngest MEN 2A or FMTC Patients

R34. MEN 2A or FMTC patients who undergo prophylactic thyroidectomy within the first 3 to 5 years should have this procedure performed in an experienced tertiary care setting, and preservation of parathyroid and recurrent laryngeal nerve function should be given a high priority. Grade: C Recommendation

R35. MEN 2A or FMTC patients undergoing prophylactic thyroidectomy within their first 3 to 5 years should not undergo prophylactic level VI compartmental dissection unless there is clinical or radiological evidence of lymph node metastases, or thyroid nodules >5 mm in size at any age, or a basal serum Ct >40 pg/mL (see Figure 1 in the original guideline document). Grade: E Recommendation

R36. In MEN 2A or FMTC, the clinical or radiological evidence of lymph node metastases or thyroid nodules ≥5 mm in size at any age, or a serum basal serum Ct of >40 pg/mL when >6 months old, suggests the possibility of more extensive disease that requires further evaluation and treatment (see Figure 1 in the original guideline document). Grade: B Recommendation

Preoperative Imaging and Biochemical Testing to Evaluate for MTC in Older RET Mutation–positive Patients

R37. In asymptomatic MEN 2A and FMTC patients who present at age >5 years and asymptomatic MEN 2B patients who present at age >1 year, preoperative basal serum Ct and neck ultrasonography should be performed. Grade: B Recommendation

R38. In asymptomatic MEN 2A and FMTC patients who present at age >5 years and asymptomatic MEN 2B patients who present at age >1 year, further evaluation prior to surgery and more extensive surgery are needed if the basal serum Ct is >40 pg/mL, if thyroid nodules are ≥5 mm, or if suspicious lymph nodes are identified on neck US. Grade: B Recommendation

Surgery for the Older MEN 2B Patients Without Evidence of Cervical Lymph Node Metastases and Normal or Minimally Elevated Ct Levels

R39. In an MEN 2B patient >1 year old with all thyroid nodules <5 mm on US and with a serum Ct level <40 pg/mL, a total thyroidectomy is recommended. Grade: A Recommendation

R40. In an MEN 2B patient >1 year old with all thyroid nodules <5 mm on US and with a serum Ct level <40 pg/mL, inadequate data are available to guide decisions on prophylactic lymph node dissections. Based on expert opinion, the Task Force favored a prophylactic central neck dissection (recognizing that this would likely require autotransplantation of at least the inferior parathyroid glands), without lateral compartment neck dissection except in the setting of radiographic or clinically proven metastases to these regions. Grade: C Recommendation

Surgery for the Older MEN 2A or FMTC Patients Without Evidence of Cervical Node Metastases and Normal or Minimally Elevated Ct Levels

R41. In an MEN 2A or FMTC patient >5 years old with all thyroid nodules <5 mm on neck US and with a serum Ct level <40 pg/mL, a total thyroidectomy is recommended. The age when this is performed is based on the ATA risk level (see Tables 5 and 6 in the original guideline document). Grade: B Recommendation

R42. In an MEN 2A or FMTC patient >5 years old with all thyroid nodules <5mm on neck US and with a serum Ct level <40 pg/mL, a prophylactic lymph node dissection is not recommended. Grade: E Recommendation

Diagnostic Testing for RET Mutation–positive Patients Suspected of Having Metastases Based on Imaging or Serum Ct Level

R43. Patients harboring RET oncogene mutations who have clinical or radiographic findings suspicious for metastatic MTC, including those with thyroid nodules ≥5 mm or a serum Ct level >40 pg/mL, should be considered for further evaluation prior to surgery as outlined in Figure 2 of the original guideline document. Grade: B Recommendation

Management for Normal Parathyroid Glands Resected or Devascularized During Surgery

R44. Devascularized normal parathyroid glands from patients with MEN 2B or FMTC should be autografted into the sternocleidomastoid muscle of the neck. Grade: C Recommendation

R45. Devascularized normal parathyroid glands from patients with MEN 2A in a kindred with strong family history of PHPT, or a RET mutation carrying a significant risk of PHPT, should be autografted into the forearm. Grade: C Recommendation

R46. Devascularized normal parathyroid glands from patients with a RET mutation associated with both MEN 2A with a low risk of PHPT and FMTC, whose kindred suggests FMTC, may undergo autograft of the parathyroid tissue into either the forearm or the sternocleidomastoid muscle. Grade: C Recommendation

