Thyroid storm and ventricular tachycardia.

Abstract: A 34-year-old woman was brought to our emergency department because of sudden loss of consciousness. Ventricular tachycardia and fibrillation were noted on electrocardiographic monitoring and reverted to sinus rhythm after repeated defibrillation. She was treated as a case of thyroid storm. Although tachycardia and fever normalized after 2 days, she remained comatose and died. This is an unusual case because the patient's initial presentation was cardiac arrest without previous history of cardiac disease. To our knowledge, this is the first reported case where ventricular tachyarrhythmia was the initial presenting sign of thyroid storm.

Key Words: nonthyroid illness, thyroid storm, ventricular arrhythmia

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Thyroid storm is a rare clinical emergency that is fatal when left untreated. Even with early diagnosis and aggressive treatment, mortality is still high at 20 to 30%. (1,2) The storm is usually due to a severe exacerbation of a preexisting thyrotoxicosis, which later leads to decompensation in different organ systems. (3) The thin line demarcating these two disease entities remains obscure and, to date, no one criterion or any pathognomonic feature is present to make a definite diagnosis of thyroid storm. A diagnostic point system (4) is available to aid doctors in arriving at the diagnosis earlier.

Case Report

A 34-year-old woman was brought to our hospital because of sudden loss of consciousness. She had a history of hyperthyroidism for 7 years with irregular intake of medications (propylthiouracil 50 mg and propranolol 10 mg administered every 8 hours), but stopped taking them 6 months previously. She was lost to follow-up and had not been taking any medications since. One month before admission, her family and friends noted gradual bulging of her eyeballs and anterior neck, as well as a loss of weight. The patient ignored this, refusing to see a doctor. She was at work when dyspnea and palpitations occurred. After resting for 5 minutes, she suddenly fell down, losing consciousness. She was rushed to our hospital.

On examination, the patient was cyanotic and unresponsive. Pupils were fixed and dilated. There was no spontaneous respiration and pulses were not palpable. Cardiopulmonary resuscitation was performed and electrocardiography showed ventricular tachycardia (Fig. 1A) and then fibrillation (Fig. 1B). Defibrillation was performed repeatedly, alternating with epinephrine (1:1,000) infusion and lidocaine (50-mg IV bolus). After 28 minutes, her heart rate was restored and a dopamine drip was started. After 1 hour, her blood pressure was 140/90 mm Hg and her heart rate was 147 beats/min, with regular rate and rhythm. Her rectal temperature was 41.5[degrees]C.

Laboratory examinations were as follows: white blood cell count, 9.34 X [10.sup.3]/[micro]L (normal range [NR], 5.0-10.0 X [10.sup.3]/[micro]L); hemoglobin, 12.0 g/dL (NR, 12.0-16.0 g/dL); lymphocyte predominance of differential count, 58%; segmenters, 32%; serum glutamic oxaloacetic transaminase, 33 U/L (NR, 10-35 U/L); serum glutamic pyruvic transaminase, 23 U/L (NR, 0-40 U/L); blood urea nitrogen, 12.5 mg/dL (NR, 8-20 mg/dL); creatinine, 0.9 mg/dL (NR, 0.6-1.5 mg/dL); blood sugar, 117 mg/dL (NR, 50-110 mg/dL); serum sodium, 140.9 mEq/L (NR, 137-149 mEq/L); potassium, 4.55 mEq/L (NR, 3.6-5.0 mEq/L); chloride, 108.9 mEq/L (NR, 96-107 mEq/L); calcium, 8.5 mg/dL (NR, 8.5-10.5 mg/dL); phosphorus, 3.5 mg/dL (NR, 2.31-4.66 mg/dL); and magnesium, 2.2 mg/dL (NR, 1.7-2.2 mg/dL). Postresuscitation creatine phosphokinase and creatine kinase-MB were 2,150 U/L (NR, 60-190 U/L) and 48 U/L (NR, 0-16 U/L), respectively. Chest radiograph, urinalysis, and abdominal ultrasonography were normal. Postresuscitation electrocardiography showed significant ST-segment elevation over leads [V.sub.2] through [V.sub.6], I, and aVL, and ST-segment depression over leads III and aVF. Toxicology screen for amphetamine and morphine was negative. Erythrocyte sedimentation rate and C-reactive protein were elevated. Thyroid-stimulating hormone was 0.001 mIU/mL (NR, 0.5-5.5 mIU/mL), free thyroxine (T4) was 4.22 ng/dL (NR, 0.89-1.80 ng/dL), and triiodothyronine (T3) was 125 ng/dL (NR, 75-175 ng/dL). Antinuclear antibody was 1:80 (normal, <1:40), antithyro-globulin antibody was 1:400 (normal, <1:100), and antimicrosomal antibody was 1:25,600 (normal, <1:100).

