DOI:10.4158/EP13460.OR © 2013 AACE.

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A DIAGNOSTIC SCORING SYSTEM FOR MYXEDEMA COMA

Running title: Diagnostic Scoring for Myxedema Coma

Geanina Popoveniuc, MD1, 2, Tanu Chandra, MD3, 4, Anchal Sud, MD1, Meeta Sharma, MD1, Marc R. Blackman, MD 2, 4, 5, Kenneth D. Burman, MD1, Mihriye Mete,

PhD 6,7 , Sameer Desale, MS 6,7 , Leonard Wartofsky, MD1

From: 1Division of Endocrinology, Department of Medicine, MedStar Washington Hospital Center, Washington DC; 2Division of Endocrinology, Department of Medicine, Georgetown University Hospital, Washington DC; 3Division of Endocrinology, Department of Medicine, Veterans Affairs Medical Center, Washington DC; 4Division of Endocrinology, Department of Medicine, George Washington University Hospital, Washington, DC; 5Research Service (151), Veterans Affairs Medical Center, Washington DC; 6 Department of Biostatistics and Bioinformatics, Medstar Health Research Institute, Hyattsville, MD; 7 Georgetown-Howard Universities Center for Clinical and Translational Sciences, Washington, DC (GHUCCTS-CTSA)

Correspondence address: Geanina Popoveniuc MD, address: 110 Irving Street NW, 2A72, Washington, DC, 20010-2975. Email: geanynar@yahoo.com

DOI:10.4158/EP13460.OR © 2013 AACE.

Keywords: myxedema coma; hypothyroidism; diagnosis; scoring system.

Abstract

Objective: To develop diagnostic criteria for myxedema coma (MC), a decompensated state

of extreme hypothyroidism with a high mortality rate if untreated, in order to facilitate its

early recognition and treatment.

Methods: The frequencies of characteristics associated with MC were assessed

retrospectively in patients from our institutions, in order to derive a semiquantitative

diagnostic point scale that was further applied on selected patients from literature. Logistic

regression analysis was used to test the predictive power of the score. Receiver operating

characteristic (ROC) curve analysis was performed to test the discriminative power of the

score.

Results: Of the 21 patients, 7 were re-classified as not having MC (non-MC), and they were

used as controls. The scoring system included a composite of alterations of thermoregulatory,

central nervous, cardiovascular, gastrointestinal, and metabolic systems, and presence or

absence of a precipitating event. All our 14 MC patients had a score of ≥ 60, whereas 6/7 non-

MC patients had scores of 25-50. Sixteen of 22 MC patients from literature had a score ≥ 60,

and 6/22 scored between 45 - 55. The odds ratio per each score unit increase as a continuum

was 1.09 (95% CI, 1.01-1.16; p =0.019); a score of 60 identified coma with an odds ratio of

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1.22.The area under the ROC curve was 0.88 (95% CI, 0.65-1.00), and the score of 60 had

100% sensitivity, and 85.71% specificity.

Conclusions: The scoring system proposed indicates a score of ≥ 60 potentially diagnosing

MC, whereas scores between 45-59 could classify patients at risk for MC.

Abbreviations: MC = myxedema coma; ROC = receiver operating characteristic; TSH = thyroid stimulating hormone; T4 = thyroxine; T3 = triiodothyronine; GCS = Glasgow Coma Scale APACHE II = Acute Physiology and Chronic Health Evaluation; SOFA = Sequential Organ Failure Assessment; SD = standard deviation; MWHC = Medstar Washington Hospital Center; VAMC = Veterans Affair Medical Center.

Introduction

Myxedema coma is a rare form of extreme hypothyroidism with a mortality rate that may

approach 60% [1]. The condition represents a state of decompensated hypothyroidism that

usually occurs after a period of longstanding, unrecognized or poorly controlled thyroid

hypofunction and is often precipitated by a superimposed systemic illness. Such precipitating

or exacerbating factors include infection, trauma, certain medications, hypothermia,

cerebrovascular accident, congestive heart failure, metabolic disturbances, and electrolyte

abnormalities [1-3]. If left untreated, the clinical course is one of multi-organ dysfunction with

characteristic lethargy progressing to altered sensorium (stupor, delirium, and coma).

Hypothermia is a key early manifestation in most patients and may be quite profound (less

than 26° C). Respiratory depression leading to hypoventilation and hypercapnia may

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necessitate intubation and mechanical ventilation. Decreased cardiac contractility,

bradycardia, cardiomegaly, and arrhythmias may lead to hypoperfusion and cardiogenic

shock. Other common abnormalities seen in patients with myxedema coma include

gastrointestinal dysfunction, renal impairment, hyponatremia, hypoglycemia, hypoxemia and

anemia [1].

