Author: Douglas S Ross, MD

Section Editor: David S Cooper, MD

Deputy Editor: Jean E Mulder, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Mar 2021. | This topic last updated: Jan 20, 2021.

INTRODUCTION

Thyroid storm is a rare, life-threatening condition characterized by severe clinical

manifestations of thyrotoxicosis [1]. In national surveys from the United States and
Japan, the incidence of thyroid storm was 0.57 to 0.76 and 0.20 per 100,000 persons
per year, respectively, and 4.8 to 5.6 per 100,000 hospitalized patients per year [2-4].
In the United States survey, 16 percent of inpatients with thyrotoxicosis were
diagnosed with storm [4]. It may be precipitated by an acute event such as thyroid or
nonthyroidal surgery, trauma, infection, an acute iodine load, or parturition. In
addition to specific therapy directed against the thyroid, supportive therapy in an
intensive care unit (ICU) and recognition and treatment of any precipitating factors is
essential since the mortality rate of thyroid storm is substantial (10 to 30 percent)
[2,5-8].

The clinical manifestations, diagnosis, and management of thyroid storm will be

reviewed here. The general topic of hyperthyroidism (without thyroid storm),
including diagnosis, causes, and treatment, is reviewed separately. (See "Overview of
the clinical manifestations of hyperthyroidism in adults" and "Diagnosis of
hyperthyroidism" and "Disorders that cause hyperthyroidism" and "Graves'
hyperthyroidism in nonpregnant adults: Overview of treatment" and
:
 "Hyperthyroidism during pregnancy: Treatment" and "Treatment of toxic adenoma
and toxic multinodular goiter".)

RISK FACTORS

Although thyroid storm can develop in patients with longstanding untreated

hyperthyroidism (Graves' disease, toxic multinodular goiter, solitary toxic adenoma),
it is often precipitated by an acute event such as thyroid or nonthyroidal surgery,
trauma, infection, an acute iodine load (including amiodarone use), or parturition. In
addition, irregular use or discontinuation of antithyroid drugs is a commonly
reported precipitant of thyroid storm [2,3,5,8,9]. The advent of appropriate
preoperative preparation of hyperthyroid patients undergoing nonthyroidal surgery
or thyroidectomy for hyperthyroidism has led to a dramatic reduction in the
prevalence of surgically induced thyroid storm [10].

It is unclear why certain factors result in the development of thyroid storm.

Hypotheses include a rapid rate of increase in serum thyroid hormone levels,
increased responsiveness to catecholamines, or enhanced cellular responses to
thyroid hormone [1]. The degree of thyroid hormone excess (elevation of thyroxine
[T4] and triiodothyronine [T3], suppression of thyroid-stimulating hormone [TSH])
typically is not more profound than that seen in patients with uncomplicated
thyrotoxicosis. However, one study found that while the total T4 and T3 levels were
similar to those seen in uncomplicated patients, the free T4 and free T3
concentrations were higher in patients with thyroid storm [11].

CLINICAL FEATURES

Patients with severe and life-threatening thyrotoxicosis typically have an

exaggeration of the usual symptoms of hyperthyroidism. (See "Overview of the
clinical manifestations of hyperthyroidism in adults".)

Symptoms and signs — Cardiovascular symptoms in many patients include

:
 tachycardia to rates that can exceed 140 beats/minute and congestive heart failure.
Hypotension, cardiac arrhythmia, and death from cardiovascular collapse may occur
[12]. In one series of 28 cases, cardiac manifestations were predominant, with >60
percent having severe tachycardia and/or atrial fibrillation [5].

Hyperpyrexia to 104 to 106°F is common. Agitation, anxiety, delirium, psychosis,

stupor, or coma are also common and are considered by many to be essential to the
diagnosis. In one series, altered mentation was the only clinical finding that
distinguished "storm" from "compensated" hyperthyroidism [6], and in another
series, it was statistically associated with mortality [5]. In a retrospective study from
Japan, older age >60 years, central nervous system dysfunction, requirement of
mechanical ventilation, and nonuse of antithyroid drugs or beta blockers were
associated with higher mortality [7]. Other symptoms may include severe nausea,
vomiting, diarrhea, abdominal pain, or hepatic failure with jaundice.

Physical examination may reveal goiter, ophthalmopathy (in the presence of Graves'
disease), lid lag, hand tremor, and warm and moist skin.

