Download Thyroid Board Questions 2012

Thyroid Board Questions
2012
Henry B. Burch, M.D.
Walter Reed National Military Medical Center
[email protected]
1.
A 59‐year‐old woman with weight gain and fatigue is found by her primary care physician to have an elevated serum TSH and begun on levothyroxine. She is referred to you for assistance in managing thyroid replacement therapy. In addition to thyroid hormone, she takes calcium and multivitamins with iron. Physical examination shows a pulse rate of 80 beats per minute, no goiter or thyroidectomy scar, and normal deep tendon reflexes.
Date
TSH
Free T4
(0.4-4.5 mU/L)
(0.8-1.8 ng/dL)
Levothyroxine
dose (mg)
January 2012
11.9
1.3
None
March 2012
May 2012
10.2
10.7
1.8
2.1
.075
.112
Which one of the following is the most likely explanation for these findings?
A.Poor absorption of levothyroxine
B.Resistance to thyroid hormone
C.A TSH‐secreting pituitary adenoma
D.Heterophilic antibody interference with the TSH assay
E.Poor adherence to therapy
Heterophilic Antibodies
Signal Ab
Capture Ab
Mouse
Monoclonal
IgG
TSH
Capture Ab
Signal Ab
Mouse
Monoclonal
IgG
Interfering
Antibody
(anti- mouse IgG)
2. A patient with a history of papillary thyroid cancer is noted to have an enlarged lateral neck lymph node on routine examination.
Which one of the following is the most sensitive and specific indicator of metastatic disease within the enlarged lymph node?
A. Neck ultrasound B. Fine needle aspiration cytology
C. Stimulated serum thyroglobulin D. PET‐CT scanning
E. Thyroglobulin wash‐out testing 3. A 45‐year‐old male with a recent diagnosis of Graves’ disease on methimazole develops bilateral ophthalmopathy. On examination he has a pulse of 80 beats per minute, conjunctival injection, caruncle swelling, dyscongjugate lateral gaze but no proptosis or change in visual acuity. He is begun on prednisone with some improvement in inflammatory symptoms but his diplopia has progressed over the past 4 weeks. Laboratory evaluation shows a free T4 1.7 ng/mL (normal 0.8‐1.8 ng/dL) and TSH 0.4 mU/L.
What is the next step in the management of this patient?
A.Radioactive iodine therapy
B.Strabismus surgery
C.Decompression surgery
D.Advise patient to wear an eye patch
E.Increase methimazole and add levothyroxine
4. A 46‐year‐old woman undergoes total thyroidectomy for a 3.4 cm thyroid nodule with benign results but is noted to have unifocal 0.9 cm thyroid cancer. Which one of the following pathology results suggests a diagnosis for which radioiodine would likely provide benefit?
AA
B
C
D
5. A 24‐year‐old male with a history of attention deficit disorder is noted to have a goiter and referred for further evaluation. The patient’s past medical history is otherwise unremarkable. On examination the patient’s pulse is 90 beats per minute. He has a diffuse goiter without nodule or bruit. Deep tendon reflexes are normal and he has no tremor. Laboratory testing shows a free T4 2.7 ng/mL (0.8‐1.8 ng/dL), T3 4.1 (1.3‐3.1 nmol/L), TSH 3.8 mU/L. Alpha subunit is 0.4 ng/mL (normal 0.6 or less) and MRI of the pituitary is normal. Which one of the following is the most likely diagnosis?
A.Thyroid hormone resistance
B.TSH‐producing pituitary adenoma
C.Heterophilic antibody interference with the TSH assay
D.Anti‐T4 antibody interference with the free T4 assay
E.Surreptitious use of thyroid extract
6. A 29‐year‐old woman is noted to have a 1.0 cm right thyroid nodule during the 9th week of pregnancy. The patient has no other medical history and her family history is negative for thyroid cancer. Ultrasound reveals no suspicious features and fine‐needle aspiration (FNA) is deferred. At 18 weeks the nodule is noted to now have a maximal diameter of 2.0 cm and is solid on ultrasound. A 2 cm ipsilateral central compartment lymph node is noted. FNA confirms papillary thyroid cancer in both the nodule and lymph node. Serum TSH is 0.9 mU/L.
Which one of the following is the next step in the management of this patient?
A.Start LT4 suppressive therapy
B.Refer for right thyroid lobectomy
C.Refer for total thyroidectomy
D.Repeat FNA in the third trimester
E.No intervention until after delivery
7. A 53‐year‐old woman undergoes thyroidectomy for a 3.5 cm papillary thyroid cancer on the left, with microscopic invasion through the thyroid capsule and positive lymph nodes in the central neck and left lateral neck compartments. She receives 150 mCi 131I six weeks after surgery, and post‐treatment scan reveals thyroid bed uptake with no evidence of distant metastasis.
Which one of the following corresponds to the correct AJCC‐7 staging for this patient’s thyroid cancer?
A.T2,N1a,M0; Stage II
B.T3,N1a,M0; Stage III
C.T3,N1b,M0; Stage IVA D.T4,N1a,M0; Stage IVB
E.T4,N1b,M0; Stage IVC
8. A 37‐year‐old woman with an ovarian mass undergoes laparotomy and bilateral oophorectomy, with findings of malignant struma ovarii and peritoneal studding with tumor. Neck examination reveals a normal thyroid and no cervical adenopathy. Serum TSH is normal and thyroid ultrasound reveals no abnormality. What should be the next step in the management of this patient?
A.Total thyroidectomy followed by radioiodine therapy
B.High dose radioiodine therapy C.Thyroid hormone suppressive therapy D.Chemotherapy with an ovarian cancer regimen
E.Multikinase inhibitor therapy
9. An 87‐year‐old woman with long‐standing hypothyroidism is noted to have progressive thyroid enlargement, dyspnea, and dysphagia over a period of 6 weeks. Examination reveals a firm,
asymmetrically enlarged thyroid, approximately three‐times normal size, which moves poorly with swallowing. CT scan of the
neck shows the thyroid to completely encircle the trachea. Which of the following is the most expected finding on fine needle aspiration?
A.Uniform‐appearing lymphocytes
B.Neoplastic C‐cells
C.Metastatic breast cancer
D.Sclerosing thyroiditis
E.Adenomatous hyperplasia
10. Which of the following nodules is likely to have a thyroid fine‐needle aspiration result suggestive of thyroid cancer? A
B
C
D
11. A 32‐year old nurse in her 14th week of pregnancy is referred for thyrotoxicosis. At 8‐weeks gestation, the patient noted palpitations with moderate nausea, vomiting, and abdominal pain, which gradually improved. On examination, pulse is 109 beats per minute and she has no ophthalmopathy. Thyroid is normal size without tenderness, bruit, or nodules. Serial thyroid function tests are shown below. TSH‐
receptor antibody and anti‐thyroid peroxidase testing are negative, the serum thyroglobulin level and ESR are normal. Quantitative hCG level is 62,000 mU/mL. Thyroid ultrasound shows normal vascular flow.
Weeks gestation
TSH
(0.550-4.780 mU/L)
Free T4
(0.89-1.76 ng/dL)
T3
(60-181 ng/dL)
Pre-pregnancy
0.51 L
0.9
--
8 weeks
0.012 L
1.61
--
12 weeks
<0.008 L
1.78 H
250 H
14 weeks
<0.008 L
1.51
203 H
Which one of the following is the most likely etiology of this patient’s thyrotoxicosis?
