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The Work-up of a Thyroid Nodule:
A Case Presentation and DiscussionJunko Ozao
PGY-3
Mount Sinai General Surgery
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CC: thyroid nodule on PET scan
HPI: A.P. is a 52 y.o. F s/p sigmoid resection for a4.9 cm mod-differentiated adenoca c 2/14lymph nodes positive on 5/6/2005 (T3bN1Mx).In preparation for surgery, the pt underwent a
PET scan, where an increased uptake in herthyroid was noted. Pt denies pain, troublebreathing, hoarseness or dysphagia. No hx ofradiation exposure.
Med and Surg Hx: hysterectomy 2000 for fibroids.
Meds: none All: none
Fam Hx: mother with hypothyroidism
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P.E.- 2cm firm nodule in right mid-pole of
thyroid, no LAD Labs: TSH: 2.24 (0.35-5.5) PTH 42(10-65)
Ultrasound:2.4x1.6x1.3cm nodule on R lobe
with calcifications seen, smaller 0.5x0.3x0.5cmnodule in R superior pole; left lobeunremarkable
Thyroid scan: non-diagnostic FNA: papillary thyroid cancer
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Uncomplicated total thyroidectomy was
performed on 6/5/2005 Pathology-1.7cm papillary thyroid carcinoma,
uninvolved tissue Hashimotos thyroiditis, 2
lymph nodes negative for tumor Currently undergoing chemo for sigmoid ca
Possibility and timing of iodine ablation being
discussed with oncology
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Work-up of a Thyroid Nodule
Prevalence and risk factors
H&P
Labs Imaging Modalities
Biopsy
Management Controversial topics
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Prevalence Large population studies-Framingham study showed
clinically significant nodules in 6.4% women and 1.5%men ages 30-59 (total 4.2%) but thought to besignificantly understated
Ultrasounds- 20% to 76% of females had at least onethyroid nodule on ultrasound
Autopsy surveys show 37 to 57% of patients withthyroid nodules
Vander JB, et al. The significance of nontoxic thyroid nodules. Final report of a 15 year study of theincidence of thyroid malignancy. Ann Intern Med 1968;69:537.Belfiore et al. High frequency of cancer in cold thyroid nodules occuring at a young age. Acta Endocrinol1989;121:197
Rice CO et al. Incidence of nodules in the thyroid. Arch Surg 1932;24:505. Mortensen JD, Woolner LB,Bennett, WA. Gross and microscopic findings in clinically normal thyroid glands. J Clin Endocrinol Metab1955; 15:1220
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Risk Factors of nodules and of
carcinoma
Increased risk of nodules with age Increased risk of carcinoma in adults over 60
and under 30
Solitary palpable nodules are about 4x moreprevalent in women than in men However, among pts with nodules- rate of
carcinoma 2x as high in men as in women (8%
vs. 4%)
Wong CKM, et al. Thyroid nodules: Rational management. World J Surg 2000;24:934-941
Mazzaferri EL. Management of a solitary thyroid nodule. NEJM 1993;328:553-559
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Nodules are very commonestimates of 9million adults in the US have a thyroid nodule
New nodules appear at a rate of 0.8%/yrThyroid cancer is rare 4/100,000 per year-12,000
new cases/yr in US
1% of all malignancies
0.5% of all cancer deaths-1,000/yr
Up to 35% of thyroids at autopsy containclinically silent carcinoma Wong CKM, et al. Thyroid nodules: Rational management. World J Surg 2000;24:934-941
Mazzaferri EL. Management of a solitary thyroid nodule. NEJM 1993;328:553-559
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Exposure to radiation, especially in childhood isassociated with increased prevalence of thyroid
nodules and malignancy-2%/yr increased riskwith peak incidence 15-20 years Presence of a nodule in a child is 2x as likely to be
carcinoma
Two large series 20-27% of patients with priorradiation exposure had thyroid nodularity and 30 to33% of the nodules were carcinomas
Prior family history of thyroid cancer
Schneider AB et al. Radiation-induced tumors of the head and neck following childhood
irradiation.J Clin Endocrinol Metab. 1985;61(3):547-50.Favus MJ et al. Thyroid cancer occurring as a late consequence of head and neck irradiation.Evaluation of 1056 patients. N Engl J of Med 1976;294:1019; Cerletty JM et al. Radiation-related thyroid carcinoma. Arch Surg 1978;113:1072.
