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Thomas Repas D.O.
Diabetes, Endocrinology and Nutrition Center, Affinity Medical Group, Neenah, Wisconsin
Member, Diabetes Advisory Group, Wisconsin Diabetes Prevention and Control ProgramMember, Inpatient Diabetes Management Committee, St. Elizabeths Hospital, Appleton, WI
Chairman, Diabetes Steering Committee, AMG/NHP, Appleton, WI
Tuesday March 15, 2005
Website: www.endocrinology-online.com
Neoplastic Thyroid Disease:Thyroid Nodules, Goiter, and Thyroid
Cancer
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Neoplastic Thyroid Disease
Thyroid Nodules
Goiter
Multinodular
Diffuse
Endemic
Thyroid Cancer
Well differentiated and poorly differentiated
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Thyroid Nodular Disease
Thyroid gland nodules are common in the
general population
Palpable nodules occur in approximately 5%of the US population, mainly in women
Most thyroid nodules are benign
Less than 5% are malignant Only 8% to 10% of patients with thyroid nodules
have thyroid cancer
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Multinodular Goiter (MNG)
MNG is an enlarged thyroid gland containing
multiple nodules
The thyroid gland becomes more nodular with
increasing age In MNG, nodules typically vary in size
Most MNGs are asymptomatic
MNG may be toxic or nontoxic
Toxic MNG occurs when multiple sites of autonomousnodule hyperfunction develop, resulting in
thyrotoxicosis
Toxic MNG is more common in the elderly
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Endemic Goiter
No longer a problemin the US and thedeveloped world
Still a serious healthconcern in parts ofthe world with iodinedeficiency includingmountainous areasor areas with highrainfall/flooding
Kaplan, E. et al. Thyro id Disease ManagerSurgery of the Thyroid Gland Chapter 21, May 99
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Thyroid Carcinoma
Incidence Thyroid carcinoma occurs relatively infrequently compared to the
common occurrence of benign thyroid disease
Thyroid cancers account for only 0.74% of cancers among men, and2.3% of cancers in women in the US
The annual rate has increased nearly 50% since 1973 toapproximately 18 000 cases
Thyroid carcinomas (percentage of all US cases) Papillary (80%)
Follicular (about 10%)
Medullary thyroid (5%-10%)
Anaplastic carcinoma (1%-2%)
Primary thyroid lymphomas (rare)
Metastatic from other primary sites (rare)
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Initial Evaluation of a Thyroid
Nodule/Mass
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Risk factors for Malignancy
Solitary thyroid nodules in patients >60
or 3 or 4 cm)
Growth of nodule
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Evaluating Thyroid Nodules
TSH measurement
Ultrasound of the thyroid
Fine needle aspiration
Radioactive iodine imaging
Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.
Braverman LE, Utiger RD, eds. Werner & IngbarsThe Thyroid: A Fundamental and
Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.Castro MR, et al. Endocr Pract. 2003;9:128-136.
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Thyroid Ultrasonography
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Thyroid Ultrasonography
Excellent for
characterizing size and
other features of nodule Useful in localizing
nodule for FNA
Cannot distinguish
between benign vs.