Treatment for PHPT in MEN 2A

R47. Because of the high rate of biochemical cure of PHPT in MEN 2A with surgery, initial surgical therapy is preferred to medical therapy, in the absence of contraindications such as excessive surgical risk or limited life expectancy. Grade: C Recommendation

R48. Surgical management of PHPT at the time of initial thyroidectomy should always be performed if the diagnosis of PHPT is established. Surgical options include resection of just the visibly enlarged glands (with a forearm autograft), subtotal parathyroidectomy leaving one or a piece of one gland in situ (with a forearm autograft), and total parathyroidectomy with forearm autografting. Because of the risk for permanent hypoparathyroidism following one or more neck operations in patients with MEN 2A, combined with the frequent delay in autograft function, forearm parathyroid autografting should always be performed with the initial PHPT surgery. Most experts avoid total parathyroidectomy unless all four glands are obviously abnormal and preservation of an in situ parathyroid remnant is not possible. Grade: C Recommendation

R49. For patients who are found to develop PHPT after a prior thyroidectomy, operative management should be directed parathyroid surgery and based on the findings from preoperative parathyroid localization studies. Forearm parathyroid autografting should always be performed unless a functioning forearm autograft is known to already be present; even if intra-operative parathyroid hormone (PTH) values suggest the presence of additional parathyroid tissue in the neck. Grade: C Recommendation

R50. Medical therapy to control PHPT in MEN 2A should be considered in patients with high risk of surgical mortality, limited life expectancies, or persistent or recurrent PHPT after one or more surgical attempts for cure. Grade: C Recommendation

Initial Diagnosis and Therapy of Clinically Apparent Disease

R52. This Guideline defers the recommended approach to thyroid nodules, including fine-needle aspiration (FNA) and serum Ct testing, to the ATA Guideline that addresses thyroid nodules (Cooper et al., 2006). However, if obtained, a basal or stimulated* serum Ct level >100 pg/mL should be interpreted as suspicious for MTC and further evaluation and treatment should ensue (see Fig. 2 in the original guideline document). Grade: A Recommendation

Preoperative Laboratory Testing for Presumed MTC When an FNA or Ct Level Is Diagnostic or Suspicious for MTC

R53. Preoperative evaluation of patients presumed to have MTC (when an FNA or Ct level is diagnostic or suspicious for MTC) should include serum measurements of basal Ct, carcino-embryonic antigen (CEA), and calcium (albumin-corrected or ionized); and RET protooncogene analyses. PHEO preoperative screening should begin by age 8 years for those with MEN 2B, and mutated RET codons 634 and 630; and by age 20 years for other RET mutations. Exclusion of PHEO may include any of the following tests: 1) negative RET protooncogene analysis and family history; 2) negative plasma free metanephrines and normetanephrines, or negative 24-hour urine metanephrines and normetanephrines; 3) negative adrenal computed tomography (CT) or magnetic resonance imaging (MRI). Grade: A Recommendation

Evaluation and Treatment of PHEO

R54. Patients with MTC and elevated plasma free metanephrines or normetanephrines, or elevated 24-hour urine metanephrines or normetanephrines should undergo adrenal imaging for PHEO with magnetic resonance imaging or CT scan. Grade: A Recommendation

R55. In the setting of MTC, routine extra-abdominal imaging for PHEO is not indicated. Grade: E Recommendation

R56. PHEO should be surgically resected after appropriate preoperative preparation and prior to surgery for MTC or PHPT, preferably by laparoscopic adrenalectomy. Grade: A Recommendation

R57. Cortical-sparing adrenal surgery may be considered in patients requiring surgery when there is only one remaining adrenal gland, or when bilateral PHEOs are present. Grade: C Recommendation

Preoperative Imaging for Presumed MTC When an FNA or Ct Level Is Diagnostic or Suspicious for MTC

R58. Preoperative neck US is recommended for all patients when an FNA or Ct level is diagnostic or suspicious for MTC. Grade: A Recommendation

R59. Preoperative chest CT, neck CT, and three-phase contrast-enhanced multidetector liver CT or contrast-enhanced MRI is recommended for all patients with suspected MTC when local lymph node metastases are detected (N1), or the serum Ct is >400 pg/mL. Grade: C Recommendation

R60. Fluorodeoxyglucose positron emission tomography (FDG PET) imaging and somatostatin receptor imaging are not recommended for routine initial screening for MTC metastases in patients when an FNA and/or Ct level is diagnostic or suspicious for MTC. Grade: E Recommendation

