Introduction
Worldwide, the most common cause of hypothyroidism
is iodine
deficiency. However, in areas with normal or adequate iodine intake,
Hashimoto thyroiditis remains the most common cause of hypothyroidism,
with an estimated annual incidence of 0.3-1.5 cases per 1000 persons
[1]. Muscular manifestations of hypothyroidism range from muscle
weakness, myalgia, muscle cramps with mild to moderately elevated
creatinine kinase to more severe forms such as Hoffman’s syndrome or
rhabdomyolysis [2]. Nevertheless, rhabdomyolysis due to
hypothyroidism, even in the presence of precipitating factors, is
seldomly rare [3]. Here we report an unusual case of rhabdomyolysis
due to hypothyroidism without any other associated precipitating
factors.
Case presentation A 42-year-old gentleman with no prior medical illness, admitted with
the complaints of generalized muscle pain, dry skin, and mild facial
puffiness of eight days duration, associated with choking sensation in
his throat. The review of systems was negative for fever, hoarse voice,
cold intolerance, hair loss, dysphagia, constipation, weight gain, focal
limb weakness, or changes in memory. He denied doing strenuous exercise
recently, alcohol consumption, trauma, or recent medications use. There
was no family history of autoimmune thyroid diseases.
His vital signs were: pulse rate 65/min (regular), blood pressure
120/85mmHg, respiratory rate 19/min, and an oral temperature of
37.1◦C. Physical examination revealed mild facial
puffiness, dry skin, and minimal non-pitting lower limb edema. A small
goiter without tenderness or nodule was found on neck examination. The
musculoskeletal examination did not show muscle wasting, hypertrophy, or
weakness. Other systems examinations were unremarkable.
Laboratory investigations were suggestive of severe hypothyroidism:
Thyroid- stimulating hormone (TSH); > 100 µIU/mL, (normal
range < 4.35 mIU/L), Free T4; <0.3 ng/dL, (normal
range 11 - 23.3 pmol/L) Antithyroid peroxidase antibody titre;
> 600 IU/mL, (normal range < 34 IU/mL),
anti-thyroglobulin antibody (TgAb) titre; 1831 IU/mL, (normal range
< 115). Elevated levels of antithyroid peroxidase antibody and
anti-thyroglobulin antibody titres were suggestive of Hashimoto’s
thyroiditis. Serum creatinine kinase (21,644 U/L, normal range 39-308
U/L) and myoglobin (2,208 ng/ml, normal range 28-72 ng/ml) levels were
also raised, Table 1. This was associated with acute kidney injury with
mild elevation of serum creatinine (127 Umol/l). Urine examination was
negative for myoglobinuria or hematuria. The daily urine output was
normal (250-300 mL/h).
Electrocardiogram (ECG) and
chest x-ray were normal. Transthoracic echocardiography (TTE) showed
minimal circumferential pericardial effusion without regional wall
motion abnormalities and with a left ventricular ejection fraction of
(EF) 58%. Fiberoptic (flexible) laryngoscopy was normal.A probable diagnosis of hypothyroidism due to Hashimoto’s thyroiditis
with rhabdomyolysis was made based on the clinical and laboratory
parameters. He was treated with intravenous fluids and was started on
oral levothyroxine. His symptoms improved with the treatment, and the
levels of CK and myoglobin showed a decreasing trend. He was discharged
on day four, and on further follow-up, the muscle enzymes showed a
further decreasing trend and normalization of renal parameters. Since
there was complete resolution of symptoms with the patient returning to
his regular day-to-day activities, further workup to exclude muscle
diseases was not done.Discussion:
Hypothyroidism manifest with a broad spectrum of clinical features. The
Involvement of muscle in various forms is frequently found in
hypothyroidism [3]. The muscular symptoms range from stiffness,
weakness, myalgia, cramps, pseudohypertrophy, and rhabdomyolysis
[2, 4]. Rhabdomyolysis is a syndrome characterized by muscle
necrosis and the release of intracellular muscle constituents into the
circulation [4]. The causes of rhabdomyolysis can be due to
traumatic or non-traumatic. The various non traumatic causes include
heat exhaustion, electrolyte imbalance, seizures, endocrine disorders,
infections, and heavy exercise [5]. However, hypothyroidism causing
rhabdomyolysis is an infrequent clinical entity and Hashimoto’s
thyroiditis causing rhabdomyolysis is even rarer, and as per our
knowledge, only two cases have been reported so far [7, 8].
Very few cases of hypothyroidism causing rhabdomyolysis has been
reported in the literature [9]. Our patient was diagnosed to have
rhabdomyolysis without any apparent cause or risk factors. We could not
find a definite cause for rhabdomyolysis in the initial evaluation;
hence hypothyroidism was considered an underlying etiology, which was
confirmed by the laboratory investigations. A review of literature on
ten reported hypothyroidism cases causing rhabdomyolysis, it was
observed that only four cases had pre-existing hypothyroidism when they
presented with rhabdomyolysis. In the remaining six cases the
hypothyroidism was diagnosed concurrently with rhabdomyolysis
[10].
In cases with rhabdomyolysis due to hypothyroidism, the levels of CK
have been reported to be elevated, usually less than ten times the
normal range [7, 15]. In the present case, the levels were elevated
up to more than 70 times the normal range, which is very unusual in
hypothyroidism-induced rhabdomyolysis. The risk of rhabdomyolysis in
hypothyroidism is greater in patients using statins or after rigorous
exercise. However, there was no history suggestive of any risk factors
in the present case, including statin use or exercise. The
pathophysiology of rhabdomyolysis in hypothyroidism is unclear. Various
hypotheses have been postulated, like mitochondrial oxidative
metabolism, induction of insulin-resistant state, and decreased muscle
carnitine levels, including autoimmune mechanism [11, 13]. Also,
deficiency in thyroxine leads to abnormal glycogenolysis and increased
triglyceride turnover, thus leading to impairment of muscle function by
causing a transition of fast-twitching type two muscle fibers to
slow-twitching type one fibers, low myosin ATPase activity, and low ATP
turnover in the skeletal muscles [14].