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II.3 KRISIS TIROID
Kata kunci : hipertiroidisme ekstrem, eksaserbasi, keadaan mengancam nyawa,
hipermetabolik
Tirotoksikosis adalah sindroma klinis yang dihasilkan saat jaringan terpapar dengan
hormon tiroid kadar tinggi
II.3.1 Definisi
Krisis tiroid (thyroid storm) merupakan suatu keadaan hipertiroid yang mengalami
eksaserbasi sehingga mengancam kehidupan yang ditandai dengan dekompensasi dari satu
atau lebih sistem organ, dengan keadaan status hipermetabolik.1,2
III.3.1 Etiologi
Penyakit Grave (paling sering)
Struma multinoduler toksik
Adenoma toksik
IV.3.1 Gambaran klinis
Gambaran klinis yang ditunjukkan merupakan manifestasi dekompensasi organ.
Manifestasi dari eksaserbasi secara akut keadaan tirotoksik.
II.3.1 Patofisiologi
Patofisiologi detail mengenai krisis tiroid belum dimengerti sepenuhnya, tetapi
diperkirakan terkait dengan peningkatan jumlah dari reseptor beta1-adrenergik akibat
peningkatan kadar katekolamin dalam keadaan stres.3
Pemindahan dari hormon tiroid bebas oleh inhibitor pengikat pada penyakit sistemik
(mis. sitokin) juga berperan penting.3
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Richard Carroll, Glenn Matfin. Endocrine and metabolic emergencies: thyroid storm. Ther
Adv Endocrinol Metab (2010) 1(3) 139-145
Referensi :
1. Nayak Bindu MD, Burman Kenneth MD. Thyrotoxicosis and Thyroid Storm. Available
from: Endocrinology and Metabolism Clinics of North America (2006) 663-‐686.
Elsevier journals.
2. Ross Douglas S. Thyroid Storm. Available from: Uptodate
3. Richard Carroll, Glenn Matfin. Endocrine and metabolic emergencies: thyroid storm.
Ther Adv Endocrinol Metab (2010) 1(3) 139-145
4. Thyroid Storm. Chapter 41: Metabolic & Endocrine Emergencies.Current Diagnosis &
Treatment in Emergency Medicine. 6th edition.
5. Thyrotoxic crisis: Assessment. Oxford Handbook of Acute Medicine, 2nd Edition. 1997,
2004
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THYROID DISORDERS
1. Thyroid Storm
ESSENTIALS OF DIAGNOSIS
• Typical stigmata of hyperthyroidism, thyromegaly, ophthalmopathy, tremor, stare, diaphoresis,
and agitation
• Fever (usually)
• Tachycardia (out of proportion to fever) often with associated atrial arrhythmias
• Mental status changes ranging from confusion to coma
General Considerations
Thyroid storm is a life-threatening disorder that occurs in 1-2% of patients with thyrotoxicosis. A
history of previous thyrotoxic symptoms should be sought such as nervousness, restlessness, heat
intolerance, sweating, fatigue, muscle cramps, and weight loss. Thyroid storm should be
suspected with a sudden change in mental status (confusion, agitation, delirium more frequent
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than lethargy or obtundation) with fever and tachycardia out of proportion to fever, and
gastrointestinal, cardiac, or CNS symptoms. Once suspected, treatment should begin
immediately and concurrently with treatment for identifiable or suspected precipitating event.
Mortality from thyroid storm is high even with proper treatment.
Causes
Thyroid storm usually occurs when an already thyrotoxic patient suffers a serious concurrent
illness, event, or injury. Common factors that may trigger a thyroid storm include infection,
surgery, trauma, pregnancy, stroke, DKA, ketosis, radioiodine therapy, drug use (usually
stimulants), ETOH, iodine contrast material, or discontinuation of antithyroid medication.
Clinical Findings
The diagnosis of thyroid storm should be made clinically. Often a history of partially treated
hyperthyroidism or signs of thyroid disease such as thyromegaly, proptosis, stare, myopathy, or
myxedema can be found. The diagnosis should be made in the patient with a probable history of
thyroid disease, which rapidly decompensates in the setting of fever, tachycardia, gastrointestinal
symptoms, and mental status change. Laboratory results will not only be delayed but difficult to
interpret. Elevated thyroid hormone levels are common in significant illness and there is no
significant difference in levels in thyroid storm and thyrotoxicosis. Therefore, no test will
confirm this diagnosis.
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A. Symptoms and Signs
Fever may exceed 40°C (104°F). This may be due to the catabolic state of thyrotoxicosis or
secondary to precipitating infection. Appropriate cultures and broad-spectrum antibiotics are
indicated.