Surgery for MTC Patients Without Advanced Local Invasion or Cervical Node or Distant Metastases

R61. Patients with known or highly suspected MTC with no evidence of advanced local invasion by the primary tumor, no evidence of cervical lymph node metastases on physical examination and cervical US, and no evidence of distant metastases should undergo total thyroidectomy and prophylactic central compartment (level VI) neck dissection. Grade: B Recommendation

Surgery for MTC Patients with Limited Local Disease and Limited or No Distant Metastases

R62. MTC patients with suspected limited local metastatic disease to regional lymph nodes in the central compartment (with a normal US examination of the lateral neck compartments) in the setting of no distant (extracervical) metastases, or limited distant metastases should typically undergo a total thyroidectomy and level VI compartmental dissection. A minority of the Task Force favored prophylactic lateral neck dissection when lymph node metastases were present in the adjacent paratracheal central compartment. Grade: B Recommendation

R63. MTC patients with suspected limited local metastatic disease to regional lymph nodes in the central and lateral neck compartments (with US-visible lymph node metastases in the lateral neck compartments) in the setting of no distant metastases, or limited distant metastases should typically undergo a total thyroidectomy, central (level VI), and lateral neck (levels IIA, III, IV, V) dissection. Grade: B Recommendation

R64. In the presence of distant metastatic disease, less aggressive neck surgery may be appropriate to preserve speech, swallowing, and parathyroid function while maintaining locoregional disease control to prevent central neck morbidity. Grade: C Recommendation

Surgery for MTC Patients with Advanced Local Disease or Extensive Distant Metastases

R65. In the presence of advanced local or distant disease, less aggressive neck surgery may be appropriate to maintain local disease control while preserving speech, swallowing, and parathyroid function. Grade: C Recommendation

R66. In patients with extensive distant metastases a palliative neck operation may still be needed when there is pain, or evidence of tracheal compromise and the need to maintain a safe airway. Otherwise, in the setting of moderate to high volume extra-cervical disease, neck disease may be observed and surgery deferred (Task Force opinion was not unanimous). Grade: C Recommendation

Thyrotropin Suppression Therapy in MTC

R67. Replacement rather than suppressive thyroxine (T4) therapy with target serum thyrotropin (TSH) levels between 0.5 and 2.5 mIU/L is recommended for patients with MTC. Grade: B Recommendation

Somatic RET Testing in Sporadic MTC

R68. Currently, sporadic MTC tumors should not be routinely evaluated for somatic RET mutations, although agreement amongst the Task Force was not unanimous. Grade: D Recommendation

Initial Evaluation and Treatment of Postoperative Patients

Postoperative Staging Systems

R69. Postoperatively, the tumor-node-metastasis (TNM) classification (see Table 4 in the original guideline document) and other factors, such as the postoperative Ct level and the Ct and CEA doubling times (DTs), should be used to predict outcome and to help plan long-term follow-up of patients with MTC (see Figures 3 and 5 in the original guideline document). Grade: C Recommendation

Completion Thyroidectomy and Lymph Node Dissection After Hemithyroidectomy

R70. Patients with MTC diagnosed after hemithyroidectomy (including those with microscopic MTC) should undergo RET oncogene testing, measurement of serum Ct, and neck US. Grade: A Recommendation

R71. Additional testing and therapy (to likely include completion thyroidectomy and central lymph node dissection) should be offered if histology shows multicentric tumor, CCH, extra-thyroidal extension, or positive surgical margin; when neck US is suspicious for persistent local disease in the contralateral thyroid lobe, or central or lateral neck compartments; when RET mutation is positive; or when family history is positive for MEN 2. See Figure 2 in the original guideline document. Grade: B Recommendation

R72. Patients treated with hemithyroidectomy who demonstrate unifocal intrathyroidal sporadic MTC confined to the thyroid who have no CCH, negative surgical margin, and no suspicion for persistent disease on neck US may be considered for additional surgery or follow-up without additional surgery if the basal serum Ct is below the upper normal of the reference range more than 2 months after surgery (see Figure 5 in the original guideline document). Those with a basal serum Ct above the normal reference range should undergo additional testing and therapy (to often include completion thyroidectomy and central lymph node dissection) per Figure 2 in the original guideline document. Grade: B Recommendation

Laboratory Testing After Resection of MTC

R73. MTC serum tumor markers (Ct and CEA) should be measured 2 to 3 months postoperatively. Grade: B Recommendation

