General Surgery (Board Review Series) 1st Edition

19

Thyroid and Parathyroid

James J. Gangemi

1. Functional Anatomy
2. The thyroid gland

• develops from endoderm of the first and second pharyngeal pouches.

1. Altered migration may result in

• thyroglossal remnants(cysts).
• ectopic thyroid tissue (lingual thyroid).

2. Lingual thyroid tissue

• may persist in the region of the foramen cecum at the base of the tongue.
• that causes dysphagia, dyspnea, or dysphonia may be treated via suppression with thyroid hormone or ablation with radioactive iodine.

3. The pyramidal lobe

• extending upward from the isthmus is a remnantof this migration.
• is present in 80% of patients.

1. The small parathyroid glands

• are characteristically located adjacent and posterior to the thyroid gland.

1. Most individuals (80%–90%)

• have 4 parathyroid glands, 2 on each side.

2. The paired superior parathyroid glands

• arise from the fourth branchial pouchin close proximity to the origin of the thyroid gland (floor of foregut).

3. The paired inferior parathyroid glands

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• arise from the third branchial pouchalong with the thymus.
• migrate farther and thus are more likely to be found in ectopic locationssuch as the anterior mediastinum.

4. Other potential ectopic sites include

• intrathyroid, posterior mediastinum, or near the tracheoesophageal groove.

1. Arterial supply and venous drainage

• of the thyroid and parathyroid (Figure 19-1)

1. Arterial supply

• is via the inferior and superior thyroid arteries.

2. Venous drainage

• is via the superior, middle, and inferior thyroid veins.

3. The middle thyroid veins

• drain directly into the internal jugular veins.
• are present in 50% of individuals.

Figure 19-1. Arterial and venous supply of the thyroid.

1. The recurrent laryngeal nerve

• runs in the tracheoesophageal groove lateral to the ligament of Berry (a posteromedial suspensory ligament of the thyroid) before entering the larynx.

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1. Unilateral injury to the nerve

• causes ipsilateral paralysis of the vocal cordand failure of cord abduction, which may result in hoarseness.

2. Bilateral cord injuries

• may result in either complete loss of voice or airway obstruction, requiring immediate intubation or tracheostomy.

1. Superior laryngeal nerve

• runs adjacent to the superior pole of the thyroid to innervate the cricothyroid muscle.
• injury may result in an inability to attain high tones.

1. Physiology
2. Thyroxine (T₄) and triiodothyronine (T₃)

• are the principal hormones secreted by the thyroid.

1. T₄and T₃are stored

• in the colloidvia linkages with thyroglobulin.

2. T₄and T₃ become instantly bound

• to albumin and thyroxine-binding globulin.

3. Most T₃in euthyroid patients

• is produced by peripheral conversion of T₄to T₃.

1. Thyroid hormone secretion

• is regulated by feedback mechanisminvolving the hypothalamus and pituitary gland.

1. Thyrotropin-releasing factor(TRF)

• is formed in the hypothalamus.
• stimulates the release of thyrotropin (thyroid stimulating factor [TSH]) from the pituitary.

2. TSH secretionis controlled in feedback manner by serum thyroid hormone levels.
3. TSHbinds to specific receptors on the thyroid plasma membrane, stimulating increased cyclic adenosine monophosphate (cAMP) production and thyroid cellular function.

III. The Thyroid Nodule

1. Overview
2. Eighty-five percent of thyroid nodules are benign.
3. Nodules are four times more common in women

• although there is an equal distribution of thyroid cancer.

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1. Risk factors for malignancy

• are outlined in Table 19-1.

1. Evaluation
2. Aspiration cytology

• is the single most helpful procedure for evaluation of a thyroid nodule.

2. Fine needle aspiration(FNA)

• is very accurate in colloid nodules and papillary cancer.
• can be used to diagnose and treat cystic lesions, which are rarely malignant.

3. “Follicular cytology”

• on fine needle aspirates can represent a benign follicular nodule or a follicular cancer.
• In this setting of an indeterminate diagnosis, excision is recommended.

4. Ultrasound

• may be used to characterize very small nodules (as small as 1 mm).
• can delineate cystic from solid lesions.

5. Thyroid nuclear medicine scan

• uses ^99mtechnetium to identify hyperfunctional (“hot”) or hypofunctional (“cold”) nodules within the thyroid.
• is used less frequently today because both cold and hot nodules may harbor a malignancy (Table 19-1).

6. Thyroid function tests

• are notvery useful as a diagnostic test, because most thyroid cancers are euthyroid.

7. Excision

• is required for any nodule, cystic or solid, that persists for 3 months.

