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

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

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

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.

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.

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

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.

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.

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]

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

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

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.

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.

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.

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.

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.)

Stathatos N, Wartofsky L: Thyroid emergency: Are you prepared? Emerg Med 2003;2:22.