Thyroid Disorders in Older Adults · Thyroid Disorders in Older Adults Alvin M. Matsumoto, M.D. Professor, Department of Medicine Acting Head, Division of Gerontology & Geriatric

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Thyroid Disorders in Older Adults

Alvin M. Matsumoto, M.D.

Professor, Department of Medicine

Acting Head, Division of Gerontology & Geriatric Medicine

University of Washington School of Medicine

Geriatric Research, Education and Clinical Center

V.A. Puget Sound Health Care System

Seattle, WA

Geriatric Health Series

May 13, 2014Matsumoto 05/13/14

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Thyroid Disorders in Older AdultsClinical Presentation and Diagnosis

• Atypical, nonspecific

– Cognition, depression, falls, function

• Multiple co-morbidities

– Alter presentation, mask or mimic thyroid disease

• Symptoms attributed to “old age”

• Diagnosis difficult

– Rely on thyroid function tests (TFTs)

– TFTs misleading with non-thyroidal illness (NTI)

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Thyroid (Matsumoto), NWGEC Spring 2014 1

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Thyroid Disorders in Older AdultsTreatment and Prognosis

• Clearance and sensitivity– Start low/go slow, replacement dose

• Co-morbidities– Compromised thyroid dose (e.g. angina)

– Worsened by inappropriate treatment (e.g. osteoporosis, mood, cognition)

– Predispose to drug interaction, poor compliance

• Prognosis– Worse for well-differentiated thyroid cancer

– Lymphoma, anaplastic cancer more common

– Affected by co-morbid illnesses

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Clinical Evaluation of Thyroid Disease

• Function

– Hyperthyroid, hypothyroid or euthyroid?

– Non-thyroidal illness (sick euthyroid)?

– Clinical, TSH and free T4

• Anatomy

– Normal?

– Goiter (enlargement)?

• Diffuse or multinodular

– Solitary nodule?

• Benign or malignant

• Age may modify presentation and management

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Physiology

TRH

TSH

T4

T3

rT3

T2’s

5’-deiodinase

+

+

Hypothalamus

Pituitary

Thyroid

99.97%

bound

99.7%

bound

Iodine

free T4Matsumoto 05/13/14

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Physiology: Age-Related Changes

TRH

TSH

T4

T3

rT3

T2’s

5’-deiodinase

+

+

Hypothalamus

Pituitary

Thyroid

99.97%

bound

99.7%

bound

Iodine



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Non-Thyroidal Illness (NTI): Effects on TFTs

TRH

TSH

T4

T3

rT3

T2’s

5’-deiodinase

+

+

Hypothalamus

Pituitary

Thyroid

99.97%

bound

99.7%

bound

Iodine

NTI

NTINTI

NTI


Refer

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TSH in Thyroid and Non-Thyroidal Disease

Hyperthyroid Thyroid

Autonomy

(Euthyroid)

Non-thyroidal

Illness

Central Primary

Hypothyroid

Normal

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Thyroid Function Tests

• TSH

– Outpatient screening

– Not sufficient alone in sick patients

– Glucocorticoids, dopamine, fasting, head trauma

– Transiently during recovery from illness

• Free T4 (fT4)

– Free T4 equilibrium dialysis

• Gold standard, but send-out

– Free T4 direct estimates

• Available in local labs

• Unreliable when extremely high or low TBG

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Sick Euthyroid Syndromes

• Low T4 syndrome ( total T4, normal fT4)

– TBG

– T4 binding inhibitor

– Dilantin ( fT4)

• Low T3 syndrome ( total T3)

– Acute or chronic illness

– -blocker, glucocorticoids, amiodarone

• High T4 syndrome ( total T4, normal fT4)

– TBG

– Acute T4 T3

– Psychiatric hospitalization ( fT4)

Matsumoto 05/13/14 Refer


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Thyroid Disorders in Older AdultsScreening