Table 19-1. Characteristics Associated with a Relatively Higher Probability of Malignancy in Thyroid Nodules

Age < 30 or age > 60 Solid lesions > cystic lesions Cold nodules > hot nodules on thyroid scan (20%–25% of cold nodules are malignant versus < 1% of hot nodules) History of radiation to head/neck (30% develop nodules; 30% are malignant) Multiple endocrine neoplasias Single nodules > multiple nodules Enlarging nodules on thyroid hormone suppression Nodules associated with dysphasia, dyspnea, hoarseness, vocal cord paralysis, Horner syndrome, or adenopathy

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1. Benign Diseases of the Thyroid
2. Causes of hyperthyroidism (thyrotoxicosis)
3. Graves' disease or toxic diffuse goiter

• accounts for 80% of all cases of hyperthyroidism.

1. This is an autoimmune diseaseresulting from thyroid-stimulating immunoglobulin.
2. Incidence

• is six to seven times higher in females.

1. Manifestations include

• thyrotoxicosissymptoms, which include heat intolerance, thirst, increased appetite, weight loss, sweating, and palpitations (e.g., atrial fibrillation).
• diffuse goiter.
• exophthalmos.
• vitiligo.

1. Diffuse, increased uptake of radioiodine(¹³¹I) within a symmetrically enlarged gland is diagnostic and differentiates Graves' disease from other causes of thyrotoxicosis.
2. Medical treatment
3. Antithyroid drugs

• Medical management with antithyroid drugs may be used as definitive treatment or in preparation for surgery or radioiodine treatment.
• Propylthiouracil (PTU) or methimazoleinhibits function of the gland without destroying tissue.
• The recurrence rate is high(43% 1-year), and there is a risk of agranulocytosis with these agents.

2. Radioactive ¹³¹I thyroid ablation

• is effective treatment associated with low recurrence, although 70% develop hypothyroidismwithin 10 years.
• is contraindicated in children, women of childbearing years, patients with concomitant thyroid nodules, or those with extremely large glands.

1. Surgery

• is rarely required.

1. Indications for surgeryinclude

• noncompliant patients.
• recurrence after medical therapy.
• children and women of childbearing age.
• presence of a very large gland or concomitant thyroid nodules.

2. Bilateral subtotal thyroidectomy or total thyroidectomymay be performed.

• β-Adrenergic blockers(propranolol) are initiated 1 week before surgery to control symptoms.

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• Potassium iodide or Lugol's solutionis initiated 2 weeks before surgery to decrease the vascularity of the gland.

2. Toxic multinodular goiter (Plummer disease)

. This disease typically affects women older than 50 years.

1. Treatmentinvolves thyroidectomy after adequate medical therapy.
2. Bilateral subtotal thyroidectomyis most commonly used.

• ¹³¹I does not reduce goiter size and may cause acute enlargement.

3. Solitary toxic nodule

. These nodules are most commonly found in women in the fifth decade of life.

1. Functional nodules causing hyperthyroidismare usually larger than 3 cm in diameter.
2. The noduleseventually develop central necrosis and become cold.
3. Evaluation and treatment

• is similar to that described for a thyroid nodule (see III C).

1. Thyroiditis

• Causes and treatments are characterized in Table 19-2.

1. Hashimoto's thyroiditis

• or chronic lymphocytic thyroiditis, is the most common formof chronic thyroiditis.

2. Subacute thyroiditis (de Quervain thyroiditis)

• typically occurs in younger females with a recent viral infection.

3. Acute suppurative thyroiditisand Reidel thyroiditis

• are rare.

1. Thyroid storm

• represents a massive uncontrolled release of thyroid hormone.

1. Precipitating eventsmay include

• surgery.
• anxiety.
• excessive palpation of gland.
• adrenergic stimulants.
• This typically occurs in patients with undiagnosed hyperthyroidism who are undergoing major stress.

2. Symptoms include

• tachycardia.
• fever.
• numbness.
• irritability.

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• vomiting.
• diarrhea.

Table 19-2. Causes and Treatment of Thyroiditis

Cause Pathology Clinical Findings Treatment Hashimoto's thyroiditis (chronic lymphocytic thyroiditis) Autoimmune: anti-microsomal and antithyroglobulin antibodies in serum; diffuse lymphocytic infil-trate with germinal centers on histology Most common cause of spontaneous hypothyroidism; middle-age women; diffuse, slowly progressive goiter with firm, rubbery, lobulated gland; may mimic a neoplasm Treat with thyroid hormone replacement (levo-thyroxine) Subacute thyroiditis (de Quervain thyroiditis) Etiology unknown Young females with recent viral infection; tender to palpation, weakness, fatigue, referred pain to jaw Often self-limited for a few weeks with aspirin and steroids helpful; surgery only for refractory disease Acute suppur-ative thyroiditis (rare) Acute bacterial infection caused byStreptococcus or Staphylococcus species, pneumococci, coliforms Typically follow URI: severe neck pain, dysphagia, fever, chills Surgical drainage and débridement Reidel's struma (rare) “Woody” and fibrous thyroid involving adjacent strap muscles and carotid sheath; etiology unknown Localized pain and compression of adjacent structures may occur: retro-peritoneal fibrosis, fibrosing medias-tinitis, sclerosing cholangitis Often self-limited; steroids may be beneficial URI = upper respiratory tract infection.

