Thyroid Surgery

From the 37th Annual Phoenix Surgical Symposium sponsored by the Phoenix Surgical Society

Cord Sturgeon, MD, Assistant Professor of Surgery, Director of Endocrine Surgery, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL

Educational Objectives

The goal of this program is to review current approaches to evaluating and managing thyroid nodules and primary as­ymptomatic hyperparathyroidism. After hearing and assimilating this program, the clinician will be able to:

1.   Identify the red flags suggesting a thyroid nodule may be malignant.

2.   Explain why fine needle aspiration biopsy is the diagnostic test of first choice for thyroid nodules.

3.   Discuss the guidelines for managing thyroid nodules established by the American Thyroid Association.

4.   Describe surgical indications for the various forms of hyperthyroidism, including Graves’ disease, toxic multi­nodular goiter, hot nodules, and thyroid storm.

5.   Determine a treatment course for patients with primary asymptomatic hyperparathyroidism.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any per­sonal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, Dr. Sturgeon and plan­ning committee reported nothing to disclose.

Acknowledgements

Dr. Sturgeon was recorded at the 37th Annual Phoenix Surgical Symposium, held February 11-14, 2009, in Phoe­nix, AZ, and sponsored by the Phoenix Surgical Society. The Audio-Digest Foundation thanks Dr. Sturgeon and the Phoenix Surgical Society for their cooperation in the production of this program.

The Comprehensive Evaluation of Thyroid Nodules

Background: most incidental nodules benign, but all should be evaluated for malignancy

Patient selection

History: key features include history of therapeutic head and neck irradiation, especially in childhood; associated with rate of nodule development of 2% per yr; lag phase between administration of radiation and cancer develop­ment is  »30 yr; higher doses associated with faster development; radiation exposure also increases risk for hy­perparathyroidism (takes »40 yr to develop) and salivary gland tumors; 40% of thyroid nodules in patients exposed to radiation as children harbor malignancies; personal history of cancer significant (renal cell carcinoma commonly metastasizes to thyroid); having >2 first-degree relatives with papillary thyroid cancer increases pa­tient’s risk 5 to 9-fold; family history of syndrome associated with thyroid cancer also significant

Symptoms: voice change (suggests possible compression or invasion of recurrent nerve); difficulty swallowing or breathing; local pain; disfigurement; symptomatic nodules of any size require excision; red flags for malignancy  —  symptoms; rapid growth; nodules in children or people >60 yr; solitary nodules in males

Physical examination: fixation to trachea or infrahyoid (strap) muscles “very concerning for malignancy”; ipsilat­eral cervical lymphadenopathy “cancer until proven otherwise”; nodule size >4 cm; positive Pemberton’s sign in­dicates substernal goiter

Diagnostic tests: fine needle aspiration (FNA) biopsy first choice; speaker biopsies all incidental findings >1 cm, nodules that are growing, cysts, and suspicious ipsilateral lymph nodes; overall accuracy of FNA for thyroid cancer  »95%; most are papillary cancers; medullary cancers stain positive for calcitonin and have amyloid; anaplastic and metastatic disease harder to distinguish; suspicious for cancer  —  at speaker’s institution,  »50% of suspicious nodules cancerous; indeterminate nodules  —follicular or Hurthle cell neoplasms; usually adeno­mas or carcinomas

Distinguishing between benign adenoma and cancer: adenomas do not have vascular or capsular invasion; cells retrieved on FNA from center of either nodule are indistinguishable; excision required for accurate diagnosis

Biopsy categories: benign  —  accounts for >70% of biopsies; inadequate  —  10% to 15%; suspicious or indeterminate  —  11% to 13%; malignant  — »4%

Treatment: if patient lacks risk factors for thyroid cancer, FNA findings can dictate; if inadequate, repeat biopsy; if benign, follow up with ultrasonography (US) or physical examination ( »4% of FNAs are false negatives); excise if suspicious growth or symptoms develop

