Thyroid Disorders in the Elderly: Does it
Matter
Don Bodenner MD-PhD
Associate Professor
Central Arkansas VAMC, Geriatric
...
TSH
T4
T3
Brain
Kidney
Muscle
Liver
Skin
Heart thyroid
pituitary
T4
T3
TSH moves opposite of thyroid
hormone levels
Changes with Aging
 Some decrease in
pituitary/hypothalamic response
 Most elderly not clinically significant.
 The inc...
Subclinical Thyroid Disease: Difficult
Cases
 Thyroid levels in the normal range
 TSH levels abnormally high or low
 No...
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 me...
Subclinical Hypothyroidism: prevalence
 Geriatric Clinic US 15 %
 Community England 17 %
 Senior Citizen Center US 14 %...
Subclinical hypothyroidism: Is it
important
 Homocysteine decreased
Diekman, Clin Endo (2001) 54: 197-204
 subclinical h...
Subclinical hypothyroidism: Cardiac
effects
 Rotterdam Study
Population based study
studying chronic disease in
the agin...
Rotterdam Study
Hak, A. E. et. al. Ann Intern Med 2000;132:270-278
1.7 1.9
2.3 2.3
Rotterdam Study
Japan: Ischemic Heart Disease and SCH
2,856 subjects screened for thyroid
dysfunction
257 with subclinical hyothyroidism...
Japan: Ischemic Heart Disease and SCH
 Ischemic heart disease:
 EKG changes consistent with
MI
 Enzyme elevation
 Posi...
Japan: Ischemic Heart Disease and SCH
Controls (%) Subclinical
Hypothyroidism (%)
OR (95%
CI)
All subjects 1.3 3.5 2.5
mal...
Japan: Ischemic Heart Disease and SCH
Men had significant
increase in all cause
mortality
Increase trend for
women
Men ...
Basel Thyroid Study
 66 women with SCH, Randomized to
placebo and titration with T4 until TSH
normalized
 Age 57 years (...
Subclinical hypothyroidism: natural
history
 30 patients (24 men, 6 women) referred
with subclinical hypothyroidism
Kabad...
Pathogenic factors leading to
hypothyroidism
 Previous iodine 131 or subtotal thyroidectomy for
hyperthyroidism 7
 Hashi...
Hashimoto’s and
development of
hypothyroidism
30% at five years,
60% at 10 years with
positive antibodies
Jcem 87:3221
Who to treat with mild TSH elevations?
 Measure anti-TPO aby, if positive, then
treat. If negative, follow every 6 months...
Evaluation and treatment of
hypothyroidism
 All patients over the age of 50, screening TSH
 Repeat every 5 years with fa...
Sublcinical Hyperthyroidism
 Very poorly understood
 TSH must be suppressed (< .1), not
lower than normal
 Common in el...
Hyperthyroidism:Signs and Symptoms
 Nervousness
 Fatigue/weakness
 Heat Intolerance
 Hyperdefecation
 Palpitations
 ...
Elderly: Apathetic Thyrotoxicosis
-may present as depression
-apathy, lethargy, pseudo-dementia, extreme
weight loss, are ...
 Subacute thyroiditis
 Viral induced, self-limiting, hyperthyroidism
followed by hypothyrodism. Uptake very low.
ESR ele...
TSH vs number
of nodules
Cardiovascular disease and subclinical
hyperthryoidism
 All cause mortality increased 1.8
fold after 5 years of followup
...
 24 Hour Holter Monitoring after therapy
Increase in atrial premature beats
(p<.001)
Increase in premature ventricular ...
Atrial Fibrillation development with
suppressed TSH
NEJM 331:1249
Atrial Fibrillation with suppressed TSH
NEJM 331:1249
Subclinical hyperthyroidism and bone
 Increase in markers of bone resorption
 Postmenopausal women
 Loss of up to 1.8% ...
 Rotterdam study
 1843 participants over age 55
 2 years of follow-up
 TSH level <.4
 Dementia assessed by
 MMSE < 2...
