Thyroid storm can occur in children with thyrotoxicosis from any cause but is most commonly

associated with Graves disease. Other reported causes of thyrotoxicosis associated with thyroid
storm include the following:

 Transplacental passage of maternal thyroid-stimulating immunoglobulins in neonates

 McCune-Albright syndrome with autonomous thyroid function[5]

 Hyperfunctioning thyroid nodule

 Hyperfunctioning multinodular goiter

 Thyroid-stimulating hormone (TSH)-secreting tumor

Graves disease may also occur in children with Down syndrome or Turner syndrome and in
association with other autoimmune conditions, including the following:

 Juvenile rheumatoid arthritis  Chronic lymphocytic (Hashimoto)

thyroiditis
 Addison disease
 Systemic lupus erythematosus
 Type I diabetes
 Chronic active hepatitis
 Myasthenia gravis
 Nephrotic syndrome

The pathophysiologic mechanisms of Graves disease are shown in the image below.
Pathophysiologic mechanisms of Graves disease relating thyroid-stimulating immunoglobulins to
hyperthyroidism and ophthalmopathy. T4 is levothyroxine. T3 is triiodothyronine.

Although the exact pathogenesis of thyroid storm is not fully understood, the following theories
have been proposed:

 Patients with thyroid storm reportedly have relatively higher levels of free THs than patients
with uncomplicated thyrotoxicosis, although total TH levels may not be increased.

 Adrenergic receptor activation is another hypothesis. Sympathetic nerves innervate the

thyroid gland, and catecholamines stimulate TH synthesis. In turn, increased THs increase
the density of beta-adrenergic receptors, thereby enhancing the effect of catecholamines.
The dramatic response of thyroid storm to beta-blockers and the precipitation of thyroid
storm after accidental ingestion of adrenergic drugs such as pseudoephedrine support this
theory. This theory also explains normal or low plasma levels and urinary excretion rates of
catecholamines. However, it does not explain why beta-blockers fail to decrease TH levels in
thyrotoxicosis.

 Another theory suggests a rapid rise of hormone levels as the pathogenic source. A drop in
binding protein levels, which may occur postoperatively, might cause a sudden rise in free
hormone levels. In addition, hormone levels may rise rapidly when the gland is manipulated
during surgery, during vigorous palpation during examination, or from damaged follicles
following RAI therapy.

 Other proposed theories include alterations in tissue tolerance to THs, the presence of a
unique catecholaminelike substance in thyrotoxicosis, and a direct sympathomimetic effect
of TH as a result of its structural similarity to catecholamines.

Approach Considerations

The approach to treatment of thyroid storm includes the following:

 Supportive measures  Glucocorticoids

 Antiadrenergic drugs  Bile acid sequestrants

 Thionamides  Treatment of the underlying condition

 Iodine preparations  Rarely plasmapheresis

Patients with contraindications to thionamides need to be managed with supportive measures,
aggressive beta blockade, iodine preparations, glucocorticoids, and bile acid sequestrants for about
a week in preparation for a thyroidectomy. Plasmapheresis may be attempted if other measures are
not effective.

Medical Care

Patients with thyroid storm should be treated in an ICU setting for close monitoring of vital signs and
for access to invasive monitoring and inotropic support, if necessary. Initial stabilization and
management of systemic decompensation is as follows:

 Supportive measures

o If needed, immediately provide supplemental oxygen, ventilatory support, and

intravenous fluids. Dextrose solutions are the preferred intravenous fluids to cope
with continuously high metabolic demand.

o Correct electrolyte abnormalities.

o Treat cardiac arrhythmia, if necessary.

o Aggressively control hyperthermia by applying ice packs and cooling blankets and by
administering acetaminophen (15 mg/kg orally or rectally every 4 hours).

