Hypothyroidism in the dog can be classified asprimary, secondary and tertiary depending upon whether the cause resides in the thyroid gland, pituitary gland or hypothalamus. The roles of the pituitary gland and hypothalamus, which control thyroid hormone levels via secretion of TSH and TRH, respectively, have been discussed elsewhere. A fourth class of hypothyroidism is congenital...implying a defect at birth that affects thyroid hormone synthesis, transport to tissues or iodine metabolism. These are rare! Puppies with severe forms of congenital hypothyroidism are said to have “Cretinism”. These usually have developmental defects of the pituitary gland (Secondary Hypothyroidism) and are stunted mentally, and, with time are malformed physically. Finally, there are some animals that concurrently manifest deficiencies in several endocrine glands (adrenal, pancreatic islet [diabetes], parathyroid, and gonads [testicles or ovaries]). Failure of multiple glands can be the result of an immune system disorder causing a “polyendocrinopathy” or “autoimmune polyglandular syndrome” ...that will not be further discussed here... or a pituitary gland insufficiency (see Secondary Hypothyroidism).
A simple list of the most common and least common causes of hypothyroidism is available. The most common causes are Lymphocytic Thyroiditis & Idiopathic Atrophy. These account for nearly all the causes of primary hypothyroidism.
Primary (more than 95%):
There may be a genetic predisposition to this disorder. Other causes are not understood, but are suspected. It may be part of the “autoimmune polyglandular syndrome” in some animals.
This is an immune system disorder in which there is increased circulating and glandular antibodies to several thyroid hormones--mostly to thyroglobulin (thyroid hormone precursor molecule). Other facets (“cell mediated components”) of the immune system are also involved in the immune system’s attack on the thyroid gland.
There is infiltration of immune cells (producing autoantibodies to thyroid tissue) and inflammatory cells into the substance of the thyroid gland, then interaction of autoantibodies with hormones and hormone precursors that results in the formation of complexes. The presence of immune complexes within the gland triggers subsequent cascade of inflammation, resulting in biochemical events that damage and, ultimately, completely destroy the gland. This process is insidious...taking several years.
Cause is unknown, hence the moniker “idiopathic”...but speculation is that this represents the end stage of lymphocytic thyroiditis.
Follicular Cell Hyperplasia (+ dyshormonogenesis) precedes end stage disease. This is characterized by increased numbers of small thyroid “follicles”...the compartmental “units” where hormone is synthesized. The small sizes indicate that little hormone is present. The increased number of these follicles is due to stimulation of the gland by TSH (as a result of low circulating thyroid hormones and the absence of feedback inhibition...as discussed in the “thyroid primer”).
Ultimately, the disease is characterized by loss of functional thyroid tissue that is replaced by fat.
Though rare, Squamous Cell Carcinoma and Thyroid Carcinoma, may infiltrate and destroy thyroid tissue. These tumors do not usually synthesize hormones...hence, animals become hypothyroid as functional tissue is destroyed. A few tumors MAY autonomously and continuously synthesize thyroid hormones (and synthesis is NOT controlled by circulating TSH levels). These latter animals develop signs of hyperthyroidism (not discussed here)
Diseases that result in decreased pituitary secretion of normal TSH result in atrophy of the thyroid gland. These account for less than 5% of the incidences of hypothyroidism. Since the pituitary is intimately a part of the regulation of several other important endocrine glands (e.g. adrenal, gonadal), it is likely that pituitary insufficiency will result in clinical signs attributed to multiple abnormalities. Additionally, because of the proximity of the pituitary to the base of the brain, neurological deficits may also accompany pituitary gland abnormalities, particularly where a space occupying mass is present.