3. High output cardiac failure

• may occur and is the usual cause of death.

4. Preventative measuresinclude

• administration of PTU and beta-blocking agents (e.g., propranolol) for 3–4 weeks before surgery.

5. Treatment of thyroid stormincludes

• mechanical cooling, and administering oxygen and fluids.
• preventing adrenal failure: steroid therapy.
• administering Β blockersto relieve symptoms.
• administering PTUalong with iodine (potassium iodide), which decreases serum thyroid hormone levels by inhibiting release of hormone from the thyroid gland.
• emergent subtotal thyroidectomy, although rarely required.

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1. Thyroid Cancer (Table 19-3)
2. Overview
3. Thyroid canceris the most common endocrine malignancy in the United States.
4. These cancers are an uncommon cause of deathbecause the majority of these lesion are well differentiated and relatively nonaggressive.
5. Papillary carcinomas

represent the majority of thyroid tumors.

• Mixed papillary/follicular carcinoma acts like very aggressive papillary carcinomas.

1. Follicular carcinomas

are generally more aggressive than papillary carcinomas.

1. Follicular carcinomas areoccasionally difficult to differentiate from follicular adenomas on FNA.

• Microvascular or local invasion on FNAis characteristic of carcinoma, although indeterminate lesions may require resection.

2. Hürthle cell tumors are variants of follicular carcinomathat generally present at an older age.
3. Unlike most follicular carcinomas, these tumors are generally resistant to ¹³¹I radioablation.
4. Treatment

• Large(> 2 cm) or locally invasive Hürthle cell tumors are treated with total thyroidectomy with local lymph node biopsy.
• With positive nodes, modified lymph node dissectionof the neck is indicated, unlike with follicular lesions.
• For smaller, less aggressive lesions, lobectomymay be appropriate.

1. Medullary carcinoma

• arise from parafollicular, or C, cellsof the thyroid that secrete calcitonin.

1. Sporadic casesare usually unilateral.
2. Familial cases, associated with multiple endocrine neoplasia (MEN) II (see Chapter 20), are often bilateral.
3. Anaplastic carcinoma

• is the most aggressive tumorof the thyroid.
• may present with airway compromise.
• is often fatal despite surgery.

1. Treatment options for each tumor

• are outlined in Table 19-3.

1. For metastatic papillaryor follicular carcinoma diagnosed preoperatively, total thyroidectomy is performed to facilitate uptake of ¹³¹I into the metastases for ablation.

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2. Thyroid hormones are also administered to suppress TSH stimulation of tumor growth.

Table 19-3. Characteristics of Thyroid Cancer

Tumor Epidemiology Pathology Prognosis Treatment Papillary (80%) Affects young adults and children, women > men; most common tumor following neck irradiation Slow-growing, often multicentric; psammona bodies on histology are characteristic; spread is via lymph nodes Tumors < 1.5 cm rarely metastasize; 5%–15% have lung metas-tases at diagnosis; 90% 5-year survival Small tumors (< 1.5 cm) may be treated with lobectomy and isthmusec-tomy; large tumors and metastases treated with total thyroid-ectomy and 131I ablation Follicular (10%) Peaks at age 50–60, women > men May be confused with adenoma on FNA; capsular or vascular invasion is diagnostic. Spread is characteristically hema-togenous (bone, lung, brain, and liver) 85% 5-year survival without angioinvasion; 45%–50% with angioinvasion Subtotal or total thyroidectomy depending on lesion size and location; postoperative131I ablation reduces recurrence rate and effectively treats meta-stases Medullary (5%) Sporadic cases peak at age 50–60; familial cases (10%–15%) associated with MEN II peak at 20–40 Secretes calcitonin; arises from para-follicular C-cells (neural crest tissue); presence of amyloid on histology is characteristic Lymph node metastases frequently present at diagnosis; 30% will have microscopic disease in uninvolved lobe Total thyroid-ectomy with lymph node dissection (bilateral if tumor bilateral) Anaplastic (1%–2%)* Peaks at age > 70; seen in patients with longstanding nodular goiter Poorly differentiated rapidly growing carcinoma Often associated with lymph node metastases at diagnosis, most aggressive thyroid cancer with < 2% 1–2 year survival Total thyroid-ectomy for rare resect-able lesions; palliative chemoradi-ation therapy, palliative resection *Lymphoma and squamous cell carcinoma account for the rest of thyroid tumors. 131I = iodine 131; FNA = fine needle aspiration; MEN = multiple endocrine neoplasia.

