Transcript Thyroid Cancer

Thyroid Disorders in the Elderly: Does it
Matter
Don Bodenner MD-PhD
Associate Professor
Central Arkansas VAMC, Geriatric
Research Education and Clinical Center
Department of Geriatrics
Reynolds Institute on Aging
Chief, Endocrine Oncology
Director, Thyroid Center
TSH moves opposite of thyroid
hormone levels
pituitary
T4
Brain
Kidney
Muscle
Liver
Skin
Heart
T3
TSH
T4
T3
thyroid
Changes with Aging
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Some decrease in
pituitary/hypothalamic response
Most elderly not clinically significant.
The incidence of hypothyroidism
increases with age
The incidence of hyperthyroidism
increases with age (nodules)
Subclinical Thyroid Disease: Difficult
Cases
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Thyroid levels in the normal range
TSH levels abnormally high or low
No overt clinical signs or symptoms of
thyroid dysfunction
ATA prefers “mild thyroid failure or
dysfunction”
Individual TSH/freeT4 relationship
Normal Ranges:
Individual vs. Group
individual <<group
e.g. free T4
individual  group
e.g. TSH (?)
Clinical Presentation of Hypothyroidism
(all patients)
Scoring system
established in 1969.
Review of utility of
these measures in
1997 (average age
55 years)
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Zulewski JCEM (1997) 82:771
Subclinical Hypothyroidism: prevalence
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Highly dependent upon screening
norms in community and Iodine intake
Geriatric Clinic
Community
Senior Citizen Center
Community
Community
Senior Citizen Center
US
England
US
US
New Zealand
Italy
15 %
17 %
14 %
14 %
4%
0.6 %
Subclinical hypothyroidism: Is it
important
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Homocysteine decreased
Diekman, Clin Endo (2001) 54: 197-204
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subclinical hypothyroidism 2-3 times more frequent
in people with elevated cholesterol
Tanis, Clin Endo (1996) 44: 643-649
Subclinical hypothyroidism: Cardiac
effects
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Rotterdam Study
Population based study
studying chronic disease in
the aging population (>55 at
entry
3105 men, 4878 women
TSH > 4.0 with normal free
thyroxine
Rotterdam Study
1.7
2.3
Hak, A. E. et. al. Ann Intern Med 2000;132:270-278
1.9
2.3
Rotterdam Study
Japan: Ischemic Heart Disease and SCH
2,856 subjects screened for thyroid
dysfunction
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257 with subclinical hyothyroidism TSH > 5
Prior thyroid disease or thyroid hormone
therapy excluded
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Initial screening 1984 to 1987
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10 year follow-up
Japan: Ischemic Heart Disease and SCH
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Ischemic heart disease:
EKG changes consistent with
MI
 Enzyme elevation
 Positive exercise test
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Death as second endpoint
Japan: Ischemic Heart Disease and SCH
Controls (%)
Subclinical
Hypothyroidism (%)
OR (95%
CI)
All subjects
1.3
3.5
2.5
males
1.6
6.8
3.8
females
1.1
1.8
1.8
Japan: Ischemic Heart Disease and SCH
men
Men had significant
increase in all cause
mortality
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Increase trend for
women
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Men had increase in
non-neoplastic related
deaths
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women
Basel Thyroid Study
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66 women with SCH, Randomized to
placebo and titration with T4 until TSH
normalized
Age 57 years (18-75), TSH greater than
5 on two tests
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Total and LDL reduced after T4
Apo B-100 decreased (p<.03)
Billewicz scores improved (p=.02)
Subclinical hypothyroidism: natural
history
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30 patients (24 men, 6 women) referred
with subclinical hypothyroidism
16/30
progressed to frank
hypothyroidism
14/30
remained stably elevated
Kabadi, Arch Intern Med (1993) 153: 957-961
Pathogenic factors leading to
hypothyroidism
Patients
Cause
Previous iodine 131 or subtotal thyroidectomy for
hyperthyroidism
7
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Hashimoto’s (autoimmune thyroiditis)
4
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Radical neck dissection or neck radiation therapy
2
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for malignancy
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Long-term lithium therapy
1
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idiopathic
2
Kabadi, Arch Intern Med (1993) 153: 957-961
Hashimoto’s and
development of
hypothyroidism
30% at five years,
60% at 10 years with
positive antibodies
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Jcem 87:3221
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Who to treat with mild TSH elevations?