Laboratory findings — All patients with overt primary hyperthyroidism have low TSH
and high free T4 and/or T3 concentrations. The degree of thyroid hormone excess
typically is not more profound than that seen in patients with uncomplicated
thyrotoxicosis. Other nonspecific laboratory findings may include mild
hyperglycemia, mild hypercalcemia, abnormal liver function tests, leukocytosis, or
leukopenia. Hyperglycemia is secondary to a catecholamine-induced inhibition of
insulin release and increased glycogenolysis. Hypercalcemia may occur due to
hemoconcentration and enhanced bone resorption [13].

DIAGNOSIS

The diagnosis of thyroid storm is based upon the presence of severe and life-
threatening symptoms (hyperpyrexia, cardiovascular dysfunction, altered mentation)
in a patient with biochemical evidence of hyperthyroidism (elevation of free T4 and/or
T3 and suppression of TSH).
:
 There are no universally accepted criteria or validated clinical tools for diagnosing
thyroid storm. In 1993, Burch and Wartofsky introduced a scoring system using
precise clinical criteria for the identification of thyroid storm ( table 1) [14]. A score
of 45 or more is highly suggestive of thyroid storm, whereas a score below 25 makes
thyroid storm unlikely. A score of 25 to 44 is suggestive of impending storm. While
this scoring system is likely sensitive, it is not very specific. Another diagnostic system
based upon similar clinical findings (central nervous system manifestations, fever,
tachycardia, congestive heart failure, gastrointestinal manifestations) has been
proposed [2], but this latter system may have reduced sensitivity for making the
diagnosis [6].

● Evaluation

• Thyroid function tests (TSH) should be assessed in all patients in whom there
is a clinical suspicion of thyroid storm (hyperpyrexia with temperature >103°F
[39.4°C], goiter, cardiovascular dysfunction, altered mentation, atrial
fibrillation, history of antithyroid drug therapy for hyperthyroidism, recent
thyroid or nonthyroidal surgery, recent exposure to iodine-containing
contrast). If the TSH is below normal, free T4 and T3 should be measured.
The degree of hyperthyroidism (elevation of T4 and/or T3 and suppression of
TSH) in patients with thyroid storm is, in general, comparable with that in
patients with uncomplicated overt hyperthyroidism. Thus, the degree of
hyperthyroidism is not a criterion for diagnosing thyroid storm. (See
"Diagnosis of hyperthyroidism", section on 'Diagnosis'.)

• Determining the etiology of thyrotoxicosis in patients with thyroid storm by

measuring thyrotropin receptor antibodies (TRAb) or determining a
radioiodine uptake should not delay prompt treatment of patients with
clinical manifestations of thyroid storm. Most patients have Graves' disease,
and some have toxic adenoma or toxic multinodular goiter. A destructive
thyroiditis associated with the use of checkpoint inhibitors in compromised
oncology patients may rarely be associated with thyroid storm [15]. (See
"Diagnosis of hyperthyroidism", section on 'Determining the etiology'.)
:
 TREATMENT

The therapeutic options for thyroid storm are expanded from those used for
uncomplicated hyperthyroidism, with additional drugs often used such as
glucocorticoids and an iodine solution, and the standard drugs are given in higher
doses and with more frequent dosing. In addition, full support of the patient in an
intensive care unit (ICU) is essential since the mortality rate of thyroid storm is
substantial [2,5-8]. In two series of patients with thyroid storm (patients seen
between 2006 and 2013), mortality was 8 percent in a Los Angeles hospital and 25
percent in a Singapore hospital [5,6]. In a French series (patients seen between 2000
and 2017), mortality was 17 percent in the ICU and 22 percent 6 months after
hospital admission [8].