1. Operative and postoperative complications
2. Recurrent laryngeal nerve injury

• The overall risk is 0.2%–3% at primary operation, but increases to 6% for re-operations.

2. Hypoparathyroidism with resultant hypocalcemia

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• may result from bilateral dissection via devascularizationof the parathyroid glands.

3. Excessive postoperative hemorrhage

• may lead to airway compromise and requires immediate re-exploration and possible drain placement.

4. Injury to the superior laryngeal nerve

• may result in a weak voice, which frequently goes unnoticed except in singers.

1. Parathyroid
2. Functions of parathyroid hormone (PTH)

include

• increasing mobilization of calcium and phosphate from bone.
• promoting active calcium reabsorption in distal nephron.
• inhibiting phosphate reabsorption in the proximal tubule.
• stimulating 1,25-dihydroxyvitamin D₃and increasing gut absorption of calcium and phosphorous.

1. Primary hyperparathyroidism

• is characterized by excessive, abnormally regulated secretion of PTH, which results in hypercalcemia.

1. Overview
2. A small percentage of patients have a history of radiation exposureas a child.
3. Primary hyperparathyroidism peaks between the ages of 50–60, with a female:male ratio of 3:1.
4. Etiology and pathology
5. Adenomas

• There is single adenomain 80%–85% of patients.
• There is a 2%–4% incidence of multiple adenomas.
• Histologically, there is proliferation of chief cells in a single focus with a compressed rim of surrounding normal tissue.

1. Diffuse hyperplasia of all 4 glands

• occurs in 15% of patients.
• may be associated with MEN I in 25%–35% of patients (see Chapter 20).
• Histologically, diffuse chief cell hyperplasia is seen with cords or sheets of chief cells.

1. Parathyroid carcinoma

• occurs in 0.5–1.0% of patients.

3. The causes of hypercalcemiaare outlined in Table 19-4.
4. Humoral hypercalcemia of malignancy

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• (50% of cancer hypercalcemia) leads to increased bone resorption and suppressed bone formation.
• is characterized by elevated calcium and urinary cAMP with low serum phosphateand normal or low PTH.
• is caused by a PTH-related proteinsecreted by the tumor.

1. Hematologic malignancies

• (e.g., multiple myeloma, lymphoma) may be associated with elevated phosphates and low urinary cAMP.
• Lytic bone lesions may be caused by interleukin (IL)-β and tumor necrosis factor (TNF)-β that cause increased osteoclastic bone resorption.

Table 19-4. Causes of Hypercalcemia

Cause Pathogenesis PTH Malignancy* Hematologic: 25% (myeloma, leukemia) Nonhematologic: 75% (lung, breast, head and neck tumors) Decreased or normal Primary hyperpara-thyroidism* Adenoma (80%–85%), diffuse hyperplasia (15%), parathyroid carcinoma (rare) Increased Familial hypocalciuric hypercalcemia Autosomal dominant mutation in calcium sensing receptor Decreased or normal Immobilization Associated with bone demineralization Decreased or normal Granulomatous disease Sarcoidosis, tuberculosis Decreased or normal Vitamin D and vitamin Aexcess Increased absorption Decreased or normal Other drugs Thiazide diuretics, lithium Decreased or normal Other endocrine disorders Addison disease, hyperthyroidism Decreased or normal Tertiary hyperpara-thyroidism Hypercalcemia associated with chronic renal failure persisting after correction of renal failure (e.g., kidney transplant) Increased Milk-alkali syndrome Excessive intake of calcium supplements in addition to milk Decreased or normal *Malignancy and primary hyperparathyroidism are the two most common causes of hypercalcemia. PTH = parathyroid hormone.

4. Clinical manifestations

• of hypercalcemia are characterized in Table 19-5.

1. Mild chronic hypercalcemia

• Most patients are asymptomatic.

1. Hypercalcemic symptoms

• are related to the magnitude and the rate of rise.
• Hypercalcemia related to malignancyis often associated with a rapid rise and is frequently symptomatic.

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5. Diagnosis

Table 19-5. Clinical Manifestations of Hypercalcemia

Neuromuscular Mental confusion, obtundation, coma, fatigue, lethargy, malaise, muscle weakness, depression, apathy, inability to concentrate Renal Nephrolithiasis (most frequent complication of primary hyperparathyroidism developing in 15%–20% of patients) Nephrocalcinosis (calcification of renal parenchyma): severe cases may not improve with parathyroidectomy Cardiovascular Hypertension that correlates with degree of renal impairment Shortened QT interval on electrocardiogram Heart block Skeletal Bone pain Radiographic evidence (uncommon, 1%–2%) Pathologic fractures Subperiosteal cortical resorption on radial aspect of middle phalanx of second/third finger Salt-and-pepper pattern of skull on radiograph “Brown tumor”: localized proliferation of osteoclasts typically involving long bones Osteitis fibrosa cystica (rare) Gastrointestinal Nausea and vomiting, anorexia, constipation, peptic ulcer disease, pancreatitis: rare, cholelithiasis: elevated calcium in bile

. Hypercalcemia and elevated levels of PTH

• (> 60 mEq/mL) are hallmarks of primary hyperparathyroidism.

