Executive Summary of the American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults

Kepal N. Patel, MD; Linwah Yip, MD; Carrie C. Lubitz, MD, MPH; Elizabeth G. Grubbs, MD; Barbra S. Miller, MD; Wen Shen, MD; Peter Angelos, MD; Herbert Chen, MD; Gerard M. Doherty, MD; Thomas J. Fahey III, MD; Electron Kebebew, MD; Virginia A. Livolsi, MD; Nancy D. Perrier, MD; Jennifer A. Sipos, MD; Julie A. Sosa, MD; David Steward, MD; Ralph P. Tufano, MD; Christopher R. McHenry, MD; Sally E. Carty, MD

Disclosures

Annals of Surgery. 2020;271(3):399-410.

Abstract and Introduction

Abstract

Objective: The aim of this study was to develop evidence-based recommendations for safe, effective and appropriate thyroidectomy.

Background: Surgical management of thyroid disease has evolved considerably over several decades leading to variability in rendered care. Over 100,000 thyroid operations are performed annually in the United States.

Methods: The medical literature from January 1, 1985 to November 9, 2018 was reviewed by a panel of 19 experts in thyroid disorders representing multiple disciplines. The authors used the best available evidence to construct surgical management recommendations. Levels of evidence were determined using the American College of Physicians grading system, and management recommendations were discussed to consensus. Members of the American Association of Endocrine Surgeons reviewed and commented on preliminary drafts of the content.

Results: These clinical guidelines analyze the indications for thyroidectomy as well as its definitions, technique, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Fine Needle Aspiration Biopsy Diagnosis, Molecular Testing, Indications, Extent and Outcomes of Surgery, Preoperative Care, Initial Thyroidectomy, Perioperative Tissue Diagnosis, Nodal Dissection, Concurrent Parathyroidectomy, Hyperthyroid Conditions, Goiter, Adjuncts and Approaches Laryngology Familial Thyroid Cancer, Postoperative Care and Complications, Cancer Management, and Reoperation.

Conclusion: Evidence-based guidelines were created to assist clinicians in the optimal surgical management of thyroid disease.

Introduction

Surgical management of thyroid disease has evolved considerably over several decades leading to variability in rendered care. To help provide safe, effective, and appropriate care of patients, these AAES-sponsored multidisciplinary clinical guidelines analyze the conduct, indications, and outcomes of adult thyroid surgery guided by a comprehensive evidence-based review of the medical literature. Several specific cautions to implementation exist. These guidelines were endorsed by the American Thyroid Association, the International Association of Endocrine Surgeons, the Society of Surgical Oncology, and the Graves' Disease and Thyroid Foundation.

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Table 1. Commercially Available Molecular Tests for Bethesda III and IV Nodules
Test Name	Type of Test	False Negatives*	Sensitivity (95% CI)*	Specificity (95% CI)*
Afirma Gene Sequencing Classifier	Multigene expression (RNA-based)	4/103 (4%)	91% (79%–98%)	68% (60%–76%)
Interpace ThyGenX+ThyraMir	7 gene panel + 10 miRNA	4/67 (6%)	89% (73%–97%)	85% (75%–92%)
CBLPath ThyroSeq version 3	Multigene NGS	4/150 (3%)	94% (86%–98%)	82% (75%–87%)

*Includes only results with histologic correlation and before post hoc exclusions.
CI indicates confidence intervals; miRNA, micro-RNA; NGS, next-generation sequencing; RNA, ribonucleic acid.

Table 2. Clinical Factors That Favor Initial Total Thyroidectomy Versus Lobectomy
Favor total thyroidectomy	1) Planned RAI for known or suspected DTC, including:
	a. Malignant FNAB for >4 cm lesion
	b. Gross ETE on US or intraoperatively
	c. Clinical, IOPE or US evidence for CLNM
	d. Known distant metastasis
	e. Adverse MT result (ie, BRAF V600E + TERT)
	2) MTC
	3) Bilateral thyroid disease, including:
	a. Euthyroid or toxic nodular goiter
	b. Graves' Disease
	c. Contralateral dominant/index nodule
	d. History of XRT
	e. Familial predisposition syndrome
	f. Need for concurrent contralateral parathyroidectomy
	4) Struma ovarii
Controversial/no consensus	1) Uni-lobar known or suspected DTC 1– 4 cm that appears low-risk on US
	2) Index lesion plus existing thyroid hormone dependence
	3) Uni-lobar DTC with need to facilitate Tg/US surveillance
	4) Uni-lobar lesion with complex medical situation
	5) Uni-lobar lesion and patient preference for TT
Favor lobectomy and isthmusectomy	1) Uni-lobar PTMC that appears low-risk on US
	2) Uni-lobar lesion with indolent MT result
	3) Unilateral goiter

When thyroidectomy is already indicated, the listed factors can help inform decision-making about the initial surgical extent, that is, the choice of initial bilateral versus unilateral thyroidectomy. The content is based on the expert opinion of the authors and is not intended to be proscriptive or rotely applicable to individual clinical circumstances (see ''Cautions to Implementation,'' ''Abbreviations Table'').