The diagnosis of myxedema coma is usually based on clinical manifestations, a history of

moderate to severe hypothyroidism, and is confirmed by laboratory testing, with elevated

serum thyrotropin (TSH), and decreased total and free thyroxine (T4), and triiodothyronine

(T3). Early diagnosis, supportive care, and treatment with intravenous thyroxine have been

shown to improve outcomes [4]. Recent reports including prospective studies [2, 3, 5] have

focused on establishing predictors of poor outcome in patients with myxedema coma.

Coma on admission, lower GCS (Glasgow Coma Scale) score and an APACHE II (Acute

Physiology and Chronic Health Evaluation) score of < 20 were demonstrated to be reliable

predictors of higher mortality in the prospective study of Rodriquez et al. [2] of 11 patients

with myxedema coma. They also noted that the mean age of survivors was lower than that of

non-survivors, albeit not statistically significantly. Heart rate, body temperature, mean free

T4, and mean TSH did not differ between survivors and non-survivors. Dutta et al [3], in a

report of 23 patients with myxedema coma, found hypotension and bradycardia on admission,

need for mechanical ventilation, hypothermia unresponsive to treatment, sepsis, intake of

sedative drugs, lower GCS score, and high APACHE II and SOFA (Sequential Organ Failure

Assessment) scores highly predictive of a poor outcome. Results from a Medline search of 82

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cases of myxedema coma [5] revealed that older age, cardiac complications, such as

hypotension and sinus bradycardia with low voltage QRS, and high dose thyroid hormone

replacement during treatment for myxedema coma were associated with a fatal outcome after

1 month of therapy. There was no significant difference in mortality based upon the APACHE

II score and the presence of pulmonary complications.

The diagnosis of myxedema coma is mainly clinical, with no clear cut criteria that might

distinguish either hypothyroidism alone or coma of other etiologies from true myxedema

coma. In view of the high morbidity and mortality of myxedema coma [2], the development

and application of criteria for its identification could allow earlier diagnosis and treatment that

may have a salutary effect on prognosis for recovery and outcome. [4]

Materials and Methods

Study population

Our study population was based on all patients age 18 years and older who presented to

MedStar Washington Hospital Center (MWHC), Washington DC and Veterans Affair (VA)

Medical Center, Washington DC from 1989 to 2009, with an admitting or discharge diagnosis

of myxedema coma.

Definitions

The following definitions and grading systems were employed: hypothermia was defined as a

temperature lower than 35°C. Bradycardia was defined as heart rate less or equal to 60 beats

per minute and hypotension as blood pressure less than 90/60 mmHg, or a mean arterial

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pressure less than 70. Neurological findings were graded based on the severity of mental

status changes, from somnolence to obtundation, stupor and coma. Obtundation was defined

as less than full mental capacity, but still easy arousable with persistence of alertness for brief

periods of time [1]. Stupor was applied to the state of lack of critical cognitive function and

level of consciousness, responsiveness only to painful stimuli, while coma was considered to

be the state of complete lack of responsiveness. Hypoglycemia was defined as a blood glucose

level < 60 mg/dL and hyponatremia was classified as a serum sodium < 135 mEq/L . To

define hypoxemia we used a threshold for oxygen saturation at room temperature of less than

88% or pO2 less than 55 mmHg, while hypercapnia was indicated by a pCO2 level of 50

mmHg or greater. The diagnosis of primary hypothyroidism was based on levels of total or

free thyroxine (T4) below the reference range together with an elevated serum TSH.

Reference ranges were as follows: total T3 71-180 ng/dL, total T4 4.5 -12 ug/dL, free T4 0.8 -

1.7 ng/dL, and TSH 0.45 – 4.5 mIU/L.

Methodology

Each chart was retrospectively reviewed (by GP and TC) to note patient demographics and the

clinical manifestations of myxedema coma in each patient on presentation. The following

characteristics were recorded for each patient: demographics (gender, age, race, past medical

history, to include history of hypothyroidism, or thyroid surgery, medications, medication

non-compliance), vital signs at the time of MC diagnosis (temperature, heart rate, respiratory

rate, blood pressure, oxygen saturation), respiratory status (supplemental oxygen, mechanical

ventilation), neurological status (somnolence, lethargy, obtundation, stupor, coma, seizures),

gastrointestinal manifestations (anorexia, abdominal pain, constipation, decreased/absent

intestinal motility), laboratory findings (complete metabolic panel, TSH, free T4 and total T3,

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blood cultures, urine cultures), electrocardiographic findings, chest X Ray reports, and history

of precipitating insults, if present.

The frequency of various factors distinguishing myxedema coma from hypothyroidism

without coma or non-thyroidal causes of coma was assessed and weighted to further develop a

diagnostic point scale in order to enable a semiquantitative distinction between uncomplicated

hypothyroidism, severe hypothyroidism and myxedema coma. The potential utility of the

diagnostic scoring system was assessed by application to selected patients reported in the

literature.