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Rate of Carcinoma in Thyroid Nodules
Significant selection bias in surgical series
North Carolina study in a community hospital pts withnodules were referred to surgery without biopsy and
6.5% of excised nodules were carcinomas Catania, Italy 2327 pts with nodules were evaled by
FNA and of those 391 were selected for surgery.Carcinomas were found in 28 which was 5% of total
Werk EE, Vernon BM, Gonzalez, JJ. Cancer in thyroid nodules. A community hospital survey. Arch InternMed 1984; 144:474.Belfiore et al. High frequency of cancer in cold thyroid nodules occuring at a young age. Acta
Endocrinol 1989;121:197
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Causes of Thyroid Nodules
Benign- >90% Multinodular goiter (colloid
adenoma) Hashimotos (chronic
lymphocytic) thyroiditis Cysts: colloid, simple, or
hemorrhagic-7-14% can bemalignant- most commonlypapillary ca with a cysticcomponent with most increasedsize 2-4cm
Follicular Adenoma Macrofollicular adenoma
Microfollicular or cellular Hurthle-cell (oxyphil cell)
adenomas- macro ormicrofollicular
Malignant -about 6%
Papillary
Follicular
Minimally or widely invasive
Oxyphilic type
Medullary
Anaplastic
Primary thyroid lymphoma
Metastatic carcinoma
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Toxic Multinodular Goiter
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Papillary Carcinoma
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Work-up of a Thyroid Nodule
Prevalence and risk factors
H&P
Labs Imaging Modalities
Biopsy
Management Controversial topics
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H&P
Age and gender Recent history of hoarseness, dysphagia or
dyspnea
Sxs of hypothyroidism or hyperthyroidism Family h/o thyroid or endocrine disease
h/o prior radiation exposure, especially early in
life
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Thorough history of other endocrine disorders-MEN type IIand other malignant syndromes ---familial adenomatous polyposis, Gardnerssyndrome
Palpate thyroiddetermine size and consistencyof thyroid nodule(s), shape, location andmobility
Examine for cervical LAD Hard, fixed, irregular-shaped nodules and LAD
are suggestive of malignancy
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Work-up of a Thyroid Nodule
Prevalence and risk factors
H&P
Labs Imaging Modalities
Biopsy
Management Controversial topics
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Laboratory
Thyroid function tests- should be assessed
Calcitonin if suspect medullary thyroid disease
Most thyroid nodules are euthyroid
However, if TSH is low, the possibility of a hot noduleis increased- may want to consider thyroid scintigraphy
TSH is high suggestive of Hashimotos thyroiditis- maywant to ultrasound to see if nodularity is lymphocytic
infiltrate vs. TSH induced hyperplasia vs. thyroid tumor Still should fully evaluate a nodule- may have co-existence of
malignancy and thyroiditis
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Work-up of a Thyroid Nodule
Prevalence and risk factors
H&P
Labs Imaging Modalities
Biopsy
Management Controversial topics
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Imaging- Thyroid Scintigraphy
Utilizes iodine or technetium-99m pertechnate- more is taken upand organified by functional tissue
Non-functioning thyroid nodule is cold and mandates furtherwork-up by FNA
The scan is often used in working up nodules in patients withhigh TSH levels but has many problems Nelson et al. showed that only slightly more than one-half of
their excised malignant thyroid nodules appeared cold becausethe scan is 2-D there is apposition of normal thyroid tissue nextto abnormal tissue
Nelson RL et al. Rectilinear thyroid scanning as a predictor of malignancy. Ann of Intern Med 1978;88:41.
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Also although 80% of nodules greater than 2cm appear cold-smaller nodules can be indeterminate
Malignancy has been shown to occur 15-20% of cold nodulesand, additionally, in 5-9% of nodules with uptake that is warmor hot
This is not very sensitive or specific for malignancythus, warmor hot nodules still mandate a continued aggressive approach to
work-up- may not really change management Traditionally hot nodules rxed in past with radioactive iodine or
taken to surgery Thyroid scintigraphy has fallen out of favor- definitely questions
about how cost-effective it is for routine evaluation for patientswith nodules
Nelson RL et al. Rectilinear thyroid scanning as a predictor of malignancy. Ann of Intern Med 1978;88:41.Price DC et al. Radioisotopic evaluation of the thyroid and the parathyroid. Radiol Clin North Am 31:967-989.
1993.
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Ultrasound
Provides considerable anatomic information but nofunctional information
Determine the volume of a nodule, multicentricity and
whether it is cystic or solid- often performed beforeFNA
Extremely useful in also following patients beingmanaged conservatively for possible increasing size of
lesion Unable, however, to accurately predict the diagnosis of
solid nodules
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Cystic lesion are reassuring but only 1-5% of totalthyroid nodules
In addition, as many as 25% of well-differentiated
thyroid cancers had cystic components and up to 60-70% of all nodules Physician can correlate the nuclear medicine and u/s
finding and determine the function of the particular
nodule Additional nodules can be found 20-48% of patients Many times the u/s findings differ from the physical
exam, in one retrospective series up to 63% of thetime
Burch HB et al. Evaluation and management of the solid thyroid nodule. Endocrinol Metab ClinNorth Am 24:663-710
Tan GH et al. Thyroid incidentalomas: management approaches to non-palpable nodules discoveredincidentally on thryoid imaging. Ann Intern Med 1997;126:226.
Marqusee E et al. Usefulness of ultrasonography in the management of nodular disease. Ann Intern
Med 1997;126:226.