A.
B.
C.
D.
E.
Surreptitious use of thyroid hormone
Graves’ disease
Silent thyroiditis
Gestational (hCG mediated) thyrotoxicosis
Molar pregnancy
12. A 37‐year‐old male with a family history of thyroid cancer affecting his brother and father is noted to have a 1.3 cm right
thyroid nodule. Other past medical history is unremarkable. On
physical examination the patient has a palpable thyroid nodule but no cervical adenopathy. The remainder of the examination is normal with the exception of the finding shown in the picture below. Which disorder should be investigated further in this patient?
A.Cowden syndrome
B.Familial adenomatous polyposis C.Hirschprung’s disease
D.Multiple endocrine neoplasia type 1
E.Multiple endocrine neoplasia type 2
13. An 18‐year old girl is noted to have a thyrotoxicosis. Past medical history is significant for precocious puberty and recurrent humeral fracture. Family history is negative. On physical examination, the pulse is 92 beats per minute a small goiter is noted. Skin examination reveals the abnormality shown (figure). Which one of the following is the most likely cause of this patient’s thyrotoxicosis ?
A.Graves’ disease
B.McCune‐Albright syndrome
C.Familial hyperthyroidism
D.Polyglandular autoimmune syndrome
E.Hyperfunctional thyroid cancer
14. A 28‐year‐old woman is referred for a 2.5 cm right thyroid nodule. The patient has been in good health previously. Physical exam confirms the right thyroid nodule and reveals no cervical adenopathy. The remainder of the physical exam is unremarkable with the exception of an erythematous patch of skin on the mid back (figure), which the patient notes to be highly pruritic and present since childhood.
Which of the following is the most likely thyroid diagnosis?
A.Medullary thyroid cancer
B.Papillary thyroid cancer
C.Metastatic disease to the thyroid D.Thyroid amyloidosis
E.Hashimoto’s thyroiditis
15. An 18‐year‐old college freshman complains of intermittent early morning inability to move his legs. He has had several such episodes over the past 3 months, usually occurring after drinking alcohol the evening before. Episodes have resolved spontaneously within 1‐2 hours. His last episode was one week ago. He has lost 10 pounds during the past 6 months. On physical examination, his pulse is 90 beats per minute and he has a slight goiter. A fine tremor is noted and deep tendon reflexes are brisk, but neurological exam is otherwise completely normal. Laboratory testing shows a serum free T4 level of 2.5 ng/dL (0.8‐1.8 ng/dL), TSH < 0.01. Serum potassium is 4.1 mmol/L, calcium 9.5 mg/dL, albumin 4.1 g/dL, and magnesium is 2.2 mg/dL. Which of the following is the most rapid means to prevent additional episodes?
A.Start methimazole
B.Start propranolol
C.Start a daily potassium supplement
D.Start a supervised exercise program
E.Pyridostigmine 16. A 67 year old male with a remote history of papillary thyroid cancer undergoes rhTSH‐stimulated whole body scanning (WBS) and thyroglobulin testing. His original tumor was a 2.5 cm papillary thyroid cancer without local invasion or cervical adenopathy, treated with total thyroidectomy and radioiodine remnant ablation. Currently, the patient’s WBS shows two areas of intense uptake corresponding to the left wrist and right knee. Serum thyroglobulin on day five after rhTSH is undetectable, with negative thyroglobulin antibodies. What should be the next step in the management of this patient?
A.FDG‐PET scan
B.Bone scan C.Repeat WBS after showering D.Serum dilution to eliminate the “hook effect” on thyroglobulin testing
E.Treat with high dose radioiodine and obtain a post‐treatment scan
17. A 64‐year‐old woman with hyperlipidemia has unstable angina. Cardiac catheterization shows three‐vessel disease and she is scheduled for bypass surgery. Serum TSH is 52 mIU/L and free T4 0.5 ng/dL (0.8‐1.8 ng/dL). Which one of the following is the best means to prepare this patient for surgery?
A.Proceed with surgery; replace thyroid hormone postoperatively
B.Give levothyroxine 300 mcg intravenously and proceed with surgery
C.Start levothyroxine 25 mcg daily, increase gradually until euthyroid before surgery
D.Give liothyronine, 50 µg twice daily for 3 days and then perform surgery
E.Give a weight‐based dose of levothyroxine for 2 weeks preoperatively
18. A 27‐year‐old woman with Graves’ disease is treated with total thyroidectomy and one year later becomes pregnant. Fetal tachycardia is noted during the third trimester and ultrasound reveals a large fetal goiter. The mother is taking levothyroxine 0.125 mg daily and prenatal vitamins. Maternal free T4 is 1.1 ng/dL (normal 0.8‐1.8 ng/dL), and TSH is 1.2 mIU/L. Thyroid stimulating immunoglobulin (TSI) titers are 240% (normal < 120%). Which one of the following should be the next step in the management of mother and fetus?
A.Decrease maternal levothyroxine dose
B.Plasmapheresis to remove maternal TSI
C.Administer intraamniotic methimazole
D.Treat mother with methimazole, no change in levothyroxine dose E.Treat mother with methimazole, increase levothyroxine dose
19. An 18‐year‐old girl is referred for hypothyroidism. She notes mild difficulty swallowing but otherwise is without complaint. On examination she has no palpable thyroid tissue. Laboratory testing shows a serum TSH 36 mU/L, free T4 0.6 (normal 0.8‐1.8 ng/dL), thyroid peroxidase and anti‐
thyroglobulin antibodies are negative. Ultrasound of the neck reveals hypoplastic thyroid tissue bilaterally. Thyroid scan results are shown below.
Which one of the following is the most likely diagnosis?
A.Graves’ disease with TSH‐receptor blocking antibodies
B.Thyroid hemiagenesis
C.Thyroglossal duct cyst
D.Lingual thyroid
E.Branchial cleft cyst
ANT
LAT
20. A 62‐year‐old woman with hypothyroidism is admitted to the surgical intensive care unit with acute necrotizing pancreatitis. Serum TSH one month prior to admission was 1.8 mIU/L. Her outpatient dose of levothyroxine is 0.1 mg daily. Her surgical team is concerned about poor levothyroxine absorption due to bowel edema and wishes to change to parenteral thyroid hormone therapy. Which one of the following once daily intravenous regimens would be most appropriate?
A.Levothyroxine 0.15 mg
B.Levothyroxine 0.125 mg
C.Levothyroxine 0.1 mg
D.Levothyroxine 0.05 mg
E.Levothyroxine .025 mg
21. A 55‐year old woman with idiopathic chronic urticaria and angioedema is found to have a goiter. Serum TSH is 3.5 mIU/L.
Further testing is most likely to reveal which one of the following?
