12 Endocrine Disorders

Question 1

1 How common is a supernumerary parathyroid gland, and where is the supernumerary gland most likely to be found? (▶ Fig. 12.1)

Answer 1

The incidence of a supernumerary parathyroid gland is up to 15%. They are most often found in:

• Thymus
• Thyrothymic tract
• Carotid sheath.

Question 2

2 Where do the superior and inferior parathyroid glands obtain their blood supply?

Answer 2

Most of the blood supply comes from the inferior thyroid artery, although occasionally the superior glands may get their blood supply from the superior thyroid artery (in 15% of cases).

Question 3

3 What options are available for minimally invasive parathyroidectomy?

Answer 3

Minimally invasive parathyroidectomy is gaining popularity among surgeons. Typically, a technetium-99 sestamibi scan preoperatively determine a single hyperfunctioning para thyroid adenoma, and exploration of that gland alone is done using intravenous (IV) sedation and intraoperative parathyroid hormone assay monitoring.

Question 4

4 When conducting a subtotal parathyroidectomy, what tissue should be left behind?

Answer 4

Approximately three and one-half glands should be excised and the remaining half of a gland left to its blood supply. Most prefer to leave a portion of an inferior parathyroid gland because there would less risk to the recurrent laryngeal nerve.

Question 5

5 How can PTH levels be used intraoperatively to determine the completeness of a parathyroidec tomy?

Answer 5

PTH has a half-life of 2–5 minutes, so PTH levels can be drawn from the patient before incision and then 5 to 10 minutes after excision. If there is at least a 50% decrease in the PTH level, into the normal or near normal range, the excised gland was likely the offending gland.

Question 6

6 What structures have been described as landmarks to identify the superior parathyroid gland?

Answer 6

About 80% of superior parathyroid glands are found on the posterior aspect of the thyroid gland within a 1-cm diameter centered 1 cm superior to the intersection of the recurrent laryngeal nerve and inferior thyroid artery.

Question 7

7 What branchial pouch gives rise to the superior and inferior parathyroid glands? (▶ Fig. 12.2)

Answer 7

The fourth branchial pouch gives rise to the superior parathyroid gland and C cells. The third branchial pouch gives rise to the inferior parathyroid gland and thymus.

Question 8

8 How does PTH maintain calcium levels?

Answer 8

PTH increases calcium absorption from the gut, mobilizes calcium from the bones, inhibits calcium excretion from the kidneys, and stimulates renal hydroxylase to maintain activated vitamin D levels

Question 9

9 What is the most potent regulator of PTH release?

Answer 9

Serum calcium levels

Question 10

10 Where can one find PTH receptors, and what downstream effects do they have in each location?

Answer 10

PTH binds to PTH receptors in two locations: bone and kidney. In bone, PTH receptors on osteoblasts cause release of receptor activator of nuclear factor-κ ligand, which then activates osteoclasts, which break down bone to increase serum calcium. In the kidney, PTH binds to renal tubule cells and induces reabsorption of calcium and decreases reabsorption of phosphate from the filtrate. It also induces the expression of an enzyme that converts the inactive form of vitamin D (25-hydroxyvitamin D) to the active form (1,25-dihydroxyvitamin D).

Question 11

11 When monitoring total calcium levels in a patient, what factor do you also need to note?

Answer 11

Albumin level. Total calcium can vary with albumin level. In a patient with normal albumin, total calcium can be monitored. In a patient with abnormal albumin levels, the corrected total calcium can be calculated (total serum calcium decreases by 0.8 g/dL for every 1-g/dL decrease in albumin), or the ionized calcium level can be followed.

Question 12

12 What test results support the diagnosis of familial hypocalciuric hypercalcemia?

Answer 12

Hypercalcemia with 24-hour urinary calcium:creatinine clearance ratio below 0.01, as well as one or more first degree relatives with hypercalcemia

Question 13

13 What are common symptoms of chronic hypercalcemia?

Answer 13

The symptoms of chronic hypercalcemia can be remembered by the mnemonic “bones, stones, abdominal groans, and psychiatric moans,” referring to renal calculi, bone pains, abdominal pain, and depression, anxiety, cognitive dysfunction or other psychiatric problems.

Question 14

14 What testing is necessary to diagnose primary hyperparathyroidism?

Answer 14

Elevated albumin-corrected serum calcium or ionized calcium and elevated PTH. Imaging serves as an adjunct but is not part of the diagnostic criteria of primary hyperparathyroidism

Question 15

15 Name the most common cause of hypercalcemia in an outpatient clinic setting.

Answer 15

Parathyroid adenoma

Question 16

16 Name the most common cause of hypercalcemia in an inpatient hospital setting.

Answer 16

Underlying malignancy

Question 17

17 A patient has hypercalcemia and low or undetectable PTH levels. What is the likely diagnosis?

Answer 17

Primary hyperparathyroidism is ruled out by the low or undetectable PTH level. This patient likely has a paraneoplastic-induced hypercalcemia mediated by PTH-related protein.

Question 18

18 What is the incidence of primary hyperparathy roidism in Western countries?

Answer 18

22 cases per 100,000 persons per year The incidence has increased since the 1970s because of increased detection of asymptomatic patients with elevated calcium levels. In postmenopausal women, the most common demographic, the incidence may be as high as 1 per 1,000/year.

Question 19

19 What are the different types of parathyroid hyperplasia?

Answer 19

Parathyroid hyperplasia is predominantly caused by pro liferation of the chief cells within the gland. Very rarely, water clear cell hyperplasia, which is a proliferation of vacuolated water clear cells, can be found. The water clear cell variant is clinically more severe and predominantly occurs in females.

Question 20

20 Describe the typical patient population with primary hyperparathyroidism.

Answer 20

Most cases occur in women (74%); incidence peaks in the seventh decade of life. Before age 45, incidence in men and women is similar.

Question 21

21 What causative factors are associated with primary hyperparathyroidism?

Answer 21

● Head and neck radiation in childhood ● Long-term lithium therapy ● Genetic predisposition

Question 22

22 What are the guidelines for surgical treatment (parathyroidectomy) in an asymptomatic patient with primary hyperparathyroidism?

Answer 22

Despite being devoid of classic symptoms, some patients should be treated for hyperparathyroidism, including those with serum calcium greater than 1.0 mg/dl above the upper limit of the normal reference range, those with a calculated creatinine clearance less than 60 ml/minute, those with bone mineral density T score less than –2.5 at any site or previous fragility fracture. Patients younger than 50 years should also be considered to prevent long-term damage from elevated calcium.

Question 23

23 What are the typical laboratory values of calcium, PTH, and phosphate in secondary hyperparathy roidism?

Answer 23

In secondary hyperparathyroidism, one would expect low normal calcium and elevated PTH. Phosphate levels vary based on the etiology (high in renal insufficiency, low in vitamin D deficiency).

