Endocrine and Metabolic 4: Thyroid Storm Portal
(Severe Thyrotoxicosis/Hyperthyroidism)
Introduction
Thyroid storm is a relatively rare, life-threatening condition in which the
patient develops severe manifestations of thyrotoxicosis. Thyroid storm
most often occurs in partially treated or untreated thyrotoxic patients
who are exposed to some form of physiologic stress or precipitating
factor. These may include infection, trauma, surgery, psychological
stress, MI, CNS lesions, pregnancy (especially during labor), DKA,
radioactive iodine treatment not pre-treated with anti-thyroid drugs,
or abrupt discontinuation of anti-thyroid medications.
Cardinal Findings
- Elevated temperature, usually > 38.5°C (101.3°F)
- CNS abnormalities of restlessness, confusion, agitation, or coma
- Tachycardia (greater than expected from the fever)
- Nausea, vomiting, and/or diarrhea
- Dehydration
Other Symptoms of Thyrotoxicosis
Tremor, weight loss, nervousness, heat intolerance, muscle weakness,
palpitations
Other Signs of
Thyrotoxicosis
Warm, smooth skin; tremor; thyroid enlargement; tachyarrhythmias; wide
pulse pressure
Laboratory Tests to Obtain
- Serum T4, T3, TSH, free-T4
- CBC
- Sodium, potassium, chloride, calcium
- Plasma cortisol
- ECG
- Chest x-ray
Laboratory Findings (Similar to other hyperthyroid patients)
- Elevated serum free-T4, T4, and T3 with suppressed TSH. (The thyroid function test results are frequently not available to assist in the initial diagnosis of hyperthyroidism.)
- Leukocytosis and anemia are common findings.
- Hyperglycemia
- Hypercalcemia
- Elevated liver function tests
- Adrenal insufficiency
- Tachycardia, either sinus tachycardia or other tachyarrhythmias like atrial fibrillation
- Chest x-ray showing signs of CHF or pneumonia.
Diagnosis
The
diagnosis of thyroid storm is primarily a clinical diagnosis based on
the severity of symptoms rather than on the level of the patient's
thyroid hormone. Burch and Wartofsky have devised criteria
for
the diagnosis of thyroid storm.1
Diagnostic Criteria for Thyroid
Storm*†
Thermoregulatory
dysfunction |
Cardiovascular
dysfunction |
||
Temperature |
Score |
Tachycardia |
Score |
99-99.9 |
5 |
99-109 |
5 |
100-100.9 |
10 |
110-119 |
10 |
101-101/0 |
15 |
120-129 |
15 |
102-103.9 |
20 |
130-139 |
20 |
103-103.9 |
25 |
> 140 |
25 |
> 104 |
30 |
||
Central nervous system effects |
Congestive heart failure |
||
Mild—agitation |
10 |
Mild-pedal
edema |
5 |
Moderate—delirium, psychosis, extreme lethargy |
20 |
Moderate—bibasilar rales |
10 |
Severe—seizures, coma |
30 |
Severe—pulmonary edema |
15 |
Atrial fibrillation |
10 |
||
Gastrointestinal—hepatic dysfunction |
Precipitant history |
||
Moderate—diarrhea, N/V abdominal pain |
10 |
Negative |
0 |
Severe—unexplained jaundice |
20 |
Positive |
10 |
* A score of > 45 supports the diagnosis of thyroid storm; a score of 25 to 44 suggests the diagnosis, and a score < 25 makes thyroid storm unlikely.
Treatment of Thyroid Storm
Initial
treatment of patients with thyroid storm consists of many components
and requires the simultaneous use of multiple medications. This
therapeutic regimen includes2:
- General critical care to support the patient’s ABCs.
- A beta blocker to control the increased adrenergic tone induced by the excess thyroid hormone already in the circulation.
- A thionamide, like propylthiouracil (PTU) or methimazole, to inhibit the syntheses of new thyroid hormone.
- Agents to prevent the peripheral conversion of circulating T4 to T3 (the active form of thyroid hormone).
- Agents to prevent the release from the thyroid gland of pre-formed thyroid hormone.
- Corticosteroids to reduce the T4 to T3 conversion and help treat the autoimmune process in Graves’ disease.
- General critical care to support the patient’s ABCs. Mortality
from thyroid storm is high so aggressive supportive care of the patient
in an intensive care unit is essential. Larger and
more-frequent-than-usual doses of medications may be necessary.
- Treat severe hyperpyrexia. See Vol I—PATHWAY 1, #3 and Vol III—ENV2 Hyperthermia/Heat Stroke. Use external cooling, such as cooling blankets, and acetaminophen. (Avoid aspirin, as salicylates may increase free thyroid hormone levels.)