A.Elevated serum calcitonin level
B.Marked elevation in serum thyroglobulin
C.An autonomous nodule on thyroid scan
D.Positive thyroid peroxidase antibodies
E.C1 inhibitor deficiency
22. A 35‐year‐old woman with Hashimoto’s thyroiditis and vitamin D deficiency is referred for advice regarding levothyroxine dosing. She was previously well‐
controlled on 0.1 mg levothyroxine daily, but in order to maintain a normal TSH value, her levothyroxine has been gradually increased to 0.3 mg daily. The patient uses a pill sorter to take her prescription each morning on an empty stomach. She waits until lunch before taking a multivitamin with iron and a calcium supplement. Her weight is stable and she denies diarrhea or abdominal pain. Physical exam reveals a small firm goiter but is otherwise unremarkable. Serum TSH is 11.6 mU/L, and free T4 value of 1.0 ng/dL (0.8‐1.8 ng/dL). Complete cell count, liver associated enzymes, and serum albumin levels are all normal. What is the next step in the evaluation of this patient’s increasing levothyroxine dose requirement?
A.Pill counting and psychiatric evaluation
B.Move calcium tablets and multivitamins to before the evening meal C.Screen for occult celiac disease
D.Change to a different brand of levothyroxine
E.Recheck the TSH in another assay
23. A 54‐year‐old male with long‐standing hypothyroidism is referred for very high levothyroxine dose requirements. Over the past 2 years the patient’s levothyroxine dose has been as high as 1000 mcg daily. He claims strict adherence with his regimen. On examination there is no goiter but a large abdominal mass is noted, extending into the pelvis. Serum TSH is 178 mIU/L, free T4 is 0.4 (normal 0.8‐1.8 ng/dL); and free T3, 0.7 pg/mL (normal 2.3‐4.2 pg/mL), and reverse T3 413 ng/dL (normal 15‐40 ng/dL).
The tumor is likely to contain excessive amounts of which of the following enzymes?
A.Type 1 deiodinase (D1)
B.Type 2 deiodinase (D2)
C.Type 3 deiodinase (D3)
D.Thyroid peroxidase
E.Glutathione peroxidase
24. A 24‐year‐old woman develops thyrotoxicosis three months following an uncomplicated pregnancy. She is breastfeeding. On physical exam, pulse is 104 beats per minute, and the thyroid is 30 grams and non‐tender. Free T4 is 2.4 ng/mL (normal 0.8‐1.8 ng/dL), and TSH is undetectable. Which one of the following should be performed next to establish the correct diagnosis?
A.131I uptake at 24 hrs
B.Serum anti‐TPO antibodies C.Serum thyroglobulin level
D.Thyroid stimulating immunoglobulins E.An empiric trial of antithyroid drugs 25. An 87‐year‐old male with no prior history of thyroid disease is noted to have persistent serum TSH elevation in the 7.0‐7.5 mIU/L range, with normal serum free T4 levels. The patient is asymptomatic. On examination he has no goiter and deep‐
tendon reflexes are normal. Additional laboratory testing shows normal CBC and lipid levels. What should be the next step in the management of this patient?
A.Observation only, repeat serum TSH in 6 months B.Start levothyroxine at 0.4 micrograms/ kilogram daily
C.Start levothyroxine at 0.8 micrograms/ kilogram daily
D.Start levothyroxine at 1.6 micrograms/ kilogram daily
E.Arrange stress test before starting levothyroxine at 1.6 micrograms/ kilogram daily
26. A 20‐year‐old woman with diffuse euthyroid goiter is referred for further evaluation. The goiter was first noted in her teens and has gradually increased in size. She has otherwise been in good health. Her mother and maternal uncle also have been diagnosed with goiter. On examination the thyroid is approximately twice‐normal size, nontender, and without nodules. Laboratory testing reveals a serum TSH 3.3 mIU/L, free T4 1.3 (0.8‐1.8 ng/dL), negative anti‐thyroid peroxidase and anti‐thyroglobulin antibodies. Thyroid ultrasound shows a homogeneous echotexture. Which one of the following is the most likely cause of this patient’s goiter?
A.Dietary goitrogens
B.Inherited organification defect
C.Hashimoto’s thyroiditis
D.Pendred’s syndrome
E.TSH resistance
27. A 56‐year old woman is found to have a thyroid nodule by her gynecologist. She has been in excellent health and takes no medications. Family history is negative for thyroid cancer. Serum TSH is 1.8 mU/L. Fine‐needle aspiration shows a predominance of normal‐appearing groups of follicular cells and colloid as well as a few focal groups of cells with enlarged nuclei and nuclear grooves. According to the Bethesda System for Reporting Thyroid Cytopathology, which one of the following is the correct classification for this FNA?
A.Follicular neoplasm
B.Benign
C.Atypia of undetermined significance
D.Suspicious for malignancy
E.Malignant
Bethesda System: AUS/ AFLUS
9 Sub‐Categories
1.
2.
3.
4.
5. 6. 7. 8. 9. Prominent microfollicles but not enough to call follicular neoplasm
Predominance of Hürthle cells in an otherwise sparse specimen
Predominance of Hürthle cells in a hypercellular specimen, but clinical history suggests a benign Hürthle cell nodule as in Hashimoto’s or MNG
Sample preparation artifact‐ air drying nuclear changes, crowding appearance due to clotting
Focal nuclear features of PTC in an otherwise benign‐appearing aspirate
Cyst‐lining cells with atypical features such as nuclear grooves, prominent nucleoli, nuclear inclusions, in an otherwise benign‐appearing aspirate
A minor population of cells shows nuclear enlargement or prominent nucleoli, particularly in the setting of prior 131‐I, ATDs or repair after cystic degeneration
Atypical lymphoid infiltrate but insufficient to call suspicious for malignancy (flow cytometry recommended)
Not otherwise categorized
Cibas ES, Am J Clin Path 2009; 132:658.
28. A 37‐year‐old male is noted to have a 3.0 cm left thyroid nodule. He denies symptoms of pain, dysphagia, or hoarseness. Physical exam confirms the thyroid nodule and no cervical adenopathy is noted. Serum TSH is 1.3 mIU/L and thyroid ultrasound shows a 3.2 cm solitary hypoechoic nodule without suspicious features. Which of the following thyroid FNA results should result in a referral for thyroidectomy?
A
B
C
D
29. A 75‐year‐old male is taking amiodarone for a refractory arrhythmia. After two years of therapy he notes weight loss and worsening palpitations. In addition to amiodarone, the patient takes metoprolol and simvastatin. On examination , pulse is 90 beats per minute. he has a normal sized non‐
tender thyroid gland. Laboratory testing shows a serum TSH < 0.01 mU/L, free T4 4.2 ng/mL (normal 0.8‐1.8 ng/mL) T3 235 ng/dL (70‐200 ng/dL). RAIU is 5% at 4 hours, and thyroid ultrasound shows normal or slightly increased vascularity, without nodules. TSH‐receptor antibody testing and interleukin‐6 levels are pending.
Which one of the following is the next step in the management of this patient?
A.SSKI for 5 days, followed by thyroidectomy
B.Perchlorate
C.Methimazole
D.Prednisone
E.Methimazole plus prednisone 30. A 72‐year‐old male is admitted to the medical intensive care unit for treatment of urosepsis. One month earlier serum TSH was 2.7 mIU/L. Which one of the following patterns of thyroid laboratory testing would be expected in this patient?
Test
Normal
TSH
(mIU/L)
0.27-4.2
Total T4
(g/dL)
4.5-12.0
T3
(nmol/L)
Reverse T3
(ng/dL)
1.3-3.1
1.0
Free T4
(ng/dL)
11-32
20
0.8-1.8
A.
20.0
3.0
0.5
B.
3.0
4.5
1.0
50
0.8
C.