 Antiadrenergic drugs

o Promptly administer antiadrenergic drugs (eg, propranolol) to minimize

sympathomimetic symptoms. Propranolol is administered orally or via nasogastric
tube at a dose of 60-80 mg every 4-6 hours and the dose adjusted based on heart
rate and blood pressure. It may also be given intravenously when necessary for rapid
onset of action (0.5-1 mg over 10 min followed by 1-2 mg over 10 min every few
hours, adjusted based on vital signs). It is important to avoid propranolol in
conditions such as asthma, chronic obstructive pulmonary disease, peripheral
vascular disease, or decompensated heart failure. Cardioselective beta blockers such
as atenolol or metoprolol may be administered in patients with reactive airway
disease, and calcium channel blockers may be used when beta blockers are
contraindicated. The use of intravenous short acting beta-1 blockers, such as
esmolol (loading dose of 250-500 mcg/kg, followed by an infusion of 50-100 mcg/kg
per minute), allows quick dose titration with minimization of side effects.

o Dosing of beta blockers for thyroid storm in a pediatric population:

 Propranolol: Neonates: 2 mg/kg per day PO/NGT divided every 6-12

hours; Children: 0.5-4 mg/kg per day PO/NGT divided every 6 hours (not to
exceed 60 mg per day) or 0.01-0.02 mg/kg IV over 10 minutes (may repeat
over 10’ every few hours to a maximum cumulative dose of 5 mg)

 Esmolol: Loading dose: 250-500 mcg/kg over 1 minute, repeat as needed,

maintenance dose: 50-100 mcg/kg per minute IV infusion

 Thionamides: Correct the hyperthyroid state. Administer antithyroid medications to block

further synthesis of thyroid hormones (THs).
o High-dose propylthiouracil (PTU) is preferred over methimazole for treatment of
severe thyroid storm because of its early onset of action and capacity to inhibit
peripheral conversion of T4 to T3. Methimazole may be used in less severe cases.
Dosing for thyroid storm in adults is as follows: PTU 200 mg every four hours or
methimazole 20 mg orally every four to six hours; these drugs may need to be
administered through a nasogastric tube.

o Dosing of PTU for thyroid storm in children: Neonates: 5-10 mg/kg per day PO/NGT
divided every 6-8 hours; Children: 15-20 mg/kg per day PO/NGT divided every 6-8
hours (up to 40 mg/kg per day has been used; not to exceed 1200 mg per day)

o Of note, the US Food and Drug Administration (FDA) has added a boxed warning, the
strongest warning issued by the FDA, to the prescribing information for PTU.

 The boxed warning emphasizes the risk for severe liver injury and acute liver
failure, some of which have been fatal. The boxed warning also states that
PTU should be reserved for use in those who cannot tolerate other
treatments such as methimazole, radioactive iodine, or surgery.

 The decision to include a boxed warning was based on the FDA's review of
postmarketing safety reports and meetings held with the American Thyroid
Association, the National Institute of Child Health and Human Development,
and the pediatric endocrine clinical community.

 The FDA has identified 32 cases (22 adult and 10 pediatric) of serious liver
injury associated with PTU. Among adults, 12 deaths and 5 liver transplants
occurred; among the pediatric patients, 1 death and 6 liver transplants
occurred. PTU is indicated for hyperthyroidism due to Graves disease. These
reports suggest an increased risk for liver toxicity with PTU compared with
methimazole. Serious liver injury has been identified with methimazole in 5
cases (3 resulting in death).

 PTU is now considered as a second-line drug therapy for treatment of

hyperthyroidism in general (though not thyroid storm), except in patients
who are allergic or intolerant to methimazole, or women who are in the first
trimester of pregnancy. Rare cases of embryopathy, including aplasia cutis,
have been reported with methimazole during pregnancy. For more
information, see the FDA Safety Alert.[9] The FDA recommends the following
criteria be considered for prescribing PTU.

 Reserve PTU use for during first trimester of pregnancy or for patients who
are allergic to or intolerant of methimazole.

 Closely monitor patients undergoing PTU therapy for signs and symptoms of
liver injury, especially during the first 6 months after initiation of therapy.

