Background

Mortality Without treatment: 80-100% With treatment: 10-30% [1]

Difference between severe thyrotoxicosis and thyroid storm is clinical diagnosis [2] Must empirically treat before laboratory confirmation Death caused by multi-organ dysfunction, congestive heart failure, respiratory failure, disrhythmias, DIC, hypoxic brain injury, or sepsis [3]



Precipitants

Thyroid physiology

Clinical Features

Bilateral infiltrative thyroid-associated exophthalmos

Enlarged and homogeneous thyroid.

"Plummer's nail" demonstrating onycholysis (separation of the nail from the nail bed). Abnormal nail findings occurs in about 5% of hyperthyroid patients.

Classic Triad

Complications

Apathetic Hyperthyroidism

Strikingly different rare form, dominated by depressed mental status, cardiac complications [11]

Treatment with antithyroid therapy is still mainstay

More common in elderly patients [12]

Differential Diagnosis

Wide Pulse Pressure

Evaluation

Workup

TSH Low or undetectable

Free T3/T4 Elevated

Chemistry Calcium may be elevated Hyperglycemia often present [13]

CBC May have thrombocytopenia Leukocytosis common [14]

LFTs Mild elevation in AST, ALT, LDH, bilirubin, ALP may be seen [15]

Cortisol level (rule-out concurrent adrenal insufficiency)

ECG

Rule out infection: CXR Blood culture UA Consider lumbar puncture after CTH



Diagnosis

Burch & Wartofsky Diagnostic Criteria

Category Points Thermoregulatory dysfunction (°F) Tmax= 99-99.9 5 Tmax= 100-100.9 10 Tmax= 101-101.9 15 Tmax= 102-102.9 20 Tmax= 103-103.9 25 Tmax= 104 30 Central nervous system effects Mild (Agitation) 10 Moderate (delirium, psychosis, extreme lethargy) 20 Severe (seizure, coma) 30 Gastrointestinal-hepatic dysfunction Moderate (diarrhea, nausea and vomiting, abdominal pain) 10 Severe (unexplained jaundice) 20 Cardiovascular dysfunction (tachycardia) HR= 99-109 5 HR= 110-119 10 HR= 120-129 15 HR= 130-139 20 HR= 140 25 Congestive Heart Failure Mild (pedal edema) 5 Moderate (bibasilar rales) 10 Severe (pulmonary edema, A. fib) 15 Precipitant history Negative 0 Positive 10

Scoring[16]

>45 = Highly suggestive of thyroid storm

25-44 = Suggestive of impending storm

<25 = Unlikely to represent storm

Identify precipitant (i.e. med noncompliance, DKA, infection). When in doubt of diagnosis, the EP should treat given the high mortality rate, as a few doses of anti-thyroid medication are unlikely to harm euthyroid patient[18]

Supportive care

Fever Do not aggressively cool as this can lead to vasoconstriction [19]

Careful cooling measures (ice packs & cooling blankets)

Acetaminophen (avoid aspirin or NSAIDS because they displace thyroid hormone from TBG) Dehydration/hypoglycemia D5NS (most patients have depleted glycogen stores)

Crackles in lungs are likely high output heart failure, NOT fluid overload Cardiac decompensation (CHF, A-fib) Rate control, inotropes, diuretics as needed (short acting always better) Agitation Benzodiazepines are the preferred agent

Treat Increased Adrenergic Tone

Propranolol PO 60-80 mg q4hr (if can tolerate PO, no PR form)

or

Propranolol IV 1-2mg over 10 min; if tolerates then 1-2mg boluses q15 minutes until HR <100 [20] Followed by drip at dose required for heart rate control (3-5mg/hr) Relative contraindications are same as for other medical conditions (e.g. CHF, Reactive Airway Disease, see alternative therapies) In addition to decreasing peripheral conversion, propranolol will improve tremor, hyperpyrexia, and agitation Unlike other beta-blockers, propranolol also partially blocks conversion of T3 to T4



or

Esmolol 250-500mcg/kg loading dose, then 50-100mcg/kg/min [21] B1 selective so can be used with active CHF, asthma, etc Does not have T3 to T4 blocking properties of propranolol



or

Reserpine 2.5 - 5 mg IM q4h Option for patients in whom beta-blockers are contraindicated [22]



[23] Block New Hormone Synthesis

Thionamides are the main class of medications which prevent new hormone synthesis by inhibiting the iodination of tyrosine residues by thyroid peroxidase (TPO) enzymes. Propylthiouracil (PTU) is prefered over methimazole because it will also bock T4→T3 conversion

PTU 500-1000mg PO or NG followed by 250mg q4hr May provide PR, but PO or NG are preferred routes (IV formulations not available in US)

Note black box warning of hepatotoxicity so check LFTs prior

Avoid in patients with significant liver disease; use methimazole instead

Theoretically first line and offers advantage over methimazole PTU has earlier onset of action and capacity to inhibit peripheral conversion of T4 to T3 However, no significant difference in mortality between PTU and methimazole [24]

Methimazole 20-25mg q4hr (80 - 100 mg daily in divided doses) Longer acting than PTU

IV formulations may be available in Europe

Should be avoided in pregnancy by classic teaching (freely crosses placenta, birth defects)

Available in IV formulations outside America, but use supported by case reports only [25] Potassium iodide (SSKI) Give 1hr after PTU or methimazole to prevent increased hormone production (Jod-Basedow effect) [26]

Block hormone release: (Wolff-Chaikoff effect) only after hormone synthesis is inhibited. Iodine concentration leads to transient decrease of T3/T4

5 drops (0.25 mL or 250mg) orally every 6 hours

Avoid potassium iodide if patient is on amiodarone

Can substitute radiocontrast dyes (Iopanoic acid, ipodate and iopanoate), PO Lugol solution, OR IV sodium iodide [27] Lithium carbonate[28] Consider if iodine allergic

Lithium carbonate 300mg PO q8hr

300mg PO q8hr Lithium inhibits thyroid hormone release from the gland and reduces iodination of tyrosine residues, but its use is complicated by the toxicity that can ensue

Treatment of choice for iodine-induced hyperthyroidism as the result of contrast load or amiodarone Lugol’s Solution 8 drops PO q 6 (alternative iodine source) Sodium Iodide 0.5mg IV Q 12 hours (alternative iodine source)

Adrenal Insufficiency Treatment

Often there may be associated adrenal insufficiency (also blocks T4>T3)

Hydrocortisone 300mg IV bolus, followed by 100mg TID for several days OR

Dexamethasone 4mg IV q6hr

Note that corticosteroids also inhibit conversion of T4 to T3 and block release of hormone from thyroid gland

For recalcitrant thyroid storm, with remaining cardiac and neurologic symptoms

Especially in the case of fulminant liver failure, in which anti-thyroid drugs are contraindicated [30]

Repeat sessions until TFTs normalize

Removes cytokines, auto-antibodies, thyroid hormones, thyroid hormone bound proteins

Antibiotics

Second most common etiology of thyroid storm (after medication noncompliance) is infection [31]

Low threshold to start broad spectrum antibiotics

Disposition

Admission to ICU

See Also

References