Cardiac findings usually include either sinus or supraventricular tachycardia. The rate is often
characterized as out of proportion to fever. Mental status changes are also common.
Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal pain.
Neuromuscular findings such as agitation, tremor, generalized weakness (especially in the
proximal muscles), and periodic paralysis are also seen.
Findings consistent with prior thyroid disease include thyromegaly, orbitopathy, tremor, stare,
pretibial myxedema, and other integumentary changes such as coarse hair and thick, dry skin.
Death may occur from hypovolemic shock, coma, congestive heart failure, or
tachydysrhythmias.
Apathetic hyperthyroidism is important to consider in the elderly population. With advanced age
and other comorbid conditions, the classic symptoms and signs of thyroid storm and
thyrotoxicosis may be subtle.
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B. Ancillary Diagnostic Findings
Draw blood samples to test for free T4, T3 and TSH, and serum cortisol levels. A complete
blood count, serum electrolytes, glucose, renal and hepatic function tests, and ABG should be
performed; obtain cultures of the blood, urine, and possibly sputum; chest X-ray and ECG are
indicated to look for precipitating causes or complications. Cranial CT scan is indicated for
delirious or comatose patients.
Previous abnormal thyroid function tests may suggest a preexisting thyrotoxicosis. Current
values should be obtained but should not be depended upon to make the diagnosis. Thyroid-
stimulating hormone (TSH) will be markedly low in most patients with thyroid storm or
thyrotoxicosis. Free thyroxine (T4) will be elevated, again similar to thyrotoxicosis. Electrolyte
and glucose abnormalities may also be present due to gastrointestinal losses, dehydration,
physiologic stress, and fever.
C. Electrocardiographic Findings
The ECG is usually abnormal; common findings are sinus tachycardia, increased QRS interval
and P wave voltage, nonspecific ST-T wave changes and atrial dysrhythmias, usually atrial
fibrillation or flutter. Conduction defects, most commonly first-degree AV block and nonspecific
intraventricular conduction delay, may occur. Ischemic findings or myocardial infarction may be
present, especially in older patients with concurrent illness such as diabetes or hypertension.
Treatment
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A. Emergency Measures
Initiate standard resuscitative measures.
Volume replacement is commonly indicated with at least 1 L of normal saline or lactated
Ringer's solution in the first hour due to volume depletion from fever. Frequent reassessment is
required to prevent fluid overload, especially in patients exhibiting signs of high output cardiac
failure (tachycardia, dyspnea, wide pulse pressure). Vasopressors may be required for
hypotension not correcting with volume resuscitation. Hypotension, however, may be a sign of
another problem such as sepsis or adrenal insufficiency.
Phenobarbital should be considered for sedation since it stimulates the clearance of thyroid
hormone by inducing hepatic microsomal enzymes. Fever should be treated aggressively with
cool IV fluids, cool mist sprays, cooling blankets, and antipyretics.
B. Hormone Synthesis Blockers
Propylthiouracil (PTU) 600-1000 mg first dose and 200-250 mg PO every 4 hours is the drug of
choice. Methimazole 40 mg PO initially and then 25 mg every 6 hours can also be used. PTU has
the additional benefit of blocking the peripheral conversion of T4 to the active form of T3.
Neither of the thionamides are available parenterally and must be given PO or via nasogastric
tube.
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C. Hormone Release Blockers
Iodine therapy is an adjunct to the thionamides. It should not be given until at least 2 hours after
PTU or methimazole is administered. Early administration can promote further hormone
production thus worsening hyperthyroidism.
Several forms are available such as potassium iodide (SSKI, 35 mg/drop) 5 drops PO every 6
hour or Lugol's solution 10 drops every 8 hours. Other forms include contrast agents such as
sodium ipodate (Oragrafin) or sodium iopanoate (Telepaque), both of which would be 1 g a day
or 500 mg twice a day by mouth. If iodine allergy is a concern, lithium carbonate can be given
instead at 300 mg every 6-8 hours to maintain levels of 1.0-1.2 mEq/L.
D. Hormone Action Blockers
β-Adrenergic agonists such as propanolol block the peripheral effects of excess thyroid hormone.
A typical dose is 0.5-1 mg IV every 10 min until pulse reduction is achieved and then every 2-3
hours. Caution should be used in patients with bronchospastic disease. Esmolol with a 250-500
μg/kg IV load and then 50-100 μg/kg/min, or guanethidine 30-40 mg PO every 6 hours, or
reserpine 2.5-5 mg IM every 6 hours can be used alternatively.