 For suspected liver injury, promptly discontinue PTU therapy and evaluate
for evidence of liver injury and provide supportive care.

 PTU should not be used in pediatric patients unless the patient is allergic to
or intolerant of methimazole and no other treatment options are available.
  Counsel patients to promptly contact their health care provider for the
following signs or symptoms: fatigue, weakness, vague abdominal pain, loss
of appetite, itching, easy bruising, or yellowing of the eyes or skin.

o If the patient is given PTU during treatment of thyroid storm, this should be
switched to methimazole at the time of discharge unless methimazole is
contraindicated. If methimazole is contraindicated, alternative methods to treat
hyperthyroidism should be considered after discharge, such as radioactive iodine or
surgery.

 Iodine compounds:

o Administer iodine compounds (Lugol iodine or potassium iodide) orally or via a

nasogastric tube to block the release of THs (at least 1 h after starting antithyroid
drug therapy). In adults, SSKI is a given at a dose of 5 drops every 6 hours, or Lugol's
iodine at a dose of 10 drops every 8 hours. If available, intravenous radiocontrast
dyes such as ipodate and iopanoate can be effective in this regard. These agents are
particularly effective at preventing peripheral conversion of T4 to T3.

o Dosing of iodine compounds for thyroid storm in children:

 SSKI (50 mg iodide per drop): Neonates: 2 drops PO/NGT every 6-8
hours; Children: 2-5 drops PO/NGT every 6 hours

 Lugol's iodine (8 mg iodine/drop): 10 drops PO/NGT every 8 hours

 Glucocorticoids

o Administer glucocorticoids to decrease peripheral conversion of T4 to T3. This may

also be useful in preventing relative adrenal insufficiency due to hyperthyroidism
and improving vasomotor symptoms. Hydrocortisone is administered intravenously
at a dose of 100 mg every 8 hours or dexamethasone at a dose of 1-2 mg every 6
hours.

o Dosing of glucocorticoids for thyroid storm in children:

 Hydrocortisone: 5 mg/kg (up to 100 mg) intravenously every 6-8 hours

 Dexamethasone: 0.1-0.2 mg/kg per day divided every 6-8 hours

 Bile acid sequestrants prevent reabsorption of free THs in the gut (released from conjugated
TH metabolites secreted into bile through the enterohepatic circulation). A recommended
dose is 4 g of cholestyramine every 6 hours via a nasogastric tube

 Treat the underlying condition, if any, that precipitated thyroid storm and exclude
comorbidities such as diabetic ketoacidosis and adrenal insufficiency. Infection should be
treated with antibiotics.

 Rarely, as a life-saving measure, plasmapheresis has been used to treat thyroid storm in
adults. [10]

Iodine preparations should be discontinued once the acute phase resolves and the patient becomes
afebrile with normalization of cardiac and neurological status. Glucocorticoids should be weaned
and stopped and the dose of thioamides adjusted to maintain thyroid function in the normal range.
Beta-blockers may be discontinued once thyroid function normalizes.

If the patient is given PTU during treatment of thyroid storm, this should be switched to
methimazole at the time of discharge unless methimazole is contraindicated. If there is a
contraindication for the use of methimazole, alternative methods to treat hyperthyroidism should
be considered after discharge, such as radioactive iodine or surgery.

Patients with contraindications to thionamides need to be managed with supportive measures,

aggressive beta blockade, iodine preparations, glucocorticoids and bile acid sequestrants for about a
week in preparation for a thyroidectomy. Plasmapheresis may be attempted if other measures are
not effective.

Surgical Care

Patients with Graves disease who need urgent treatment of hyperthyroidism but have absolute
contraindications to thioamides may be treated acutely with beta-blockers, iodine preparations,
glucocorticoids, and bile acid sequestrants as described. Plasmapheresis is sometimes used as a last
resort if other measures are not effective. Subsequently, thyroidectomy may be performed after
about 7 days of iodine administration. Iodine reduces the vascularity of the gland and the risk for
thyroid storm.

