Applied Evidence

Hyperthyroidism: A stepwise approach to management

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Clinical presentation and an algorithm-guided laboratory assessment can quickly narrow the diagnosis and help direct your choice, timing, and sequence of treatments.




Measure TSH in any patient >60 years presenting with fatigue, atrial fibrillation, weight loss, and shortness of breath. B

Achieve faster control of symptoms in elderly patients and those with cardiac disease by pursuing the ablative method with radioactive iodine (RAI). This method is also recommended for patients with toxic multinodular goiter and toxic adenoma. A

Initiate steroid prophylaxis for patients with Graves’ ophthalmopathy undergoing RAI. A

Opt for a 12- to 18-month course of an antithyroid drug, rather than a 6-month course. The longer course is associated with a lower relapse rate. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

A 72-year-old man arrives at the clinic with insomnia and fatigue. His medical history is significant for hypertension, hyperlipidemia, and degenerative joint disease, for which he is taking, respectively, metoprolol 25 mg twice daily, simvastatin 20 mg daily, and acetaminophen as needed for joint pain. He has experienced no weight loss, anxiety, or gastrointestinal or urinary symptoms. He does not smoke or drink alcohol. His blood pressure is 140/75 mm Hg, pulse is 85, respiratory rate is 20, and temperature is 97.1°F. The rest of the physical examination is unremarkable except for 1+ lower extremity edema, unchanged since his previous visit. Routine blood work, however, reveals his thyroid-stimulating hormone (TSH) level to be 0.03 mIU/L.

Clues from the clinical presentation

The subtle, "apathetic presentation" with few symptoms, as described in the case above, is typical of older individuals with hyperthyroidism.1 In contrast, younger patients with hyperthyroidism and those with comorbidities can manifest a number of signs and symptoms (TABLE 1).2

Graves’ disease, the most common cause of hyperthyroidism,3 causes such ocular disturbances as exophthalmos, lid lag, lid retraction, and proptosis in 60% of patients with the condition.3 These findings help differentiate Graves’ disease from other causes of hyperthyroidism. (See “Common [and not so common] causes of hyperthyroidism”.) Palmar sweating, pretibial myxedema, and Plummer’s nails (onycholysis) are also unique for Graves’ disease.4

When you suspect hyperthyroidism, assess the thyroid for size, nodularity, and vascularity. Goiter is less prevalent in the elderly, occurring in less than 50% of patients 61 and older, compared with 77% of patients younger than 60 years.5 Diffuse goiter is typical with Graves’ disease, while a mass with multiple nodules suggests possible toxic multinodular goiter. A solitary palpable nodule could mean toxic adenoma. A thyroid that is tender on palpation may point to subacute thyroiditis, particularly if the patient has had a viral illness recently (TABLE 2).

Measuring a patient’s TSH level is warranted with the above findings. Additionally, measure TSH in any patient older than 60 years presenting with fatigue, atrial fibrillation, weight loss, and shortness of breath.5

Clinical manifestations of hyperthyroidism

Acropachy (swelling of the fingers)
Bruit (thyroid)
Decreased attention span
Exertional dyspnea
Goiter (smooth or nodular)
Hair loss
Heat intolerance
Hyperactive deep tendon reflex
Increased appetite
Lid lag, proptosis
Muscle weakness
Nervousness and irritability
Palmar erythema
Paralysis (sudden)
Photophobia, eye irritation, diplopia
Pretibial myxedema
Warm, moist skin
Weight loss

Common (and not so common) causes of hyperthyroidism

Graves’ disease—an autoimmune disorder in which antibodies target thyroid tissue and enzymes and activate thyroid hormone synthesis—affects more than 3 million people in the United States and accounts for 60% of hyperthyroidism cases.3 Remission does occur; however, the recurrence rate is as high as 60%.50 Factors associated with recurrence include tobacco use; male sex; young age; large goiter size or increase in goiter size during treatment; elevated TSH receptor antibodies (TRab); presence of Graves’ ophthalmopathy; markedly elevated thyroid hormones, or delayed treatment.51

Toxic multinodular goiter, also known as Plummer’s disease, is the underlying condition in 15% to 20% of hyperthyroidism cases; it is more common in young patients and in iodine-deficient locations (eg, Denmark).52 However, it also occurs in elderly patients with longstanding goiter.

Toxic adenoma causes just 3% to 5% of cases of hyperthyroidism.53 It, too, occurs more commonly in young patients and in iodine-deficient regions. The radioactive iodine uptake test shows a hot nodule, with suppressed uptake in the surrounding thyroid gland.

Subacute thyroiditis, also known as de Quervain’s thyroiditis, is the reason for 15% to 20% of hyperthyroidism cases; it is usually preceded by viral infection and inflammation that lead to destructive release of preformed thyroid hormone. Symptoms—typically fever, malaise, and tender goiter—usually occur more abruptly than symptoms of Graves’ disease.54 Most cases resolve spontaneously within a few months, and relapse is less common than in Graves’ disease. Other lab abnormalities include increased erythrocyte sedimentation rate and low radioiodine uptake.

Postpartum thyroiditis is an autoimmune disease. Prevalence ranges from 1% to 17% of new mothers.55 It is characterized by a thyroid gland that is painless on palpation and low radioiodine uptake.56 Most cases are reversible with treatment.

Factitious or iatrogenic hyperthyroidism is due to an exogenous intake of thyroid hormone, and typically exhibits a normal or low radioactive iodine uptake and a low thyroglobulin level.

Secondary hyperthyroidism, or TSH-mediated hyperthyroidism, is rare. It is always associated with goiter, and approximately 40% of patients have visual field defects.57


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