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© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
in the clinic
Hyperthyroidism
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
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© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
Who has an elevated risk for hyperthyroidism?
Individuals with:

Diffuse or nodular goiters

Type 1 diabetes, other endocrine/ nonendocrine AI diseases

Family histories of hyperthyroidism or hypothyroidism
Medications that increase risk:

Amiodarone

Alpha-interferon

Interleukin-2

Lithium

Iodide

Iodinated contrast agents in those with preexisting
autoimmune or nodular thyroid disease
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
Should clinicians screen for hyperthyroidism?
 Screen: Individuals with risk factors
 High risk comorbid conditions, family Hx, medication use
 Consider screening: those with other medical conditions
caused or aggravated by hyperthyroidism
 e.g., osteoporosis, supraventricular tachycardia, A-Fib
 Screen: Women >50 years
 1 in 71 have unsuspected but symptomatic
hyperthyroidism or hypothyroidism responsive to Rx
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
If clinicians screen for hyperthyroidism,
which test should they use?
 Serum TSH levels
 Low in both overt and subclinical hyperthyroidism
(due to negative feedback by  thyroid hormone
levels on pituitary gland)
 Screens for both hyperthyroidism & hypothyroidism
 TSH assays: standardized, accurate, widely available
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
CLINICAL BOTTOM LINE: Screening…
 Don’t screen: general population (not cost-effective)
 Do screen: those with…
 Diffuse or nodular goiters
 Type 1 diabetes, other endocrine/ nonendocrine AI diseases
 Osteoporosis, supraventricular tachycardia, or A-Fib
 Family Hx hyperthyroidism or hypothyroidism
 Amiodarone, α-interferon, interleukin-2, lithium, iodide use
 Women > 50 years of age
 Use serum TSH test
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
What symptoms should prompt clinicians
to consider hyperthyroidism?
 Nervousness (frequency: 99%)
 Increased sweating (91%)
 Palpitations (89%) or tachycardia (82%)
 Heat intolerance (89%)
 Fatigue (88%)
 Weight loss (85%)
 Shortness of breath (75%), weakness (70%)
 Leg swelling (65%)
 Eye symptoms (54%)
 Hyperdefecation (33%)
 Menstrual irregularity (22%)
 Emotional lability (30–60%)
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
What physical examination findings
indicate possible hyperthyroidism?
 Tachycardia (100% frequency)
 Goiter (100%)
 Skin changes (97%)
 Tremor (97%)
 Bruit (77%)
 Eye signs (30-45%)
 Atrial fibrillation (10%)
 Splenomegaly (10%)
 Gynecomastia (10%)
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
What lab tests should be used for
diagnosis?
 Serum TSH measurement
 If low: order free T4 or free T4 index (FT4I)
 If free T4 or FT4I not elevated: order total T3 or free T3
 Radioiodine uptake (RAIU): helps determine cause
 Thyroid scan: helps distinguish Graves disease, toxic
multinodular goiter, toxic adenoma
 If radioisotope studies contraindicated…
 Blood tests: TSH-receptor antibodies; thyroid-stimulating
immunoglobulins; thyroid-peroxidase antibodies;
thyroglobulin; human chorionic gonadotropin; sed rate
 Color Doppler US (thyroid)
 Whole-body radioiodine scan
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
Differential Diagnosis (with radioiodine uptake )
High or Normal
Low
• Graves disease
• Silent thyroiditis
• Toxic multinodular goiter
• Postpartum thyroiditis
• Toxic adenoma
• Subacute (granulomatous) thyroiditis
• HCG-induced
hyperthyroidism
• Iodine-induced hyperthyroidism
• TSH-producing pituitary
tumor
• Iatrogenic hyperthyroidism
• Amiodarone-induced hyperthyroidism
• Metastatic follicular thyroid cancer
• Struma ovarii
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
Lab and Other Studies for Hyperthyroidism (plus indication)

TSH (suspected hyperthyroidism)

Free thyroxine FT4 (suppressed TSH)

Free triiodothyronine FT3 (suppressed TSH, normal FT4)

Thyroglobulin (suspected thyroiditis)

Erythrocyte sed rate ESR (suspected subacute thyroiditis)

TSH-receptor antibodies (euthyroid Graves ophthalmopathy; assess
remission with antithyroid drug Rx in Graves disease; assess neonatal
risk in pregnant patients with Graves disease)

Thyroid peroxidase antibodies (confirm Hashimoto thyroiditis and
autoimmune thyroid disease; assess risk for Rx-induced thyroid
dysfunction and postpartum thyroiditis

RAIU (confirmed biochemical thyrotoxicosis, if cause unclear)

