12 Endocrine Disorders Flashcards
1
Q
1 How common is a supernumerary parathyroid gland, and where is the supernumerary gland most likely to be found? (▶ Fig. 12.1)
A
The incidence of a supernumerary parathyroid gland is up to 15%. They are most often found in:
- Thymus
- Thyrothymic tract
- Carotid sheath.
2
Q
2 Where do the superior and inferior parathyroid glands obtain their blood supply?
A
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).
3
Q
3 What options are available for minimally invasive parathyroidectomy?
A
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.
4
Q
4 When conducting a subtotal parathyroidectomy, what tissue should be left behind?
A
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.
5
Q
5 How can PTH levels be used intraoperatively to determine the completeness of a parathyroidec tomy?
A
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.
6
Q
6 What structures have been described as landmarks to identify the superior parathyroid gland?
A
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.
7
Q
7 What branchial pouch gives rise to the superior and inferior parathyroid glands? (▶ Fig. 12.2)
A
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.
8
Q
8 How does PTH maintain calcium levels?
A
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
9
Q
9 What is the most potent regulator of PTH release?
A
Serum calcium levels
10
Q
10 Where can one find PTH receptors, and what downstream effects do they have in each location?
A
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).
11
Q
11 When monitoring total calcium levels in a patient, what factor do you also need to note?
A
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.
12
Q
12 What test results support the diagnosis of familial hypocalciuric hypercalcemia?
A
Hypercalcemia with 24-hour urinary calcium:creatinine clearance ratio below 0.01, as well as one or more first degree relatives with hypercalcemia
13
Q
13 What are common symptoms of chronic hypercalcemia?
A
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.
14
Q
14 What testing is necessary to diagnose primary hyperparathyroidism?
A
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
15
Q
15 Name the most common cause of hypercalcemia in an outpatient clinic setting.
A
Parathyroid adenoma
16
Q
16 Name the most common cause of hypercalcemia in an inpatient hospital setting.
A
Underlying malignancy
17
Q
17 A patient has hypercalcemia and low or undetectable PTH levels. What is the likely diagnosis?
A
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.
18
Q
18 What is the incidence of primary hyperparathy roidism in Western countries?
A
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.
19
Q
19 What are the different types of parathyroid hyperplasia?
A
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.
20
Q
20 Describe the typical patient population with primary hyperparathyroidism.
A
Most cases occur in women (74%); incidence peaks in the seventh decade of life. Before age 45, incidence in men and women is similar.
21
Q
21 What causative factors are associated with primary hyperparathyroidism?
A
● Head and neck radiation in childhood ● Long-term lithium therapy ● Genetic predisposition
22
Q
22 What are the guidelines for surgical treatment (parathyroidectomy) in an asymptomatic patient with primary hyperparathyroidism?
A
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.
23
Q
23 What are the typical laboratory values of calcium, PTH, and phosphate in secondary hyperparathy roidism?
A
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).
24
Q
24 What are some possible causes of secondary hyperparathyroidism?
A
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.
25
25 What is the treatment of secondary hyperpara thyroidism?
● 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.
26
26 What is tertiary hyperparathyroidism?
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.
27
27 What is the pathophysiology of tertiary hyper parathyroidism?
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.
28
28 What is the treatment of tertiary hyperparathyroidism?
Total parathyroidectomy with autotransplantation or subtotal parathyroidectomy (3 and ½ gland resection)
29
29 What are the components of hyperparathyroidism-jaw tumor syndrome?
Recurrent parathyroid adenomas, fibroosseous tumors of the mandible, and Wilms tumors
30
30 How do the symptoms of acute and chronic hypoparathyroidism differ?
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.
31
31 What are the most common causes of hypoparathyroidism?
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.
32
32 What is the histologic description of a parathyroid adenoma?
A parathyroid adenoma appears as a hypercellular gland consisting of chief and oncocytic cells with decreased intercellular fat.
33
33 What are some intraoperative techniques used to identify a parathyroid adenoma?
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.
34
34 What is the most sensitive imaging study for identifying the location of a parathyroid adenoma?
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.
