Among primary thyroid dysfunction, hypothyroidism is a common endocrine disorder found in dogs; hyperthyroidism is more common in cats. Neuro-muscular signs associated with thyroid dysfunction have been recognized for years although central neurological signs have been described more recently.
Thyroid function testing is usually performed by serum thyroxin concentration measurement. The more accurate diagnosis of hypothyroidism is based on low-resting free T4 concentration (100% predictive value). Basal T4 has a 95% positive predictive value, the 5% lacking are due to the presence of T4 antibodies. If the value is intermediary, a final diagnosis cannot be made. The TSH stimulation test improves the diagnosis in 70% of these cases; an inadequate response to TSH stimulation is in favor of hypothyroidism. Anaphylactic reactions with bovine or porcine TSH may be lethal. Recombinant TSH is expensive. A high TSH seric measurement may improve the final diagnosis. 20% of false negative and 30% of false positive are expected. Alone, this test is diagnostic in 37% of the cases. TRH stimulation is so weak that it helps to rule out hypothyroidism only if T4 normalizes. T3, reverse T3, TSH post TRH stimulation are useless.
Collateral biochemical changes may be found: hypercholesterolemia is in favor although a third of the cases may have normal values.1
In the literature, hypothyroidism is often named as an etiology for numerous diseases. Most of theses studies were single or few clinical cases carried out before than modern more sensitive T4 and TSH assays were available. Since, this idea has been carried out in the literature without verification until recently, mainly by Dr A Jaggy.2-5
Primary hypothyroidism is characterized by lethargy, weight gain, symmetrical alopecia, bradycardia, and generalized weakness. In human medicine, hypothyroidism as been associated with the clinical feature of myopathy (prevalence of 20 to 80%), mono-neuropathy, and sensory-motor axonal polyneuropathy (prevalence of 10 to 70%). Sensory symptoms predominate initially. Among clinical signs encountered in hypothyroid dogs, cranial, laryngeal and appendicular neuropathies have been described. Signs of encephalopathy have been less observed although hypothyroidism is incriminated in case of peripheral vestibular syndrome. In people, hearing loss has also been described. The patho-physiology behind the neurological signs in acquired hypothyroidism is poorly understood. The decreased ATPase activity in these patients drives to ATP deprivation responsible for the alteration of the axonal transport, leading to axonal degeneration and clinical neuropathy.
Generalized weakness: Large and giant breeds of dogs presenting with generalized weakness have Lower Motor Neurons signs (flaccid paresis or paralysis: hypotonia, hyporeflexia and muscle atrophy). Clinical signs usually progress from weakness to non ambulatory tetraplegia within 4 to 6 weeks, which is characteristic of a polyneuropathy. The diagnosis of polyneuropathy is based on electromyographic (fibrillation potentials, positive sharp waves, complex repetitive discharges), electroneurographic (decrease nerve conduction velocity, conduction blocs), and histo-pathological (neurogenic muscle atrophy, wallerian type degeneration and demyelinisation) findings. The myopathic electrodiagnostic changes (polyphasic or giant motor unit action potentials as an evidence of reinnervation activity) do not correlate with muscle weakness in human hypothyroid patients.6
Cranial nerve involvement: Hypothyroidism has been recognized as a cause of peripheral vestibular syndrome. These dogs are presented with head tilt, asymmetrical ataxia (hypertonia on the side opposite to the head tilt, and hypotonia on the same side) and nystagmus without postural reaction deficit. The history (no exposure to ototoxic drugs, no history of trauma) and the normal findings of complementary diagnostic procedures (otoscopic examination, Brainstem Auditory Evoked Response, radiographs, computerized tomography or magnetic resonance imaging (bullae, petrous bone, and brain stem) and cerebrospinal fluid analysis) rule out middle or internal ear structural causes. The Brainstem Auditory Evoked Response may show decreased amplitude and latency, consistent with a degenerative neuropathy. Mild EMG or ENG finding consistent with a diffuse polyneuropathy without clinical expression may also be found concomitantly. Facial paralysis has been associated with hypothyroidism in dog.7
Megaoesophagus: Megaoesophagus is a common finding in myasthenia gravis, neuropathy of congenital or metabolic origin, hypoadrenocorticism, LE, However, a large number of cases have an idiopathic etiology. Some of those have a concomitant hypothyroid status and their megaoesophagus may be reversed by thyroid supplementation.
