Transcript Neoplastic Thyroid Disease - Endocrinology

Neoplastic Thyroid Disease:
Thyroid Nodules, Goiter, and Thyroid
Cancer
Thomas Repas D.O.
Diabetes, Endocrinology and Nutrition Center, Affinity Medical Group, Neenah, Wisconsin
Member, Diabetes Advisory Group, Wisconsin Diabetes Prevention and Control Program
Member, Inpatient Diabetes Management Committee, St. Elizabeth’s 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
– Multinodular
– Diffuse
– Endemic
• Thyroid Cancer
– Well differentiated and poorly differentiated
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
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 autonomous
nodule hyperfunction develop, resulting in
thyrotoxicosis
– Toxic MNG is more common in the elderly
Endemic Goiter
• No longer a problem
in the US and the
developed world
• Still a serious health
concern in parts of
the world with iodine
deficiency including
mountainous areas
or areas with high
rainfall/flooding
Kaplan, E. et al. Thyroid Disease Manager “Surgery of the Thyroid Gland” Chapter 21, May 99
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, and
2.3% of cancers in women in the US
– The annual rate has increased nearly 50% since 1973 to
approximately 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)
Initial Evaluation of a Thyroid
Nodule/Mass
Risk factors for Malignancy
• Solitary thyroid nodules in patients >60
or <30 years of age
• Irradiation of the neck or face during
infancy or teenage years
• Symptoms of pain or pressure
(especially a change in voice)
• Male sex
• Large Nodules (>3 or 4 cm)
• Growth of nodule
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 & Ingbar’s The Thyroid: A Fundamental and
Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.
Castro MR, et al. Endocr Pract. 2003;9:128-136.
Thyroid Ultrasonography
Thyroid Ultrasonography
• Excellent for
characterizing size and
other features of nodule
• Useful in localizing
nodule for FNA
• Cannot distinguish
between benign vs.
malignant
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
RAI imaging
• Formerly had been used extensively in the initial
work up of nodular thyroid disease
FNA is now considered the gold standard
RAI imaging
• The problem:
–
Although “hot” nodules are usually
never cancer, only 5% of all nodules
are hyperfunctioning
–
The remaining 90-95% that are warm
or cold could be cancer and thus
require FNA
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
Thyroid FNA
• Now considered the
most cost effective and
sensitive/specific
diagnostic test of thyroid
nodules
• The use of US has
expanded the role of
FNA in evaluating
nodules and improved
the validity of the results
Thyroid FNA
Possible FNA Results
–
Benign: 70 -75 %
–
Malignant: Up to 5%
–
Suspicious: About 10%
–
Nondiagnostic: About 10 - 20%
Thyroid FNA
Limitations
• False negatives: (< 5% of FNA) more likely in large (>4cm)
or small (<1cm) nodules
• Suspicious FNA (Follicular and Hurhtle cell neoplasm):
cannot distinguish benign vs malignant of hypercellular
nodules by FNA alone, ALWAYS require surgical pathology
for dx (up to 10 – 30% of these will be CA)
• Non-diagnostic results: NEVER consider equivalent to
benign, up to 10% of ND FNA will contain CA on resection
Management and Follow up
Management of Thyroid Nodules
Depends on FNA results (see algorithm)
• Benign:
– False negatives rare, but be cautious in large
(>4cm) or small nodules (<1cm) , repeat US in
6 to 12 months to assess for interval change
– Consider surgical resection if change or
suspicious
• Malignant:
– Surgery and RAI ablation
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
Non-diagnostic FNA
• About 15% of all FNA results
• NEVER consider equivalent to benign
FNA
• Up to 10% of ND FNA will contain CA on
resection
• Be very cautious of a pathology report:
“consistent with benign colloid nodule”; if
limited/no follicular epithelial cells noted,
then this is a ND FNA rather than benign
Non-diagnostic FNA cont’d
Three options:
• Repeat FNA now- may get valid FNA on
repeat up to 30 – 50% of the time
• Follow-up US in 6 months, repeat FNA or
resect then if any interval change
• Surgical resection now- usually reserved
only for patients with history suggestive of
increased risk or patients who are very
anxious and do not want to wait
LT4 Suppression of Thyroid
Nodules
LT4 Suppression of Nodules
• Although once more commonly used, it has
begun to fall out of favor
• Some endocrinologists still recommend LT4
suppression for a TSH between 0.1 – 0.5
• However, studies demonstrate lack of efficacy or
improved outcome
• There is significant risks associated with long
term iatrogenic hyperthyroidism (loss of bone
density, arrhythmias in the elderly, etc.)