Table 3. Thyroidectomy Nomenclature
Name of Procedure	Extent of Resection
Lobectomy	One entire thyroid lobe without isthmus
Lobectomy and isthmusectomy	One entire thyroid lobe with isthmus and pyramidal lobe
Isthmusectomy	Isolated isthmus resection
Subtotal thyroidectomy	Preservation of small posterior remnant(s) of the contralateral or bilateral lobe(s)
	(Rarely recommended today)
Near-total thyroidectomy	Resection of all but a very small posterior remnant, ie, at the ligament of Berry
Total thyroidectomy	All visible thyroid tissue
Completion Thyroidectomy	Reoperative resection of any remaining thyroid tissue

Table 4. Anatomic Boundaries of the Neck and Involvement in PTC
Level	Anatomic Boundaries	Likelihood of LNM [95% CI]
I	S: body of the mandible	5%–9% [na]
	P: stylohyoid muscle
	A: anterior belly of the contralateral digastric muscle
	I: hyoid
	Triangular boundaries comprising anterior bellies of digastric muscles and hyoid separates Ia and Ib
II	S: skull base	IIa: 53% [47%–60%]
	P: posterior SCM A: stylohoid muscle	IIb: 16% [8%–27%]
	I: hyoid
	CN XI separates IIa and IIb IIa nodes lie anterior to IJV
III	S: hyoid	71% [67%–74%]
	P: posterior SCM
	A: sternohyoid muscle
	I: horizontal plane defined by the cricoid cartilage
IV	S: inferior border of the cricoid cartilage	66% [61%–71%]
	P: posterior SCM
	A: sternohyoid muscle
	I: clavicle
V	S: convergence of SCM and trapezius	Va: 8% [3%–20%]
	P: anterior border of trapezius	Vb: 22% [8%–48%]
	A: posterior SCM
	I: clavicle
	Inferior border of cricoid separates Va and Vb
VI	S: hyoid superiorly	40%–60% [na]
	P: deep layer of the cervical fascia
	A: anterior layer of the cervical fascia
	I: sternal notch
VII	S: sternal notch
	P: deep layer cervical fascia A: sternum
	I: innominate on right and equivalent plane on the left

A indicates anterior; I, inferior; na, not available; P, posterior; S, superior; SCM, sternocleidomastoid muscle.

Table 5. Recommended Treatment for Causes of Hyperthyroidism
Cause of Thyrotoxicosis	Typical Treatmenth*	Additional Treatment Options	Other (ETOH Ablation, RFA)	Extent of Surgery
Single toxic nodule	Surgery	RAI	ETOH ablation or RFA	Lobectomy and isthmusectomy
TMNG	Surgery	RAI		Total thyroidectomy
Graves' disease 1)No or mild GO 2) + GO	1) RAI or Surgery 2) Surgery	Methimazole		Total thyroidectomy
Acute, subacute, chronic thyroiditis	Supportive (Beta-blockers, NSAIDs)	Steroids Surgery^†		Total thyroidectomy^†
Functional thyroid cancer metastases or benign thyroid deposits	RAI or surgery	Image/catheter guided therapy Chemotherapy	ETOH ablation RFA	Complete resection
Hypothalamic pituitary axis	Surgery	XRT	Medication (octreotide, bromocriptine)	Complete resection
Extrathyroidal neoplasms	Surgery	Image/catheter guided therapy		Complete resection

*Selection of therapy depends on the clinical situation and patient factors.
^†Surgery for thyroiditis is rarely needed is performed in highly selected situations.
ETOH indicates ethanol; GO, Graves ophthalmopathy; NSAID, nonsteroidal anti-inflammatory drug; RFA, radiofrequency ablation.