Our initial approach — The principles of treatment outlined below are based upon
clinical experience and case studies since there are no prospective studies. They are
frequently also applied to patients with severe hyperthyroidism who do not fully
meet the criteria for thyroid storm. The therapeutic regimen typically consists of
multiple medications, each of which has a different mechanism of action [13,16,17]:

● A beta blocker to control the symptoms and signs induced by increased

adrenergic tone
● A thionamide to block new hormone synthesis
● An iodine solution to block the release of thyroid hormone
● An iodinated radiocontrast agent (if available) to inhibit the peripheral conversion
of T4 to T3
● Glucocorticoids to reduce T4-to-T3 conversion, promote vasomotor stability,
possibly reduce the autoimmune process in Graves' disease, and possibly treat
an associated relative adrenal insufficiency
● Bile acid sequestrants may also be of benefit in severe cases to decrease
enterohepatic recycling of thyroid hormones

For patients with clinical features of thyroid storm or with severe thyrotoxicosis who
do not fully meet the criteria for thyroid storm (ie, impending storm), we begin
:
 immediate treatment with a beta blocker (propranolol in a dose to achieve adequate
control of heart rate, typically 60 to 80 mg orally every four to six hours, with
appropriate adjustment for heart rate and blood pressure) and either propylthiouracil
(PTU) 200 mg every four hours or methimazole (20 mg orally every four to six hours).
PTU is favored over methimazole because of PTU's effect to decrease T4-to-T3
conversion. One hour after the first dose of thionamide is taken, we administer
iodine (saturated solution of potassium iodide [SSKI], 5 drops orally every six hours or
Lugol's solution, 10 drops every eight hours). The administration of iodine should be
delayed for at least one hour after thionamide administration to prevent the iodine
from being used as substrate for new hormone synthesis in patients with toxic
adenoma or toxic multinodular goiter (since the etiology of the thyrotoxicosis is
frequently uncertain at the time of admission).

For patients with clinical features of thyroid storm, we also administer glucocorticoids
(hydrocortisone, 100 mg intravenously every eight hours). Cholestyramine (4 g orally
four times daily) may also be of benefit in severe cases to reduce enterohepatic
recycling of thyroid hormones. Supportive therapy and recognition and treatment of
any precipitating factors (eg, infection), in addition to specific therapy directed
against the thyroid, may be critical to the final outcome. Many patients require
substantial amounts of fluid, while others may require diuresis because of congestive
heart failure. Digoxin and beta blocker requirements may be quite high because of
increased drug metabolism as a result of hyperthyroidism. Infection needs to be
identified and treated, and hyperpyrexia should be aggressively corrected.
Acetaminophen should be used instead of aspirin since the latter can increase serum
free T4 and T3 concentrations by interfering with their protein binding.

Propranolol, PTU, and methimazole can be administered through a nasogastric tube.

Other formulations are reviewed below. (See 'Beta blockers' below and 'Thionamides'
below.)

Beta blockers — For patients with thyroid storm or severe thyrotoxicosis, we

begin immediate treatment with a beta blocker (typically propranolol in a dose to
achieve adequate control of heart rate, typically 60 to 80 mg orally every four to six
:
 hours, with appropriate adjustment for heart rate and blood pressure). The Japanese
guidelines recommend esmolol over propranolol because of increased mortality in
patients with congestive heart failure treated with propranolol [18]. In patients with
reactive airways disease, cardioselective beta blockers such as metoprolol or atenolol
could be considered, but this should be done carefully. In some patients with severe
asthma in whom beta blockers might be contraindicated, rate control can be
achieved with calcium-channel blockers such as diltiazem [19]. (See "Beta blockers in
the treatment of hyperthyroidism".)

Beta blockers should be used with extreme caution if the patient has decompensated
heart failure with systolic dysfunction or other contraindications to beta blockade (eg,
asthma or chronic obstructive pulmonary disease, severe peripheral vascular
disease). It is important to note, however, that control of tachycardia may lead to
improvement in cardiac function. (See "Initial pharmacologic therapy of heart failure
with reduced ejection fraction in adults", section on 'Beta blocker'.)

Propranolol is frequently selected for initial therapy because in high doses, it inhibits
the type 1 deiodinase, which may help reduce serum T3 levels [20]. In addition, it can
be given intravenously, but this should only be done in a setting where
hemodynamics can be monitored. The intravenous dose is 0.5 to 1 mg over 10
minutes followed by 1 to 2 mg over 10 minutes every few hours [14,21]. Higher doses
may occasionally be required, but care should be taken to avoid hypotension and
aggravation of existing heart failure. As an alternative to intravenous administration,
propranolol can be given orally or via nasogastric tube in a dose to achieve adequate
control of heart rate, typically 60 to 80 mg orally every four to six hours. When
transitioning from intravenous to oral/nasogastric treatment, intravenous therapy
may need to be continued until adequate effectiveness of the oral/nasogastric
treatment is ascertained.