Question 24

24 What are some possible causes of secondary hyperparathyroidism?

Answer 24

Secondary hyperparathyroidism can occur from renal fail ure, which causes a decline in the formation of activated 1,25 vitamin D and calcium absorption in the gut. Phosphate excretion is also impaired, which together cause low serum calcium. It can also result from low vitamin D levels in the setting of adequate renal function, such as in cases of dietary insufficiency. In addition, patients with short gut syndrome or a history of gastric bypass surgery are at risk for secondary disease resulting from malab sorption of both calcium and vitamin D. In all cases, low serum calcium triggers secretion of PTH and growth of the parathyroid glands.

Question 25

25 What is the treatment of secondary hyperpara thyroidism?

Answer 25

● Correction of the underlying cause, such as renal trans plant in patients with renal failure or vitamin D therapy in vitamin D deficiency ● Patient symptoms from secondary disease may improve with medications such as cincalcet or bisphosophate therapy. ● There is a role for subtotal parathyroidectomy if medical management fails.

Question 26

26 What is tertiary hyperparathyroidism?

Answer 26

Tertiary hyperparathyroidism is a state of excess secretion of PTH after long-standing secondary hyperparathyroidism. Phosphate levels in tertiary hyperparathyroidism are de creased; however, renal dysfunction may lead to hyper phosphatemia despite elevated PTH levels. A classic example is hyperparathyroidism persisting after renal transplantation.

Question 27

27 What is the pathophysiology of tertiary hyper parathyroidism?

Answer 27

The hypertrophied parathyroid glands become autonomous in their function and hypersecrete PTH, leading to hyper calcemia despite withdrawal of calcium and calcitriol. High calcium levels can cause diffuse calcinosis.

Question 28

28 What is the treatment of tertiary hyperparathyroidism?

Answer 28

Total parathyroidectomy with autotransplantation or subtotal parathyroidectomy (3 and ½ gland resection)

Question 29

29 What are the components of hyperparathyroidism-jaw tumor syndrome?

Answer 29

Recurrent parathyroid adenomas, fibroosseous tumors of the mandible, and Wilms tumors

Question 30

30 How do the symptoms of acute and chronic hypoparathyroidism differ?

Answer 30

Acute hypoparathyroidism, such as after surgery, can cause dramatic hypocalcemia and associated paresthesias, muscle spasms, tetany, and seizures. The hypocalcemia induced by chronic hypoparathyroidism is gradual in onset and may not present until the patient develops blurry vision from cataracts.

Question 31

31 What are the most common causes of hypoparathyroidism?

Answer 31

By far, the most common cause of hypoparathyroidism is iatrogenic, by either treatment of hyperparathyroidism or injury during thyroid surgery. The next most common causes are congenital, when the third and fourth branchial arches fail to develop properly.

Question 32

32 What is the histologic description of a parathyroid adenoma?

Answer 32

A parathyroid adenoma appears as a hypercellular gland consisting of chief and oncocytic cells with decreased intercellular fat.

Question 33

33 What are some intraoperative techniques used to identify a parathyroid adenoma?

Answer 33

Localization of an adenoma can be assisted by preoperative injection of methylene blue, which stains abnormal para thyroid glands preferentially. Preoperative injection of sestamibi in conjunction with intraoperative gamma probes can also be used to identify a parathyroid gland.

Question 34

34 What is the most sensitive imaging study for identifying the location of a parathyroid adenoma?

Answer 34

Technetium-99 m sestamibi with single-photon emission CT (or SPECT; sensitivity from 70 to 100%). Ultrasound imaging is reported to be successful in localization in 50 to 90% of cases but is highly user dependent. 4D CT scan is an emerging technology, but the localization success rate remains to be determined.

Question 35

35 How frequently is primary hyperparathyroidism caused by a single adenoma versus four-gland hyperplasia?

Answer 35

A single parathyroid adenoma is the cause in 80 to 85% of cases and four-gland hyperplasia in 10 to 15% of cases. Other causes of primary hyperparathyroidism include double adenomas (5%) and parathyroid carcinoma (< 1%).

Question 36

36 What features of a patient with hypercalcemia and elevated PTH are more concerning for a para thyroid carcinoma compared with benign para thyroid adenoma?

Answer 36

Aside from a palpable neck mass, other features worrisome for parathyroid carcinoma include markedly elevated serum calcium levels (> 14), markedly elevated PTH, concomitant renal and bone disease, symptoms consistent with severe hypercalcemia, and evidence of invasion such as recurrent laryngeal nerve palsy.

Question 37

37 What proportion of primary hyperparathyroidism is caused by parathyroid carcinoma?

Answer 37

About 0.1 to 1% of persons with primary hyperparathy roidism have a parathyroid carcinoma.

Question 38

38 What are the incidence and prevalence of para thyroid carcinoma?

Answer 38

Parathyroid carcinoma is one of the rarest of all human cancers, with an incidence of 0.015 per 100,000 population and a prevalence of 0.005% in the United States.

Question 39

39 How does the patient population with parathyroid carcinoma compare with patients with parathyroid adenoma?

Answer 39

There is an even distribution of males and females with parathyroid carcinoma, whereas there is female predom inance in parathyroid adenoma. Patients on average are younger with parathyroid carcinoma (average age in 40s) compared with parathyroid adenoma (average age 50 to 60s).

Question 40

40 What feature on physical examination is most concerning for parathyroid carcinoma?

Answer 40

A palpable neck mass (reported in 30 to 76% of patients with parathyroid carcinoma), which is rarely associated with a benign adenoma

Question 41

41 What is the gross pathologic description of a parathyroid carcinoma compared with a benign adenoma?

Answer 41

Benign adenomas are generally soft, round, or oval and reddish brown. Parathyroid carcinoma is frequently a large, lobulated, and firm to stony-hard mass, with a grayish white capsule that is frequently adherent or invasive to sur rounding tissues.

Question 42

42 What is the American Joint Committee on Cancer (AJCC) staging system for parathyroid carcinoma?

Answer 42

There is no AJCC staging system for parathyroid carcinoma because of its low incidence.

Question 43

43 What is the most common cause of death in patients with parathyroid carcinoma?

Answer 43

Patients often die from the effects of excessive PTH secretion and uncontrolled hypercalcemia rather than growth from tumor mass.

Question 44

44 What is the best prognostic factor in parathyroid carcinoma?

Answer 44

Early recognition and complete surgical resection at initial operation offer the best prognosis.

Question 45

45 Describe the prognosis for parathyroid carcinoma.

Answer 45

Surgical cure and survival can be achieved in patients undergoing an R0 (complete) resection. Patients with recurrent disease can be palliated with aggressive surgical therapy and calcimimmetic medications such as cincalcet.