Statistical analysis

Microsoft excel spreadsheet software was used to note the frequency of clinical events.

Baseline characteristics between the two groups (MC vs. non-MC) were compared by using

Fisher’s exact test for categorical variables and two sample t-test for continuous variables. A

p- value of <0.05 was considered to be statistically significant. Logistic regression analysis

was used to test the predictive power of the score for myxedema coma. Results were

expressed using odds ratio and 95% confidence interval. Further, receiver operating

characteristic (ROC) curve analysis was performed to test the discriminative power of the

score. The discriminative power was measured by using area under ROC curve. Sensitivities

and specificities were calculated for all values of the score and the cutoff point was identified

with left topmost point on ROC curve (representing the highest sensitivity and specificity).

Statistical analyses were performed in SAS 9.3, SAS Institute Inc., Cary, NC, USA.

The study protocol was approved by the Institutional Review Boards of MWHC and VAMC.

Results

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Chart review identified twenty one patients who had been diagnosed with myxedema coma by

an endocrinologist. We re-classified seven patients as non-myxedema coma (non-MC) as we

believed they were misdiagnosed with myxedema coma, and we used them as a control group

(Table 3). Reasons for re-classification included normal free T4 levels and only marginally

elevated serum TSH (patients 1, 2, 4, 7), or absence of any degree of mental status changes

(patients 3, 5 and 6), since mental status alteration was a criteria historically used to diagnose

myxedema coma in patients with hypothyroidism.

The frequency of demographics and clinical characteristics of the patients in each group is

presented in Table 1 and a summary of the patients clinical characteristics is detailed in Tables

2 and 3 (page 1 and 2). As noted in Table 1, there were no statistical significant differences

between the two groups in terms of patient clinical characteristics, to distinguish patients with

myxedema coma, from those with other forms of hypothyroidism. The age (mean ± SD) at

presentation was 68 ± 15 years in MC group vs. 66 ± 23 years in non-MC group (p = 0.81),

with 57% of men in MC group vs. 43% in non-MC group (p = 0.66). The distribution of the

neurological alterations in MC group was relatively similar throughout the entire spectrum of

neurocognitive dysfunction, with 36% of the patients described as somnolent or lethargic, and

with coma being present in 29% of the subjects (Table 1).The most common clinical

manifestations in MC patients were hypothermia (50% in MC vs. 29% in non-MC, p = 0.64)

and hypotension (50% in MC vs. 14% in non-MC, p = 0.17). A wide spectrum of EKG

alterations was noted in patients with MC, with bradycardia present in 36% of the cases.

Myxedema coma patients had more frequent and wider distribution of EKG alterations,

metabolic disturbances and gastrointestinal manifestations, than non-MC patients, although

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none reaching statistical significance (Table 1). Each patient was noted to have had one or

more identifiable precipitating events.

Based on the above findings, we constructed a diagnostic scoring system to enable a

semiquantitative distinction between uncomplicated hypothyroidism, severe hypothyroidism

and myxedema coma (Table 4). The lack of statistically significant difference between all the

clinical characteristics of the two groups, combined with the wide and relatively similar

distribution of events in each category led to the construction of a comprehensive

multisystemic diagnostic scale, in which points were assigned using a stratified approach

based on the severity of each condition in a particular system. The highest weighted

description applicable in each category was considered and scores were totalled. When a

given descriptive characteristic was encountered in more than one category (i.e., precipitating

event and metabolic disturbance), the condition was counted once.

When applied to the fourteen patients with MC, a score of 60 or higher (60 - 120) was

calculated to be diagnostic of myxedema coma (Table 2, page 2). Six of the seven patients

with non-MC had scores ranging between 25 and 50 (Table 3, page 2). A single patient from

this latter cohort had a score of 110, but he was excluded because of a normal free T4 of 1.14

ng/dL and an only mild TSH elevation.

Logistic regression univariate analysis identified the score as a continuum to be predictive of

the outcome with an odds ratio of 1.09 per unit of the score (95% CI, 1.01-1.16; p =0.019). A

score of 45 predicted coma with a probability of 0.27 and an odds ratio of 0.37, respectively,

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whereas a score of 60 had a predictive probability of 0.55, with an odds ratio of 1.22. The

model overall was significant (Chi-square test p-value = 0.0006).

The area under the ROC curve of the prediction score was 0.88 (95% CI, 0.65 – 1.00) (Fig 1).

The cutoff point on ROC curve corresponded to the score of 60, which had the highest

sensitivity (100%) and specificity (85.71%), with a positive likelihood ratio of 7.0 and

negative likelihood ratio of 0.0. The score of 45 had 100% sensitivity, but a lower specificity

of 42.86%, whereas a score of less than 25 had 0% specificity (Fig 1).

