BASIC SCIENCE QUESTIONS
1. The most common position of the RIGHT recurrent laryngeal nerve is
A. Anterior to the inferior thyroid artery
B. Posterior to the inferior thyroid artery
C. Between the branches of the inferior thyroid artery
D. Absent (nonrecurrent laryngeal nerve)
Answer: B
The left RLN arises from the vagus nerve where it crosses the aortic arch, loops around the ligamentum arteriosum, and ascends medially in the neck within the tracheoesophageal groove. The right RLN arises from the vagus at its crossing with the right subclavian artery. The nerve usually passes posterior to the artery before ascending in the neck, its course being more oblique than the left RLN. Along their course in the neck, the RLNs may branch, and pass anterior, posterior, or interdigitate with branches of the inferior thyroid artery (Fig. 38-1). The right RLN may be nonrecurrent in 0.5 to 1% of individuals and often is associated with a vascular anomaly. (See Schwartz 9th ed., p 1346.)
FIG. 38-1. Relationship of recurrent laryngeal nerve to the inferior thyroid artery—the superior parathyroid is characteristically dorsal to the plane of the nerve, whereas the inferior gland is ventral to the nerve.
2. Thyroid hormone receptors
A. Bind T4
B. Bind T3
C. Are present in the mitochondria
D. Are present on the cell membrane
Answer: B
Free thyroid hormone enters the cell membrane by diffusion or by specific carriers and is carried to the nuclear membrane by binding to specific proteins. T4 is deiodinated to T3 and enters the nucleus via active transport, where it binds to the thyroid hormone receptor. The T3 receptor is similar to the nuclear receptors for glucocorticoids, mineralocorticoids, estrogens, vitamin D, and retinoic acid. In humans, two types of T3 receptor genes (α and β) are located on chromosomes 3 and 17. (See Schwartz 9th ed., p 1348.)
3. The inferior parathyroid glands are derived from the
A. 1st branchial pouch
B. 2nd branchial pouch
C. 3rd branchial pouch
D. 4th branchial pouch
Answer: C
In humans, the superior parathyroid glands are derived from the fourth branchial pouch, which also gives rise to the thyroid gland. The third branchial pouches give rise to the inferior parathyroid glands and the thymus. (See Schwartz 9th ed., p 1374.)
4. Parathormone secretion is stimulated by
A. Hypermagnesemia
B. Hypovitaminosis D
C. Parasympathetic stimulation
D. Severe hypokalemia
Answer: B
The parathyroid cells rely on a Gprotein coupled membrane receptor, designated the calcium-sensing receptor (CASR), to regulate PTH secretion by sensing extracellular calcium levels. PTH secretion also is stimulated by low levels of 1,25-dihydroxy vitamin D, catecholamines, and hypomagnesemia. (See Schwartz 9th ed., p 1376.)
5. Which of the following receptors has the greatest affinity for epinephrine?
A. α adrenergic receptor
B. β1 adrenergic receptor
C. β2 adrenergic receptor
D. γ adrenergic receptor
Answer: A
Adrenergic receptors are transmembrane-spanning molecules, which are coupled to G proteins. They may be subdivided into α and β subtypes, which are localized in different tissues, have varying affinity to various catecholamines, and mediate distinct biologic effects (Table 38-1). The receptor affinities for α receptors are—epinephrine > norepinephrine >> isoproterenol; β1 receptors—isoproterenol > epinephrine = norepinephrine; and β2 receptors—isoproterenol > epinephrine >> norepinephrine. There is no γ adrenergic receptor. (See Schwartz 9th ed., p 1392.)
TABLE 38-1 Catecholamine hormone receptors and effects they mediate
6. The left adrenal vein drains into the
A. IVC
B. Left renal vein
C. Left gonadal vein
D. Splenic vein
Answer: B
In contrast to the arterial supply, each adrenal usually is drained by a single, major adrenal vein. The right adrenal vein is usually short and drains into the IVC, whereas the left adrenal vein is longer and empties into the left renal vein after joining the inferior phrenic vein. (See Schwartz 9th ed., p 1389.)
7. Which of the following is an effect of thyroid hormones?
A. Positive inotropic effect on the heart
B. Maintenance of the normal hypoxic drive to breathe
C. Increased protein turnover
D. All of the above
Answer: D
Thyroid hormones affect almost every system in the body. They are important for fetal brain development and skeletal maturation. T3 increases oxygen consumption, basal metabolic rate, and heat production by stimulation of Na+/K+ ATPase in various tissues. It also has positive inotropic and chronotropic effects on the heart by increasing transcription of the Ca2+ ATPase in the sarcoplasmic reticulum and increasing levels of beta-adrenergic receptors and concentration of G proteins. Myocardial alpha receptors are decreased and actions of catecholamines are amplified. Thyroid hormones are responsible for maintaining the normal hypoxic and hypercapnic drive in the respiratory center of the brain. They also increase GI motility, leading to diarrhea in hyperthyroidism and constipation in hypothyroidism. Thyroid hormones also increase bone and protein turnover and the speed of muscle contraction and relaxation. They also increase glycogenolysis, hepatic gluconeogenesis, intestinal glucose absorption, and cholesterol synthesis and degradation. (See Schwartz 9th ed., p 1349.)
8. The origin of the superior thyroid artery is
A. Internal carotid artery
B. External carotid artery
C. Thyrocervical trunk
D. Innominate artery
Answer: B
The superior thyroid arteries arise from the ipsilateral external carotid arteries and divide into anterior and posterior branches at the apices of the thyroid lobes. The inferior thyroid arteries arise from the thyrocervical trunk shortly after their origin from the subclavian arteries. The inferior thyroid arteries travel upward in the neck posterior to the carotid sheath to enter the thyroid lobes at their midpoint. A thyroidea ima artery arises directly from the aorta or innominate in 1 to 4% of individuals to enter the isthmus or replace a missing inferior thyroid artery. (See Schwartz 9th ed., p 1345, and Fig. 38-2.)
