Thyrotoxic Myopathy Mimicking Myasthenic Syndrome Associated with Thymic Hyperplasia

□ CASE REPORT □

Emiko Tsuda 1, Tomihiro Imai 1, Akihiro Matsumura 1, Shin Hisahara 1, Michio Nonaka 1, Hirokazu Shiraishi 2, Masakatsu Motomura 2 and Shun Shimohama 1

Abstract

A 41-year-old man with progressive limb weakness manifested fluctuating muscle weakness as seen in myasthenia gravis (MG). Laboratory investigations revealed hyperthyroidism without the complication of MG. Electrophysiological studies demonstrated abnormal features of neuromuscular transmissions resembling those of the Lambert-Eaton myasthenic syndrome rather than those of MG. A CT scan showed a mediastinal mass that suggested thymic hyperplasia which often complicates MG or hyperthyroidism. Medical treatment of hyperthyroidism resulted in resolution of MG-like symptoms and regression of thymic hyperplasia on CT concomitant with normalization of thyroid function. This case highlights the fact that careful investigations are needed to differentiate MG-like symptoms from genuine MG in cases of hyperthyroidism with thymic lesions.

Key words: hyperthyroidism, Graves’ disease, thyrotoxic myopathy, myasthenia gravis, Lambert-Eaton myasthenic syndrome, thymic hyperplasia

(Inter Med 47: 445-447, 2008) (DOI: 10.2169/internalmedicine.47.0682)

of progressive limb weakness that had developed six months Introduction before admission. Orthopedic surgery based on a diagnosis of cervical disc herniation failed to control the progression Muscle fatigue, exercise intolerance, and breathlessness of limb weakness, which finally led to gait instability 2 are well known complaints in thyrotoxic myopathy (1-4). months prior to admission. There was no family history of However, clinical and laboratory findings do not show the autoimmune disease. fluctuating nature of myasthenic weakness unless the condi- On admission, he was clearly conscious and well ori- tion is complicated with myasthenia gravis (MG) or ented, and did not show any mental problems. His body Lambert-Eaton myasthenic syndrome (LEMS). On the other weight was 65.3 kg (lost 15 kg in two months), BMI 20.8, hand, both hyperthyroidism and MG are often associated heart rate 108 bpm, and blood pressure 118/68 mm Hg. with thymic hyperplasia (1, 5), which correlates significantly There was neither systolic murmur nor palpable thyroid en- with the disease process and therapeutic effects. We describe largement. No ophthalmologic abnormalities including pto- a patient with thyrotoxic myopathy, who responded to an- sis, exophthalmos and extraocular muscle weakness were tithyroid drug resulting in improvement of the characteristic observed. Neurological examination revealed global weak- myasthenic weakness concomitant with resolution of hyper- ness in his limbs, more marked in the proximal muscles. He thyroidism and thymic hyperplasia. felt fatigable weakness in his limbs after exercise. The weakness varied throughout the course of a single day, with Case Report relatively stable gait without support in the morning and se- vere lower limb weakness requiring wheel chair use in the A 41-year-old man was admitted to our hospital because evening. A fine postural tremor was observed in his hands.

１Department of Neurology, Sapporo Medical University School of Medicine, Sapporo and ２The First Department of Internal Medicine, Graduate School of Biomedical Science, Nagasaki University, Nagasaki Received for publication October 18, 2007; Accepted for publication December 9, 2007 Correspondence to Dr. Tomihiro Imai, [email protected]

445 Inter Med 47: 445-447, 2008 DOI: 10.2169/internalmedicine.47.0682

Figure 1. A) A CT scan of the chest before treatment showing anterior mediastinal enlargement (large arrow). B) A CT scan of the chest after medical treatment demonstrating marked reduction of the anterior mediastinal enlargement (small arrow).