When applied to patients in the literature for whom enough clinical data were available, the

diagnostic scoring system identified 16 out of 22 patients as having myxedema coma (score ≥

60) (Table 5). The remaining six patients would have been classified as being at risk for

myxedema coma (scores ranged between 45 - 55), but did not quite meet the criteria for a

diagnosis of myxedema coma. None of the twenty two patients had scores at presentation that

qualified them as unlikely to have myxedema coma.

Discussion

Although it is generally accepted that the diagnosis of myxedema coma should rely on some

degree of mental status alteration, impaired thermoregulatory response and the presence of a

precipitating event [6], clear cut diagnostic criteria to define myxedema coma have not been

established. Moreover, uncertainty of diagnosis is suggested by the numerous hypothyroid

patients with presumed myxedema coma reported in the literature in whom at least one of

these features was minor or absent.

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Although altered mental status was a prominent aspect of the presenting clinical picture in all

our patients, it would be tenuous to base a diagnosis on this alone. There may be innumerable

etiologies for mental status change, but it is through combination with other signs and

symptoms of our scoring system, along with thyroid function test results, that the mental

status changes allow a more precise focus on the diagnosis of myxedema coma.

To our knowledge, there have been no previous reports of clinical algorithms to define

diagnostic criteria for myxedema coma, likely due to the paucity of cases and consequent

lack of studies to address this issue. Accordingly, we have developed a diagnostic scoring

system for myxedema coma, and assessed its potential utility in a cohort of patients from our

two institutions, as well as applying it to selected patients identified in the literature [2, 13-

23]. Our hope is that this scoring system will enable earlier diagnosis and treatment of

patients with myxedema coma.

Importantly, most of the patients whom we evaluated from the literature were likely

“underscored” due to limited clinical data availability. Thus, an assigned score of 60 could

easily have been achieved with one or two more variables being present, such as the lacking

details of metabolic abnormalities, EKG changes, and/or gastrointestinal manifestations.

Patient 14 [Table 5] [15] was of particular interest, as she initially presented to the hospital

with biochemical evidence of subclinical hypothyroidism, and clinical features that would not

have diagnosed her with myxedema coma, given a score of 40. Shortly after admission, her

clinical status deteriorated and she was diagnosed with myxedema coma, achieving a score of

80, based on our diagnostic scale. Of note, the patient’s biochemical markers continued to

reflect a state of subclinical hypothyroidism throughout her hospitalization, showing that a

reliance on thyroid function tests alone could have potentially missed the development of

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myxedema coma, thereby delaying diagnosis and treatment of this patient.

The predictive power of the score as a continuum showed an odds ratio of 1.09 (95% CI, 1.01-

1.16; p =0.019) suggesting that with each unit increase in the score within the range of

available data, the odds of myxedema coma increases by a factor of 1.09, or by 9%. For

instance, a change in score from 50 to 51 would change the predictive probability of coma

from 0.35 to 0.37, or from odds ratio of 0.54 to odds ratio of 0.58. The score of 60 represented

a turning point and predicted coma with a high accuracy, given its predicted probability of

0.55, which conferred an odds ratio of 1.22. The odds of coma for a score of 45 was

approximately 1/3 (0.37), which corresponded to a predicted probability of 0.27.

The discriminative power of the scoring system was high, with area under the ROC curve of

0.88 (95% CI, 0.65 – 1.00). The score of 60 had the highest sensitivity (100%), and specificity

(85.71%) of the scores calculated which makes it a good screening tool given the highest

sensitivity and the relatively high specificity. The score of 45 had 100% sensitivity, but a

lower specificity of 42.86%. Given the above considerations, we propose that with application

of the recommended scoring system, a score of 60 or higher will be highly suggestive of

myxedema coma, a score between 45 and 59 will represent risk for myxedema coma, and that

a score of less than 45 is unlikely to indicate myxedema coma. Given the small sample size,

our model was not capable of producing a threshold score for patients at risk for myxedema

coma, therefore the scores between 45-59 are only our suggestion of representing patients in

this category, based on the given probabilities.

Neurocognitive dysfunction in patients with myxedema coma may vary from disorientation

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and lethargy to slow mentation, confusion, cognitive dysfunction, minimal responsiveness, or

coma. The decompensated neurologic state may be primary, such as from a cerebrovascular

event or due to a drug overdose with sedatives or hypnotics; whereas sepsis, hyponatremia, or

other metabolic disturbances are secondary events, which may worsen the cognitive function.