malignant
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Thyroid Ultrasonography
Certain features may suggest greater risk of cancer:
Irregular or poorly defined borders of nodule
Lack of a "halo
Hypo-echogenicity
Evidence of microcalcifications Increased blood flow
Growth and interval change on serial
ultrasounds
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RAI imaging
Formerly had been used extensively in the initial
work up of nodular thyroid disease
FNA is now considered the gold standard
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RAI imaging
The problem:
Although hot nodules are usually
never cancer, only 5% of all nodulesare hyperfunctioning
The remaining 90-95% that are warm
or cold could be cancer and thusrequire FNA
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RAI imaging
Circumstances where RAI imaging may be
useful and indicated:
Suppressed TSH (more likely to have a
autonomously functioning nodule)
Multiple nodules, none dominant Other
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Thyroid FNA
Now considered the
most cost effective and
sensitive/specific
diagnostic test of thyroidnodules
The use of US has
expanded the role of
FNA in evaluatingnodules and improved
the validity of the results
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Thyroid FNA
Possible FNA Results
Benign: 70 -75 %
Malignant: Up to 5%
Suspicious: About 10%
Nondiagnostic: About 10 - 20%
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Thyroid FNA
Limitations
False negatives: (< 5% of FNA) more likely in large (>4cm)
or small (
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Management and Follow up
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Management of Thyroid Nodules
Depends on FNA results (see algorithm)
Benign:
False negatives rare, but be cautious in large(>4cm) or small nodules (
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Suspicious FNA
About 10% of all FNA results
CANNOT distinguish benign vs malignant
of hypercellular nodules (follicular/Hurthle
cell) by FNA alone
ALWAYS require surgical resection for dx
Up to 10 30% of these will be malignant
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Non-diagnostic FNA
About 15% of all FNA results
NEVER consider equivalent to benignFNA
Up to 10% of ND FNA will contain CA onresection
Be very cautious of a pathology report:
consistent with benign colloid nodule; iflimited/no follicular epithelial cells noted,then this is a ND FNA rather than benign
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Non-diagnostic FNA contd
Three options:
Repeat FNA now- may get valid FNA onrepeat up to 30 50% of the time
Follow-up US in 6 months, repeat FNA orresect then if any interval change
Surgical resection now- usually reserved
only for patients with history suggestive ofincreased risk or patients who are veryanxious and do not want to wait
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LT4 Suppression of Thyroid
Nodules
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LT4 Suppression of Nodules
Although once more commonly used, it hasbegun to fall out of favor
Some endocrinologists still recommend LT4suppression for a TSH between 0.1 0.5
However, studies demonstrate lack of efficacy orimproved outcome
There is significant risks associated with longterm iatrogenic hyperthyroidism (loss of bonedensity, arrhythmias in the elderly, etc.)
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LT4 Suppression of Goiter
Patients with a MNG especially could laterdevelop an autonomously functioning nodulewith subsequent thyrotoxicosis if not followed
closely
Is useful for goiter suppression in patientswith subclinical or overt hypothyroidism
May also have a role in goiter patients withTSHs in the upper limits of normal (>3.0) whoalso have + thyroid autoantibodies(controversial)
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Thyroid Carcinoma
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Typical Presentation of
Thyroid Cancer
Painless lump
Normal thyroid function tests
Found on routine examination or by the patient
Slow growth or no growth over several months
Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.
Thyroid Disease Manager Web site. Available at:
http://www.thyroidmanager.org. Accessed December 10, 2003.Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.
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Newly Diagnosed Cancer in the
United States
Breast
Prostate
Lung
Colon
Lymphoma
Leukemia
Kidney
Thyroid
Multiple Myeloma
Hodgkin
0 50 100 150 200 250
Thyroid Cancer
22 000 new cases
1400 deaths
Cancer facts and figures.
American Cancer Society Web
site. Available at:
http://www.cancer.org/downloads/
STT/CAFF2003PWSecured.pdf.Accessed December 10, 2003.New Cases, Thousands
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Types of Thyroid Cancer
Papillary (80%-85%): develops from thyroid follicle cells in
1 or both lobes; grows slowly but can spread
Follicular (5%-10%): common in countries with insufficient
iodine consumption; lymph node metastases areuncommon
Medullary: develops from C-cells, can spread quickly;
sporadic and familial types
Anaplastic: develops from existing papillary or follicular
cancers; aggressive, usually fatal
Lymphoma: develops from lymphocytes; uncommon
Detailed guide: thyroid cancer. American Cancer Society Web site. Available at:http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=43. Accessed December 10, 2003.
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Papillary Thyroid Cancer
Most common type
Makes up about 80% of all
thyroid carcinomas in the UnitedStates
Females outnumber males 3:1
Highest incidence in women inmidlife
Detailed guide: thyroid cancer. American Cancer Society Web site. Available at:
http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=43. Accessed December 10, 2003.
Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org.Accessed December 10, 2003.
