Successfully treated case of severe hypothermia secondary to myxedema coma

Abstract

Background

Myxedema coma is an extremely rare but fatal endocrine emergency that requires urgent recognition and treatment. We describe a case of severe hypothermia that rapidly deteriorated to cardiac arrest that was attributed to myxedema coma.

Case Presentation

A 52-year-old man without a history of hypothyroidism was transferred to our emergency department due to coma and profound hypothermia. The patient developed cardiac arrest immediately after hospital arrival but return of spontaneous circulation was achieved shortly after resuscitation. The patient was noted to have generalized, nonpitting edema, dry skin, severe respiratory acidosis, hyponatremia, and elevated creatinine kinase, which was indicative of hypothyroidism. Myxedema coma was confirmed by a thyroid profile. The patient was successfully treated with intravenous levothyroxine and glucocorticoid.

Conclusion

Although myxedema coma is a rare cause of severe hypothermia, emergency physicians should be familiar with its clinical features and management.

INTRODUCTION

Myxedema coma is a lethal endocrine emergency with a high mortality rate due to decompensation of severe hypothyroidism.¹ Prompt diagnosis and specific treatment are imperative for successful outcomes. However, in addition to its rarity, estimated as 1.08 per million people per year in Japan, early recognition of the disease can be challenging, especially in patients presenting with deep coma or impending cardiac arrest due to unavailability of comprehensive history and patients without a history of hypothyroidism.^2,3 From the standpoint of accidental hypothermia, hypothyroidism-induced severe hypothermia is assumed to be considerably rare in the emergency setting.⁴ Nonetheless, emergency physicians should be knowledgeable about several important clinical features of myxedema coma, which can lead to correct diagnosis and management. Once myxedema coma is considered, both thyroid and steroid hormone replacement therapy are particularly important in addition to supportive care.⁵ Remarkably, the recent approval of intravenous (IV) levothyroxine (LT4) in Japan allows us to treat patients more efficiently and quickly.⁶ Herein, we report an undiagnosed case of hypothyroidism presenting with unconsciousness and severe hypothermia, which led to cardiac arrest upon arrival at the emergency department (ED). The patient was successfully treated with IV LT4. Although myxedema coma is extremely rare, emergency physicians should be aware of this disease and become familiar with its management.

CASE PRESENTATION

A 52-year-old man, a prisoner in a jail, was brought to our ED in winter due to deep coma and profound hypothermia. He appeared restless and drowsy in the morning of the day of presentation. At night, he went to bed after urinating and became unresponsive, so emergency services were called. The patient's medical history included hepatitis C, angina pectoris, and methamphetamine-associated psychosis. Upon arrival at the ED, his vital signs were as follows: Glasgow Coma Scale score, 3 (E1V1M1); respiratory rate, 10 breaths/min; heart rate, 33 b.p.m.; blood pressure, 40/30 mmHg; core temperature, 27.5°C; and unmeasurable oxygen saturation. On physical examination, he was 182 cm in height and 128.2 kg in weight. Generalized, nonpitting edema was evident as well as thick lips, tongue hypertrophy, and dry skin. No goiter was palpated, and no surgical scar was seen on the neck. Arterial blood gas analysis showed severe respiratory acidosis and the laboratory data showed hyponatremia and elevated creatinine kinase levels (Table 1).

Table 1 Laboratory data on admission

Arterial blood gas (10 L/min of oxygen)		Biochemistry
pH	6.983	Total protein	7.0 g/dl
PaCO2	137.4 mmHg	Albumin	4.0 g/dl
PaO2	50.3 mmHg	Total bilirubin	0.3 mg/dl
$$$ {\mathrm{HCO}}_3^{-} $$$	20.2 mmol/L	AST	484 IU/L
Base excess	−4.5 mmol/L	ALT	74 IU/L
Lactate	4.1 mmol/L	Creatine kinase	39,321 IU/L
		BUN	9.4 mg/dl
Complete blood count		Creatinine	0.93 mg/dl
White blood cells	7,350/μl	Sodium	127 mEq/L
Hemoglobin	10.9 g/dl	Potassium	3.3 mEq/L
Hematocrit	33.6%	Chloride	87 mEq/L
Platelet count	19.0 × 104/μl	Glucose	248 mg/dl
Coagulation		CRP	0.06 mg/dl
PT-INR	1.12	Thyroid profile
APTT	38.8	fT3	0.80 pg/ml
Fibrinogen	236 mg/dl	fT4	<0.04 ng/dl
D-dimer	<0.5 μl/ml	TSH	116.0 μIU/ml
Antithrombin III	81%	TGAB	180.7 IU/ml

ALT, alanine aminotransferase; APTT, activated partial thromboplastin time; AST, aspartate aminotransferase; BUN, blood urea nitrogen; CRP, C-reactive protein; fT3, free triiodothyronine; fT4, free thyroxine, PT-INR, prothrombin time–international normalized ratio; TGAB, thyroglobulin antibodies; TSH, thyroid stimulating hormone.

Immediately after arrival, the patient developed pulseless electrical activity arrest; however, return of spontaneous circulation was achieved after one cycle of cardiopulmonary resuscitation, during which intubation was performed and 1 mg adrenaline was administered intravenously. Echocardiogram showed normal left ventricular function with neither regional wall motion abnormality nor pericardial effusion. A J-wave was observed on electrocardiogram. Head computed tomography was unremarkable. Based on the clinical features and data including deep coma, hypocapnia, circulatory collapse, nonpitting edema, hyponatremia, and elevated creatine kinase, myxedema coma was highly suspected. On the same day, the diagnosis of myxedema was confirmed by a thyroid profile consistent with hypothyroidism (i.e., markedly elevated thyroid-stimulating hormone, low free triiodothyronine, and low free thyroxine levels; Table 1). A significant increase in antithyroglobulin antibodies was identified thereafter.