• Failure to thrive, cognitive impairment, chronic

disability

• Well elderly with h/o thyroid or autoimmune

disease, unexplained depression or cognitive

dysfunction, cholesterol

• Atrial fibrillation, CVD or CHF, osteoporosis

• Asymptomatic well-elderly – controversial

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Risk of Developing Overt Hypothyroidism

and Hyperthyroidism

MPJ Vanderpump, Clin Endocrinol, 1995Matsumoto 05/13/14


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HypothyroidismSymptoms

• Dry skin, sweating

• Cold intolerance

• Hoarseness

• Weight gain

• Constipation

• Paresthesias, hearing

• Fatigue, weakness, muscle cramps

• Depressed mood

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HypothyroidismSigns

• Slow movements

• Dry skin and coarse hair

• Cold skin

• Periorbital puffiness

• Bradycardia

• Slow relaxation of reflexes

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Hypothyroidism in Older AdultsManifestations

• Dry skin, hair loss, periorbital edema, cold

intolerance (myxedema)

• Paresthesias (carpal tunnel), ataxia, cognitive

dysfunction

• Depression, apathy, psychosis

• Weight gain, cholesterol and TG, edema

• Myopathy, arthralgia

• Bradycardia, pericardial effusion, CHF

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Hypothyroidism: Bradycardia

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Hypothyroidism: Cardiomegaly Due to

Pericardial Effusion

Untreated After thyroid hormone

replacementMatsumoto 05/13/14

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HypothyroidismDiagnosis

• fT4

• TSH

– TSH in primary hypothyroidism

– Normal to TSH in secondary hypothyroidism

– Transient or TSH with NTI

• TSH, normal fT4 (subclinical)

• Anti-thyroid peroxidase (anti-TPO) Ab (Hashimoto’s)

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HypothyroidismCauses

• Primary

– Hashimoto’s disease (autoimmune) most common

– Neck irradiation (lymphoma, head & neck CA)

– Thyroiditis (recovery phase)

– Surgical removal

– Iodine, lithium, amiodarone, anti-thyroid drugs,

sunitinib

– [Iodine deficiency, enzymatic defects, agenesis]

• Secondary

– Hypothalamic-pituitary disease

• Destructive process, e.g. tumor


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Hypothyroidism in Older Adults

• Common (2-10%) – most subclinical

• Atypical, nonspecific presentation

– Insidious, often subclinical

– Neuropsychiatric (confusion, cognition, neuropathy,

weakness, ataxia, hearing)

– Myxedema (cold, puffiness)

– Cardiovascular (bradycardia, CHF, effusions)

– Anemia, hyponatremia, CPK, cholesterol/TG

• Falls, mobility, urinary incontinence

• NTI affects thyroid function tests

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Subclinical Hypothyroidism


– Prevalence 4-10%, with age

• 1-2% per year overt hypothyroidism

• Greater TSH (> 10)

• Goiter

• Low-normal fT4

• Anti-TPO Ab (Hashimoto’s)

• 50% TSH normalizes

• Associated with CVD, CHF and CV mortality

– TSH > 10

• Thyroid hormone treatment outcomes?

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Hypothyroidism in Older AdultsTreatment

• Symptoms, goiter, TSH > 10, anti-TPO – treat

• Asymptomatic and TSH 4-10 – monitor

• Goal – normal TSH (and fT4)

• T4 (levothyroxine) fasting

– Start low (25-50 g/d)/go slow ( 25-50 g/d q 4-6 wks)

– More rapid for severe

– Requirement less (~110 g/d)

– Ca, bisphosphonates, Fe, PPIs, resins absorption

– Dilantin, carbamazepine clearance

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HyperthyroidismSymptoms

• Nervousness

• Sweating, heat intolerance

• Dyspnea, palpitations

• Fatigue, weakness

• Weight loss, appetite

• Eye symptoms

• Hyperdefecation

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HyperthyroidismSigns

• Thyroid enlargement, bruit

• Ophthalmopathy, lid retraction and lag

• Hyperkinesis

• Tremor

• Warm, moist hands and skin

• Tachycardia, atrial fibrillation

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Hyperthyroidism in Older AdultsManifestations

• Palpitations, atrial fibrillation, CHF

• Depression, apathy, lethargy, irritability

• Appetite, weight loss, nausea, constipation

• Proximal muscle wasting and weakness

• Peripheral neuropathy

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Hyperthyroidism due to Toxic Multinodular