Table 6. Inherited Predisposition Syndromes for Thyroid Cancer
	Familial Adenomatosis Polyposis	PTEN-Hamartoma Tumor (Cowden)	Carney Complex Type 1	RET-Associated	DICER1
Gene	APC	PTEN	PRKAR1A	RET	DICER1
Pathognomonic criteria	>100 colorectal adenomatous polyps	Mucocutaneous lesions, cerebellar tumors (Lhermitte-Duclos disease)	Multiple pigmented skin lesions (eg, nevi, blue nevi, lentigines)	Medullary thyroid cancer	Pleuropulmonary blastoma
Other major manifestations	–	Breast, endometrial, thyroid cancer, macrocephaly	Blue nevi, pigmented nodular adrenals, cardiac myxomas	Primary hyperparathyroidism, pheochromocytoma, mucosal neuromas	Ovarian sex cord-stromal tumors, cystic nephroma, and multinodular goiter
Minor manifestations	Extracolonic polyps, congenital hypertrophy of retinal pigment epithelium, thyroid nodules/cancer, soft tissue tumors, desmoids, osteomas	Fibrocystic breast disease, gastrointestinal hamartomas, lipomas, fibromas, renal cell carcinomas uterine fibromas	Thyroid nodules, melanotic schwannomas, adrenal or pituitary adenomas, hepatocellular carcinoma, pancreatic cancer	Hirschsprung's disease, cutaneous lichen amyloidosis	Wilms tumor, rhabdomyosarcoma, ciliary body medulloepithelioma, pineoblastoma, pituitary blastoma, nasal chondromesenchymal hamartoma
Thyroid disease prevalence:
Benign
Cancer	40%	75%	Up to 75%	–	Up to 30%
	0.4–12%	35%	<5%	100%	–
Cancer		PTC 50%	PTC
Subtypes	CMV-PTC 63%	FV-PTC 28%	FTC	MTC	FTC
	FV-PTC 25%	FTC 14%			FV-PTC
	PTC 12%

CMV indicates cribriform-morular variant. FV, follicular variant.

Table 7. ATA Risk Stratification Definitions and Treatment
Risk Category	Characteristics	Likelihood of NED After TT and RAI Ablation, %	Minimal Extent of Thyroidectomy	RAI?	Goal TSH, mU/L
Low	Intrathyroidal, completely resected PTC or encapsulated FV-PTC	78–91	Lobectomy	Usually no	0.5–2
	No local or distant metastasis
	No aggressive histology (tall cell, hobnail, or columnar cell)
	Intrathyroidal FTC with capsular and/or <4 foci vascular invasion
	Clinical N0 or ≤5 pathologic N1 micrometastasis (<2 mm)
Intermediate	PTC with microscopic extrathyroidal extension, vascular invasion	52–64	Total	Strongly considered esp with aggressive histologies, older age, and/or lateral LNM	0.1–0.5
	Incomplete response to treatment
	Clinical N1 or >5 pathologic N1 <3 cm
High	Gross extrathyroidal extension	31–32	Total	Yes	<0.1
	Incomplete tumor resection
	Distant metastases
	Nodal metastasis ≥3 cm
	FTC with extensive vascular invasion

NED indicates no evidence of disease, for example, Tg undetectable and no radiographic evidence of disease.

Authors and Disclosures

Kepal N. Patel, MD*, Linwah Yip, MD† Carrie C. Lubitz, MD, MPH‡, Elizabeth G. Grubbs, MD§, Barbra S. Miller, MD¶, Wen Shen, MD||, Peter Angelos, MD**, Herbert Chen, MD††, Gerard M. Doherty, MD‡‡, Thomas J. Fahey III, MD§§, Electron Kebebew, MD¶¶, Virginia A. Livolsi, MD||||, Nancy D. Perrier, MD§, Jennifer A. Sipos, MD***, Julie A. Sosa, MD||, David Steward, MD†††, Ralph P. Tufano, MD‡‡‡, Christopher R. McHenry, MD§§§ and Sally E. Carty, MD†

*Division of Endocrine Surgery, NYU Langone Health, New York, NY; †Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA; ‡Department of Surgery, Massachusetts General Hospital, Boston, MA; §Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX; ¶Division of Endocrine Surgery, University of Michigan, Ann Arbor, MI; ||Department of Surgery, University of California San Francisco, San Francisco, CA; **Department of Surgery and MacLean Center for Clinical Medical Ethics, The University of Chicago, Chicago, IL; ††Department of Surgery, University of Alabama at Birmingham, Birmingham, AL; ‡‡Department of Surgery, Brigham and Women's Hospital, Boston, MA; §§Department of Surgery, The New York Presbyterian Hospital-Weill Cornell Medical Center, New York, NY; ¶¶Department of Surgery and Stanford Cancer Institute, Stanford University, Stanford, CA; ||||Department of Pathology and Laboratory Medicine, Perelman School of Medicine of University of Pennsylvania, Philadelphia, PA; ***Division of Endocrinology and Metabolism, The Ohio State University, Columbus, OH; †††Department of Otolaryngology, University of Cincinnati College of Medicine, Cincinnati, OH; ‡‡‡Division of Head and Neck Endocrine Surgery, Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins School of Medicine, Baltimore, MD; and §§§MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH.

kepal.patel@nyumc.org

Authors' Contributions
S.E.C. and C.R.M. directed the project and coordinated the authors and topics. S.E.C., C.R.M., and K.N.P. developed the methodology, managed disclosures, and prepared the work for publication. C.C.L., E.G.G., B.S.M., K.N.P., W.T.S., and L.Y. carried out the systematic topic reviews and were the primary authors of text. All authors participated directly in editing the text and recommendations. AAES legal counsel approved the language in the section, Cautions to Implementation