3.0
4.5
2.0
30
0.8
D.
6.0
8.0
1.3
40
1.5
E.
0.01
12.0
4.0
30
2.2
Henry Burch, MD
Answers to Thyroid Board Questions- Cleveland Clinic 2012
1. A 59-year-old woman with weight gain and fatigue is found by her primary care physician to have an
elevated serum TSH and is begun on levothyroxine therapy.
Answer D) Heterophilic antibody interference with the TSH assay
This pattern is typical of heterophilic antibody interference with the TSH assay. The interference occurs
in patients having antibodies that recognize the mouse monoclonal antibody used many sandwich assays
for TSH, creating a link between the capture and signal antibodies in the absence of antigen (in this case,
TSH- see figure below). The human anti-mouse monoclonal antibodies (HAMA) may occur naturally in
up to 10% of the general population (not just laboratory workers with mouse exposure, as was previously
described), and they result in a false elevation of serum TSH. Pre-incubation of the patient’s serum with
non-immune mouse antibodies is an added step in the assay intended to eliminate the effect of HAMA.
Clues to the presence of HAMA in this case are the unchanged serum TSH despite progressively
increasing free T4 values as the dose of levothyroxine was increased.
Krishnan SGS, et al. Falsely raised TSH levels due to human anti-mouse antibody interfering with
thyrotropin assay. Postgrad Med J 2006; 82: e27.
Heterophilic Antibodies
Signal Ab
Capture Ab
Mouse
Monoclonal
IgG
Capture Ab
TSH
Signal Ab
Mouse
Monoclonal
IgG
Interfering
Antibody
(anti- mouse IgG)
2. A patient with a history of papillary thyroid cancer is noted to have an enlarged lateral neck lymph
node on routine examination.
Answer: E) – Thyroglobulin measurement in FNA rinse
Thyroglobulin (Tg) measurement in washings from fine-needle aspirates of lymph nodes (LN) has
become commercially available. Several papers in the literature have described the utility of this
technique in cases such as the one described here. Two papers noted a lack of interference from
circulating anti-Tg antibodies. The higher the aspirate Tg level, the more accurate the result. Kim and
colleagues found that wash-out Tg concentrations >10 ng/mL were 91% sensitive and 90% specific for
tumor metastatic to the sampled LN.
Kim MJ, Kim EK, Kim BM, et al. Thyroglobulin measurement in fine-needle aspirate washouts: the
criteria for neck node dissection for patients with thyroid cancer. Clin Endocrinol 2009;70(1):14551.
3 A 45-year-old male with a recent diagnosis of Graves disease on methimazole develops bilateral
ophthalmopathy manifested by periorbital soft-tissue inflammatory changes, pain, and diplopia with
lateral eye movement.
Answer: D) – Advise patient to wear an eye patch
This patient has active Graves’ ophthalmopathy with progressive diplopia. While awaiting stability of the
eye muscle inflammation and fibrosis, temporizing measures, such as an eye patch (on either eye- usually
the most severely affected) or glasses with prisms, can be used to relieve his diplopia. Ultimately, he will
require strabismus surgery (answer B), but not until extraocular muscle fibrosis has stabilized, since
premature surgery will need to be repeated later when maximal fibrosis has occurred in the affected eye
muscle. Radioactive iodine with or without corticosteroids is not advised in patients with advanced active
ophthalmopathy, due to the risk of worsening disease. He does not have proptosis or optic neuropathy, so
he does not have an indication for orbital decompression (which may aggravate the diplopia). No
beneficial effect of higher methimazole doses with added levothyroxine have been demonstrated.
Bahn RS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the
American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid 2011;
21 (6): 593.
4. A 46-year-old woman undergoes total thyroidectomy for a 0.9 cm thyroid cancer.
Answer: C) – Figure C
This question deals with recognition of the typical histological appearance of thyroid cancer and an
awareness of current management guideline recommendations for the use of radioiodine remnant ablation
(RRA). Figure A shows spindle-cell formation typical of anaplastic thyroid cancer, which does not take
up radioiodine in the majority of cases. Figure B shows a typical papillary thyroid cancer, and because the
lesion size is <1 cm with unifocal disease, no RRA is recommended in current management guidelines.
Figure D is a stained section that shows granules on immunohistochemical staining (for calcitonin)
typical of medullary thyroid cancer, for which RRA is not useful. Figure C, the correct choice, shows a
tall-cell variant of papillary thyroid cancer, with more than 50% of cells taller than they are wide. Because
this is a more aggressive form of thyroid cancer, RRA is generally recommended.
5. A 24-year-old male with a history of attention deficit disorder is noted to have a goiter and is referred for
further evaluation.
Answer: A) – Thyroid hormone resistance
This patient has discordant TSH and free T4 values, suggesting inappropriate TSH release. The alpha
subunit:TSH molar ratio <1.0 favors thyroid hormone resistance rather than a TSH-producing pituitary
tumor (the MRI is also negative and the majority of TSH-producing tumors are macroadenomas). Other
possible causes are heterophilic antibodies, but serial dilutions would not be expected to yield linear
results if these were present. T4 antibodies tend to increase the measured value of free T4. Surreptitious
use of thyroid hormone is unlikely to give the consistent pattern described in this patient.
Distinguishing TSH‐Adenoma from Thyroid Hormone Resistance
TEST
TSH-oma
GTHR
Clinical
thyrotoxicosis
(+)
(-)
Family history
(-)
(+)
Alpha/TSH ratio
> 1.0
< 1.0
MRI
Tumor
Normal
Elevated
Normal
SHBG
6. A 31-year-old woman was noted to have a 1.0 cm right thyroid nodule during the 9th week of
pregnancy.
Answer: C) – Refer for total thyroidectomy
Current guidelines for the management of thyroid disease in pregnancy suggest that it is safe to wait until
after delivery to perform thyroid surgery for thyroid cancer discovered early in pregnancy. The
exception, however, is in patients demonstrating a more aggressive course, including growth by 50% of
nodule volume (or 20% in two dimensions) or aggressive baseline features, such as local invasion. This
patient had a doubling of her tumor size and the new appearance of metastatic disease to lymph nodes;
therefore, she qualifies for thyroidectomy during the second trimester of pregnancy. Radioactive iodine
scanning or therapy is absolutely contraindicated during pregnancy. The remaining options are
inadequate (A, B, and E) or unnecessary (D).
Stagnaro-Green A, et al. Guidelines of the American Thyroid Association for the diagnosis and
management of thyroid disease during pregnancy and postpartum. Thyroid 2011; 21(10): 1.
Thyroid 2011
 RECOMMENDATION 58
Pregnant patients with an FNA sample that is suspicious for thyroid cancer do not require surgery while pregnant except in cases of rapid nodular growth and/or the appearance of lymph node metastases. Thyroid hormone therapy is not recommended. Level I‐USPSTF
7. A 58-year-old woman is found at thyroidectomy to have a 3.7 cm papillary thyroid cancer on the left,
with microscopic invasion through the thyroid capsule and positive lymph nodes in the central neck and
left lateral neck compartments.
Answer: C) – T3, N1b, M0; Stage IVA
AJCC-7 staging for this patient first takes into account that she is ≥age 45. If she were younger than age
45, she would only be stage I or II, no matter how advanced her disease in the current staging system.
