- Approaching the diagnosis
- Diagnostic criteria
- Refractory thyroid storm
- Questions & discussion
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approaching the diagnosis
Thyroid storm is the most severe form of hyperthyroidism, wherein organ failure begins to occur. If left untreated, this may lead to multi-organ failure and death. Due to the rarity of this condition and its multitude of diverse presentations, diagnosis can be extremely challenging.
when to consider thyroid storm
- Thyroid storm is very rare, so the main challenge is considering it. The possibility should be entertained in the following situations:
- (1) Patient with known hyperthyroidism plus any acute illness/deterioration.
- (2) New-onset atrial fibrillation and/or dilated cardiomyopathy.
- (3) New-onset delirium/psychosis plus abnormal vital signs (fever, tachycardia).
- (4) Hyperthermia (temperature above ~40C).
- (5) Septic-appearing patient without any focus of infection (i.e. distributive shock of unknown origin).
precipitants of thyroid storm
- General stressors
- #1 = Infection
- Surgery or trauma (especially trauma involving the neck, such as strangulation)
- Pulmonary embolism, myocardial infarction, stroke
- Labor, preeclampsia
- Diabetic ketoacidosis, hypoglycemia
- Thyroid surgery, radioiodine therapy
- Noncompliance with anti-thyroid medications
- Overdose of thyroid hormone
- Acute iodine load from contrast dye or amiodarone
- Checkpoint inhibitors, Sorafenib (NEXAVAR, agent used for renal cell carcinoma)
- ~30% of patients have no identifiable precipitant.1
signs & symptoms
- Cardiac (often predominant feature)
- Tachycardia, atrial fibrillation
- High-output, distributive heart failure state
- Systolic heart failure can occur
- Delirium, agitation, psychosis
- Hyperthermia is nearly universal
- May reach 40-41C (104-106F), classically with associated diaphoresis
- Diarrhea, nausea, vomiting
- Abdominal pain
- Jaundice, hepatic failure
- Other features may suggest hyperthyroidism
- Goiter, scar from partial thyroidectomy
- Thyroid labs aren't worse than uncomplicated hyperthyroidism. The differentiation between hyperthyroidism and thyroid storm is based on clinical findings – not how severe the lab abnormality is.
- Key findings: Low TSH & elevated free T4 and free T3
- May also see:
- Low or high WBC
- Abnormal liver function tests
— Dustin Morrow MD (@SonoSerious) December 20, 2015
Burch criteria for thyroid storm
- 37.2-37.7 (99-99.9) = 5 points
- 37.8-38.2 (100-100.9) = 10 points
- 38.3-38.8 (101-101.9) = 15 points
- 38.9-39.4 (102-102.9) = 20 points
- 39.5-39.9 (103-103.9) = 25 points
- 40+ (104+) = 30 points
- 99-109 = 5 points
- 110-119 = 10 points
- 120-129 = 15 points
- 130-139 = 20 points
- >140 = 25 points
- CNS effects
- Mild (e.g. agitation) = 10 points
- Moderate (e.g. delirium, psychosis) = 20 points
- Severe (e.g. seizure, coma) = 30 points
- Diarrhea, n/v, abdominal pain = 10 points
- Unexplained jaundice = 20 points
- Heart failure
- Mild (e.g. edema) = 5 points
- Moderate (e.g. rales) = 10 points
- Severe (e.g. pulmonary edema) = 15 points
- Atrial fibrillation present = 10 points
- Precipitant history present = 10 points
interpretation of Burch criteria
- 45 or more: Highly suggestive of thyroid storm
- 25-44: Supports diagnosis of thyroid storm or impending storm
- <25: Thyroid storm unlikely
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- Thyroid storm is difficult to diagnose because there is a continuum of severity, ranging from severe hyperthyroidism to thyroid storm. Any specific binary cutoff is artificial.
- These diagnostic criteria are helpful because they provide a systematic framework to think about the diagnosis. However, we aren't forced to adhere rigidly to these criteria, for a few reasons:
- 1) The diagnosis of thyroid storm is a partially a diagnosis of exclusion. For example, sepsis with multi-organ failure could easily score >45 points on the above criteria. Therefore, a score >45 doesn't prove a diagnosis of thyroid storm.