After admission to the intensive care unit, the patient was referred to an endocrinologist. He then received both 300 mg hydrocortisone and 400 μg LT4 IV for 16 h following hospital arrival. With active external rewarming, his core temperature returned to 35°C at 12 h. Although the patient required mechanical ventilation and a high dose of vasopressors, ongoing intensive care as well as thyroid and steroid hormone replacement therapy gradually improved the patient's condition. His blood, sputum, and urine cultures obtained at presentation showed no growth. On day 7, LT4 treatment was converted from IV to an enteral route at an equivalent dose. The patient was successfully extubated on day 12 and discharged on day 15 without any complications (Fig. 1).

Fig. 1. Clinical course of a 52-year-old man with severe hypothermia secondary to myxedema coma. HC, hydrocortisone; LT4, levothyroxine.

DISCUSSION

This report illustrates an exceedingly rare case of myxedema coma presenting with deep coma and severe hypothermia that led to cardiac arrest immediately after arrival at the ED. A careful physical examination and adjunctive data guided us to a prompt diagnosis of myxedema coma. Once suspected, in addition to intensive supportive care, treatment with thyroid hormone as well as glucocorticoids was essential to resolve this critical condition.

Accidental hypothermia is frequently encountered in the ED during the winter season in Japan. According to a nationwide study of accidental hypothermia, 8.5% of the study population suffered from cardiac arrest on hospital arrival. Although detailed information was not collected, only 1.2% of the patients had hypothermia caused by endocrine diseases.⁴ As severe hypothermia is usually accompanied by bradycardia and coma, physical findings such as generalized puffiness, no-pitting edema, and dry skin and laboratory data including hyponatremia, elevated creatinine kinase, and hypercapnia can be key clues leading to suspicion of myxedema coma.^3,5 Although pericardial effusion was not observed in our patient, low voltage or nonspecific ST-T changes in electrocardiogram could be detected in association with pericardial effusion, which is common in overt hypothyroidism.⁵ A diagnostic scoring method for myxedema coma has been proposed by Popoveniuc et al. (Table 2).⁷ However, this would not be practical for severe hypothermic patients in or near cardiac arrest, such as our case, because the majority would inevitably meet these diagnostic criteria for myxedema coma. Although our institution has resources to perform 24/7 thyroid function testing, treatment of myxedema coma should be initiated without waiting for the results of confirmatory thyroid testing.⁸ Although we should have given hormone replacement therapy much earlier, the fact that the patient responded to rewarming allowed us to wait until direct endocrinologist involvement, who was not available immediately because the patient was admitted on a weekend.

Table 2 Diagnostic scoring system for myxedema coma^†

Thermoregulatory dysfunction		Cardiovascular dysfunction
>35°C	0	Bradycardia
32°C–35°C	10	Absent	0
<32°C	20	50–59 b.p.m.	10
Central nervous system effects		40–49 b.p.m.	20
Absent	0	<40 b.p.m.	30
Somnolent/lethargic	10	Other EKG changes‡	10
Obtunded	15	Pericardial/pleural effusions	10
Stupor	20	Pulmonary edema	15
Coma/seizures	30	Cardiomegaly	15
Gastrointestinal findings		Hypotension	20
Anorexia/abdominal pain/constipation	5	Metabolic disturbances
Decreased intestinal motility	15	Hyponatremia	10
Paralytic ileus	20	Hypoglycemia	10
Precipitating event		Hypoxemia	10
Absent	0	Hypercarbia	10
Present	10	Decrease in GFR	10

^†A score of 60 or higher is highly suggestive/diagnostic of myxedema coma, a score of 25 to 59 is suggestive of risk for myxedema coma, and a score below 25 is unlikely to indicate myxedema coma.

^‡Other electrocardiogram (EKG) changes: QT prolongation, or low voltage complexes, or bundle branch blocks, or nonspecific ST-T changes, or heart blocks.

GFR, glomerular filtration rate.

An IV loading dose of 300–500 μg LT4 is recommended for myxedema coma, followed by a daily maintenance dose of 50–100 μg.⁵ Notably, IV LT4 has been available since 2020 in Japan.⁶ Simultaneously, stress doses of glucocorticoid should be provided as part of the initial therapy.⁹ Based on the currently available evidence, the patient was successfully treated with IV LT4 and glucocorticoid. Caution is needed when switching LT4 treatment from IV to the oral or enteral route, in which absorption is reported to be approximately 70–80% of the administered dose.⁹

In addition to its rarity, our case is exceptional in that the patient manifested with profound hypothermia resulting in cardiac arrest, which emergency physicians commonly encounter in the ED, secondary to undiagnosed hypothyroidism. Despite its rarity, the high mortality rate and need for specific treatment of myxedema coma mandate emergency physicians to consider this disease. A high index of suspicion should be aroused when a patient with coma and hypothermia manifests with the above-described clinical features.

CONCLUSION

Although myxedema coma is a rare event, it should be considered as a potential cause of severe hypothermia based on clinical findings. Once suspected, thyroid and steroid hormone replacement therapy combined with supportive care are crucial.

ACKNOWLEDGEMENTS

We thank Christine Burr for editing the manuscript.

DISCLOSURE

Approval of the research protocol with approval no. and committee name: N/A.

Informed consent: The patient provided consent for publication.

Registry and registration no. of the study/trial: N/A.

Animal studies: N/A.

Conflict of interest: None.