Thyroid scan (confirmed biochemical thyrotoxicosis, if cause unclear)

Whole body scan (suspected struma ovarii)

Color Doppler US (type I vs. type II amiodarone-induced thyrotoxicosis)

Human chorionic gonadotropin HCG (choriocarcinoma)
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
What alternative explanations should
clinicians consider?
 Infection
 Sepsis
 Anxiety
 Depression
 Chronic fatigue syndrome
 Atrial fibrillation of other causes
 Pheochromocytoma
 TSH testing usually distinguishes these from hyperthyroidism
 But serum TSH levels often low in pregnancy; hyperemesis
gravidarum; euthyroid sick syndrome; central hypothyroidism;
with some medications (glucocorticoids, dopamine, heparin)
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
When should clinicians consult an
endocrinologist?
 Presence of hyperthyroidism uncertain
 Serum TSH level low, but T4 and T3 within reference range
 TSH level normal, but T4 or T3 above reference range
 Cause unclear
 RAIU low or undetectable (Dx usually clear when elevated)
 Uncertain or suspicious about risk for or presence of
thyroid storm or Graves orbitopathy
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
CLINICAL BOTTOM LINE: Diagnosis…
 To make diagnosis, use:
 History and physical exam
 Low serum TSH level with elevated serum levels for free T4,
FT4 I, total T3, or free T3
 To identify cause, use:
 Clinical features
 RAIU and thyroid scan
 Additional tests (TRAb, TSI, TPO antibodies, thyroglobulin,
ESR, HCG, color Doppler US, whole-body scanning)
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
What nondrug therapies should clinicians
recommend?
Until thyroid disease adequately controlled…
 Avoid heavy physical exertion
 Reduce or eliminate caffeine intake
 Avoid OTC decongestants and cold remedies
 Discontinue smoking
 Avoid exogenous sources of iodine
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
How should clinicians choose and
prescribe drug therapy?
 Beta-adrenergic blockade
 Propranolol, atenolol, metoprolol, nadolol
 For symptomatic hyperthyroidism of any cause
 Side effects: CHF, asthma exacerbation
 Antithyroid medications
 Methimazole: preferred
 Propylthiouracil: alternative (in 1st trimester pregnancy, if
methimazole allergy, thyroid storm); beware liver failure
 Inhibit thyroid hormone synthesis, lower thyroid hormone
 Use for: Graves, toxic multinodular goiter, toxic adenoma
 Don’t use for: low RAIU hyperthyroidism
 Agranulocytosis occurs in 0.2%-0.4%
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
Ancillary Therapy

Potassium iodine
 Acutely reduces thyroid hormone release
 Use before thyroidectomy for Graves
 Don’t use before radioactive iodine therapy