Testing and Treatment of Patients with Undetectable Postoperative Basal Serum Ct

R74. When the postoperative basal serum Ct is undetectable (along with an undetectable stimulated serum Ct if performed, although the majority of the Task Force felt it was unnecessary), the risk of persistent or recurrent residual disease is low, and other tests or imaging techniques are not immediately required and the patient may enter into long-term follow-up. A neck US may be considered to establish a baseline. Grade: E Recommendation

Testing and Treatment of Patients with a Detectable, But Modestly Elevated Postoperative Basal Serum Ct

R75. Postoperative MTC patients with detectable serum Ct levels <150 pg/mL should be evaluated with neck US. Grade: B Recommendation

R76. In addition to neck US, postoperative MTC patients with detectable serum Ct levels that are <150 pg/mL may be considered for additional imaging to serve as baseline examinations for future comparison even though these studies are usually negative. Alternatively, this additional imaging can be deferred and subsequently implemented should the serum Ct rise over time. Grade: C Recommendation

R77. Surgical resection of locoregional recurrent or persistent MTC in patients without distant metastases or with minimal distant metastases should include compartmental dissection of image or biopsy-positive disease in the central (level VI) or lateral (levels IIA, III, IV, V) neck compartments. Removal of only grossly metastatic lymph nodes, or other limited procedures, should be avoided in the absence of extensive prior surgery in that compartment. Grade: B Recommendation

R78. In the absence of residual anatomically identifiable disease (neck US and CT) in a thyroidectomized patient with a measurable Ct level who has not previously undergone a level VI compartmental dissection, an empiric central compartment dissection may be considered but remains controversial. Grade: C Recommendation

Testing and Treatment of Patients with a Significantly Elevated Postoperative Basal Serum Ct

R79. In addition to neck US, postoperative MTC patients with serum Ct levels ≥150 pg/mL should undergo additional imaging techniques to evaluate for distant metastases (see Figure 3 in the original guideline document). Grade: Recommendation B

R80. In postoperative MTC patients with serum Ct levels ≥150 pg/mL with small (<1 cm) locoregional lymph node metastases that are nonthreatening, and with no evidence of distant metastases, immediate intervention is of unknown benefit and such lymph nodes may be observed or undergo re-operative compartmental dissection of image or biopsy-positive compartments. Grade: C Recommendation

R81. In postoperative MTC patients with serum Ct levels ≥150 pg/mL with small (<1 cm) locoregional metastatic disease that is asymptomatic and nonthreatening, and with distant metastases, immediate intervention towards the locoregional disease is of unknown benefit and such lymph nodes may be observed. Grade: C Recommendation

R82. Postoperative MTC patients with serum Ct levels ≥150 pg/mL with symptomatic and/or progressive locoregional disease >1 cm should be considered for locoregional therapy (e.g., surgery), while those with symptomatic distant metastases should be considered for clinical trials and palliative therapies such as surgery, external beam radiation therapy (EBRT), percutaneous interventions, and hepatic embolization. Grade: B Recommendation

R83. The routine use of cytotoxic chemotherapy should be discouraged in patients with MTC. It may be considered for selected patients with rapidly progressive disease not amenable to clinical trials or other palliative therapies discussed below under "Management of Persistent or Recurrent Metastatic MTC." Grade: E Recommendation

R84. Somatostatin analogs are ineffective to control tumor growth and typically should not be considered for this purpose. Grade: F Recommendation

Role of Postoperative Radioiodine Ablation

R85. Postoperative radioactive iodine is not recommended for patients with MTC in the absence of concomitant epithelial cell–derived differentiated thyroid cancer. Grade: E Recommendation

Role of Empiric Liver or Lung Biopsy, Hepatic Vein Sampling, Systemic Vascular Sampling, or Hepatic Angiography

R86. We do not recommend the routine use of empiric liver or lung biopsies, hepatic vein sampling, systemic vascular sampling, or hepatic angiography prior to re-operation. These diagnostic procedures should be used sparingly, if at all. Grade: D Recommendation

Management of Persistent or Recurrent MTC

Goal of Management of Patients with Metastatic MTC: Choosing When Metastases Require Treatment

R87. Active treatment is most often indicated in patients with lesions in critical locations such as brain metastases, impending or active central nervous system compression, airway compromise, symptomatic lesions, hormonal secretion, and impending or active fracture of a weight-bearing bone. Grade: A Recommendation