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Measure anti-TPO aby, if positive, then
treat. If negative, follow every 6 months
Monitor patients closely every 6
months, with history of neck irradiation,
lithium exposure, radioactive iodine
treatment
Evaluation and treatment of
hypothyroidism
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All patients over the age of 50, screening TSH
Repeat every 5 years with family history. Sooner
with symptoms.
If 5-10, repeat TSH on at least two occasions
Treat for even mild elevations in TSH if indicated
(antibodies, I131, radical neck, radiation
Any hint of CAD, start at 25 mcg/day, increase
every month with TSH measured to normal
Sublcinical Hyperthyroidism
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Very poorly understood
TSH must be suppressed (< .1), not
lower than normal
Common in elderly with multinodular
goiter
Treatment controversial
Hyperthyroidism:Signs and Symptoms
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Nervousness
Fatigue/weakness
Heat Intolerance
Hyperdefecation
Palpitations
Weight
loss/Increase
appetite
Tremor
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Hyperactivity
Lid retraction
Hyperreflexia
Goiter
Opthalmopathy
Localized edema
Menstrual
disturbances
Elderly: Apathetic Thyrotoxicosis
-may present as depression
-apathy, lethargy, pseudo-dementia, extreme
weight loss, are common
-pulse can be minimally elevated
-goiter, heat intolerance, eye signs often
absent
-scan and uptake can be normal
Causes of Subclinical hyperthyroidism
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Subacute thyroiditis
 Viral
induced, self-limiting, hyperthyroidism
followed by hypothyrodism. Uptake very low.
ESR elevated
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Exogenous thyroid hormone
Iodine exposure (IV contrast, kelp, amiodarone)
Graves’
Autonomous nodule or toxic multinodular goiter
TSH vs number
of nodules
Cardiovascular disease and subclinical
hyperthryoidism
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All cause mortality increased 1.8
fold after 5 years of followup
Cardiovascular events increased 2.2
fold
Cerebrovascular events incresed
2.8 fold
Lancet 358:861
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Cardiovascular disease and subclinical
hyperthryoidism
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24 Hour Holter Monitoring after therapy
Increase in atrial premature beats
(p<.001)
Increase in premature ventricular beats
(p<.003)
JCEM 88: 1672
Atrial Fibrillation development with
suppressed TSH
NEJM 331:1249
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Atrial Fibrillation with suppressed TSH
NEJM 331:1249
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Subclinical hyperthyroidism and bone
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Increase in markers of bone resorption
Postmenopausal women
 Loss
of up to 1.8% of bone mass per
year in femoral neck and lumbar spine
 Fracture risk unknown
 Treatment increased BMD at hip and
spine by 1 to 2 % vs a drop of 2 to 5% in
untreated patients
Dementia and subclinical
hyperthyroidism
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Rotterdam study
 1843
participants over age 55
 2 years of follow-up
 TSH level <.4
 Dementia assessed by
 MMSE
< 26,
 Cambridge examination for disorder of elderly
 Examination by neurologist and neyropsychologist
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Exclusions: prior dementia, antithyroid
medications, amiodarone,
Dementia and subclinical
hyperthyroidism (RR, 95% CI)
Total dementia
Alzheimer’s
disease
TSH < .4
3.5
3.5
TSH < .4 with
positive antibodies
23.7
14.3
TSH > 4.0
.5
.6
Evaluation and treatment of subclinical
hyperthyroidism
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Repeat TSH on at least 2 occasions
24 hour radioactive iodine uptake
Thyroid ultrasound
Exclude medications (amiodarone) and
recent IV contrast
Evaluation and treatment of subclinical
hyperthyroidism
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No signs, symptoms, depression or
weight loss
 Monitor
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TSH, free T4 and T3
Signs, symptoms, weight loss or
depression
 Trial
of antithyroid medications or
 I131 ablative therapy
 Surgery rarely required
Thyroid Nodules in the Elderly
•
Nodules are very common
Prevalence: 5% palpation, 50%
autopsy and ultrasound
•
By middle age, half of the
population will have a nodule.
•
The prevalence is much higher in
women
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Trends in Incidence of Thyroid Cancer (1973-2002) and Papillary Tumors by Size (1988-2002) in
the United States
Davies, L. et al. JAMA 2006;295:2164-2167.
On the other hand…..
