THYROID DISEASE
Selections from the 34th Annual Phoenix Surgical Symposium, January 25-28, 2006, Scottsdale, Arizona
Orlo H. Clark, MD, Professor of Surgery, University of California, San Francisco, School of Medicine, and Chief of
Surgery, UCSF/Mt. Zion Medical Center, San Francisco
| MULTINODULAR GOITER: INDICATIONS FOR OPERATIONS AND EXTENT OF THYROIDECTOMY
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| Introduction: most patients euthyroid; some can develop hyperthyroidism (common in countries where iodine not added to
food, eg, in Germany, where 15% of people have thyroid operation)
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| Clinical manifestations of goiter: symptoms—pressure sensation; dysphagia; trouble swallowing; hoarseness;
shortness of breath; inability to sleep flat; hyper-, hypo-, or euthyroidism; physical signs—tracheal or esophageal compression
seen on chest x-ray or computed tomography (CT); cervical or superior mediastinal mass; positive Pemberton
sign (patient will not raise arms above head because this pushes thyroid down, causing superior vena cava obstruction
symptom, evidenced by markedly flushed face and dilated neck veins)
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| Suspicious thyroid nodules: history of radiation exposure; 5- to 10-fold increased risk for nodule being cancerous
with family history of thyroid or breast cancer; 50% to 75% of patients with hard or fixed nodule have thyroid cancer; ipsilateral
lymphadenopathy; growing nodule (rapid increase usually signals hemorrhage of benign nodule); distant metastases;
new clinical presentation in patients <20 yr or >70 yr of age associated with malignant tumor
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| Familial thyroid syndromes: familial adenomatous polyposis—associated with germline mutation in APC gene; associated
with thyroid cancer; very specific cribriform pattern; ≈80% of patients have somatic RET/PTC rearrangement;
Cowden’s syndrome—≈85% of patients have benign multinodular goiters, ≈10% have thyroid cancer; patients often present
with skin tags around eyes and lips, and papillomas (lumps) on tongue; Werner’s syndrome—associated with premature aging;
17% of Japanese patients have benign and malignant thyroid tumors; most common cause of epithelial tumors or thyroid
cancers in Japanese patients; Hürthle cell carcinoma—mutation on chromosome 19q13.2 associated with benign and malignant
tumors; papillary renal neoplasia—associated with mutation on chromosome 1
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| Clinical evaluation: physical evaluation helpful (speaker does not recommend CT, particularly for small goiters); fine
needle aspiration (FNA) cytology very useful; flow loop studies essential; thyroglobulin and calcitonin useful for following
patients; ultrasonography (US) changing management of thyroid cancer and useful for following patients with benign
thyroid lesions; preoperative US important in many patients to evaluate lymph nodes; radioiodine (131 I) scan useful for
patients with suppressed thyroid-stimulating hormone (TSH; may indicate hot nodule; hot nodules rarely cancerous)
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| Indications for thyroidectomy: malignant or suspicious cytology (follicular or Hürthle cell neoplasms in which cytology
does not indicate whether benign or malignant; diagnostic lobectomy indicated); suspicious nodule or nodules on
US; family history of thyroid cancer (familial thyroid cancer accounts for 3%-7% of papillary thyroid cancer and ≈25%
of medullary thyroid carcinoma [MTC]); obstructive symptoms; cosmesis; substernal extension (no area for goiter to
grow into and usually cannot be biopsied)
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| Thyroid US: can help determine nodule size and configuration, whether solitary, dominant, solid or cystic, and whether
suspicious for malignancy (criteria include microcalcifications, irregular border, central vascularity, microcyst formation,
and adjacent suspicious adenopathy)
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| TSH suppressive therapy: review of literature suggests suppression of TSH with small doses of thyroid hormone may be
helpful in smaller nodules, ie, may make nodule decrease in size or stop growth; not indicated for patients with osteoporosis or
underlying cardiovascular disease; safe and beneficial for young patients
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| Recurrence: benign goiter—familial disease ≤50%; sporadic ≤20%; malignant goiter—relatively high recurrence
rate for papillary, follicular, and medullary cancer; prevention—total or near-total thyroidectomy of bilateral disease
(even benign disease); thyroidectomy and isthmusectomy for unilateral disease; ≈98% of substernal goiters removable
with cervical approach (exceptions are recurrent goiters, invasive cancer, and completely mediastinal goiter with no thyroid
tissue in neck)
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| Thyroidectomy technique: ensure incision appropriate size for goiter; incision 1 cm below cricoid cartilage simplifies
operation (isthmus of thyroid usually just below cricoid cartilage); large incision indicated if cricoid cartilage in suprasternal
notch; place incision on normal skin line to limit scarring; divide isthmus early; take down superior thyroid
vessels first (stay away from cricothyroid muscle and external laryngeal nerve); identify recurrent laryngeal nerve at level
of cricoid and trace in cephalad to caudad direction; traction stitches helpful for benign lesion, particularly substernal goiters,
to deliver thyroid through relatively small incision