Laboratory tests: include thyroid function studies in initial evaluation; most thyroid cancer patients euthyroid, but recent studies suggest thyrotropin (TSH) level is independent predictor of thyroid malignancy; TSH <1 mIU/mL suggests lower likelihood of cancer than TSH of 3 mIU/mL to 4 mIU/mL; thyroglobulin reflects volume of normal or thyroid tissue present and status of TSH receptors; useful as marker for recurrence; antithyroglobulin antibody titers not associated with thyroid disease; thyroid peroxidase (TPO) antibodies associated with Hashimoto’s thy­roiditis, but not with cancer; calcitonin and carcinoembryonic antigen (CEA) used to evaluate for medullary thyroid cancer

Imaging studies: US most sensitive way of imaging thyroid nodules; inexpensive, noninvasive, painless, and in­volves no radiation; can be performed in office or operating room; detects lesions  ³3 mm; differentiates between cystic and solid structures; radioiodine scan  —  most nodules are “cold”; cannot distinguish benign from suspicious nodules; FNA more accurate predictor of malignancy; <1% of “hot” nodules malignant; positron emission tomog­raphy (PET)  —  »2% of nodules PET-positive; malignant poorly differentiated tumors most likely to be PET-posi­tive; »35% chance that PET-positive thyroid nodule malignant; most helpful at imaging recurrent, poorly differentiated cancers; cross-sectional imaging  —  speaker uses to follow patients with recurrent metastatic cancer; shows invasion of trachea or other areas not easily seen on US; computed tomography  —do not perform with con­trast if patient scheduled to receive radioactive iodine (RAI); sestamibi  scan — used for parathyroid imaging; thy­roid cancer false positive

American Thyroid Association guidelines for managing thyroid nodules: evaluation of thyroid incidentalomas  —history and physical, focusing on thyroid and adjacent lymph nodes, history of radiation exposure and family his­tory of thyroid cancer; cancer until proven otherwise— rapid growth; hoarseness; vocal cord paralysis ipsilateral to nodule; ipsilateral cervical lymph node enlargement; fixed lymph nodes

Work-up: TSH and US; RAI scan only if TSH low

FNA: most accurate and cost-effective way of evaluating thyroid nodules; biopsy all nodules >1 cm unless radiolo­gist strongly suspects cancer

Multinodular goiter: if all nodules similar, aspirate dominant one

Follow-up of benign nodules: serial US; if diameter increases by 20% or 2 mm in at least 2 different dimensions, repeat biopsy; speaker removes any rapidly growing nodule; TSH suppression no longer recommended (shrinks about one-third of nodules; in white women, TSH may increase risk for osteoporosis)

Children with thyroid nodules: same approach as adults

Pregnant women: biopsy during first two trimesters; if cancer diagnosed, remove during second trimester; if follic­ular neoplasm diagnosed, wait until after delivery

Small unifocal papillary cancer: observation recommended

Thyroidectomy for Hyperthyroidism: Indications, Extent, and Timing

Background: prevalence of hyperthyroidism in United States 1% to 2% in women, 0.1% to 0.2% in men; most com­mon cause Graves’ disease, especially in people <40 yr of age; toxic multinodular goiter (Plummer’s disease) most common cause in people >60 yr of age; other causes include hot (autonomous) nodule (single hyperfunctioning nodule in young person); iodine-induced (occurs when patient with somewhat autonomous nodule receives large dose of iodine, leading to toxicity); and thyroid storm; destructive processes  —  can cause hyperthyroidism if pro­cesses elaborate preformed hormone (eg, Hashimoto’s thyroiditis (Hashitoxicosis), postpartum thyroiditis (com­mon but self-limiting), thyrotoxicosis factitia (toxicity from thyroid hormone overdose)

Diagnosis: causes may be difficult to tease out; all forms share low TSH levels, high or high-normal levels of triiod­thyronine (T₃) or thyroxine (T₄), and high levels of thyroglobulin (exception  —  thyrotoxicosis factitia)

Antibodies: thyroid-stimulating immunoglobulin (TSI) antibodies common; thyroid peroxidase (TPO) antibodies associated with Hashitoxicosis; also seen in Graves’ disease or postpartum thyroiditis

RAI scan findings: Graves’ disease  —  diffuse goiter with plentiful uptake; hot nodule  —  resembles light bulb; Plummer’s disease  —  multiple hot nodules throughout thyroid; destructive processes  —  low iodine uptake