Lithium
 Reduces thyroid hormone release

Cholestyramine
 Binds thyroid hormone in intestines

Nonsteroidal anti-inflammatory
 Treats subacute thyroiditis

Glucocorticoids
 For severe subacute thyroiditis
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
When should clinicians consider I-131 as
primary therapy for hyperthyroidism?
 Graves disease
 Achieves remission in ≈90%
 Good choice if no remission with antithyroid medications
Side effects
 Hypothyroidism: in almost all patients within 3–6 months
 Sialadenitis (due uptake by salivary glands)
 Worsening of Graves orbitopathy
 Possible small increase in thyroid cancer
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
When should clinicians consider I-131 as
primary therapy for hyperthyroidism?
 Toxic multinodular goiters & toxic adenomas
 Pretreat with β-adrenergic blockade &/or methimazole:
if very symptomatic or free T4 or FT4I levels exceed
upper limit of reference range more than 2-fold
 Discontinue methimazole 7 days before I-13
Side effects
 Hypothyroidism: 50%-75%
Note: Contraindicated in
pregnancy!
 Worse symptoms from thyroid hormone  in first 2 weeks
 Thyroid storm, if severely hyperthyroid
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
When should clinicians consider
thyroidectomy as primary therapy?
 High RAIU hyperthyroidism (primary therapy)
 Refractory amiodarone-induced cases (primary therapy)
 Most often recommended for…
 Those with thyroid nodules and suspected cancer
 Those who can’t tolerate or refuse alternative forms Rx
 Pregnancy
 Patients who don’t achieve remission with antithyroid Rx
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
How should clinicians monitor patients
who are being treated for hyperthyroidism?
 At baseline:
Perform CBC w/ differential WBC count, liver panel
 Once euthyroid:
Assess clinically
Measure serum TSH every 6 to 12 months for lifetime
 Monitoring differs depending on chosen treatment…
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
 Antithyroid medications
 Agranulocytosis, liver injury, vasculitis: discontinue
 Fever or pharyngitis: repeat CBC with differential WBC
 Symptoms of liver injury: order liver profile
Once symptoms resolved + results in reference range…
 Discontinue β-adrenergic blocker + reduce antithyroid Rx
 Continue clinical and lab assessments every 3–6 months
After 12-18 months reduced dose + normal TSH: ? remission
 Taper or stop antithyroid Rx
 Measure TRAb: normal = greater likelihood remission
 No remission: consider I-131 or surgery
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
 Radioactive iodine (I-131)
 Repeat clinical and lab assessments at 1-2 months
 Measure TSH and free T4 in first 1-3 months
 TSH suppression may last up to 6 wks after T4 and T3
fall to normal range
 Start thyroid hormone-replacement when free T4 level low or
TSH elevated
 Adjust dose every 6-8-weeks until TSH in desired range
 Thyroidectomy
 Start levothyroxine before hospital discharge
 Adjust dose every 6-8 weeks until TSH in desired range
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
What is subclinical hyperthyroidism, and
what are the indications for treatment?
 Definition: Low serum TSH levels + T4 and T3 levels
within reference ranges
 Asymptomatic or mild symptoms
 RAIU typically in reference range
 Thyroid scan findings consistent with underlying cause
 TSH levels often normalize w/o treatment
 Treat: if TSH <0.1 mU/L or symptomatic
 Consider treating: if TSH ≥0.1 mU/L but still lower than
reference range
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
How does a clinician recognize thyroid storm?
 “Thyroid crisis” 
exaggerated manifestations of thyrotoxicosis
 Unrecognized or inadequately treated thyrotoxicosis +
precipitating event (infection, trauma)
 Radioiodine therapy may precipitate
 Dx often based on suspicious, nonspecific clinical findings
 Cardinal manifestation: fever >102° F
 Other features: Tachycardia, tachypnea; nausea/vomiting,
diarrhea, CNS manifestations, anemia, hyperglycemia
 Elevated serum total, free T4 and T3 levels; undetectable
serum TSH level
Use Thyroid Storm
Scoring System 
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
Thyroid Storm Scoring System (feature, score)
Fever ° F
Score
99–99.9
Cardiac–pulse, bpm
GI signs
5
99–109
5
100–100.9
10
110–119
10
N, V, D, Pain
10
101-101.9
15
120–129
15
Jaundice
20
102-102.9
20
130–139
20
Precipitant history
103-103.9
25
≥140
25
Absent
0
>104
30
Atrial fibrillation
10
Present
10
0
Cardiac–CHF
CNS agitation
Absent 0
Absent
0
Absent
0
5
Mild
10
Mild (edema)
Moderate
20
Moderate (rales)
10
Severe
30
Severe (pulm
edema)
15
Total Score
<25 = unlikely
25-44 = suggestive
>45 = likely
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
How does a clinician treat thyroid storm?
1. Decrease thyroid hormone synthesis
 Propylthiouracil or methimazole
2. Inhibit thyroid hormone release
 Sodium iodide (IV) or potassium iodide (oral)
3. Reduce heart rate
 β-blocker (esmolol, metoprolol, propranolol) or diltiazem
4. Support circulation
 Glucocorticoids in stress doses
 Fluids (IV), oxygen, cooling
5. Treat precipitating cause
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
When should patients be hospitalized?
 When thyroid storm present, impending, or suspected
 Prognosis with aggressive therapy  ≈20% mortality (was
once 100%)
 Dx usually based on suspicious, nonspecific findings
 Do not wait for test results on serum TSH levels: delays
potentially lifesaving therapy
 Also, TSH levels don’t reliably distinguish thyroid storm
from uncomplicated thyrotoxicosis
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
When should clinicians consult an
endocrinologist or ophthalmologist?
Endocrinologist
 Help developing optimal management plan
 Unexpected events or Rx complications
 Significant Graves eye disease present
 Patient is pregnant
 Thyroid storm present, impending, or suspected
 Some guidelines suggest co-management in all cases
Ophthalmologist
 Double vision or impaired visual acuity, visual fields, color vision
 Significant eye discomfort
 Proptosis >22 mm or extraocular muscle dysfunction
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.
CLINICAL BOTTOM LINE: Treatment…
 If RAIU high or normal: Rx usually required
 Inform patients on benefits and risks and jointly decide
on preferred treatment
 Graves disease: antithyroid meds, I-131, thyroidectomy
 Toxic multinodular goiter: I-131 or thyroidectomy
 Toxic adenoma:I-131 or thyroidectomy
 Before definitive treatment, use antithyroid medications
to improve thyroid hormone levels
 If RAIU low: treat underlying cause or monitor
 Condition may be transient
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 157 (1): ITC1-1.