FIG. 38-2. Anatomy of the thyroid gland and surrounding structures, viewed anteriorly (A) and in cross-section (B). a. = artery; m. = muscle; n. = nerve; v. = vein.
B
9. The most common location of the superior parathyroid glands is
A. Dorsal to the recurrent laryngeal nerve (RLN), within 1 cm of the junction of the RLN and inferior thyroid artery
B. Ventral to the recurrent laryngeal nerve (RLN), within 1 cm of the junction of the RLN and inferior thyroid artery
C. Dorsal to the recurrent laryngeal nerve (RLN), within 3 cm of the junction of the RLN and inferior thyroid artery
D. Ventral to the recurrent laryngeal nerve (RLN), within 3 cm of the junction of the RLN and inferior thyroid artery
Answer: A
About 85% of individuals have four parathyroid glands that can be found within 1 cm of the junction of the inferior thyroid artery and the RLN. The superior glands are usually located dorsal to the RLN, whereas the inferior glands are usually found ventral to the RLN (Fig. 38-3). (See Schwartz 9thed., p 1349.)
FIG. 38-3. Relationship of the parathyroids to the recurrent laryngeal nerve. a. = artery; v. = vein.
10. Secreted parathormone has a half-life of
A. 2-4 minutes
B. 45-60 minutes
C. 3 hours
D. 8 hours
Answer: A
Secreted PTH has a half-life of 2 to 4 minutes. In the liver, PTH is metabolized into the active N-terminal component and the relatively inactive C-terminal fraction. The C-terminal component is excreted by the kidneys and accumulates in chronic renal failure. (See Schwartz 9th ed., p 1376.)
11. Which of the following is the substrate for all catecholamines?
A. Alanine
B. Leucine
C. Tryptophan
D. Tyrosine
Answer: D
Catecholamine hormones (epinephrine, norepinephrine, and dopamine) are produced not only in the central and sympathetic nervous system but also in the adrenal medulla. The substrate, tyrosine, is converted to catecholamines via a series of steps shown in Fig. 38-4. (See Schwartz 9th ed., p 1392.)
FIG. 38-4. Synthesis of catecholamines.
12. The adrenal cortex arises from
A. Ectoderm
B. Mesoderm
C. Endoderm
D. Neural crest
Answer: B
The cortex originates around the fifth week of gestation from mesodermal tissue near the gonads on the adrenogenital ridge. Therefore, ectopic adrenocortical tissue may be found in the ovaries, spermatic cord, and testes. The cortex differentiates further into a thin, definitive cortex and a thicker, inner fetal cortex. The latter is functional and produces fetal adrenal steroids by the eighth week of gestation, but undergoes involution after birth, resulting in a decrease in adrenal weight during the first three postpartum months. The definitive cortex persists after birth to form the adult cortex over the first 3 years of life. In contrast, the adrenal medulla is ectodermal in origin and arises from the neural crest. (See Schwartz 9th ed., p 1389.)
13. The inferior adrenal artery originates from the
A. Phrenic artery
B. Splenic artery
C. Renal artery
D. Aorta
Answer: C
Each adrenal gland is supplied by three groups of vessels—the superior adrenal arteries derived from the inferior phrenic artery, the middle adrenal arteries derived from the aorta, and the inferior adrenal arteries derived from the renal artery. Other vessels originating from the intercostal and gonadal vessels may also supply the adrenals. These arteries branch into about 50 arterioles to form a rich plexus beneath the glandular capsule and require careful dissection, ligation, and division during adrenalectomy. (See Schwartz 9th ed., p 1389.)
14. Which of the following is NOT an effect of glucocorticosteroids?
A. Decreased muscle protein synthesis
B. Decreased lipolysis
C. Inhibition of bone formation
D. Increased cardiac output
Answer: B
Glucocorticoids have important functions in intermediary metabolism but also affect connective tissue, bone, immune, cardiovascular, renal, and central nervous systems, as outlined in Table 38-2. (See Schwartz 9th ed., p 1391.)
TABLE 38-2 Functions of glucocorticoid hormones
15. The RET proto-oncogene is associated with
A. Papillary thyroid cancer
B. Hirschsprung’s disease
C. Pheochomocytoma
D. All of the above
Answer: D
The RET proto-oncogene plays a significant role in the pathogenesis of thyroid cancers. It is located on chromo-some 10 and encodes a receptor tyrosine kinase, which binds several growth factors such as glial-derived neurotrophic factor and neurturin. The RET protein is expressed in tissues derived from the embryonic nervous and excretory systems. Therefore, RET disruption can lead to developmental abnormalities in organs derived from these systems, such as the enteric nervous system (Hirschsprung’s disease) and kidney. Germline mutations in the RET protooncogene are known to predispose to MEN2A, MEN2B, and familial MTCs, and somatic mutations have been demonstrated in tumors derived from the neural crest, such as MTCs (30%) and pheochromocytomas. (See Schwartz 9th ed., p 1361, and Table 38-3.)
TABLE 38-3 Oncogenes and tumor-suppressor genes implicated in thyroid tumorigenesis
16. Thyroxine (T4) is composed of
A. Two Diiodotyrosine (DIT) molecules
B. One Diiodotyrosine (DIT) molecules and two monoiodohyrosin (MIT) molecules
C. Four monoiodohyrosin (MIT) molecules
D. None of the above
Answer: A
The synthesis of thyroid hormone consists of several steps. The first, iodide trapping, involves active (ATP-dependent) transport of iodide across the basement membrane of the thyrocyte via an intrinsic membrane protein, the sodium/iodine (Na+/I–) symporter. Thyroglobulin (Tg) is a large (660 kDa) glycoprotein, which is present in thyroid follicles and has four tyrosyl residues. The second step in thyroid hormone synthesis involves oxidation of iodide to iodine and iodination of tyrosine residues on Tg, to form monoiodotyrosines (MIT) and diiodotyrosines (DIT). Both processes are catalyzed by thyroid peroxidase (TPO). A recently identified protein, pendrin, is thought to mediate iodine efflux at the apical membrane. The third step leads to coupling of two DIT molecules to form tetra-iodothyronine or thyroxine (T4), and one DIT molecule with one MIT molecule to form 3,5,3’-triiodothyronine (T3) or 3,3’,5’–triiodothyronine reverse (rT3). (See Schwartz 9th ed., p 1348.)