The patient was administered propylthiouracil 250 mg every 4 hours, propranolol 40 mg every 8 hours, hydrocortisone 100 mg IV every 6 hours, acetaminophen 500 mg every 6 hours, and vitamin B complex 1 ampule IV every day. One hour after propylthiouracil was given, Lugol solution was administered at 20 drops every 8 hours. Amoxicillin/clavulanic acid (1.2 g) and gentamicin (80 mg) drip were administered IV every 8 hours for possible infection but were discontinued after 3 days when blood cultures tested negative and chest films remained normal. Cardiac ultrasound showed no chamber dilation with adequate global performance, no valvular defects, and an estimated left ventricular ejection fraction of 80%. Cardiac catheterization was suggested, but the family refused. Fever, diaphoresis, and tachycardia were controlled on the second day. Brain computed tomography was negative and electroencephalography showed flat tracings. Follow-up free T4 level was 0.79 ng/dL (NR, 0.70-2.1 ng/dL). No occurrence of cardiac arrhythmia was noted afterward. Follow-up electrocardiography showed normal sinus rhythm without ST-segment and T-wave changes. She remained comatose and died after 16 days of hospital stay due to pneumonia. Her family refused an autopsy.

Discussion

The pathogenesis of thyroid storm remains unclear, with numerous proposed hypotheses. (3) Clinical features are usually indistinguishable from uncomplicated thyrotoxicosis. Diagnosis is difficult when the crisis presents with atypical features masquerading as other diseases, thus causing delay in diagnosis and treatment. Responding to treatment may be the only means of confirmation. Unusual presenting signs of thyroid storm include cerebrovascular accidents, ventricular tachycardia, coma, jaundice, complete heart block, status epilepticus, rhabdomyolysis with acute renal failure, intractable shock, hypoglycemic coma complicated with posterior leukoencephalopathy syndrome, and normothermia, adrenal insufficiency, and lactic acidosis, with multiorgan failure.

[FIGURE 1 OMITTED]

The rapid rise of these hormones, as well as the sudden increase in the amount of free hormone available to the cells, is more important than the absolute hormone levels. (1,2) These hormones affect the cardiovascular and gastrointestinal systems in particular, with the former being life threatening because cardiac decompensation frequently occurs in longstanding thyrotoxicosis, even without any underlying cardiac disease. In hyperthyroid patients, there is usually a decrease in systemic vascular resistance; an increase in cardiac output, heart rate, and systolic blood pressure; an enhanced left ventricular contractility, ejection fraction, and blood volume; and a wide pulse pressure. This increases myocardial oxygen consumption, cardiac workload, and hypertrophy. (5,6) Eventually, it leads to irreversible cardiovascular collapse.

Arrhythmias are usually supraventricular, with atrial fibrillation being the most common. Atrial flutter and paroxysmal atrial tachycardia are uncommon, whereas ventricular premature contractions and ventricular fibrillation are rare. (7,8) They are due to the direct augmenting effect of the thyroid hormones on the [beta]-adrenergic receptor's sensitivity to catecholamines and increasing myocardial excitability, and on the intrinsic sinoatrial electrophysiologic function, thus decreasing conduction time and resulting in nodal blockade in longstanding disease. (7,9,10)

This case is unusual because there are only two cases in the literature with ventricular tachyarrhythmia accompanying a thyroid problem. In the first case, coarse ventricular fibrillation was noted only after palpating the thyroid gland during surgery while under anesthesia. (11) The second case involved a 4-year-old boy who was admitted because of febrile convulsions. Asymptomatic, monomorphic ventricular tachycardia was noted and responded to antithyroid treatment after antiarrhythmic drugs were deemed ineffective. (12) These two cases are different from ours because it was not the arrhythmia that brought the patient to the emergency department.

[beta]-adrenergic blockers provide relief from the undesirable symptoms of thyrotoxicosis by attenuating the effects of catecholamines induced by the hyperthyroid state. They also reverse or block thyroid hormone-induced cardiac hypertrophy, (13,14) and are weak inhibitors of extrathyroidal conversion of T4 to T3. (15) Poor compliance and discontinuation of these drugs may have contributed to her arrhythmia and initial presentation. During the 6-month period between discontinuation and presentation, the cumulative effect of uncontrolled sustained tachycardia may have altered both ventricular systolic and diastolic functions, predisposing the patient to ventricular arrhythmia.

The patient worked in an air-conditioned and well-ventilated environment, ruling out heatstroke as the cause. Causes of hyperthermia, such as amphetamines, cocaine abuse, tricyclic antidepressants, phenothiazines, inhaled anesthetics, and anticholinergics were ruled out after a thorough history and physical and laboratory examinations. The patient was not on birth control pills, did not smoke, did not ingest any alcoholic beverages, and was in no emotional distress. There was no trauma or surgical history. Toxicology screening for amphetamines and morphine, taken immediately in the emergency room, were negative. Serum magnesium, calcium, and potassium were normal. There was no anemia, and cardiac ultrasonography did not reveal any structural or valvular defects, outlet obstruction, or chamber dilation. Wall motion and left ventricular function were good. Serial electrocardiography did not reveal any evidence of myocardial ischemia, QT prolongation, atrial fibrillation, or bundle branch blocks, and arterial blood gases were normal. Brain computed tomography was also normal.

