The Tissue -Pathies of Hypothyroidism and the Controversy

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The Tissue -Pathies of Hypothyroidism and the Controversy | Canine Thyroid Awareness Month

Hypothyroidism can be an effect of, or impetus for, several secondary diseases and dysfunctions. Whether or not hypothyroidism is the singular cause or due to multiple factors depends on the dysfunction in question. 

To complicate matters, not all hypothyroid patients develop these secondary diseases and most if not all of these conditions can occur without the presence of thyroid dysfunction. In some instances, the medical community is unsure how thyroid dysfunction actually creates these additional problems.

Endocrinopathy

Individuals genetically susceptible to autoimmune thyroid disease may also become more susceptible to immune-mediated diseases affecting other target tissues and organs, especially the bone marrow, liver, adrenal gland, pancreas, skin, kidney, joints, bowel, and central nervous system. 

The resulting “polyglandular autoimmune syndrome” of humans is becoming more commonly recognized in the dog, and probably occurs in other species as well. The syndrome tends to run in families and is understood to have an inherited basis. 

Multiple endocrine glands and nonendocrine systems become involved in a systemic immune-mediated process. This multiple endocrinopathy often occurs in patients with underlying autoimmune thyroid disease (hypo- or hyperthyroidism) and concurrent Addison’s disease, diabetes, reproductive gonadal failure, skin disease and alopecia, and malabsorption syndrome. The most common nonendocrinologic autoimmune disorders associated with this syndrome are autoimmune hemolytic anemia (AIHA), idiopathic thrombocytopenic purpura (ITP), chronic active hepatitis, and immune-complex glomerulonephritis (systemic lupus erythematosus; SLE).

The most commonly recognized polyglandular endocrinopathy of dogs is Schmidt’s syndrome (thyroiditis and Addison’s disease).  Examples of breeds genetically predisposed to this disorder include the Standard Poodle, Old English Sheepdog, Bearded Collie, Portuguese Water Dog, Nova Scotia Duck Tolling Retriever, and Leonberger, although any breed or mixed breed can be affected.  

Our study cohort of 162 cases of autoimmune blood and endocrine disorders in Old English Sheepdogs (1980-1989) included 115 AIHA and/or ITP, 99 thyroid disease, 23 Addison’s disease, 7 vaccine reactions, 3 SLE, 2 diabetes, 1 rheumatoid arthritis and 1 hypoparathyroidism.  The group comprised 110 females (15 spayed) and 52 males (3 neutered).  Seven of the most recent 103 cases had two or more endocrine disorders, and 101 of the 108 cases where pedigrees were available showed a familial relationship going back several generations. Data from surveying the Bearded Collie breed reported 55 hypothyroid, 17 Addison’s disease, and 31 polyglandular autoimmunity (5 were hypothyroid).

Other -Pathies Secondary to Hypothyroidism

Myopathy

A myopathy is a skeletal muscle tissue disease which is not caused by nerves or the junction between nerves and muscles (neuromuscular junction). Muscular dystrophy is the best known and most severe myopathy in humans. However, most myopathies in humans and animals are not fatal and the mild symptoms include muscle weakness, pain, cramps and atrophy (wasting of the muscle).

Neuropathy

Neuropathies (nerve dysfunctions or degeneration) can present as a variety of symptoms (humans) and signs (animals). 

Meaning: the medical community has dissected and isolated the various forms due to symptoms and signs, the areas of the body affected and so much more. They occur from damage to or disease affecting nerves, which may impair sensation, movement, gland or organ function, or other aspects of health, depending on the type of nerve affected. Common causes include systemic diseases, immune system disease, gluten-intolerant bowel disorders or viral infection.

Nerves are like electrical wiring; they have a protective cover and have a lot more wires on the inside. Neuropathies happen two ways. Myelin, the protective coat of nerve fibers, deteriorates, the process is called demyelination. Axonal degeneration occurs when the interior nerve fibers start to deteriorate underneath the myelin. Symptoms include weakness, knuckling or dragging feet, stiffness, atrophy, weak reflexes, lack of muscle tone and tremors.

The two basic neuropathies are cranial and peripheral. In the simplest terms, cranial neuropathy occurs in the head and spinal cord (brain and brain stem), and affects the face, ears and eyes. They are often called the sensory nerve disorders. Dogs who manifest this form of neuropathy generally have facial paralysis, drooping eyelids, or inner ear problems (vestibulocochlear, a mouthful) with head tilting as the most obvious symptom.

Peripheral neuropathies are basically everything below the neck and do not involve the spinal cord. The distinguishing factor between the two neuropathies is that the peripheral nerves are not protected by a skeletal mass like the cranial nerves. Peripheral nerve disorders are colloquially known as neuromuscular diseases.