Her thyroid cancer is 3.7 cm, which by size would be a T2 lesion, but since there is also microscopic
invasion through the thyroid capsule, the tumor is a T3 lesion. She also has lymph node involvement
outside of the central compartment, making her lymph node status N1b, and because she has no indication
of distant metastases on post-treatment scan, her TNM status is T3, N1b, M0. Her staging is stage IVA,
due to the lymph node status N1b (had her involved lymph nodes been confined to the central
compartment, her staging would have been stage III).
8. A 37-year-old woman with an ovarian mass undergoes laparotomy and bilateral oophorectomy, with
findings of malignant struma ovarii and peritoneal studding with tumor.
Answer: A) – Total thyroidectomy followed by radioiodine therapy
This patient has malignant struma ovarii with evidence of metastatic disease. She should be treated in the
same manner as any other patient with metastatic differentiated thyroid cancer; namely, removal of both
the tumor and normal thyroid tissue followed by radioiodine therapy. In a review of 24 cases of
malignant struma ovarii, 16 patients were followed conservatively postoperatively while 8 received varied
additional therapy (4 received 131I). There were 8 recurrences and all occurred in the conservatively
managed patients. 131I for recurrent disease provided an initial complete response in 7 women with
recurrent disease. Struma ovarii generally presents as a pelvic mass, but it may present with
thyrotoxicosis in up to 10% of cases. Occasionally, patients with previously treated Graves disease have
stimulation of the ectopic ovarian tissue by persistent TSH-receptor antibodies. Approximately one-third
of struma ovarii cases have at least some histological evidence of malignancy, such as nuclear features of
papillary thyroid cancer, and, of these, approximately 5% have metastatic disease. The remaining options
are incorrect. High-dose radioiodine would be taken up largely by the normal thyroid gland. Suppressive
therapy with thyroid hormone is insufficient in this circumstance, and more aggressive chemotherapy is
not warranted.
Marcy PY, Thariat J, Benisvy D, Azuar P. Lethal, malignant, metastatic struma ovarii. Thyroid. 2010
Sep;20(9):1037-40.
DeSimone CP, Lele SM, Modesitt SC. Malignant struma ovarii: a case report and analysis of cases
reported in the literature with focus on survival and 131I therapy. Gynecol Oncol. 2003
Jun;89(3):543-8.
9. An 88-year-old woman with long-standing hypothyroidism is noted to have progressive thyroid
enlargement, dyspnea, and dysphagia over a period of 6 weeks.
Answer: A) – Uniform-appearing lymphocytes
This case presents a classic description of thyroid lymphoma—a rapidly growing goiter in an elderly
woman with a history of Hashimoto thyroiditis. Initial fine-needle aspiration may be suggestive of
lymphoma, but frequently a repeat aspiration with flow cytometry or open biopsy is needed for
confirmation. Encircling of the trachea by a thyroid lymphoma on cross-sectional imaging is referred to
as the “donut” sign. The remaining choices are less likely in this clinical scenario. Medullary thyroid
cancer (answer B, neoplastic C-cells) generally does not grow as rapidly as described in this patient.
Metastatic breast cancer (answer C) would appear as discrete thyroid masses, and the rapid growth is not
suggestive of benign adenomatous hyperplasia (answer D). Sclerosing (Reidel) thyroiditis (answer E) is
very uncommon and presents as a fixed, wood-hard thyroid mass.
Derringer GA, Thompson LDR, Frommelt RA, et al. Malignant lymphoma of the thyroid gland: A
clinicopathologic study of 108 cases. Am J Surg Pathol 2000;24:623–639.
Mack LA, Pasieka JL. An evidence-based approach to thyroid lymphoma. World J Surg 2007; 31:978.
10. Which of the following nodules is likely to have a thyroid fine-needle aspiration result suggestive of
thyroid cancer?
Answer: A) – Figure A
The correct answer to this question is best arrived at by exclusion of the nodules with benign ultrasound
appearances. The nodule in B is a simple cyst. The nodule in C has a spongiform appearance, which has
been shown to be very low risk for malignancy. The nodule in D is hyperechoic relative to the
surrounding thyroid parenchyma, making it most likely a benign lesion. That leaves the nodule shown in
A. This nodule has somewhat irregular borders, but also has the “taller than wide” feature in the
transverse view shown, which is an independent predictor of malignancy.
11. A 32-year-old nurse in her 13th week of pregnancy is referred for evaluation of thyrotoxicosis.
Answer: D) – Gestational thyrotoxicosis
This patient has mild to moderate thyrotoxicosis in the first and early second trimester, which appears to
be improving spontaneously. TSH-receptor antibody testing is negative and thyroid peroxidase
antibodies are negative, making answers B, and C, respectively, unlikely. Serum thyroglobulin levels
would be low with surreptitious thyroid hormone ingestion (answer A). Molar pregnancy, a form of
gestational trophoblastic disease, frequently presents with abnormal vaginal bleeding, an enlarged uterus,
and a false-positive pregnancy test resulting from hCG elevation. Hyperthyroidism occurs in
approximately 5% of women with gestational trophoblastic disease due to hCG stimulation of the TSH
receptor (1 U of hCG is equivalent to approximately 0.001 U of TSH). Her total T3 levels, which appear
elevated, reflect the effects of estrogen on thyroxine-binding globulin, rather than hyperthyroidism.
12. A 37-year-old man with a family history of thyroid cancer in his brother and father is noted to have a
1.3 cm right thyroid nodule.
Answer: A) – Cowden syndrome
The picture illustrates mucosal hamartomas and this patient appears to have a familial papillary thyroid
cancer (PTC). Cowden syndrome (multiple hamartoma syndrome) is associated with papillary thyroid
cancer in up to 10% of cases. It belongs to a collection of syndromes known as PTEN-hamartoma tumor
syndrome. Mutations in PTEN, a tumor suppressor gene, occur in 85% of patients with Cowden
syndrome. The typical oral papules seen with Cowden syndrome are 1–3 mm and present in the gingival,
labial, and palatal surfaces of the mouth in more than 80% of patients. Lesions often coalesce and are
described as having a cobblestone appearance. Histologically, they are benign fibromas. Another familial
disorder that can include PTC in approximately 2% of cases is familial adenomatous polyposis,
characterized by predisposition to multiple colonic polyps that progress to colon cancer, as well as benign
cysts of the jaw and sebaceous glands. Both Cowden syndrome and FAP are inherited in an autosomal
dominant pattern. First-degree relatives in families like this patient’s should have annual thyroid
examination or ultrasound (preferred) and undergo evaluation for other associated malignancies, such as
breast cancer. MEN-1 has been associated with both benign and malignant non-medullary thyroid
tumors, but the oral lesions are not seen in this setting. MEN-2 is associated with medullary thyroid
cancer, rather than PTC. Hirschsprung disease is associated with megacolon and occurs in patients with
RET proto-oncogene mutations; it is not associated with familial PTC.
Syndromic Familial DTC
Syndrome
Features
Mutated Gene
Function of
mutated gene
Thyroid cancer types
Prevalence of thyroid cancer in syndrome
Cowden’s Syndrome
Multiple hamartomas, Breast cancer,
PTEN
Tumor suppressor
gene
PTC, FTC
10%
Familial polyposis
(Gardner’s syndrome)
Intestinal
polyposis, Retinal lesions, desmoid
tumors
APC
Tumor suppressor
gene
PTC/ cribiform
variant
10%
Carney Complex
Lentigenes,
Atrial
myxomas, PPNAD (Cushing’s)
PRKAR1A Tumor suppressor
Gene ?