Consultations

The following consultations are indicated:

 Endocrinologist

 Intensivist

Prevention

Promptly and appropriately treat thyrotoxicosis after diagnosis. Perform surgery in thyrotoxic
patients only after appropriate thyroid and/or beta-adrenergic blockade.

Thyroid storm following radioactive iodine (RAI) therapy for hyperthyroidism may be related to (1)
withdrawal of antithyroid medications for RAI administration (usually withdrawn 5-7 d before
administration of RAI and held until 5-7 d after RAI therapy), (2) release of large amounts of thyroid
hormone from damaged follicles, and (3) RAI itself. Because TH levels are often higher immediately
before RAI treatment than they are afterward, many endocrinologists believe that withdrawal of
antithyroid drugs is the cause of thyroid storm. One option is to stop antithyroid drugs (including
methimazole) only 3 days (rather than 5-7 d) before RAI therapy and to restart antithyroid drugs 3
days after RAI administration. Early institution of antithyroid drugs after RAI therapy may decrease
the efficacy of treatment, requiring a second dose.

Consider testing thyroid function before operative procedures in children at high risk for
hyperthyroidism (eg, patients with McCune-Albright syndrome).

Minor complications

Postoperative surgical site seromas may be followed clinically and allowed to resorb, if small and
asymptomatic; large seromas may be aspirated under sterile conditions. Poor scar formation is
frequently preventable with proper incision location and surgical technique.
Postoperative bleeding

The incidence of bleeding after thyroid surgery is low (0.3-1%), but an unrecognized or rapidly
expanding hematoma can cause airway compromise and asphyxiation. Patients present with neck
swelling, neck pain, and/or signs and symptoms of airway obstruction (eg, dyspnea, stridor, hypoxia).
Evaluation is as follows:

 Physical examination; remove all bandaging and examine the neck for swelling

 Imaging studies may be useful in cases of mild neck swelling without airway compromise

 Fiberoptic laryngoscopy may be warranted in patients with airway issues without apparent
wound hematoma, to assess vocal fold function/LI>

Prevention

 Avoid traumatizing the thyroid tissue during the procedure

 Provide good intraoperative hemostasis

 Avoid the use of neck dressings, as dressing that covers the wound may mask hematoma
formation

 No definitive evidence suggests that drains prevent hematoma or seroma formation

Injury to the recurrent laryngeal nerve

Recurrent laryngeal nerve (RLN) injury results in true vocal-fold paresis or paralysis. Deliberate
intraoperative identification and preservation of the RLN minimizes the risk of injury.

Evaluation

 Techniques for assessing vocal fold mobility include indirect and fiberoptic laryngoscopy

 Documentation of vocal fold mobility should be a routine part of the preoperative workup

 Postoperative visualization should also be performed, as patients may be asymptomatic at

first

 Laryngeal electromyography (EMG) may be useful to distinguish vocal fold paralysis from
injury to the cricoarytenoid joint secondary to intubation, and it may yield prognostic
information

Presentation

 In unilateral vocal cord paralysis, hoarseness or breathiness may not manifest for days to
weeks; other potential sequelae are dysphagia and aspiration

 Bilateral vocal-fold paralysis usually manifests immediately after extubation; patients may
present with biphasic stridor, respiratory distress, or both

Treatment

 In unilateral vocal cord paralysis, corrective procedures may be delayed for at least 6 months
to allow time for improvement in a reversible injury, unless the nerve was definitely
transected during surgery; surgical treatment options are medialization (most common) and
reinnervation
  In bilateral vocal cord paralysis, emergency tracheotomy may be required, but if possible,
first perform endotracheal intubation; cordotomy and arytenoidectomy, the most
commonly performed surgical procedures, enlarge the airway and may permit
decannulation of a tracheostomy

 The patient must be counseled that his or her voice will likely worsen after surgery

Hypoparathyroidism

Hypoparathyroidism can result from direct trauma to the parathyroid glands, devascularization of
the glands, or removal of the glands during surgery. Postoperative hypoparathyroidism, and the
resulting hypocalcemia, may be permanent or transient. Hypocalcemia after thyroidectomy is
initially asymptomatic in most cases.

