The Journal of Emergency Medicine, Vol. -, No. -, pp.

15, 2016
2016 Elsevier Inc. All rights reserved.
0736-4679/$ - see front matter

http://dx.doi.org/10.1016/j.jemermed.2016.11.006

Clinical
Communications: Pediatric

LOWER-EXTREMITY WEAKNESS IN A TEENAGER DUE TO THYROTOXIC

PERIODIC PARALYSIS

Matthew D. Thornton, MD
Department of Emergency Medicine, SUNY Upstate Medical University, Syracuse, New York
Reprint Address: Matthew D. Thornton, MD, Department of Emergency Medicine, SUNY Upstate Medical University, 550 East Genesee Street,
Suite 103, Syracuse, NY 13202

, AbstractBackground: Thyrotoxic hypokalemic paral-
ysis is the hallmark of thyrotoxic periodic paralysis (TPP).
TPP is a potentially deadly complication of hyperthyroidism
that occurs because of rapid and dramatic intracellular shift
of potassium. This transference results in severe hypokale-
mia and clinically manifests itself as muscle weakness or pa-
ralysis. This condition predominantly affects males of Asian
descent, and its presentation can range from mild to severe,
as seen in our case. Case Report: We present the case of a
15-year-old Asian-American male who presented to a
tertiary-care pediatric emergency department complaining
of generalized weakness and flaccid paralysis of his lower ex-
tremities. The differential for such a complaint is extremely
broad, and the symptoms can result from etiologies arising
from the cerebral cortex, the spinal cord, peripheral nerves,
the neuromuscular junction, or even the muscles themselves.
Our patient was found to have an extremely low serum po-
tassium concentration, as well as an electrocardiogram
that revealed a prolonged QT interval and right bundle
branch block. The etiology of these abnormalities and the
patients symptoms was found to be undiagnosed and uncon-
trolled hyperthyroidism from Graves disease, which re-
sulted in this dramatic presentation of thyrotoxic
hypokalemic paralysis. Why Should an Emergency Physi-
cian Be Aware of This?: This entity is common in Asia but
still somewhat rare in the United States and other Western
countries. Our case illustrates that careful history taking
and a focused diagnostic evaluation, in conjunction with
having an awareness of this disease, can help expedite diag-
nosis and management, as well as avoid unnecessary and
potential harmful testing in the emergency department
setting. 2016 Elsevier Inc. All rights reserved.
, Keywordsthyrotoxic hypokalemic paralysis; thyro-
toxic periodic paralysis; hypokalemia; hyperthyroidism;
Graves disease; paralysis; weakness
INTRODUCTION
Thyrotoxic hypokalemic paralysis is the hallmark of thy-
rotoxic periodic paralysis (TPP). TPP is a potentially
deadly complication of hyperthyroidism that occurs
because of rapid and dramatic intracellular shift of potas-
sium. This transference results in severe hypokalemia and
clinically manifests itself as muscle weakness or paraly-
sis. This condition predominantly affects males of Asian
descent, and its presentation can range from mild to se-
vere. We present the case of a teenager who presented
with acute-onset flaccid paralysis of his lower extremities
that was the result of TTP from previously undiagnosed
Graves disease and severe hypokalemia.
CASE REPORT
A 15-year-old Chinese-American boy presented to a
tertiary-care pediatric emergency department (PED) with
complaint of weakness, more pronounced in the lower ex-
tremities than the upper extremities. The patient stated that

RECEIVED: 28 October 2016;