- 2) Treatment for thyroid storm is reasonable in any patient with severe hyperthyroidism causing organ failure (especially heart failure). Therefore, even if the patient doesn't have a score >45, it may be prudent to initiate therapy for thyroid storm. Patients with borderline storm may improve rapidly and then therapy can be de-escalated.
getting started: evaluation & tx of cause
Evaluation includes securing a diagnosis of thyroid storm and simultaneously looking for any potential trigger of the episode. Consider the list of common precipitants above.
basic studies to order
- Glucose, electrolytes including Ca/Mg/Phos
- Liver function tests
- Coagulation studies (can cause DIC)
- Creatinine kinase (can cause rhabdomyolysis)
if infection is suspected
- Blood cultures & infectious workup as indicated.
- There should generally be a low threshold for initiation of antibiotics (e.g. if the patient has vasodilatory shock, or focal signs of infection). If antibiotics are being started, check procalcitonin.
- Steroid blocks release of T4 from the thyroid and also blocks peripheral activation of T4 into T3.
- The loading dose of hydrocortisone is 300 mg IV.
- The maintenance dose of hydrocortisone 100 mg IV Q8hr. This dose may be continued for several days until the thyroid storm improves, at which point it can be rapidly tapered off.
- If hydrocortisone isn't immediately available, may use methylprednisolone 125 mg initially, with a subsequent reduction to methylprednisolone 60 mg daily.
- Thionamides block thyroid hormone synthesis. This is generally a cornerstone of therapy, although it may be ineffective in rare cases of thyroid storm due to thyroiditis.2
- Methimazole [Medscape monograph]
- The safest thionamide (less hepatotoxic).
- Clinical evidence suggests that it may be equally effective as propylthiouracil.
- May be the preferred agent, especially in patients with hepatitis or with unknown liver function tests.
- Methimazole dose: 40 mg loading dose, then 20 mg q4 hours. After 24 hours, the dose may be reduced to 20 mg q12 hours.
- Propylthiouracil [Medscape monograph]
- Theoretically more effective than methimazole, because it reduces peripheral conversion of T4 into T3.
- Propylthiouracil is more hepatotoxic, with an FDA black box warning for causing hepatic failure.
- Might be preferred in more fulminant and definite cases of thyroid storm, or in pregnancy.
- Dose is 200 mg propylthiouracil q4.
- Transition to methimazole once patient is improving clinically.
- Immediately suppresses thyroid hormone release via the Wolff-Chiakoff effect.
- Must be given at least an hour after thionamide (to prevent increasing thyroid hormone synthesis).
- Different hospitals have different formulations:
- Lugol's Solution 8 drops (0.4 ml) PO q6hr (take with fluid/food to avoid gastritis).
- Saturated solution of KI (SSKI), 5 drops (0.25 ml) PO q6hr.
- To convert between drops and ml: 1 drop = 0.05 mL.
- Iodine may be continued for up to ten days (eventually the suppressive effect will wear off).
- For patients allergic to iodide, lithium may be used instead (300 mg PO q6-8hr, target lithium level of 0.6-1 mEq/L).
- This binds thyroid hormone in the gut and prevents enterohepatic re-absorption.3
- Cholestyramine is effective even in patients who haven't taken exogenous thyroid hormone (e.g. Graves disease).
- This is extremely safe (available over-the-counter, for treatment of diarrhea).
- Dose is 4 grams orally q6hrs.
- Continue until patient is fully improved.
thyroid storm may cause numerous hemodynamic derangements:
- 1) Hypovolemia (from diaphoresis, vomiting, diarrhea)
- 2) Systolic heart failure, including cardiogenic shock
- 3) Distributive shock (increased tissue oxygenation causes systemic vasodilation)
- 4) Tachycardia (either sinus tachycardia or atrial fibrillation).
- Moderate tachycardia may be a compensatory response to shock, which improves cardiac output.
- Severe tachycardia may be pathological, reducing ventricular filling and thereby exacerbating cardiovascular dysfunction.
Recent onset dyspnoea. This is the ECG. Bedside echo showed EF 30%. The cause- recent onset thyrotoxicosis pic.twitter.com/YFGFLzKZBa
— Victoria Stephen (@EMcardiac) April 2, 2014
- Volume should be repleted based on echocardiography, lung sonography, and history (e.g. history of poor oral intake, fever, and diarrhea suggest volume depletion).