An alternative regimen is to utilize the short-acting beta blocker esmolol. A loading

dose of 250 to 500 mcg/kg is given, followed by an infusion at 50 to 100 mcg/kg per
minute. This regimen permits rapid titration of the drug to achieve adequate beta
blockade while minimizing adverse reactions [22].
:
 Thionamides — Thionamides block de novo thyroid hormone synthesis within one
to two hours after administration. However, they have no effect on the release of
preformed hormone from the thyroid gland. For patients with thyroid storm or
severe thyrotoxicosis, we begin immediate treatment with either PTU 200 mg every
four hours or methimazole (20 mg orally every four to six hours). Carbimazole, a third
drug that is metabolized to methimazole, is available in many countries but not in
North America. (See "Thionamides in the treatment of Graves' disease".)

● We suggest PTU for the acute treatment of life-threatening thyroid storm in an

ICU setting, where it can be administered regularly every four hours. PTU, but
not methimazole, blocks T4-to-T3 conversion, and T3 levels drop by
approximately 45 percent within 24 hours after PTU but only 10 to 15 percent
within 24 hours after methimazole [23,24].

● Methimazole may be preferred for severe, but not life-threatening,

hyperthyroidism because methimazole has a longer duration of action and, after
weeks of treatment, results in more rapid normalization of serum T3 compared
with PTU and because methimazole is less hepatotoxic.

Patients started on PTU in the ICU should be transitioned to methimazole before

discharge from the hospital. In Japan, methimazole is preferred over PTU, and in a
retrospective study of 356 patients, there was no difference in mortality or disease
severity in patients receiving methimazole or PTU [18,25]. (See "Thionamides: Side
effects and toxicities".)

The dose of thionamide given to patients with thyroid storm is likely higher than that
required to completely block thyroid hormone synthesis. Both the substantial
mortality associated with thyroid storm and the possibility of poor absorption
because of concurrent gastrointestinal dysfunction have been used to justify the
higher dose. We typically administer 200 mg of PTU every four hours or 20 mg of
methimazole every four to six hours, orally or via nasogastric tube.

Both drugs can be suspended in liquid or made up as a suppository or retention

enema for rectal administration, which should be ordered well in advance from the
:
 pharmacy ( table 2) [13,26-29]. In one study comparing the use of an enema versus
a suppository preparation of PTU, 15 patients with newly diagnosed hyperthyroidism
were randomly assigned to a PTU enema (eight 50 mg tablets of PTU were dissolved
in 90 mL of sterile water) versus two PTU suppositories (200 mg of PTU were
dissolved in a polyethylene glycol base and put into each suppository) [29]. The
enema form provided better bioavailability than the suppository form (time to peak
level 85 versus 172 minutes, maximum peak level 3.89 versus 2.01 mcg/mL).
However, both preparations proved to have comparable therapeutic effect, as
measured by a significant decrease in serum free T3 levels.

For patients intolerant of oral or rectal thionamides, methimazole can be prepared

for intravenous administration by dissolving the tablets in pH-neutral isotonic saline
and by filtering through a 0.22 micrometer filter [30]. PTU can be prepared for
intravenous administration by dissolving the tablets in isotonic saline made alkaline
(pH 9.25) with sodium hydroxide [31]. Routine pharmacologic sterility tests are
required as dictated by individual hospitals. In one preliminary report, intravenous
PTU given in a dose of 576 mg/day (50 mg/mL) was used to attain euthyroidism [32].
Lower doses are used in patients with severe thyrotoxicosis who do not meet criteria
for thyroid storm.

Patients unable to take a thionamide — Although thionamide toxicity is

uncommon, some patients are unable to continue thionamides because of rare side
effects such as agranulocytosis or hepatotoxicity or because of allergy. Thyroid storm
has been reported in patients with Graves' disease after discontinuation of
thionamides due to agranulocytosis or hepatotoxicity [33,34]. In such patients who
require urgent treatment of hyperthyroidism, thyroidectomy is the treatment of
choice. Patients who are to undergo surgery require preoperative treatment of
thyrotoxicosis. We typically treat with beta blockers (if not contraindicated,
propranolol in a dose to achieve adequate control of heart rate, typically 60 to 80 mg
every four to six hours), glucocorticoids to inhibit conversion of T4 to T3 (eg,
dexamethasone, 1 to 2 mg every six hours), bile acid sequestrants (eg,
cholestyramine 4 g orally four times daily) to reduce enterohepatic circulation of
thyroid hormone, and, in patients with Graves' disease, iodine (SSKI, 5 drops [20
:
 drops/mL, 50 mg iodide/drop] orally every six hours or Lugol's solution, 10 drops [20
drops/mL, 6.25 mg iodine/drop] every eight hours) [35,36].