P ill Th id C
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Papillary Thyroid Cancer
Characteristics
Unencapsulated tumor nodule with ill-defined
margins
Tumor typically firm and solid
May present as nodal enlargement
Commonly metastasizes to neck and mediastinal
lymph nodes
40% to 60% in adults and 90% in children
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Follicular Thyroid Cancer
Second most common type
of thyroid cancer
Solid invasive tumors,
usually solitary and
encapsulated
Usually stays in the thyroid
gland, but can spread to the
bones, lungs, and central
nervous system Usually does not spread to
the lymph nodesThyroid gland disorders. Beers MH, Fletcher AJ, Jones TV, et al, eds. Merck Manual of Medical Information
Home Edition. 2nd ed. Whitehouse Station, NJ: Merck & Co., Inc.; 2003.
Braverman LE, Utiger RD, eds. Werner & IngbarsThe Thyroid: A Fundamental and Clinical Text. 8th ed.
Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org. Accessed December 10, 2003.
Follicular Thyroid
Cancer
F lli l Th id C
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Follicular Thyroid Cancer
Diagnosis and Prognosis
Most FTCs present as an asymptomatic
neck mass
If caught early, this type of thyroid cancer
is often curable
Tumors >3 cm have a much higher
mortality rateHebra A, et al. Solitary thyroid nodule. eMedicine Web site. Available at:http://www.emedicine.com/ped/topic2120.htm. Accessed December 10, 2003.
Thyroid gland disorders. Beers MH, Fletcher AJ, Jones TV, et al, eds. Merck Manual of Medical
Information Home Edition. 2nd ed. Whitehouse Station, NJ: Merck & Co., Inc.; 2003.
DeGroot LJ, et al. J Clin Endocrinol Metab. 1990;71:414-424.
Kloos RT, Mazzaferri E. Thyroid carcinoma. In: Cooper DS, ed. Medical Management of ThyroidDisease. Monticello, NY:Marcel Dekker, Inc.: 2001;239-241.
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Hrthle Cell Cancer
A variant of follicular
cancer that tends to be
aggressive
Represents about 3% to
5% of all types of thyroid
cancer High power magnification
Hrthle Cell Tumor
Aytug S, et al. Hrthle cell carcinoma. eMedicine Web site. Available at:
http://www.emedicine.com/med/topic1045.htm. Accessed December 10, 2003.
Kloos RT, Mazzaferri E. Thyroid carcinoma. In: Cooper DS, ed. Medical Management of ThyroidDisease. Monticello, NY: Marcel Dekker, Inc.: 2001:239-241.
H thl C ll C
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Hrthle Cell Cancer
Prognosis
May be benign or malignant, based on
demonstration of vascular or capsular
invasion
Malignancies tend to have a worse
prognosis than other follicular tumors
and rarely respond to 131I therapy
Tend to be locally invasiveBraverman LE, Utiger RD, eds. Werner & IngbarsThe Thyroid: A Fundamental and Clinical Text. 8th ed.
Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.
Mazzaferri EL. Thyroid carcinoma: papillary and follicular. In: Mazzaferri, EL, Samaan N, eds. EndocrineTumors. Cambridge, MA: Blackwell; 1993:278-333.
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Anaplastic Thyroid Cancer
Extremely aggressive
and exceptionally
virulent Composed wholly or in
part of undifferentiated
cells
Braverman LE, Utiger RD, eds. Werner & IngbarsThe Thyroid: A Fundamental and Clinical Text. 8th ed.
Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.
Sherman SI. Lancet. 2003;361:501-511.
Thyroid gland disorders. Beers MH, Fletcher AJ, Jones TV, et al, eds. Merck Manual of MedicalInformation Home Edition. 2nd ed. Whitehouse Station, NJ: Merck & Co., Inc.; 2003.
Anaplastic Th roid Cancer
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Anaplastic Thyroid Cancer
(Continued)
Tumor is typically hard, poorly circumscribed,
and fixed to surrounding structures
Often occurs in the elderly population (meanage: 65 years)
3-fold greater risk in iodine-deficient areas
Braverman LE, Utiger RD, eds. Werner & IngbarsThe Thyroid: A Fundamental and Clinical Text. 8th ed.Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.