There was no atrophy and fasciculation in his limbs. Deep limbs. A blinded tensilon test was not possible because of tendon reflexes were generally hyperactive with bilateral ex- the refusal of the procedure by the patient. tensor plantar responses. He showed no cranial nerve in- The patient was treated with thiamazole (30 mg bid) re- volvements including ocular or bulbar signs. Sensory and sulting in a dramatic improvement of limb weakness. One cerebellar functions were intact. month later, neurological examinations showed full strength Routine hematological and biochemical tests were within of limb muscles, normal deep tendon reflexes, flexor plantar the normal limits except mild microcytic anemia and de- responses and disappearance of postural hand tremor. Re- creases of creatinine phosphokinase (37 IU/ml) as well as peated thyroid function studies showed normalization of total cholesterol (123 mg/dl). Hypokalemia was not evident TSH and FT4 levels. A follow-up CT scan demonstrated sig- during the entire course of illness. Erythrocyte sedimentation nificant reduction in size of the thymus (Fig. 1B). rate was normal, and C-reactive protein was negative. The CSF analysis and urinalysis were also normal. Thyroid func- Discussion tion results indicated a diagnosis of hyperthyroidism as fol- lows: thyroid stimulating hormone (TSH), 0.01 μU/ml; se- Although the association of hyperthyroidism with MG or rum free triiodothyronine (FT3), 21.77 pg/ml; and serum free LEMS has been reported (1, 7, 8), the electrophysiological thyroxine (FT4), 5.63 ng/ml. Immunological investigations and immunological findings of the present case did not fully revealed elevated titers of thyroid stimulating antibody satisfy the diagnostic criteria of either MG (9) or LEMS (TSAB)at 2,060%, anti-TSH receptor antibody at 43.2%, (6), in spite of the myasthenic nature of limb weakness. anti-thyroid peroxidase antibody at 203.2 IU/ml, and posi- It is known that fatigability observed in thyrotoxic tive anti-microsome antibody (×6,400). Other relevant re- myopathy could be partly attributed to myasthenia. Electro- sults included negative acetylcholine receptor (AchR) and physiological studies have revealed that some patients with voltage-gated P/Q calcium channel (VGCC) antibodies. thyrotoxic myopathy have abnormal inhibition of neuromus- A thyroid ultrasound study revealed diffuse swelling of cular transmission as in MG or abnormal facilitation of thyroid glands with heterogeneous echoic pattern, which was neuromuscular transmission as in LEMS (10). One possible consistent with Graves’ disease. A CT scan of the upper me- explanation is a direct effect of thyroid hormones on diastinum showed a 30.9 mm ×18.0 mm anterior mediastinal neuromuscular transmission causing disturbances in the mass, leading to a suspicion of thymic hyperplasia neuromuscular junction or in electrical properties of the (Fig. 1A). Iodine123 scintigraphy did not demonstrate any ec- muscle fiber membrane. The fact that his myasthenic symp- topic thyroid glands in the mediastinum. toms were dramatically improved with thiamazole alone Electrophysiological study using surface electrodes without specific immunosuppressive therapy may support showed electrophysiological features resembling the LEMS the direct effect of thyroid hormones in causing myasthenic (6): 1) significant reduction of compound muscle action po- weakness. tential (CMAP) amplitude after single nerve stimulus; 2) no Thymic hyperplasia appears to be induced as a conse- significant decrement above 10% in CMAP recorded from quence of immunological and hormonal reactions in hyper- abductor pollicis brevis (APB) during 3-Hz stimulation; 3) thyroidism (11). The thymic enlargement gradually resolves increase in CMAP amplitude of 180% recorded from APB with medical therapy (12, 13) as seen in the present case. during repetitive nerve stimulation at 60 Hz. Needle electro- Therefore, thymectomy may not be essential to treat the thy- myography showed no abnormality in any muscle of the mus lesions in hyperthyroidisms, in contrast to the signifi-

446 Inter Med 47: 445-447, 2008 DOI: 10.2169/internalmedicine.47.0682 cant indication of thymectomy in MG patients (14). investigations are required to make a diagnosis of hyperthy- Myasthenic features may be similar in hyperthyroidisms roidism with myasthenia features and to choose the appro- and MG, and thymic hyperplasia may occur in both. Careful priate therapy for thymic hyperplasia.

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