35
35 How frequently is primary hyperparathyroidism caused by a single adenoma versus four-gland hyperplasia?
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%).
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?
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.
37
37 What proportion of primary hyperparathyroidism is caused by parathyroid carcinoma?
About 0.1 to 1% of persons with primary hyperparathy roidism have a parathyroid carcinoma.
38
38 What are the incidence and prevalence of para thyroid carcinoma?
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.
39
39 How does the patient population with parathyroid carcinoma compare with patients with parathyroid adenoma?
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).
40
40 What feature on physical examination is most concerning for parathyroid carcinoma?
A palpable neck mass (reported in 30 to 76% of patients with parathyroid carcinoma), which is rarely associated with a benign adenoma
41
41 What is the gross pathologic description of a parathyroid carcinoma compared with a benign adenoma?
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.
42
42 What is the American Joint Committee on Cancer (AJCC) staging system for parathyroid carcinoma?
There is no AJCC staging system for parathyroid carcinoma because of its low incidence.
43
43 What is the most common cause of death in patients with parathyroid carcinoma?
Patients often die from the effects of excessive PTH secretion and uncontrolled hypercalcemia rather than growth from tumor mass.
44
44 What is the best prognostic factor in parathyroid carcinoma?
Early recognition and complete surgical resection at initial operation offer the best prognosis.
45
45 Describe the prognosis for parathyroid carcinoma.
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.
46
46 What is the preferred treatment approach to parathyroid carcinoma?
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.
47
47 What is the most common pattern of malignant spread of disease in parathyroid carcinoma?
Parathyroid carcinoma is generally indolent with local recurrence and involvement of contiguous neck structures representing the most likely pattern of spread.
48
48 What is the rate of recurrence in parathyroid carcinoma?
About 40 to 60% of patients have a postsurgical recurrence, which usually occurs 2 to 5 years after surgery.
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?
Aggressive hydration restores fluid volume and increases urinary calcium excretion. Loop diuretics increase calciu resis. Bisphosphonates interfere with osteoclast-mediated bone resorption.
50
50 What is the pattern of metastatic disease in parathyroid carcinoma?
Late metastases occur via both lymphatic and hematoge nous spread with the most common site being the lungs.
51
51 From what branchial structures does the thyroid develop?
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.
52
52 The ultimobranchial bodies develop into what structures?
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.
53
53 What is the relationship of the ultimobranchial bodies to the thyroid gland?
The ultimobranchial bodies fuse with the thyroid gland during its descent, consistently in the middle to upper thirds of thyroid gland.
54
54 What is the most common pattern of descent of the thyroid gland in relation to the hyoid bone? (▶ Fig. 12.3)
The thyroid gland descends anterior to the hyoid bone during gestational weeks 4 through 7.
55
55 What is the most common location of ectopic thyroid tissue?
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).
56
56 What does the proximal portion of the thyroglos sal duct form?
Foramen cecum of the tongue
57
57 What does the caudal remnant of the thyroglossal duct form?
Pyramidal lobe of the thyroid, which is present in 40 to 55% of patients
58
58 What is the recommended surgical treatment for a thyroglossal duct cyst?
The Sistrunk procedure, which includes complete removal of the thyroglossal duct along with a portion of the central hyoid bone
59
59 What is the most common path of the right and left recurrent laryngeal nerves?
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.
60
60 What does the recurrent laryngeal nerve inner vate? (▶ Fig. 12.4)
The intrinsic muscles of the larynx and sensory innervation of the glottis (shared innervation with internal branch of superior laryngeal nerve) and subglottis
61
61 What is the relationship of the recurrent laryngeal nerve and the cricothyroid joint?
The recurrent laryngeal nerve enters the larynx posterior to the cricothyroid joint.
62
62 What does the external branch of the superior laryngeal nerve innervate?
The cricothyroid muscle
63
63 What is the function of the cricothyroid muscle?
The cricothyroid increases tension on vocal cords, inducing a higher pitch when vocalizing, and is innervated by the superior laryngeal nerve.