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Medullary Thyroid Cancer
Tumor arising from the
calcitonin-secreting C-cells
of the thyroid gland
Mortality rate of 10% to
20% at 10 years Medullary (C-cell)Carcinoma
Braverman LE, Utiger RD, eds. Werner & IngbarsThe Thyroid: A Fundamental and Clinical Text. 8th ed.
Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.
Sherman SI. Lancet. 2003;361:501-511.
Types of thyroid cancer. Virginia Masen Medical Center Web site. Available at:http://www.vmmc.org/dbCancer/sec180604.htm. Accessed December 10, 2003.
Medullary Thyroid Cancer
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Medullary Thyroid Cancer
Types
70% to 80% of cases are
sporadic disease
(median age=51 years)
20% to 30% are part of 3
familial autosomal
dominant syndromes
(MEN-2A, MEN-2B, orfamilial non-MEN medullary
thyroid cancer [median
age=21 years])Braverman LE, Utiger RD, eds. Werner & IngbarsThe Thyroid: A Fundamental and Clinical Text. 8th ed.Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.
Thyroid Cancer Detailed Guide. American Cancer Society Web site. Available at:http://documents.cancer.org/196.00/196.00.pdf. Accessed December 10, 2003.
Medullary Thyroid Cancer
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Medullary Thyroid Cancer
Metastases
Cervical lymph node metastases occur early
Tumors >1.5 cm are likely to metastasize,
often to bone, lungs, liver, and the centralnervous system
Metastases usually contain calcitonin and
stain for amyloid
Types of thyroid cancer. Virginia Masen Medical Center Web site. Available at:
http://www.vmmc.org/dbCancer/sec180604.htm. Accessed December 10, 2003.
Thyroid gland disorders. Beers MH, Fletcher AJ, Jones TV, et al, eds. Merck Manual of Medical Information
Home Edition. 2nd ed. Whitehouse Station, NJ: Merck & Co., Inc.; 2003.
Thyroid Cancer Detailed Guide. American Cancer Society Web site. Available at:http://documents.cancer.org/196.00/196.00.pdf. Accessed December 10, 2003.
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Primary Thyroid Lymphoma
A rare type of thyroid
cancer
Affects fewer than 1in 2 million people
Constitutes 5% of thyroid
malignancies
Large Cell Lymphoma of the Thyroid
Braverman LE, Utiger RD, eds. Werner & IngbarsThe Thyroid: A Fundamental and Clinical Text.
8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.
Cabanillas F. Thyroid lymphoma. eMedicine Web site. Available at:http://www.emedicine.com/med/topic2271.htm. Accessed December 10, 2003.
Primary Thyroid Lymphoma
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Primary Thyroid Lymphoma
Characteristics and Diagnosis
Develops in the setting of pre-existing
lymphocytic thyroiditis
Often diagnosed because of airwayobstruction symptoms
Tumors are firm, fleshy, and usually pale
Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org.
Accessed December 10, 2003.
Braverman LE, Utiger RD, eds. Werner & Ingbars The Thyroid: A Fundamental and
Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.Ansell SM, et al. Semin Oncol. 1999;26:316-323.
Newly Detected and Fatal Cases of
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Thyroid Cancer Cases
Diagnosed in 2000
(N=18 000 )
Deaths by 2010
(N=1426)
Papillary
80%
Follicular
14%
Anaplastic 1%Hrthle4% Papillary
50%
Follicular
27%
Anaplastic 11%
Hrthle
12%
Newly Detected and Fatal Cases of
Thyroid Cancer
Robbins R, et al.Adv Intern Med. 2001;46:277-294.
R d D th Aft
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Recurrence and Death After
Diagnosis of Thyroid Cancer
0
10
20
30
40
0 10 20 30 40 50
Years After Diagnosis
Cumulative,
%
Recurrence
Death
Mazzaferri EL, et al.Am J Med. 1994;97:418-428.
N=1355
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Etiology of Thyroid Cancers
Usually unknown
Radiation exposure
Medical uses during childhood in the1950s
Current medical uses in cancer
therapy
Nuclear accidents
Ron E, et al. Radiat Res. 1995;141:259-277.Tuttle RM, et al.Semin Nucl Med. 2000;30:133-140.
