THYROID PROBLEMS IN THE YOUNG AND OLD
| EVALUATION AND TREATMENT OF HYPERTHYROIDISM —Francis S. Greenspan, MD, Clinical Professor of
Medicine, and Chief of Thyroid Clinic, University of California, San Francisco, School of Medicine
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| Signs of thyroid problems: weight loss despite normal appetite; fatigue; palpitations; sweats; positive family history for
thyroid disease; marked enlargement of thyroid gland, often with audible bruit over gland
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| Thyroid function testing: total thyroxine (T4 )—modified by amount of circulating T4 -binding protein; free thyroxine
(FT4 )—amount of FT4 constant; eliminates variability of thyroid-binding globulin; may not be completely reliable in patients
with marked dysproteinemia (eg, patient with severe albumin deficiency); triiodothyronine (T3 )—may be elevated
in patients with functioning nodules; thyroid-stimulating hormone (TSH)—most sensitive and accurate test; when
T4 increases, pituitary shuts down, resulting in suppression of TSH; thyroid antibodies—useful as index for autoimmune
disease (eg, Graves’ disease); radioiodine uptake scanning—useful for functional nodules; thyroid ultrasonography
(US)—useful for nodules, but not for Graves’ disease
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| Graves’ disease: autoimmune disease; production of antibodies against TSH receptor; antibodies stimulate gland to increase
activity independently, not based on TSH level; TSH suppressed, FT4 and T3 elevated; antithyroid drug therapy—used
with β-blocker to control cardiac rhythm; methimazole preferred over propylthiouracil (PTU) because incidence of reactions
slightly lower and can be given once daily; start with 10 to 30 mg daily and taper to 5 to 10 mg daily for maintenance; requires
1 to 2 yr of therapy; toxicity <1%; can cause rash or low white blood cell (WBC) count (patients present with fever and sore
throat and should be admitted to emergency department immediately); ≈40% of patients treated for 2 yr have recurrence when
drug discontinued
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| Radioiodine therapy: safe; effective; few complications; ablation of gland results in permanent cure, but patients required
to take thyroid medication for life
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| Case presentation: woman 68 yr of age complains of palpitations, weakness, weight loss, and feeling hot and sweaty; positive
family history for thyroid disease; thyroid gland enlarged and irregular, with multiple nodules; atrial fibrillation; FT4 in
upper range of normal; T3 elevated 3 times normal (in patients with nodular disease, T3 often elevated disproportionately to
T4 ); antibodies negative; radioiodine uptake elevated; scan showed functioning nodules; treatment options—antithyroid
drugs until euthyroid; nodules autonomous and continue to function when drug discontinued; β-blocker useful for cardiac
arrhythmia; after patient euthyroid, radioiodine ablation of toxic nodules can be considered; if most of gland not nodular and
toxic, patient may not require supplemental T4 therapy; total thyroidectomy for large goiters (patients require T4 therapy)
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| Subclinical hyperthyroidism: patients present with suppressed TSH, but FT4 and T3 normal; T4 overdose—most common
cause; elevated FT4 level may be in normal range (eg, 9-24 pmol/L), but TSH suppressed; adjust dose of T4 ; detrimental
effects on heart and bones; other causes—early Graves’ disease; toxic multinodular goiter; dopamine,
corticosteroids, metformin, and somatostatin; in severely ill patients, TSH may be suppressed due to illness and not by
hyperthyroidism (patients do not have elevated FT4 or free T3 , but may have suppressed TSH)
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| Thyroiditis: viral—subacute; de Quervain’s thyroiditis; striking feature pain in thyroid gland; associated with malaise, fever,
aching, and tenderness in gland; acute viral infection causes dumping of thyroid hormone and transient phase of hyperthyroidism
with elevated FT4 and suppressed TSH; chronic—Hashimoto’s thyroiditis; painless; enlarged gland;
hyperthyroid phase with suppressed TSH, elevated T4 , and suppressed radioiodine uptake; course of disease—subacute
thyroiditis begins with dumping of T4 ; patients thyrotoxic; radioiodine uptake and TSH completely suppressed (subsides
in 4-12 wk); hypothyroid phase may occur (radioiodine uptake and TSH elevated); management—illness self-limited;
β-blocker for tachycardia; ibuprofen for pain or fever; short course of prednisone for severe symptoms; patients may
need T4 during hypothyroid phase
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| Iodine effects: large amounts of iodine can activate latent Graves’ disease or multinodular goiter; sources of iodine—contrast
media used for angiography and computed tomography (CT); kelp tablets; amiodarone; management—discontinue
iodine; half-life of amiodarone 6 mo; methimazole; amiodarone-associated thyroiditis may require steroids if methimazole
alone ineffective
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| Thyrotoxicosis and pregnancy: low-dose PTU (50-150 mg daily) safe during pregnancy and lactation; consider surgery or