ACCEPTED: 1 November 2016

1
2 M. D. Thornton
he started having minor muscle aches and weakness
approximately 2 weeks before presentation. On the day
of presentation, the patient stated that his joints felt
sore at 1 AM. Upon waking in the late morning, he was un-
able to move his legs, and had to ask his father to reposition
his legs in bed. Due to this drastic change from the pa-
tients baseline, he was brought to the PED.
On review of systems, the patient complained of weak-
ness and fatigue, and stated that he was having intermit-
tent difficulty breathing. He also endorsed nausea and
mild abdominal pain, which he attributed to not eating.
He denied any recent travel, vomiting, diarrhea, fevers,
chills, weight or appetite changes, cough, headaches,
vision changes, palpitations, or rashes.
The patient had a history of asthma, which was well
controlled and for which he used only albuterol as needed.
After detailed probing for previous neurologic issues, the
patient stated that he had a resting tremor, which he
described as mild, longstanding, and unchanged.
The patients social history revealed that he lives at
home with his mother and father. He attends a technical
high school. He has never been sexually active. He does
not smoke cigarettes or marijuana. He does admit to
drinking approximately one beer per week and states
that he used Ritalin recreationally approximately
1 week before presentation. He denied other drug use.
On physical examination the patient was unable to
ambulate on his own. He was brought by wheelchair to
the treatment room and helped onto the stretcher. He
was awake and alert, in no apparent distress. Vital signs
revealed a temperature of 36.9 C, pulse of 96 beats/
min, respiratory rate of 22 breaths/min, blood pressure
of 130/60 mm Hg, and oxygen saturation 100% on
room air. His head, eyes, ears, throat, and neck examina-
tions were normal, with no obvious facial asymmetry or
neck masses. His heart and lung examinations were unre-
markable. The patients neurologic examination revealed
normal cranial nerve function. Strength in the upper ex-
tremities was 4/5 bilaterally, and he had normal biceps
and brachioradialis reflexes. Upper-extremity sensation
was intact. Examination of his lower extremities showed
that he was able to wiggle his toes and could move his feet
against gravity. Strength was 0/5 in both legs, and he was
unable to move either leg. He refused to attempt to bear
weight. He had 1+ ankle reflexes but absent patellar re-
flexes. He had normal sensation to pain and light touch,
as well as normal proprioception. His back was not tender
to palpation.
Complete blood count showed white blood cell count
8.9  1,000/mL (76% neutrophils, 17% lymphocytes, 4%
monocytes, 2% eosinophils), hemoglobin 15.4 g/dL
(11.214.8 g/dL), hematocrit 45.3% (34%43.9%), plate-
lets 315  1,000/mL. Erythrocyte sedimentation rate
was 9 mm/h (0 20 mm/h) and C-reactive protein was
0.6 mg/L (0.13.0 mg/L). Creatine kinase was 172 U/L
(24 195 U/L), and creatine kinase MB was 2.7 ng/mL
(<5 ng/mL). Urine and serum toxicology screens were
negative. Results of negative inspiratory force testing per-
formed in the PED were normal.
Serum chemistries showed sodium of 139 mmol/L,
potassium of 1.7 mmol/L (3.55.0 mmol/L), chloride of
104 mmol/L, bicarbonate of 23.0 mmol/L, blood urea ni-
trogen of 12 mg/dL, creatinine of 0.7 mg/dL, and a
glucose of 118 mg/dL (70 100 mg/dL). Calcium was
9.4 mg/dL (8.810.2 mg/dL), magnesium was 1.6 mg/
dL (1.72.6 mg/dL), and phosphorus was 1.5 mg/dL
(3.14.7 mg/dL). Liver enzymes were normal, other
than an alanine aminotransferase of 66 U/L (0 34 U/
L). An electrocardiogram was performed due to the se-
vere hypokalemia and it revealed a rate of 84 beats/min
with prolonged QT interval and right bundle branch
block, but no T wave changes.
Careful questioning about the patients family history
revealed thyroid issues. His mother had radioablation
of a thyroid nodule, although she was uncertain why it
was ablated. His father stated that he believes he had hy-
perthyroidism, but that he is not currently on any medica-
tions and did not have any ablation or other procedures.
He did report one episode similar to his sons presenta-
tion, for which he received potassium supplementation.