There is no proof that tertiary hypothyroidism occurs in the dog...primarily because there is no reliable assay for measuring circulating TRH (nor TSH). Thus, the possibility is there...and clinical signs and histological appearance of the thyroid would parallel those described for secondary hypothyroidism. Recent work, however, indicates that reliable assays for TRH and TSH may be forthcoming in the relatively near future. (see discussion of Tests for Thyroid Function)
Congenital Hypothyroidism of Toy Fox Terriers
This heritable form of hypothyroidism is present at birth. It is estimated that about 31% of normal toy fox terriers carry the gene(s) responsible for the defect, and about one in four members of a litter are affected when bitch and sire are carriers. There is a DNA test available to screen for animals which carry the trait...which is recommended prior to any breeding
Animals are developmentally (physically and mentally) stunted and less active than their littermates. Many die early (or are euthanized)...but if the animal survives, other abnormalities consistent with congenital hypothyroidism, such as disproportionate dwarfism (e.g. short legs, large tongue, abnormal or absent development of permanent teeth) and poor cognition/mental development (dull, "retarded"?).
Clinical Signs of Common Canine Hypothyroidism
The thyroid hormones affect virtually every organ system in the body. Any or all of the many signs and symptoms of Hypothyroidism (in the absence of multiple glandular involvement) may be noticed:
Lethargy, mental dullness or behavioral changes, increased appetite and/or weight gain/obesity, cold intolerance (seeking of warm places), poor wound healing, poor skin and hair coat, including hair loss or abnormal hair turnover, dull or brittle hair, altered pigmentation, oily or dry skin, thickened skin (“myxedema” [see below...Myxedema Coma...for definition]) with a “sad" facial expression, odiferous skin that may be pruritic (itchy) because of secondary bacterial, and/or yeast dermatitis/pyoderma (superficial infections) with or without concurrent demodecosis (skin parasite), diarrhea or constipation, bleeding problems (rare), neurological signs...seizures, cranial nerve deficits (blind, and/or droopy eyelids..which may also occur with myxedema, dry irritated/red eyes due to paralysis of eyelids (no blinking) or decreased tear production causing eye surfaces to dry and be irritated, vestibular (equilibrium) deficits (acts “drunk”), proprioceptive deficits (dragging of feet...”knuckling”), swallowing problems (rare), general weakness.
Some of the common physical attributes of these dogs are shown in the montages, below:
Other signs may be found on physical exam and lab work, including heart arrhythmias...particularly a slow heart rate, anemia and high serum cholesterol.
In rare incidences, an animal may be severely hypothyroid, and present to the clinician with profound weakness and diminished consciousness, hypothermia (below normal temperature), myxedema (a "non-pitting" swelling in the skin due to abnormal turnover of dermal milieu known as "ground substance),
bradycardia (abnormally slow heart), hypotension (low blood pressure), hypoventilation (inadequate respiratory activity). This condition is known as a myxedema coma and is a medical emergency (there is a high mortality associated with myxedema coma)
Clinical history consistent with Hypothyroidism
Physical exam consistent with Hypothyroidism
General laboratory findings consistent with Hypothyroidism
Thyroid Function Tests:
Total T4 is low (but remember effects of non-thyroidal illness) and also false elevations in some instances of true hypothyroidism (i.e. when there is antibody to thyroglobulin)
. It is estimated that 7% of dogs with mild non-thyroidal illness,will test low (positive); for mild non-thyroidal illness the corresponding false positive is 28% and in dogs with severe non-thyroidal illness, the incidence of false positive is 60%(VIN Intervet® Symposium 6/27/06). Note also that recent evidence (Journal of Veterinary Internal Medicine, January 2009) shows that T4 can be falsely lowered several days following certain anesthetic protocols
free T4 by equilibrium dialysis is low (but could be low with certain non-thyroidal illnesses. It is currently estimated that free T4 is low in 8% of normal dogs with mild non-thyroidal illness, low in 17% of dogs with moderate non-thyroidal illness and low in 44% of normal dogs with serious non-thyroidal illness (VIN Intervet® Symposium 6/27/06). Note also that recent evidence (Journal of Veterinary Internal Medicine, January 2009) shows that free T4 can be falsely elevated several days following certain anesthetic protocols
Serum TSH is high (but 27% to 33% of non-hypothyroidal animals with non-thyroidal illness will have low serum TSH)and TSH is normal in at least 25% of hypothyroid dogs and is elevated in about 10% - 20% of dogs who are NOT hypothyroid. This test alone is not useful for diagnosing hypothyroidism but in conjunction with Total T4 and free T4 , the specificity of the combined diagnostics is improved in comparison to the specificity of the other two tests individually.
