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
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.
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.
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
- Berry MJ, Larsen PR. The role of selenium in thyroid hormone action. Endocr Rev 1992;13:207-19.
- Glass CK, Holloway JM. Regulation of gene expression by the thyroid hormone receptor. Biochem Biophys Acta 1990;1032:157-76.
- Brent GA, Moore DD, Larsen PR. Thyroid hormone regulation of gene expression. Annu Rev Physiol 1991;53:17-35.
- Dillmann WH. Biochemical basis of thyroid hormone action in the heart. Am J Med 1990;88:626-30.
- Woeber KA. Thyrotoxicosis and the heart. N Engl J Med 1992;327:94-8.
WM, Touber JL. The influence of beta-adrenoreceptor blocking agents on
plasma thyroxine and triiodothyronine. J Clin Endocrinol Metab
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
- 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.
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.
- Wiersinga WM. Propranolol and thyroid hormone production metabolism. Thyroid 1991;1:273-7.
G, Ljunggren JG, Tryselius M. The effect of propranolol on serum
levels of T4, T3 and reverse-T3 in hyperthyroidism. Acta Med Scand
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.
- Feely J, Forrest A, Gunn A et al. Propranolol dosage in thyrotoxicosis. J Clin Endocrinol Metab 1980;51:658-61.
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
R, Leow MK. Cardiovascular collapse associated with beta-blockade in
thyroid storm. Exp Clin Endocrinol Diabetes 2007;115:392-6.