Homeostatic dysfunction resulting from thyroid hormone deficiency is generally insufficient

to cause myxedema coma, as the body can compensate through neurovascular mechanisms. A

triggering event is usually required to overcome the compensatory mechanisms in a

hypothyroid patient. [7] Infection, cerebrovascular or cardiovascular events, cold temperature

exposure, medications such as amiodarone, beta blockers, lithium, narcotics, sedatives,

diuretics, and metabolic derangements are several examples of such insults. [2, 3] Each

patient had at least one identifiable precipitating event and the frequency of these events was

in concordance with the findings reported in other studies. [3]

Prolonged untreated hypothyroidism coupled with a triggering event may lead to

cardiovascular collapse and shock which may not be responsive to vasopressor therapy alone,

until thyroid hormone also is administered [8]. Electrocardiographic abnormalities such as

bradycardia, low voltage, nonspecific ST wave inversion, QT prolongation, as well as rhythm

abormalities may be seen [9]. Hypotension was commonly seen in our myxedema coma cases,

and the frequency of electrocardiographic abnormalities was similar to that reported in the

literature [3].

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An impaired ventilatory response and a need for mechanical ventilation are common

manifestations in patients with myxedema coma. Decreased respiratory center sensitivity to

hypercarbia and hypoxemia may lead to hypoventilation, which may be aggravated further by

impaired respiratory muscle function, obesity, and other obstructive processes of the airway

such as macroglossia, myxedema of the larynx and nasopharynx, intrinsic processes such as

pneumonia, reduced lung volumes, or extrinsic compressive processes such as pleural

effusions [1, 10, 11].

Reduced glomerular filtration rate (GFR) in hypothyroid patients is a result of decreased renal

plasma flow withwater retention and hyponatremia usually being concomitant findings in

these patients [12]. Fluid extravasation, resulting from altered vascular permeability, may

present as effusions, nonpitting edema and anasarca. Effects of profound thyroid hormone

deficiency on the gastrointestinal system may include decreased intestinal motility with

constipation and may progress to paralytic ileus with a quiet and distended abdomen,

anorexia, nausea and abdominal pain [23]. In our patients, the metabolic abnormalities

occurred with relative equal frequencies but independent of each other, suggesting the

importance of appreciation of the multisystemic basis for development of myxedema coma.

The ultimate diagnosis of myxedema coma should be made with biochemical evidence of low

levels of serum free T4 and T3, and elevated TSH in patients with primary hypothyroidism,

whereas in secondary hypothyroidism the biochemical diagnosis should rely on low, or

normal TSH, and low free T4 and total T3 hormone levels and evidence of pituitary

dysfunction. None of our patients had biochemical evidence of secondary hypothyroidism.

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Particular attention should be given to patients with biochemical evidence of secondary

hypothyroidism that could be difficult to distinguish from the “sick euthyroid” state. The latter

entity represents a physiologic adaptive response of the thyrotropic feedback control to severe

illness, and is reflected by biochemical evidence of normal, low, or slightly elevated TSH,

depending of the severity of the illness, and low free T4 and T3. Therefore, in order to avoid

misclassifying patients with “sick euthyroid” syndrome as having myxedema coma in the

setting of commonly present multiorgan dysfunction, we suggest that appropriate diagnosis of

secondary hypothyroidism should be done first, either from history of hypothalamic-pituitary

dysfunction, or through imaging studies reflecting organic hypothalamic, or pituitary disease.

This study is limited by virtue of its retrospective design and relatively small sample size,

which precluded accurate comparison between groups due to lack of statistical power. Also,

due to insufficient published data in all the case reports of myxedema coma assessed from

literature, it was not possible to fully validate the scoring system. However, the score

demonstrated to have positive predictive value and a high discriminative power.

In conclusion, considering the complex, multisystemic manifestations of hypothyroidism in

patients with myxedema coma and the high mortality associated with delays in therapy, a

practical guide to earlier diagnosis could be of value. We propose a diagnostic scoring system

for myxedema coma based upon data from restrospective cases diagnosed at our institutions,

as well as from selected case reports culled from the literature. This scoring system assessed

an array of the diagnostic features associated with myxedema coma and found a similar

frequency of findings in our cohort of patients as in those assessed from the literature [2, 3, 5].

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This scoring system should be considered in the clinical context of the patient. Further large

prospective, well controlled studies are needed to confirm the current findings, and to inform

whether such a diagnostic approach to patients with myxedema coma will enable earlier

recognition and more effective treatment of this potentially fatal endocrine emergency.

Disclosure Summary: The authors have nothing to disclose.