Given the patients hypokalemia, strong family history
of hyperthyroidism, and Chinese nationality, we had a
high suspicion for thyrotoxic hypokalemic paralysis.
Thyroid studies confirmed our suspicion, revealing a
thyroid stimulating hormone level of 0.008 uIU/mL
(normal range 0.34.3 uIU/mL), total thyroxine level of
12.6 mg/dL (normal range 5.010.6 mg/dL), free
thyroxine level of 2.8 ng/dL (normal range 1.02.2 ng/
dL), thyroxine binding capacity of 20.7 mg/dL (normal
range 19.028.0 mg/dL), and total triiodothyronine level
of 240 ng/dL (normal range 79 149 ng/dL).
For his severe hypokalemia, the patient was given 40
mEq potassium chloride (KCl) orally, and was started
on maintenance i.v. fluids with 20 mEq/L KCl. He was
admitted to the pediatric intensive care unit for electrolyte
repletion and careful cardiac monitoring. Repeated nega-
tive inspiratory force testing was normal. Three hours af-
ter oral KCl, the patients potassium level was found to be
1.5 mmol/L, so he was given an i.v. run of 20 mEq KCl. A
repeat potassium level 2 h later was 2.5 mmol/L, so he
received a second 20 mEq KCl. Follow-up levels 2 and
6 h later revealed serum potassium of 4.3 and
4.8 mmol/L, respectively. Physical examination returned
to baseline, with normal lower-extremity strength and re-
flexes by the time his serum potassium was 4.3 mmol/L.
The maintenance fluids with KCl were discontinued at
that point and the patient was transitioned to a
high-potassium diet.
Thyrotoxic Periodic Paralysis
During the patients hospital admission, the pediatric
endocrine team diagnosed him with Graves disease,
and confirmed the diagnosis of thyrotoxic hypokalemic
paralysis. He was started on methimazole and atenolol
for treatment of his underlying thyroid condition and
symptomatology, and was discharged home the next
day with subsequent subspecialty follow-up.
DISCUSSION
Before eliciting the history of familial thyroid issues, our
patient had five main concerning problems: hypokalemia,
flaccid paralysis, lower-extremity areflexia, prolonged
QT interval, and right bundle branch block. This makes
for a broad differential diagnosis.
Hypokalemia can result from myriad different causes.
In general terms, hypokalemia can result from decreased
potassium intake, increased potassium influx into cells,
dialysis, plasmaphoresis, or increased losses of potassium
from the gastrointestinal tract (upper or lower), urinary
system, or sweat (1).
Flaccid paralysis can be a frightening and striking pre-
sentation, and can result from injury or insult to many
different anatomical sites. Acute paralysis can stem
from the cerebral cortex as a result of intracranial hemor-
rhage, stroke, brain tumor, seizure, hemiplegic migraine,
or alternating hemiplegia of childhood (2). Lower-
extremity paralysis can result from pathology at the level
of the spinal cord as well. This would include trauma, tu-
mor, transverse myelitis, paraspinal infection or inflam-
mation, or poliomyelitis (2). In children, flaccid
paralysis that originates at the level of the peripheral
nerves can result from many different causes. Infections
such as Lyme disease, Chagas disease, and rabies can
cause peripheral neuropathy (3). Inflammatory condi-
tions, particularly Guillain-Barre syndrome, and rheuma-
tologic conditions, including inflammatory bowel
disease, juvenile idiopathic arthritis, and systemic lupus
erythematosus, among others, can result in peripheral
neuropathy as well (3). Other disorders that can result
in this condition include diabetes mellitus, hypothyroid-
ism, celiac disease, malignancy, deficiency or excess of
many different vitamins, and heavy metal toxicity (3).
At the level of the neuromuscular junction, botulism,
myasthenia gravis, snake envenomation, or tick paralysis
could lead to flaccid paralysis (2). Familial or hypokale-
mic periodic paralysis could result in paralysis, as could
electrolyte disturbances of hyperkalemia, hypokalemia,
and hypermagnesemia (4). Lastly, it is important to
remember that psychiatric conditions, such as conversion
or factitious disorder, can result in flaccid paralysis (2).
Another important clinical feature seen in our patient
was areflexia. Loss of reflexes suggests a neuropathic
lesion, which can affect sensory or motor fibers. Dimin-
3