radioactive iodine therapy after delivery; postpartum thyroiditis—during course of pregnancy, mother’s immune activity
suppressed, followed by high surge of immune activity after delivery; activation of Graves’ disease may occur 3 to 6
mo after delivery; may be transient
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| Ophthalmopathy and dermopathy: eyelids incapable of closing due to enlargement of eyeballs; white sclerotic lines
around cornea visible; protrusion of eyes; severe cases include acute inflammation with periorbital edema, redness, congestion,
and marked diplopia; muscles in eye enlarged and swollen; dermopathy presents as thickening of skin, usually in
pretibial areas; management—consult ophthalmologist; control thyroid disease with short-term antithyroid drug or
long-term radioactive iodine (can result in release of antigen and acute worsening of problem; cover with steroids); total
thyroidectomy; high-dose steroids reduce acute inflammatory response (give for several months and taper slowly); external
orbital irradiation effective (particularly in patients who relapse after steroids discontinued or do not respond adequately
to steroids); orbital decompression may be necessary if vision threatened; late muscle surgery for marked
diplopia and cosmetic discomfort
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| Thyroid storm: rare; acute life-threatening exacerbation of thyrotoxicosis; usually presents in previously hyperthyroid patient
with Graves’ disease in whom treatment discontinued; sudden onset of high fever, agitation, delirium, atrial fibrillation,
nausea, vomiting, and diarrhea; occasionally, patient apathetic with weakness, confusion, gastrointestinal (GI)
symptoms, and fever; diagnosis based on clinical findings; laboratory findings—T4 , FT4 , and T3 elevated; TSH suppressed;
not significantly different from patients with Graves’ disease; may be due to exacerbation of thyrotoxicosis
caused by sudden release of T4 due to acute problem (eg, cessation of medication, surgery, illness); results in increased
sensitivity to surge of catecholamines and thyrotoxic organ decompensation; management—intensive care; supportive
fluids; O2 ; cooling blanket; acetaminophen; phenobarbital; vitamins; antibiotics; digoxin; β-blocker; antithyroid drug; iodine
to inhibit release of hormone; dexamethasone to reduce inflammatory process; cholestyramine binds with T4 in gut,
reducing level of circulating T4
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| Questions and answers: radioiodine uptake—use radioiodine therapy in patients who relapse after 1 to 2 yr of PTU therapy;
performing uptake and scan before initiating radioiodine therapy essential to calculate dose; drug-induced subclinical
hyperthyroidism—discontinue drug; postpartum thyroiditis—incidence 2% to 4%; usually occurs in patients with autoimmune
thyroid disease; in patients with history of thyroid disease and positive antibodies, incidence as high as 50% to
60%; methimazole—start with higher dose because quickly metabolized by thyrotoxic patients; maximum dose 40 mg
daily; start with 30 mg daily for first month, 20 mg daily for second month, then taper to 5 to 10 mg daily; if patient becomes
hypothyroid, reduce dose; if methimazole causes fever, sore throat, and low WBC count, discontinue methimazole
and do not use PTU (give antibiotics and colony-stimulating factor if indicated); monitor FT4 levels
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| THYROID DISORDERS IN THE ELDERLY —David S. Cooper, MD, Professor of Medicine, and Director, Division of
Endocrinology, Johns Hopkins University School of Medicine, Baltimore, MD
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| Prevalence of thyroid problems: hyperthyroidism same in older people as in younger people; in older people, toxic nodules
and toxic multinodular goiters more common than Graves’ disease; subclinical hyperthyroidism, hypothyroidism, subclinical
hypothyroidism, and thyroid nodules more common in older people; goiters less common in older people than younger
people; prevalence of thyroid cancer similar in older people as in younger people, but prognosis worse in older patients;
hypothyroidism ≈10 times more common than hyperthyroidism; study found ≤11% of elderly men and 14% to 20% of
older women have mild hypothyroidism; 5% to 10% of older people have palpable thyroid nodule; by US, 70% to 80% of
people >50 yr of age have ≥1 thyroid nodule
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| Thyroid function: does not change with age (eg, rise in TSH with increased age not normal); T3 levels may decrease
slightly, but remain normal; T4 to T3 conversion may be marker of illness; production and degradation of thyroid hormone
slower in older people; dose of thyroid hormone needed for replacement in older hypothyroid patient lower than in
younger patient
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| Hyperthyroidism or thyrotoxicosis: associated with hyperadrenergic effects; does not correlate with thyroid function tests;
age affects clinical manifestations; causes in elderly—higher frequency of toxic multinodular goiter and toxic nodules;
Graves’ disease; symptoms in elderly vs young—anorexia, 32% vs 4%; increased appetite, 0% vs 57%; heat intolerance
uncommon in older people vs younger people; many older patients with hyperthyroidism who lose weight have poor appetites;