1. Because of extensive calcium binding by albumin

• total serum calcium levels vary based upon albumin levels.
• For every 1 mg/dL fall in serum albumin, total serum calcium levels drop 0.8 mg/dL even in the setting of normal calcium balance.
• True hypocalcemiais characterized by decreased ionized calcium levels, which accurately reflect functional extracellular calcium levels despite hypoalbuminemia.

1. Hypophosphatemia

• will occur in 35% of patients.

1. Elevated urinary cAMP and urinary calcium

• may be present (35%–40%).

1. Bone densitometry

• is very sensitive and determines the extent of cortical bone loss.

1. Preoperative localization of lesions

• with ultrasound or nuclear medicine scan is rarelyindicated for primary disease.
• Localization is frequently indicated for reoperative procedures.

6. Treatment of primary hyperparathyroidism

. Symptomatic disease

• Surgeryis the only definitive therapy for treatment of symptomatic disease.

1. Asymptomatic or mild disease

• at the time of diagnosis seldom progresses clinically, biochemically, or radiologically.

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1. The cure rate

• for initial operation is 90%–95%.

7. Principles of surgical correction

. Location and number of glands

• may be highly variable.

1. To rule out lesions in multiple glands

• bilateral neck dissection with identification of all 4 glandsmay be necessary.

1. To confirm the presence or absence of parathyroid tissue

• frozen sections should be performed.

2. This is not helpful in differentiating diseased tissue from normal tissue.
3. Intraoperative measurement of local venous PTH may also be used to confirm removal of a functional parathyroid lesion.
4. Treatment of adenomas
5. Single or multiple enlarged glands

• should be resected, leaving normal or atrophic glands.

1. If only 3 normal glands are identified

• after thorough exploration, ipsilateral thyroidectomy is often performed on the side where only 1 gland was found.

1. In this setting, 96% of the remaining glands are intrathyroidal.
2. Videoscopic parathyroid resection is also being used for the surgical treatment of benign parathyroid disease.
3. Multiglandular hyperplasia

• may be treated with subtotal or total parathyroidectomy.

1. Subtotal parathyroidectomy

• involves removing 3.5 glands, while leaving the remaining tissue with the native blood supply.

1. Total parathyroidectomy

• is followed by autotransplantationof gland fragments to the nondominant forearm or sternocleidomastoid muscle.

1. Autotransplantation makes reoperation for recurrence easier.
2. This is the preferred procedure for familial disease.
3. Permanent hypoparathyroidism

• occurs in 5% of patients.

1. Persistent or recurrent disease
2. Persistent hyperparathyroidism

• after surgical exploration occurs in less than 5% of patients.
• is often related to a single diseased gland remaining in the neck.

2. Recurrent disease

• often develops after a period of hypocalcemia.
• is often related to regrowth of diseased tissue.

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• may occur because of inadvertent microscopic implantation during resection.
• Recurrent parathyroid carcinoma should be considered in this setting.

3. Preoperative localization

• is recommended for recurrent disease.

1. Adhesionsmake reoperation more difficult.
2. Ectopic location

• of glands is also more likely in this setting.

1. Localization methods
2. Ultrasonographyis most useful for lesions close to or within the thyroid.
3. Computed tomography (CT) or magnetic resonance imaging (MRI)offers superior visualization of deeper structures and ectopic adenomas, especially in the mediastinum.
4. A technetium-99m-Sestamibiscan may also help localize diseased tissue.
5. Invasive localization

• is reserved for unsuccessful noninvasive localization

1. Selective angiography.
2. Venous sampling with measurement of PTH can be combined with angiography for complete identification.
3. Surgical reexploration

• has 60%–80% success rate.

1. There is an increased incidence of complicationssuch as unilateral recurrent nerve injury (5%–10%) and permanent hypoparathyroidism (10%–20%).
2. Median sternotomyand mediastinal exploration is necessary in 1%–2% of patients.
3. The superior parathyroidsmay be posterior to the esophagus and as superior as the pharynx.
4. Secondary hyperparathyroidism

• is a consequence of chronic renal failure.