TSH stimulation...expensive but worthy of consideration when other tests are inconclusive.BovineTSH formerly used in this test is not available anymore and the human recombinant form of TSH that can be used may be cost prohibitive
Thyroid hormone autoantibodies levels...may be helpful (but inconsistently) in the presence of lymphocytic thyroiditis...where antibody-mediated destruction of the thyroid occurs; detection of anti-thyroglobulin antibody (not anti-T4 or anti-T3 antibody levels) is helpful when used in conjunction with other tests). Remember though that about 57% of dogs with elevated thyroid hormone autoantibodies will never progress to overt hypothyroidism. And many dogs who are severely hypothyroid will not have autoantibodies (because they are made by lymphocytes destroying the thyroid....when there is destruction of the gland, the process of inflammation and antibody production ceases).
Treatment in routine cases of hypothyroidism consists in supplementation with thyroid hormone (L-thyroxine).
Keep in mind that there are many brands of commercial thyroid hormone supplementation, tablets, chewable tablets and liquid forms, and that the bioavailability of the active ingredient is significantly different, brand to brand, type to type (tablet vs chewable vs liquid). This means that even at the same oral dosage, the actual amount of thyroid supplement absorbed and available to the body will differ among brands or forms of medication. Therefore, it is important that once an animal is stabilized on a particular brand of the oral thyroid hormone supplement, the brand and type of that medication should never be changed. Unfortunately, many clinics will stock the least expensive brand of thyroid hormone supplement any any given purchase time. The stocked brand may differ week to week or month to month. Because of the significant differences in bioavailability noted above, the veterinarian should be especially careful to not refill an L-thyroxine prescription with a brand other than the brand the animal has been taking (even if the dose is the same as before) because the steady-state level of serum hormone may change when different brands are administered.
The actual starting dose and frequency of administration for medium sized breeds is 0.02 mg/kg either once or twice daily. For large or small breeds, the dose should be based on body surface area (BSA), rather than weight. The recommended starting dose for large and small breeds is 0.5 mg/M2 . The dose may need to be changed, depending on laboratory results (a T4 or free T4 is checked 3-6 weeks later). Periodic rechecks are needed until a clinical signs are resolved and thyroid hormone levels are stable and within the normal range. Semi-annual or annual rechecks may be routinely recommended.
Some of the clinical signs may respond to thyroid supplementation, but mental retardation is permanent unless replacement therapy is begun very early, within the first week of life.
Many afflicted puppies are euthanized because of a general belief that their quality of life would be significantly diminished
In emergency situation, such as myxedema coma, intravenous thyroid hormone supplement may be required usually starting dose is 5 µg/kg twice daily plus other emergency and supportive care measures.
Time to Respond
Activity: Increased activity will be noticed within the first two weeks of treatment in cases of common hypothyroidism
Weight: In animals who are overweight because they are hypothyroid, weight loss usually is seen by eight weeks after normalization of circulating thyroid hormone
Skin: Notable improvement in coat and regrowth of hair in dogs that have experienced hair loss (alopecia) takes months. In fact...early on, there may be some additional loss of hair due to telogen defluvion (see Skin, and scroll to the area on "Alopecia"...then scroll a little further )...as hair follicle activity recommences on therapy, older, dormant hairs are lost well (months) before newer hairs are generated. One other important point about skin is that animals with poor hair coat due to other causes (i.e. animals who are not hypothyroid) may show improvement on thyroid supplement. Thyroid supplementation in this instance is inappropriate, however; the primary cause of the skin problem should be ascertained and treated accordingly.
Laboratory abnormalities: are usually significantly improved or normal by four weeks of appropriate thyroid supplementation