|Year : 2011 | Volume
| Issue : 2 | Page : 201-203
HoffMann's syndrome: A rare neurological presentation of hypothyroidism
K.A.S. Praveen, Sarfaraz Aslam, TK Dutta
Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India
|Date of Submission||29-Mar-2011|
|Date of Acceptance||24-May-2011|
|Date of Web Publication||23-Aug-2011|
Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry
| Abstract|| |
The neurological manifestations of hypothyroidism are very unusual to see as initial symptoms and they usually occur late in the course of disease. Muscle hypertrophy is an extremely rare finding in hypothyroid patients. Hypothyroidism presenting as muscle stiffness and muscle pseudo hypertrophy in adults is known as Hoffmann's syndrome. Laboratory investigation in hypothyroid myopathy generally shows increased levels of muscle enzyme. The electrophysiological study may reveal features suggestive of myopathy, neuropathy or mixed pattern. The symptoms and also the serum levels of enzymes return to normal with hormone replacement therapy. We report a case of hypothyroidism with calf muscle hypertrophy and proximal myopathy as the initial symptoms.
Keywords: Hashimoto′s thyroiditis; Hoffmann′s syndrome; pseudo hypertrophy of muscles; thyroid peroxidase antibodies.
|How to cite this article:|
Praveen K, Aslam S, Dutta T K. HoffMann's syndrome: A rare neurological presentation of hypothyroidism. Int J Nutr Pharmacol Neurol Dis 2011;1:201-3
|How to cite this URL:|
Praveen K, Aslam S, Dutta T K. HoffMann's syndrome: A rare neurological presentation of hypothyroidism. Int J Nutr Pharmacol Neurol Dis [serial online] 2011 [cited 2014 Apr 19];1:201-3. Available from: http://www.ijnpnd.com/text.asp?2011/1/2/201/84215
| Introduction|| |
The common symptoms of myopathy due to hypothyroidism are proximal muscle weakness, muscle cramps, myoedema on percussion, delay in deep tendon reflexes and rarely development of muscle hypertrophy.  Severity of myopathy generally correlates with the duration and the degree of thyroid hormone deficiency. Hoffmann's syndrome is a rare specific form of hypothyroid myopathy, which causes proximal muscle weakness and hypertrophy of muscles. The muscular hypertrophy with muscle stiffness is reported in less than 10% of hypothyroid patients.  The hypothyroidism presenting with initial neurological manifestations is very unusual and rare. In children with congenital hypothyroidism, a similar syndrome of muscle hypertrophy (but without cramps) is termed as Kocher-Debre-Semelaigne syndrome.
| Case Report|| |
A forty year old farmer presented with a history of weakness of all the four limbs for the past four months and difficulty in carrying out his routine daily activities. The weakness is more of proximal muscles than distal, and there was no history of sensory involvement, bowel/bladder disturbance or muscle cramps/stiffness. There was no history of cold intolerance, weight gain or pedal edema. The clinical examination revealed mild periorbital puffiness, large tongue [Figure 1]a, dry coarse skin [Figure 1]b and hoarse voice. His pulse rate was 69/minute and blood pressure was 130/80 mmHg. Neurological examination showed normal higher mental functions and cranial nerves. Motor system examination revealed muscle power of 4/5 in all four limbs with predominant proximal muscle weakness, normal muscle tone with generalized hyporeflexia and delayed ankle jerk. There was hypertrophy of calf muscles of both the lower limbs [Figure 2]a and b. Sensory system examination and bowel, bladder functions were normal. The systemic examination was normal.
|Figure 1: Photograph of the patient in the case report showing large tongue (a) and dry coarse skin (b)|
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|Figure 2: Photograph of the patient in the case report showing Hypertrophy of calf muscles of both the lower limbs|
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The laboratory investigations revealed T3 levels of 1 pg/dl (normal 2.3- 4.2 pg/dl), a T4 of 0.5 ng/dl (normal 0.89-1.76 ng/dl) and thyroid stimulating hormone (TSH) level of 100 mIU/ml (normal 0.35-5.5 mIU/ml). Antibody to thyroid peroxidase (TPOAb) was positive. Creatine phosphokinase levels revealed a value of 890 IU/l (normal <140 U/l). Lipid profile revealed elevated total cholesterol (200 mg/dl) and triglyceride levels (160 mg/dl). The chest radiograph, electrocardiogram and echocardiography were normal. The renal function tests, liver function tests and haemogram were normal. Electromyography (EMG) showed myopathic motor unit potentials (MUAPs) with small amplitude and duration in the proximal muscles. The nerve conduction study was normal in both the common peroneal nerves. The muscle biopsy was not done as patient refused to give consent.
| Discussion|| |
Hoffmann's Syndrome was first described by Hoffmann in 1897 in an adult who developed muscle stiffness and difficulty in relaxation of muscles after thyroidectomy.  The first presentation with myopathy and pseudo hypertrophy of muscles is very rare and unusual to see. Primary hypothyroidism accounts for 95% of the cases of thyroid insufficiency. The main etiology is Hashimoto's thyroiditis,  an autoimmune chronic thyroiditis characterized by high levels of thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb). Both TgAb and TPOAb are found in almost 100% of patients with Hashimoto's thyroiditis.  The TPOAb is of higher affinity and found in higher concentrations and is the best choice if only a single test is ordered. The etiology of pseudo hypertrophy in Hoffman's syndrome remains obscure and is a matter of discussion. It has been postulated that the mechanisms involved could include an increase in connective tissue, increase in size and the number of muscular fibers. , There is also change in muscle fibers from fast twitching type II to slow twitching type-I fibers, , abnormalities in oxidative enzymatic activity and hypertrophy due to accumulation of glycosaminoglycans.  The most common muscles groups involved are the tongue, arm and leg muscles. The muscle hypertrophy and muscle weakness will recede following treatment with thyroid hormones.
The creatine phosphokinase levels (CPK) will be elevated in thyroid myopathy and very high in some patients (10-100 times greater than the normal level), however, it has no correlation with weakness.  The CPK is the best biochemical marker of myopathies.  The fall of the enzyme levels with the treatment occurs slowly, varying from weeks, months or even years. The electrophysiological study in hypothyroid myopathy may show findings compatible with neurogenic, myogenic, or a mix of those patterns. The EMG findings compatible with myogenic pattern are diminished duration, and amplitude of motor unit potentials.  The voluntary muscle contraction results in early recruitment of short action motor units, spontaneous fibrillations and complex repetitive discharges.  The nerve conduction studies (NCS) may show entrapment neuropathies and axonal sensorimotor polyneuropathy. Our patient presented with predominant proximal muscle weakness and hypertrophy of calf muscles. His CPK levels were elevated 4 times the normal, and TPOAb titers were also elevated. EMG showed myopathic motor unit potentials (MUAPs) with small amplitude in proximal muscles, and nerve conduction study was normal. The patient was started on L-thyroxine (100 μgms once a day) and discharged from hospital. The patient on follow up after 4 weeks of oral thyroxine showed decreased CPK enzyme levels and improvement in muscle power with mild reduction in muscle bulk.
In conclusion, Hoffmann's syndrome is very rare condition and its initial presentation with myopathic manifestations can raise diagnostic problems as calf muscle hypertrophy can present in other diseases as well, like Duchenne and Becker's muscular dystrophy, amyloidosis, and focal myositis. Therefore special awareness about this syndrome will lead to the correct diagnosis. It is also important to emphasize that both the symptoms and serum levels of muscle enzymes return to normal with hormone replacement therapy.
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[Figure 1], [Figure 2]