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| Postoperative complications: rare; include recurrent laryngeal nerve palsy, hypoparathyroidism, and bleeding
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| MANAGEMENT OF PATIENTS WITH PAPILLARY THYROID CANCER
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| Introduction: most common thyroid cancer; in women, prevalence increasing faster than any other cancer (accounts for 3%
of all cancers); ≈1% of well-differentiated thyroid cancers progress to anaplastic cancer; in iodine-rich areas, papillary cancers
more common; in iodine-poor areas, endemic goiter, follicular cancer, and anaplastic cancer more common; Robbins et al—
“although mortality rate from thyroid cancer low, it is the highest among cancers affecting endocrine glands (excluding
ovary)”
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| Risk factors: history of thyroid cancer (risk 30%-40%); exposure to low-dose therapeutic radiation (for patient with thyroid
nodule, risk ≈40%); familial predisposition; multinodular goiter; goitrogens and iodine deficiency; carcinogens
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| Recurrent clinical carcinoma in contralateral thyroid lobe: data suggest 7% to 8% of patients develop clinical
recurrence in thyroid gland if contralateral lobe not removed
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| Recurrent thyroid cancer: ensure patient euthyroid; Mazzaferri et al (1977)—recurrence rate over 15 yr decreased
from >40% to <20% by giving thyroid hormone; total or near-total thyroidectomy and 131 I decrease recurrence rate from
≈18% to 5% to 6%; survival—studies show that one third of patients with recurrent thyroid cancer die from thyroid cancer;
in retrospective study by Staunton and Greening, thyroid hormone decreased recurrence rate of papillary and follicular
cancers (biggest reduction seen soon after operation); study—141 patients followed retrospectively; TSH >0.1 µIU/
mL associated with increased recurrence rate and decreased survival; recommended TSH levels—for high-risk patients,
<0.05 µIU/mL; for low-risk patients, ≈0.1 µIU/mL; Cady et al—recurrence rate 11% in patients categorized as
low risk, but subsequent mortality rate 36%; Grant et al—in low-risk patients, significantly higher recurrence rate after
unilateral resection (14%), compared to bilateral resection (2%); in high-risk patients, significant reduction in recurrence
rate with bilateral resection
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| Near-total thyroidectomy: leaving small amount of thyroid tissue can protect contralateral recurrent nerve; no reason
to leave tissue if parathyroids off thyroid gland, little manipulation required, and nerve clearly visible
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| Pulmonary metastases: one of primary reasons to perform total thyroidectomy; Casara et al—134 patients with pulmonary
metastases; of 42 patients with normal chest x-ray and positive 131 I uptake, 78% had complete remission (thyroglobulin-negative
when scan repeated), and 10-yr survival 96%; of 54 patients with positive chest x-ray and positive 131 I
scan, 4% had complete remission and 10-yr survival 36%
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| Conclusion: total thyroidectomy treatment of choice for virtually all patients with thyroid cancer when it can be performed
safely; no study documents that lesser operations have better results than total thyroidectomy, whereas numerous
studies suggest that patients treated with total thyroidectomy have fewer recurrences and better survival
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| Introduction: accounts for ≈7% of all thyroid cancers and 14% to 17% of thyroid cancer deaths; occurs in sporadic (≈75%) and
familial (≤25%) forms; familial forms include MTC, multiple endocrine neoplasia (MEN)-2A syndrome (patients also have
pheochromocytomas [≈50%] and hyperparathyroidism [≈25%]), and MEN-2B syndrome (patients also have bilateral pheochromocytomas
[50%-60%] mucosal neuromas, bad dentition, and marfanoid habitus); screen all patients for RET point mutations
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| Tumor location: most tumors occur at junction of upper one third and lower two thirds of thyroid, where multiple branchial
bodies join with endoderm of thyroid at base of tongue and where concentration of C cells in normal thyroid gland
highest; recurrent laryngeal nerve and upper parathyroid gland situated in this area, together with cricoid cartilage
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| Clinical evaluation: FNA cytology—most common method of diagnosis; Hürthle cell tumor (follicular tumor) and medullary
cancer sometimes confused; can stain for calcitonin or carcinoembryonic antigen (CEA; found in patients with MTC);
blood testing—calcitonin elevated in virtually all patients with MTC; most patients have RET oncogene; notes—rule out
pheochromocytoma; calcium important before any thyroid operation (20%-25% of patients with MEN-2A have hyperparathyroidism);
US—very helpful; gives information on unifocal or multifocal disease, thyroid size, level of risk, and presence of
cervical lymphadenopathy; studies show preoperative US changes operative approach in 33% to 70% of cases
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| Tumor aggression: Bergholm et al (1997)—of patients with gene for MTC but no clinical manifestations, survival 100%
after removal of thyroid gland; 75% of patients had sporadic disease, 25% had familial disease; stage I (confined to thyroid)