ished or absent reflexes are frequently associated with
Guillain-Barre syndrome. Unless the disease process is
severe, reflexes are generally preserved in muscle dis-
ease. Neuromuscular junction disorders do not follow a
clear pattern. In myasthenia gravis, reflexes are generally
normal, although they might be diminished (5). In
Lambert-Eaton myasthenic syndrome, reflexes are
reduced or absent (5). Peripheral neuropathy, the causes
of which were discussed here, is currently the most com-
mon cause of absent reflexes (5).
Our patient also exhibited concerning electrocardio-
gram changes of QT prolongation and right bundle branch
block. Long QT syndrome can be either genetic or ac-
quired. Genetic causes of long QT include Jervell and
Lange-Nielsen syndrome and Romano-Ward syndrome.
It can also be idiopathic (6). Acquired long QT usually re-
sults from medications, hypokalemia, or hypomagnese-
mia (6). The most common causes of right bundle
branch block include myocarditis, hypertension, pulmo-
nary embolus, myocardial infarction, scar tissue from
heart surgery, or a congenital heart abnormality, such as
an atrial septal defect (7). In addition, right bundle branch
block can rarely occur in an otherwise normal heart (7).
There was clearly a very broad differential diagnosis
for our patients symptoms, but one entity can be a
possible cause of each of these complaintshypokale-
mia. Without knowledge of thyrotoxic hypokalemic pa-
ralysis, a very extensive, costly, and potentially invasive
work-up could have ensued. The multiple organ systems
affected by the patients underlying condition illustrate
the importance of not only correcting the potentially
causative electrolyte disturbance, but also determining
why a previously healthy teenager could become so
acutely hypokalemic and symptomatic.
Thyrotoxic hypokalemic paralysis is the hallmark of
thyrotoxic periodic paralysis (TPP). TPP is a potentially
deadly complication of hyperthyroidism that occurs
because of rapid and dramatic intracellular shift of potas-
sium. This transference results in severe hypokalemia and
clinically manifests itself as muscle weakness or paraly-
sis. This condition predominantly affects males of Asian
descent, including Chinese, Japanese, Vietnamese, Fili-
pino, and Korean (8). Despite a much higher incidence
of thyrotoxicosis in women, > 95% of TPP cases occur
in men (9). In thyrotoxic Chinese patients, it was found
that TPP occurred in approximately 13% of males and
only 0.17% of females (10). TPP has been seen in non-
Asian races as well, including Caucasians, Hispanics, Af-
rican Americans, and Native Americans. Although males
with TPP generally range from 20 to 40 years of age, it
has also been reported in adolescents, as was seen in
our case (11).
TPP only occurs in the presence of hyperthyroidism,
and once the patient has normal thyroid levels they, by
4 M. D. Thornton
definition, cannot get TPP (8). In many patients, clinical
features of hyperthyroidism can precede the onset of TPP
by months or years. This might have been the case with
our patients longstanding, unchanged resting tremor.
Patients with TPP present with muscle complaints that
can range from aches to mild weakness to complete
flaccid paralysis. Our patient had initially complained
of sore joints late at night, but by the morning he had
flaccid paralysis, which may illustrate progression of
symptoms. Interestingly, a high frequency of TPP attacks
occur at night or in the early morning, with more than
two-thirds of patients presenting to emergency depart-
ments between 9 PM and 9 AM (8,12).
As was seen with our patient, attacks generally affect
lower limbs first and then progress to girdle muscles and
upper limbs. Sensory dysfunction is not seen (8). Prox-
imal muscles are more affected than distal muscles,
which might explain why our patient could move his
feet and had 1+ ankle reflexes, but could not move his
legs at all and had absent patellar reflexes (13). Deep
tendon reflexes are diminished or absent in most patients,
though they may be normal even in the setting of paraly-
sis (14). Bowel and bladder function are never affected
(8). Paralysis of respiratory muscles is rare, but respira-
tory failure in the setting of TPP has been described (15).
The pathogenesis of thyrotoxic hypokalemic paralysis
