Thyroid Research and Practice

: 2014  |  Volume : 11  |  Issue : 3  |  Page : 118--120

Thyrotoxic neuropathy; an under recognized condition: A clinical vignette

Partha Pal1, Sayantan Ray2, Kaushik Biswas2, Animesh Maiti3, Deep Mukhopadhyay1, Rintu George1, Debabrata Mukherjee1,  
1 Department of General Medicine, Calcutta National Medical College and Hospital, Kolkata, West Bengal, India
2 Departments of Endocrinology and Metabolism, Institute of Post Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, West Bengal, India
3 Departments of Endocrinology and Metabolism, Medical College and Hospital, Kolkata, West Bengal, India

Correspondence Address:
Sayantan Ray
Department of Endocrinology and Metabolism, IPGMER and SSKM Hospital, 244, AJC Bose Road, Kolkata 700 020, West Bengal


Neurological sequelae such as neuromuscular or primary muscle disorders are well recognized complications of hyperthyroidism. However, the association of neuropathy with thyrotoxicosis is uncommon. Thyrotoxic neuropathy or Basedow«SQ»s paraplegia is a rarely reported entity, which was first described by Charcot in 1889. We are reporting the case of a middle-aged man with subacute distal neuropathy as the presenting manifestation of thyrotoxicosis which improved on antithyroid treatment. Peripheral neuropathy in hyperthyroidism is underdiagnosed and may be found even in patients with mild thyrotoxicosis. Thyroid function tests can be helpful in the diagnosis of this treatable neuropathy in such cases and hence should be included in the routine workup in patients with peripheral neuropathy.

How to cite this article:
Pal P, Ray S, Biswas K, Maiti A, Mukhopadhyay D, George R, Mukherjee D. Thyrotoxic neuropathy; an under recognized condition: A clinical vignette.Thyroid Res Pract 2014;11:118-120

How to cite this URL:
Pal P, Ray S, Biswas K, Maiti A, Mukhopadhyay D, George R, Mukherjee D. Thyrotoxic neuropathy; an under recognized condition: A clinical vignette. Thyroid Res Pract [serial online] 2014 [cited 2022 Nov 26 ];11:118-120
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Neuromuscular manifestations of hyperfunctioning thyroid gland include acute and chronic thyrotoxic myopathies, exophthalmic ophthalmoplegia, periodic paralysis, and myasthenia gravis. However, peripheral nerve involvement in hyperthyroidism is not frequently recognized. [1] The existence of any association between the two disorders has often been questioned due to inconclusive electrodiagnostic and pathologic findings seen in these patients. We describe here the case of a middle-aged man with subacute motor-sensory distal neuropathy as the main presenting manifestation of hyperthyroidism. Treatment of thyrotoxicosis coincided with recovery of symptoms. We believe that the neurological complication is consequent to thyrotoxicosis.


A 45-year-old man presented with a 3-month history of progressive weakness of lower limbs and slowly increasing diffuse swelling on the anterior aspect of the neck for 4 months. He also complained of significant weight loss. His past medical, family, occupational, and personal histories were unremarkable. The patient was tachycardiac (pulse rate 102/min) with normal systolic blood pressure. Examination revealed a diffuse goiter of 8 cm diameter [Figure 1]a]. There was bilateral mild exophthalmos. Neurological examination showed weakness of grade 3/5 (Medical Research Council grading) in lower limbs distally, with marked muscle atrophy [Figure 1]b] and absent ankle jerks. There was mild sensory loss to touch, vibration, and pain below the knees. There was no evidence of vitamin deficiency, malnutrition, or skin changes.{Figure 1}