64
64 What does the internal branch of the superior laryngeal nerve innervate?
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.
65
65 Where does the superior laryngeal nerve branch off from the vagus?
Immediately below the nodose ganglion (inferior ganglion) of the vagus nerve, which is located just inferior to the jugular foramen
66
66 Where does the thyroid gland obtain its blood supply?
Typically from the superior and inferior thyroid arteries but occasionally from a thyroid ima artery
67
67 What is the name of the prelaryngeal lymph node?
Delphian node
68
68 What are the boundaries of the level VI cervical lymph nodes?
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.
69
69 What is the name of the naturally occurring thyroidal enlargement on the lateral portion of the gland?
The tubercle of Zuckerkandl
70
70 What is the name of the posterior suspensory ligament of the thyroid?
Berry ligament
71
ligament of the thyroid? 71 Define the borders of the Simon triangle.
The Simon triangle is defined as the space between the esophagus medially, the carotid artery laterally, and the inferior thyroid artery superiorly.
72
72 Define the borders of the Joll triangle.
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.
73
73 Which is the active form of thyroid hormone?
Triiodothyronine (T3). Thyroxine (T4)must be deiodinated to T3 to act on peripheral tissue.
74
74 Describe the internal regulatory pathway of thyroid hormonogenesis.
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.
75
75 What is the Wolff-Chaikoff effect?
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.
76
76 What hormones are produced by the thyroid gland?
The thyroid produces T3 and T4. These are made by iodinating the amino acid tyrosine.
77
77 Thyroid storm is a medical emergency. What medications are the mainstay of treatment in the acute setting?
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.
78
78 What are the key components of thyroid hormone?
Thyroglobulin and iodine represent the key components to make and store thyroid hormone.
79
79 What is the name of the key enzyme required for thyroid hormonogenesis?
TPO, an enzyme that performs the iodination of thyroglobulin and coupling of monoiodotyrosine and diiodotyrosine to form T3 and T4
80
80 What is the most common cause of unilateral proptosis?
Graves' ophthalmopathy, which results in deposition of glycosaminoglycans and lipogenesis in the orbit.
81
81 What are the two ways in which amiodarone can cause hyperthyroidism?
● 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.
82
82 Describe the preferred treatment for subacute (de Quervain) thyroiditis in the hyperthyroid stage.
Symptomatic treatment with β-blockers and NSAIDs is the standard treatment. Severe cases are treated with highdose prednisone.
83
83 A rare cause of thyrotoxicosis is a hydatidiform mole. What is the mechanism?
Hydatidiform moles, a form of gestational trophoblastic disease, produce chorionic gonadotropin, which has TSHlike activity.
84
84 Where is a hormone-producing focus of metastatic follicular carcinoma typically found on radioactive body scan?
Usually in the lungs or bone
85
85 In a nongravid woman with thyrotoxicosis, radioactive iodine uptake is found in the pelvis. What is the diagnosis?
Struma ovarii, a teratoma of the ovary that contains functional thyroid tissue
86
86 What findings indicate a diagnosis of thyrotoxicosis factitia?
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.
87
87 Name the four main classifications of hypothyroidism.
● 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.
88
88 What is the most common cause of hypothyroidism in the world?
Iodine deficiency
89
89 What is the most common cause of hypothyroidism in the United States?
Hashimoto thyroiditis
90
90 What is the cause of myxedema coma?
Myxedema coma is an extreme hypothyroid state that is typically brought on by some systemic stress, often infection, in a hypothyroid patient.
91
91 Why should head and neck cancer patients have thyroid function closely monitored?
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.
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?
● 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.
93
93 Approximately how long does the hypothyroid phase of thyroiditis last?
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.
94
94 What is the likely cause of subacute granulomatous thyroiditis (de Quervain thyroiditis)?
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.
95
95 What laboratory values are elevated in patients with Hashimoto thyroiditis?
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.
96
96 What causes the initial hyperthyroid state in some patients with Hashimoto thyroiditis?
Transient release of stored thyroid hormone from damaged thyroid cells (hashitoxicosis) causes a temporary surge in serum thyroid hormone.