Goiter in the Elderly

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Graves Disease

• Autoimmune disease

– TSI TSH receptor

• Hyperthyroidism with diffuse goiter

• Opthalmopathy infiltrative

– Exophthalamos (proptosis), EOMs

– Chemosis (edema), periorbital soft tissue

• Dermopathy infiltrative

– Localized (pretibial) myxedema

– Thyroid acropachy (nails)

• Elderly may not have any of these signs


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Thyroid Palpation: Landmarks

Thyroid lobe

(“rule of thumb”)

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Thyroid Palpation: Landmarks

Thyroid lobe

(“rule of thumb”)

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Hyperthyroidism: Atrial fibrillation

Slow ventricular response

may be present in elderly

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HyperthyroidismDiagnosis

• fT4

• Sometimes only T3 (T3 thyrotoxicosis)

• Undetectable or TSH

• Normal T4 and T3 (subclinical)

• Thyroid-stimulating immunoglobulins – TSI

(Graves)

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Radioactive Iodine Uptake (RAIU)

DDx of Hyperthyroidism

• High uptake

– Graves disease

– Toxic multinodular goiter or adenoma

– [TSH-secreting tumor, choriocarcinoma]

• Low to no uptake

– Thyroiditis

– Exogenous (20-40%) or facticious

– Iodine-induced (contrast, exogenous)

– [Struma ovarii, metastatic thyroid cancer]

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Refer


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Hyperthyroidism in Older Adults

• Not uncommon (0.5-2.0%) – most subclinical

• Atypical or subclinical presentation

– No heat intolerance, tachycardia, hyperkinesis

– Apathetic, depressed

– Anorexia, weight loss, constipation, weakness

– Dyspnea, slow atrial fibrillation, CHF

• Graves disease most common (atypical)

• Multinodular goiter more common

• T3 thyrotoxicosis

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Subclinical Hyperthyroidism


– Prevalence 1-5% > 65 years old

• Progression to overt hyperthyroidism

– Greater TSH (< 0.1)

– High-normal fT4 or total or free T3

– Goiter

– Graves disease (thyroid-stimulating

immunoglobulins, TSI)

• Associated with atrial fibrillation, CVD, CV

mortality, hip fracture, cognitive impairment, QOL

– TSH < 0.1

• Anti-thyroid or RAI treatment outcomes?Matsumoto 05/13/14 Refer


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Hyperthyroidism in Older AdultsTreatment

• Symptoms and TSH < 0.1 (undetectable)

• Asymptomatic and TSH < 0.3 (low)

– Atrial fibrillation

– Osteoporosis

– Heart disease

– Cognitive impairment

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Hyperthyroidism in the ElderlyTreatment of Graves Disease

• Symptomatic/prior to radioactive iodine

– blockers

• Propanolol 40-120 mg/d

• Anti-thyroid drugs

• Methimazole 5-15 mg/d

• Radioactive iodine

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Nodular Thyroid Disease

• Multinodular

– Usually benign

– Suspicious nodule may be cancer

• Solitary nodule – most nonpalpable

– Most benign and cold on scan

– Some cancer

• Cysts

– Usually benign and cold on scan

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Nontoxic Multinodular Goiter: Excessive Iodine

Intake May Induce Hyperthyroidism

Kombu Kelp 1500 mg =

600-900 g iodine vs.

RDA = 150 g iodine

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Nontoxic Multinodular GoiterManagement

• Issues

– Local compressive symptoms

– Cosmetic

– Risk iodine-induced hyperthyroidism

– Risk of malignancy

• Treatment

– No treatment

– TSH suppression with T4 – not recommended

• Poor (30-50%) partial response

• Risk of symptomatic hyperthyroidism ( risk in elderly with autonomous secretion)

– Surgery

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Solitary Thyroid Nodule

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Solitary Thyroid Nodule

• Common (prevalence ~5%)

– Palpable in ~7% women and 2% men

– Prevalence with neck irradiation and in elderly

– ~50% at autopsy

– Greater incidental detection with ultrasound

• Majority benign ~85%

– ~15% malignant (most clinically suspicious)

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Prevalence of Thyroid Nodules

EL Mazzaferri, NEJM, 1993Matsumoto 05/13/14


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Solitary Thyroid NoduleCommon Causes

• Benign 85%

– Colloid nodule (in multinodular goiter)