17. Which of the following is a function of aldosterone?
A. Increased potassium absorption
B. Increased hydrogen ion absorption
C. Increased sodium absorption
D. None of the above
Answer: C
Aldosterone functions mainly to increase sodium reabsorption and potassium and hydrogen ion excretion at the level of the renal distal convoluted tubule. Less commonly, aldosterone increases sodium absorption in salivary glands and GI mucosal surfaces. (See Schwartz 9th ed., p 1390.)
18. Glucocorticoids are produced in the
A. Zona glomerulosa
B. Zona fasciculate
C. Zona reticularis
D. Adrenal medulla
Answer: B
The adrenal cortex appears yellow due to its high lipid content and accounts for about 80 to 90% of the gland’s volume. Histologically, the cortex is divided into three zones—the zona glomerulosa, zona fasciculata, and zona reticularis. The outer area of the zona glomerulosa consists of small cells and is the site of production of the mineralocorticoid hormone, aldosterone. The zona fasciculate is made up of larger cells, which often appear foamy due to multiple lipid inclusions, whereas the zona reticularis cells are smaller. These latter zones are the site of production of glucocorticoids and adrenal androgens. The adrenal medulla constitutes up to 10 to 20% of the gland’s volume and is reddish brown in color. It produces the catecholamine hormones epinephrine and norepinephrine. (See Schwartz 9th ed., p 1389.)
19. The paired lateral thyroid anlages fuse with the median thyroid anlage in the 5th week of gestation. These paired lateral anlages originate from
A. Ectoderm
B. Mesoderm
C. Endoderm
D. Neural crest
Answer: C
The thyroid gland arises as an outpouching of the primitive foregut around the third week of gestation. It originates at the base of the tongue at the foramen cecum. Endoderm cells in the floor of the pharyngeal anlage thicken to form the medial thyroid anlage that descends in the neck anterior to structures that form the hyoid bone and larynx. During its descent, the anlage remains connected to the foramen cecum via an epithelial-lined tube known as the Thyroglossal duct. The epithelial cells making up the anlage give rise to the thyroid follicular cells. The paired lateral anlages originate from the fourth branchial pouch and fuse with the median anlage at approximately the fifth week of gestation. The lateral anlages are neuroectodermal in origin (ultimobranchial bodies) and provide the calcitonin producing parafollicular or C cells, which thus come to lie in the superoposterior region of the gland. (See Schwartz 9th ed., p 1344.)
20. Cholesterol is the precursor of all hormones produced in the adrenal gland. The first step in the synthesis of all adrenal hormones is to cleave cholesterol to produce
A. Progesterone
B. Pregnenolone
C. 17α-hydroxypregnenolone
D. 11-deoxy-corticosterone
Answer: B
Pregnenolone is produced by cleaving the cholesterol side chain and becomes the precursor to all adrenal hormones (Fig. 38-5). (See Schwartz 9th ed., p 1390.)
FIG. 38-5. Synthesis of adrenal steroids. The enzymes involved are (1) p450scc (cholesterol side chain cleavage), (2) 3β-hydroxysteroid dehydrogenase, (3) p450c21 (21 β-hydroxylase), (4) p450c11 (11 β-hydroxylase), (5) p450c11AS (aldosterone synthase), (6) p450c17 (17α-hydroxylase activity), (7) p450c17 (17, 20-lyase/desmolase activity), and (8) sulfokinase. DHEAS = dehydroepiandrosterone sulfate.
CLINICAL QUESTIONS
1. Propylthiouracil
A. Can be given once a day in patients with hyperthyroidism
B. Can cause agranulocytosis
C. Does not affect the peripheral conversion of T4 to T3
D. Does not cross the placenta
Answer: B
Antithyroid medications generally are administered in preparation for RAI ablation or surgery. The drugs commonly used are propylthiouracil (PTU, 100 to 300 mg three times daily) and methimazole (10 to 30 mg three times daily, then once daily). Methimazole has a longer half-life and can be dosed once daily. Both drugs reduce thyroid hormone production by inhibiting the organic binding of iodine and the coupling of iodotyrosines (mediated by TPO). In addition, PTU also inhibits the peripheral conversion of T4 to T3, making it useful for the treatment of thyroid storm. Both drugs can cross the placenta, inhibiting fetal thyroid function, and are excreted in breast milk, although PTU has a lower risk of transplacental transfer. Methimazole also has been associated with congenital aplasia; therefore, PTU is preferred in pregnant and breastfeeding women. Side effects of treatment include reversible granulocytopenia, skin rashes, fever, peripheral neuritis, polyarteritis, vasculitis, and, rarely, agranulocytosis and aplastic anemia. Patients should be monitored for these possible complications and should always be warned to stop PTU or methimazole immediately and seek medical advice should they develop a sore throat or fever. Treatment of agranulocytosis involves admission to the hospital, discontinuation of the drug, and broad-spectrum antibiotic therapy. Surgery should be postponed until the granulocyte count reaches 1000 cells/m3. (See Schwartz 9th ed., p 1354.)