LT4 Suppression of Goiter
• Patients with a MNG especially could later
develop an autonomously functioning nodule
with subsequent thyrotoxicosis if not followed
closely
• Is useful for goiter suppression in patients
with subclinical or overt hypothyroidism
• May also have a role in goiter patients with
TSHs in the upper limits of normal (>3.0) who
also have + thyroid autoantibodies
(controversial)
Thyroid Carcinoma
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.
Newly Diagnosed Cancer in the
United States
Hodgkin
Multiple Myeloma
Thyroid Cancer
22 000 new cases
1400 deaths
Thyroid
Kidney
Leukemia
Lymphoma
Colon
Lung
Prostate
Breast
0
50
100
150
200
New Cases, Thousands
250
Cancer facts and figures.
American Cancer Society Web
site. Available at:
http://www.cancer.org/downloads/
STT/CAFF2003PWSecured.pdf.
Accessed December 10, 2003.
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 are
uncommon
• 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.
Papillary Thyroid Cancer
• Most common type
• Makes up about 80% of all
thyroid carcinomas in the United
States
• Females outnumber males 3:1
–
Highest incidence in women in
midlife
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.
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
• <5% of patients have distant metastases at time of
diagnosis
Braverman LE, Utiger RD, eds. Werner & Ingbar’s The 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.
Lung is most common site
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 nodes
Follicular Thyroid
Cancer
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.
Braverman LE, Utiger RD, eds. Werner & Ingbar’s The 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
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
Hebra A, et al. Solitary thyroid nodule. eMedicine Web site. Available at:
mortality http://www.emedicine.com/ped/topic2120.htm.
rate
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 Thyroid
Disease. Monticello, NY:Marcel Dekker, Inc.: 2001;239-241.
Hürthle Cell Cancer
• A variant of follicular
cancer that tends to be
aggressive
• Represents about 3% to
5% of all types of thyroid
cancer
Hürthle Cell Tumor
High power magnification
Aytug S, et al. Hürthle 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 Thyroid
Disease. Monticello, NY: Marcel Dekker, Inc.: 2001:239-241.
Hürthle 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
• Braverman
TendLE,to
be locally invasive
Utiger RD, eds. Werner & Ingbar’s The 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. Endocrine
Tumors. Cambridge, MA: Blackwell; 1993:278-333.
Anaplastic Thyroid Cancer
• Extremely aggressive
and exceptionally
virulent
• Composed wholly or in
part of undifferentiated
cells
Braverman LE, Utiger RD, eds. Werner & Ingbar’s The 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 Medical
Information – Home Edition. 2nd ed. Whitehouse Station, NJ: Merck & Co., Inc.; 2003.
Anaplastic Thyroid Cancer
(Continued)
• Tumor is typically hard, poorly circumscribed,
and fixed to surrounding structures
• Often occurs in the elderly population (mean
age: 65 years)
• 3-fold greater risk in iodine-deficient areas
Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed.
Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.
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 & Ingbar’s The 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
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, or
familial non-MEN medullary
thyroid cancer [median
Braverman
LE, Utiger
RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed.
age=21
years])
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
Metastases
• Cervical lymph node metastases occur early
• Tumors >1.5 cm are likely to metastasize,
often to bone, lungs, liver, and the central
nervous 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.