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Table 1. Frequency of events in 21 patients with and without

myxedema coma presenting between 1989 – 2009

at MWHC and VA Medical Center, Washington DC

MC Non-MC

n (%) n (%) p-value

Patients 14 7

Gender

Male 8 (57) 3 (43) 0.6594

Female 6 (43) 4 (57)

Age (mean ± SD ) 68 ± 15 66 ± 23 0.8120

Date of admission (Nov - Feb) 6 (43) 3 (43) 1.0000

History of hypothyroidism 12 (86) 4 (57) 0.2800

Hypothermia (T < 35o C) 7 (50) 2 (29) 0.6424

Central nervous system

Somnolence/lethargy 5 (36) 1 (14) 0.6126

Obtunded 4 (29) 1 (14) 0.6244

Stupor 1 (7) 2 (29) 0.2474

Coma 4 (29) 0 (0) 0.2550

Cardiovascular system

Bradycardia (HR < 60) 5 (36) 2 (29) 1.0000

Hypotension 7 (50) 1 (14) 0.1736

Prolonged QT 3 (21) 1 (14) 1.0000

Non-specific ST-T changes 3 (21) 0 (0) 0.5211

Low voltage complexes 1 (7) 0 (0) 1.0000

Bundle branch blocks 1 (7) 0 (0) 1.0000

Pericardial effusion 1 (7) 0 (0) 1.0000

CXR findings

Cardiomegaly 5 (36) 3 (43) 1.0000

Pleural effusions 5 (36) 2 (29) 1.0000

Pulmonary edema 3 (21) 3 (43) 0.3544

Pulmonary infiltrates 2 (14) 2 (29) 0.5743

Gastrointestinal symptoms

Anorexia, abdominal pain,

constipation

2 (14) 2 (29) 0.5743

Decreased bowel sounds 2 (14) 0 (0) 0.5333

Distended, quiet abdomen 1 (7) 0 (0) 1.0000

Metabolic disturbances

Decrease in GFR 6 (43) 1 (14) 0.3371

Hypoxemia 5 (36) 2 (29) 1.0000

Hypercarbia 5 (36) 2 (29) 1.0000

Hyponatremia 5 (36) 0 (0) 0.1235

Hypoglycemia 4 (29) 0 (0) 0.2550

Precipitating event

Infection 5 (36) 4 (57) 0.3972

Medication non-compliance 4 (29) 3 (43) 0.6514

Furosemide use 4 (29) 1 (14) 0.6244

Cold exposure 4 (29) 1 (14) 0.6244

Medications 3* (21) 0 (0) 0.5211

Hypoglycemia 2 (14) 0 (0) 0.5333

Gastrointestinal bleed 2 (14) 0 (0) 0.5333

Congestive heart failure 2 (14) 0 (0) 0.5333

Hypercapnia 1 (7) 0 (0) 1.0000

Cerebrovascular event 1(7) 0 (0) 1.0000

Treatment

Levothyroxine IV with Steroids 9 (64) 1 (14) 0.0635

Levothyroxine IV without

Steroids

3 (21) 0 (0) 0.5211

Levothyroxine PO 1 (7) 6 (86) 0.0009

*Amiodarone (n=2), Amitriptyline (n=1)

SD, standard deviation; T, temperature; HR, heart rate; CXR, chest X Ray; GFR, glomerular

filtration rate.

Table 2: Features and variables in 14 patients with myxedema coma (page 1/2)

Pa-

tient

Age Gen-

der

History

of hypo-

thyro-

idism

Cold

season

(Nov-

Feb)

Tempera

-ture (°C)

Neuro-

cognition

Precipitating

events

TSH

(mU/L)

Free T4

(ng/dL)

Total T3

(ng/dL)

1 49 M Yes Yes 33.3 Obtunded Hypoglycemia

Cold exposure

53.4 0.68 50.6

2 67 F Yes No 36.4 Coma Infection (PNA)

Hypercarbia

28.6 0.59 56.3

3 84 M Yes No 33.6 Coma Infection (UTI)

GI bleed

125 < 0.3

4 41 F Yes No 36.4 Lethargic Amitriptyline 122 0.56

5 76 M No Yes 36.2 Obtunded Infection (UTI)

Amiodarone

Cold exposure

170 0.49 66.3

6 82 F Yes No 36.3 Lethargic Infection (UTI) 71 < 0.2 < 40

7 67 F Yes Yes 36.3 Obtunded Hypoglycemia 326 0.39 < 40

8 49 F Yes Yes 37 Lethargic GI bleed

Furosemide

57 0.42 < 40

9 74 M Yes Yes 34.4 Coma Amiodarone 45 0.2

Cold exposure

10 65 M Yes No 35 Coma CHF

Furosemide

58* 0.6*

11 64 M Yes No 35 Lethargic ? (died at

presentation)

128.8 0.9

12 89 M No Yes 33.8 Stupor CHF

Furosemide

Cold exposure

84 0.3

13 83 F Yes No 34.4 Obtunded Infection (PNA,

UTI)

116 0.59

14 61 M Yes No 36.9 Lethargic/

seizures

CVA

Furosemide

107 0.44 41.2

*TFTs (thyroid function tests) obtained 1 month prior

SI conversion factors: To convert freeT4 to nmol/L, multiply by 12.8717; to convert total T3 to pmol/L, multiply by 15.361

PNA, pneumonia; UTI, urinary tract infection; CVA, cerebrovascular accident, CHF, congestive heart failure;

GI bleed, gastrointestinal bleed

Table 2: Features and variables in 14 patients with myxedema coma (page 2/2)

Pa-

tient

Heart

rate

Hypo-

ten-

sion

Hypo-

xemia

Hyper-

carbia

Mecha

-nical

ventila

-tion

So-

dium

(mEq/

L)

Glu-

cose

(mg/d

L)

Change

in GFR

(Δ)

EKG

findings

CXR

findings

GI

symp-

toms

Score

1 87 Yes No

No No 137 42 no QT pro-

long.