Management of Patients with Metastatic MTC: Determining Tumor Burden and Rate of Progression Using Sequential Imaging and Tumor Marker Doubling Times (DTs)

R88. Asymptomatic patients with small volume metastatic disease that is stable to slowly progressive as determined by anatomic imaging, or Ct and CEA DT >2 years, typically do not require systemic therapy, and the decision to initiate such treatment should be made with the patient only after a thorough discussion. Grade: E Recommendation

R89. Patients with rapidly progressive disease by anatomic imaging or biochemical DT <2 years should be considered for treatment, ideally in the context of a well-designed clinical trial. Grade: B Recommendation

Management of Ct-positive, But Imaging-negative Patients

R90. Patients with detectable basal serum Ct levels postoperatively with negative imaging should have the basal Ct and CEA levels obtained approximately every 6 months initially to determine the DTs. Ongoing follow-up of these tumor markers and physical examination should occur at one fourth the shortest DT or annually, whichever is more frequent (i.e., follow the patient every 6 months if the shortest DT is 24 months). Grade: B Recommendation

R91. In patients with detectable basal serum Ct levels postoperatively with negative imaging, if the Ct or CEA rises substantially since the previous anatomic imaging evaluation, then a neck US should be performed. The Ct elevation required to trigger this action typically depends on the basal serum Ct and the clinical situation, but elevation by more than 20% to 100% may prompt this evaluation. If the serum Ct is >150 pg/mL then systemic imaging should be repeated as well (see Figure 5 in the original guideline document). Grade: C Recommendation

Adjunctive External Beam Irradiation to the Neck

R92. External beam radiation therapy (EBRT) should not be used as a substitute for surgery in patients in whom neck tumor foci can be resected without excessive morbidity. Grade: E Recommendation

R93. Postoperative EBRT to the neck and mediastinum may be indicated in patients who undergo a gross incomplete resection (R2 resection). Prior to initiating EBRT, physicians should ensure that optimal surgery has been performed as re-operation (other than major ablative procedures) is much more difficult, and may not be safely or technically possible, after EBRT. Grade: B Recommendation

R94. Postoperative adjuvant EBRT to the neck and mediastinum may be considered in patients who are found to have microscopic positive margin(s) (R1 resection) following surgery for moderate to high volume disease involving the central compartment (level VI) and one or both lateral neck compartments (levels 2A–V). EBRT may also be considered in those who appear to have undergone a margin-negative (R0) operation in the setting of moderate to high volume disease with extra-nodal soft tissue extension of tumor when the post-operative serum Ct remains detectable in the absence of distant metastases. Physicians should be sure that optimal surgery has been performed before proceeding with EBRT. (Task Force opinion was not unanimous as some questioned the benefits of EBRT in these settings.) Grade: C Recommendation

R95. Postoperative adjuvant EBRT to the neck should not be performed in an effort to treat a persistent elevation in serum level of Ct in the absence of a gross or microscopic positive margin or moderate to high volume neck disease with extra-nodal soft tissue extension. Grade: E Recommendation

Brain Metastases

R96. Patients with isolated or limited brain metastases should be considered for surgical resection. EBRT (including stereotactic radiosurgery) may be indicated for brain metastases not amenable to surgery. Grade: C Recommendation

Bone Metastases

R97. Patients with spinal cord compression require urgent glucocorticoid therapy, surgical evaluation, and subsequent radiation oncology consultation. Grade: C Recommendation

R98. Surgery is indicated in weight-bearing bone metastases with fracture or impending fracture. Grade: C Recommendation

R99. EBRT should be considered to treat painful bone metastases and is indicated for clinically significant lesions that are not candidates for surgery, especially if they demonstrate disease progression or may threaten adjacent structures if they progress. Grade: C Recommendation

R100. EBRT is indicated postoperatively for bone metastases that are incompletely resected. Grade: C Recommendation

R101. Minimally invasive percutaneous methodologies (alone or in combination) should be considered to treat painful bone metastases, especially those that have failed or are not candidates for surgery or EBRT. Grade: C Recommendation

R102. Small bone metastases that are asymptomatic and are not an immediate threat may be followed. Grade: C Recommendation

R103. Recommend neither for nor against the use of bisphosphonates in the setting of MTC with osseous metastases. Grade: I Recommendation