In very severe cases when thyroid hormone effects are not controlled with the above measures,
plasmapheresis, plasma exchange, peritoneal dialysis, or charcoal plasma perfusion may be
attempted.
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E. Corticosteroids
Corticosteroids inhibit peripheral conversion of T4 to T3. In addition, they also treat the relative
adrenal insufficiency that may be present. Intravenous hydrocortisone, 100 mg every 8 hours, is
the treatment of choice for concurrent adrenal insufficiency, however, dexamethasone, 0.1 mg/kg
intravenously every 8 hours, may be given. The advantage of dexamethasone is that an
adrenocorticotropic hormone (ACTH) stimulation test of the adrenocortical axis may still be
undertaken by consultants.
Disposition
Hospitalization in an intensive care unit is indicated for all patients with thyroid storm. Invasive
hemodynamic monitoring may be necessary to facilitate fluid management and assess progress
of therapy in cases complicated by cardiac failure.
McKeown NJ et al.: Hyperthyroidism. Emerg Med Clin North Am 2005;23(3):669. [PMID:
15982540]
Pimentel L, Hansen KN: Thyroid disease in the emergency department: A clinical and laboratory
review. J Emerg Med 2005;28(2):201-209. [PMID: 15707817]
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Ringel MD: Management of hypothyroidism and hyperthyroidism in the intensive care unit. Crit
Care Clin 2001;17:59. [PMID: 11219235] (Complete coverage of hyperthyroid treatments,
detailing both medical and surgical options.)
Stathatos N, Wartofsky L: Thyroid emergency: Are you prepared? Emerg Med 2003;2:22.
2. Myxedema Coma
ESSENTIALS OF DIAGNOSIS
• A potentially lethal complication of severe hypothyroidism
• Look for typical stigmata: dry skin, delayed reflex relaxation, generalized weakness, edema, or
a transverse scar across the low anterior neck
• Alteration in mental status (although coma is rare).
• Often hypothermic (< 35.5°C [95.9°F])
General Considerations
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Myxedema coma is a rare complication of extreme hypothyroidism. Although it can occur as an
initial presentation of hypothyroidism, myxedema coma usually occurs in patients with known
hypothyroidism or after surgery or ablative therapy for hyperthyroidism. The incidence mirrors
that of hypothyroidism with a 4:1 female predominance. Myxedema coma typically occurs in the
winter months after exposure to cold in those 60 years and older.
Other predisposing factors include cerebrovascular accident, anesthesia, surgery, trauma,
medications, or infection. The cardinal features are central nervous system depression with
hypothermia and hypothyroidism. Hyporeflexia, generalized swelling, coma, bradycardia, and
respiratory depression are also common. Onset is often rapid but can be insidious, especially in
the elderly. If untreated, mortality is estimated at up to 60-70%. If recognized and treated
appropriately, mortality drops to 15-35%.
Clinical Findings
The presumptive diagnosis of myxedema coma should be made when clinical manifestations of
hypothyroidism are accompanied by disturbances of consciousness, hypothermia,
hypoventilation, and hypotension.
A. History
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Cold intolerance, dry skin, constipation, weight gain, muscle cramps, and general fatigue or
weakness are common. Slowing of speech, disorientation, apathy, inappropriate humor
(myxedema wit) or psychosis may also occur. Discontinuation of thyroid replacement, previous
radioactive iodine treatment, thyroidectomy, or medication administration, such as sedatives,
iodides, or amiodarone, are common historical findings.
B. Symptoms and Signs
These include cold intolerance, dry skin, constipation, weight gain, irregular or absent menses,
muscle cramps, paresthesias, angina, or seizures. Neurologic complaints such as generalized
weakness, slow speech, disorientation, apathy, ataxia, inappropriate humor (myxedema wit), or
psychosis are also seen. As hypothyroidism worsens, neurologic symptoms progress to lethargy,
disorientation, and coma. Seizures may also occur.
Hypothermia is found in approximately 80% of patients with myxedema coma. Hypoventilation
is due to decreased respiratory drive and generalized muscle weakness. Hypotension may be
present along with gastrointestinal ileus or urinary retention.
Physical findings include bradycardia; generalized puffiness; periorbital edema; ptosis;
cutaneous myxedema; coarse, dry skin; macroglossia; delayed relaxation phase of deep tendon
reflexes; thyroidectomy scar or a goiter; or coarse, sparse hair may be the only clues of this
condition in a comatose patient.
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C. Laboratory Findings
Thyroid studies are rarely available on an emergency basis. They typically reveal a low serum
free T4 and T3. The TSH is usually high in primary hypothyroidism; however, it may be low in
secondary and tertiary hypothyroidism.