No Decreased

intestinal

motility

90

2 65 No No Yes Yes 104 147 Yes (35) No Pleural

effusion

Infiltrates

Decreased

intestinal

motility

95

3 62 No No No Yes 146 50 Yes (9) No No No 70

4 130 Yes No No No 138 58 Yes (64) No Pleural

effusions

Pulmonary

edema

No 95

5 54 No No No No 132 102 Yes (27) No No Consti-

pation

60

6 59 Yes Yes Yes Yes 142 88 Yes (13) No Cardiomegaly No 95

7 83 Yes Yes No Yes 133 <20 No QT pro- Cardiomegaly No 105

long. Pulmonary

edema

8 61 No No No No 133 81 Yes (19) No Cardiomegaly

Pleural

effusions

No 65

9 70 Yes Yes No No 135 109 N/A No cardiomegaly Abdomin

al pain

100

10 56 No No No Yes 136 135 N/A No No Ileus 90

11 46 Yes No No Yes 133 71 N/A No No No 80

12 61 No No Yes No 156 128 N/A No Pleural

effusions

No 60

13 67 Yes Yes Yes Yes 145 175 Yes (15) QT pro-

long.

Pleural

effusions

Pulmonary

edema

Infiltrates

No 120

14 56 No No No No 138 145 No No Cardiomegaly No 75

GFR, glomerular filtration rate; CXR, chest X Ray

Heart rate in beats/min; GFR in mL/min.

Table 3: Features and variables in 7 patients without myxedema coma (page 1/2)

Pa-

tient

Age Gen-

der

History

of hypo-

thyro-

idism

Cold

season

(Nov-

Feb)

Tempe

-rature

(°C)

Neuro-

cognitio

n

Precipitating

events

TSH

(mU/L)

Free T4

(ng/dL)

Total T3

(ng/dL)

1 32 M No Yes 31.3 Lethargic Infecion

(bacteremia)

5.67 0.62 56.2

2 73 M No No 36.8 Stupor Infection (PNA) 5.83 1.06

3 52 F Yes Yes 37 Normal Non-compliance 80.6 0.39

4 77 F Yes No 37 Obtunded Non-compliance 9.0 1.3

5 94 F Yes No 36.6 Normal Infection (UTI) 7.2 2.03

6 45 F Yes No 36.6 Normal Non-compliance 145 0.28

7 90 M No Yes 34.4 Stupor Infection (PNA)

Cold exposure

Furosemide

11.9 1.4 70.8

PNA, pneumonia; UTI, urinary tract infection

Table 3: Features and variables in 7 patients without myxedema coma (page 2/2)

Pa-

tient

Heart

rate

Hypo-

tension

Hypo-

xemia

Hyper-

carbia

Mecha

-nical

venti-

lation

Sodium

(mEq/L)

Glucose

(mg/dL)

Change

in GFR

(Δ)

EKG

findings

CXR

findings

GI

symp-

toms

Score

1 50 No No N/A No 140 75 No(on

HD)

QT

prolong.

N/A No 50

2 85 No Yes No Yes 137 80 No (on

HD)

No Pleural

effusions,

infiltrates

No 50

3 87 No No No No 140 263 No N/A Cardio-

megaly

No 25

4 102 No Yes Yes No 145 86 No No No No 45

5 72 No No No No 144 96 No No Cardio-

megaly

No 25

6 57 No No No No 140 127 No No No consti

pation

25

7 72 Yes No Yes No 145 80 Yes (15) Atrial

flutter

Cardio-

megaly,

pleural

N/V/c

onsti-

pation

100

effusions,

infiltrates

Heart rate in beats/min; GFR in mL/min; EKG, electrocardiogram; CXR, chest X Ray; GI, gastrointestinal; Δ, delta;

HD, hemodialysis.

Table 4. Diagnostic Scoring System for Myxedema Coma

Termoregulatory dysfunction (Temperature, oC) Cardiovascular dysfunction

>35 0 Bradycardia

32-35 10 Absent 0

<32 20 50-59 10

Central Nervous System Effects 40-49 20

Absent 0 <40 30

Somnolent/Lethargy 10 Other EKG changes* 10

Obtunded 15 Pericardial/pleural effusions 10

Stupor 20 Pulmonary edema 15

Coma/Seizures 30 Cardiomegaly 15

Gatrointestinal 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

*Other EKG changes: QT prolongation, or low voltage complexes, or bundle branch blocks, or non-specific ST-T

changes, or heart blocks.