– Follicular adenoma

– Cyst (simple or hemorrhagic)

– Hashimoto’s disease

• Malignant 15%

– Papillary or follicular carcinoma (85%)

– Medullary or anaplastic carcinoma

– Other (lymphoma, metastatic)

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Solitary Thyroid NoduleRisk of Cancer

• Male, child or elderly

• History of neck irradiation

• Family history of medullary thyroid cancer/MEN

• Recent size, large (> 4 cm)

• Rock hard

• Hoarseness, fixed, dysphagia, dyspnea

• Lymphadenopathy, distant metastasis

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Solitary Thyroid NoduleManagement

• Surgery if suspicious for cancer

• Fine needle aspiration biopsy (FNAB) US-guided

– Nodule > 1 cm

– Suspicious US


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Nodular Thyroid Disease in the Elderly

• Multinodular goiter very common (60-90%)

– Autonomy risk of hyperthyroidism

– Resistant to T4 suppression

– Sensitive to iodine

• Solitary nodules also very common

– Mortality with well-differentiated thyroid carcinoma

– Lymphoma and anaplastic thyroid carcinoma

– More sensitive to hyperthyroidism with TSH

suppression

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Well-Differentiated (Papillary or Follicular)

Thyroid Cancer

• Occult or intrathyroidal ~ normal survival

• Poor prognostic factors survival

– Large tumor (>2.5 cm)

– Age > 40 yrs old

– Local invasion (capsule or blood vessel)

– Distant metastasis (mediastinum, lung, bone)

– Less well-differentiated anaplastic

– Local lymph nodes?


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Increased Incidence and Death Rate of

Thyroid Cancer with Aging

JL Young Jr, NCI Pub NIH81-2330, 1981Matsumoto 05/13/14


Matsumoto 05/13/1449

Siegel R, et al, CA Cancer J Clin 64:9-29, 2014

Secular Increase in Incidence and Mortality with Thyroid Cancer

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Well-Differentiated (Papillary or Follicular)

Thyroid Cancer

• Treatment

– Near-total or total thyroidectomy

– RAI ablation

– Chronic TSH suppression

• High – intermediate risk

– Capsular or blood vessel invasion

– Incomplete resection

– Distant metastases

– Cervical node metastases

– Aggressive histology

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Matsumoto 05/13/14 51

Grogan RH, et al, J Clin Endocrinol Metab 97:1645-1653, 2012

Post-Operative Complications with

Thyroidectomy in Older Patients

Matsumoto 05/13/14 52Mazzaferri EL, Jiang SM, Am J Med 97:418-428, 1994

Thyroid Hormone Suppression Recurrence

of Thyroid Cancer Post-Thyroidectomy


Matsumoto 05/13/14 53McLeod DS, et al, Lancet 381:1046-1057, 2013

Degree of TSH SuppressionConsider Risk of Cancer Progression vs. Risk of

Adverse Effects

Refer

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Thyroid Disorders in Older AdultsSummary

• Clinically atypical, nonspecific, confounded by co-morbidities, attributed to “old age”

• Subclinical > overt disease

• Measure fT4 and TSH if sick, misleading in NTI

• Subclinical hypothyroidism common

• Replacement dose lower

• Hyperthyroidism very atypical presentation

• Thyroid cancer prognosis worse

• TSH suppression consider risk of thyroid cancer progression vs. risk of adverse effects

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Thyroid Disorders in Older AdultsReferences

• Boelaert K. Thyroid dysfunction in the elderly. Nat Rev Endocrinol 9:`94-204, 2013

• Visser ED, et al. Thyroid disorders in older adults. Endocrinol Metab Clin N Am 42:287-303, 2013

• Papaleontiou M, Haymart MR. Approach to and treatment of thyroid disorders in the elderly. Med Clin N Am 96:297-310, 2012

• Mitrou P, et al. Thyroid disease in older people. Maturitas 70:5-9, 2011

• McLeod DA, et al. Controversies in primary treatment of low-risk papillary thyroid cancer. Lancet 381:1046-1057, 2013

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Thyroid Disorders in Older Adults · Thyroid Disorders in Older Adults Alvin M. Matsumoto, M.D. Professor, Department of Medicine Acting Head, Division of Gerontology & Geriatric