Thyroid Disorders in the Elderly: Does it Matter

Don Bodenner MD-PhDAssociate Professor

Central Arkansas VAMC, Geriatric Research Education and Clinical Center

Department of Geriatrics

Reynolds Institute on Aging

Chief, Endocrine Oncology

Director, Thyroid Center

TSH

T4

T3

BrainKidneyMuscleLiverSkinHeart 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 incidence of hypothyroidism

increases with age The incidence of hyperthyroidism

increases with age (nodules)

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”

Individual TSH/freeT4 relationship

Normal Ranges:Individual vs. Group

individual <<groupe.g. free T4

individual groupe.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)

Zulewski JCEM (1997) 82:771

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

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

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

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 TSH > 5 Prior thyroid disease or thyroid hormone

therapy excluded Initial screening 1984 to 1987 10 year follow-up

Japan: Ischemic Heart Disease and SCH

Ischemic heart disease: EKG changes consistent with

MI Enzyme elevation Positive exercise test

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 had significant increase in all cause mortality

Increase trend for women

Men had increase in non-neoplastic related deaths

men

women

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)

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

Pathogenic factors leading to hypothyroidism

Previous iodine 131 or subtotal thyroidectomy for hyperthyroidism7

Hashimoto’s (autoimmune thyroiditis)4

Radical neck dissection or neck radiation therapy2

for malignancy Long-term lithium therapy

1 idiopathic

2

Cause Patients

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

Jcem 87:3221

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

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

Sublcinical Hyperthyroidism

Very poorly understood TSH must be suppressed (< .1), not

lower than normal Common in elderly with multinodular

goiter Treatment controversial

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

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

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

TSH vs number of nodules

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

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

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% 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

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

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

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

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

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

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

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

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. Follicular (15%) a.) Invasion into vessels, metastasis more likely b.) Good prognosis (10 year survival 65-85%)

Thyroid Cancer:

Medullary a.) Associated with MEN syndromes b.) Fair prognosis

Anaplastic a.) Local invasion and distant metastasis b.) Fast growing c.) Poor prognosis

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.

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 %

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

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

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 nodules rare in the US (app 1%)

Very limited role for scan and uptake in initial evaluation of thyroid nodule

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

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

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)

Fine needle aspiration resultsBenign Indeterminant Malignant Insufficient

percent of all 70% 20% 5% 5-20%fine-needle aspirations

Cytology Abundant Little colloid: Cancer cells Not enough appearancecolloid: sheets of normal present material for

normal or atypical diagnosisfollicular follicular orcells Hurthle cells

Treatment no surgery surgery for cold surgery repeat fineor warm nodules needle

aspiration

Ultrasound features Indicative of Cancer

Papini JCEM 87:1941

% occurrence RR specificity

Blurred margin 77 16 87

Intranodal vascularity 74 14 85

Microcalcifications 29 4.9 96

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 %

The Conundrum…..

Contact InformationContact 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

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