A score of 60 or higher is highly suggestive/diagnostic of myxedema coma; a score of 25 -59 is suggestive of risk

for myxedema coma, and a score below 25 is unlikely to represent myxedema coma.

Table 5: Features and variables in 22 patients from literature diagnosed with myxedema coma

Ref Pt Age Gen-

der

Temp

(°C)

Neuro-

cognition

Precipi-

tating

events

Conco-

mitant

disorder

Heart

Rate

MAP EKG

chan-

ges

Hypo-

xemia

Hyper-

carbia

Sodium

(mEq/L)

TSH

(mU/L)

Free T4

(ng/dL)

Score

2 1 84 M 34.5 Obtunded Urinary

infection

Pleural

effusion

39 110 N/A No N/A 133 51.3 0.46 85

2 2 75 F 34.4 Coma Pneumonia

, sepsis

Anemia,

DIC,

ARDS,

septic

shock

124 108 N/A Yes N/A 122 0.43 0.25 90

2 3 70 F 33.9 Coma Abdominal

surgery

Respiratory

failure,

shock

38 115 N/A Yes N/A 144 71 0.18 110

2 4 65 F 34.9 Obtunded Urinary

infection

Pericardial

effusions

104 74 N/A No N/A 124 2.4 0.23 55

2 5 20 F 34.2 Obtunded Typhoid

fever

Anemia,

pneumonia

114 72 N/A No N/A 128 76.04 0.28 45

2 6 81 F 34.8 Coma Ileus Respiratory

failure,

pleural

effusion,

shock

38 68 N/A Yes N/A 126 28 0.17 130

2 7 63 F 35.0 Obtunded Urinary

infection

Anemia,

respiratory

failure

124 88 N/A No N/A 110

38 0.15 55

2 8 83 F 35.0 Coma Urinary

infection

None 65 95 N/A No N/A 122 60.6 0.15 60

2 9 79 F 34.8 Obtunded Respiratory

infection

None 52 128 N/A No N/A 120 153 0.15 55

2 10 47 F 34.9 Obtunded Urinary

infection

Anemia,

Respiratory

failure

144 112 N/A No N/A 126 9.85 0.37 55

2 11 82 F 33.6 Obtunded Pneumonia Respiratory

failure,

shock

38 80 N/A Yes N/A 120 78.2 0.5 105

13 12 84 F 30.0 Global

amnesia

N/A 33 60 N/A No No 135 63.2 0.17 85

14 13 62 M 35.3 Delayed

response

Non-

compliance

Pleural

effusions

50 74 Low

volt

N/A N/A 134 >60 undetec

table

60

15 14 47 F 33.2 Lethargic None Pericardial

effusion

88 73 None N/A N/A Low 6.09 0.83 40-

>80

16 15 88 F 36.1 Lethargic Bok Choy 58 119 N/A Yes Yes 132 74.4 undetec

table

60

17 16 68 F 29.1 Changes in

MS

Sunitinib 46 107 N/A No No 115 41.4 undetec

table

75

18 17 27 F 36.6 Changes in

MS

Diabetic

ketoacidosi

s

None 40 98 Low

volt

N/A N/A 132 48 0.4 45

19 18 64 F 30.1 Changes in

MS

Urinary

infection

None 60 84 N/A No Yes 138 > 200 <0.35 70

20 19 33 F 35 Coma Non-

compliance

Hypoglyce

mia

50 76 N/A No N/A 138 >100 0.24 60

21 20 74 F 34.8 Stupor CVA 59 50 Low Yes No 121 30.12 0.05 100

volt

Prol

QT

22 21 78 M 35.5 Coma N/A Hypoactive

BS

52 70 N/A N/A Yes 106 61.24 <0.3 75

23 22 60 F 37.7 Altered

sensorium

(obtunded)

sepsis Ogilvie’s

syndrome

(ileus)

bradic 125 Juncti

onal

rythm

N/A N/A 122 341.57 1.6* 75

Ref, reference; Pt, patient; Temp, temperature; MAP, mean arterial pressure; EKG, electrocardiogram; N/A, not available.

DIC, disseminated intravascular coagulation; ARDS, acute respiratory distress syndrome; MS, mental status;

CVA, cerebrovascular accident; BS, bowel sounds; Heart rate in beats/min.

*Total T4: 1.6 ug/dL (5.6 – 13.7ug/dL)

a

Figure 1. ROC curve of the scoring system for myxedema coma

0.00

0.25

0.50

0.75

1.00

Sen

sitiv

ity

0.00 0.25 0.50 0.75 1.001 - Specificity

Area under ROC curve = 0.8827

≥60

≥65

≥70

≥75

≥80

≥105

≥120

>120

≥90

≥95

≥100

≥25 ≥50 ≥45