weight loss more common with increased age; weight gain rarely seen in older patients; apathetic thyrotoxicosis—
patients not hyperkinetic and not animated; physical examination—usually no goiter in older patients; nonpalpable thyroid
more common in older patients; atrial fibrillation common; treatment—radioactive iodine; patients with mild disease
can be given long-term (eg, 2 yr) antithyroid drug therapy; pretreat with antithyroid drug before radioiodine therapy
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| Subclinical hyperthyroidism: thyroid test normal; TSH low; symptoms (eg, heat intolerance, palpitations) usually in
younger patients; consider in patients with lower levels of TSH (eg, 0.1-0.5 µIU/mL); caused by excessive thyroid hormone
therapy, Graves’ disease, autonomous nodules, and multinodular goiter; some patients treated with radioiodine and
some patients in remission after course of antithyroid drugs have low TSH and normal thyroid function tests; progression
to overt hyperthyroidism—occurs over decades; occurs in ≈5% of people; study saw 38 of 50 people with less severely
depressed TSH level return to normal TSH levels after 1 yr with no intervention (TSH remained low in people
who had severely depressed TSH levels)
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| Adverse effects of subclinical hyperthyroidism: skeletal—patients with slightly low TSH had slightly increased risk for
fracture; patients with severely low TSH had significantly increased rates of fracture; compared to baseline, study saw
improvement in bone density in patients treated with radioactive iodine; cardiac—risk for atrial fibrillation same as in
overt hyperthyroidism; increased all-cause and cardiovascular mortality in people with TSH <0.5 µIU/mL; all-cause
mortality in people with TSH >0.5 µIU/mL same or slightly better than in people with normal TSH; benefits of treating
patients with persistently reduced TSH uncertain, but consensus panel recommends treatment for older people with cardiovascular
risks or postmenopausal women who have TSH <0.1 µIU/mL
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| Hypothyroidism: symptoms in older people vs younger people—older patients relatively asymptomatic compared to
younger people; cold sensitivity more common in patients <55 yr of age; weight gain not often seen in older people; muscle
cramps and paresthesias rarely seen in older patients; thyroid hormone therapy dosing—1) lower dose with higher
age; 2) start low, go slow; eg, start with 25 µg daily and increase slowly while monitoring TSH; use smallest T4 dose
needed to meet therapeutic goals; consider age, degree of hypothyroidism, cause of hypothyroidism (higher dose often
needed for patients with history of thyroidectomy), and comorbidities (lower dose often needed) for determining dose; increase
dose slightly if patients on other drugs (eg, amiodarone); goal TSH variable (less aggressive in elderly patients);
consider cost; generic products may be inconsistent; many agents (eg, calcium, iron, soy) impair absorption of thyroid
hormone (dose may need to be increased; recommend taking thyroid hormone 4 hr apart from supplements)
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| Subclinical hypothyroidism: thyroid function normal, TSH elevated; usually mild; 80% to 85% of patients have TSH <10
µIU/mL; most people have positive antibodies; some people may have mild symptoms of hypothyroidism; risk
factors—age >60 yr; history of hypothyroidism; autoimmune disease; history of head and neck irradiation; use of lithium
or amiodarone; treatment—may improve morbidity and mortality, lipid profile, and atherosclerosis; potential effects
on symptoms, mood, and memory may not be clinically significant; may prevent progression to overt
hypothyroidism; no evidence that subclinical hypothyroidism causes coronary heart disease; study of patients >85 yr of
age followed for 4 yr with no intervention saw patients with high TSH levels lived longer than people with normal TSH;
progression to overt hypothyroidism—unpredictable; risk dependent on baseline TSH and whether antibodies positive
or negative; arguments against treatment—effects on cardiovascular disease mortality and morbidity unclear; data on
improved symptoms equivocal; benefits of cognitive outcomes unclear; cost and risk for overtreatment; patients often revert
to normal thyroid function; treatment recommended for patients positive for antibodies
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| Goiter: determine whether malignant or compressing trachea or esophagus; patients often asymptomatic; rule out hyperthyroidism;
perform US and scanning; consider performing biopsy on large cold area within nodule; CT or magnetic resonance
imaging (MRI) to evaluate airway; pulmonary function testing with flow-volume loops to evaluate upper airway
function; substernal goiters common and must be followed with CT; treatment—surgery; suppression therapy usually
ineffective; radioiodine for patients who cannot tolerate surgery
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Educational Objectives
| The goal of this program is to educate the listener about common thyroid conditions in young and old patients. After hearing
and assimilating this program, the participant will be better able to:
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 | 1. Assess thyroid function based on laboratory and clinical findings.