Laryngeal paralysis and megaesophagus are two common conditions. However, the debate continues about whether these conditions are cranial or peripheral neuropathies. What we do know is that they are neuropathies. 

Neuropathy vs. Myopathy and Hypothyroidism

The primary distinguishing factor between a neuropathy and a myopathy is that a neuropathy is the degeneration of the junction between nerves and muscles. As previously mentioned, a myopathy occurs solely in the skeletomuscular region.

Medical professionals are usually able to figure out which condition is causing the symptoms or signs. For instance, if muscle weakness is distal (further away from the central part of the body), it is a neuropathy. 

Muscle weakness closer to the body or more centrally located is called proximal and generally points to a myopathy. 

Neuropathies are associated with the absence of muscle reflexes and the presence of sensory loss. Both conditions cause atrophy but it depends on when it develops. Tests such as nerve conduction velocity, electromyography, creatine phosphokinase level from blood work, and muscle biopsies will further detect the condition.

What we know is that myopathies can be secondary to hypothyroidism because the decreased amount of thyroxine circulating in the blood affects the body’s ability to metabolize protein, carbohydrates and fats – the building blocks of any metabolism based upon the diet.

Now…this is where it gets really interesting. What we do not know is exactly how hypothyroidism causes a secondary neuropathy and multiple factors could be in play. My colleague, J. H. Rossmeisl, Jr., stated it best (in technical language):

Some studies in humans and dogs report sensorimotor clinical, electrophysiologic, and morphologic evidence of a predominantly axonal neuropathy, while others report demyelination as the principal lesion. In humans with spontaneous disease and experimental rodent models, it is suggested that hypothyroid neuropathy may result in nerve entrapment from the accumulation of mucinous deposits, demyelination caused by disordered Schwann cell metabolism, vascular nerve damage secondary to hypothyroid-induced alterations in the blood-nerve barrier, or variably severe metabolic defects ranging from in disturbed axonal transport to overt axonal loss.

Controversy

It is widely accepted that hypothyroid neuropathy does exist throughout the medical communities – even though we are still not too sure how it does so yet.

Rossmeisl, noted above, conducted a study approximately seven years ago to deduce how hypothyroidism causes neuropathies. He and his fellow researchers induced hypothyroidism with radioactive iodine in nine dogs and compared them to a control group of another nine dogs. They evaluated the dogs for up to 18 months. They concluded that chronic induced hypothyroidism does not result in evidence of neuropathy but causes a subclinical myopathy.

I am pleased that Rossmeisl qualified his study with “induced” as this is the operative word. Unfortunately, many in my profession point to this study as affirming that some or all neuropathies are not secondary to hypothyroidism. I beg to differ and I assume that Rossmeisl would too. This study only lasted 18 months. Clinical findings demonstrate that neuropathies are typically from long-term, undiagnosed hypothyroidism.

Skeptics also note that some neuropathies (particularly laryngeal paralysis) are not reversed, slowed or lessened with the introduction of thyroid medication. [My personal experience over several decades would disagree with this belief.] 

On the flip side, Eric Glass et al. looked at three profound case studies that showed that thyroid medication did in fact help lessen the neuropathies. My arguments are: 1) Sometimes the hypothyroid neuropathy is so advanced that not only is thyroid medication necessary but also additional medication and treatment is needed; and, 2) If a dog presents  as hypothyroid, common sense begets to prescribe thyroid medication, at least on a clinical trial basis.

W. Jean Dodds, DVM
Hemopet / NutriScan
11561 Salinaz Avenue
Garden Grove, CA 92843

References

Bagley, Rodney. “Cranial Nerve Neuropathy.” Vetstream, n.d. Web. 11 Sept. 2016. https://www.vetstream.com/canis/Content/Disease/dis02290.

Dodds WJ and Laverdure DR. The Canine Thyroid Epidemic: Answers You Need for Your Dog. DogWise Publ., Wenatchee, WA, 2011.

Doyle, Victoria. “Neurological Manifestations of Endocrine Disease: Part Three.” Vet Times, 16 Apr. 2012. Web. 11 Sept. 2016. http://www.vettimes.co.uk/article/neurological-manifestations-of-endocrine-disease-part-three/.

Glass, Eric N., DVM, et al. “Hypothyroid-associated Neurologic Signs in Dogs.” Veterinary Medicine. DVM360, 01 May 2013. Web. 11 Sept. 2016. http://veterinarymedicine.dvm360.com/hypothyroid-associated-neurologic-signs-dogs.

Rossmeisl, J.H., Jr. “Resistance of the Peripheral Nervous System to the Effects of Chronic Canine Hypothyroidism.” Journal of Veterinary Internal Medicine 24 (2010): 875-81. Wiley. Web. 11 Sept. 2016. http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2010.0515.x/epdf.

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