Case Report

Thyroid storm precipitated by organophosphate intoxication

Thyroid storm is a fatal complication of hyperthyroidism, and many medical events precipitate it. Organophosphate (OP) pesticides inhibit the function of acetylcholinesterase and cause an excess of acetylcholine in synapses and neuromuscular junctions, resulting in muscarinic and nicotinic effects; both could cause secretion by the thyroid gland. We report a case of thyroid storm precipitated by OP intoxication. A 44-year-old woman presented to the emergency department after ingesting OP pesticide (Di- methoate, Sinon Corp, Taichung, Taiwan, ROC). She presented with obvious nicotinic effects such as tachycardia and hypertension but little muscarinic effects. She was treated with pralidoxime, but no atropinization was given because there was no muscarinic crisis. Low-grade fever and tachycardia were persistent in this patient. Fourteen hours later, she experienced high fever, alerted mental status, and heart failure; she deteriorated to death rapidly. Diagnosis of thyroid storm was confirmed based on clinical findings and later thyroid function tests. To our best knowledge, this is the first case report to address thyroid storm precipitated by OP intoxication.

Hyperthyroidism is a common medical disorder that affects up to 2% of the population [1]. Thyroid storm is a fatal complication of hyperthyroidism. It typically occurs in patients with untreated or partially treated thyrotoxicosis who experience a precipitating event. A woman, previously undiagnosed with hyperthyroidism, developed thyroid storm after ingestion of organophosphate (OP) pesticide in a suicide attempt. To our best knowledge, OP-precipitated thyroid storm has never been reported.

A 44-year-old woman was brought to the emergency department by her family one hour after she ingested 200 mL of 44% Dimethoate (an OP pesticide) in a suicide attempt. On arrival, she was in a confused conscious state with a Glasgow Coma Scale score of 13. Her temperature was 37.58C, pulse 135 beats per minute, Blood pressure 164/95 mm Hg, and respiratory rate 21 breaths per minute. Physical examination showed only mild muscle weakness and miosis (pupil of 2 mm in diameter). No other muscarinic effects associated with OP intoxication could be found. There were also neither crackles nor cardiac murmur in the chest field. Her plasma cholines-

terase level was 172 U/L (reference range, 3000-9000 U/ L); other laboratory studies such as white blood cell count, hemoglobin, blood glucose, creatinine, sodium, potassium, alanine aminotransferase, and lipase were all within the reference range. A resting electrocardiogram (ECG) showed sinus tachycardia with a heart rate of 141/min, and a supine chest radiograph revealed cardiome- galy without pulmonary infiltration. Based on the history provided by her family and the bottle of OP pesticide she drank, we suspected acute organophosphate intoxication. Intravenous infusion with 2 g of pralidoxime was given immediately, and 1 g every 6 hours was prescribed for her. Besides, gastric lavage and 80 g of oral activated charcoal were prescribed, too. No atropinization was given because there were no obvious muscarinic effects such as bradycardia, bronchorrhea, and bronchospasm.

The patient was a quiet, healthy woman before this admission. There was no other medical history except of palpitation and nervousness in the past 2 months. She also did not take any medication.

The patient became clearly conscious about 2 hours later. She still had low-grade fever (body temperature, 37.78C), tachycardia (pulse rate, 136 beats per minute), and hypertension (BP, 165/95 mm Hg). Besides, nervous and fine tremors of the upper extremities were also noted. Physical examination and urinalysis revealed no evidence of infection. She suffered from dyspnea about 8 hours later, with BP of 210/105 mm Hg, pulse rate of 148 beats per minute, respiration rate of 32 breaths per minute, and temperature of 37.98C. Physical examination revealed bilateral basal crackles over the lungs and an engorged jugular vein. Pink frothy sputum was noted, too. Arterial blood gas analysis showed only hypoxemia (Pao₂, 50.2 mm Hg) without acidosis or hypercapnia. A CXR showed bilateral pulmonary infiltration up to the lower third of the lung field. An ECG showed sinus tachycardia with a heart rate of 142/min without evidence suggesting myocardial ischemia or infarction. Cardiac enzymes were also revealed to be within the reference range (troponin I, b0.02 ng/mL). Congestive heart failure was suspected; the patient received oxygen mask (Fio₂, 50%); furosemide 40 mg IV infusion was given immediately; and every 8 hours, the hypertension

was controlled with nitroglycerin (50 lg/min initially, up to 150 lg/min). Unfortunately, she became comatose about 14

hours later (Glasgow Coma Scale, E2V1M4). Her pupils

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were symmetrical and 3 mm in diameter, BP 238/153 mm Hg, pulse 193 beats per minute, respiration rate 40 breaths per minute, temperature 428C, and Pulse oximeter showed oxygen saturation of 76% (Fio₂, less than 50%). She thus underwent emergent intubation. Nitroglycerin was adjusted to a dose of 200 lg/min, and a total of 40 mg IV labetalol

