Why Propranolol Is Preferred to Other Beta-Blockers in Thyrotoxicosis or Thyroid Storm

Summary:
 In patients with thyrotoxicosis (thyroid storm), or symptomatic hyperthyroidism, there is an
excess of thyroid hormone (T4 & T3) production and secretion that may result in increases in
heart rate, tremors and nervousness.
 Propranolol is the most widely studied non-selective, beta-1 and beta-2-blocker that can treat
the increased heart rate and tremor. Additionally, it may reverse some of the reduced systemic
vascular resistance and inhibit the peripheral conversion of T4 to the more biologically active
hormone, T3.
 The American Association of Clinical Endocrinologists Medical Guidelines for the Evaluation
and Treatment of Hyperthyroidism and Hypothyroidism discuss the use of beta blockers in this
situation but do not specifically recommend one over another.

Editor-in-Chief: Anthony J. Busti, MD, PharmD, FNLA, FAHA

Reviewers: Jon D. Herrington, PharmD, BCPS, BCOP and Donnie Nuzum, PharmD, BCACP, CDE
Last Reviewed: October 2015

Explanation

Patients experiencing thyrotoxicosis (thyroid storm), or symptomatic hyperthyroidism, can experience a

number of effects that can include tachycardia, palpitations, tremor and/or nervousness. Patient's with
this condition are known to have an increased production of the thyroid hormones, thyroxine (T4) and
3,5,3'-triiodothyronine (T3). While the thyroid gland primarily releases T4 into the circulation, T4 is
generally metabolized to T3 in the peripheral tissue by two enzymes: monodeiodinase type I (5'D-I) and
monodeiodinase type II (5'D-II). The production of T3 is important because it is more biologically
potent than T4.1

Increases in T3 result in a number of effects, including an increase in myocardial contractility and speed
of diastolic relaxation of the heart.2-,3,4,5 In addition, systemic vascular resistance is reduced, which
may put the patient at increased risk for developing high output cardiac failure or even shock.5 The
treatment of this potentially emergent situation requires the use of medications that not only inhibit the
synthesis of T4 and T3, but also inhibit the peripheral conversion of T4 to T3 by 5'D-I and/or 5'D-II.

Propranolol, a non-selective beta-1 and beta-2-blocker, is frequently used to help treat this
condition. Propranolol will not only help control the symptomatic tachycardia and tremors associated
with thyroid storm, but there is also data that shows propranolol may also known to inhibit the
monodeiodinase type I enzyme responsible for conversion of T4 to the more biologically potent T3
hormone.6-10 This reduction in T4's metabolism, via the inhibition of monodeiodinase type I, may
cause the T4 to then be shunted through the enzyme monodeiodinase type III (5'D-III) resulting in the
production of 3,3',5'-triiodothyronine (reverse T3 or rT3).11,12 Reverse T3 is known to be metabolically
inactive.
Since blocking beta-2-receptors in blood vessels can result in vasoconstriction, propranolol's beta-2-
blocking properties may also treat some of the reduced systemic vascular resistance occurring in this
clinical scenario. In addition, propranolol is also a beta-blocker without intrinsic sympathomimetic
activity and thus will not mimic the symptoms of thyrotoxicosis. It is for all of these reasons that
propranolol has been most studied and is the most commonly used beta-blocker in this setting.6-
12 Doses of propranolol of 160 mg or more maybe needed to control symptoms, especially in younger
patients with thyrotoxicosis.13 Interestingly, the American Association of Clinical Endocrinologists
Medical Guidelines for the Evaluation and Treatment of Hyperthyroidism and Hypothyroidism do not
specifically recommend one beta-blocker over another when discussing the use of beta blockers in this
situation.14 In patients who have contraindications to propranolol (e.g., asthma or reactive airway
disease), the use of diltiazem can be considered as an alternative. If patients have concurrent low-output
heart failure during thyrotoxicosis, all negative inotropic medications (including propranolol) should be
used with caution.15

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