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THYROTOXIC CRISIS or THYROID STORM
- is an acute, life-threatening, hypermetabolic state
induced by excessive release of thyroid hormones in individuals with thyrotoxicosis.
- clinical presentation includes fever, tachycardia, hypertension, and neurological and GI abnormalities.
- diagnosis is primarily clinical, and no specific
laboratory tests are available.
- Patients may have a known history of thyrotoxicosis.
In the absence of previously diagnosed thyrotoxicosis, the history may include symptoms such as irritability, agitation, emotional
lability, a voracious appetite with poor weight gain, excessive sweating and heat intolerance, and poor school performance
caused by decreased attention span.
- Thyroid storm is precipitated by the following factors
in individuals with thyrotoxicosis:
o Sepsis
o
Surgery
o
Anesthesia induction
o
Radioactive iodine (RAI) therapy
o
Drugs (anticholinergic and adrenergic drugs such as pseudoephedrine; salicylates NSAIDs, chemotherapy)
o
Excessive thyroid hormone ingestion
o
Withdrawal of or noncompliance with antithyroid medications
o Diabetic ketoacidosis
o
Direct trauma to the thyroid gland
o
Vigorous palpation of an enlarged thyroid
o
Toxemia of pregnancy and labor in older adolescents; molar pregnancy
o
- Thyroid storm diagnosis is based on clinical features,
not on laboratory test findings. If the patient's clinical picture is consistent with thyroid storm, do not delay treatment
pending laboratory confirmation of thyrotoxicosis.
- Results of thyroid studies are usually consistent
with
hyperthyroidism and are useful only if the patient has not been previously diagnosed.
- Usual findings include elevated triiodothyronine (T3), thyroxine (T4) and free T4 levels; increased T3 resin uptake;
suppressed thyroid-stimulating hormone (TSH) levels; and an elevated 24-hour iodine uptake.
- 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:
·
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.
·
Correct electrolyte abnormalities.
·
Treat cardiac arrhythmia, if necessary.
·
Aggressively control hyperthermia by applying ice packs and cooling blankets and by administering
acetaminophen (15 mg/kg orally or rectally every 4 h).
·
Promptly administer antiadrenergic drugs (eg, propranolol) to minimize sympathomimetic symptoms.
·
Correct the hyperthyroid state. Administer antithyroid medications to block further synthesis
of thyroid hormones (THs). High-dose propyl thiouracil is preferred because of its early onset of action and capacity to inhibit
peripheral conversion of T4 to T3.
·
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). 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.
·
Administer glucocorticoids to decrease peripheral conversion of T4 to T3. This may also be useful
in preventing relative adrenal insufficiency due to hyperthyroidism.
·
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.
·
- Preoperative management of
the thyrotoxic patient can be subdivided into two categories: preparation for elective or nonurgent procedures and preparation
for emergent procedures.
- When rapid control of thyrotoxicosis
is not required, as would be the case for an elective or nonurgent procedure,
the standard course of therapy would be to achieve euthyroidism before surgery.
- Therapy is aimed at (1) ameliorating hyperadrenergic effects of thyroid hormone (TH) on peripheral tissues with use
of beta-blockers (eg, propranolol, labetalol); (2) decreasing further synthesis of THs with antithyroid medications (eg, propylthiouracil
[PTU], methimazole); (3) decreasing hormonal release from the thyroid, using iodides; and (4) preventing further TH secretion
and peripheral conversion of T4 to T3, using glucocorticoids or iodinated radiocontrast dyes when available.
I.
Antithyroids
· These agents
belong to the thioureylene (thionamide) class and inhibit synthesis of THs within 1-2 hours.
· They have
no effect on decreasing the release of preformed THs.