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Work-up of a Thyroid Nodule
Prevalence and risk factors
H&P
Labs Imaging Modalities
Biopsy
Management Controversial topics
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FNA
Simple, safe office procedure
Tissue sample obtained by 25 gauge needle
With experience adequate sample may be obtained in 90 -97% ofaspirates of solid nodules,
False negative rate (FNA benign but nodule turn out malignant)is 0-5% usually due to sampling error
False positive rates (malignant but turns out benign)
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La Rosa et al. series of 5605 FNA procedures
false negatives in 2.3% and false positives in1.1%. Overall accuracy exceeds 95%.
Euthyroid patients should be evaluated with
FNA as first step per endocrineoften surgeonswill send for u/s first to find out if cystic orsolid
Results- benign (70%), malignant (5%),indeterminate (10%), nondiagnostic (15%)
La Rosa GL et al. Evaluation of the fine needle aspiration biopsy in the preoperative selection ofcold nodules. Cancer 1991;90:967.
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Work-up of a Thyroid Nodule
Prevalence and risk factors
H&P
Labs Imaging Modalities
Biopsy
Management Controversial topics
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FNA results
Malignant- pt needs to have surgicalmanagement
Benign- observation with interval ultrasounds
and clinical examinations Inderminate- radioisotope scan- perform
suppression scan and if cold proceed to surgical
management- if hot nodule consider observation Non diagnostic- repeat FNA or U/S guided
FNA
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Wong CKM, et al. Thyroid nodules: Rational management. World J Surg 24(2000):934-941.
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Work-up of a Thyroid Nodule
Prevalence and risk factors
H&P
Labs Imaging Modalities
Biopsy
Management Controversial topics
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U/S-guided FNA
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Often used after FNA comes back non-diagnostic rather thanrepeating another FNA
Inadequate sampling cited as most common reason for falsenegative rates
Repeat FNA with u/s can decrease nondiagnostic smears from15% to 3%,
May be particularly valuable for smaller nodules
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Routine Calcitonin Screening
Calcitonin screening is advocated in several reports to identifythose with medullary cancer
Italian report- 10,864 patients screened after 1991, 44 (0.4%) hadan elevated calcitonin and ALL had medullary cancer
59% of these patients maintained a full remission of cancer as comparedto 2.7% of patients who were not screened French study only 41% of their patients with elevated calcitonin had
MTC Some false positives as high as 59% -so routine screening remains
controversialElisei et al. Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary
and thyroid cancer: experience in 10,864 patients with nodular thyroid disorders. J of Endocrinol Metab2004;89:163.
Niccoli P et al. Interest of routine measurement of serum calcitonin: study in a large series ofthyroidectomized patients. J Clin Endocrinol MEtab 1997;82:338.
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PET Scans and the Thyroid Nodule
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History56 year old female with a history of papillary thyroidcarcinoma, status post thyroidectomy with risingthyroglobulin level and negative I-131 scan.
Nuclear MedicineIn this particular case, a small normal appearing
jugulodigastric lymph node was found to have FDGuptake and was subsequently resected and found to be
positive for recurrent papillary carcinoma. Courtesy of
Todd Blodgett, MD, University of Pittsburgh MedicalCenter
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PET scan-reflects glucose metabolism of tissuesin vivo
Consensus considers faint homogenous uptakeof FDG by thyroid tissue to be physiologic
Cohen et al. found 102/4250 (2.3%) thyroid
incidentalomasCytology only available in 15 ptsbut 47% werecarcinoma 40% nodular hyperplasia and 1 thyroiditis/1
atypical cellsMcDougall IR et al. Positron emission tomography of the thyroid, with an emphasis on thyroidcancer. Nucl Med Commun 22:485-492.
Cohen MS et al. Risk of malignancy in thyroid incidentalomas identified by fluorodeoxyglucose-
positron emission tomogrpahy. Surgery 130:941-946.
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Adler et al. showed by pooling data that if a peak standarduptake value (SUV)>8 used that successfully able to indentify7/7 thyroid cancers and 31/33 of benign lesions
Others studies show that papillary and follicular carcinoma havesignificantly different SUV values compared to benign nodules
Other studies show that regardless of SUV- malignancy rates arehigh in positive PET scans
However, still not known if PET scans can reliably distinguishbetween benign and malignant disease
Adler LP et al. Positron emission tomography of thyroid masses. Thyroid 3:957-963.
Sasaki M et al. An evaluation of FDG-PET in the detection and differentiation of thyroid tumors.Nucl Commun 18:957-963.
Kim TY. 18F-fluorodeoxyglucose uptake in thyroid from positron emission tomogram (PET) for evaluation incancer patients: high prevalence of malignancy in thyroid PET incidentaloma. Laryngoscope. 2005;115(6):1074-8.
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Never advance anything that cannot be proved in
a simple and decisive fashion. Worship thespirit of criticism. If reduced to itself, it is notan awakener of ideas or a stimulant to great
things, but, without it, everything is fallible; italways has the last word.
-Louis Pasteur 1888 on the opening of the
Pasteur Institute (Paris, France)
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