97
97 What is the relationship between Hashimoto thyroiditis and thyroid cancer?
Patients with Hashimoto thyroiditis have a slightly increased incidence of papillary thyroid carcinoma compared with the general population.
98
98 What are the indications for surgery in a patient with Hashimoto thyroiditis?
Large goiter with obstructive symptoms, cosmetic concerns, or worrisome nodularity
99
99 Is subacute thyroiditis always painful?
No. Painless thyroiditis is sometimes seen. The inflammatory component may be mild and not require therapy.
100
100 What are the characteristic physical examination findings of Riedel thyroiditis?
Rock-hard, fixed, painless goiter. Compressive symptoms including dysphagia, dysphonia, cough, and dyspnea may also occur.
101
101 What organisms most commonly cause acute suppurative thyroiditis?
Staphylococcus aureus, Streptococcus pneumoniae, β-hemolytic streptococci are the most common offenders. Occasionally, it can be caused by Fusobacterium and Haemophilus species as well.
102
102 What criteria for a thyroid FNA must be met in order to be considered diagnostic?
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.
103
103 Why is FNA of cystic thyroid nodules of low diagnostic yield?
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.
104
104 What are the false-negative and false-positive rates of thyroid nodule FNA?
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%.
105
105 When should a benign (based on results of previous FNA) thyroid nodule undergo rebiopsy?
When it changes significantly in size, a cyst recurs, or the nodule changes texture
106
106 What is the Pemberton sign?
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
107
107 What is the Chvostek sign?
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.
108
108 What is the Trousseau sign?
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.
109
109 What are the main complications of thyroid surgery?
Major complications include hematoma, infection, superior laryngeal nerve injury (most common nerve injured), recurrent laryngeal nerve injury, and hypocalcemia.
110
110 Name the four main types of thyroid surgeries, and define each one.
● 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
111
111 Name some disease-specific risk factors for permanent recurrent laryngeal nerve injury during thyroidectomy.
Recurrent thyroid carcinoma, substernal goiter, and thyroiditis
112
112 At what point in the thyroid dissection must one be aware of the superior laryngeal nerve?
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.
113
114 What is the most common pathology of a thyroid nodule?
Benign follicular adenoma
114
115 Why are thyroid nodules often found during pregnancy?
The incidence of thyroid nodules during pregnancy is 5 to 20%. Increased hormones and relative iodine deficiency may be associated with increased thyroid nodularity.
115
116 How often are thyroid nodules cancerous?
Approximately 5% are cancerous.
116
117 Is a thyroid cyst benign?
Not always. Malignancies such as papillary thyroid carcinoma and parathyroid carcinoma can be cystic.
117
118 What are the factors that increase suspicion of malignancy in a patient with a thyroid nodule?
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
118
119 Are thyroid nodules more likely to be malignant in adults or in the pediatric population?
Pediatric. Approximately 5% of adult thyroid nodules are malignant and 20 to 50% of pediatric thyroid nodules are malignant.
119
120 What is the most common cause of a thyroid nodule in the pediatric population?
Follicular adenoma, just as it is with adults
120
121 What signs and symptoms in a patient with a thyroid nodule are worrisome for cancer?
● 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.
121
122 What is the most common presentation of a patient with thyroid cancer?
Nontender, palpable thyroid mass
122
123 What are the ultrasound imaging characteristics of a lymph node that are concerning for metastatic thyroid cancer?
Loss of the fatty hilum, increased vascularity, rounded node configuration rather than ovoid, hypoechogenicity of a solid nodule, microcalcifications, and peripheral vascularity
123
124 What is the value of PET imaging in thyroid cancer?
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.
124
125 What are the subtypes of well-differentiated thyroid cancer?
Papillary thyroid cancer, follicular thyroid cancer, and Hürthle cell thyroid cancer are all considered well-differentiated
125
126 What are the most common staging systems available for well-differentiated thyroid cancer?
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
126
127 Which tumor staging system for thyroid cancer includes gross resection of tumor in its prognostic calculation?
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)
127
128 How does extrathyroidal extension impact thyroid cancer staging?
● 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
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)
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.
