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Introduction

    Thyroid storm , also known as thyroid crisis, is an rare form thyrotoxicosis in an extreme fashion

    The mortality that has been published has ranged from 20-100%, especially if prompt treatment isn’t initiated

    Thyroid storm often occurs in people with Graves disease who have stopped medication or whose underlying condition is

    undiagnosed

    The pathophysiology is characterized by adrenergic hyperactivity either by increased release of thyroid hormones (with or

    without increased synthesis) or increased receptor sensitivity.

    Precipitants of Thyroid Storm include Infection, trauma, surgery, DKA, withdrawal of anti-thyroid medication, or radioactive

    iodine therapy

    Diagnosis can be difficult due to the disease mimicking other disease states such as withdrawal syndromes and sepsis

Clinical Detail

PropertyPropranolol / EsmololMethimazole / PTUSSKIHydrocortisone
DosePropranolol: IV 0.5–1 mg over 10 min or PO 60–80 mg q4h. Esmolol: IV 500 mcg/kg bolus then 50–200 mcg/kg/min infusion.Methimazole 60–80 mg/day in divided doses. PTU 500–1000 mg load then 250 mg q4h.5 drops PO q6h.IV 300 mg load then 100 mg q8h.
AdministrationPropranolol IV: slow IV push over ~10 min. Esmolol: bolus + continuous infusion.PO.Place drops in water or juice; delay administration at least 1 hour after starting methimazole or PTU.Via IV push.
FormulationPropranolol PO/IV; Esmolol IV.PO.PO.IV/PO.
Adverse effectsBradycardia, hypotension.PTU: FDA black-box warning (2010) for severe/life-threatening hepatotoxicity. Methimazole: not preferred in pregnancy.If given before a thionamide, iodide can serve as substrate for thyroid hormone synthesis and worsen thyroid storm.Further hyperglycemia.
CommentsPropranolol is the only beta-blocker documented to inhibit peripheral T4→T3 conversion. Preferred, but may be hard to access emergently — esmolol is a reasonable alternative until propranolol is available.———

How each drug class works

Drug classPurpose
Iodide — Lugol solution, potassium iodide (SSKI), lithiumPrevents release of pre-formed thyroid hormone from the thyroid gland.
Thioureas — methimazole, propylthiouracil (PTU)Inhibit thyroid peroxidase, blocking production of T3 and T4.
Beta-blockers — propranolol, esmololBlock β-adrenergic effects (tremor, tachycardia, agitation, fever, diaphoresis). Propranolol also blocks peripheral T4→T3 conversion.
Steroids — hydrocortisone, dexamethasoneInhibit peripheral T4→T3 conversion and treat relative adrenal insufficiency.

Evidence for these agents is limited (case reports/series, 1970s–90s); they are recommended in the 2016 American Thyroid Association guidelines for hyperthyroidism and thyrotoxicosis.

Evidence

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    Drug

    Purpose

    Iodide: Lugol solution, Potassium Iodine (SSKI),

    and lithium

    Used to prevent the release of pre-formed thyroid hormone from the thyroid

    gland

    Thioureas: Methimazole/Propylthiouracel (PTU)

    Inhibit thyroid peroxidase, an enzyme involved in the production of T3 and T4

    through the iodination of tyrosine residues on thyroglobulin

    Beta Blocker: Propranolol and Esmolol

    Blocks β-adrenergic receptors to allow for effective treatment of systemic

    effects, such as tremor, tachycardia, agitation, fever, diaphoresis, psychosis

    Propranolol also blocker peripheral conversion of T4T3

    Steroids: Hydrocortisone and Dexamethasone

    Inhibition of peripheral conversion of T4 to T3 and treat relative adrenal

    insufficiency.

    There is very limited evidence for the use of these agents that are limited to case reports and data dating back to 1970s-90.

    A great review article is Thyroid emergencies written by Joanna Klubo-Gwiezdzinska in the references below.

    However, these drugs are recommended in the 2016 American Thyroid Association Guidelines for Diagnosis and

    Management of Hyperthyroidism and other causes of Thyrotoxicosis.

Conclusions

  • Thyroid storm is a rare, life-threatening extreme of thyrotoxicosis with reported mortality of 20–100% when prompt treatment is delayed, so therapy is started empirically on clinical suspicion.
  • Management layers four drug classes that each target a different step: a beta-blocker (propranolol or esmolol) for adrenergic symptoms, a thionamide (methimazole or PTU) to block hormone synthesis, iodide (SSKI) to block release of pre-formed hormone, and a corticosteroid (hydrocortisone) to blunt peripheral T4→T3 conversion and cover relative adrenal insufficiency.
  • Sequence matters: give the thionamide first and delay iodide at least 1 hour, because iodide given before a thionamide can act as substrate and worsen the storm.
  • Propranolol is preferred among beta-blockers as the only one documented to inhibit peripheral T4→T3 conversion; the supporting evidence is limited (case reports/series from the 1970s–90s), but these agents are recommended by the 2016 American Thyroid Association guidelines.

References

Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved September 6, 2018, from http://www.micromedexsolutions.com/

Idrose A. Hyperthyroidism. In: Tintinalli JE, Stapczynski J, Ma O, Yealy DM, Meckler GD, Cline DM. eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e New York, NY: McGraw-Hill; 2016.

Bahn RS, et al; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract 17:456-520, 2011. Erratum in: Endocr Pract 19:384, 2013.

Thiessen MEW. Thyroid and Adrenal Disorders in: Walls, R. Hockberge RS, Gausche-Hill M. (2018). Rosen’s emergency medicine: Concepts and clinical practice (9th ed.). Philadelphia, PA: Elsevier/Saunders.

Klubo-Gwiezdzinska J, Wartofsky L. Thyroid emergencies. Med Clin North Am. 2012 Mar;96(2):385-403.

Devereaux D and Tewelde SZ. Hyperthyroidism and thyrotoxicosis. Emerg Med Clin North Am. 2014 May;32(2):277-92.

Busti AJ, Herrington JD, Nuzum D. ” Why Propranolol Is Preferred to Other Beta-Blockers in Thyrotoxicosis or Thyroid Storm”, Evidence Based Consult blog, December 21, 2018. Available at: https://www.ebmconsult.com/articles/propranolol-preferred-thyroid-storm-thyrotoxicosis

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