Methods

 Presentation of results and recommendations

Table 1 presents the organization of the Task Force’s results, recommendations, and definitions. Readers of the print version are referred to the page number for information about specific topics, recommendations, and definitions. The location key can be used if viewing the guidelines in a file or web page. Each location key is unique and can be copied into the Find or Search functions to rapidly navigate to the section of interest. Specific recommendations and definitions are presented as bulleted points in the main body of this scholarly guidelines dialog. Table 2 presents a guide to the abbreviations used.

 Table 1. Organization of Medullary Thyroid Carcinoma Guidelines, Recommendations, and Definitions

Location keya
Page
Section Subsection R or D number
[A]
568
Background  
 
[B]
569
Initial diagnosis and therapy of preclinical disease in MEN 2 syndromes
 
[B1]
569
  Clinical manifestations and syndromes of RET mutations in MEN 2A
D1
[B2]
570
  Clinical manifestations and syndromes of RET mutations in FMTC
D2
[B3]
572
  Clinical manifestations and syndromes of RET mutations in MEN 2B
D3
[B4]
573
  Role of germline RET testing in MTC patients
R1–R5
[B5]
574
  Prophylactic thyroidectomy
R6–R8
[B6]
575
  RET testing in asymptomatic people
R9–R10
[B7]
576
  RET testing methodologies
R11–R15
[B8]
576
  Genetic testing: privacy vs. notification of potentially affected family members
R16
[B9]
577
  Reproductive options of RET mutation carriers
R17
[B10]
577
  Possibility of inherited disease in RET mutation–negative MTC patients and families
R18
[B11]
577
  Preoperative testing of asymptomatic RET mutation–positive patients for MTC, PHPT, and PHEO
R19–R26
[B12]
578
  Sources of Ct assay interference
R27
[B13]
579
  Effects of age and sex on the normal Ct range
R28–R31
[B14]
579
  Surgery for the youngest MEN 2B patients
R32–R33
[B15]
580
  Surgery for the youngest MEN 2A or FMTC patients
R34–R36
[B16]
580
  Preoperative imaging and biochemical testing to evaluate for MTC in older RET mutation–positive patients
R37
[B17]
580
  Surgery for the older MEN 2B patients without evidence of cervical lymph node metastases and normal or minimally elevated Ct levels
R39–R40
[B18]
581
  Surgery for the older MEN 2A or FMTC patients without evidence of cervical lymph node metastases and normal or minimally elevated Ct levels
R41–R42
[B19]
581
  Diagnostic testing for RET mutation–positive patients suspected of having metastases based on imaging or serum Ct level
R43
 
[B20]
581
  Management of normal parathyroid glands resected or devascularized during surgery
R44–R46
[B21]
581
  Treatment of PHPT in MEN 2A
R47–R50
[C]
582
Initial diagnosis and therapy of clinically apparent disease
R52
[C1]
583
  Preoperative laboratory testing for presumed MTC when an FNA or Ct level is diagnostic or suspicious for MTC
R53
[C2]
583
  Evaluation and treatment of PHEO
R54–R57
[C3]
584
  Preoperative imaging for presumed MTC when an FNA or Ct level is diagnostic or suspicious for MTC
R58–R60
[C4]
584
  Surgery for MTC patients without advanced local invasion or cervical node or distant metastases
R61
[C5]
585
  Surgery for MTC patients with limited local disease and limited or no distant metastases
R62–R64
[C6]
585
  Surgery for MTC patients with advanced local disease or extensive distant metastases
R65–R66
[C7]
586
  Thyrotropin suppression therapy in MTC
R67
[C8]
586
  Somatic RET testing in sporadic MTC
R68
[D]
586
Initial evaluation and treatment of postoperative patients
 