is not completely understood, but TPP attacks tend to occur
after stress, high-carbohydrate load, or strenuous physical
activity. Thyroid hormone increases tissue responsiveness
to b-adrenergic stimulation, which, in conjunction with the
thyroid hormone, increases sodium-potassium ATPase ac-
tivity on the skeletal muscle membrane (16). As a result,
there is massive shift of potassium from the extracellular
compartment into the cells. Additionally, exercise releases
potassium from skeletal muscle cells, whereas rest pro-
motes influx of potassium, which might explain why
TPP occurs after, but not during, exercise (8). Insulin resis-
tance with compensatory hyperinsulinemia is also sus-
pected to have a role in TPP (17). Insulin activates the
sodium-potassium ATPase pump and can also act with thy-
roid hormone to drive potassium into cells. This explains
why carbohydrate-heavy meals can be a precipitant for
TPP attacks. When questioned during hospitalization, the
patient and his father did state that the patient had a high
carbohydrate load the evening before presentation.
Other laboratory findings that are often found in the
setting of TPP include hypomagnesemia and hypophos-
phatemia, both of which were found in our patient.
Both of these derangements spontaneously return to
normal without supplementation when the patient re-
covers from the paralytic attack (12). Creatine kinase
levels may be normal, as was seen with our patient, but
they are elevated in two-thirds of patients, and rhabdo-
myolysis has been reported (12).
Electrocardiogram changes consistent with hypokale-
mia are seen commonly in TPP. These include ST
depression, sinus tachycardia, U waves, abnormal PR
intervals, a pseudo-prolonged QT interval (which is
actually a QU interval with an absent T wave), and
first-degree heart block (18). Other severe dysrhythmias,
such as sinus arrest, second-degree heart block, ventric-
ular tachycardia, and ventricular fibrillation are rare, but
have been described.
Acute treatment of TPP consists of cardiac stabiliza-
tion and potassium repletion. There may be a delayed
response of a few hours after potassium administration,
and an initial drop in serum potassium was seen in
approximately 25% of patients in one case series (19).
This was seen in our patient, as his level dropped from
1.7 to 1.5 mmol/L in the initial 3 h of treatment. Any-
where from 40%59% of patients can experience
rebound hyperkalemia after treatment (12,19). As a
result, unless there is evidence of cardiac instability, it
is recommended that potassium replacement occur at a
slow rate, as was done with our patient.
In patients for whom potassium replacement alone is
insufficient to resolve a TPP attack, both i.v. and oral pro-
pranolol have been shown to be effective in reversing
weakness and hypokalemia (8). Propranolol presumably
reverses the b-adrenergic stimulation of the sodium-
potassium ATPase and shifts potassium out of the cells
and into the extracellular space.
Because TPP does not occur with normal thyroid hor-
mone levels, the definitive treatment is restoration of a
euthyroid state. Potassium supplementation alone is inef-
fective in preventing TPP attacks. The use of b-blockers,
however, has been shown to decrease the severity and fre-
quency of attacks and may be used as a temporizing mea-
sure until a euthyroid state is achieved (8,16,20).
WHY SHOULD AN EMERGENCY PHYSICIAN BE
AWARE OF THIS?
This case is illustrious of thyrotoxic hypokalemic paral-
ysis from Graves diseasea rare and potentially fatal
complication of a rather common illness. Our patients
symptomatology shows some of the dangerous compli-
cations that can result from hypokalemia, a condition
with which emergency clinicians must be familiar.
With increased global population mobility, TPP is
becoming more common in the United States and West-
ern countries. A thorough history, physical examination,
and basic laboratory tests can lead to an accurate diag-
nosis. Being aware of this entity and its potential dan-
gers can help manage the condition safely and
efficiently, and eliminate the need for invasive proced-
ures and diagnostic testing in the emergency department
setting.
Thyrotoxic Periodic Paralysis
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