Question 46

46 What is the preferred treatment approach to parathyroid carcinoma?

Answer 46

Parathyroid carcinoma should be aggressively treated with en bloc resection of the tumor, ipsilateral central neck components, including thyroid lobectomy, tracheoesopha geal soft tissue, and central lymph node dissection.

Question 47

47 What is the most common pattern of malignant spread of disease in parathyroid carcinoma?

Answer 47

Parathyroid carcinoma is generally indolent with local recurrence and involvement of contiguous neck structures representing the most likely pattern of spread.

Question 48

48 What is the rate of recurrence in parathyroid carcinoma?

Answer 48

About 40 to 60% of patients have a postsurgical recurrence, which usually occurs 2 to 5 years after surgery.

Question 49

49 In a patient with recurrent and widely dissemi nated parathyroid carcinoma, surgical resection is no longer effective. Therapeutic goals should be control of hypercalcemia and decreasing bone resorption. How can this be treated medically?

Answer 49

Aggressive hydration restores fluid volume and increases urinary calcium excretion. Loop diuretics increase calciu resis. Bisphosphonates interfere with osteoclast-mediated bone resorption.

Question 50

50 What is the pattern of metastatic disease in parathyroid carcinoma?

Answer 50

Late metastases occur via both lymphatic and hematoge nous spread with the most common site being the lungs.

Question 51

51 From what branchial structures does the thyroid develop?

Answer 51

The thyroid develops from an endodermal diverticulum of the floor of the primitive pharynx. The medial primordia is derived from the first and second pharyngeal pouches. The lateral primordia is derived from the fourth and fifth pharyngeal pouches.

Question 52

52 The ultimobranchial bodies develop into what structures?

Answer 52

Ultimobranchial bodies derive from the fourth pharyngeal pouch neural crest cells and give rise to parafollicular cells (C cells) of the thyroid, which release calcitonin.

Question 53

53 What is the relationship of the ultimobranchial bodies to the thyroid gland?

Answer 53

The ultimobranchial bodies fuse with the thyroid gland during its descent, consistently in the middle to upper thirds of thyroid gland.

Question 54

54 What is the most common pattern of descent of the thyroid gland in relation to the hyoid bone? (▶ Fig. 12.3)

Answer 54

The thyroid gland descends anterior to the hyoid bone during gestational weeks 4 through 7.

Question 55

55 What is the most common location of ectopic thyroid tissue?

Answer 55

As the thyroid forms from an endodermal diverticulum of the pharynx, the most common location of ectopic thyroid tissue is found in the base of tongue (lingual thyroid).

Question 56

56 What does the proximal portion of the thyroglos sal duct form?

Answer 56

Foramen cecum of the tongue

Question 57

57 What does the caudal remnant of the thyroglossal duct form?

Answer 57

Pyramidal lobe of the thyroid, which is present in 40 to 55% of patients

Question 58

58 What is the recommended surgical treatment for a thyroglossal duct cyst?

Answer 58

The Sistrunk procedure, which includes complete removal of the thyroglossal duct along with a portion of the central hyoid bone

Question 59

59 What is the most common path of the right and left recurrent laryngeal nerves?

Answer 59

The right recurrent laryngeal nerve wraps around and passes deep to the right subclavian artery. It then travels in a more oblique path to enter the larynx just posterior to the cricothyroid joint. The left recurrent laryngeal nerve wraps around and passes deep to the arch of the aorta. The nerve then travels in a more medial path within the tracheoeso phageal groove.

Question 60

60 What does the recurrent laryngeal nerve inner vate? (▶ Fig. 12.4)

Answer 60

The intrinsic muscles of the larynx and sensory innervation of the glottis (shared innervation with internal branch of superior laryngeal nerve) and subglottis

Question 61

61 What is the relationship of the recurrent laryngeal nerve and the cricothyroid joint?

Answer 61

The recurrent laryngeal nerve enters the larynx posterior to the cricothyroid joint.

Question 62

62 What does the external branch of the superior laryngeal nerve innervate?

Answer 62

The cricothyroid muscle

Question 63

63 What is the function of the cricothyroid muscle?

Answer 63

The cricothyroid increases tension on vocal cords, inducing a higher pitch when vocalizing, and is innervated by the superior laryngeal nerve.

Question 64

64 What does the internal branch of the superior laryngeal nerve innervate?

Answer 64

The internal branch of the superior laryngeal nerve pierces the thyrohyoid membrane to enter the larynx. The superior laryngeal nerve provides sensation to the supraglottic structures and shares sensation of the glottis with the recurrent laryngeal nerve.

Question 65

65 Where does the superior laryngeal nerve branch off from the vagus?

Answer 65

Immediately below the nodose ganglion (inferior ganglion) of the vagus nerve, which is located just inferior to the jugular foramen

Question 66

66 Where does the thyroid gland obtain its blood supply?

Answer 66

Typically from the superior and inferior thyroid arteries but occasionally from a thyroid ima artery

Question 67

67 What is the name of the prelaryngeal lymph node?

Answer 67

Delphian node

Question 68

68 What are the boundaries of the level VI cervical lymph nodes?

Answer 68

Level VI represents the central neck compartment and is bordered by the hyoid bone superiorly, the brachiocephalic (innominate) vein inferiorly, and the carotid arteries laterally.

Question 69

69 What is the name of the naturally occurring thyroidal enlargement on the lateral portion of the gland?

Answer 69

The tubercle of Zuckerkandl

Question 70

70 What is the name of the posterior suspensory ligament of the thyroid?

Answer 70

Berry ligament

Question 71

ligament of the thyroid? 71 Define the borders of the Simon triangle.

Answer 71

The Simon triangle is defined as the space between the esophagus medially, the carotid artery laterally, and the inferior thyroid artery superiorly.

Question 72

72 Define the borders of the Joll triangle.

Answer 72

The Joll triangle is defined as the space between the inferior pharyngeal constrictor and cricothyroid muscle medially, the sternothyroid muscle laterally, and the superior thyroid pole inferiorly.

Question 73

73 Which is the active form of thyroid hormone?

Answer 73

Triiodothyronine (T3). Thyroxine (T4)must be deiodinated to T3 to act on peripheral tissue.

Question 74

74 Describe the internal regulatory pathway of thyroid hormonogenesis.

Answer 74

Hypothalamus releases thyroid-releasing hormone (TRH). TRH binds a receptor in the anterior pituitary that increases production and release of thyroid-stimulating hormone (TSH). TSH stimulates the release of stored T3 and T4, increases production of T3 in relation to T4, and increases the production of thyroglobulin and thyroperoxidase (TPO). The entire system is controlled by negative feedback by downstream hormones.

Question 75

75 What is the Wolff-Chaikoff effect?

Answer 75

The Wolff-Chaikoff effect describes decreased thyroid hormone production as a result of excess iodine ingestion such as with Lugol iodine administration in patients with Graves disease.