Lung and Mediastinal Metastases

R104. Lung or mediastinal lesions that are progressive should be considered for clinical trials, or focal therapy. Grade: C Recommendation

Hepatic Metastases

R105. Liver metastases that are progressive, large, or associated with symptoms such as diarrhea or pain should be considered for active treatment. The method of treatment often depends on whether the lesions requiring therapy are limited or multiple and disseminated. Grade: B Recommendation

Palliative Surgery

R106. Palliative therapy, including surgery, should be considered for symptomatic lesions causing pain, mechanical compression, or hormonal secretion. Grade: C Recommendation

Chemotherapy and Clinical Trials

R107. The use of standard chemotherapeutic agents should not be considered as first-line therapy for patients with persistent or recurrent MTC given the low response rates and the advent of promising new compounds entering clinical trials and other available treatment options. Grade: D Recommendation

R108. Treatment with radio-labeled molecules may be considered in selected patients, ideally in the setting of a well-designed clinical trial. Grade: C Recommendation

R109. Given the absence of an established effective systemic therapy for patients with advanced MTC, physicians should give high priority to facilitating enrollment of their patients into well-designed clinical trials. Grade: C Recommendation

Symptoms, Evaluation, and Treatment of Hormonally Active Metastases

R110. Therapy to reduce the frequency and amount of diarrhea in the setting of MTC should be employed. Initial therapy should include antimotility agents. Alternative therapies may include treatment with somatostatin analogues and local therapies such as surgery or chemoembolization in selected cases. Grade: C Recommendation

R111. Clinicians should maintain a heightened vigilance for Cushing syndrome due to tumoral production of adrenocorticotropic hormone (ACTH) and/or corticotropin-releasing hormone (CRH) from MTC. Grade: C Recommendation

R112. While MTC patients with Cushing syndrome typically have a poor prognosis, treatment should be considered even in the setting of widely metastatic MTC because the syndrome can be severe and debilitating. Grade: C Recommendation

R113. Cushing syndrome from MTC may be treated in a multimodality manner with therapy directed towards the tumor and medical therapy directed towards the Cushing syndrome, or bilateral adrenalectomy. The choice of therapy may depend on multiple factors including the severity and the stability of the MTC and the response of the Cushing syndrome to medical therapy. However, expert opinion of the Task Force generally favored bilateral adrenalectomy. Grade: C Recommendation

Long-term Follow-up and Management

Goals of Long-term Follow-up and Management of Patients with and Without Residual Disease

R114. Long-term biochemical monitoring for patients with MTC who achieve a complete biochemical cure should be performed. Grade: B Recommendation

R115. Long-term biochemical monitoring for MTC patients who achieve a complete biochemical cure should include annual measurement of serum Ct. Grade: C Recommendation

R116. Patients with persistent MTC should be monitored by measuring Ct and CEA levels, along with history and physical examinations. The timing of follow-up anatomic imaging may be based on the relative stability of these tests, presence or absence of symptoms, and the location of known or likely sites of metastatic deposits. Grade: C Recommendation

R117. Patients with detectable basal serum Ct levels postoperatively should have the basal Ct and CEA levels obtained approximately every 6 months to determine their DTs. Ongoing follow-up of these tumor markers and physical examination should occur at one fourth the shortest DT or annually, whichever is more frequent (i.e., follow patient every 6 months if the shortest DT is 24 months). Grade: C Recommendation

R118. In patients with detectable basal serum Ct levels postoperatively, if the Ct or CEA rises substantially since the previous anatomic imaging evaluation, then a neck US should be performed. The Ct elevation required to trigger this action typically depends on the basal serum Ct and the clinical situation, but elevation by more than 20% to 100% may prompt this evaluation. If the serum Ct is >150 pg/mL then systemic imaging should be repeated as well. Grade: C Recommendation

Follow-up of Patients Without MTC at Thyroidectomy

R119. After prophylactic thyroidectomy demonstrates no evidence of MTC, the risk of developing MTC is low, and the optimal follow-up for these patients is uncertain. Annual measurement of basal serum Ct without measurement of CEA should be considered. Less frequent testing may be considered if there is no evidence of disease after prolonged follow-up. Grade: C Recommendation

Role of Stimulation Testing for Serum Ct

R120. Stimulated serum Ct testing may detect low levels of residual disease despite undetectable basal Ct values. Such minimal disease is currently unlikely to be able to be localized or treated, and therefore this follow-up testing is not recommended (agreement amongst the Task Force was not unanimous). Grade: D Recommendation