1. These patients are unableto synthesize the active form of vitamin D, which results in hypocalcemia and compensatory elevation of PTH.
2. Untreated patients become symptomatic with

• bone demineralization.
• calcification of soft tissues.
• accelerated vascular calcification.
• pruritus.
• painful skin ulcerations from subcutaneous calcium deposition.

3. Treatmentis generally medical with

• dialysiswith high-calcium bath.

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• phosphate-binding antacids.
• calcium supplements.

4. Surgical treatment

• is rarely indicated except for refractory cases.

1. Tertiary hyperparathyroidism
2. This type of hyperparathyroidism

• is characterized by persistent disease in patients with secondary hyperparathyroidism despite renal transplantationsecondary to dysregulated parathyroid function.
• is associated with hypercalcemia and elevated PTH levels.

2. Treatmentoften requires surgical resection with subtotal thyroidectomy.
3. Parathyroid carcinoma
4. Compared with adenomaspatients with parathyroid carcinomas are younger, with an equal male:female ratio.
5. Patients are more frequently symptomaticwith elevated levels of calcium, PTH, and alkaline phosphatase.
6. Histologically, characteristics include

• a trabecular pattern.
• mitotic figures.
• capsular invasion.
• angioinvasion.

4. The affected glandsare often adherent to surrounding tissue.
5. Treatmentis with radical resection of the involved gland, the ipsilateral thyroid gland, and regional lymph nodes.

• Chemotherapyand radiation therapy provide no additional benefit.
• The recurrence rateis ~50%.
• Long-term prognosisis poor.
• Survivaldepends on complete resection at the initial operation.

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Review Test

Directions: Each of the numbered items or incomplete statements in this section is followed by answers or by completions of the statement. Select the ONE lettered answer or completion that is BEST in each case.

1. During a routine check-up, an otherwise healthy 38-year-old woman is found to have hypercalcemia on a routine chemistry panel. Additional work-up reveals an elevated parathyroid hormone (PTH) levels as well. At the time of operation, which of the following histopathologic findings would suggest the presence of parathyroid carcinoma in this patient?

(A) Diffuse proliferation of chief cells in all 4 glands

(B) Sheets of chief cells in all 4 glands

(C) Focal chief cell hyperplasia extending through the capsule

(D) Focal chief cell hyperplasia compressing a normal rim of tissue

(E) Focal chief cell hyperplasia in 2 different glands

1–C. Differentiating a parathyroid adenoma from a carcinoma may sometimes be difficult. Adenomas are characterized by focal chief cell hyperplasia compressing a normal rim of parathyroid tissue. Characteristic histologic findings of a carcinoma include microvascular invasion and invasion of the surrounding capsule. Focal hyperplasia in 2 glands is suggestive of multiple adenomas. Diffuse proliferation of chief cells, or sheets or cords of chief cells in all 4 glands is suggestive of diffuse parathyroid hyperplasia.

2. A 35-year-old woman presents with flank pain and hematuria, and during evaluation is found to have calcium phosphate stones in her urine along with hypercalciuria and hypercalcemia. Subsequent work-up reveals an elevated parathyroid (PTH) level. After resolution of this episode of renal colic, she undergoes elective neck exploration. Initial exploration of the right neck posterior to the right lobe of the thyroid reveals 2 diffusely enlarged parathyroid glands, which are successfully removed. Which of the following is the most appropriate statement regarding the subsequent management of this patient?

(A) No additional exploration if an adenoma is identified on frozen section

(B) Exploration of the left side only if hyperplasia is identified

(C) Exploration of the left side only if an adenoma is identified

(D) Resection of 3.5 parathyroid glands if an adenoma is seen on frozen section

(E) Performance of frozen sections and exploration of the left side

2–E. As many as 15%–20% of patients will have multiple adenomas at the time of surgery. During a neck exploration for parathyroid disease, identification of all glands is important if diffuse hyperplasia is a concern. In the patient described, frozen sections of the initial 2 glands should be performed to confirm the presence of parathyroid tissue in the resected specimens. Despite the findings, exploration of the left side should be performed for the reasons mentioned above.

3. A 42-year-old woman presents for elective total thyroidectomy for a follicular carcinoma of the thyroid gland diagnosed by fine needle aspiration (FNA). Intraoperatively, ligation of which of the following vessels is necessary to obtain complete vascular control of the thyroid gland in this patient?

(A) Inferior and superior thyroid arteries; and inferior, middle, and superior thyroid veins

(B) Inferior, middle, and superior thyroid arteries; and inferior and superior thyroid veins

(C) Inferior and superior thyroid arteries and veins; and thyroid ima artery

(D) Inferior, superior, and middle thyroid veins; and superior, middle, and thyroid ima arteries

(E) Inferior, middle, and superior thyroid arteries and veins; and thyroid ima vein

3–A. A general understanding of the arterial and venous supply to the thyroid gland is essential for adequate vascular control during resection. The thyroid gland is generally supplied by 2 major arteries: the inferior and superior thyroid arteries. A small percentage of patients (10%–15%) will have an accessory thyroid ima artery arising directly from the aortic arch. There are 3 major veins draining the thyroid gland: the superior, inferior, and middle thyroid veins. Variations of both the arterial and venous systems may exist.