Blood and urine cultures should be obtained. Arterial blood gases may reveal hypoxemia,
hypercapnia, and a respiratory or mixed acidosis. Hyponatremia and hypoglycemia may be
potential contributors to CNS depression. Serum creatinine kinase may be elevated. Myocardial
pathology or rhabdomyolysis must be excluded as causes.
D. Imaging
Chest radiography may show an enlarged heart (from a pericardial effusion) or other
precipitating cause for the myxedema coma, such as pneumonia. Bedside ultrasonography can
confirm a pericardial effusion.
E. Electrocardiographic Findings
The ECG may show bradycardia, low voltage of the QRS complex in all leads, flattening or
inversion of the T waves, and conduction abnormalities.
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Treatment
A. General and Supportive Measures
1. Stabilization—Patients with myxedema coma will need mechanical ventilation if hypoxemia
and hypoventilation are found. Otherwise supplemental oxygen is indicated. Obtain venous
access and blood samples for free T4, free T3, TSH, cortisol, CBC, renal and hepatic function
tests, arterial blood gases, cultures, and electrolytes and glucose levels.
2. Fluid replacement—Isotonic crystalloid solution (normal saline or lactated Ringer's) should be
given for hypotension. Avoid hypotonic solutions because hyponatremia may be present. Treat
severe hyponatremia (≤120 mEq/L) with careful administration of 3% saline if mental status is
depressed. Thyroid replacement therapy and corticosteroids along with restriction of free water
will generally correct mild hyponatremia.
3. Treatment for hypothermia—Active rewarming methods are contraindicated due to the risk of
cardiovascular collapse. Passive methods of rewarming such as blankets are preferred.
4. Other therapies—Avoid unnecessary medications that may further depress mental status.
Empiric antibiotics are indicated initially in critically ill patients. Hypoglycemia and other
electrolyte abnormalities can be treated in the usual manner. Vasopressors are not likely to be
effective because of a reduced adrenergic receptor response and may provoke dysrhythmias,
especially during intravenous thyroid replacement therapy.
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5. Treatment of precipitating causes—Any precipitating cause for myxedema coma must be
addressed. Recovery from myxedema coma is slow since reversal of severe metabolic
abnormalities is required.
B. Specific Therapy
Levothyroxine (T4) is most often recommended for replacement therapy. This form, however,
depends on conversion to the active T3 form that may be inhibited by severe illness.
Liothyronine (T3) does not require conversion and can also be given, but higher doses have been
associated with increased mortality. Combinations of both are also given as a more physiologic
replacement. Some of the protocols are as follows:
• Levothyroxine (T4) alone with an intravenous loading dose of 200-500 μg over the first hour
then 50-100 μg/d, or oral dosing at 50-100 μg/d when tolerated.
• Liothyronine (T3) given as a loading dose of 5-20 μg IV or PO and then 5-10 μg/8 h until
improvement.
• Levothyroxine (T4) at 200-300 μg bolus and 50 μg daily and liothyronine (T3) 5-20 μg IV or
PO load and 2.5-10 μg every 8 hours. Maintenance doses are appropriate when the patient is
clinically stable.
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All three methods may precipitate a cardiac event such as angina, dysrhythmia, or infarction.
Lower dosing regimens are recommended in those at increased risk for cardiac events. All
patients receiving intravenous thyroid hormone replacement should have continuous cardiac
monitoring.
Corticosteroids are also recommended since there is a 5-10% incidence of concurrent adrenal
insufficiency. In this situation, thyroid replacement before corticosteroid replacement can cause
further deterioration. Therefore, early corticosteroid replacement is indicated. This can be given
as intravenous hydrocortisone 100 mg every 8 hours. This is the preferred replacement method
due to its action as both a glucocorticoid and a mineralocorticoid. Acutely however,
dexamethasone 2-4 mg IV every 6 hours is often used since it will not alter a cosyntropin
stimulation test. This will allow consultants to evaluate the need for chronic replacement once
the patient has stabilized.
Disposition
Hospitalization in an intensive care unit is indicated for all patients with myxedema coma.
Ringel MD: Management of hypothyroidism and hyperthyroidism in the intensive care unit. Crit
Care Clin 2001;17:59. [PMID: 11219235] (Good overview of thyroid pathology, diagnosis, and
treatment. Details the rationale and various methods of thyroid hormone replacement.)
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Stathatos N, Wartofsky L: Thyroid emergency: Are you prepared? Emerg Med 2003;2:22.