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Thyroid cancer “uncommon”
In 2001, ACS estimates thyroid cancer 1.5
% of all new cancers
SEER (NCI) estimates prevalence 0.1% of
all Americans
Death even more uncommon, 0.23% of all
cancer deaths, IN THE YOUNG
Everyone does well with thryoid CA
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recurrence
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Age 70 at dx,
40% mortality
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death
Thyroid Cancer:
1. Papillary most common, (> 70%)
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a.) Local invasion
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b.) Good prognosis (10 year survival >90%)
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2. Follicular (15%)
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a.) Invasion into vessels, metastasis more likely
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b.) Good prognosis (10 year survival 65-85%)
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Thyroid Cancer:
Medullary
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a.) Associated with MEN syndromes
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b.) Fair prognosis
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Anaplastic
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a.) Local invasion and distant metastasis
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b.) Fast growing
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c.) Poor prognosis
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Ionizing radiation and thyroid
cancer
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No threshold dose
cancers develop 20-30 years later
50% of patients develop thyroid
abnormalities
15-30% will develop thyroid cancer
earlier the exposure, higher risk of cancer.
Thyroid “Facts”
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Cancer is unlikely in a gland with Hashimoto’s
thyroiditis.
Cancer is less likely in a multinodular goiter.
Its only a cyst.
Bigger nodule, more likely cancer
……
The risk of cancer is almost the same in any
thyroid nodule …. 4 - 6 %
Simple Cyst is always benign
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Uncommon, 1% of all cysts
Complex cysts
 septations
 intracystic
cells or sedimentation
 Risk of thyroid cancer identical to
nodule in a multinodular gland
Size and Malignancy
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NO CORRELATION BETWEEN SIZE
AND PRESENCE OF THYROID CA
Prevalence of thyroid cancer in subcentimeter lesions greater than in
those over one centimeter 1
Prevalence the same (app 6%) as in
clinically apparent solitary thyroid
nodules. 2
1 Leenhardt JCEM 84:24
2 Hagag Thyroid 8:989
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Frequency of Malignancy in MNG
4.7 % vs 4.1%
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Belfiore A et al. Am J Med 1992. 93:363
Thyroid Scan
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Malignant nodules are cold
Benign nodules are cold
 Benign
colloid nodules
 Hashimotos
 Cysts
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Hot nodules rare in the US (app 1%)
Very limited role for scan and uptake in
initial evaluation of thyroid nodule
thyroid cancer in incidental PET positive
thyroid nodules
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Very useful in staging many cancers including thyroid
cancer
Initial reports had incidence of thyroid ca as high as
75%
Author
PET scans
Incidentaloma
Biopsy
Malignancy
Cohen
4525
102 (2.3%)
15
7 (47%)
Kim
4136
45 (1.1%)
32
16 (50%)
Chu
6241
76 (1.2%)
14
4(28%)
140
7 (4.3%)
7
4 (57%)
1285
-
5
5 (100%)
-
8
7
5 (71%)
Yi
Davis
Van den Bruel
FNA: the procedure
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4-8 passes of a 22 or usually 25 gauge needle to
obtain the specimen
20 minutes start to finish
no local anesthetic (expect ice in a plastic bag)
neck tenderness for about 24 hrs afterwards
Among >11000 FNA procedures over 12 years at
Mayo Clinic: no infections, one patient required surgery
for acute tracheal compression after bleeding into the
nodule
FNA: the results
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92-98% predictive values for a result either of a
malignancy or a benign lesion
35-75% reduction on patients undergoing
thyroidectomy
suspicious lesions referred for surgery
about 15-20% of all aspirations yield inadequate
material for diagnosis -- more in MNG (degenerated
or hemorrhagic nodules)
Fine needle aspiration results
Benign
Indeterminant
Malignant
Insufficient
percent of all
fine-needle
aspirations
70%
20%
5%
5-20%
Cytology
appearance
Abundant
colloid:
normal
follicular
cells
Little colloid:
sheets of normal
or atypical
follicular or
Hurthle cells
Cancer cells
present
Not enough
material for
diagnosis
Treatment
no surgery
surgery for cold
or warm nodules
surgery
repeat fine
needle
aspiration
Ultrasound features Indicative of Cancer
% occurrence
RR
specificity
Blurred margin
77
16
87
Intranodal
vascularity
74
14
85
Microcalcificati
ons
29
4.9
96
Papini JCEM 87:1941
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Insufficient Samples
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Take time to read the cytopath report carefully
“negative for cancer” is often used for insufficient
samples
10-15% of nodules with repeatedly insufficient
samples will be malignant
“three strikes and your out”. Incidence
approximates 20 %
The Conundrum…..
Contact Information
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please contact Dr. David Bodenner at
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