2. Which of the following is NOT commonly seen in patients with MEN1 syndrome?
A. Gastrinoma
B. Insulinoma
C. Prolactinoma
D. Pheochromocytoma
Answer: D
Pheochromocytomas are seen in patients with MEN2 syndrome. PHPT is the earliest and most common manifestation of MEN159 and develops in 80 to 100% of patients by age 40 years old. These patients also are prone to pancreatic neuroendocrine tumors and pituitary adenomas and, less commonly, to adrenocortical tumors, lipomas, skin angiomas, and carcinoid tumors of the bronchus, thymus, or stomach. About 50% of patients develop gastrinomas, which often are multiple and metastatic at diagnosis. Insulinomas develop in 10 to 15% of cases, whereas many patients have nonfunctional pancreatic endocrine tumors. Prolactinomas occur in 10 to 50% of MEN1 patients and constitute the most common pituitary lesion. (See Schwartz 9th ed., p 1377.)
3. Painful subacute thyroiditis
A. Results in hypothyroidism in >80% of patients
B. Occurs most commonly in women >70 years of age
C. Is often preceded by an upper respiratory tract infection
D. Requires thyroidectomy for relief of symptoms in >50% of patients
Answer: C
Painful thyroiditis most commonly occurs in 30- to 40-year-old women and is characterized by the sudden or gradual onset of neck pain, which may radiate toward the mandible or ear. History of a preceding upper respiratory tract infection often can be elicited. The gland is enlarged, exquisitely tender, and firm. The disorder classically progresses through four stages. An initial hyperthyroid phase, due to release of thyroid hormone, is followed by a second, euthyroid phase. The third phase, hypothyroidism, occurs in about 20 to 30% of patients and is followed by resolution and return to the euthyroid state in >90% of patients. A few patients develop recurrent disease.
Painful thyroiditis is self-limited, and therefore, treatment is primarily symptomatic. Aspirin and other NSAIDs are used for pain relief, but steroids may be indicated in more severe cases. Short-term thyroid replacement may be needed and may shorten the duration of symptoms. Thyroidectomy is reserved for the rare patient who has a prolonged course not responsive to medical measures or for recurrent disease. (See Schwartz 9th ed., p 1356.)
4. Which of the following tests has the highest sensitivity in localizing parathyroid adenomas?
A. Ultrasound
B. Fine cut CT scan
C. PET scan
D. Sestamibi scan
Answer: D
99mTc-labeled sestamibi is the most widely used and accurate modality with a sensitivity >80% for detection of parathyroid adenomas. Sestamibi (Cardiolite) initially was introduced for cardiac imaging and is concentrated in mitochondria-rich tissue. It was subsequently noted to be useful for parathyroid localization due to the delayed washout of the radionuclide from hypercellular parathyroid tissue compared to thyroid tissue. Sestamibi scans generally are complemented by neck ultrasound, which can identify adenomas with >75% sensitivity in experienced centers, and are most useful in identifying intrathyroidal parathyroids. Single-photon emission computed tomography, particularly when used with CT, has been shown to be superior to other nuclear medicine-based imaging. Specifically, single-photon emission computed tomography can indicate whether an adenoma is located in the anterior or posterior mediastinum (aortopulmonary window), thus enabling the surgeon to modify the operative approach accordingly. CT and MRI scans are less sensitive than sestamibi scans, but are helpful in localizing large paraesophageal and mediastinal glands. (See Schwartz 9th ed., p 1381.)
5. Which of the following drugs can cause thyroid storm in patients with hyperthyroidism?
A. Amiodarone
B. Labetalol
C. Corticosteroids
D. None of the above
Answer: A
Thyroid storm is a condition of hyperthyroidism accompanied by fever, central nervous system agitation or depression, cardiovascular dysfunction that may be precipitated by infection, surgery, or trauma. Occasionally, thyroid storm may result from amiodarone administration. This condition was previously associated with high mortality rates but can be appropriately managed in an intensive care unit setting. Beta blockers are given to reduce peripheral T4 to T3conversion and decrease the hyperthyroid symptoms. Oxygen supplementation and hemodynamic support should be instituted. Non-aspirin compounds can be used to treat pyrexia and Lugol’s iodine or sodium ipodate (intravenously) should be administered to decrease iodine uptake and thyroid hormone secretion. PTU therapy blocks the formation of new thyroid hormone and reduces peripheral conversion of T4 to T3. Corticosteroids often are helpful to prevent adrenal exhaustion and block hepatic thyroid hormone conversion. (See Schwartz 9th ed., p 1355.)
6. In patients with elevated thyroglobulin after total thyroidectomy for thyroid cancer, many physicians recommend a dose of 100 mCi of 131I. Which of the following is a reported complication of this treatment?
A. Sialadenitis
B. Cerebral edema
C. Bone marrow suppression
D. Vocal cord paralysis
Answer: A
Sialadenitis, nausea, and vomiting are symptoms reported to occur with as little as 50 mCi of 131I. (See Schwartz 9th ed., p 1367, and Table 38-4.)
TABLE 38-4 Complications of radioactive iodine therapy (131|) and doses at which they are observed
7. The most common cause of Cushing’s syndrome is
A. Adrenal adenoma
B. Adrenal hyperplasia
C. Ectopic ACTH production
D. Pituitary adenoma
Answer: D
Although a bit confusing, the most common cause of Cushing’s syndrome is Cushing’s disease. Cushing’s syndrome refers to a complex of symptoms and signs resulting from hypersecretion of cortisol regardless of etiology. In contrast, Cushing’s disease refers to a pituitary tumor, usually an adenoma, which leads to bilateral adrenal hyperplasia and hypercortisolism. Cushing’s syndrome (endogenous) is a rare disease, affecting 10 in 1 million individuals. It is more common in adults but may occur in children. Women are more commonly affected (male:female ratio 1:8). Although most individuals have sporadic disease, Cushing’s syndrome may be found in MEN1 families and can result from ACTH-secreting pituitary tumors, primary adrenal neoplasms, or an ectopic ACTH-secreting carcinoid tumor (more common in men) or bronchial adenoma (more common in women).