129
130 In which types of thyroid cancer are there different staging systems based on age of the patient?
Papillary thyroid carcinoma and follicular carcinoma have separate staging criteria based on age. Medullary and anaplastic carcinoma do not.
130
131 What is the most significant predictor of overall prognosis for well-differentiated thyroid cancer?
Distant metastasis is the most significant prognostic factor.
131
132 Review low-, intermediate- and high-risk features of well-differentiated thyroid carcinoma.
● 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
132
133 Which risk factor most significantly increases the risk of thyroid carcinoma?
Exposure to ionizing radiation, especially as a child or adolescent
133
134 What is the recommended surgical treatment for patients with well-differentiated thyroid cancer?
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.
134
135 How should local invasion of the esophagus by thyroid carcinoma be treated?
Local invasion of the pharynx or esophagus by thyroid carcinoma should be resected and then repaired by primary closure of the defect.
135
136 What adjuvant forms of treatment exist for welldifferentiated thyroid carcinoma?
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.
136
137 What is TSH suppression?
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.
137
138 Why is radioiodine ablation treatment used after surgery?
To destroy microscopic residual disease
138
139 How does radioiodine ablation assist in long-term management of well-differentiated thyroid carcinoma?
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.
139
140 What are the complications of radioiodine ablation?
Sialadenitis, dental caries, nasolacrimal duct obstruction, xerostomia, and rarely secondary malignancies
140
141 What is the recommended treatment for welldifferentiated thyroid carcinoma found in a thyroglossal duct cyst?
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.
141
142 How often do patients with thyroglossal duct cyst carcinoma have concurrent intrathyroidal cancer?
Based on a Mayo Clinic study from 1997, 33% of patients with thyroglossal duct cyst carcinoma had concurrent intrathyroidal malignancy.
142
143 What is the recommended treatment for a pregnant woman with well-differentiated thyroid carcinoma?
Surgical excision is recommended, either during the second trimester or after delivery.
143
144 Does thyroid cancer discovered during pregnancy behave differently from disease found in nonpregnant females?
No, there is no difference.
144
145 What are the recommendations for radioiodine ablation in regard to women of childbearing age?
Pregnancy should be avoided for 12 months after radioiodine ablation.
145
146 What is the treatment for locoregional metastatic well-differentiated thyroid carcinoma?
Ideally, surgical excision. Radioiodine ablation, externalbeam radiation, or clinical trials, if available, may be considered.
146
147 What is the treatment for well-differentiated thyroid carcinoma with tracheal invasion?
Complete surgical resection is the best treatment. It may include shaving tumor from the trachea or esophagus, segmental tracheal resection and reanastomosis, or laryngopharyngectomy.
147
148 As a general rule, what is the best treatment for well-differentiated thyroid carcinoma with pulmonary metastasis?
I-131 radioiodine ablation therapy
148
149 In a case of well-differentiated thyroid cancer, how should involvement of the recurrent laryngeal nerve be managed?
If preoperative vocal cord function is normal, the nerve should be left intact if at all possible.
149
150 What are the two most sensitive tests for tumor surveillance after treatment of well-differentiated thyroid carcinoma?
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.
150
151 How might anti-thyroglobulin antibodies affect posttreatment thyroglobulin levels?
The antibodies can produce a falsely low level of thyroglobulin and its utility as a tumor marker becomes invalid.
151
152 Describe the role of chemotherapy in treating welldifferentiated thyroid malignancies.
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.
152
153 Which age group most commonly has cervical and distant metastases in papillary thyroid carcinoma: adults or children?
Children more commonly manifest with advanced disease.
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?
Thyroid lobectomy
154
155 What should the detectable level of thyroglobulin be after total thyroidectomy and postoperative radioactive iodine therapy for advanced papillary carcinoma?
The goal is for an undetectable thyroglobulin level.