[D1]
586
  Postoperative staging systems
R69
[D2]
587
  Completion thyroidectomy and lymph node dissection after hemithyroidectomy
R70–R72
[D3]
588
  Laboratory testing after resection of MTC
R73
[D4]
588
  Testing and treatment of patients with an undetectable postoperative basal serum Ct
R74
[D5]
588
  Testing and treatment of patients with a detectable, but modestly elevated postoperative basal serum Ct
R75–R78
[D6]
590
  Testing and treatment of patients with a significantly elevated postoperative basal serum Ct
R79–R84
[D7]
591
  Role of postoperative radioiodine ablation
R85
[D8]
591
  Role of empiric liver or lung biopsy, hepatic vein sampling, systemic vascular sampling, or hepatic angiography
R86
[E]
591
Management of persistent or recurrent MTC
 
[E1]
591
  Goal of management of patients with metastatic MTC: choosing when metastases require treatment
R87
[E2]
592
  Management of patients with metastatic MTC: determining tumor burden and rate of progression using sequential imaging and tumor marker DTs
R88–R89
[E3]
592
  Management of Ct-positive, but imaging-negative patients
R90–R91
[E4]
592
  Adjunctive external beam irradiation to the neck
R92–R95
[E5]
593
  Brain metastases
R96
[E6]
593
  Bone metastases
R97–R103
[E7]
594
  Lung and mediastinal metastases
R104
[E8]
594
  Hepatic metastases
R105
[E9]
594
  Palliative surgery
R106
[E10]
594
  Chemotherapy and clinical trials
R107–R109
[E11]
595
  Symptoms, evaluation, and treatment of hormonally active metastases
R110–R113
[F]
596
Long-term follow-up and management
 
[F1]
596
  Goals of long-term follow-up and management of patients with and without residual disease
R114–R118
[F2]
596
  Follow-up of patients without MTC at thyroidectomy
R119
[F3]
597
  Role of stimulation testing for serum Ct
R120
[F4]
597
  Management of CEA-positive, but Ct-negative patients
R121
[F5]
597
  Lichen planus amyloidosis
R122
[G]
597
  Directions for future research
 

aIf viewing these guidelines on the Web, or in a File, copy the Location Key to the Find or Search Function to navigate rapidly to the desired section.
MTC, medullary thyroid carcinoma; R, recommendations; D, definitions; MEN, multiple endocrine neoplasia; FMTC, familial medullary thyroid carcinoma; Ct, calcitonin; PHPT, primary hyperparathyroidism; FNA, fine-needle aspiration; DT, doubling time; CEA, carcinoembryonic antigen.

Table 2. Definitions Used for Medullary Thyroid
Cancer Management Guidelines

ACTH  Adrenocorticotropic hormone
CEA Carcinoembryonic antigen
CEA DT Carcinoembryonic antigen doubling time
CLA Cutaneous lichen amyloidosis
CRH Corticotropin-releasing hormone
Ct Calcitonin
Ct DT Calcitonin doubling time
CT Computed tomography
DT Doubling time
DTPA Diethylenetriamine pentaacetic acid
EBRT External beam radiation therapya
FMTC Familial medullary thyroid cancer
FNA Fine-needle aspiration
HSCR Hirschsprung disease
MEN Multiple endocrine neoplasia
MIBG Metaiodobenzylguanidine
MRI Magnetic resonance imaging
MTC Medullary thyroid carcinoma
OS Overall survival
PHEO Pheochromocytoma
PHPT Primary hyperparathyroidism
PTH Parathyroid hormone
RAI Radioactive iodine
US Ultrasound

aMay include intensity-modulated radiation therapy.

Administration

The ATA Executive Council selected a 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, and all members disclosed potential conflicts of interest. Guidelines funding was derived solely from the general funds of the ATA and Thyroid Cancer Survivors’ Association, Inc. (ThyCa) through an unrestricted educational grant and were devoid of commercial support.

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. The final document was approved by the ATA Board of Directors, and officially endorsed (in alphabetical order) by: 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).

Literature review and evidence-based medicine

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.

The Task Force categorized our recommendations using criteria adapted from the United States Preventive Services Task Force, Agency for Healthcare Research and Quality (Table 3) as was used in the ATA publication Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer (5).

Table 3. 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.