Robin George Manappallil, Nandini Valsala,
Jayameena Peringat, Priya Padmanabhan
Baby Memorial Hospital, Kozhikode 673004
Abstract
Hashimoto's thyroiditis is the most common form of primary
hypothyroidism. Patients may present with muscular
manifestations like weakness, stiffness, pain and elevated
muscle enzymes. Rhabdomyolysis has been reported in severe
asthma. This is a case of a middle aged male, who presented
with acute exacerbation of asthma accompanied by severe muscle
aches and pain, and was found to have rhabdomyolysis.
Following treatment for asthma, his symptoms of dyspnoea and
muscle aches decreased, but rhabdomyolysis was persistent. On
further evaluation, he was found to have Hashimoto's
thyroiditis. He was managed with intravenous fluids and
levothyroxine along with nebulisations and intravenous
steroids, following which he improved.
Key words: Hashimoto's thyroiditis, hypothyroidism,
rhabdomyolysis, creatine kinase, asthma
Case presentation
A middle aged male presented with wheezing and breathlessness
since morning. He is a known asthmatic on inhalers (formoterol
and budesonide). He has also been experiencing muscle aches
for the past 4 months; with exaggeration of symptoms during
asthma attacks. There were no other significant or associated
symptoms.
On examination, he was conscious, oriented and afebrile. He
was overweight with BMI of 27 Kg/m
2.
His pulse rate was 60/minute, blood pressure 140/90 mmHg and
respiratory rate 30/ minute with saturation 90% (in room air).
His respiratory system revealed bilateral diffuse rhonchi.
Neurologically, he had sluggish deep tendon reflexes but no
muscle weakness. Other general and systemic examinations were
normal.
His complete hemogram showed eosinophilia (total counts 9000
cells/cmm with neutrophils 58%, lymphocytes 30%, eosinophils
12%) with normal haemoglobin and platelet counts. Absolute
eosinophil count and serum IgE levels were elevated (1080
cells/cmm and 990 IU/ml respectively). Peripheral smear also
revealed eosinophilia. Renal functions were deranged with urea
44 mg/dL (10-40) and creatinine 3.81 mg/dL (0.9-1.3). His
liver functions, electrolytes, calcium and HbA1c were normal.
His fasting lipid profile showed dyslipidemia with LDL 197
(< 130), HDL 30mg/dL (40-60), VLDL 36mg/dL (6-38) and
triglycerides 285mg/dL (< 150). Low voltage complexes were
seen on ECG. Echocardiography and chest X-ray were normal. His
CK and LDH levels were elevated, 1055 U/L (24-190) and 339 U/L
(114-240) respectively. Urine examination was normal, with no
myoglobinuria or haematuria. Troponin I and ANA profile were
negative. His thyroid profile was suggestive of Hashimoto's
thyroiditis, with TSH 66.59 µIU/ml (0.40-4.20), T3 34.6 ng/dL
(40-181) and T4 2.44 µg/dL (4.60-10.50), and positive
antithyroid peroxidase antibody of 176 U/ml (< 35).
Ultrasound of neck revealed features suggestive of
thyroiditis.
He was managed with salbutamol, budesonide and ipratropium
bromide nebulisations, along with montelukast and intravenous
methyl prednisolone (40 mg q8h). He had two episodes of fever
following admission, and was started on oral cefuroxime (250
mg twice daily) empirically. Oral levothyroxine was given at
125 mcg once daily, along with aggressive intravenous fluid
administration.
By day 6 of admission, his creatinine levels started
normalizing; and he was discharged on day 10 with a normal
renal functions. Since the patient had improved
symptomatically, electromyography and muscle biopsy were not
done. His discharge medications comprised of levothyroxine 125
mcg (once daily), montelukast 10 mg (once daily),
acebrophylline 100 mg (twice daily), and formoterol-budesonide
inhaler. On follow-up after 2 weeks, the patient was
asymptomatic. His blood investigations showed a normal thyroid
profile, CK levels and renal functions.
Discussion
Rhabdomyolysis can manifest as myalgia, limb weakness and
swelling along with passing of dark coloured urine in the
absence of haematuria. Myoglobinuria may be present. The
condition is characterised by muscle necrosis and release of
intracellular muscular components like myoglobin, creatine
kinase (CK), lactate dehydrogenase (LDH), aldolase, aspartate
aminotransferase, and potassium into the circulation.
