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ENDOCRINE PRACTICE Rapid Electronic Article in Press Rapid
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AACE. Original Article EP13460.OR
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:
[email protected]
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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 35C. 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
Fishers exact test for categorical variables and two sample
t-test for continuous variables. A
p- value of
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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 patients
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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unfamiliar medical emergency. Thyroid. 2007;17:371-372
20. Yu CH, Stovel R, Fox S. Chorea--an unusual manifestation in
a woman recovering from
myxedema coma. Endocr Pract. 2012;18:e43-e48
21. Ahn JY, Kwon HS, Ahn HC, Sohn YD. A case of myxedema coma
presenting as a
brain stem infarct in a 74-year-old Korean woman. J Korean Med
Sci. 2010;25:1394-
1397
22. Kargili A, Turgut FH, Karakurt F, Kasapoglu B, Kanbay M,
Akcay A. A forgotten
but important risk factor for severe hyponatremia: myxedema
coma. Clinics (Sao Paulo).
2010; 65:447-448
23. Yanamandra U, Kotwal N, Menon A, Nair V. Ogilvies syndrome
in a case of
myxedema coma. Indian J. Endocrinol Metab. 2012;16:447-449
-
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
()
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
-
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
()
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; , 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
-
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 > 200 100 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
-
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
Article FileTable 1Table 2 page1Table 2 page2Table 3 page1Table
3 page2Table 4Table 5Figure 1