Question 76

76 What hormones are produced by the thyroid gland?

Answer 76

The thyroid produces T3 and T4. These are made by iodinating the amino acid tyrosine.

Question 77

77 Thyroid storm is a medical emergency. What medications are the mainstay of treatment in the acute setting?

Answer 77

Propranolol to control tachyarrhythmias, and methimazole to reduce thyroid hormone production. An hour after methimazole has been given, potassium iodide can be given to decrease hormone release and vascularity of the thyroid gland if surgery is considered.

Question 78

78 What are the key components of thyroid hormone?

Answer 78

Thyroglobulin and iodine represent the key components to make and store thyroid hormone.

Question 79

79 What is the name of the key enzyme required for thyroid hormonogenesis?

Answer 79

TPO, an enzyme that performs the iodination of thyroglobulin and coupling of monoiodotyrosine and diiodotyrosine to form T3 and T4

Question 80

80 What is the most common cause of unilateral proptosis?

Answer 80

Graves’ ophthalmopathy, which results in deposition of glycosaminoglycans and lipogenesis in the orbit.

Question 81

81 What are the two ways in which amiodarone can cause hyperthyroidism?

Answer 81

● Type 1 amiodarone-induced thyrotoxicosis: Excess iodine (amiodarone is 37% iodine) causes excessive thyroid hormone production and is best treated with thionamides and discontinuation of amiodarone. ● Type 2 amiodarone-induced thyrotoxicosis: Amiodaroneinduced thyroiditis causes a destructive thyrotoxicosis and is best treated with prednisone. Amiodarone use can continue.

Question 82

82 Describe the preferred treatment for subacute (de Quervain) thyroiditis in the hyperthyroid stage.

Answer 82

Symptomatic treatment with β-blockers and NSAIDs is the standard treatment. Severe cases are treated with highdose prednisone.

Question 83

83 A rare cause of thyrotoxicosis is a hydatidiform mole. What is the mechanism?

Answer 83

Hydatidiform moles, a form of gestational trophoblastic disease, produce chorionic gonadotropin, which has TSHlike activity.

Question 84

84 Where is a hormone-producing focus of metastatic follicular carcinoma typically found on radioactive body scan?

Answer 84

Usually in the lungs or bone

Question 85

85 In a nongravid woman with thyrotoxicosis, radioactive iodine uptake is found in the pelvis. What is the diagnosis?

Answer 85

Struma ovarii, a teratoma of the ovary that contains functional thyroid tissue

Question 86

86 What findings indicate a diagnosis of thyrotoxicosis factitia?

Answer 86

Thyrotoxicosis factitia is a disorder in which a patient takes exogenous thyroid hormone surreptitiously, typically for weight loss. Typical findings are a suppressed TSH, low thyroglobulin, high T4 and T3, a negative radioactive iodine uptake level, and absence of a goiter.

Question 87

87 Name the four main classifications of hypothyroidism.

Answer 87

● Primary hypothyroidism is the result of a dysfunctional thyroid gland. ● Secondary hypothyroidism is caused by a dysfunctional pituitary gland. ● Tertiary hypothyroidism results from hypothalamic dysfunction. ● Finally, peripheral hypothyroidism is caused by hormone receptor resistance.

Question 88

88 What is the most common cause of hypothyroidism in the world?

Answer 88

Iodine deficiency

Question 89

89 What is the most common cause of hypothyroidism in the United States?

Answer 89

Hashimoto thyroiditis

Question 90

90 What is the cause of myxedema coma?

Answer 90

Myxedema coma is an extreme hypothyroid state that is typically brought on by some systemic stress, often infection, in a hypothyroid patient.

Question 91

91 Why should head and neck cancer patients have thyroid function closely monitored?

Answer 91

Hypothyroidism is common in patients with head and neck cancer after surgery and particularly after radiation therapy. Patients should havethyroid function tests drawn after 6 weeks of intervention and then every 6 to 12 months thereafter.

Question 92

92 What is the recommended starting dose of levothyroxine for young healthy adults with hypothyroidism, and how is this different for older adults with underlying ischemic heart disease?

Answer 92

● For young adults, the typical starting dose is 1.6 μg/kg and adjusted depending on the TSH level after 6 to 12 weeks on a stable levothyroxine dose. ● For those with known ischemic heart disease or arrhythmias or for elderly adults, the typical starting dose is 25 μg daily with 25 μg increases every few weeks.

Question 93

93 Approximately how long does the hypothyroid phase of thyroiditis last?

Answer 93

Thyroiditis typically produces a transient hyperthyroid state and then either recovery or a transient hypothyroid state. When it occurs, the hypothyroid state typically lasts 2 to 8 weeks.

Question 94

94 What is the likely cause of subacute granulomatous thyroiditis (de Quervain thyroiditis)?

Answer 94

Most likely a viral illness is the cause. Common associations include mumps, influenza, coxsackievirus, and adenovirus. Some believe it is more likely a result of a postviral inflammatory response than of viral infection itself.

Question 95

95 What laboratory values are elevated in patients with Hashimoto thyroiditis?

Answer 95

TSH (evidence of primary thyroid disorder), antimicrosomal antibodies (anti-thyroperoxidase antibodies), and anti-thyroglobulin antibodies are usually elevated. However, 10% of patients with clinical Hashimoto thyroiditis may be antibody negative.

Question 96

96 What causes the initial hyperthyroid state in some patients with Hashimoto thyroiditis?

Answer 96

Transient release of stored thyroid hormone from damaged thyroid cells (hashitoxicosis) causes a temporary surge in serum thyroid hormone.

Question 97

97 What is the relationship between Hashimoto thyroiditis and thyroid cancer?

Answer 97

Patients with Hashimoto thyroiditis have a slightly increased incidence of papillary thyroid carcinoma compared with the general population.

Question 98

98 What are the indications for surgery in a patient with Hashimoto thyroiditis?

Answer 98

Large goiter with obstructive symptoms, cosmetic concerns, or worrisome nodularity

Question 99

99 Is subacute thyroiditis always painful?

Answer 99

No. Painless thyroiditis is sometimes seen. The inflammatory component may be mild and not require therapy.

Question 100

100 What are the characteristic physical examination findings of Riedel thyroiditis?

Answer 100

Rock-hard, fixed, painless goiter. Compressive symptoms including dysphagia, dysphonia, cough, and dyspnea may also occur.

Question 101

101 What organisms most commonly cause acute suppurative thyroiditis?

Answer 101

Staphylococcus aureus, Streptococcus pneumoniae, β-hemolytic streptococci are the most common offenders. Occasionally, it can be caused by Fusobacterium and Haemophilus species as well.

Question 102

102 What criteria for a thyroid FNA must be met in order to be considered diagnostic?

Answer 102

The presence of at least six follicular cell groups, each with at least 10 cells, that are derived from at least two aspirates of the cyst or nodule.