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Genetic Basis of Thyroid Cancer
Papillary and follicular thyroid cancer
Usually sporadic
Approximately 5% of patients have
other family members with thyroid
cancer
Rare genetic syndromes in which
thyroid cancer is associated with
other benign and malignantAlsanea O, et al. Curr Opin Oncol. 2001;13:44-51.
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Management and Follow up of Thyroid
Carcinoma
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Thyroid Cancer Risk Stratification
4 cm
Extraglandular
High
Present
Low Risk High RiskIntermediate Risk
Mixture of
Features
Shaha AR, et al.Acta Otolaryngol. 2002;122:343-347.Shaha AR. Cancer Control. 2000;7:240-245.
Age
Gender
Size
Extent
Grade
Distant
Metastases
Treated, %
Death Rate, %
39
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Surgery
Total
Thyroidectomy
Lobectomy
Isthmusectomy
Intermediate
and High RiskLow Risk
Diagnosis of Thyroid Cancer
Shaha AR. Cancer Control. 2000;7:240-245.Kinder BK. Curr Opin Oncol. 2003;15:71-77.
Thyroid Cancer
Initial Treatment Strategy
Th roid Cancer
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RAI AblationPhysical Exam
Ultrasound
Thyroid Cancer
Initial Treatment Strategy
Surgery
Total
Thyroidectomy
Lobectomy
Isthmusectomy
Intermediateand High RiskLow Risk
Diagnosis of Thyroid Cancer
Kinder BK. Curr Opin Oncol. 2003;15):71-77.
Sherman SI. Lancet. 2003;361:501-511.Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.
Treatment of Thyroid Cancer With
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Treatment of Thyroid Cancer With
Radioactive Iodine
Destroys remnants of normal thyroid tissue
Destroys thyroid cancer cells Identifies distant metastases
Maximizes sensitivity and specificity of
serum thyroglobulin
Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.Cohen EG, et al. Otolaryngol Clin North Am. 2003;36:129-157.
Standard Treatment of
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Standard Treatment of
Thyroid Cancer
Whole Body Scan
Tg Assay
Suppression
Therapy
Total
Thyroidectomy
1 Year
RAI
Ablation
Cohen EG, et al. Otolaryngol Clin North Am. 2003;36:129-157.
Mazzaferri EL, et al. J Clin Endocrinol Metab. 2003;88:1433-1441.
Sherman SI. Lancet. 2003;361:501-511.
Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.Mazzaferri EL, et al. Endocr Relat Cancer. 2002;9(4):227-247.
Standard Treatment of Thyroid Cancer
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Standard Treatment of Thyroid Cancer
Phases of Follow-Up
Initial surgery
RAI ablation
Whole body scan
Stimulated Tg
Suppressed Tg assayTSH assay
T4 assay
Neck examination
Phase 1Determine extent of disease
Treat detectable disease
Phase 2No detectable diseaseAt risk for recurrence
Phase 3Long-term disease-free survivor
Low risk for recurrence
Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.Cohen EG, et al. Otolaryngol Clin North Am. 2003;36:129-157.
Thyroid Stimulating Hormone Suppression
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Thyroid Stimulating Hormone Suppression
in Patients With Thyroid Cancer
Pituitary
TSH
ThyroidT4
-
+
Pituitary
TSH
ThyroidT4
-
+
Normal Thyroid Cancer Patients
Minimum LT4 to
suppress TSH
without thyrotoxicosisBraverman LE, Utiger RD, eds. Werner & Ingbars The Thyroid: A Fundamental and
Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.
Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.Sherman SI. Lancet. 2003;361:501-511.
Target TSH Suppression in Patients With
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Target TSH Suppression in Patients With
Thyroid Cancer
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Treatment of Thyroid Cancer
Summary
Papillary and follicular thyroid cancer Generally excellent prognosis
Risk for recurrence for as long as 30 years
Initial management Surgery and radioactive iodine
LT4 suppressive therapy Follow-up
Physical examination
Radioactive iodine scans
Serum Tg