4. A 56-year-old woman presents to the office with a 2-cm neck mass just left and lateral to the trachea in the inferior lobe of the left thyroid gland. Fine needle aspiration (FNA) reveals a moderately differentiated tumor that stains strongly for amyloid. In addition, her calcitonin is elevated. Which of the following is the most appropriate therapy for this patient?

(A) Total thyroidectomy with radioiodine (¹³¹I) ablation therapy

(B) Total thyroidectomy with bilateral lymph node dissection

(C) Total thyroidectomy with left-sided lymph node dissection

(D) Left lobectomy and isthmusectomy with left-sided lymph node dissection

(E) Left lobectomy and isthmusectomy alone

4–C. The presence of amyloid on histologic examination is a classic finding for medullary carcinoma of the thyroid. These tumors arise from parafollicular, or C, cells and may secrete calcitonin, which is also a characteristic diagnostic finding. Treatment involves total thyroidectomy and central lymph node dissection on the side of the lesion. If bilateral tumors are identified, then bilateral lymph node dissection may be required. A lobectomy and isthmusectomy would be inadequate therapy for this tumor. These tumors are insensitive to radioiodine (¹³¹I) ablation therapy, although external beam radiation therapy to the neck is considered in some patients with this disease.

5. A 47-year-old woman presents to the office with complaints of a 4-month history of worsening fatigue and weight gain. Palpation of the thyroid gland reveals an irregular lobulated gland bilaterally. Laboratory evaluation demonstrates serum antimicrosomal antibodies. Which of the following best describes the histologic findings that are likely to be identified upon biopsy of this patient's thyroid?

(A) Diffuse sheets and cords of chief cells

(B) Proliferation of parafollicular cells with amyloid

(C) Well differentiated tumor with psammoma bodies

(D) Diffuse lymphocytic infiltrate with germinal centers

(E) Follicular cell proliferation with vascular invasion

5–D. The presence of antimicrosomal or antithyroglobulin antibodies in the serum is suggestive of Hashimoto's thyroiditis, which is a frequent cause of hypothyroidism. This disease can present with a diffusely enlarged gland although a firm, rubbery, multilobulated gland may also be present and may mimic thyroid tumors. The characteristic histopathologic finding of Hashimoto's thyroiditis is diffuse lymphocytic infiltrate with normal germinal centers. Diffuse sheets and cords of chief cells suggests diffuse parathyroid hyperplasia. Parafollicular, or C, cell proliferation with the presence of amyloid is suggestive of medullary thyroid carcinoma. Psammoma bodies are characteristic of papillary tumors. Extensive follicular cell proliferation with vascular invasion is suggestive of a follicular carcinoma.

6. A 41-year-old woman presents to the office with a 3-cm nodule in the right lobe of the thyroid gland involving part of the isthmus. Fine needle aspiration (FNA) of the lesion reveals a well differentiated lesion with lamellar mineral deposits surrounding necrotic cells (psammoma body). Which of the following is the most appropriate treatment for this patient?

(A) Right lobectomy with isthmusectomy and radioiodine (¹³¹I) therapy

(B) Total thyroidectomy and postoperative ¹³¹I therapy

(C) Total thyroidectomy alone

(D) Right lobectomy with isthmusectomy alone

(E) Total thyroidectomy with right-sided lymph node dissection

6–B. Psammoma bodies are a classic histologic finding of papillary carcinoma of the thyroid gland. Appropriate surgical treatment of large papillary carcinomas near the isthmus includes total or near total thyroidectomy with postoperative radioiodine (¹³¹I) ablation therapy because these lesions are sensitive to ¹³¹I. A lymph node dissection is generally not required in these patients. For some small papillary carcinomas (< 1.5 cm) involving 1 lobe only, some advocate lobectomy and isthmusectomy alone; however, in this setting this would be considered inadequate treatment.

7. A 54-year-old woman undergoes an elective total thyroidectomy for follicular cell carcinoma. The dissection was noted to be somewhat difficult but the patient tolerated the procedure well. Twelve hours postoperatively the patient is noted to be very anxious. On physical examination she is noted to have facial fasiculations and facial muscle twitching to palpation. Which of the following is the most appropriate therapy for this patient?