Management of CEA-positive, but Ct-negative Patients

R121. Elevated CEA levels that are out of proportion to the serum Ct may occur from several causes, including some unrelated to MTC, which should be considered and evaluated as appropriate based on clinical judgment. Grade: C Recommendation

Lichen Planus Amyloidosis (LPA)

R122. LPA should be treated symptomatically to minimize pruritus. Grade: C Recommendation

*Stimulated Ct testing historically was done by measuring serum Ct levels at intervals after intravenous administration of the secretagogue pentagastrin and/or calcium. Pentagastrin is not available in the United States and many other countries. Additionally, newer calcitonin assays have significantly improved functional sensitivities, currently as low as 1 to 2 pg/mL. Resultingly, most experts believe that there is rarely a need for stimulated Ct testing in the diagnosis or follow-up of MTC.

Definitions:

Strength of Recommendations Based on Available Evidence

Rating Definition
A Strongly recommends. The recommendation is based on good evidence that the service or intervention can improve important health outcomes. Evidence includes consistent results from well-designed, well-conducted studies in representative populations that directly assess effects on health outcomes.
B Recommends. The recommendation is based on fair evidence that the service or intervention can improve important health outcomes. The evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies; generalizability to routine practice; or indirect nature of the evidence on health outcomes.
C Recommends. The recommendation is based on expert opinion.
D Recommends against. The recommendation is based on expert opinion.
E Recommends against. The recommendation is based on fair evidence that the service or intervention does not improve important health outcomes or that harms outweigh benefits.
F Strongly recommends against. The recommendation is based on good evidence that the service or intervention does not improve important health outcomes or that harms outweigh benefits.
I Recommends neither for nor against. The panel concludes that the evidence is insufficient to recommend for or against providing the service or intervention because evidence is lacking that the service or intervention improves important health outcomes, the evidence is of poor quality, or the evidence is conflicting. As a result, the balance of benefits and harms cannot be determined.

Adapted from the U.S. Preventive Services Task Force, Agency for Healthcare Research and Quality.

Clinical Algorithm(s)

Clinical algorithms are provided in the original guideline document for the following:

  • Initial diagnosis and therapy of pre-clinical disease
  • Initial diagnosis and therapy of clinically apparent disease
  • Initial evaluation and treatment of postoperative patients
  • Management of medullary thyroid cancer (MTC) after hemithyroidectomy
  • Long-term surveillance

Evidence Supporting the Recommendations

References Supporting the Recommendations
Type of Evidence Supporting the Recommendations

The type of supporting evidence is specifically stated for each recommendation (see the "Major Recommendations" field).

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Accurate and appropriate diagnosis, management, and treatment of medullary thyroid cancer (MTC)

Potential Harms
  • Central compartment lymph dissection is associated with a higher rate of hypoparathyroidism and vocal cord paralysis.
  • Tiered approaches are at risk of failing to detect rare double mutations.
  • Children undergoing thyroid or parathyroid surgery have higher complication rates than adult patients.
  • The parathyroid glands are very small and translucent in infants. Proper identification and handling is critical to avoiding hypoparathyroidism.
  • Normal parathyroid glands can be accidentally removed or devascularized during thyroidectomy or central neck lymph node dissection procedures.
  • There may be pitfalls in the diagnosis of medullary thyroid cancer (MTC) with fine-needle aspiration (FNA).
  • Lateral neck compartmental dissection can be associated with long-term cosmetic and functional consequences.
  • The morbidity of external beam radiation therapy (EBRT) is typically greater in the elderly.
  • Toxicities seen with pretargeted radio-immunotherapy with bispecific monoclonal antibody (BsMAb) and a 131I-labeled bivalent hapten are mainly hematologic and related to bone or bone-marrow tumor spread.

Contraindications

Contraindications

Contraindications to surgical therapy include excessive surgical risk or limited life expectancy.