Question 103

103 Why is FNA of cystic thyroid nodules of low diagnostic yield?

Answer 103

FNA of cystic nodules often yield nondiagnostic findings because of the scant cellularity of fluid and the difficulty in obtaining a biopsy of the very thin cyst wall.

Question 104

104 What are the false-negative and false-positive rates of thyroid nodule FNA?

Answer 104

For thyroid nodules, FNA is a sensitive and specific test. The false-negative rate is approximately 1 to 6%, and the falsepositive rate is less than 5%.

Question 105

105 When should a benign (based on results of previous FNA) thyroid nodule undergo rebiopsy?

Answer 105

When it changes significantly in size, a cyst recurs, or the nodule changes texture

Question 106

106 What is the Pemberton sign?

Answer 106

Distension of the jugular veins, facial edema or erythema when a patient extends both arms above the head, indicating cervicothoracic inlet obstruction seen in patients with a substernal goiter

Question 107

107 What is the Chvostek sign?

Answer 107

The Chyostek sign is seen in cases of hypocalcemia and is positive when tapping a finger on a patient’s cheek over the course of the facial nerve results in contraction of the ipsilateral facial muscles.

Question 108

108 What is the Trousseau sign?

Answer 108

The Trousseau sign is seen in cases of hypocalcemia, where inflation of a blood pressure cuff above systolic blood pressure for 3 minutes results in ipsilateral spasm of the wrist and hand muscles.

Question 109

109 What are the main complications of thyroid surgery?

Answer 109

Major complications include hematoma, infection, superior laryngeal nerve injury (most common nerve injured), recurrent laryngeal nerve injury, and hypocalcemia.

Question 110

110 Name the four main types of thyroid surgeries, and define each one.

Answer 110

● Thyroid lobectomy: Removal of a single lobe with or without the isthmus ● Subtotal thyroidectomy: Incomplete removal of thyroid tissue, leaving more than 1 g of thyroid remaining ● Near-total thyroidectomy: Incomplete removal of thyroid tissue, leaving behind a small amount of tissue adjacent to the recurrent laryngeal nerve ● Total thyroidectomy: Removal of all grossly visible thyroid tissue

Question 111

111 Name some disease-specific risk factors for permanent recurrent laryngeal nerve injury during thyroidectomy.

Answer 111

Recurrent thyroid carcinoma, substernal goiter, and thyroiditis

Question 112

112 At what point in the thyroid dissection must one be aware of the superior laryngeal nerve?

Answer 112

The external branch of the superior laryngeal nerve, which supplies the cricothyroid muscle, lies near the superior pole vessels. Special care should be undertaken during division of the superior pole to protect the superior laryngeal nerve.

Question 113

114 What is the most common pathology of a thyroid nodule?

Answer 113

Benign follicular adenoma

Question 114

115 Why are thyroid nodules often found during pregnancy?

Answer 114

The incidence of thyroid nodules during pregnancy is 5 to 20%. Increased hormones and relative iodine deficiency may be associated with increased thyroid nodularity.

Question 115

116 How often are thyroid nodules cancerous?

Answer 115

Approximately 5% are cancerous.

Question 116

117 Is a thyroid cyst benign?

Answer 116

Not always. Malignancies such as papillary thyroid carcinoma and parathyroid carcinoma can be cystic.

Question 117

118 What are the factors that increase suspicion of malignancy in a patient with a thyroid nodule?

Answer 117

Age younger than 20 years, male sex, family history of thyroid cancer, pheochromocytoma, hyperparathyroidism, Gardner syndrome, Cowden disease, and a history of head and neck radiation

Question 118

119 Are thyroid nodules more likely to be malignant in adults or in the pediatric population?

Answer 118

Pediatric. Approximately 5% of adult thyroid nodules are malignant and 20 to 50% of pediatric thyroid nodules are malignant.

Question 119

120 What is the most common cause of a thyroid nodule in the pediatric population?

Answer 119

Follicular adenoma, just as it is with adults

Question 120

121 What signs and symptoms in a patient with a thyroid nodule are worrisome for cancer?

Answer 120

● Rapid growth, a solid and fixed lesion, lymphadenopathy, pain, or compressive symptoms such as dysphagia or stridor ● In addition, dysphonia may be secondary to compressive symptoms or invasion of the recurrent laryngeal nerve.

Question 121

122 What is the most common presentation of a patient with thyroid cancer?

Answer 121

Nontender, palpable thyroid mass

Question 122

123 What are the ultrasound imaging characteristics of a lymph node that are concerning for metastatic thyroid cancer?

Answer 122

Loss of the fatty hilum, increased vascularity, rounded node configuration rather than ovoid, hypoechogenicity of a solid nodule, microcalcifications, and peripheral vascularity

Question 123

124 What is the value of PET imaging in thyroid cancer?

Answer 123

PET imaging allows for initial staging of poorly differentiated thyroid cancer and tumor surveillance after treatment of more advanced/metastatic thyroid cancer; it also offers prognostic data for patients with known metastasis.

Question 124

125 What are the subtypes of well-differentiated thyroid cancer?

Answer 124

Papillary thyroid cancer, follicular thyroid cancer, and Hürthle cell thyroid cancer are all considered well-differentiated

Question 125

126 What are the most common staging systems available for well-differentiated thyroid cancer?

Answer 125

AJCC tumor node metastasis (TNM) classification system, AMES (age, metastasis, extent of disease, size), AGES (age, grade, extent of disease, size), MACIS (metastasis, age, completeness of surgical resection, invasion, size), Ohio State University, and Memorial Sloan-Kettering Cancer Center

Question 126

127 Which tumor staging system for thyroid cancer includes gross resection of tumor in its prognostic calculation?

Answer 126

Specimen size is included in the MACIS score, calculated by the following formula: 3.1 (patient age < 40) or 0.08 x age (patient ≥ 40) + 0.3 x tumor size (cm) + 1 (if extrathyroidal extension) + 1 (if incomplete resection) + 3 (if distant metastasis)

Question 127

128 How does extrathyroidal extension impact thyroid cancer staging?

Answer 127

● T3: Any extrathyroidal extension ● T4a: Extrathyroidal invasion of subcutaneous soft tissue, larynx, trachea, esophagus, or recurrent laryngeal nerve ● T4b: Invasion of prevertebral fascia or encasement of the carotid artery or mediastinal great vessels

Question 128

129 How is age used in the AJCC TNM stage classification for thyroid cancer? (▶ Table 12.1; ▶ Table 12.2; ▶ Table 12.3; ▶ Table 12.4)

Answer 128

There are different staging systems for patients younger than 45 years compared with those who are 45 years old or greater. Patients over the age of 45 years generally have a greater (worse) stage of disease than younger patients with similar disease characteristics.