- Vasopressors may be needed to maintain an adequate blood pressure. If the patient is already very tachycardic, phenylephrine might be a reasonable consideration to avoid exacerbating tachycardia.
- Magnesium repletion is a good first step for patients with atrial fibrillation and rapid ventricular rate. Hyperthyroidism itself may cause hypomagnesemia.
be careful about beta-blockers
- Widely recommended for thyroid storm, but be very careful: beta-blockade may exacerbate shock (especially in patients with systolic heart failure). A moderate degree of compensatory tachycardia (e.g. heart rate 110-130 b/m) may be necessary to maintain adequate perfusion in some patients.
- Tachycardia is not the primary problem here. Aggressive beta-blockade may cause more harm than benefit.
- The literature contains numerous reports of patients who crash within 6 hours of initiation of therapy for thyroid storm. In many of these cases, beta-blockade may be the cause of deterioration.4
- Don't blindly give beta-blockers without first performing a complete hemodynamic evaluation (echocardiogram plus lung ultrasonography to look for evidence of cardiogenic pulmonary edema).
- More on hemodynamic evaluation in heart failure here.
- Contraindications to beta-blockade:
- Shock (especially cardiogenic shock with severely reduced ejection fraction)
- Cardiogenic pulmonary edema
- Esmolol infusion is probably the safest initial agent [Medscape monograph on esmolol]
- Up-titrate to ensure that the patient can tolerate beta-blockade.
- Japanese guidelines recommend esmolol, due to increased mortality in patients with heart failure treated with propranolol.5
- Propranolol [Medscape monograph on propranolol]
- Ideal beta-blocker, because it blocks peripheral activation of T4 to T3.
- Starting dose is 20-40 mg PO q6hr. If tolerated, may up-titrate to a dose of 80 mg q6.
— Scott K Aberegg MD MPH (@medevidenceblog) February 8, 2019
management of hyperthermia & agitation
- General principles:
- Hyperthermia is harmful because it increases cardiac workload and can also cause organ damage (e.g. rhabdomyolysis, delirium).
- However, induction of shivering is potentially dangerous, as this also increases myocardial workload. Fortunately, hyperthermia is due to increased heat generation by the tissues (rather than a change in hypothalamic set point), so shivering may not be a problem in these patients.
- Acetaminophen 650-1000 mg q6hr scheduled.
- Use of cooling blankets is recommended for high fever, if tolerated without shivering.1,5
- Avoid salicylates or NSAIDs, since these may increase free thyroid hormone levels.
- Agitation may worsen hyperthermia and impede ability to provide care.
- Olanzapine might be a good choice, either by PO, IM, or IV routes.5
- Case studies exist suggesting that haloperidol may precipitate thyroid storm. Although this is dubious, it might be a reason to prefer olanzapine over haloperidol.5
refractory thyroid storm
- Clinical improvement should ideally be seen reasonably soon (e.g. ~24-48 hours).
- Some patients will fail to respond to optimal medical management.
- Treatment options for refractory thyroid storm include plasmapheresis or thyroidectomy.
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questions & discussion
To keep this page small and fast, questions & discussion about this post can be found on another page here.
- Maintain a high index of suspicion for thyroid storm, as this will commonly mimic other conditions (e.g. psychosis, meningitis, hyperthermia, sepsis, cardiogenic shock).
- Avoid salicylates or NSAIDs, as these may bind to thyroid-binding globulin, causing increased levels of free thyroid hormone levels.
- Be cautious with beta-blockers, because some patients have thyrotoxicosis-induced cardiomyopathy and distributive shock. Aggressive beta-blockade may cause hemodynamic collapse in this situation, because the tachycardia is a compensatory response.
5-minute video to review everything (by Anna Pickens)
- Thyroid storm (EMCrit podcast 149)
- Thyroid storm (Nadia Award, ALIEM)
- Thyroid storm (Justin Morgenstern, First 10 in EM)
- Thyroid storm (Anand Swaminathan, CoreEM)
- Thyroid storm (Chris Nickson, LITFL)
- Thyroid storm (WikEM)
- Methimazole vs PTU (Jeff Hall & David Slattery, Vegas EM)
- 2016 Japan guidelines for thyroid storm (Satoh et al).
- Thyroid ultrasonography in Graves disease