Hyperthyroidism: A stepwise approach to management

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Applied Evidence

Hyperthyroidism: A stepwise approach to management

J Fam Pract. 2011 July;60(7):388-395

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References

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Using RAI to treat Graves’ disease increases the risk that ophthalmopathy will develop or worsen. Worsening of Graves’ ophthalmopathy secondary to RAI treatment occurs in 20% of treated patients (transient in 15%; permanent in 5%).²⁷ Steroid prophylaxis is beneficial for patients with ophthalmopathy,²⁸ and prednisone 40 to 80 mg per day tapered over at least 3 months can help reduce the condition.¹⁹ In patients with moderate to severe active ophthalmopathy, intravenous corticosteroid therapy has a small but statistically significant advantage over oral therapy and causes significantly fewer adverse events.²⁹

Orbital radiotherapy is also used, and has been shown to decrease diplopia.³⁰ However, the best available evidence recommends combining orbital radiotherapy and oral corticosteroids, which yields efficacy beyond that achievable with either radiotherapy or oral corticosteroids alone.¹⁶ Moreover, intravenous methylprednisolone combined with orbital radiotherapy seems to be most efficacious.³¹ The course of ophthalmopathy is the same whether total or subtotal thyroidectomy is used.³²

Prognosis without treatment

Individuals with high-normal thyroid function tests, subclinical hyperthyroidism, and clinical hyperthyroidism are at increased risk for atrial fibrillation.^33-35 Hyperthyroidism is also associated with increased risk of heart failure (6% of patients), which might be secondary to coexisting atrial fibrillation or tachycardia-mediated cardiomyopathy.³⁶ Heart failure is usually reversible when the hyperthyroidism is treated.

Patients with overt hyperthyroidism are also at risk for pulmonary hypertension secondary to increased cardiac output and decreased pulmonary vascular resistance.³⁷

In patients with preexisting cardiac disease, hyperthyroidism increases risk of death (hazard ratio [HR]=1.57),³⁸ and might even do so in patients without cardiac disease.^39,40 It also increases risk of ischemic stroke (HR=1.44) among adults ages 18 to 44 years.⁴¹ Untreated hyperthyroidism also contributes to low bone mineral density and increases the risk of hip fracture.⁴²

Subclinical hyperthyroidism

Subclinical hyperthyroidism occurs in 2% of the US population and is characterized by low serum TSH (<0.1 mIU/L) with normal levels of free T₃ and free T₄. The causes are similar to overt hyperthyroidism. In addition, it can result from overtreating hypothyroidism with thyroid hormone, thereby inducing a subclinical hyperthyroid state.

The most common endogenous cause of subclinical hyperthyroidism (~60% of patients) is multinodular goiter.⁴³ Subclinical hyperthyroidism carries significant health risks, and yet evidence is lacking on when to treat this condition. Prolonged subclinical hyperthyroidism can lead to atrial fibrillation,^24,44 and to systolic and diastolic cardiac dysfunction.⁴⁵ Subclinical hyperthyroidism is also associated with decreased bone density,⁴⁶ and an increased risk of dementia.⁴⁷

The American Association of Clinical Endocrinologists recommends periodic clinical and laboratory assessment for patients with subclinical hyperthyroidism (TSH=0.1-0.5 mIU/mL), including rechecking TSH, free T₃ and free T₄ at 2- to 4-month intervals.

FAST TRACK

Treat the underlying cause of subclinical hyperthyroidism if the serum TSH level is <0.1 mIU/mL.

Treatment of the underlying cause of hyperthyroidism is indicated if serum TSH is <0.1 mIU/mL.

For patients older than 65 years who have persistent subclinical hyperthyroidism, consider treatment in the following scenarios:⁴⁸

nodular thyroid disease (due to high conversion rate to overt hyperthyroidism)
osteopenia or osteoporosis (in women)
atrial fibrillation
underlying cardiac disease.

Hyperthyroidism in pregnancy

FAST TRACK

Hyperthyroidism symptoms usually resolve after delivery. If symptoms persist, however, the treatment of choice is antithyroid drugs.

PTU is the first choice for treating hyperthyroidism in pregnancy. It crosses the placenta less readily than MMI, and is thus less likely to cause fetal hypothyroidism. Additionally, MMI is associated with increased risk of fetal anomalies, such as aplasia cutis and esophageal atresia. MMI may be considered if the patient is intolerant to PTU or fails to become euthyroid while receiving PTU.⁴⁹ Use the lowest possible dose of either PTU or MMI to maintain thyroid function within the upper limit of normal. The dose of the antithyroid medication is usually decreased as pregnancy progresses and discontinued in the last few weeks, as pregnancy is thought to improve the course of Graves’ disease.

The use of RAI is contraindicated during pregnancy and breastfeeding. Hyperthyroidism symptoms usually resolve after delivery. If symptoms persist, however, the treatment of choice is ATD. Surgery is an option in severe Graves’ disease not responding to ATD.

CORRESPONDENCE
Abdulraouf Ghandour, MD, Department of Family and Community Medicine, University of Missouri-Columbia, One Hospital Drive, Columbia, MO 65212; ghandoura@health.missouri.edu