Question 129

130 In which types of thyroid cancer are there different staging systems based on age of the patient?

Answer 129

Papillary thyroid carcinoma and follicular carcinoma have separate staging criteria based on age. Medullary and anaplastic carcinoma do not.

Question 130

131 What is the most significant predictor of overall prognosis for well-differentiated thyroid cancer?

Answer 130

Distant metastasis is the most significant prognostic factor.

Question 131

132 Review low-, intermediate- and high-risk features of well-differentiated thyroid carcinoma.

Answer 131

● Low risk: Localized disease without aggressive histologic subtypes or vascular invasion; all macroscopic disease removed at first surgery; no postoperative I-131 uptake outside thyroid bed ● Intermediate risk: Microscopic tumor invasion outside the thyroid bed, positive cervical lymph nodes, aggressive histologic subtype or vascular invasion, and I-131 uptake outside thyroid bed ● High-risk: Macroscopic extrathyroidal invasion, distant metastasis, incomplete surgical resection, and elevated postoperative thyroglobulin

Question 132

133 Which risk factor most significantly increases the risk of thyroid carcinoma?

Answer 132

Exposure to ionizing radiation, especially as a child or adolescent

Question 133

134 What is the recommended surgical treatment for patients with well-differentiated thyroid cancer?

Answer 133

Total thyroidectomy is recommended in cases of welldifferentiated thyroid carcinoma except in cases of papillary thyroid carcinoma of low risk and < 1 cm in size. In this case, a thyroid lobectomy is considered sufficient treatment by many surgeons.

Question 134

135 How should local invasion of the esophagus by thyroid carcinoma be treated?

Answer 134

Local invasion of the pharynx or esophagus by thyroid carcinoma should be resected and then repaired by primary closure of the defect.

Question 135

136 What adjuvant forms of treatment exist for welldifferentiated thyroid carcinoma?

Answer 135

TSH suppression with exogenous thyroid hormone, radioiodine ablation, or external beam radiation. Other treatments such as tyrosine kinase inhibitors may delay disease progression but have not been proven to increase survival.

Question 136

137 What is TSH suppression?

Answer 136

Increased thyroxine levels administered to decrease the concentration of TSH released by the pituitary gland. Side effects of TSH suppression include bone loss, cardiac arrhythmias, and symptoms of hyperthyroidism.

Question 137

138 Why is radioiodine ablation treatment used after surgery?

Answer 137

To destroy microscopic residual disease

Question 138

139 How does radioiodine ablation assist in long-term management of well-differentiated thyroid carcinoma?

Answer 138

Complete removal of microscopic and macroscopic disease by surgery and adjuvant radioiodine ablation allows for closer management of recurrence or persistent disease with thyroglobulin measurements and whole-body radioiodine scans.

Question 139

140 What are the complications of radioiodine ablation?

Answer 139

Sialadenitis, dental caries, nasolacrimal duct obstruction, xerostomia, and rarely secondary malignancies

Question 140

141 What is the recommended treatment for welldifferentiated thyroid carcinoma found in a thyroglossal duct cyst?

Answer 140

A Sistrunk procedure is adequate in cases in which clinical and radiologic examinations demonstrate normal thyroid and regional lymph nodes. Proceeding with total thyroidectomy should be considered in high-risk patients, as defined by age greater than 45 years, tumor diameter greater than 4 cm, extracapsular spread, regional or distant metastasis, or clinical or radiologic evidence of disease in the thyroid gland or regional lymph nodes.

Question 141

142 How often do patients with thyroglossal duct cyst carcinoma have concurrent intrathyroidal cancer?

Answer 141

Based on a Mayo Clinic study from 1997, 33% of patients with thyroglossal duct cyst carcinoma had concurrent intrathyroidal malignancy.

Question 142

143 What is the recommended treatment for a pregnant woman with well-differentiated thyroid carcinoma?

Answer 142

Surgical excision is recommended, either during the second trimester or after delivery.

Question 143

144 Does thyroid cancer discovered during pregnancy behave differently from disease found in nonpregnant females?

Answer 143

No, there is no difference.

Question 144

145 What are the recommendations for radioiodine ablation in regard to women of childbearing age?

Answer 144

Pregnancy should be avoided for 12 months after radioiodine ablation.

Question 145

146 What is the treatment for locoregional metastatic well-differentiated thyroid carcinoma?

Answer 145

Ideally, surgical excision. Radioiodine ablation, externalbeam radiation, or clinical trials, if available, may be considered.

Question 146

147 What is the treatment for well-differentiated thyroid carcinoma with tracheal invasion?

Answer 146

Complete surgical resection is the best treatment. It may include shaving tumor from the trachea or esophagus, segmental tracheal resection and reanastomosis, or laryngopharyngectomy.

Question 147

148 As a general rule, what is the best treatment for well-differentiated thyroid carcinoma with pulmonary metastasis?

Answer 147

I-131 radioiodine ablation therapy

Question 148

149 In a case of well-differentiated thyroid cancer, how should involvement of the recurrent laryngeal nerve be managed?

Answer 148

If preoperative vocal cord function is normal, the nerve should be left intact if at all possible.

Question 149

150 What are the two most sensitive tests for tumor surveillance after treatment of well-differentiated thyroid carcinoma?

Answer 149

Blood thyroglobulin levels and neck ultrasound. Thyroglobulin is a reliable marker in patients who do not produce anti-thyroglobulin antibodies, as its production is a marker for functioning thyroid tissue.

Question 150

151 How might anti-thyroglobulin antibodies affect posttreatment thyroglobulin levels?

Answer 150

The antibodies can produce a falsely low level of thyroglobulin and its utility as a tumor marker becomes invalid.

Question 151

152 Describe the role of chemotherapy in treating welldifferentiated thyroid malignancies.

Answer 151

In well-differentiated thyroid cancers, there are no data to support the use of adjunctive chemotherapy, but doxorubicin may be used as a radiation sensitizer in patients undergoing external beam radiation therapy. Also, tyrosine kinase inhibitors have been used to improve progressionfree survival but do not have a synergistic effect with radiation.

Question 152

153 Which age group most commonly has cervical and distant metastases in papillary thyroid carcinoma: adults or children?

Answer 152

Children more commonly manifest with advanced disease.

Question 153

154 What is the current recommended treatment for papillary thyroid microcarcinoma (< 1 cm) isolated to one lobe without extracapsular extension, positive lymph nodes, or distant metastasis?

Answer 153

Thyroid lobectomy

Question 154

155 What should the detectable level of thyroglobulin be after total thyroidectomy and postoperative radioactive iodine therapy for advanced papillary carcinoma?

Answer 154

The goal is for an undetectable thyroglobulin level.

