Rhabdomyolysis Associated with
Hyperthyroidism
DANIEL M. LICHTSTEIN, MD; ROQUE B. ARTEAGA, MD
ABSTRACT: Background: Nontraumatic rhabdomyolysis
has been associated with alcohol and drug abuse, seizures,
strenuous exercise, muscle hypoperfusion, hyperthermia,
electrolyte disturbances, diabetic coma, and hypothyroid-
ism. Hyperthyroidism can be associated with several neu-
romuscular manifestations, such as thyrotoxic myopathy
and thyrotoxic periodic paralysis, both associated with
weakness and normal creatine phosphokinase levels.
There have been only three reported cases of rhabdomy-
olysis as a result of thyrotoxicosis. We are reporting the
fourth case of such association. Case Report: The patient is
a 26-year-old black woman with history of hypertension.
She presented to the clinic with blurred vision, headaches,
palpitations, weight loss, weakness, and persistent high
blood pressure. She was found to have exophthalmus, lid
lag, and a symmetric, smooth, and diffuse goiter. Ptosis and
diplopia were absent; neurologic examination findings was
normal. The patient had positive TPO antibodies, elevated
free T4 level, and low thyroid-stimulating hormone (TSH)
N ontraumatic rhabdomyolysis has been reported
to be associated with metabolic abnormalities
such as electrolytes disturbances, diabetic coma, and
hypothyroidism.1,2 However, there have been three
documented cases of rhabdomyolysis associated with
hyperthyroidism published in the medical litera-
ture.1,3–5 We present here the fourth case of such
association.
Case Report
The patient is a 26-year-old African American woman who had
been diagnosed with hypertension and administered nifedipine
during an emergency room visit secondary to blurred vision and
headaches 10 months prior to her clinic visit. She went to the
Ambulatory Medical Clinic for her initial visit secondary to
weight loss, weakness, and persistent high blood pressure despite
nifedipine therapy. She was found to have proptosis, evidenced by
visualization of the sclera between the lower border of the iris and
From the Department of Medicine, Miller School of Medicine,
University of Miami Jackson Memorial Medical Center, Miami,
Florida.
Submitted for publication August 4, 2005; accepted in revised
form March 14, 2006.
Correspondence: Roque B. Arteaga, MD, 4411 Silverton Road Au-
gusta, GA 30909 (E-mail: roquearteagamd@yahoo.com rarteaga@
mail.mcg.edu).
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
level. Graves disease was diagnosed and propylthiouracil
was prescribed. The patient then returned to the clinic 2
weeks later with weakness and myalgias. Her physical
examination findings were unchanged except for mild
muscle weakness. Laboratory evaluation showed normal
electrolytes, normal renal function, and negative urine
drug screening. Creatine phosphokinase was 1276 U/L.
Her free T4 and T3 levels were elevated and TSH level was
low. The patient was treated with aggressive oral fluid
resuscitation. Propylthiouracil was continued and free T4
and T3 normalized along with creatine phosphokinase
with resolution of symptoms. Conclusions: Hyperthyroid-
ism may, theoretically, cause rhabdomyolysis by means of
increasing energy consumption associated with depletion
of muscle energy stores and substrates. Our patient consti-
tutes the fourth reported case of rhabdomyolysis associated
with hyperthyroidism. KEY INDEXING TERMS: Rhabdo-
myolysis; Hyperthyroidism; Creatine phosphokinase. [Am
J Med Sci 2006;332(2):103–105.]