PTC, FTC
4%
PTEN hamartoma syndromes 2011. http://www.ncbi.nlm.nih.gov/books/NBK1488/
Malchoff CD, Malchoff DM. The genetics of hereditary nonmedullary thyroid carcinoma. J Clin Endocrinol
Metab. 2002;87:2455-2459.
13. An 18-year-old girl is noted to have thyrotoxicosis.
Answer: B) – McCune-Albright syndrome
This patient has a goiter, a “coast of Maine” café au lait spot (the darker areas are the abnormal lesions,
not the lighter ones), and a history of precocious puberty and recurrent fractures due to fibrous dysplasia.
McCune-Albright syndrome is the best fit for this clinical scenario. The thyroid lesions leading to
thyrotoxicosis are caused by activating mutations in the Gs alpha subunit of the G-protein apparatus.
Somatic activating mutations of the TSH receptor have been implicated in many cases of solitary hot
nodules, but they are not associated with McCune-Albright, nor is hyperfunctional thyroid cancer.
Celi FS, et al. The role of type 1 and type 2 5'-deiodinase in the pathophysiology of the 3,5,3'triiodothyronine toxicosis of McCune-Albright syndrome. J Clin Endocrinol Metab 2008;93: 23832389.
14. A 25-year-old male is referred for a 2.5 cm right thyroid nodule.
Answer: A) – Medullary thyroid cancer
The figure shows cutaneous lichen amyloidosis (CLA), an autosomal dominant condition that has been
strongly associated with MEN 2A, particularly in families harboring a mutation in codon 634 of the RET
protooncogene, with a prevalence as high as 36%. CLA typically occurs in the location shown, between
the spine and the scapula and is pruritic. This lesion may precede the diagnosis of MEN 2A by many
years. The current theory regarding the pathogenesis of this lesion is that it is due to patient’s scratching
the area to relieve a neurally mediated pruritus.
Verga U, Fugazzola L, Cambiaghi S, et al. Frequent association between MEN 2A and cutaneous
lichen amyloidosis. Clin Endocrinol (Oxf) 2003 Aug;59(2):156-161.
15. An 18-year-old Asian college freshman complains of intermittent early morning inability to move his
legs.
Answer: B) – Start propranolol
This patient has thyrotoxic hypokalemic periodic paralysis. Both thyrotoxic and familial varieties of
periodic paralysis are caused by an intermittent intracellular shift of potassium, resulting in ineffective
sarcolemmal activity within muscle fibrils. The severity of attacks is linked to the severity of
hypokalemia. Serum potassium levels return to normal between episodes—hence the normal level in this
patient at the time of testing. Attacks may be precipitated by ingestion of large carbohydrate loads or by
intense physical exertion followed by a period of rest, during which paralysis occurs. The predominance
in Asian males suggests an X-linked abnormality with additional race-specific genetic influences.
Mutations within Kir2.6, an inward-rectifier potassium channel, have recently been implicated in the
susceptibility of at least one-third of thyrotoxic periodic paralysis patients. Thyroid hormone and
adrenergic stimulation are known to stimulate the Na,K-ATPase pump, which contributes to the
intermittent hypokalemia. During an episode, judicious potassium therapy assists with recovery of
normal muscle function, but it is recommended that the total dose given should be less than 50 mEQ, in
order to avoid rebound hyperkalemia. There is no evidence that a daily potassium supplement prevents
subsequent attacks, since total body potassium stores are normal in these patients. Controlling
thyrotoxicosis is important and, in fact, attacks stop with restoration of a euthyroid state, but this will take
many weeks. Propranolol inhibits adrenergic stimulation of the Na,K-ATPase pump and has been found
to rapidly prevent recurrent episodes of periodic paralysis. As noted, vigorous exercise may actually
precipitate attacks, so an exercise program would not be a useful at this time. Pyridostigmine is used to
treat myasthenia gravis, not periodic paralysis.
Lin SH. Thyrotoxic periodic paralysis. Mayo Clin Proc. 2005 Jan;80(1):99-105. Review.
Ryan, D.P., et al. Mutations in potassium channel Kir2.6 cause susceptibility to thyrotoxic hypokalemic
periodic paralysis. Cell 2010;140(1):88-98.
16. A 67-year-old male with a remote history of papillary thyroid cancer undergoes rhTSH-stimulated
whole body scanning (WBS) and thyroglobulin testing.
Answer: C) – Repeat WBS after showering
Although recurrence is certainly possible in this patient at 10 years from the initial presentation, the
discordance of the WBS and the serum thyroglobulin level, as well as his 10-year history without
evidence of disease, increases the likelihood of a false-positive scan. False- positive WBS results can
occur from a long list of benign and malignant conditions, such as parotid gland cysts, tracheostomy sites,
head and neck tumors, Meckel diverticulum, normal thymus, normal breast tissue (women), ovarian cysts,
renal cysts, psoriatic skin plaques, skin burns. Contamination of the skin with isotope in saliva, sweat,
urine, or feces is among the more common sources of a false positive scan. In the latter circumstance,
washing the area of skin contamination will often eliminate the unexpected uptake. In cases described in
the reference below, false-positive skin contamination occurred beneath a wristwatch due to perspiration,
and on the knee due to probable urine contamination.
Carlisle MR, Lu C, McDougall IR. The interpretation of 131I scans in the evaluation of thyroid cancer,
with an emphasis on false-positive findings. Nuc Med Comm 2003;24(6):715-735.
17. A 64-year-old woman with hyperlipidemia has unstable angina.
Answer: A) – Proceed with surgery; replace thyroid hormone postoperatively
Retrospective studies have shown that hypothyroidism does not greatly increase the risk of surgery. In
this patient with unstable coronary artery disease (CAD), therapy with thyroid hormone could increase
myocardial metabolic demands and precipitate myocardial infarction (MI). Therefore, the best approach
would be to proceed with coronary artery revascularization, then cautiously treat the hypothyroidism
postoperatively.
Hay ID, Duick DS, Vlietstra RE, Maloney JD, et al. Thyroxine therapy in hypothyroid patients
undergoing coronary revascularization: a retrospective analysis. Ann Intern Med 1981;95:456-457.
Ladenson PW, Levin AA, Ridgway EC, et al. Complications of surgery in hypothyroid patients. Am J
Med. 1984 Aug;77(2):261-266.
18. A 22-year-old woman with Graves disease is treated with total thyroidectomy and 1 year later she
becomes pregnant.
Answer: D) – Treat mother with methimazole, no change in levothyroxine dose
This is a case of fetal thyrotoxicosis due to transplacental passage of thyroid- stimulating antibodies.
Maternal administration of an antithyroid drug, which also crosses the placenta, has been used
successfully in this setting. The fetus should be followed by monitoring of goiter size and heart rate and
assessment of amniotic fluid volume and intrauterine growth. Only rarely should cord blood sampling be
utilized, given the increased risk of fetal morbidity and mortality (approximately 3% pregnancy loss)
associated with this procedure. Decreasing maternal levothyroxine could have adverse effects on the
pregnancy. Plasmapheresis and intraamniotic methimazole are too invasive in this case. Since this mother
is not dependent on endogenous synthesis of thyroid hormone, her levels will not be appreciably affected
by the methimazole. Since she is already in her third trimester of pregnancy, a further increase in
levothyroxine dose requirement is not expected, so no adjustment in her levothyroxine dose is required.