|
Drug Name |
Propylthiouracil (PTU, Propyl-Thyracil) |
|
Description |
DOC that inhibits synthesis of TH by preventing organification and trapping of iodide to iodine and by inhibiting coupling
of iodotyrosines; also inhibits peripheral conversion of T4 to T3, an important component of management. Comatose patients
may require administration via NG tube because the agent is available solely as PO preparation; has been successfully administered
PR. |
|
Adult Dose |
Initial: 200-400 mg PO/NG q4-8h
Hyperthyroidism without thyroid storm: 150-450 mg/d PO divided q8h initially
Maintenance:
100-150 mg/d PO divided q8-12h |
|
Pediatric Dose |
Neonate dose: 5-10 mg/kg/d PO/NG divided q6-8h
Children: 15-20 mg/kg/d PO/NG divided q6-8h initially; higher doses
of up to 30-40 mg/kg/d have been successfully used; not to exceed 1200 mg/d
Hyperthyroidism without thyroid storm: 5-7
mg/kg/d PO divided q6-8h initially
Children, maintenance dose: one-third to two-thirds of initial dose q8-12h |
|
Contraindications |
Documented hypersensitivity |
|
Interactions |
Concurrent use with other drugs known to cause bone marrow suppression may cause agranulocytosis; may cause hypothyroidism
if used with lithium or potassium iodide; may cause bleeding diathesis if used with anticoagulants (eg, warfarin) |
|
Pregnancy |
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
|
Precautions |
Adverse effects higher in children; aplastic anemia has been described, but leukopenia more often observed; dermatitis,
especially urticarial rash; arthritis; arthralgia; lupuslike syndrome; idiosyncratic reactions (eg, hepatitis, hepatic failure)
may occur; discontinue upon neutropenia or abnormal LFT results; administer with food to minimize adverse GI effects |
·
|
Drug Name |
Methimazole (Tapazole) |
|
Description |
Inhibits synthesis of TH by preventing organification of iodide to iodine and coupling of iodotyrosines. Although at
least 10 times more potent than PTU on a weight basis, it does not inhibit peripheral conversion of T4 to T3. May be used
instead of PTU in thyroid storm if iodinated radiocontrast agents are used in conjunction to prevent the conversion of T4
to T3. Comatose patients may require administration via NG tube because agent is available solely as PO preparation. |
|
Adult Dose |
Initial dose: 60-120 mg/d PO/NG divided q6-8h
Hyperthyroidism without thyroid storm: 15-60 mg/d PO divided q8-24h
initially
Maintenance dose: 10-20 mg/d PO divided q8-24h |
|
Pediatric Dose |
Initial dose: 0.5–1 mg/kg/d PO/NG divided q8h
Hyperthyroidism without thyroid storm: 0.5-0.7 mg/kg/d PO divided
q8-24h
Maintenance dose: One-third to one-half of initial daily dose divided in 1-3 doses; not to exceed 30 mg/d |
|
Contraindications |
Documented hypersensitivity |
|
Interactions |
Concurrent use with lithium or potassium iodide may cause hypothyroidism; concurrent use with anticoagulants (eg, warfarin)
may cause bleeding diathesis |
|
Pregnancy |
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
|
Precautions |
Adverse effects higher in children; aplastic anemia has been described, but leukopenia observed more often; dermatitis,
especially urticarial rash; arthritis; arthralgias; lupuslike syndrome; idiosyncratic reactions (eg, cholestatic jaundice)
may occur; liver failure has not been identified; discontinue if neutropenia occurs and if abnormal LFT results persist; administer
with food to minimize adverse GI effects; infants born to mothers receiving methimazole have suffered from aplasia cutis |
II.
Iodides
- Iodides inhibit the release of TH from the thyroid gland.
- Precede iodide administration with thionamides by at least 1 hour to prevent increased intrathyroidal TH synthesis.
- Iodinated radiographic contrast dyes that contain ipodate (Oragrafin) or iopanoic acid (Telepaque) have also been used
and effectively prevent conversion of T4 to T3
- Another benefit of these radiocontrast agents is the once-daily dosing regimen, as opposed to 3-4 daily doses with
iodine-containing oral solutions.
- Lithium carbonate may be used if the patient is hypersensitive to iodine.
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Drug Name |
Potassium iodide, saturated solution (Pima, SSKI, Thyro-Block) |
|
Description |
Used to inhibit TH release from thyroid gland. 1 mL of SSKI contains 1 g of potassium iodide (ie, approximately 50
mg/drop). In adults, sodium iodide 0.25 g IV q6h or 0.5 g IV q12h has also been used successfully. |
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Adult Dose |
2-5 drops (approximately 100-250 mg) PO/NG q6h |
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Pediatric Dose |
Neonates: 100 mg PO/NG q6-8h
Children: Administer as in adults |
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Contraindications |
Documented hypersensitivity; hyperkalemia; pregnant adolescents; impaired renal function, Addison disease |
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Interactions |
Use with other potassium-containing agents, potassium-sparing diuretics, and ACE inhibitors may result in hyperkalemia;
use with lithium or potassium iodide may precipitate hypothyroidism; administer propylthiouracil before iodides in thyroid
storm so that the effect of the propylthiouracil is fully manifested; iodides may inhibit the action of the thiourea drugs
because iodine uptake may be initially increased |
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Pregnancy |
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
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Precautions |
Hypersensitivity reactions; arrhythmias; GI bleeding; angioedema; administer PO after meals with food or milk or dilute
with large quantity of juice, water, or milk |
III.