- Correct dehydration (that can be severe) and electrolyte imbalance. See Vol II—Circ Skills 1 Arterial and Venous Catheter Insertion; Vol III—END/M7 Disorders of Electrolyte Concentration, Trau Care 1 Shock. Evaluate carefully for fluid overload and CHF. (See the following.) The IV fluids should contain dextrose.
- Evaluate and treat CHF: Be aware that CHF may be ‘high output’ heart failure due to the increased circulating thyroid hormone. Beta blocker therapy can help heart failure that is due to the thyrotoxic effects on rate and myocardial muscle. However, beta blockers can worsen CHF due to other causes, such as ischemia. (See the following about the use of beta blockers in thyroid storm.)
- Control rapid supraventricular tachyarrhythmias. If the patient doesn’t need emergency cardioversion, consider an intravenous beta blocker if no contraindications exist. (See discussion that follows about the use of beta blockers in thyroid storm.) Note that atrial fibrillation due to thyroid storm may be unresponsive to usual methods of rate control and conversion until anti-thyroid treatment has begun. The normal doses of digoxin may be ineffective. See Vol III—CV8 Tachycardia Treatment.
- Treat precipitating or concomitant diseases, such as infection or DKA.
-
Consider consultation with an appropriate specialist.
-
A beta blocker to control the increased adrenergic tone induced by the
excess thyroid hormone already in the circulation. Beta-adrenergic
blocking agents are considered a mainstay in the
treatment of most patients with severe hyperthyroidism due to the
ability of beta blockers to block the peripheral (tissue) effects of
the excess circulating thyroid hormone. These drugs must be used with
caution in patients with CHF or other relative contraindications (such
as asthma or COPD) to their use.
- Propranolol is frequently used for the initial therapy. Give propranolol, IV or PO, depending on severity. IV dosage: 1 to 2 mg (given at rate of < 1 mg/min) and repeat every 10 to 15 min until the patient is adequately beta blockaded as indicated by the reduction of symptoms or until 5 to 10 mg have been given. Once the patient’s symptoms are controlled, give maintenance doses of propranolol 1 to 3 mg IV every 4 hours; or give PO or NG 20 to 120 mg every 4 to 6 hours.3 PEDS: 0.05 to 0.15 mg/kg IV; give half at rate of < 1 mg/min and observe; give other half if needed. Maintenance doses in pediatric patients PO: 2 mg/kg/d divided every 6 h.
- An alternative regimen to the use of propranolol if you are in doubt as to the cause of CHF in the thyrotoxic patient, is to consider beginning beta blocker therapy with esmolol, a short-acting (half life ~ 9 minutes) titratable beta blocker. Dose: IV loading dose of 500 µg/kg over 1 min, then 50 to 100 µg /kg/min.4 This regimen allows rapid titration of the beta blocker to achieve adequate beta blockade while minimizing the adverse side effects.2
-
Guanethidine
or reserpine (mechanism: autonomic sympathetic blockade) are
alternatives to consider if beta blockers are contraindicated.
-
A thionamide, like propylthiouracil (PTU) or methimazole, to inhibit
the syntheses of new thyroid hormone. Thionamides, PTU or methimazole,
block the synthesis of further hormone synthesis within 1 to 2 hours
after administration, but they do not stop the release of the hormone
by the thyroid gland that has already been formed.2 PTU has the added
advantage in thyroid storm of blocking the T4 to T3 conversion in the
periphery. Methimazole has the advantage of having a much longer
duration of action than PTU and thus does not need to be dosed as
often. (See more on methimazole and PTU in Special Notes About Treating
Thyroid Storm, this portal.)
- PTU is given PO or NG. Different regimens exist: one is 800 to 1200 mg/24 h divided every 4 to 6 h on day 1, then 100 to 150 mg every 6 h.
- Methimazole 30 mg every 6 h PO or NG.
- Both drugs can be suspended in liquid for rectal administration.5,6
- Agents to prevent the peripheral conversion of circulating T4 to T3
(the active form of thyroid hormone).
- Iodinated radiocontrast agents such as Iopanoic acid (Telepaque) or Iodate (Oragrafin) are potent inhibitors of T4 to T3 conversion in the periphery. The dose is 0.5 to 1.0 g IV every 24 h. Since they are iodinated, the chosen thionamide must be given at least 1 hour before the iodine-containing substance to prevent the iodine from being used by the thyroid to produce more thyroid hormone.2,7
- Glucocorticoids also reduce T4 to T3 conversion. (See #6 for dosage)
-
Propylthiouracil helps to reduce T4 to T3 conversion.
-
Agents to prevent the release from the thyroid gland of pre-formed
thyroid hormone. Iodides are the most effective agents in this setting.