Stagnaro-Green A, et al. Guidelines of the American Thyroid Association for the diagnosis and
management of thyroid disease during pregnancy and postpartum. Thyroid 2011;21(10):1.
Srisupundit K, Sirichotiyakul S, et al. Fetal therapy in fetal thyrotoxicosis: a case report. Fetal Diagn
Ther 2008;23(2):114-116.
19. An 18-year-old girl is referred for hypothyroidism.
Answer: D) – Lingual thyroid
This patient has a lingual thyroid, which is insufficient to maintain euthyroidism. Although surgical
resection and radioiodine have both been used to ablate lingual thyroids, levothyroxine therapy has been
shown to reduce the size of some lingual thyroids and thus obviate the need for ablation. None of the
other options would give the thyroid scan findings of uptake at the base of the tongue shown in the
picture. A thyroglossal duct cyst would generally be lower in the neck, most frequently at the level of the
hyoid bone, and hemiagenesis would appear as unilateral uptake in the thyroid bed. A branchial cleft cyst
is a remnant of the second pharyngeal cleft and is not involved in thyroid embryogenesis.
Reference: Moaddab MH. Lingual thyroid. N Engl J Med 2008;358(16):1712
20. A 62-year-old woman with hypothyroidism is admitted to the surgical intensive care unit with acute
necrotizing pancreatitis.
Answer: D) – Levothyroxine 0.05 mg intravenously once daily
Intravenous levothyroxine dosing is generally started at 50% of the patient’s usual oral therapy dosing.
The remaining choices are either too high or inappropriately substitute triiodothyronine.
Hays MT. Parenteral thyroxine administration. Thyroid 2007;17(2):127.
21. A 55-year-old woman with idiopathic chronic urticaria and angioedema is found to have a firm
diffuse goiter.
Answer: D) – Positive thyroid peroxidase antibodies
There is a strong association between chronic idiopathic urticaria and autoimmune thyroid disease,
particularly Hashimoto thyroiditis. Several studies have shown that patients with this dermatological
condition are 2-3 times more likely than control subjects to have evidence of thyroid autoimmunity. Less
clear from the existing literature is the effect of treatment of the thyroid on the course of urticaria, since
no prospective, well-controlled trials have been done in this area. Recent retrospective reviews have not
substantiated a beneficial effect of thyroid hormone therapy in limiting the frequency or severity of
attacks. There is no association between medullary thyroid cancer and chronic urticaria. Although
Graves’ disease is also associated with chronic idiopathic urticaria, autonomously functioning thyroid
nodules are not. Serum thyroglobulin would not be expected to be markedly elevated in Hashimoto
thyroiditis and C1 inhibitor deficiency is not associated with goiter.
Doutre MS. Chronic urticaria and thyroid autoimmunity. Clin Rev Allergy Immunol. 2006;30:31-37.
22. A 45-year-old woman with Hashimoto thyroiditis and vitamin D deficiency is referred for advice
regarding levothyroxine dosing.
Answer: D) – Screen for occult celiac disease
Celiac disease is a relatively common autoimmune condition that results in intolerance to dietary gluten.
Malabsorption is characteristic of overt celiac disease, and refractory hypothyroidism due to
levothyroxine malabsorption is well recognized. Recently, a higher-than-expected incidence of occult or
previously unrecognized celiac disease has been found in patients with autoimmune thyroid disease.
Similarly, unexplained vitamin D deficiency, and resultant low bone density can occur in patients with
previously unrecognized celiac disease. Several studies have shown the prevalence of celiac disease in
patients with autoimmune thyroid disease to be approximately 3%–5%, compared to approximately 1% of
control populations. Similarly, a higher-than-expected prevalence of autoimmune thyroid disease has
been described in patients with known celiac disease. Previously unsuspected celiac disease has been
described both in patients with malabsorption for levothyroxine and in patients with vitamin D deficiency.
Levothyroxine malabsorption in celiac disease is reversed with a gluten-free diet. The remaining options
are not likely since there is no evidence at this stage that the etiology is factitious, and 4 hours of
separation of levothyroxine from calcium supplements is generally considered sufficient.
Virili C, et al. Atypical celiac disease as cause of increased need for thyroxine: a systematic study. J
Clin Endocrinol Metab. 2012 Jan 11. [Epub ahead of print]
23. A 54-year-old male with long-standing hypothyroidism is referred for very high levothyroxine dose
requirements.
Answer: D) – Type 3 deiodinase (D3)
Type 3 deiodinase is an inactivating enzyme located in the placenta and brain. This enzyme inactivates
T4 to reverse T3 and to 3,3΄-T2 and likely has a major role in modulating the thyroid hormone status of
the early fetus. Conversely, both D1 and D2 are activating enzymes, converting T4 to T3. Ectopic or
paraneoplastic expression of type 3 deiodinase has been described in hepatocellular carcinoma, and
recently in patients with hepatic hemangioblastomas. Patients with paraneoplastic synthesis of this
enzyme require very large amounts of exogenous T4 and T3 to keep up with the enhanced deactivation
occurring through tumor expression of type 3 deiodinase. This process has been referred to as
“consumptive hypothyroidism.”
Howard D, et al. Consumptive hypothyroidism resulting from hepatic vascular tumors in an athyreotic
adult. J Clin Endocrinol Metab. 2011 Jul;96(7):1966-1970. Epub 2011 Apr 20.
Jassam N, et al. Consumptive hypothyroidism: a case report and review of the literature. Ann Clin
Biochem. 2011 Mar;48(Pt 2):186-189. Epub 2011 Mar 7. Review.
24. A 27-year-old woman develops thyrotoxicosis 4 months after an uncomplicated pregnancy.
Answer: D) – Thyroid-stimulating immunoglobulin
This woman has developed thyrotoxicosis following pregnancy. The primary diagnostic distinction to be
made is between postpartum thyroiditis and activation of Graves’ disease following pregnancy. Thyroidstimulating immunoglobulins will be positive in most cases of the former but not in the latter.
Radioiodine uptake will be low in the former and elevated in the latter. However, since radioiodine is
secreted into breast milk, only isotopes with short half lives (such as 123I) can be used, and the breast milk
must be discarded for several days in order to clear the isotope. In comparison, 131I has a duration of
activity that precludes further breastfeeding after it is used. Answers B and C do not distinguish between
Graves disease and postpartum thyroiditis. TPO antibodies will likely be positive in both disorders, as is
serum thyroglobulin. Antithyroid drugs (Answer E) are better reserved for confirmed Graves’ disease in
this setting. Doppler flow ultrasound has also found increasing utility in distinguishing postpartum
thyroiditis (low blood flow) from Graves’ disease (high blood flow)
25. An 87-year-old man with no prior history of thyroid disease is noted to have persistent serum
TSH elevation in the 5–7 mIU/L range, with normal serum free T4 levels.
