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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. 

                                         Propranolol for Thyroid Storm 

    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

    References:

    1. Berry MJ, Larsen PR.  The role of selenium in thyroid hormone action.  Endocr Rev  1992;13:207-19.        
    2. Glass CK, Holloway JM.  Regulation of gene expression by the thyroid hormone receptor.  Biochem Biophys Acta 1990;1032:157-76.  
    3. Brent GA, Moore DD, Larsen PR.  Thyroid hormone regulation of gene expression.  Annu Rev Physiol 1991;53:17-35.  
    4. Dillmann WH.  Biochemical basis of thyroid hormone action in the heart.  Am J Med 1990;88:626-30.  
    5. Woeber KA.  Thyrotoxicosis and the heart.  N Engl J Med 1992;327:94-8. 
    6. Wiersinga WM, Touber JL.  The influence of beta-adrenoreceptor blocking agents on plasma thyroxine and triiodothyronine.  J Clin Endocrinol Metab  1977;45:293-8.  
    7. Verhoeven RP, Visser TJ, Doctor R et al.  Plasma thyroxine, 3,3'5-triiodothryonine and 3,3',5'-triiodothyronine during beta-adrenergic blockade in hyperthyroidism.  J Clin Endocrinol Metab  1977;44:1002-5.  
    8. Chambers JB, Pittman CS,  Suda AK. The effects of propranolol on thyroxine metabolism and triiodothyronines production in man. J Clin Pharmacol 1982; 22:110-6.  
    9. Lumholtz IB, Faber J, Kirkegaard C et al: The extrathyroidal effect of D, L-propranolol on 3,3',5'-triiodothyronine, 3',5'-diiodothyronine, 3,3'-diiodothyronine and 3'-monoiodothyronine kinetics. J Clin Endocrinol Metab 1982; 54:1097-100.  
    10. Wiersinga WM.  Propranolol and thyroid hormone production metabolism.  Thyroid  1991;1:273-7.  
    11. Kallner G, Ljunggren JG, Tryselius M.  The effect of propranolol on serum levels of T4, T3 and reverse-T3 in hyperthyroidism.  Acta Med Scand  1978;204:35-7.  
    12. Nilsson OR, Karlberg BE, Kagedal B et al.  Non-selective and selective beta-1 adrenoreceptor blocking agents in the treatment of hyperthyroidism.  Acta Med Scand  1979;206:21-5.  
    13. Feely J, Forrest A, Gunn A et al.  Propranolol dosage in thyrotoxicosis.  J Clin Endocrinol Metab  1980;51:658-61.  
    14. Baskin HJ, Cobin RH, Duick DS et al.  American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism.  Endocr Pract  2002;8:457-69.  
    15. Dalan R, Leow MK.  Cardiovascular collapse associated with beta-blockade in thyroid storm.  Exp Clin Endocrinol Diabetes  2007;115:392-6.

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MESH Terms & Keywords

  • Monodeiodinase Type I, 5'D-I, Monodeiodinase Type II, 5'D-II, Propranolol, Beta Blockers for Thyroid storm, Beta Blockers for Thyrotoxicosis, Propranolol for Thyroid Storm