However, iodides also promote new hormone synthesis. Therefore, it is
important not to give iodides until 1 hour after PTU has been
administered, which gives PTU time to begin to inhibit any new hormone
synthesis. Do not use iodides in pregnancy unless the benefits outweigh
the risks.
- Sodium iodide (not widely available) Dose: 0.5 to 1 g slow IV (over 30 min) every 8 to 12 h. PEDS: Dose for < 12 years is not established.
- Iodide preparations: Lugol’s solution, 10 drops every 8 h or SSKI drops (1 g/mL) 5 drops every 6 h PO.2 The Lugol’s solution may be added to IV fluids since it is sterile,8 or it may be given rectally.9
- Iodinated radiographic contrast agents (see above) probably release enough iodine to be effective, but there is no data to confirm this.2
- Lithium may be used if iodides are contraindicated. However it must be used with caution due to its neurological and renal toxicity.2
- Corticosteroids to reduce the T4 to T3 conversion and help treat the autoimmune process in Graves’ disease. Corticosteroids reduce the conversion of the inactive T4 to the active form of thyroid hormone, T3. There is some evidence that the use of steroids in thyroid storm improves the outcome of the treatment.2 Steroids also may have a suppressive effect on the autoimmune process if the thyroid storm is due to Graves’ disease.2
- Hydrocortisone2 100 mg IV every 8 h or
- Dexamethasone 2 mg every 6 h. PEDS: Loading dose: 0.15 mg/kg/dose every 6 h.
Special Notes About Treating Thyroid Storm
- Do not use salicylates to lower the patient's temperature because salicylates may increase free thyroid hormone levels (free T4 and T3) by interfering with protein binding.
- Both of the thionamides, propylthiouracil and methimazole, are effective for the treatment of thyroid storm. Although both drugs block iodine organification and thyroid hormone synthesis by the thyroid gland by inhibiting thyroid peroxidase, PKU has the added benefit of impairing the peripheral conversion of T4 to T3. However, methimazole has the advantage of a longer duration of action than PTU so does not need to be dosed as often. If an iodinated radiocontrast agent (such as iopanoic acid) is given with methimazole to block the T4 to T3 conversion, then both of the thionamides are of equal efficacy.
- Iodides (I-) given PO or IV are the most effective agents in blocking preformed thyroid hormone release from the thyroid gland. Do not give the iodides until after the anti-thyroid drugs have been administered since loading the thyroid with iodide promotes new hormone synthesis, and this is blocked by the PKU. Iodides also reduce the conversion of T4 to T3 in the periphery.
- Give patients with a history of iodine allergy lithium carbonate 300 mg PO every 6 hours in place of the iodides. Lithium carbonate inhibits thyroid hormone release.
- To achieve a more rapid decrease in thyroid hormone levels, add iodides to the PTU therapy during the first week of treatment for patients with severe symptoms.
- Beta blockers may be useful for patients who have severe symptoms from their hyperthyroidism, as long as they do not have non-dysrhythmia related CHF, such as ischemic heart disease causing CHF, chronic bronchitis, or asthma.
† Adopted from Burch HB, Wartofsky L.
References
- Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrine Metab Clin North Am. 1993;22:263.
- Ross DS. Treatment of Thyroid Storm. In UpToDate. Rose BD. (Ed) UpToDate, Wellesley, MA, 2002.
- Das G, et al. treatment of thyrotoxic storm with intravenous administration of propranolol. Ann Intern Med. 1969;70:985.
- Brunette DD, et al. Emergency department management of thyrotoxic crisis with esmolol. Am J Emerg Med. 1991;9:232.
- Nareem N, et al. Methimazole: an alternative route of administration. J Clin Endocrinol Metab. 1982;54:180.
- Walter RM, et al. Rectal administration of propylthiouracil in the treatment of Graves’ disease. Am J Med. 1990;88:69.
- Baeza A, et al. Rapid preoperative preparation in hyperthyroidism. Clin Endocrinol. 1991;35:439.
- Benua RS, et al. Thyroid storm. In: Current Therapy in Endocrinology and Metabolism, 5th ed, Bardin, CW (Ed), Mosby, St Louis, 1994. p. 75.
- Yeung SCM, et al. Rectal administration of iodide and propylthiouracil in the treatment of thyroid storm. Thyroid. 1995;5:403.
- Klein I, Ojamaa K. Mechanisms of disease: thyroid hormone and the cardiovascular system. N Engl J Med. 2001;344:501-509.
- Ragland G. Thyroid storm. In: Emergency Medicine: A Comprehensive Study Guide. 4th ed. NY,NY. McGraw Hill; 1996:736-9.
- Tietgens ST, Leinung MC. Thyroid storm. Med Clin North Am 1995 Jan;79(1):169-84.