Qualifying Statements

Qualifying Statements
  • The American Thyroid Association (ATA) develops Clinical Practice Guidelines to provide guidance and recommendations for particular practice areas concerning thyroid disease and thyroid cancer. The Guidelines are not inclusive of all proper approaches or methods, or exclusive of others. The Guidelines do not establish a standard of care and specific outcomes are not guaranteed.
  • Treatment decisions must be made based on the independent judgment of health care providers and each patient's individual circumstances. A guideline is not intended to take the place of physician judgment in diagnosing and treating particular patients.
  • The ATA develops guidelines based on the evidence available in the literature and the expert opinion of the task force in the recent timeframe of the publication of the guidelines. Management issues have not been and cannot be comprehensively addressed in randomized trials; therefore, the evidence cannot be comprehensive. Guidelines cannot always account for individual variation among patients. Guidelines cannot be considered inclusive of all proper methods of care or exclusive of other treatments reasonably directed at obtaining the same results.
  • Therefore, the ATA considers use of this guideline to aid in clinical decision-making to be voluntary, with the ultimate determination regarding its application to be made by the treating physician and health care professionals with the full consideration of the individual patient's clinical history and physical status. In addition, the guideline concerns the therapeutic interventions used in clinical practice and do not pertain to clinical trials.

Implementation of the Guideline

Description of Implementation Strategy

An implementation strategy was not provided.

Implementation Tools
Clinical Algorithm
For information about availability, see the Availability of Companion Documents and Patient Resources fields below.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
End of Life Care
Getting Better
Living with Illness
IOM Domain
Effectiveness
Patient-centeredness

Identifying Information and Availability

Bibliographic Source(s)
American Thyroid Association Guidelines Task Force, Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H, Moley JF, Pacini F, Ringel MD, Schlumberger M, Wells SA Jr. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009 Jun;19(6):565-612. [398 references] PubMed External Web Site Policy
Adaptation

Not applicable: The guideline was not adapted from another source.

Date Released
2009 Jun
Guideline Developer(s)
American Thyroid Association - Professional Association
Source(s) of Funding

Guidelines funding was derived solely from the general funds of the American Thyroid Association (ATA) and Thyroid Cancer Survivors' Association, Inc. (ThyCa) through an unrestricted educational grant and were devoid of commercial support.

Guideline Committee

The American Thyroid Association Guidelines Task Force

Composition of Group That Authored the Guideline

Task Force Members: Richard T. Kloos (Chair), Departments of Internal Medicine and Radiology; Divisions of Endocrinology, Diabetes and Metabolism & Nuclear Medicine, The Ohio State University, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, and The Ohio State University Comprehensive Cancer Center, Columbus, Ohio. Charis Eng, Genomic Medicine Institute, Lerner Research Institute and Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, Ohio, and Department of Genetics and CASE Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio. Douglas B. Evans, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin. Gary L. Francis, Department of Pediatrics, Virginia Commonwealth University, Richmond, Virginia. Robert F. Gagel, Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas. Hossein Gharib, Mayo Clinic College of Medicine, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Rochester, Minnesota. Jeffrey F. Moley, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri. Furio Pacini, Section of Endocrinology and Metabolism, Department of Internal Medicine, Endocrinology and Metabolism and Biochemistry, University of Siena, Policlinico Santa Maria alle Scotte, Siena, Italy. Matthew D. Ringel, Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, and The Ohio State University Comprehensive Cancer Center, Columbus, Ohio. Martin Schlumberger, Department of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy and University Paris XI-Sud, Villejuif, France. Samuel A. Wells Jr, Department of Surgery, Washington University Medical Center, St. Louis, Missouri,

Financial Disclosures/Conflicts of Interest

Task Force disclosure information is provided for the two years prior to March 2008 and the known future as of February 2009. RTK served as a consultant for AstraZeneca, Bayer Pharmaceuticals Corporation, and Onyx Pharmaceuticals, Inc. (without compensation) and received grant support from Exelixis and Eisai. GLF is a stockholder of Pfizer Inc. RFG served as a consultant for Exelixis and received grant support from AstraZeneca. MDR served as a consultant for Amgen and received grant support from Exelixis and Eisai. MS served as a consultant for AstraZeneca; received speaker honoraria from AstraZeneca and Pfizer Inc.; and received or is the potential recipient of grant support from AstraZeneca, Amgen, Exelixis, and Eisai. SAW received speaker honoraria from AstraZeneca. CE, DBE, HG, JFM, and FP report that no competing financial interests exist.

Guideline Status

This is the current release of the guideline.

Guideline Availability

Electronic copies of the updated guideline: Available from American Thyroid Association Web site External Web Site Policy.

Print copies: Available from American Thyroid Association, 6066 Leesburg Pike, Suite 550, Falls Church, VA 22041.

Availability of Companion Documents

None available

Patient Resources

None available

NGC Status

This NGC summary was completed by ECRI Institute on May 7, 2010.

Copyright Statement

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.

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