155
156 What histologic features are unique to papillary thyroid carcinoma? (▶ Fig. 12.5)
Psammoma bodies, which are concentric calcified structures, “Orphan Annie” eyes from large nuclear inclusions and nuclear grooves
156
157 In regard to papillary thyroid carcinoma, which pathological variants carry a worse prognosis?
Tall cell variant, columnar cell variant, and diffuse sclerosing variants of papillary thyroid carcinoma carry a worse prognosis
157
158 What type of thyroid cancer is most common in the pediatric population?
Papillary thyroid carcinoma
158
159 How is papillary thyroid microcarcinoma defined?
Papillary thyroid carcinoma measuring 1 cm or smaller irrespective of extrathyroidal extension, lymph node metastasis, or distant metastasis
159
160 How does papillary thyroid carcinoma tend to spread?
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
160
161 Is cervical lymph node metastasis more common in papillary or follicular thyroid carcinoma?
Papillary thyroid carcinoma. Cervical lymph node metastases are present in 30 to 70% of patients
161
162 What is the effect of cervical lymph node metastasis on the prognosis of papillary thyroid cancer?
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.
162
163 How is a follicular thyroid adenoma differentiated from follicular thyroid carcinoma?
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.
163
164 Are patients with follicular adenomas most commonly hyperthyroid, hypothyroid, or euthyroid?
Euthyroid
164
165 Is distant metastasis more common in papillary or follicular thyroid carcinoma?
Follicular thyroid carcinoma because it spreads via hematogenous dissemination
165
166 Name the three categories of follicular thyroid carcinoma.
● 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
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?
Approximately 15 to 20%
167
168 What is the significance of a pathology report indicating aneuploid follicular carcinoma?
Aneuploid follicular carcinomas are more aggressive in their behavior compared to other follicular carcinomas.
168
169 Describe the histopathologic findings of Hürthle cell tumors (oncocytic neoplasms).
● 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.
169
170 How do Hürthle cell carcinomas respond to radioiodine therapy?
Hürthle cell carcinomas tend to be aggressive and have decreased iodine uptake; thus, they are resistant to radioiodine therapy.
170
171 Medullary thyroid carcinoma accounts for what percent of all thyroid malignancies?
Approximately 5%
171
172 Medullary thyroid carcinoma originates from what cell type?
Parafollicular cells (C cells) of the thyroid gland, which produce calcitonin and are of neuroendocrine origin
172
173 What laboratory abnormalities are associated with medullary thyroid carcinoma?
Elevated calcitonin and often elevated CEA
173
174 What is the most common manifestation of medullary thyroid carcinoma?
● 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.
174
175 What is the most important prognostic factor in patients with medullary thyroid carcinoma?
Stage is the most important prognostic factor, followed by age.
175
176 How does radioiodine affect medullary thyroid carcinoma?
Medullary thyroid carcinoma does not take up radioiodine because it originates from the parafollicular cells, which are not involved in production of thyroid hormone.
176
177 What is the recommended treatment for patients with medullary thyroid carcinoma?
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.
177
178 What is the standard treatment for medullary thyroid carcinoma?
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.
178
179 How common is anaplastic thyroid carcinoma?
It is the rarest form of thyroid cancer, representing less than 5% of thyroid malignancies
179
180 What is the age range of patients affected by anaplastic thyroid cancer?
Most are over 70 years old, and rarely do patients younger than 50 years have anaplastic thyroid carcinoma.
180
181 What are common initial symptoms of anaplastic thyroid carcinoma?
It is a rapidly enlarging neck mass, often associated with dyspnea, dysphagia, hoarseness, and pain.
181
182 What is the relationship between anaplastic thyroid cancer and well-differentiated thyroid cancer?
In some cases, anaplastic thyroid carcinoma may develop from a long-standing well-differentiated thyroid malignancy such as papillary thyroid carcinoma.
182
183 What is the prognosis for anaplastic thyroid cancer?
It is almost universally fatal within 6 to 12 months of diagnosis.
183
184 What is an indication for surgery with anaplastic thyroid cancer?
Although controversial, tumor debulking for palliation can be considered. In addition, small, contained cancers may be approached with intent to cure.