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Drug Name |
Strong iodine (Lugol Solution) |
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Description |
Contains 100 mg potassium iodide and 50 mg iodine; provided 8 mg iodide/drop. |
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Adult Dose |
10 drops PO tid mixed in water or juice |
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Pediatric Dose |
Administer as in adults |
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Contraindications |
Documented hypersensitivity; pulmonary edema; bronchitis; tuberculosis; hyperkalemia |
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Interactions |
Increases lithium toxicity by producing additive hypothyroid effects; decreased anticoagulant effectiveness of warfarin |
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Pregnancy |
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
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Precautions |
Prolonged use may result in hypothyroidism; caution in renal failure or GI obstruction |
III. Beta-
blockers
- are used as the mainstay therapy to control autonomic effects of TH.
- block peripheral conversion of T4 to T3.
- Esmolol, a short-acting selective beta 1-antagonist, has been used successfully in children, as has labetalol in adults.
- should be used with caution in congestive cardiac failure and thyrotoxic cardiomyopathy.
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Drug Name |
Propranolol (Inderal) |
|
Description |
DOC most widely used in this group; is a nonselective beta–adrenergic antagonist. Decreases heart rate, myocardial
contractility, BP, and myocardial oxygen demand. Often the only adjunctive drug needed to control thyroid storm symptoms. |
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Adult Dose |
20-80 mg/dose PO/NG q4-6h
1-2 mg/dose slow IVP as a single dose; not to exceed administration rate of 1 mg/min;
may repeat q10-15min or until symptoms are controlled |
|
Pediatric Dose |
Neonates: 2 mg/kg/d PO/NG divided q6-12h
Children: 0.5-4 mg/kg/d PO/NG divided q6h; not to exceed 60 mg/d
0.025-0.15
mg/kg IV over 10 min; may be repeated q10min until hyperdynamic cardiovascular state is improved; not to exceed cumulative
dose of 5 mg |
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Contraindications |
Documented hypersensitivity; uncompensated CHF; cardiogenic shock; bradycardia; heart block; pulmonary edema; severe
hyperactive airway disease; chronic obstructive pulmonary disease; Raynaud disease |
|
Interactions |
Barbiturates, indomethacin, and rifampin may increase propranolol metabolism, lowering serum levels, whereas cimetidine,
hydralazine, verapamil, and chlorpromazine may increase serum levels; bioavailability may be increased in Down syndrome, so
lower doses may be required in these children; coadministration with catecholamine-depleting drugs such as reserpine may lead
to hypotension, bradycardia, and vertigo; may decrease the clearance of theophylline, antipyrine, and lidocaine |
|
Pregnancy |
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh
risk to fetus |
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Precautions |
Most common adverse drug reactions include hypotension, CHF, bradycardia, heart block, CNS depression; nausea, vomiting,
constipation, hypoglycemia agranulocytosis; do not administer IV dose faster than 1 mg/min with continuous monitoring; gradually
taper dose over 1-2 wk when discontinuing; administer at same time each day; advise patient to inform physician if using concurrently
with other adrenergic agonists |
IV.
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Drug Name |
Esmolol (Brevibloc) |
|
Description |
Beta 1–specific antagonist with a short duration of action. |
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Adult Dose |
500 mcg/kg/min IV infused over 1 min, then 50-100 mcg/kg/min for 4 min; repeat until desired effect; not to exceed
200 mcg/kg/min |
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Pediatric Dose |
Loading dose: 250-500 mcg/kg IV infused over 1 minute; may repeat frequently until desired effect
Maintenance dose:
50-100 mcg/kg/min IV infusion |
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Contraindications |
Documented hypersensitivity; uncompensated CHF; cardiogenic shock; bradycardia; heart block; Raynaud disease |
|
Interactions |
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability
and plasma levels, possibly resulting in decreased pharmacologic effect; cardiotoxicity may increase when administered concurrently
with sparfloxacin, astemizole, calcium channel blockers, quinidine, digoxin, or flecainide; toxicity increases when administered
concurrently with acetaminophen, clonidine, epinephrine, prazosin, haloperidol, phenothiazines, and catecholamine-depleting
agents |
|
Pregnancy |
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh
risk to fetus |
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Precautions |
Common adverse cardiovascular reactions include hypotension, CHF, bradycardia, and heart block; use with caution in
patients with diabetes, as drug can cause hypoglycemia and mask signs and symptoms; bronchospasm; infusion site reactions
(eg, phlebitis, skin necrosis) upon extravasation |
V.
Glucocorticoids
- These agents block conversion of T4 to T3.
- The use of corticosteroids has been associated with improved survival.
- Stress doses are required to replace accelerated production and degradation of cortisol induced by TH.