Cushing’s syndrome may be classified as ACTH-dependent or ACTH-independent (Table 38-5). The most common cause of hypercortisolism is exogenous administration of steroids. However, approximately 70% of cases of endogenous Cushing’s syndrome are caused by an ACTH-producing pituitary tumor. Primary adrenal sources (adenoma, hyperplasia, and carcinoma) account for about 20% of cases and ectopic ACTH-secreting tumors account for 10% of cases. (See Schwartz 9th ed., p 1394.)
TABLE 38-5 Etiology of Cushing’s syndrome
ACTH-dependent (70%)
• Pituitary adenoma or Cushing’s disease (~70%)
• Ectopic ACTH productiona (~10%)
• Ectopic CRH production (1%)
ACTH-independent (20–30%)
• Adrenal adenoma (10–15%)
• Adrenal carcinoma (5–10%)
• Adrenal hyperplasia—pigmented micronodular cortical hyperplasia or gastric inhibitory peptide-sensitive macronodular hyperplasia (5%)
Other
• Pseudo-Cushing’s syndrome
• Iatrogenic—exogenous administration of steroids
a From small cell lung tumors, pancreatic islet cell tumors, medullary thyroid cancers, pheochromocytomas, and carcinoid tumors of the lung, thymus, gut, pancreas, and ovary. ACTH = adrenocorticotropic hormone; CTH = corticotrophin-releasing hormone.
8. Surgery is indicated in which of the following asymptomatic patients with primary hyperparathyroidism?
A. Mildly elevated urinary calcium excretion (>100 mg/dl)
B. Reduction in creatinine clearance by 10%
C. Serum calcium >0.8 above the upper limits of normal
D. Age 50 years
Answer: D
The guidelines for surgery in asymptomatic patients with primary hyperparathyroidism were recently reassessed at a second workshop on asymptomatic PHPT held at the National Institutes of Health in 2002 as shown in Table 38-6…. It now is recommended for patients with smaller elevations in serum calcium levels (>1 mg/dL above the upper limit of normal) and if BMD measured at any of three sites (radius, spine, or hip) is greater than 2.5 standard deviations below those of gender- and race-matched, not age-matched, controls (i.e., peak bone density or T score (rather than Z score) 2.5). The panel still recommends exercising caution in using neuropsychologic abnormalities, cardiovascular disease, GI symptoms, menopause, and elevated serum or urine indices of increased bone turnover as sole indications for parathyroidectomy. (See Schwartz 9th ed., p 1380.)
TABLE 38-6 Indications for parathyroidectomy in patients with asymptomatic primary HPT (2002 NIH consensus conference guidelines)
• Serum calcium >1 mg/dL above the upper limits of normal
• Life-threatening hypercalcemic episode
• Creatine clearance reduced by 30%
• Kidney stones on abdominal x-rays
• Markedly elevated 24-h urinary calcium excretion (≥400 mg/d)
• Substantially decreased bone mineral density at the lumbar spine, hip, or distal radius (>2.5 SD below peak bone mass, T score –2.5
• Age 50 y
• Long-term medical surveillance not desired or possible
HPT = hyperparathyroidism; NIH = National Institutes of Health; SD = standard deviation.
9. A patient with a 1-cm medullary carcinoma of the right thyroid and no clinically significant adenopathy is best treated with
A. Right thyroid lobectomy and isthmusectomy
B. Right thyroid lobectomy and subtotal left thyroidectomy
C. Total thyroidectomy
D. Total thyroidectomy with central lymph node dissection
Answer: D
Total thyroidectomy is the treatment of choice for patients with MTC because of the high incidence of multicentricity, the more aggressive course, and the fact that 131I therapy usually is not effective. Central compartment nodes frequently are involved early in the disease process, so that a bilateral central neck node dissection should be routinely performed. In patients with palpable cervical nodes or involved central neck nodes, ipsilateral or bilateral, modified radical neck dissection is recommended. (See Schwartz 9th ed., p 1368.)
10. The most common cause of primary hyperparathyroidism is
A. Parathyroid adenoma
B. Multiple parathyroid adenomas
C. Parathyroid hyperplasia
D. Parathyroid carcinoma
Answer: A
PHPT results from the enlargement of a single gland or parathyroid adenoma in approximately 80% of cases, multiple adenomas or hyperplasia in 15 to 20% of patients, and parathyroid carcinoma in 1% of patients. (See Schwartz 9th ed., p 1377.)
11. Which of the following can be seen in the ophthalmopathy of Graves’ disease?
A. Chemosis
B. Proptosis
C. Blindness
D. All of the above
Answer: D
Approximately 50% of patients with Graves’ disease develop clinically evident ophthalmopathy. Eye symptoms include lid lag (von Graefe’s sign), spasm of the upper eyelid revealing the sclera above the corneoscleral limbus (Dalrymple’s sign), and a prominent stare, due to catecholamine excess. True infiltrative eye disease results in periorbital edema, conjunctival swelling and congestion (chemosis), proptosis, limitation of upward and lateral gaze (from involvement of the inferior and medial rectus muscles, respectively), keratitis, and even blindness due to optic nerve involvement. The etiology of Graves’ ophthalmopathy is not completely known; however, orbital fibroblasts and muscles are thought to share a common antigen, the TSHR. Ophthalmopathy is thought to result from inflammation caused by cytokines released from sensitized killer T lymphocytes and cytotoxic antibodies. (See Schwartz 9thed., p 1353.)
12. Papillary cancer of the thyroid
A. Is uncommon in children
B. Is the most common thyroid cancer in patients with a history of external radiation
C. Occurs more commonly in men
D. All of the above
Answer: B
Papillary carcinoma accounts for 80% of all thyroid malignancies in iodine-sufficient areas and is the predominant thyroid cancer in children and individuals exposed to external radiation. Papillary carcinoma occurs more often in women, with a 2:1 female-to-male ratio, and the mean age at presentation is 30 to 40 years. (See Schwartz 9th ed., p 1362.)