Graves’ disease: stimulatory autoantibodies bind to TSH receptors, mimicking effects of TSH; gland becomes over­active and enlarged; 50% of patients present with diffuse toxic goiter only; remaining 50% also have Graves’ ophthalmopathy; infiltrative dermopathy and pretibial myxedema rarest manifestations; thyroidectomy does not remove cause of disease

Treatment: thionamides  —  propylthiouracil (PTU) and methimazole (Tapazole) approved in United States; associ­ated with remission rate of 20% to 30% at 1 yr; RAI ablation  —  associated with 60% euthyroid rate at 1 yr; pa­tients may eventually become hypothyroid; surgery  —outcome depends on how much gland left behind; most data suggest 50% to 60% euthyroid rate at 1 yr; lower risk for hypothyroidism than with RAI

Indications for surgery: patient does not want radiation therapy; presence of suspicious nodules; severe ophthal­mopathy; history of allergy or severe reaction to thionamide; failure of medical treatment; uncontrolled hyper­thyroidism during pregnancy, or unwillingness to use thionamides while pregnant; low radioiodine uptake; need for rapid transition to euthyroid state (important for high school and college students, who “need to get back to normal permanently and quickly”)

Toxic multinodular goiter: usually presents with compression; often large goiter that began as nontoxic goiter; pa­tients develop dysrhythmias, muscle wasting, weakness, and compressive symptoms; usually occurs during sixth or seventh decade of life; treatment options similar to those for Graves’ disease; RAI often encouraged; indications for surgery include presence of substernal or compressive goiter; other indications similar to those for Graves’ disease

Hot nodule (toxic adenoma): usually benign; sometimes associated with point mutation in gene that activates TSH receptor; patients often in 30s or 40s; ideal treatment RAI; indications for surgery  —  pregnant patient who does not want methimazole; large nodule that causes compressive symptoms; inadequate response to RAI; desire for rapid resolution; wish to avoid radiation therapy

Conditions for which surgery not necessary: Hashitoxicosis or postpartum thyroiditis; usually transient and rela­tively mild; b-blockers limit effects of excess thyroid hormone; steroids occasionally prescribed

Jod-Basedow effect: hyperthyroidism associated with baseline goiter due to iodine deficiency; patient then receives iodine load (eg, amiodarone or contrast medium); treat by discontinuing iodine source

Thyroid storm: usually associated with underlying autoimmune condition; life-threatening; patients febrile and ex­tremely tachycardic; high-output heart failure common; intensive care monitoring indicated, as well as every effort to control thyroid function; some resistant to medical therapy; surgery provides definitive, rapid, and durable reso­lution, but should be deferred until patient stable; treat initially with b blockade and fever control; dexamethasone inhibits conversion and release of thyroid hormone; thionamides prevent organification; iodine also helps slow thy­roid hormone production; lithium recommended for patients who fail first-line treatment (inhibits thyroid hormone release)

Extent of surgery: depends on extent of disease; for toxic nodule, lobectomy sufficient; Harley-Dunhill procedure indicated for Graves’ disease (ipsilateral total lobectomy and contralateral subtotal lobectomy); near-total thyroid­ectomy for toxic multinodular goiter, anyone with history of life-threatening thyrotoxicosis, Graves’ disease with suspicious nodules, or lack of response to RAI or thionamide; preoperative preparation  —  b blockade first, then th­ionamides to establish euthyroid state, followed by saturated solution of potassium iodide (SSKI) to further inhibit thyroid function; Wolff-Chaikoff effect  —  autoregulatory phenomenon that temporarily reduces circulating thyroid hormone levels; SSKI temporarily stops organification and release of thyroid hormone; lasts for £2 wk; must oper­ate within 7 to 14 days; can also shrink gland

Asymptomatic Primary Hyperparathyroidism: Update from 2008 American Association of Clinical Endocrinologists Consensus Conference

Take-home message: surgery reverses natural history of disease and prevents bone-related sequelae (eg, fractures), reduces incidence of kidney stones, and protects against neurocognitive developments