Complete blood counts, electrolytes, glucose, calcium, phosphates, liver and renal function, creatine phosphokinase, and urine analysis were normal. Thyroid function tests showed free thyroxine (T4) level of 2.78 ng/dl (normal 0.7-1.48 ng/dl), free triiodothyronine (T3) level of 4.90 pg/ml (normal 1.71-3.71 pg/ml), and thyroid stimulating hormone (TSH) level of 0.01 μIU/L (normal 0.35-4.94 μIU/ml). I 131 thyroid scintigraphy revealed increased uptake and homogenous distribution of radio tracer after 24 and 48 h [Figure 2]. Nerve conduction studies revealed bilateral severe axonal neuropathy involving the bilateral tibial, peroneal, and sural [Table 1]. Electromyography showed fibrillations and few fasciculations with normal insertional activity suggestive of neurogenic involvement. Left sural nerve biopsy was done. Left sural nerve biopsy was done. Light microscopy showed focal loss of small myelinated axons in centrofascicular zone within fascicles with increase in endoneural collagen without inflammatory infiltrate [Figure 3]a]. Electron microscopy revealed large myelinated fibers showing focal myelin blebbing, splitting, and degeneration [Figure 3]b]. Vitamin B12, folic acid, angiotensin converting enzyme levels, serum protein electrophoresis, antinuclear antibodies, cytoplasmic and perinuclear anti-neutrophil cytoplasmic antibodies (c- and pANCA), anti-SSA, anti-topoisomerase, and urinary porphobilinogens were negative. Antithyroid therapy with carbimazole (30 mg/day) and propranolol (60 mg/day) was started and within 4 weeks a biochemical improvement (TSH = 0.3 μIU/l, free T4 = 1.9 ng/dl) and significant improvement in muscle strength was noted. Ankle jerks were absent but the response to sensory stimuli improved. Repeat nerve conduction studies after 3 months showed improvement, substantiating our diagnosis of thyrotoxic neuropathy.{Table 1}{Figure 2}{Figure 3}


Although patients of thyrotoxicosis experience a wide range of neuromuscular disorders: Proximal myopathy, exophthalmic ophthalmoplegia, thyrotoxic periodic paralysis, myasthenia gravis, rhabdomyolysis, neuropsychiatric syndromes, movement disorders, and thyrotoxic neuropathy is not a well-recognized entity. [2] It is not clear as to how abnormalities in thyroid function mediate neurological dysfunction. Direct effect of thyroid hormones on the nerves, immune-mediated neuropathy, and hypermetabolic state depleting the nerves of essential substances are implicated as the potential pathogenic mechanisms. The site of the primary lesion is the cell body of the motor neuron with affection of peripheral nerve, dorsal root ganglion, and anterior horn cell. Electrophysiological studies reveal a mixed axonal and demyelinating sensorimotor neuropathy. [3] Acute neuropathy associated with paraplegia was first described by Charcot [4] in 1889 and called 'Basedow's paraplegia' by Joffroy in 1894.

The incidence of peripheral neuropathy in hyperthyroid subjects detected by electrophysiological testing in studies by Duffy et al., [5] Ludin et al., [6] and Sozay et al., [7] were 19, 65.5, and 35.5%, respectively. As most of the patients with neuropathy were asymptomatic, authors concluded that electrophysiological studies are useful in diagnosing asymptomatic polyneuropathy in these patients. Thyrotoxic neuropathy had a very good response to antithyroid treatment as observed by Duffy et al. [5] 'Thyrotoxic myopathy' may actually be a neuropathic disorder in its early stages of denervation as McComas et al., [3] found neuropathic changes in 20 patients with 'thyrotoxic myopathy'. Joffroy's description of Basedow's paraplegia; "flaccid paraplegia with absent reflex, minimal or no sensory disturbance, and absent sphincter disturbances"; would very well fit the description of acute postinfective polyneuritis or Guillain-Barré syndrome. Electron microscopic studies in Guillain-Barré syndrome have shown a predominant segmental demyelination; whereas, abnormalities in mitochondria and cytoskeletal elements (mitochondrial hypertrophy, loss of mitochondria, and glycogen deposits) are usual findings of thyrotoxic neuropathy as seen in our patient. [8],[9] On the other hand, in hypothyroid neuropathy, light microscopy shows myelin breakdown, demyelination, and remyelination with ultrastructural changes like excessive glycogen deposits, crystalline inclusions in Schwann cells, mitochondrial aggregates, and disintegrated neurotubules and neurofilaments; [10] suggesting definite role of thyroid hormones in the structural and functional development of the nerves.

In conclusion, the patient here presented with subacute polyneuropathy and the absence of any other identifiable cause of neuropathy except thyrotoxicosis, and the response to anti-thyroid treatment strongly suggests the diagnosis of thyrotoxic neuropathy. Thyroid function tests can be helpful in the diagnosis of this frequently treatable peripheral neuropathy in hyperthyroid patients and should be included in the routine workup in a patient presenting with peripheral neuropathy.


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