We continue treatment for up to five to seven days. Surgery should not be delayed
for more than 8 to 10 days, because of a phenomenon called escape from the Wolff-
Chaikoff effect. Large doses of exogenous iodine inhibit the organification of iodine
in the thyroid gland (the Wolff-Chaikoff effect). However, this effect is transient. The
iodide transport system is able to adapt to higher concentrations of iodine, allowing
thyroid hormone synthesis to proceed, with potential exacerbation of thyrotoxicosis.
(See "Iodine-induced thyroid dysfunction".)

In case reports, when traditional therapy has not been successful, plasmapheresis
has been used to prepare patients with thyroid storm for thyroid surgery (see 'Other
therapies' below). Iodinated contrast agents have also been used to prepare
hyperthyroid patients for urgent surgery, but they are no longer available in most
countries. (See "Surgical management of hyperthyroidism", section on 'Preoperative
preparation'.)

Iodine — For patients with thyroid storm or severe thyrotoxicosis, we administer

iodine one hour after the first dose of thionamide is taken. The administration of
iodine should be delayed for at least one hour after thionamide administration to
prevent the iodine from being used as substrate for new hormone synthesis in
patients with toxic adenoma or toxic multinodular goiter (since the etiology of the
thyrotoxicosis is frequently uncertain at the time of admission) [13].

Iodine-containing solutions have traditionally been utilized for the treatment of

thyroid storm since iodine blocks the release of T4 and T3 from the gland within
hours (see "Iodine in the treatment of hyperthyroidism"). Oral doses are potassium
iodide-iodine (Lugol's) solution, 10 drops (6.25 mg iodide/iodine per drop [0.05 mL])
three times daily or SSKI, 5 drops (50 mg iodide/drop [0.05 mL]) every six hours [17].
There is no standard intravenous iodide preparation, but it has been suggested that
10 drops of Lugol's solution can be directly added to intravenous fluids since it is
sterile [37]. The iodine solution can also be given rectally [28].
:
 Although iodine is typically well tolerated, local esophageal or duodenal mucosal
injury and hemorrhage have been reported after oral administration of Lugol's
solution (960 mg iodine/day) for the treatment of thyroid storm [38,39]. These
solutions can be irritating and should be diluted in 240 mL or more of beverage and
taken with food.

Iodinated radiocontrast agents — Iodinated contrast agents previously used to

treat hyperthyroidism are currently not available in the United States or in most other
countries.

Iopanoic acid and other iodinated radiocontrast agents used for oral
cholecystography have been used to treat hyperthyroidism, but there are little
published data on their efficacy in thyroid storm (see "Iodinated radiocontrast agents
in the treatment of hyperthyroidism"). They are, however, potent inhibitors of T4-to-
T3 conversion, and the release of iodine in pharmacologic quantities from these
agents has the additional benefit of blocking thyroid hormone release. They have
been extremely useful in treating severe hyperthyroidism and in preparing
hyperthyroid patients for urgent surgery [40,41]. If available, these agents can be
given to patients with severe hyperthyroidism at a dose of 0.5 to 1 g once daily.

Because they are iodinated, they should be given at least one hour after the
thionamide to prevent the iodine from being used as substrate for new hormone
synthesis.

Glucocorticoids — For patients with convincing clinical features of thyroid storm,

we administer glucocorticoids (hydrocortisone, 100 mg intravenously every eight
hours). In contrast, we do not routinely use glucocorticoids in patients with severe,
but not life-threatening, hyperthyroidism.

Glucocorticoids reduce T4-to-T3 conversion. In addition, they may have a direct effect
on the underlying autoimmune process, if the thyroid storm is due to Graves'
disease, and treat potentially associated limited adrenal reserve [42]. Because of the
high mortality rate of thyroid storm, their use is commonly recommended by experts,
although data are limited [43,44]. In a retrospective study based on a claims database
:
 (811 ICU admissions for thyroid storm between 2013 and 2017), 600 patients received
glucocorticoids and 211 did not [44]. There was no change in hospital mortality or
mortality 30 days after discharge. Glucocorticoid use was associated with increased
use of insulin.