Infection is an important triggering factor for thyroid storm. Although the patient's differential count suggested a viral cause, there was no evidence of infection or sepsis before or during presentation. Leukocytosis with a shift to the left is common, even in the absence of infection. (15) However, an early stage of infection cannot be completely ruled out. In patients with thyrotoxicosis and infection, it is difficult, if not impossible, to determine whether fever and tachycardia herald an impending crisis or merely reflect infection. We do not recommend routine use of antibiotics in thyroid storm. However, given the patient's presentation, possible aspiration may have occurred before and during transport.

A normal T3 level, such as the level in this patient, can occur when hyperthyroidism is combined with a nonthyroid illness, also known as "sick euthyroid syndrome." In mild illnesses, T3 levels decrease and may appear normal. This is due to a decrease in the extrathyroidal conversion of T4 to T3 that occurs in nonthyroidal illnesses. However, as the illness progresses and increases in severity, T4 levels decline. (16)

Elevations in creatine phosphokinase can be caused by strenuous activity, trauma, prolonged muscle cramps, generalized seizures, myopathies, postsurgery, hypothyroidism, pulmonary embolism, myocardial infarction, myocarditis, and rhabdomyolysis. Except for myocarditis, which cannot be completely ruled out, the remaining causes were absent in this patient. The elevated results were probably caused by repeated cardioversion, as blood was drawn after resuscitation.

We concede that an autopsy and cardiac catheterization could have ruled out myocarditis and a coronary artery disease that could have triggered or predisposed this patient to ventricular arrhythmia. However, with the dramatic response to treatment, the normalization of the electrocardiogram, and the absence of any form of arrhythmia after medications directed at the thyroid gland, we strongly believe that it was the ignored thyroid problem that caused the cardiac decompensation, which later deteriorated into a full-blown storm. We think this was what caused the ventricular arrhythmia. Dopamine, a potent inhibitor of TSH secretion, could not have influenced the patient's TSH level, since blood was drawn before dopamine was infused. Most importantly, after ruling out the various causes of ventricular tachycardia, the history and the only abnormal data in this patient pointed to a thyroid abnormality. After treating the problem, the arrhythmia disappeared.

Conclusion

Thyroid storm is a rare but treatable emergency that is fatal when left untreated. Early diagnosis and treatment may be lifesaving, so recognition of both typical and atypical presentations of the disease is mandatory. Further studies regarding the relationship between the thyroid gland and ventricular tachyarrhythmia are needed. It is wise and prudent to alert physicians to consider thyroid storm as a possible cause of sudden unexplained arrests, and at the same time, to add ventricular tachycardia to the list of unusual initial presentations of thyroid storm.

Accepted January 10, 2003.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9706-0604

References

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7. Klein I, Ojamaa K. Thyrotoxicosis and the heart. Endocrinol Metab Clin North Am 1998;27:51-62.

8. Polikar R, Feld GK, Dittrich HC, et al. Effect of thyroid replacement therapy on the frequency of benign atrial and ventricular arrhythmias. J Am Coll Cardiol 1989;14:999-1002.

9. Fadel BM, Ellahham S, Ringel MD, et al. Hyperthyroid heart disease. Clin Cardiol 2000;23:402-408.

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11. Wolfson B, Smith K. Cardiac arrest following minor surgery in unrecognized thyrotoxicosis: A case report. Anesth Analg 1968;47:672-676.

12. Minegishi Y, Kumada S, Suzuki H, et al. Repetitive monomorphic ventricular tachycardia in a 4-year-old boy with toxic multinodular goiter. Acta Paediatr Scand 1991;80:726-731.

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14. Bondi B, Fazio S, Carella C, et al. Control of adrenergic overactivity by [beta]-blockade improves quality of life in patients on long-term suppressive therapy with levothyroxine. J Clin Endocrinol Metab 1994;78:1128-1133.

15. Wartofsky L. Thyrotoxic storm, in Braverman LE, Utiger RD (eds): Werner and Ingbar's The Thyroid: A Fundamental and Clinical Text. Philadelphia, Lippincott Williams & Wilkins, 2000, ed 8, pp 680-683.

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RELATED ARTICLE: Key Points

* This is the first reported case where a thyroid crisis presented with cardiac arrest (ventricular tachycardia and fibrillation).

* Ventricular arrhythmias are very rare in thyrotoxicosis and thyroid storm.

* Previous articles describe the occurrence of thyroid storm and ventricular tachycardia, but these were due to other intermingling factors and not the initial presentation.

* Early recognition and treatment directed at the source of the problem, when manifesting as atypical signs and symptoms, are lifesaving.

Yeun Tarl Fresner Ng Jao, MD, Yi Chen, MD, Wen-Hung Lee, MD, and Fang-Ting Tai, MD

From the Department of Emergency Medicine and the Endocrinology Section, Tainan Municipal Hospital, Tainan, Taiwan.

We have no conflict of interest regarding this article.

Reprint requests to Yi Chen, MD, Tainan Municipal Hospital, 670 Chung Te Road, Tong Chi, Tainan, Taiwan, Republic of China 701. Email: [e-mail]