Dementia and subclinical
hyperthyroidism (RR, 95% CI)
Total dementia
Alzheimer’s
disease
TSH < .4 3.5 3.5
TSH < .4 with
po...
Evaluation and treatment of subclinical
hyperthyroidism
 Repeat TSH on at least 2 occasions
 24 hour radioactive iodine ...
Evaluation and treatment of subclinical
hyperthyroidism
 No signs, symptoms, depression or
weight loss
 Monitor TSH, fre...
Thyroid Nodules in the Elderly
•Nodules are very common
•Prevalence: 5% palpation, 50%
autopsy and ultrasound
•By middle a...
Davies, L. et al. JAMA 2006;295:2164-2167.
Trends in Incidence of Thyroid Cancer (1973-2002) and Papillary Tumors by Size ...
On the other hand…..
 Thyroid cancer “uncommon”
 In 2001, ACS estimates thyroid cancer 1.5
% of all new cancers
 SEER (...
Everyone does well with thryoid CA
recurrence
death
Age 70 at dx,
40% mortality
Thyroid Cancer:
1. Papillary most common, (> 70%)
 a.) Local invasion
 b.) Good prognosis (10 year survival >90%)
2. F...
Thyroid Cancer:
Medullary
 a.) Associated with MEN syndromes
 b.) Fair prognosis
Anaplastic
 a.) Local invasion and d...
Ionizing radiation and thyroid
cancer
 No threshold dose
 cancers develop 20-30 years later
 50% of patients develop th...
Thyroid “Facts”
 Cancer is unlikely in a gland with Hashimoto’s
thyroiditis.
 Cancer is less likely in a multinodular go...
Simple Cyst is always benign
 Uncommon, 1% of all cysts
 Complex cysts
 septations
 intracystic cells or sedimentation...
Size and Malignancy
 NO CORRELATION BETWEEN SIZE
AND PRESENCE OF THYROID CA
 Prevalence of thyroid cancer in sub-
centim...
Frequency of Malignancy in MNG
Belfiore A et al. Am J Med 1992. 93:363
4.7 % vs 4.1%
Thyroid Scan
 Malignant nodules are cold
 Benign nodules are cold
 Benign colloid nodules
 Hashimotos
 Cysts
 Hot no...
Author PET scans Incidentaloma Biopsy Malignancy
Cohen 4525 102 (2.3%) 15 7 (47%)
Kim 4136 45 (1.1%) 32 16 (50%)
Chu 6241 ...
FNA: the procedure
 4-8 passes of a 22 or usually 25 gauge needle to
obtain the specimen
 20 minutes start to finish
 n...
FNA: the results
 92-98% predictive values for a result either of a
malignancy or a benign lesion
 35-75% reduction on p...
Fine needle aspiration results
Benign Indeterminant Malignant Insufficient
percent of all 70% 20% 5% 5-20%
fine-needle
asp...
Ultrasound features Indicative of Cancer
Papini JCEM 87:1941
% occurrence RR specificity
Blurred margin 77 16 87
Intranod...
Insufficient Samples
 Take time to read the cytopath report carefully
 “negative for cancer” is often used for insuffici...
The Conundrum…..
Contact Information
 For any questions about this audio conference
please contact Dr. David Bodenner at
bodennerdonald@ua...
Ionizing radiation and thyroid cancer
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  • Ionizing radiation and thyroid cancer

    1. 1. 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
    2. 2. TSH T4 T3 Brain Kidney Muscle Liver Skin Heart thyroid pituitary T4 T3 TSH moves opposite of thyroid hormone levels
    3. 3. Changes with Aging  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)
    4. 4. Subclinical Thyroid Disease: Difficult Cases  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”
    5. 5. Individual TSH/freeT4 relationship
    6. 6. Normal Ranges: Individual vs. Group individual <<group e.g. free T4 individual  group e.g. TSH (?)