184
185 What is a currently accepted protocol to treat anaplastic thyroid cancer?
Chemotherapy with doxorubicin, hyperfractionated radiotherapy, and surgical debulking.
185
186 In what type of thyroid cancer is external-beam radiation used most commonly?
External-beam radiation has been used with limited success in anaplastic carcinoma as a neoadjuvant therapy in surgically unresectable cases.
186
187 Which of the MEN subtypes includes involvement of the parathyroid glands?
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.
187
188 How does hyperparathyroidism manifest in patients with MEN-2A?
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.
188
189 Which subtype of medullary thyroid carcinoma is more common, sporadic or familial?
Sporadic cases represent 75% of medullary thyroid carcinomas.
189
190 What are the different subtypes of familial medullary thyroid carcinoma?
MEN-2A and MEN-2B. Additionally, there are several rare types of familial non-MEN medullary thyroid carcinoma.
190
191 What conditions are associated with MEN-2A syndrome?
Medullary thyroid carcinoma, pheochromocytoma, and parathyroid hyperplasia
191
192 What conditions are associated with MEN-2B syndrome?
Medullary thyroid carcinoma, pheochromocytoma, marfanoid body habitus, and mucosal neuromas
192
193 What is the inheritance pattern of familial medullary thyroid carcinoma?
Autosomal dominant
193
194 What gene mutation(s) are responsible for familial medullary thyroid carcinoma?
Gain of function mutations of the RET proto-oncogene
194
195 What is the most common subtype of familial medullary thyroid carcinoma?
MEN-2A is most common, followed by familial non-MEN and then MEN-2B.
195
196 Which form of medullary thyroid carcinoma is the most aggressive?
MEN-2B is most aggressive, followed by sporadic cases, then MEN-2A, then familial non-MEN, which has the best prognosis.
196
197 What is the recommended treatment for patients with a RET mutation and/or a family history of medullary thyroid carcinoma?
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.
197
198 What gene is involved in MEN-2?
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.
198
199 What endocrine neoplasms are associated with MEN-2A?
Medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism (parathyroid adenoma)
199
200 How frequently do individuals with MEN-2A develop the various clinical manifestations of this syndrome?
About 70 to 95% develop medullary thyroid carcinoma, 50% develop pheochromocytoma, and 15 to 30% develop primary hyperparathyroidism
200
201 What is the typical presentation of medullary thyroid carcinoma in individuals with MEN-2A?
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.
201
202 How frequently are cervical lymph node metastases present on presentation of medullary thyroid carcinoma in MEN-2A?
Up to 70%
202
203 What are the clinical findings associated with MEN- 2B?
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.
203
204 Describe the natural history of medullary thyroid cancer in MEN-2B and its recommended treatment.
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.
204
205 Describe the distinctive facial features of MEN- 2B.
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.
205
206 Describe the distinctive body habitus associated with MEN-2B.
Around 75% of individuals with MEN-2B have a marfanoid body habitus: tall and lanky, kyphoscoliosis or lordosis, joint laxity, and proximal muscle wasting.
206
207 What is the incidence of pheochromocytoma in MEN-2B?
50%; approximately half are bilateral.
207
208 What defines the clinical diagnosis of familial medullary thyroid carcinoma?
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.
208
209 Describe the age of onset and penetrance of medullary thyroid carcinoma in FMTC syndrome compared with MEN-2A and -2B.
Medullary thyroid carcinoma has a later age of onset in FMTC and decreased penetrance compared with MEN-2A and -2B.
209
210 What is the pattern of inheritance in MEN-2 syndromes?
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.
210
211 What is the recommended primary preventative measure in an individual with an identified germline RET mutation?
Prophylactic thyroidectomy
211
212 What is essential before surgery in any patient with MEN-2A, MEN-2B, or medullary thyroid carcinoma?
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.
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?
Approximately 50%
213
214 In individuals with MEN-2 who have undergone prophylactic thyroidectomy, what is the recommended screening protocol for medullary thyroid carcinoma?
Annual serum calcitonin levels