Primary Thyroid Lymphoma
• A rare type of thyroid
cancer
–
Affects fewer than 1
in 2 million people
• Constitutes 5% of thyroid
malignancies
Large Cell Lymphoma of the Thyroid
Braverman LE, Utiger RD, eds. Werner & Ingbar’s The 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
Characteristics and Diagnosis
• Develops in the setting of pre-existing
lymphocytic thyroiditis
• Often diagnosed because of airway
obstruction 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 & Ingbar’s 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
Thyroid Cancer
Thyroid Cancer Cases
Diagnosed in 2000
(N=18 000 )
Hürthle
4%
Follicular
14%
Anaplastic 1%
Deaths by 2010
(N=1426)
Anaplastic 11%
Hürthle
12%
Papillary
50%
Follicular
27%
Papillary
80%
Robbins R, et al. Adv Intern Med. 2001;46:277-294.
Recurrence and Death After
Diagnosis of Thyroid Cancer
Recurrence
Death
Cumulative, %
40
30
20
10
0
0
N=1355
10
20
30
40
50
Years After Diagnosis
Mazzaferri EL, et al. Am J Med. 1994;97:418-428.
Etiology of Thyroid Cancers
• Usually unknown
• Radiation exposure
–
Medical uses during childhood in the
1950s
–
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.
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 malignant
Alsanea O, et al. Curr Opin Oncol. 2001;13:44-51.
Management and Follow up of Thyroid
Carcinoma
Thyroid Cancer Risk Stratification
Low Risk
Intermediate Risk
High Risk
<45 years
>45 years
Gender
Female
Male
Size
<2 cm
>4 cm
Age
Mixture of
Features
Extent
Intraglandular
Grade
Low
High
Distant
Metastases
Absent
Present
Treated, %
39
39
22
Death Rate, %
<1
13
53
Extraglandular
Shaha AR, et al. Acta Otolaryngol. 2002;122:343-347.
Shaha AR. Cancer Control. 2000;7:240-245.
Thyroid Cancer
Initial Treatment Strategy
Diagnosis of Thyroid Cancer
Low Risk
Lobectomy
Isthmusectomy
Surgery
Intermediate
and High Risk
Total
Thyroidectomy
Shaha AR. Cancer Control. 2000;7:240-245.
Kinder BK. Curr Opin Oncol. 2003;15:71-77.
Thyroid Cancer
Initial Treatment Strategy
Diagnosis of Thyroid Cancer
Low Risk
Surgery
Intermediate
and High Risk
Lobectomy
Isthmusectomy
Total
Thyroidectomy
Physical Exam
Ultrasound
RAI Ablation
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
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
Thyroid Cancer
Total
Thyroidectomy
RAI
Ablation
Suppression
Therapy
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.
1 Year
Whole Body Scan
Tg Assay
Standard Treatment of Thyroid Cancer
Phases of Follow-Up
Phase 1
Determine extent of disease
Treat detectable disease
Initial surgery
RAI ablation
Phase 2
No detectable disease
At risk for recurrence
Whole body scan
Stimulated Tg
Phase 3
Long-term disease-free survivor
Low risk for recurrence
Suppressed Tg assay
TSH assay
T4 assay
Neck examination
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
in Patients With Thyroid Cancer
Normal
Pituitary
TSH
Thyroid Cancer Patients
Pituitary
TSH
-
-
+
+
Thyroid
T4
Minimum LT4 to
suppress TSH
without thyrotoxicosis
Thyroid
T4
Braverman LE, Utiger RD, eds. Werner & Ingbar’s 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
Thyroid Cancer
Optimal TSH
TSH,
mIU/L
Low to
Undetectable
Suppressed but
Detectable
Low Normal
<0.1
0.1 to 0.4
0.5 to 1
• Most patients
• Persistent or
with no
Patients recurrent disease
evidence of
• High-risk patients
disease
• Very lowrisk patients
• Long-term
survivors
Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.
Sherman SI. Lancet. 2003;361:501-511.
Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text.
8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.
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
– TSH and T