    7. 7. Clinical Presentation of Hypothyroidism (all patients) Scoring system established in 1969. Review of utility of these measures in 1997 (average age 55 years) Zulewski JCEM (1997) 82:771
    8. 8. Subclinical Hypothyroidism: prevalence  Geriatric Clinic US 15 %  Community England 17 %  Senior Citizen Center US 14 %  Community US 14 %  Community New Zealand 4 %  Senior Citizen Center Italy 0.6 %  Highly dependent upon screening norms in community and Iodine intake
    9. 9. Subclinical hypothyroidism: Is it important  Homocysteine decreased Diekman, Clin Endo (2001) 54: 197-204  subclinical hypothyroidism 2-3 times more frequent in people with elevated cholesterol Tanis, Clin Endo (1996) 44: 643-649
    10. 10. Subclinical hypothyroidism: Cardiac effects  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
    11. 11. Rotterdam Study Hak, A. E. et. al. Ann Intern Med 2000;132:270-278 1.7 1.9 2.3 2.3
    12. 12. Rotterdam Study
    13. 13. Japan: Ischemic Heart Disease and SCH 2,856 subjects screened for thyroid dysfunction 257 with subclinical hyothyroidism TSH > 5 Prior thyroid disease or thyroid hormone therapy excluded Initial screening 1984 to 1987 10 year follow-up
    14. 14. Japan: Ischemic Heart Disease and SCH  Ischemic heart disease:  EKG changes consistent with MI  Enzyme elevation  Positive exercise test  Death as second endpoint
    15. 15. 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
    16. 16. Japan: Ischemic Heart Disease and SCH Men had significant increase in all cause mortality Increase trend for women Men had increase in non-neoplastic related deaths men women
    17. 17. Basel Thyroid Study  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  Total and LDL reduced after T4  Apo B-100 decreased (p<.03)  Billewicz scores improved (p=.02)
    18. 18. Subclinical hypothyroidism: natural history  30 patients (24 men, 6 women) referred with subclinical hypothyroidism Kabadi, Arch Intern Med (1993) 153: 957-961 16/30 progressed to frank hypothyroidism 14/30 remained stably elevated
    19. 19. Pathogenic factors leading to hypothyroidism  Previous iodine 131 or subtotal thyroidectomy for hyperthyroidism 7  Hashimoto’s (autoimmune thyroiditis) 4  Radical neck dissection or neck radiation therapy 2 for malignancy  Long-term lithium therapy 1  idiopathic 2 Cause Patients Kabadi, Arch Intern Med (1993) 153: 957-961
    20. 20. Hashimoto’s and development of hypothyroidism 30% at five years, 60% at 10 years with positive antibodies Jcem 87:3221
    21. 21. Who to treat with mild TSH elevations?  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
    22. 22. Evaluation and treatment of hypothyroidism  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
    23. 23. Sublcinical Hyperthyroidism  Very poorly understood  TSH must be suppressed (< .1), not lower than normal  Common in elderly with multinodular goiter  Treatment controversial
    24. 24. Hyperthyroidism:Signs and Symptoms  Nervousness  Fatigue/weakness  Heat Intolerance  Hyperdefecation  Palpitations  Weight loss/Increase appetite  Tremor  Hyperactivity  Lid retraction  Hyperreflexia  Goiter  Opthalmopathy  Localized edema  Menstrual disturbances
    25. 25. 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
    26. 26.  Subacute thyroiditis  Viral induced, self-limiting, hyperthyroidism followed by hypothyrodism. Uptake very low. ESR elevated  Exogenous thyroid hormone  Iodine exposure (IV contrast, kelp, amiodarone)  Graves’  Autonomous nodule or toxic multinodular goiter Causes of Subclinical hyperthyroidism
    27. 27. TSH vs number of nodules
    28. 28. Cardiovascular disease and subclinical hyperthryoidism  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
    29. 29.  24 Hour Holter Monitoring after therapy Increase in atrial premature beats (p<.001) Increase in premature ventricular beats (p<.003) Cardiovascular disease and subclinical hyperthryoidism JCEM 88: 1672
    30. 30. Atrial Fibrillation development with suppressed TSH NEJM 331:1249
    31. 31. Atrial Fibrillation with suppressed TSH NEJM 331:1249
    32. 32. Subclinical hyperthyroidism and bone  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