Evaluation of parathyroid function is performed in either of the following ways:

 Follow ionized calcium (or total calcium and albumin) levels perioperatively

 Measure PTH postoperatively; a normal level accurately predicts normocalcemia

Treatment is as follows:

 Asymptomatic hypocalcemia in the early postoperative period should not be treated with
supplemental calcium

 In symptomatic patients, replace calcium with IV calcium gluconate

 Typically, patients who begin to have symptoms can be started on oral calcium and vitamin
D

 In 1-2 months, an attempt to wean the patient off oral calcium may be made

 Dependence on calcium supplementation for longer than 6 months usually indicates

permanent hypoparathyroidism

Thyrotoxic storm

Thyrotoxic storm is an unusual complication that may result from manipulation of the thyroid gland
during surgery in patients with hyperthyroidism. It can develop preoperatively, intraoperatively, or
postoperatively. Signs and symptoms of thyrotoxic storm are as follows:

 Anesthetized patients: Evidence of increased sympathetic output (eg, tachycardia

hyperthermia)

 Awake patients: Nausea, tremor, and altered mental status

 Cardiac arrhythmias may also occur

 Progression to coma in untreated patients

Treatment is as follows:

 For thyrotoxic crisis during thyroidectomy, stop the procedure

 Administer IV beta-blockers, propylthiouracil, sodium iodine, and steroids

 Use cooling blankets and cooled IV fluids to reduce the patient's body temperature
  Carefully monitor oxygenation

Injury to the Superior Laryngeal Nerve

The external branch of the superior laryngeal nerve (SLN) is probably the nerve most commonly
injured in thyroid surgery, with an injury rate estimated at 0-25%. Trauma to the nerve results in an
inability to lengthen a vocal fold and, thus, inability to create a high-pitched sound; this may be
career-threatening for singers or others who rely on their voice for their profession. Speech therapy
is the only treatment. Presentation and diagnosis are as follows:

 Most patients do not notice any change in their voice

 Occasional patients present with mild hoarseness or decreased vocal stamina

 On laryngoscopy, posterior glottic rotation toward the paretic side and bowing of the vocal
fold on the weak side may be noted; the affected vocal fold may be lower than the normal
one

 Videostroboscopy demonstrates an asymmetric, mucosal traveling wave

 Laryngeal EMG demonstrates cricothyroid muscle denervation

Infection

Currently, postoperative infection occurs in less than 1-2% of all thyroid surgery cases. Sterile
surgical technique is the key to prevention; routine use of perioperative antibiotics has not proven
to be beneficial.

Presentation

 Cellulitis typically presents as erythema, warmth, and tenderness of neck skin around the
incision

 A superficial abscess produces fluctuance and tenderness

 A deep neck abscess may manifest subtly but can produce fever, pain, leukocytosis, and
tachycardia

Evaluation

 Send purulence expressed from the wound or drained from an abscess for Gram stain and
culture

 CT imaging is useful when a deep neck abscess is thought to be possible

 To exclude esophageal perforation in patients with a deep neck abscess, an esophageal

swallow study performed with sodium amidotrizoate and meglumine amidotrizoate solution
(Gastrografin) may be useful

Treatment

 Treat cellulitis with antibiotics that provide good coverage against gram-positive organisms
(eg, staphylococci and streptococci)

 Drain abscesses, and direct antibiotic coverage according to culture findings

  For deep neck abscesses, begin with broad-spectrum antibiotics (eg, cefuroxime,
clindamycin, ampicillin-sulbactam) until definitive culture results are available

Hypothyroidism

Hypothyroidism is an expected sequela of total thyroidectomy. Measurement of TSH levels is the

most useful laboratory test for detecting or monitoring of hypothyroidism in these patients.