- If corticosteroids are not administered, acute glucocorticoid deficiency hypothetically could occur because demand
may outpace production.
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Drug Name |
Hydrocortisone succinate (Solu-Cortef) |
|
Description |
Provides mineralocorticoid activity and glucocorticoid effects. |
|
Adult Dose |
100-200 mg IV q6-8h |
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Pediatric Dose |
5 mg/kg IV q6-8h |
|
Contraindications |
Documented hypersensitivity; serious infections (excluding meningitis, septic shock); fungal infections; varicella
infections. |
|
Interactions |
Barbiturates or rifampin may decrease effect; potassium-depleting agents (eg, diuretics) may increase risk of hypokalemia;
may increase digitalis toxicity secondary to hypokalemia |
|
Pregnancy |
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh
risk to fetus |
|
Precautions |
May suppress immune function, but benefits outweigh risks in serious conditions such as thyroid storm; if PO, administer
with meals to decrease GI upset; early-onset adverse effects include glucose intolerance, hypertension, agitation, and indigestion;
late-onset adverse effects include immune suppression, increased susceptibility to sepsis, adrenal suppression, hypertension,
urinary calcium loss, osteopenia, and gastric irritation and bleeding |
VI.
|
Drug Name |
Dexamethasone (Decadron) |
|
Description |
Elicits glucocorticoid effects. |
|
Adult Dose |
2 mg PO/IV q6h |
|
Pediatric Dose |
0.1-0.2 mg/kg/d PO divided q6-8h |
|
Contraindications |
Documented hypersensitivity; serious infections (excluding meningitis, septic shock); fungal infections; varicella
infections |
|
Interactions |
Concurrent use of barbiturates, phenytoin, or rifampin can decrease effects; conversely, dexamethasone decreases effect
of salicylates and immunization vaccines |
|
Pregnancy |
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh
risk to fetus |
|
Precautions |
May suppress immune function, but benefits outweigh risks in serious conditions such as thyroid storm; administer with
meals to decrease GI upset; early-onset adverse effects include glucose intolerance, hypertension, agitation, and indigestion;
late-onset adverse effects include immune suppression, increased susceptibility to sepsis, adrenal suppression, hypertension,
urinary calcium loss, osteopenia, and gastric irritation and bleeding |
- In the preoperative preparation
of thyrotoxic patients for emergent procedures, time is of the essence.
- Rapid lowering of thyroid hormone
levels, control of thyroid hormone release, and control of peripheral manifestations of thyroid hormone are needed.
- In this situation, several
regimens have been tried with success, using the same therapeutic modalities that are used in the treatment of thyroid storm.
Table 5:
Rapid preparation of thyrotoxic patients for emergent surgery
|
Drug
class |
Recommended
drug |
Dosage |
Mechanism
of action |
Continue
postoperatively? |
|
Beta-adrenergic
Blockade |
Propranolol |
40–80
mg po tid-qid |
Beta-adrenergic
blockade; decreased T4-to-T3 conversion (high dose) |
Yes |
|
|
or |
|
|
|
|
|
Esmolol |
50–100
μg/kg/min |
Beta-adrenergic
blockade |
Change
to oral propranolol |
|
Thionamide |
Propylthiouracil |
200 mg
po q 4 h |
Inhibition
of new thyroid hormone synthesis; decreased T4-to-T3 conversion |
Stop
immediately after near total thyroidectomy; continue after nonthyroidal surgery |
|
|
or |
|
|
|
|
|
Methimazole |
20 mg po q 4 h |
Inhibition
of new thyroid hormone synthesis |
Stop
immediately after near total thyroidectomy; continue after nonthyroidal surgery |
|
Oral
cholecysto-graphic agent |
Iopanoic
acid |
500
mg po bid |
Decreased
release of thyroid hormone; decreased T4-to-T3 conversion |
Stop
immediately after surgery |
|
Corticosteroid |
Hydrocortisone |
100
mg po or IV q 8 h |
Vasomotor
stability; decreased T4-to-T3 conversion |
Taper
over first 72 h |
|
|
or |
|
|
|
|
|
Dexamethasone |
2
mg po or IV q 6 h |
Vasomotor
stability; decreased T4-to-T3 conversion |
Taper
over first 72 h |
|
|
or |
|
|
|
|
|
Betamethasone |
0.5
mg po q 6 h, IM or IV |
Vasomotor
stability; decreased T4-to-T3 conversion |
Taper
over first 72 h |
|
From Langley RW, Burch HB. Perioperative management of the thyrotoxic patient. Endocrinol Metab Clin of North Am 2003;32:519–34;
with permission. |
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