the lower eyelid, with the eyes in the primary position. Neither
ptosis nor diplopia was observed. She also manifested lid lag and
symmetric, smooth, diffuse, and mildly tender goiter. No thyroid
bruit was heard. Cranial nerves were intact, as well as the
remaining neurologic examination findings. The patient had pos-
itive TPO (thyroid peroxidase) antibodies, her free T4 level was
2.98 ng/dL and thyroid-stimulating hormone (TSH) level was less
than 0.002 uIU/mL. T3 was not measured. The patient’s clinical
and laboratory findings supported the diagnosis of Graves dis-
ease. She was prescribed atenolol, hydrochlorothiazide, and pro-
pylthiouracil, 100 mg orally three times a day. She was doing fine
until day 10 of propylthiouracil therapy, when she began to feel
worsening generalized weakness and fatigue accompanied by
upper extremity and neck muscle soreness that were neither
relieved by rest nor increased with physical activity. Her symp-
toms were getting progressively worse, until she was seen at the
clinic 14 days after propylthiouracil administration was started
and 5 days after presentation of symptoms. There was no history
of trauma, physical exertion, alcohol intake, drug abuse, heat
exposure, fever, rash, arthralgias, headaches, blurred vision,
chest pain, shortness of breath, abdominal pain, diarrhea, hema-
turia, oliguria, or anuria.
On physical examination, the patient was alert and oriented in
no acute distress. Her blood pressure was 150/69, pulse was 79
beats per minute, and she was afebrile. Examination of the head
and neck revealed a persistent stare, lid lag, and exophthalmus.
Diplopia and ptosis were absent. A diffusely enlarged, firm, smooth
and mildly tender thyroid gland was noticed. The remainder of
the physical and neurologic examination findings was unremark-
able except for muscular power grade of 4/5 on proximal muscles
of the upper extremities and normal to mildly decreased deep
103
Rhabdomyolysis Associated with Hyperthyroidism
tendon reflexes. Laboratory evaluation revealed a white blood cell
count of 8500/mm, a hemoglobin of 13 g/dL, a hematocrit of 39%,
glycemia of 91 mg/dL, serum sodium 140 mEq/L, potassium 4.2
mEq/L, chloride 99 mEq/L, bicarbonate 31 mEq/L, blood urea nitro-
gen 9 mg/dL, creatinine 0.6 mg/dL, and calcium 9.6 mg/dL. Glutamic
oxaloacetic transaminase (AST) was 62 IU/L, glutamic pyruvic
transaminase (ALT) was 53 IU/L. Serum creatine phosphokinase
(CPK) was 1276 U/L. Her urine drug screening test was negative for
cocaine, cannabinoids, benzodiazepines, opioids, and barbiturates.
Her thyroid function tests showed hyperthyroid features: her free T4
was 3.76 ng/dL, T3 was 445 ng/dL, and the TSH level was 0.002
uIU/mL. Her urinalysis showed high pH of 8.0 with otherwise
normal parameters.
At that time, the patient’s history and physical examination
findings plus elevated creatine phosphokinase (CPK) and AST levels
suggested nontraumatic rhabdomyolysis without any other appar-
ent cause but persistent hyperthyroid state. Since her electrolytes,
blood urea nitrogen level, and creatinine level and urinalysis
findings were within normal limits, the patient was instructed to
intake large amounts of water and electrolyte-containing com-
mercial beverages, to monitor her urine for any change in color, to
stay at home at rest, to continue her prior medications, and to
return to the hospital if symptoms worsen.
In the clinic follow up 5 days later, the patient did not report
any myalgias with markedly improvement on her weakness; her
laboratory tests showed AST 34 IU/L, ALT 37 IU/L, CPK 166 U/L,
free T4 2.53 ng/dL, T3 120 ng/dL, TSH less than 0.002, and a
negative urinalysis. Since the patient’s symptoms resolved, ac-
companied by normalization of free T4, T3, AST, and CPK, the
diagnosis of nontraumatic mild and transient rhabdomyolysis
associated with hyperthyroidism was made since there was not
any other precipitating or suspicious factor.