Manifestations

Musculoskeletal: muscle and joint pain most common; corresponds to degree of hypercalcemia; loss of cortical bone (most pronounced in distal radius)

Kidney stones: occur in 15% to 20% of patients; frequent urination common complaint

Fatigue: also corresponds to degree of hypercalcemia

Psychologic problems: depression, anxiety, memory loss and cognitive problems

Gastrointestinal: constipation and pancreatitis

Cardiovascular: increased risk for myocardial infarction, stroke, and irreversible hypertension

Miscellaneous: itching, thirst, and premature death

Laboratory findings: hypercalcemia; elevated intact parathyroid hormone (PTH) level; urinary calcium clearance >100 mg/day; chloride:phosphorous ratio >33; high level of 1,25-dihydroxyvitamin D; increased bone turnover

Guidelines: indications for surgery  —  serum calcium >1 mg/dL above normal in asymptomatic patient; T score <-2.5 at any site (meets World Health Organization definition of osteoporosis); glomerular filtration rate <60 mL/min; age <50 yr; presence of genes associated with syndromic hyperparathyroidism

Nonsurgical management: annual monitoring of calcium and creatinine; dual energy x-ray absorptiometry (DEXA) scans every 1-2 yr; ensure adequate serum vitamin D levels (but do not decrease dietary calcium); pharmacologic therapy not recommended

Surgery: in experienced hands, first operation curative in 95% of cases; incidence of significant complications (nerve injury or permanent hypoparathyroidism) <1%; recurrence seen in 1% of sporadic cases and one-third of familial cases; reoperation cures 90% of these patients

Preoperative localization studies: not part of diagnostic work-up; diagnosis based on laboratory findings; imag­ing studies do not always detect condition; false negatives common (eg, small glands, hyperplasia, multiple ad­enomas, sarcoidosis, and Hashimoto’s disease)

Consensus opinion: parathyroidectomy most cost-effective treatment for asymptomatic primary hyperparathyroid­ism; experienced surgeon necessary; preoperative localization for surgical planning only; focused parathyroidec­tomy or four-gland exploration both acceptable

Suggested Reading

Ambrogini E et al: Surgery or surveillance for mild asymptomatic primary hyperparathyroidism: a prospective, randomized clin­ical trial. J Clinical Endocrinol Metab 92:3114, 2007; Bilimoria KY et al: Impact of surgical treatment on outcomes for papillary thyroid cancer. Adv Surg 42:1, 2008; Cheung K et al: Calcitonin measurement in the evaluation of thyroid nodules in the United States: a cost-effectiveness and decision analysis. J Clin Endocrinol Metab 93:2173, 2008; Efremidou EI et al: The efficacy and safety of total thyroidectomy in the management of benign thyroid disease: a review of 932 cases. Can J Surg 52:39, 2009; Giles Senyurek Y et al: The risk factors for malignancy in surgically treated patients for Graves’ disease, toxic multinodular goiter, and toxic adenoma. Surgery 144:1028, 2008; Haymart MA et al: Higher serum thyroid stimulating hormone level in thyroid nodule patients is associated with greater risks of differentiated thyroid cancer and advanced tumor stage. J Clin Endocrinol Metab 93:809, 2008; Haymart MR et al: Higher serum TSH in thyroid cancer patients occurs independent of age and correlates with extrathyroidal extension. Clin Endocrinol (Oxf) 2008 Dec 3 (Epub ahead of print); King DL et al: Incidence of thyroid carcinoma in fluorodeoxyglucose positron emission tomography-positive thyroid incidentalomas. Otolaryngol Head Neck Surg 137:400, 2007; Mehta AN et al: Total thyroidectomy for medically refractory amiodarone-induced thyrotoxicosis. Proc (Bayl Univ Med Cent) 21:382, 2008; Polyzos SA et al: Serum thyrotropin concentration as a biochemical predictor of thyroid malignancy in pa­tients presenting with thyroid nodules. J Cancer Res Clin Oncol 134:953, 2008; Sturgeon C, Angelos P: Identification and treat­ment of aggressive thyroid cancers. Part I: subtypes. Oncology (Williston Park) 20:253, 2006.