(A) Administration of calcium supplements

(B) Direct laryngoscopy to identify paralyzed vocal cord

(C) Re-exploration and evacuation of hematoma

(D) Immediate reintubation

(E) Immediate forearm implantation of inadvertently resected parathyroid tissue

7–A. Postoperative hypoparathyroidism with resultant hypocalcemia is most commonly caused by devascularization of the parathyroid glands rather than removal of all the glands. After thyroid surgery, permanent hypoparathyroidism is quite rare, although temporary hypocalcemia may be present. Signs and symptoms of the resultant hypocalcemia in the postoperative period include paresthesias, tetany, seizures, mental status changes, Chvostek sign (facial twitching with tapping of the facial nerve), and Trousseau sign. Treatment involves administration of calcium supplements (e.g., intravenous calcium gluconate). Recurrent laryngeal nerve injury is unlikely to cause these signs and symptoms; thus, laryngoscopy or reintubation is not necessary. A hematoma is also unlikely to present in this manner. Delayed forearm transplantation, hours after removal of the specimen would not be helpful acutely and is unlikely to be successful.

8. A 35-year-old man with a 5-year history of end-stage renal disease requiring hemodialysis presents to the emergency room with complaints of right leg pain after minor trauma to the area. Plain radiographs reveal a fracture line along the tibia with notable bone demineralization and soft tissue calcification. Further work-up reveals elevation of parathyroid hormone (PTH) and a decreased ionized calcium level. Which of the following is the most appropriate treatment measure for this patient's underlying condition?

(A) Resection of 3.5 parathyroid glands

(B) Resection of all parathyroid glands with autotransplantation

(C) Radiation therapy to the parathyroid glands

(D) Calcium supplements, vitamin D, and alteration of dialysis fluid

(E) Calcium restriction and alteration of dialysis fluid

8–D. This patient has characteristic findings of secondary hyperparathyroidism in a patient on chronic hemodialysis. The presence of a pathologic fracture precipitated by minor trauma with bone demineralization and soft tissue calcification in association with an elevated parathyroid hormone (PTH) and hypocalcemia is characteristic of this disease. Treatment involves administering calcium supplements, vitamin D, and adding calcium to dialysate fluid. Calcium restriction and altering dialysis fluid are contraindicated in this setting. Parathyroid resection is not indicated in the treatment of secondary hyperparathyroidism. Radiation therapy plays no role in the treatment of hyperparathyroidism.

9. A 75-year-old man presents to the office for a routine check-up. The patient states that he has been doing well except for some mild low-back pain, which he attributes to working too much in the yard. A chemistry panel reveals an elevated calcium level but no other significant abnormalities. Plain radiographs reveal multiple lytic lesions within the vertebral bodies of L4 and L5. After a thorough physical examination, which of the following tests is most appropriate in the subsequent evaluation of this patient?

(A) Serum parathyroid hormone (PTH) levels and neck ultrasound

(B) Serum PTH levels and measurement of creatinine clearance

(C) Neck exploration and resection of 3.5 parathyroid glands

(D) Transrectal ultrasound of the prostate and prostate-specific antigen levels

(E) Serum PTH and computed tomography (CT) scan of the neck

9–D. Malignancy is a frequent cause of hypercalcemia. In the setting described, metastatic disease to the lumbar vertebrate should be suspected as the cause of hypercalcemia rather than a primary disorder of the parathyroid gland. Adenocarcinoma of the prostate gland frequently metastasizes to the vertebral bodies and produces characteristic osteoblastic lesions, as described. Transrectal ultrasound of the prostate and measurement of prostate-specific antigen levels would be appropriate in the evaluation of this patient before any work-up of parathyroid disease. Multiple myeloma may also cause osteoblastic lesions; this is seen most commonly in men 50–60 years old. Other tumors that should be considered in this setting include lung, colon, and breast (women > men) cancers. Measurement of PTH or neck exploration would not be useful in the evaluation or management of this patient's primary disease process.

10. A 46-year-old woman presents to the office with a 3-cm mass in the right lobe of the thyroid. On physical examination, the mass is noted to be cystic in nature. Fine needle aspiration (FNA) of the cyst reveals colloid. Which of the following is the most appropriate management strategy for this patient?

(A) No further therapy and continued observation

(B) Total thyroidectomy alone

(C) Right lobectomy and isthmusectomy

(D) Total thyroidectomy and radioiodine (¹³¹I) therapy

(E) Total thyroidectomy and right-sided lymph node dissection

10–A. Most cystic masses are benign in nature and represent simple colloid-filled cysts. Simple needle-guided drainage of these lesions is adequate therapy. Recurring lesions or cystic lesions that persist for longer than 3 months may require resection. It should be noted that some carcinomas of the thyroid may undergo central necrosis and appear cystic, although cytology will generally identify these lesions. Formal resection in the setting of a simple colloid nodule is not indicated. Formal resection or ablation therapy is not required for simple cystic lesions that respond to needle-guided drainage.