Discussion
Hyperthyroidism can be associated with several
neuromuscular manifestations, such as thyrotoxic
myopathy that is associated with gradual onset of
weakness and fatigue without myalgias and a nor-
mal CPK. Thyrotoxic periodic paralysis is another
complication that is usually seen in Asian men after
exercise, it is not associated with myalgias, and
manifests with normal CPK.5,6 However, uncompli-
cated hyperthyroidism usually leads to a decrease in
CPK levels.5,6 The only thyroid myopathy associated
with increased CPK is hypothyroid myopathy, which
is also characterized by myalgias and weakness.6
Hypothyroidism has also been clearly associated
with rhabdomyolysis.2,4
Myasthenia gravis should be considered in any
patient presenting with muscle weakness. Myasthe-
nia usually manifests with ptosis and diplopia, and
as many as 15% of patients also present with cranial
nerve involvement (dysarthria, dysphagia, fatigable
chewing). These physical findings were absent in
our patient and elevated CPK is not a feature of
myasthenia gravis.7,8
Rhabdomyolysis is defined as a syndrome resulting
from skeletal muscle injury with the release of muscle
cell contents into plasma.1,2,4 Usual etiologic factors
include alcohol and drug abuse, muscle compression,
generalized seizures, strenuous exercise, especially in
untrained subjects, and coma.1,2,4 Rhabdomyolysis may
be also caused by hypoperfusion of the muscular
vessels, electrical current, hyperthermia, metabolic
104
myopathies, infections, electrolyte abnormalities, di-
abetic coma, hypothyroidism, and polymyositis/der-
matomyositis.1–3 The severity of the illness ranges
from asymptomatic elevations of muscle enzymes in
the serum to life-threatening cases associated with
extreme enzyme elevations, electrolyte disturbances,
and acute renal failures.2– 4 In many cases, pigmen-
turia may be overlooked because the filtered load of
myoglobin is insufficient to produce grossly pig-
mented urine. Myoglobin is cleared from the serum
more rapidly than creatine kinase, so it is not un-
usual for serum CPK to remain elevated in the
absence of myoglobinuria.9 Schiff et al10 described
myoglobinemia in marathon runners without acute
renal failure. In these cases, the CPK rose from
pre-race levels to a mean of 2060 IU/L.
Hyperthyroidism may, theoretically, cause rhab-
domyolysis by means of increasing energy consump-
tion, associated with depletion of muscle energy
stores and substrates.5 However, despite the in-
creased energy consumption inherent in hyperthy-
roidism, there have been only three cases reported of
rhabdomyolysis as a result of thyrotoxicosis. Als-
hanti et al3 reported a 20-year-old man without past
medical history, who presented with generalized
weakness and lower extremity cramps, was found to
have rhabdomyolysis and elevated thyroid hormones,
and was treated with propylthiouracil, propranolol,
and intravenous fluids with resolution of the symp-
toms and normalization of CPK within 48 hours.
Bennett and Huston5 reported a 26-year-old woman,
who presented with upper respiratory tract infection
and confusion and developed acute renal failure and
rhabdomyolysis with laboratory evidence of hyper-
thyroidism. The patient’s condition returned to nor-
mal after providing treatment for hyperthyroidism.
In the other report, Hosojima and colleagues1 de-
scribed a 50-year-old man with hyperthyroidism who
presented with a thyroid storm, developed cardiac
and hepatic failure, and died of acute renal failure
and disseminated intravascular coagulation. Rhab-
domyolysis was diagnosed on autopsy examination.
Our patient had acute onset of myalgias with
worsening from preexisting baseline weakness and
elevated CPK with mild elevation of AST as well.
Most reported causes of rhabdomyolysis were ex-
cluded by history, the review of systems, physical
examination, or by laboratory data (normal cell blood
count, normal electrolytes, normal glycemia, nega-
tive drug screening). The only abnormality was ele-
vated thyroid hormones. Furthermore, the myalgias
subsided with normalization of the CPK, AST, free
T4, and T3 after continuation with the antithyroid
and antihypertensive therapy and aggressive oral
volume intake. Therefore, hyperthyroidism was the
most likely causative factor in the development of
rhabdomyolysis. In comparison with the other re-
ported cases, our patient was not overtly thyrotoxic
and did not meet the criteria for thyroid crisis.
August 2006 Volume 332 Number 2

Hyperthyroidism should be considered in the dif-
ferential diagnosis of rhabdomyolysis. This will fa-
cilitate prompt recognition and initiation of therapy
to avoid potential complications.
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