Beta blockers in the treatment of hyperthyroidism

INTRODUCTION — Beta blockers ameliorate the symptoms of hyperthyroidism that are caused by increased beta-adrenergic tone. These include palpitations, tachycardia, tremulousness, anxiety, and heat intolerance. Thus, a beta blocker should be started (assuming there are no contraindications to its use) in most patients as soon as the diagnosis of hyperthyroidism is made, even before determining the cause of the hyperthyroidism. They should be continued until resolution of hyperthyroidism.

The clinical use and efficacy of beta blockers in the treatment of hyperthyroidism will be reviewed here. The clinical manifestations, diagnosis, and treatment of hyperthyroidism are reviewed separately. (See "Overview of the clinical manifestations of hyperthyroidism in adults" and "Diagnosis of hyperthyroidism" and "Graves' hyperthyroidism in nonpregnant adults: Overview of treatment" and "Surgical management of hyperthyroidism" and "Thyroid storm".)

EFFICACY — In many tissues, hyperthyroidism is associated with an increased number of beta-adrenergic receptors [1]. The ensuing increase in beta-adrenergic activity is responsible for many of the symptoms associated with this disorder. It also explains the ability of beta blockers to ameliorate rapidly many of the symptoms, including palpitations, tachycardia, tremulousness, anxiety, and heat intolerance [2]. In a small, randomized trial, patients receiving beta blockers with methimazole, compared with patients receiving methimazole alone, had a lower heart rate and improvement in fatigability, shortness of breath, and physical functioning after four weeks of therapy [3].

Propranolol in high doses (above 160 mg/day) also slowly decreases serum triiodothyronine (T3) concentrations by as much as 30 percent [4], via inhibition of the 5'-monodeiodinase that converts thyroxine (T4) to T3. Propranolol is highly lipid soluble, allowing it to become sufficiently concentrated in tissues to inhibit monodeiodinase activity. This effect of propranolol is slow, occurring over 7 to 10 days, and contributes little to the therapeutic effects of the drug. Atenolol, alprenolol, and metoprolol similarly cause minimal reductions in serum T3 concentrations, whereas sotalol and nadolol do not [5].

Despite this theoretical advantage of propranolol and related drugs, the small effect and slow onset severely limit their usefulness for reducing serum T3 concentrations. If deiodinase inhibition is considered important in a patient with severe hyperthyroidism (eg, thyroid storm or impending thyroid storm), it is best achieved by the addition of an iodinated radiocontrast agent to the medical regimen (these agents are currently not available in the United States), or the use of propylthiouracil (PTU). (See "Iodinated radiocontrast agents in the treatment of hyperthyroidism" and "Thyroid storm".)

CLINICAL USE — Beta blockers should be given to most hyperthyroid patients who do not have a contraindication to their use. Beta blockers are relatively or, depending upon disease severity, absolutely contraindicated in patients with asthma or chronic obstructive pulmonary disease, severe peripheral vascular disease, Raynaud phenomenon, bradycardia, second- or third-degree heart block, and hypoglycemia-prone diabetics in whom the early warning symptoms of hypoglycemia may be masked. (See "Management of the patient with COPD and cardiovascular disease", section on 'Treatment of CVD in patients with COPD' and "Major side effects of beta blockers", section on 'Adverse noncardiac effects due to beta blockade'.)

In the absence of contraindications, beta blockers can be administered as soon as the diagnosis of hyperthyroidism is made, even before obtaining a definitive diagnosis as to the etiology of the thyrotoxicosis. In patients with Graves' disease, beta blockers are typically coadministered with a thionamide when a thionamide is chosen for initial treatment, and they are typically given to patients who are treated initially with radioiodine who do not require pretreatment with a thionamide.

Patients with relative contraindications to beta blockade may better tolerate beta-1-selective drugs such as atenolol or metoprolol. We generally use atenolol in an initial dose of 25 to 50 mg/day and titrate the dose as needed (up to 200 mg/day in two divided doses) to maintain a heart rate between 60 and 90 beats per minute. Daily dose requirements of 50 mg or higher can be divided and given twice daily if the patient becomes symptomatic or tachycardic in the evening or nighttime. Atenolol has the advantages of single-daily dosing and beta-1 selectivity; however, all beta-adrenergic blocking drugs effectively diminish hyperthyroid symptoms. (See "Graves' hyperthyroidism in nonpregnant adults: Overview of treatment".)

Beta blockers are also used preoperatively in patients who are having a thyroidectomy and are allergic to thionamides. The longer-acting drugs, such as atenolol, provide for more constant intraoperative and postoperative control, and minimize the need for intravenous beta blocker administration during the period that the patient is unable to take oral medications [6].

One report demonstrated an increased spontaneous abortion risk in pregnant women with hyperthyroidism treated with propranolol and a thionamide versus a thionamide alone [7]. Atenolol use during pregnancy has been associated with smaller babies [8], and beta blockers in general have been associated with rare reports of neonatal growth restriction, hypoglycemia, respiratory depression, and bradycardia [9]. These observations raise questions about the use of beta blockers to treat hyperthyroidism during pregnancy [7]. In pregnancy, we use the lowest dose and shortest duration of beta blocker treatment with metoprolol (usually 25 to 50 mg daily) or propranolol, when needed, to control symptoms. (See "Hyperthyroidism during pregnancy: Treatment".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hyperthyroidism".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Hyperthyroidism (overactive thyroid) (The Basics)")

●Beyond the Basics topics (see "Patient education: Hyperthyroidism (overactive thyroid) (Beyond the Basics)" and "Patient education: Antithyroid drugs (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Efficacy – Beta blockers rapidly ameliorate many of the symptoms of hyperthyroidism, including palpitations, tachycardia, tremulousness, anxiety, and heat intolerance. (See 'Introduction' above and 'Efficacy' above.)

●Clinical use – Assuming there are no contraindications to its use, we recommend using a beta blocker for patients with moderate-to-severe hyperadrenergic symptoms until euthyroidism is achieved by thionamides, radioiodine, or surgery (Grade 1B). (See 'Clinical use' above and 'Efficacy' above.)

●Administration – We typically start with atenolol 25 to 50 mg daily and increase the dose as needed (up to 200 mg daily in two divided doses) to reduce pulse to under 90 beats per minute if blood pressure allows. Daily dose requirements of 50 mg or higher can be divided and given twice daily if the patient becomes symptomatic or tachycardic in the evening or nighttime. (See 'Clinical use' above.)