Bile acid sequestrants — Thyroid hormones are metabolized in the liver, where
they are conjugated with glucuronide and sulfate, and the conjugation products are
excreted in the bile. Free thyroid hormones are released in the intestine and are
reabsorbed. Bile acid sequestrants (eg, cholestyramine 4 g orally four times daily)
have been found to reduce thyroid hormone levels in thyrotoxic patients by
interfering with enterohepatic circulation and recycling of thyroid hormone [45-47].
They are useful adjunctive therapy in patients with thyroid storm, particularly in
patients who are intolerant of thionamides.

Other therapies

● Plasmapheresis – Plasmapheresis has been tried when traditional therapy has

not been successful [34,48-52]. Plasmapheresis removes cytokines, antibodies,
and thyroid hormones from plasma [50]. In one case report, a woman with
Graves' disease and methimazole-induced agranulocytosis developed thyroid
storm after methimazole was discontinued. Treatment with plasmapheresis
resulted in marked improvement in thyrotoxicosis within three days, allowing
thyroidectomy for definitive therapy [34]. In a series of three patients who had
therapeutic plasma exchange for thyroid storm preoperatively, free T4 levels
were reduced on average by 21 percent after each treatment and by 55 percent
after four treatments [52].

● Lithium – Lithium has also been given to acutely block the release of thyroid
hormone. However, its renal and neurologic toxicity limit its utility.

Long-term management — After there is evidence of clinical improvement

(defervescence, resolution of central nervous system and cardiovascular
manifestations), iodine therapy can be discontinued and glucocorticoids tapered and
discontinued. Beta blockers can be withdrawn but only after thyroid function tests
:
 have returned to normal. The dose of thionamides should be titrated to maintain
euthyroidism. PTU, if given, should be switched to methimazole because of
methimazole's better safety profile and better compliance rates. Monitoring, dosing,
and duration of thionamide therapy are reviewed in detail separately. (See
"Thionamides in the treatment of Graves' disease", section on 'Monitoring'.)

In patients with Graves' disease, definitive therapy with radioactive iodine or

thyroidectomy is important to prevent a recurrence of severe thyrotoxicosis. We
suggest radioiodine therapy as our first choice for definitive therapy for
hyperthyroidism in the absence of moderate to severe orbitopathy, given its lower
cost and lower complication rate compared with surgery. If the patient received
iodine within a few weeks of planned radioiodine treatment, a radioiodine uptake
should be obtained to calculate the radioiodine treatment dose rather than using
fixed-dose radioiodine treatment. Surgery is an option, especially for patients with
hyperthyroidism due to a very large or obstructive goiter. Preparation for treatment
with radioiodine or surgery is reviewed separately. (See "Graves' hyperthyroidism in
nonpregnant adults: Overview of treatment" and "Radioiodine in the treatment of
hyperthyroidism", section on 'Approach to treatment' and "Surgical management of
hyperthyroidism", section on 'Preoperative preparation'.)

SUMMARY AND RECOMMENDATIONS

● Thyroid storm is a rare, life-threatening condition characterized by severe or

exaggerated clinical manifestations of thyrotoxicosis. Although thyroid storm can
develop in patients with longstanding untreated hyperthyroidism (Graves'
disease, toxic multinodular goiter, solitary toxic adenoma), it is often precipitated
by an acute event such as thyroid or nonthyroidal surgery, trauma, infection, an
acute iodine load, or parturition. (See 'Introduction' above and 'Risk factors'
above.)

● Patients with thyroid storm typically have an exaggeration of the usual

symptoms of hyperthyroidism. The classical symptoms of thyroid storm include
:
 tachycardia, hyperpyrexia, central nervous system dysfunction (agitation,
delirium, psychosis, stupor, or coma), and gastrointestinal symptoms (nausea,
vomiting, abdominal pain). Physical examination may reveal goiter,
ophthalmopathy (in the presence of Graves' disease), lid lag, hand tremor, and
warm and moist skin. Thyroid function tests show hyperthyroidism (suppressed
thyroid-stimulating hormone [TSH], elevated free thyroxine [T4] and
triiodothyronine [T3]) generally comparable with that in patients with
uncomplicated overt hyperthyroidism. (See 'Clinical features' above.)