13. There are 7 compartments of lymph nodes in the neck. Metastases from thyroid cancer are uncommon in
A. Level I nodes
B. Level III nodes
C. Level V nodes
D. Level VII nodes
Answer: A
The thyroid gland is endowed with an extensive network of lymphatics. Intraglandular lymphatic vessels connect both thyroid lobes through the isthmus and also drain to perithyroidal structures and lymph nodes. Regional lymph nodes include pretracheal, paratracheal, perithyroidal, RLN, superior mediastinal, retropharyngeal, esophageal, and upper, middle, and lower jugular chain nodes. These lymph nodes can be classified into seven levels as depicted in Fig. 38-6. The central compartment includes nodes located in the area between the two carotid sheaths, whereas nodes lateral to the vessels are present in the lateral compartment. Thyroid cancers may metastasize to any of these regions, although metastases to submaxillary nodes (level I) are rare (1%). There also can be ‘skip’ metastases to nodes in the ipsilateral neck. (See Schwartz 9th ed., p 1347.)
FIG. 38-6. A and B. Lymph nodes in the neck can be divided into six regions. Upper mediastinal nodes constitute level VII. m. = muscle; n. = nerve.
14. A patient with hypertension is diagnosed with hyperaldosteronism. A CT scan shows bilaterally enlarged adrenals without a mass. The most appropriate next intervention is
A. Unilateral adrenalectomy
B. Bilateral adrenalectomy
C. Selective venous catheterization
D. Medical management
Answer: C
If adrenal hyperplasia is suspected, the algorithm depicted in Fig. 38-7 is useful. Selective venous catheterization and adrenal vein sampling for aldosterone has been demonstrated to be 95% sensitive and 90% specific in localizing the aldosteronoma. Only 20 to 30% of patients with hyperaldosteronism secondary to bilateral adrenal hyperplasia benefit from surgery and, as described, selective venous catheterization is useful to predict which patients will respond. For the other patients, medical therapy with spironolactone, amiloride, or triamterene is the mainstay of management. (See Schwartz 9th ed., p 1394.)
FIG. 38-7. Management of an adrenal aldosteronoma. CT = computed tomography; MRI = magnetic resonance imaging.
15. Papillary thyroid cancer of the clear cell variant is associated with
A. Cowden’s syndrome
B. Familial adenomatous polyposis
C. Werner’s syndrome
D. McCune-Albright syndrome
Answer: D
Nonmedullary thyroid cancers can occur in association with other known familial cancer syndromes such as Cowden’s syndrome, Werner’s (adult progeroid syndrome), and familial adenomatous polyposis (Table 38-7). (See Schwartz 9th ed., p 1360.)
TABLE 38-7 Familial cancer syndromes involving nonmedullary thyroid cancer
16. The initial treatment of choice for Riedel’s thyroiditis is
A. Observation
B. Antibiotics
C. Corticosteroids
D. Surgery
Answer: D
Riedel’s thyroiditis is a rare variant of thyroiditis also known as Riedel’s struma or invasive fibrous thyroiditis that is characterized by the replacement of all or part of the thyroid parenchyma by fibrous tissue, which also invades into adjacent tissues.
Surgery is the mainstay of the treatment for Riedel’s thyroiditis. The chief goal of operation is to decompress the trachea by wedge excision of the thyroid isthmus and to make a tissue diagnosis. More extensive resections are not advised due to the infiltrative nature of the fibrotic process that obscures usual landmarks and structures. Hypothyroid patients are treated with thyroid hormone replacement. Some patients who remain symptomatic have been reported to experience dramatic improvement after treatment with corticosteroids and tamoxifen. (See Schwartz 9th ed., p 1357.)
17. Which of the following should be the first drug to be started in a patient with a symptomatic pheochromocytoma?
A. ACE inhibitor
B. Alpha blocker
C. Beta blocker
D. Calcium channel blocker
Answer: B
Alpha blockers such as phenoxybenzamine are started 1 to 3 weeks before surgery at doses of 10 mg twice daily, which may be increased to 300 to 400 mg/d with rehydration. Patients should be warned about orthostatic hypotension. Other alpha blockers such as prazosin and other classes of drugs such as ACE inhibitors and calcium channel blockers are also useful. Beta blockers such as propranolol at doses of 10 to 40 mg every 6 to 8 hours often need to be added preoperatively in patients who have persistent tachycardia and arrhythmias. Beta blockers should only be instituted after adequate alpha blockade and hydration to avoid the effects of unopposed alpha stimulation, (i.e., hypertensive crisis and congestive heart failure). Patients also should be volume repleted preoperatively to avoid postoperative hypotension, which ensues with the loss of vasoconstriction after tumor removal. (See Schwartz 9th ed., p 1399.)
18. Following a total thyroidectomy for differentiated thyroid cancer, radioactive iodine ablation would be offered for all of the following patients EXCEPT
A. Stage III disease
B. Stage II disease 45 years of age
C. Stage 1 disease with multifocal disease
D. Stage 1 disease 45 years of age
Answer: D
RAI ablation currently is recommended for all patients with stage III or IV disease, all patients with stage II disease younger than 45 years old, most patients 45 years or older with stage II disease, and patients with stage I disease who have aggressive histologies, nodal metastases, multifocal disease, and extrathyroid or vascular invasion. (See Schwartz 9th ed., p 1365.)