60%, local invasion 17%, lymph nodes or local invasion 7%, stage IV (distant metastases) 17%; Kebebew et al—analysis of
patients in Surveillance Epidemiology and End Results (SEER) database; intrathyroidal disease ≈50%, extrathyroidal (local invasion,
regional metastases, or both) 32%, and distant metastases 13% to 14%
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| Treatment success: Bergholm et al—one third of patients had persistence or recurrence at 1 yr; one third had recurrence
after 1 yr; 142 of 247 patients died; relative survival 69% at 5 yr and 65% at 10 yr; only 10% of patients with sporadic
MTC had low calcitonin level after surgery, indicating thyroid tumor likely to recur; Wells et al and Gharib et
al—although ≈70% of patients who present with MTC and nodal metastases alive at 10 yr, very few calcitonin-negative;
Kebebew et al—“patients who had total or subtotal thyroidectomy less likely to have persistent or recurrent MTC, and
patients who had total thyroidectomy with cervical lymph node clearance required fewer operations or reoperations for
persistent or recurrent disease than patients who underwent lesser operations”; SEER database (1973-2000)—≈91% of
patients treated surgically for MTC, small number treated with external irradiation, and minimal number treated with 131 I
ablation (generally not recommended because majority of patients do not have sodium iodide symporter [NIS] and do not
trap 131 I); cause-specific mortality 9.4% at 10 yr and 27% at 20 yr; 15% of patients had less than total or near-total thyroidectomy
and 41% had no neck node dissection
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| Central and bilateral lymph node dissection: study—55% of 101 patients had nodal metastases; for sporadic MTC,
central 50%, ipsilateral 57%, and contralateral 28%; hereditary tumors had same number of contralateral nodes; Machens et
al—207 RET-positive patients <20 yr of age with tumors <1 cm; age-related progression of C cell hyperplasia (occurs first in
patients with familial disease); no lymph node metastases in patients <14 yr of age; data suggest central node dissection not
required for patients <8 yr of age; 72% of patients underwent prophylactic neck dissection; 5% had normal thyroid gland,
31% had C cell hyperplasia, and ≈60% had MTC (3.4% had nodal metastases); “among patients with codon 634 mutation
(most common in patients with MEN-2A), average interval from tumor development to nodal metastases was 6.6 yr”; Cote
and Gagel—operate on patients with codon 918 mutation (aggressive mutation in MEN-2B) at diagnosis or within 1 yr of
age; for patients with codon 634 mutation, general recommendation wait until 6 yr of age (screen to ensure patient calcitonin-
negative and has no lesions in thyroid gland); Skinner et al—50 patients <20 yr of age had total thyroidectomy and central
neck dissection; after operation, 44 patients calcitonin-negative, 6 calcitonin-positive (2 had elevated basal level); 3 to 30
nodes removed in all but one patient (prophylactic central neck dissection); 3 patients had positive nodes (2 of these had elevated
calcitonin levels); no recurrent laryngeal nerve injuries, but 3 patients had hypoparathyroidism; conclusion that operation
should be performed before 8 yr of age (most say 6 yr of age), and bilateral central neck dissection unnecessary in patients
≤8 yr of age
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| Management of RET oncogene-positive, clinically negative patients: total thyroidectomy without central or lateral
neck dissection; in children, central or lateral neck dissection not required unless calcitonin elevated or lesion identified on
US; perform total thyroidectomy before 6 yr of age in patients with MEN-2A, before 8 yr of age for familial MTC, and at diagnosis
for MEN-2B
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| Classification of node distribution: level 1—submental nodes; level 2—just below mandible; level 3—level of
thyroid cartilage; level 4—jugular nodes (just above clavicle); level 5—posterior triangle; level 6—central neck; level
7—mediastinal
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| Recommended surgical treatment: total thyroidectomy (tumors often multifocal); 131 I not effective; bilateral central
node dissection (not necessary in patients <6 yr of age)
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| Calcitonin: if level >1000 pg/mL and neck scans negative, patient likely has liver metastases; micrometastases in liver
may not appear on CT; prophylactic radical surgery not indicated; patients with 10 positive nodes, nodes >1 cm, or nodal
involvement of >2 cervical lymph node compartments rarely cured; for patients with calcitonin ≈100 pg/mL (normal level
<4 pg/mL) after total thyroidectomy (with or without central neck dissection), perform prophylactic operation (do not wait
for nodes to become positive on scan because patient then incurable)
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| Treatment: repeat surgery indicated; prophylactic surgery indicated if calcitonin remains elevated; total thyroidectomy,
bilateral central neck dissection, and bilateral jugular vein lateral dissection indicated for adult patients; role of radiation
therapy unclear; no chemotherapeutic agent has resulted in complete long-term response with acceptable toxicity
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Educational Objectives
| The goal of this program is to educate the listener on issues in thyroid disease. After hearing and assimilating this program,
the clinician will be better able to:
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 | Identify and evaluate patients with multinodular goiter.