Question 155

156 What histologic features are unique to papillary thyroid carcinoma? (▶ Fig. 12.5)

Answer 155

Psammoma bodies, which are concentric calcified structures, “Orphan Annie” eyes from large nuclear inclusions and nuclear grooves

Question 156

157 In regard to papillary thyroid carcinoma, which pathological variants carry a worse prognosis?

Answer 156

Tall cell variant, columnar cell variant, and diffuse sclerosing variants of papillary thyroid carcinoma carry a worse prognosis

Question 157

158 What type of thyroid cancer is most common in the pediatric population?

Answer 157

Papillary thyroid carcinoma

Question 158

159 How is papillary thyroid microcarcinoma defined?

Answer 158

Papillary thyroid carcinoma measuring 1 cm or smaller irrespective of extrathyroidal extension, lymph node metastasis, or distant metastasis

Question 159

160 How does papillary thyroid carcinoma tend to spread?

Answer 159

Papillary carcinoma has a predilection for spreading via lymphatic channels within the thyroid gland, leading to frequent multifocal disease, as well as to local lymph nodes in the paratracheal and cervical regions

Question 160

161 Is cervical lymph node metastasis more common in papillary or follicular thyroid carcinoma?

Answer 160

Papillary thyroid carcinoma. Cervical lymph node metastases are present in 30 to 70% of patients

Question 161

162 What is the effect of cervical lymph node metastasis on the prognosis of papillary thyroid cancer?

Answer 161

Currently, this topic is debatable, but most contend that there is no decrease in survival with local lymph node involvement. However, there is an increased risk of recurrence after surgical treatment.

Question 162

163 How is a follicular thyroid adenoma differentiated from follicular thyroid carcinoma?

Answer 162

Surgical pathology is required to make the differentiation, as carcinomas have capsular or vascular invasion. Follicular thyroid carcinoma cannot be diagnosed with fine needle aspiration.

Question 163

164 Are patients with follicular adenomas most commonly hyperthyroid, hypothyroid, or euthyroid?

Answer 163

Euthyroid

Question 164

165 Is distant metastasis more common in papillary or follicular thyroid carcinoma?

Answer 164

Follicular thyroid carcinoma because it spreads via hematogenous dissemination

Question 165

166 Name the three categories of follicular thyroid carcinoma.

Answer 165

● Minimally invasive: Displays invasion of capsule but does not invade through the capsule ● Moderately invasive: Has angioinvasion with or without capsular invasion ● Widely invasive: Has invasion into extrathyroidal tissue

Question 166

167 For thyroid lobectomies with preoperative FNA results of “indeterminate” or “follicular neoplasia suspected,” what percentage of final pathology results come back positive for follicular carcinoma?

Answer 166

Approximately 15 to 20%

Question 167

168 What is the significance of a pathology report indicating aneuploid follicular carcinoma?

Answer 167

Aneuploid follicular carcinomas are more aggressive in their behavior compared to other follicular carcinomas.

Question 168

169 Describe the histopathologic findings of Hürthle cell tumors (oncocytic neoplasms).

Answer 168

● Predominance of Hürthle cells, which are large, granular, eosinophilic cells ● Malignancy is determined by the presence or absence of extracapsular spread, lymphovascular invasion, or presence of metastases.

Question 169

170 How do Hürthle cell carcinomas respond to radioiodine therapy?

Answer 169

Hürthle cell carcinomas tend to be aggressive and have decreased iodine uptake; thus, they are resistant to radioiodine therapy.

Question 170

171 Medullary thyroid carcinoma accounts for what percent of all thyroid malignancies?

Answer 170

Approximately 5%

Question 171

172 Medullary thyroid carcinoma originates from what cell type?

Answer 171

Parafollicular cells (C cells) of the thyroid gland, which produce calcitonin and are of neuroendocrine origin

Question 172

173 What laboratory abnormalities are associated with medullary thyroid carcinoma?

Answer 172

Elevated calcitonin and often elevated CEA

Question 173

174 What is the most common manifestation of medullary thyroid carcinoma?

Answer 173

● Patients with sporadic tumors usually have an enlarging palpable neck mass and cervical lymphadenopathy. ● Patients with familial disease are often diagnosed in a presymptomatic state as a result of early screening.

Question 174

175 What is the most important prognostic factor in patients with medullary thyroid carcinoma?

Answer 174

Stage is the most important prognostic factor, followed by age.

Question 175

176 How does radioiodine affect medullary thyroid carcinoma?

Answer 175

Medullary thyroid carcinoma does not take up radioiodine because it originates from the parafollicular cells, which are not involved in production of thyroid hormone.

Question 176

177 What is the recommended treatment for patients with medullary thyroid carcinoma?

Answer 176

Minimum total thyroidectomy and central compartment neck dissection are recommended. For patients with lateral cervical node involvement or primary tumors larger than 1 cm, an ipsilateral level II through V neck dissection should also be performed.

Question 177

178 What is the standard treatment for medullary thyroid carcinoma?

Answer 177

Total thyroidectomy with regional cervical lymph node dissection. In patients with tumors greater than 1 cm, an ipsilateral modified radical neck dissection should be considered. Chemotherapy and radiation are not effective treatments for medullary thyroid carcinoma.

Question 178

179 How common is anaplastic thyroid carcinoma?

Answer 178

It is the rarest form of thyroid cancer, representing less than 5% of thyroid malignancies

Question 179

180 What is the age range of patients affected by anaplastic thyroid cancer?

Answer 179

Most are over 70 years old, and rarely do patients younger than 50 years have anaplastic thyroid carcinoma.

Question 180

181 What are common initial symptoms of anaplastic thyroid carcinoma?

Answer 180

It is a rapidly enlarging neck mass, often associated with dyspnea, dysphagia, hoarseness, and pain.

Question 181

182 What is the relationship between anaplastic thyroid cancer and well-differentiated thyroid cancer?

Answer 181

In some cases, anaplastic thyroid carcinoma may develop from a long-standing well-differentiated thyroid malignancy such as papillary thyroid carcinoma.

Question 182

183 What is the prognosis for anaplastic thyroid cancer?

Answer 182

It is almost universally fatal within 6 to 12 months of diagnosis.

Question 183

184 What is an indication for surgery with anaplastic thyroid cancer?

Answer 183

Although controversial, tumor debulking for palliation can be considered. In addition, small, contained cancers may be approached with intent to cure.

Question 184

185 What is a currently accepted protocol to treat anaplastic thyroid cancer?

Answer 184

Chemotherapy with doxorubicin, hyperfractionated radiotherapy, and surgical debulking.

Question 185

186 In what type of thyroid cancer is external-beam radiation used most commonly?

Answer 185

External-beam radiation has been used with limited success in anaplastic carcinoma as a neoadjuvant therapy in surgically unresectable cases.

Question 186

187 Which of the MEN subtypes includes involvement of the parathyroid glands?

Answer 186

MEN 1 patients have multiglandular disease requiring subtotal parathyroidectomy. MEN-2A patients have a parathyroid adenoma or multiglandular disease and primary hyperparathyroidism. There is no parathyroid involvement in MEN-2B or familial non-MEN medullary thyroid carcinoma.