    33. 33.  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  Exclusions: prior dementia, antithyroid medications, amiodarone, Dementia and subclinical hyperthyroidism
    34. 34. 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
    35. 35. Evaluation and treatment of subclinical hyperthyroidism  Repeat TSH on at least 2 occasions  24 hour radioactive iodine uptake  Thyroid ultrasound  Exclude medications (amiodarone) and recent IV contrast
    36. 36. Evaluation and treatment of subclinical hyperthyroidism  No signs, symptoms, depression or weight loss  Monitor TSH, free T4 and T3  Signs, symptoms, weight loss or depression  Trial of antithyroid medications or  I131 ablative therapy  Surgery rarely required
    37. 37. 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
    38. 38. Davies, L. et al. JAMA 2006;295:2164-2167. Trends in Incidence of Thyroid Cancer (1973-2002) and Papillary Tumors by Size (1988-2002) in the United States
    39. 39. On the other hand…..  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
    40. 40. Everyone does well with thryoid CA recurrence death Age 70 at dx, 40% mortality
    41. 41. Thyroid Cancer: 1. Papillary most common, (> 70%)  a.) Local invasion  b.) Good prognosis (10 year survival >90%) 2. Follicular (15%)  a.) Invasion into vessels, metastasis more likely  b.) Good prognosis (10 year survival 65-85%)
    42. 42. Thyroid Cancer: Medullary  a.) Associated with MEN syndromes  b.) Fair prognosis Anaplastic  a.) Local invasion and distant metastasis  b.) Fast growing  c.) Poor prognosis
    43. 43. Ionizing radiation and thyroid cancer  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.
    44. 44. Thyroid “Facts”  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 %
    45. 45. Simple Cyst is always benign  Uncommon, 1% of all cysts  Complex cysts  septations  intracystic cells or sedimentation  Risk of thyroid cancer identical to nodule in a multinodular gland
    46. 46. Size and Malignancy  NO CORRELATION BETWEEN SIZE AND PRESENCE OF THYROID CA  Prevalence of thyroid cancer in sub- centimeter 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
    47. 47. Frequency of Malignancy in MNG Belfiore A et al. Am J Med 1992. 93:363 4.7 % vs 4.1%
    48. 48. Thyroid Scan  Malignant nodules are cold  Benign nodules are cold  Benign colloid nodules  Hashimotos  Cysts  Hot nodules rare in the US (app 1%) Very limited role for scan and uptake in initial evaluation of thyroid nodule
    49. 49. 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%) Yi 140 7 (4.3%) 7 4 (57%) Davis 1285 - 5 5 (100%) Van den Bruel - 8 7 5 (71%)  Very useful in staging many cancers including thyroid cancer  Initial reports had incidence of thyroid ca as high as 75% thyroid cancer in incidental PET positive thyroid nodules
    50. 50. FNA: the procedure  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
    51. 51. FNA: the results  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)
    52. 52. Fine needle aspiration results Benign Indeterminant Malignant Insufficient percent of all 70% 20% 5% 5-20% fine-needle aspirations Cytology Abundant Little colloid: Cancer cells Not enough appearance colloid: sheets of normal present material for normal or atypical diagnosis follicular follicular or cells Hurthle cells Treatment no surgery surgery for cold surgery repeat fine or warm nodules needle aspiration
    53. 53. Ultrasound features Indicative of Cancer Papini JCEM 87:1941 % occurrence RR specificity Blurred margin 77 16 87 Intranodal vascularity 74 14 85 Microcalcificati ons 29 4.9 96
    54. 54. Insufficient Samples  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 %
    55. 55. The Conundrum…..
    56. 56. Contact Information  For any questions about this audio conference please contact Dr. David Bodenner at bodennerdonald@uams.edu  For any questions about the monthly GRECC Audio Conference Series please contact Tim Foley at tim.foley@va.gov or call (734) 222- 4328  To evaluate this conference for CE credit please obtain a ‘Satellite Registration’ form and a ‘Faculty Evaluation’ form from the Satellite Coordinator at you facility. The forms must be mailed to EES within 2 weeks of the broadcast

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