was given also to control her hypertension. Acetaminophen (500 mg), a fan, and a cooling blanket were given to control fever but in vain. An ECG showed sinus tachycardia, and CXR showed that pulmonary edema deteriorated to up to two thirds of the lung field. Meanwhile, a computed tomographic scan of the head was performed and showed no evidence of hemorrhage or large infarction; there was also no hypoglycemia (blood glucose, 162 mg/dL). The patient experienced shock (BP, 65/42 mm Hg) and worsened to cardiac arrest rapidly. Resuscitation was performed but failed. Based on her symptoms of refractory high fever, tachycardia, coma, and heart failure, we inferred thyroid storm; her thyroid function was checked, but no propylth- iouracil or propranolol was given during resuscitation. Tracing of her thyroid function tests revealed thyrotropin

level less than 0.04 lIU/mL (reference range, 0.35-5.5), free

thyroxine of 5.14 ng/dL (reference range, 0.89-1.76), and triiodothyronine of 383 ng/dL (reference range, 60-181).

The life-threatening hypermetabolic state due to hyper- thyroidism in which there is evidence of decompensation of 1 or more organ systems is termed thyroid storm. Thyroid storm, if unrecognized and untreated, is often fatal. In most cases of thyroid storm, patients will often have a history of hyperthyroidism, and a precipitating event can be identified. Common precipitants include infection, acute emotional stress, trauma, vigorous palpitation of thyroid gland, surgery, discontinuation of antithyroid drug therapy, high- dose iodine administration, ingestion of thyroid hormone, parturition, and other acute medical illness [2]. A Medline search extending back to 1960 by using organophosphate and thyroid storm as key words revealed that OP intoxica- tion has never been reported in the medical literature as a precipitant of thyroid storm.

The diagnosis of thyroid storm is based on clinical suspicion. The hallmarks of this disease are fever, tachy- cardia out of proportion to the fever, changes in normal mental status, and different degrees of congestive heart failure. Burch and Wartofsky [3] proposed diagnostic scoring criteria for thyroid storm; a calculated score of 45 or higher is highly suggestive of thyroid storm. Our patient had many features of thyroid storm such as fever (score, 30), tachycardia (score, 25), altered mental status (score, 30), and congestive heart failure (score, 15). The total calculated score from the Burch and Wartofsky criteria was 100, which was highly suggestive of thyroid storm. With the elevated free thyroxine and triiodothyronine and low thyrotropin concentrations of this patient, the diagnosis of thyroid storm was confirmed. Most patients who develop thyroid storm have poorly controlled Graves disease [1]. Our patient was a quiet, healthy woman before this admission. However,

history of palpitation and nervousness in the past 2 months may be the clues that she had unrecognized Graves disease before this admission.

What is the mechanism by which OP precipitates thyroid storm? The mechanism by which OP intoxication induces thyroid storm may be through nicotinic and muscarinic effects. Excess acetylcholine (ACh) acts on cervical sympathetic neuronal nicotinic receptors, and activation of the sympathetic neurons can evoke secretion of thyroid hormones via release of norepinephrine from the interfol- licular adrenergic nerve endings [4,5]. In this patient, dominant autonomic nicotinic symptoms and signs support this mechanism. Muscarinic receptors also exist in the thyroid gland, and ACh has a stimulatory effect on iodide organification in follicles. However, this effect can be blocked by atropine [5-7]. We did not atropinize this patient because there were no obvious muscarinic effects. Excess ACh acts on muscarinic receptors in the thyroid gland without blocking by atropine and stimulates the secretion of thyroid hormone, which may have contributed to the developing of her thyroid storm. Both nicotinic and muscarinic effects on the thyroid gland cause a Rapid increase in the fraction of free thyroid hormones, which leads to thyroid storm.

In the patient with OP poisoning, diagnosis of thyroid storm is difficult because they share many of the same physical findings such as tachycardia, hypertension, altered mental status, muscle weakness, tremor, and diarrhea. However, hyperthermia is rarely seen in patients with OP intoxication. Thus, hyperthermia may be a clue to distin- guish thyroid storm from OP intoxication if there is no other evidence of infection presented. The influence of OP intoxication on thyroid hormones is still not quite fully understood. There is a need for further study.

Yao-Dong Yuan MD Chen-June Seak MD

Department of Emergency Medicine Chang Gung Memorial Hospital

Linkou, Taiwan, ROC

Chih-Chuan Lin MD

College of Medicine, Chang Gung University

Taoyuan, Taiwan, ROC Department of Emergency Medicine Chang Gung Memorial Hospital

Linkou, Taiwan, ROC E-mail address: [email protected]

Leng-Jye Lin MD Department of Emergency Medicine Chang Gung Memorial Hospital

Chiayi, Taiwan, ROC

doi:10.1016/j.ajem.2007.02.014

Case Report 861.e3

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