Question 187

188 How does hyperparathyroidism manifest in patients with MEN-2A?

Answer 187

About 15 to 30% of patients with MEN-2A develop primary hyperparathyroidism, which is typically mild or asymptomatic clinically. It can manifest as single parathyroid adenoma or multiple gland hyperplasia. The average age of onset is age 38 years, and it is usually present many years after diagnosis of medullary thyroid carcinoma.

Question 188

189 Which subtype of medullary thyroid carcinoma is more common, sporadic or familial?

Answer 188

Sporadic cases represent 75% of medullary thyroid carcinomas.

Question 189

190 What are the different subtypes of familial medullary thyroid carcinoma?

Answer 189

MEN-2A and MEN-2B. Additionally, there are several rare types of familial non-MEN medullary thyroid carcinoma.

Question 190

191 What conditions are associated with MEN-2A syndrome?

Answer 190

Medullary thyroid carcinoma, pheochromocytoma, and parathyroid hyperplasia

Question 191

192 What conditions are associated with MEN-2B syndrome?

Answer 191

Medullary thyroid carcinoma, pheochromocytoma, marfanoid body habitus, and mucosal neuromas

Question 192

193 What is the inheritance pattern of familial medullary thyroid carcinoma?

Answer 192

Autosomal dominant

Question 193

194 What gene mutation(s) are responsible for familial medullary thyroid carcinoma?

Answer 193

Gain of function mutations of the RET proto-oncogene

Question 194

195 What is the most common subtype of familial medullary thyroid carcinoma?

Answer 194

MEN-2A is most common, followed by familial non-MEN and then MEN-2B.

Question 195

196 Which form of medullary thyroid carcinoma is the most aggressive?

Answer 195

MEN-2B is most aggressive, followed by sporadic cases, then MEN-2A, then familial non-MEN, which has the best prognosis.

Question 196

197 What is the recommended treatment for patients with a RET mutation and/or a family history of medullary thyroid carcinoma?

Answer 196

For children, prophylactic thyroidectomy is the recommended treatment. In general, early intervention improves outcome by preventing metastases. In MEN-2A, thyroidectomy is recommended in pre-teenage patients, whereas in MEN-2B, resection is recommended in infancy, often before the age of 1 year.

Question 197

198 What gene is involved in MEN-2?

Answer 197

MEN-2 has three clinical subtypes: MEN-2A, MEN-2B, and familial medullary thyroid carcinoma (FMTC). All are associated with mutations in the RET proto-oncogene.

Question 198

199 What endocrine neoplasms are associated with MEN-2A?

Answer 198

Medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism (parathyroid adenoma)

Question 199

200 How frequently do individuals with MEN-2A develop the various clinical manifestations of this syndrome?

Answer 199

About 70 to 95% develop medullary thyroid carcinoma, 50% develop pheochromocytoma, and 15 to 30% develop primary hyperparathyroidism

Question 200

201 What is the typical presentation of medullary thyroid carcinoma in individuals with MEN-2A?

Answer 200

In patients with MEN-2A, medullary thyroid carcinoma typically presents with a neck mass or neck pain, usually before age 35 years. Other symptoms include diarrhea or gastrointestinal disturbance.

Question 201

202 How frequently are cervical lymph node metastases present on presentation of medullary thyroid carcinoma in MEN-2A?

Answer 201

Up to 70%

Question 202

203 What are the clinical findings associated with MEN- 2B?

Answer 202

Medullary thyroid carcinoma (particularly aggressive form), pheochromocytoma, mucosal neuromas, marfanoid body habitus, and diffuse ganglioneuromatosis of the gastrointestinal tract. There is no clinically significant involvement of the parathyroid gland in MEN-2B.

Question 203

204 Describe the natural history of medullary thyroid cancer in MEN-2B and its recommended treatment.

Answer 203

Almost all patients develop an aggressive form of medullary thyroid carcinoma, with a high rate of metastases before age 10 years. Often, patients will even have microscopic disease present before the first year of life. Prophylactic total thyroidectomy is recommended as soon as the infant is able to tolerate surgery, ideally before age one. In the past, the average life expectancy was 21 year, before when prophylactic thyroidectomy was recommended.

Question 204

205 Describe the distinctive facial features of MEN- 2B.

Answer 204

Mucosal neuromas on the dorsal surface of the tongue, palate, or pharynx; prominent “blubbery” lips; submucosal nodules on the vermillion border of the lips; and eyelid neuromas.

Question 205

206 Describe the distinctive body habitus associated with MEN-2B.

Answer 205

Around 75% of individuals with MEN-2B have a marfanoid body habitus: tall and lanky, kyphoscoliosis or lordosis, joint laxity, and proximal muscle wasting.

Question 206

207 What is the incidence of pheochromocytoma in MEN-2B?

Answer 206

50%; approximately half are bilateral.

Question 207

208 What defines the clinical diagnosis of familial medullary thyroid carcinoma?

Answer 207

Historically, it is diagnosed in families with four or more cases of medullary thyroid carcinoma without pheochromocytomas or parathyroid adenoma or hyperplasia. The RET oncogene is associated with FMTC, so FMTC may be viewed as MEN-2A with reduced organ-specific penetrance.

Question 208

209 Describe the age of onset and penetrance of medullary thyroid carcinoma in FMTC syndrome compared with MEN-2A and -2B.

Answer 208

Medullary thyroid carcinoma has a later age of onset in FMTC and decreased penetrance compared with MEN-2A and -2B.

Question 209

210 What is the pattern of inheritance in MEN-2 syndromes?

Answer 209

The RET proto-oncogene is inherited in an autosomal dominant pattern for all MEN-2 syndromes (MEN-2A, -2B, and FMTC). However, 50% of individuals with MEN-2B have a de novo germline mutation.

Question 210

211 What is the recommended primary preventative measure in an individual with an identified germline RET mutation?

Answer 210

Prophylactic thyroidectomy

Question 211

212 What is essential before surgery in any patient with MEN-2A, MEN-2B, or medullary thyroid carcinoma?

Answer 211

Screening for the presence of a functioning pheochromocytoma. Adrenalectomy should be performed before thyroidectomy in any patient with a pheochromocytoma to avoid intraoperative hypertensive crisis. Calcium and parathyroid levels should also be checked for possible primary hyperparathyroidism.

Question 212

213 What is the rate of recurrence of medullary thyroid carcinoma in individuals with MEN-2 who have undergone total thyroidectomy and cervical lymph node dissections?

Answer 212

Approximately 50%

Question 213

214 In individuals with MEN-2 who have undergone prophylactic thyroidectomy, what is the recommended screening protocol for medullary thyroid carcinoma?

Answer 213

Annual serum calcitonin levels