19. Which of the following organisms is a common cause of acute (suppurative) thyroiditis?
A. Escherichia coli
B. Pseudomonas aeruginous
C. Streptococcus species
D. Staphylococcus aureus
Answer: C
The thyroid gland is inherently resistant to infection due to its extensive blood and lymphatic supply, high iodide content, and fibrous capsule. However, infectious agents can seed it (a) via the hematogenous or lymphatic route, (b) via direct spread from persistent pyriform sinus fistulae or thyroglossal duct cysts, (c) as a result of penetrating trauma to the thyroid gland, or (d) due to immunosuppression. Streptococcus and anaerobes account for about 70% of cases; however, other species also have been cultured. Acute suppurative thyroiditis is more common in children and often is preceded by an upper respiratory tract infection or otitis media. It is characterized by severe neck pain radiating to the jaws or ear, fever, chills, odynophagia, and dysphonia. Complications such as systemic sepsis, tracheal or esophageal rupture, jugular vein thrombosis, laryngeal chondritis, and perichondritis or sympathetic trunk paralysis may also occur. (See Schwartz 9th ed., p 1356.)
20. Thyroidectomy should be recommended for patients with Graves’ disease who
A. Are of the male gender
B. Are >55 years of age
C. Have large asymptomatic goiters
D. Have a suspicious thyroid nodule
Answer: D
In North America, surgery is recommended when RAI is contraindicated as in patients who (a) have confirmed cancer or suspicious thyroid nodules, (b) are young, (c) are pregnant or desire to conceive soon after treatment, (d) have had severe reactions to antithyroid medications, (e) have large goiters causing compressive symptoms, and (f) are reluctant to undergo RAI therapy. Relative indications for thyroidectomy include patients, particularly smokers, with moderate to severe Graves’ ophthalmopathy, those desiring rapid control of hyperthyroidism with a chance of being euthyroid, and those demonstrating poor compliance to antithyroid medications. (See Schwartz 9th ed., p 1355.)
21. Which of the following is an indication for surgery in patients with secondary hyperparathyroidism?
A. Calciphylaxis
B. PTH >250
C. Progressive renal failure
D. None of the above
Answer: A
Surgical treatment in secondary hyperparathyroidism was traditionally recommended for patients with bone pain, pruritus, and (a) a calcium-phosphate product ≥70, (b) calcium >11 mg/dL with markedly elevated PTH, (c) calciphylaxis, (d) progressive renal osteodystrophy, and (e) soft tissue calcification and tumoral calcinosis, despite maximal medical therapy. The role of parathyroidectomy in the era of calcimetics will require long-term studies; however, parathyroidectomy should be considered if PTH levels remain high despite optimal therapy. Calciphylaxis is a rare, limb- and life-threatening complication of secondary HPT characterized by painful (sometimes throbbing), violaceous, and mottled lesions usually on the extremities, which often become necrotic and progress to nonhealing ulcers, gangrene, sepsis, and death. These are critically ill, high-risk patients, but successful parathyroidectomy sometimes relieves symptoms. (See Schwartz 9th ed., p 1387.)
22. Thyroglossal duct cysts are most commonly located
A. On the anterior border of the sternocleidomastoid muscle
B. In the midline at the level of the hyoid
C. Over the medial clavicular head
D. In the midline just superior to the thyroid gland
Answer: B
Thyroglossal duct cysts are the most commonly encountered congenital cervical anomalies. During the fifth week of gestation, the thyroglossal duct lumen starts to obliterate, and the duct disappears by the eighth week of gestation. Rarely, the thyroglossal duct may persist in whole, or in part. Thyroglossal duct cysts may occur anywhere along the migratory path of the thyroid although 80% are found in juxtaposition to the hyoid bone.
The thyroid gland arises as an outpouching of the primitive foregut around the third week of gestation. It originates at the base of the tongue at the foramen cecum. Endoderm cells in the floor of the pharyngeal anlage thicken to form the medial thyroid anlage (Fig. 38-8) that descends in the neck anterior to structures that form the hyoid bone and larynx. During its descent, the anlage remains connected to the foramen cecum via an epithelial-lined tube known as the thyroglossal duct. (See Schwartz 9th ed., p 1344.)
FIG. 38-8. Thyroid embryology—early development of the median thyroid anlage as a pharyngeal pouch. (Reproduced with permission from Embryology and developmental abnormalities, in Cady B, Rossi R (eds): Surgery of the Thyroid and Parathyroid Glands. Philadelphia: WB Saunders, 1991, p 6.)
23. Which of the following syndromes is NOT typically associated with an increased risk of pheochromocytoma?
A. Familial adenomatous polyposis syndrome
B. Carney’s syndrome
C. von Hippel-Lindau syndrome
D. Sturge-Weber syndrome
Answer: A
Pheochromocytomas occur in families with MEN2A and MEN2B, in approximately 50% of patients. Both syndromes are inherited in an autosomal dominant fashion and are caused by germline mutations in the RET proto-oncogene. Another syndrome with an increased risk of pheochromocytomas is von Hippel-Lindau (VHL) disease, which also is inherited in an autosomal dominant manner. This syndrome also includes retinal angioma, hemangioblastomas of the central nervous system, renal cysts and carcinomas, pancreatic cysts, and epididymal cystadenomas. The incidence of pheochromocytomas in the syndrome is approximately 14%. The gene causing VHL has been mapped to chromosome 3p and is a tumor-suppressor gene. Pheochromocytomas also are included within the tumor spectrum of neurofibromatosis type 1 (NF1 gene) and other neuroectodermal disorders (Sturge-Weber syndrome and tuberous sclerosis), Carney’s syndrome (gastric epithelioid leiomyosarcoma, pulmonary chondroma, and extra-adrenal paraganglioma), MEN1 syndrome, and the familial paraganglioma and pheochromocytoma syndrome caused by mutations in the succinyl dehydrogenase family of genes (SDHB, SDHC, and SDHD). (See Schwartz 9th ed., p 1399.)