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| Prevent recurrence of multinodular goiter.
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| Manage patients with papillary thyroid cancer.
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| Evaluate patients with medullary thyroid cancer (MTC).
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| Discuss the role of central and bilateral lymph node dissection in patients with MTC.
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Suggested Reading
Alimoglu O et al: Comparison of surgical techniques for treatment of benign toxic multinodular goiter. World J
Surg 29:921, 2005; Caplan RH et al: Long-term follow-up of a patient with papillary thyroid carcinoma, elevated
thyroglobulin levels, and negative imaging studies. Endocr Pract 11:43, 2005; Caron NR, Clark OH: Papillary
thyroid cancer: surgical management of lymph node metastases. Curr Treat Options Oncol 6:311, 2005; Cote GJ,
Gagel RF: Lessons learned from the management of a rare genetic cancer. N Engl J Med 349:1566, 2003; Cundiff
JG et al: Parathyroid adenoma after radioactive iodine therapy for multinodular goiter. Am J Otolaryngol 22:374,
2001; Gibelli B et al: Preoperative determination of serum thyroglobulin to identify patients with differentiated
thyroid cancer who may present recurrence without increased thyroglobulin. Acta Otorhinolaryngol Ital 25:94, 2005;
Giles Y et al: The advantage of total thyroidectomy to avoid reoperation for incidental thyroid cancer in multinodular
goiter. Arch Surg 139:179, 2004; Ito Y et al: Clinical significance of metastasis to the central compartment from
papillary microcarcinoma of the thyroid. World J Surg 30:91, 2006; Kebebew E et al: Extent of disease and practice
patterns for medullary thyroid cancer. J Am Coll Surg 200:890, 2005; Kebebew E et al: Id1 gene expression is
up-regulated in hyperplastic and neoplastic thyroid tissue and regulates growth and differentiation in thyroid cancer
cells. J Clin Endocrinol Metab 89:6105, 2004; Kloos RT: Papillary thyroid cancer: medical management and follow-up.
Curr Treat Options Oncol 6:323, 2005; Kushchayeva Y et al: Prognostic indications for Hurthle cell cancer.
World J Surg 28:1266, 2004; Lang BH, Lo CY: Total thyroidectomy for multinodular goiter in the elderly. Am
J Surg 190:418, 2005; Machens A et al; European Multiple Endocrine Neoplasia (EUROMEN) Study
Group: Early malignant progression of hereditary medullary thyroid cancer. N Engl J Med 349:1517, 2003; Pacini
F et al: Post-surgical use of radioiodine (131I) in patients with papillary and follicular thyroid cancer and the issue
of remnant ablation: a consensus report. Eur J Endocrinol 153:651, 2005; Rios A et al: Surgical treatment of multinodular
goiter in young patients. Endocrine 27:245, 2005; Scollo C et al: Rationale for central and bilateral lymph
node dissection in sporadic and hereditary medullary thyroid cancer. J Clin Endocrinol Metab 88:2070, 2003; Skinner
MA et al: Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med 353:1105, 2005;
Tanaka K et al: Retrospective analysis of predictive factors for recurrence after curatively resected papillary thyroid
carcinoma. Surg Today 35:714, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue,
the speaker reported no conflict.
Dr. Clark was recorded January 25, 2005, in Scottsdale, Arizona, at the 34th Annual Phoenix Surgical Symposium
presented by the Phoenix Surgical Society and Banner Health. The Audio-Digest Foundation thanks the speaker and
the sponsors for their cooperation in the production of this program.
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