Answer: A) – Observation only, repeat serum TSH in 6 months
This elderly patient has asymptomatic mild elevation in serum TSH. A 2004 JAMA article showed
improved survival in elderly patients with mild serum TSH elevation, without a decrement in cognitive
function, depression, or other disability in daily living. The reason for this finding is unclear, but may be
related to avoidance of the higher risk of arrhythmia as the TSH declines in the elderly. An analysis of
NHANES-III population survey results has shown that normal elderly patients without goiter or
serological evidence of Hashimoto thyroiditis have a rightward shift in the upper limit of normal for TSH,
up to the values in the low 7’s. Therefore, the best option in this asymptomatic octogenarian is no
intervention. The remaining choices would pose a theoretically higher risk than no intervention.
Surks MI, Boucai L. Age- and race-based serum thyrotropin reference limits. J Clin Endocrinol Metab
2010;95(2): 496.
Gussekloo J, et al. Thyroid status, disability and cognitive function, and survival in old age. JAMA.
2004 Dec 1;292(21):2591-2599.
26. A 20-year-old woman with diffuse goiter is referred for further evaluation. T
Answer: B) – Inherited organification defect
This patient likely has a disorder of organification, due to an inherited defect in thyroid peroxidase as the
source of familial goiter. Dietary goitrogens, such as those present in cassava plant roots and in yellow
turnips and cabbage, do not generally lead to clinically apparent goiters in regions of iodine sufficiency,
but they may augment the effect of iodine insufficiency on thyroid size in regions of endemic iodine
deficiency. The most common cause of a euthyroid diffuse (non-nodular) goiter in the North America is
Hashimoto thyroiditis (worldwide, the most common cause of goiter is still iodine deficiency). However,
this patient has negative TPO antibodies, which has only rarely been described in patients with
histologically proven Hashimoto thyroiditis, and the thyroid echotexture is homogeneous rather than
heterogeneous, which would occur with Hashimoto thyroiditis. Pendred syndrome is characterized by
deafness and goiter due to mutations in the pendrin protein, which controls apical iodine uptake in
thyrocytes; this patient does not fit this syndrome. Resistance to thyroid hormone would be associated
with elevated, rather than normal, thyroid hormone levels.
Ozbek MN, Uslu AB, Onenli-Mungan N, Yuksel B, Pohlenz J, Topaloglu AK. Thyroid peroxidase gene
mutations causing congenital hypothyroidism in three Turkish families. J Pediatr Endocrinol Metab.
2009 Nov;22(11):1033-1039.
Nascimento AC, et al. Thyroperoxidase gene mutations in congenital goitrous hypothyroidism with total
and partial iodide organification defect. Thyroid 2003 Dec;13(12):1145-1151.
27. A 56-year-old woman is found to have a thyroid nodule by her gynecologist.
Answer: C) – Atypia of undetermined significance
The Bethesda System for Reporting Thyroid Cytopathology, which was introduced in 2007, distributes
thyroid fine-needle aspiration results into one of 6 categories: nondiagnostic, benign, atypia of
undetermined significance or follicular lesion of undetermined significance, follicular neoplasm,
suspicious for malignancy, and malignancy. The atypia category includes 9 different subtype descriptions,
one of which applies in this patient’s case and is described as “focal features suggestive of papillary
thyroid carcinoma, including nuclear grooves, prominent nucleoli, elongated nuclei or cytoplasm, and/or
intranuclear cytoplasmic inclusions in an otherwise predominantly benign appearing sample.” The
malignancy rate for such lesions was expected to be 5%–15%.
Bethesda System: AUS/ AFLUS
9 Sub‐Categories
1.
2.
3.
4.
5. 6. 7. 8. 9. Prominent microfollicles but not enough to call follicular neoplasm
Predominance of Hürthle cells in an otherwise sparse specimen
Predominance of Hürthle cells in a hypercellular specimen, but clinical history suggests a benign Hürthle cell nodule as in Hashimoto’s or MNG
Sample preparation artifact‐ air drying nuclear changes, crowding appearance due to clotting
Focal nuclear features of PTC in an otherwise benign‐appearing aspirate
Cyst‐lining cells with atypical features such as nuclear grooves, prominent nucleoli, nuclear inclusions, in an otherwise benign‐appearing aspirate
A minor population of cells shows nuclear enlargement or prominent nucleoli, particularly in the setting of prior 131‐I, ATDs or repair after cystic degeneration
Atypical lymphoid infiltrate but insufficient to call suspicious for malignancy (flow cytometry recommended)
Not otherwise categorized
Cibas ES, Am J Clin Path 2009; 132:658.
Cibas ES, Ali SZ. The Bethesda System for Reporting Thyroid Cytopathology. Am J Clin Pathol.
2009;132:655-657.
28. A 37-year-old male is noted to have a 3.0 cm left thyroid nodule.
Answer: B) – Figure B
This picture shows typical features of papillary thyroid cancer, including nuclear overlap and inclusions.
The other pictures show: A, colloid nodule; C, adenomatous hyperplasia; and D, cystic fluid with
macrophages.
29. A 75-year-old male is taking amiodarone for a refractory arrhythmia
Answer: E) – Methimazole plus prednisone
Two subtypes of AIT have been described: type 1, which is believed to be an iodine-induced
thyrotoxicosis occurring in patients who often have preexisting thyroid autonomy, and type 2, which is a
destructive thyroiditis. There are also patients who have mixed types of AIT, and those in whom the
subtype cannot be ascertained, as in this case. According to the 2011 ATA Hyperthyroidism guidelines,
combination therapy is indicated in patients demonstrating an inadequate response to monotherapy, in
patients in whom a subtype cannot be determined using available testing, and in patients with severe
complications (generally cardiovascular compromise), in whom stepwise therapy would be inappropriate.
Basaria S, Cooper DS. Amiodarone and the thyroid. Am J Med. 2005;118:706.
Piga M, et al. Amiodarone-induced thyrotoxicosis. A review. Minerva Endocrinol. 2008;33:213-228.
Bahn RS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the
American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid
2011;21(6):593.
Thyroid 2011
 RECOMMENDATION 94
Combined antithyroid drug and anti‐inflammatory therapy
should be used to treat patients with overt amiodarone‐
induced thyrotoxicosis who fail to respond to single
modality therapy, and patients in whom the type of disease
cannot be unequivocally determined. 1/+00
30. A 72-year-old male is admitted to the medical intensive care unit for treatment of urosepsis.
1. Answer B). This patient is admitted to the ICU for urosepsis and would be expected to have classic
changes in thyroid hormone levels that occur as a result of an acute nonthyroidal illness (NTI) of this
severity. The most prevalent and pronounced change of thyroid function during NTI is a depression
in the serum total and free T3 levels and a concurrent elevation in reverse T3. A low T3, present in
70% or more of hospitalized patients, may be considered, with a few notable exceptions, the sine qua
non of the euthyroid sick syndrome. Total T4 is frequently low in patients with severe NTI and a
very low T4 portends a poor prognosis. Free T4 generally remains in the normal range. TSH is
frequently normal, but may be slightly suppressed or elevated, particularly during the recovery stages
(but generally < 20 mIU.L). Using the process of elimination, only options A, B, and D have a low
T3, and only B and D have an elevated rT3. Option D is eliminated due to the high total T4 and free
T4.
Reference:
a.
Warner MH, Beckett GJ. Mechanisms behind the non-thyroidal illness syndrome: an update.
J Endocrinol. 2010 Apr;205(1):1-13. Epub 2009 Dec 16.