24. The most common cause of hyperthyroidism is
A. Graves’ disease
B. Toxic multinodular goiter
C. Plummer’s disease
D. Thyroiditis
Answer: A
Graves’ disease is by far the most common cause of hyperthyroidism in North America, accounting for 60 to 80% of cases. It is an autoimmune disease with a strong familial predisposition, female preponderance (5:1), and peak incidence between the ages of 40 and 60 years. Graves’ disease is characterized by thyrotoxicosis, diffuse goiter, and extrathyroidal conditions including ophthalmopathy, dermopathy (pretibial myxedema), thyroid acropachy, gynecomastia, and other manifestations. (See Schwartz 9th ed., p 1353, and Table 38-8.)
TABLE 38-8 Differential diagnosis of hyperthyroidism
25. The most common adrenal mass incidentally found on CT scan (adrenal incidentaloma) is
A. Adrenal cyst
B. Adrenal hemorrhage
C. Cortical adenoma
D. Myelolipoma
Answer: C
The differential diagnosis of adrenal incidentalomas is shown in Table 38-9. Nonfunctional cortical adenomas account for the majority (36 to 94%) of adrenal incidentalomas in patients without a history of cancer. (See Schwartz 9thed., p 1401.)
TABLE 38-9 Differential diagnosis of adrenal incidentaloma
26. Which of the following would be the best initial treatment of a symptomatic lingual thyroid?
A. Intravenous thyroxine
B. Radioactive iodine ablation
C. External beam radiation
D. Local surgical excision
Answer: B
A lingual thyroid represents a failure of the median thyroid anlage to descend normally and may be the only thyroid tissue present. Intervention becomes necessary for obstructive symptoms such as choking, dysphagia, airway obstruction, or hemorrhage. Many of these patients develop hypothyroidism. Medical treatment options include administration of exogenous oral thyroid hormone to suppress thyroid-stimulating hormone (TSH) and radioactive iodine (RAI) ablation followed by hormone replacement. Surgical excision is rarely needed but, if required, should be preceded by an evaluation of normal thyroid tissue in the neck to avoid inadvertently rendering the patient hypothyroid. (See Schwartz 9th ed., p 1345.)
27. A patient is noted to have an adrenal mass on CT scan. Which of the following CT findings is most suggestive of adrenal cancer?
A. Tumor heterogeneity
B. Adjacent lymphadenopathy
C. Size >6 cm
D. Lesion enhancement
Answer: C
The size of the adrenal mass on imaging studies is the single most important criterion to help diagnose malignancy. In the series reported by Copeland, 92% of adrenal cancers were >6 cm in diameter. The sensitivity, specificity, and likelihood ratio of tumor size in predicting malignancy (based on Surveillance; Epidemiology, and End Results program data) was recently reported as 96%, 51%, and 2 for tumors ≥4 cm; and 90%, 78%, and 4.1 for tumors ≥6 cm. Other CT imaging characteristics suggesting malignancy include tumor heterogeneity, irregular margins, and the presence of hemorrhage and adjacent lymphadenopathy or liver metastases. Moderately bright signal intensity on T2-weighted images (adrenal mass to liver ratio 1.2:2.8), significant lesion enhancement, and slow washout after injection of gadolinium contrast also indicate malignancy, as does evidence of local invasion into adjacent structures such as the liver, blood vessels (IVC), and distant metastases. (See Schwartz 9th ed., p 1397.)
28. The most sensitive test to diagnose a pheochromocytoma is
A. Plasma vanillylmandellic acid (VMA)
B. Urinary vanillylmandellic acid (VMA)
C. Plasma metanephrines
D. Urinary metanephrines
Answer: C
Recent studies have shown that plasma metanephrines are the most reliable tests to identify pheochromocytomas, with sensitivity approaching 100%.
Urinary metanephrines are 98% sensitive and also are highly specific for pheochromocytomas, whereas VMA measurements are slightly less sensitive and specific. False-positive VMA tests may result from ingestion of caffeine, raw fruits, or medications (α-methyldopa). Fractionated urinary catecholamines (norepinephrine, epinephrine, and dopamine) also are very sensitive but less specific for pheochromocytomas. (See Schwartz 9th ed., p 1399.)
29. Thyroid hormone production is inhibited by
A. Epinephrine
B. Glucocorticoids
C. Human chorionic gonadotrophin
D. Alphafetoprotein
Answer: B
Epinephrine and human chorionic gonadotrophin hormones stimulate thyroid hormone production. Thus, elevated thyroid hormone levels are found in pregnancy and gynecologic malignancies such as hydatidiform mole. In contrast, glucocorticoids inhibit thyroid hormone production. In severely ill patients, peripheral thyroid hormones may be reduced, without a compensatory increase in TSH levels, giving rise to the euthyroid sick syndrome. (See Schwartz 9thed., p 1348.)
30. Which of the following should be the first diagnostic test ordered in a patient with a solitary thyroid nodule?
A. Radioactive iodine scan
B. CT or MRI
C. Fine needle aspiration
D. Core needle biopsy
Answer: C
FNAB has become the single most important test in the evaluation of thyroid masses and can be performed with or without ultrasound guidance. (See Schwartz 9th ed., p 1360, and Fig. 38-9.)
FIG. 38-9. Management of a solitary thyroid nodule. a = except in patients with a history of external radiation exposure or a family history of thyroid cancer; FNAB = fine-needle aspiration biopsy; RAI = radioactive iodine; T4 = thyroxine.
31. Which of the following cancers does NOT occur in thyroglossal duct cysts?
A. Papillary thyroid cancer
B. Follicular thyroid cancer
C. Medullary thyroid cancer
D. Hürthle cell cancer
Answer: C
Approximately 1% of thyroglossal duct cysts are found to contain cancer, which is usually papillary (85%). The role of total thyroidectomy in this setting is controversial, but is advised in older patients with large tumors, particularly if there are additional thyroid nodules and evidence of cyst wall invasion or lymph node metastases. Squamous, Hürthle cell, and anaplastic cancers also have been reported but are rare. Medullary thyroid cancers (MTCs) are, however, not found in thyroglossal duct cysts. (See Schwartz 9th ed., p 1344.)