Laryngeal paralysis: Acquired laryngeal paralysis is a middle-aged to old large or giant dog condition. The recurrent nerve degenerative changes may or may not be included in a more generalized polyneuropathy. In some of them, concomitant hypothyroidism has also been reported and clinical signs reversed by thyroid supplementation.
Central hemispheric signs: Hyperlipoproteinemia and the lipidic form of arteriosclerosis, named atherosclerosis, have been described in primary hypothyroid dogs. Involvement of cerebral arteries may induce hypoxia and spontaneous vascular accidents inducing seizures or other supra-tentorial neurological expression (circling, head pressing, hemi-negligence syndrome). Hypothyroidism is more prevalent in dogs with atherosclerosis compared to dogs without atherosclerosis on postmortem examination.8 In a retrospective study, dogs with atherosclerosis were over 51 times more likely to have concurrent hypothyroidism than dogs without atherosclerosis. Hypothyroidism has also been diagnosed in non-structural epileptic dogs. Thyroid supplementation may resolve the problem and anti-epileptic drugs may be discontinue.
Treatment: Because of the difficulties encountered to obtain a final diagnosis of hypothyroidism, a therapeutic diagnosis may often confirm the hypothesis of a neurological dysfunction related to hypothyroidism. A T4 supplementation is preferred to a T3/T4 mixed supplementation. The risk of thyrotoxicosis is null with the first one. 33% of hypothyroid human patients have residual symptoms after 1 year of therapy. The patho-physiological changes found in hypothyroid muscle (type II fibers atrophy, increased numbers of internal nuclei, core-like structures in type I fibers) may explain this. Hypothyroidism induces less a myopathy than a muscle dysfunction.
Hyperthyroidism has been associated with the clinical features of neuromuscular and central nervous system dysfunction similar to signs described in human beings. Weakness is a common feature in cats with hyperthyroidism. The most common clinical expressions are neck ventro-flexion, decrease ability to jump, fatigue after physical activity. Restlessness, hyper-excitability, irritability and aggression are behavior signs that can develop in hyperthyroid cats. Focal or generalized seizures are rarely reported.
These neurological manifestations are associated with more systemic signs, i.e., increased appetite, weight loss, polydipsia, vomiting and diarrhea associated with high liver enzyme activity and hypertrophic cardio-myopathy. There are no specific pathological changes in muscles of hyperthyroid patients. Paraclinical evidence of myopathy is lacking. It is more a functional muscle disorder than a myopathy. The muscle weakness has a good and rapid recovery once the treatment is instituted. Most of the central nervous system signs resolve also with correction of hyperthyroidism.
The physio-pathological relation of megaoesophagus, laryngeal paralysis, ocular abnormalities, and other neuropathies with hypothyroidism remains to be scientifically established. Confirmation of the relation between neurological signs and hypothyroidism will depend on the type of neurological presentation, clinico-pathological results including T4 and if possible TSH level or TSH stimulation test, electrodiagnostic findings, histo-pathological findings and response to unique T4 supplementation.
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5. Jaggy A, Oliver JE, Ferguson DC, et al. Neurological manifestations of hypothyroidism: a retrospective study of 29 dogs. JVIM 1994;8:328-336.
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7. McKeown HM. Hypothyroidism in a boxer dog. Can Vet J 2002;43:553-555.
8. Hess RS, Kass PH, Van Winkle TJ. Association between diabetes mellitus, hypothyroidism or hyperadrenocorticism, and atherosclerosis in dogs. J Vet Intern Med 2003;17:489-494.