● The diagnosis of thyroid storm is based upon the presence of severe and life-
threatening symptoms (hyperpyrexia, cardiovascular dysfunction, altered
mentation) in a patient with biochemical evidence of hyperthyroidism (elevation
of free T4 and/or T3 and suppression of TSH). There are no universally accepted
criteria or validated clinical tools for diagnosing thyroid storm. In one scoring
system ( table 1), a score of 45 or more is highly suggestive of thyroid storm,
whereas a score below 25 makes thyroid storm unlikely. (See 'Diagnosis' above.)

● The therapeutic options for thyroid storm are expanded from those used for
uncomplicated hyperthyroidism, with additional drugs typically used, such as
glucocorticoids and iodine solution (eg, saturated solution of potassium iodide
[SSKI]), and standard drugs are given in higher doses and more frequently. In
addition to specific therapy directed against the thyroid, supportive therapy in an
intensive care unit (ICU) and recognition and treatment of any precipitating
factors is essential since the mortality rate of thyroid storm is substantial (10 to
30 percent). (See 'Treatment' above.)

● For patients with clinical features of thyroid storm, we begin immediate

treatment with a beta blocker (propranolol in a dose to achieve adequate control
of heart rate, typically 60 to 80 mg orally every four to six hours), a thionamide,
and glucocorticoids (hydrocortisone, 100 mg intravenously every eight hours).
One hour after a thionamide is given, we administer iodine (SSKI, 5 drops [20
drops/mL, 50 mg iodide/drop] orally every six hours or Lugol's solution, 10 drops
[20 drops/mL, 6.25 mg iodine/drop] every eight hours). Bile acid sequestrants
:
 (cholestyramine, 4 g orally four times daily) may also be of benefit in severe cases
to decrease enterohepatic recycling of thyroid hormones. (See 'Treatment'
above.)

● For patients with life-threatening thyroid storm admitted to an ICU, we suggest

propylthiouracil (PTU) (200 mg orally every four hours) rather than methimazole
as initial therapy (Grade 2B). PTU blocks T4-to-T3 conversion and results in lower
serum T3 levels for the first several days of treatment. However, for severe, but
not life-threatening, hyperthyroidism, methimazole (20 mg every six hours) may
be preferred because of its longer half-life, lower risk of hepatic toxicity, and
because it ultimately restores euthyroidism more quickly than PTU. Patients
initially treated with PTU should be transitioned to methimazole before discharge
from the hospital. (See 'Thionamides' above and "Thionamides: Side effects and
toxicities".)

● For patients with contraindications to thionamides who require urgent correction

of hyperthyroidism, surgery is the treatment of choice. Patients who are to
undergo surgery require preoperative treatment of thyrotoxicosis. We typically
treat with beta blockers (if not contraindicated, propranolol 60 to 80 mg every
four to six hours), glucocorticoids to inhibit conversion of T4 to T3 (eg,
dexamethasone, 1 to 2 mg every six hours), bile acid sequestrants (eg,
cholestyramine 4 g orally four times daily), and, in patients with Graves' disease,
iodine (SSKI, 5 drops [50 mg iodide/drop] orally every six hours or Lugol's
solution, 10 drops [6.25 mg iodide/iodine per drop] every eight hours). We
continue treatment for up to five to seven days. (See 'Patients unable to take a
thionamide' above and "Surgical management of hyperthyroidism".)

● After the clinical manifestations of thyroid storm are improved, long-term

therapy is required to prevent a recurrence of severe thyrotoxicosis. For definitive
therapy of patients with hyperthyroidism secondary to Graves' disease, toxic
multinodular goiter, or toxic adenoma, we suggest radioiodine therapy as our
first choice in the absence of moderate to severe Graves' orbitopathy, given its
lower cost and lower complication rate than surgery (Grade 2B). Surgery is an
:
 option, especially for patients with hyperthyroidism due to a very large or
obstructive goiter. (See 'Long-term management' above and "Graves'
hyperthyroidism in nonpregnant adults: Overview of treatment" and "Treatment
of toxic adenoma and toxic multinodular goiter".)

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