Rhabdomyolysis can have a wide range of presentation; from
asymptomatic elevations in serum muscle enzymes to acute
kidney injury. Trauma is the most common aetiology; and
non-traumatic causes include seizures, endocrine disorders,
heat exposure, electrolyte imbalance, infections and heavy
exercise.
Hashimoto's thyroiditis (HT) is a form of primary
hypothyroidism, wherein the gland is destroyed by the immune
system. Proximal muscle weakness, pain or cramps are some of
the musculoskeletal symptoms associated with hypothyroidism.
Alcoholism, diabetes, liver and renal disease, and old age are
some of the risk factors associated with hypothyroid myopathy.
Rhabdomyolysis as a result of hypothyroidism is a rare
scenario; and can be precipitated by trauma, exercise, alcohol
and drugs like statins[1].
Various hypotheses like induction of insulin-resistant state,
impaired mitochondrial oxidative metabolism, decreased muscle
carnitine levels andautoimmune mechanism have been proposed
with regard to rhabdomyolysis in hypothyroidism [2,3].
Thyroxine deficiency can lead to abnormal glycogenolysis,
mitochondrial oxidative metabolism and triglyceride turnover;
which in turn can result in impaired muscle function by
causing a transition of fast-twitching type 2 muscle fibres to
slow-twitching type 1 fibres, low myosin ATPase activity and
low adenosine triphosphate turnover in the skeletal muscles
[4].
Rhabdomyolysis secondary to status asthmaticus was first
described by Chugh et al. in 1978; following which only a
handful of cases have been reported [5]. Severe respiratory
muscle exertion can cause mechanical and thermal muscle injury
and ATP depletion. Generalized hypoxemia secondary to status
asthmaticus can result in muscular ischemia and injury.
Metabolic acidosis following hypercapnia can add on to the
situation. The combination of respiratory and metabolic
acidosis may aggravate the risk of corticosteroid-induced
myopathy. Electrolyte imbalances are seen in status
asthmaticus; and of these hypokalemia is the most notorious,
as it can depolarize the muscle membrane, inhibit the
production and storage of glycogen in myocytes, and even limit
vasodilatation in the muscle microvasculature during exercise.
Asthma can be triggered by lung infections. These infections
can also precipitate rhabdomyolysis by direct tissue damage,
effect of toxins and inflammatory mediators, or associated
fever, acidosis and dehydration. Drugs like glucocorticoids,
theophylline and beta 2-Adrenergic agonists can cause
myopathy, but rarely rhabdomyolysis. Antibiotics like
levofloxacin and clarithromycin, which are used during lung
infection induced asthma exacerbations, may induce
rhabdomyolysis.
The patient being discussed had symptoms of muscle aches
initially, which were exaggerated during asthma attacks.
Following treatment with glucocorticoids and nebulisation, his
respiratory symptoms improved, but his muscle aches showed
only mild decrease. He was found to have rhabdomyolysis, which
was initially thought to be due to asthma exacerbation; but
further evaluation revealed an underlying Hashimoto's
thyroiditis. Rhabdomyolysis secondary to hypothyroidism is a
rare scenario.
Conclusion
Rhabdomyolysis has been observed in Hashimoto's thyroiditis
and during severe asthma attacks. Since both hypothyroidism
and asthma can precipitate rhabdomyolysis, this case
highlights the importance of assessing the thyroid status of
all asthmatic patients presenting with muscle aches.
References
1. Peringat J, Manappallil RG, Karadan U. Rhabdomyolysis: a
rare complication of Hashimoto's thyroiditis precipitated by
statin therapy. BMJ Case Rep. 2018 Feb 12; 2018. pii:
bcr-2017-223229.
2. Macleod A, Siddique H, Bashir A, Moulik P, Beshr A.
Rhabdomyolysis and acute renal failure due to hypothyroidism.
Endocrine Abstracts 2008; 15:384.
3. Monzani F, Caraccio N, Siciliano G, Manca L, Murri L,
Ferrannini E. Clinical and biochemical features of muscle
dysfunction in subclinical hypothyroidism. J Clin Endocrinol
Metab 1997; 82: 3315–3318.
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with hypothyroidism. Endocr J 2003; 50: 221–223.
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