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| 2. Discuss thyroid conditions, such as Graves’ disease and subclinical hyperthyroidism.
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| 3. Describe thyroid ophthalmopathy and thyroid storm.
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| 4. List effects of aging on prevalence of thyroid problems and symptoms.
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| 5. Consider risks and benefits when managing elderly patients with thyroid disease.
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Discussed on This Program
Acetaminophen (N -acetyl-P -aminophenol; APAP) (several trade names)
Amiodarone HCl [Cordarone, Pacerone]
Cholestyramine [Cholestyramine Light, Prevalite, Questran, Questran Light]
Dexamethasone (several trade names)
Digoxin [Digitek, Lanoxicaps, Lanoxin]
Ibuprofen (several trade names)
Methimazole [Tapazole]
Phenobarbital [Bellatal, Luminal Sodium, Solfoton]
Prednisone (several trade names)
Propylthiouracil (PTU)
Suggested Reading
Basaria S et al: Amiodarone and the thyroid. Am J Med 118:706, 2005; Clark OH et al: Thyroid cancer: the case for total
thyroidectomy. Eur J Cancer Clin Oncol 24:305, 1988; Col NF et al: Subclinical thyroid disease: clinical applications.
JAMA 291:239, 2004; Cooper DS et al: Management Guidelines for Patients with Thyroid Nodules and Differentiated
Thyroid Cancer. Thyroid, 2006; Cooper DS: Antithyroid drugs in the management of patients with Graves' disease: an evidence-based
approach to therapeutic controversies. J Clin Endocrinol Metab 88:3474, 2003; Cooper DS: Antithyroid
drugs. N Engl J Med 352:905, 2005; Cooper DS: Thyroid disease in the oldest old: the exception to the rule. JAMA
292:2651, 2004; Greenspan FS: Radiation exposure and thyroid cancer. JAMA 237:2089, 1977; Greenspan FS: The
problem of the nodular goiter. Med Clin North Am 75:195, 1991; Greenspan SL et al: The effect of thyroid hormone on
skeletal integrity. Ann Intern Med 130:750, 1999; Laurberg P et al: Hypothyroidism in the elderly: pathophysiology, diagnosis
and treatment. Drugs Aging 22:23, 2005; Samuels MH: Subclinical thyroid disease in the elderly. Thyroid 8:803,
1998; Singer PA et al: Treatment guidelines for patients with hyperthyroidism and hypothyroidism. Standards of Care
Committee, American Thyroid Association. JAMA 273:808, 1995; Surks MI et al: Subclinical thyroid disease: scientific
review and guidelines for diagnosis and management. JAMA 291:228, 2004; Tunbridge WM et al: Population screening
for autoimmune thyroid disease. Endocrinol Metab Clin North Am 29:239, 2000; Vanderpump MP et al: Epidemiology
and prevention of clinical and subclinical hypothyroidism. Thyroid 12:839, 2002; Wang C et al: The epidemiology of thyroid
disease and implications for screening. Endocrinol Metab Clin North Am 26:189, 1997.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship
with the manufacturer or provider of any commercial product or service discussed. For this issue, the faculty reported
nothing to disclose.
Dr. Greenspan spoke in San Francisco, CA, at the Annual Review in Family Medicine, presented March 5-7, 2006, by the
University of California, San Francisco, School of Medicine. Dr. Cooper was recorded in Baltimore, MD, at Current Topics
in Geriatrics, presented February 9-11, 2006, by Johns Hopkins University School of Medicine. The Audio-Digest
Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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