Hypothyroidism in the Cavalier King Charles Spaniel


Hypothyroidism is a genetic auto-immune disorder (lymphocytic thyroiditis) in the cavalier King Charles spaniel which destroys the thyroid gland. * It is not life-threatening by itself, but it diminishes the cavalier's quality of life.  It cannot be cured.  It also may complicate the care of cavaliers which suffer from mitral valve disease (MVD).

* See Hereditary Hypothyroidism: Understanding the disease process.

The thyroid gland produces hormones which maintain the dog's metabolic rate -- the speed at which the dog converts nutritional energy into fuel for the body.  When the thyroid deteriorates, it begins to produce insufficient quantities of the thyroid hormones.  Then the body's cells are unable to convert nutrient energy into energy fuel as quickly as normal.

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Causes

Up to 80% of all hypothyroidism in canines is due to autoimmune (lymphocytic) thyroiditis, by which T-lymphocytes destroy the thyroid gland.

Another possible cause of hypothyroidism is trauma to the thyroid gland, caused by collars. And a third possible cause, or contributing factor, is the dietary supplement quercetin. In this April 2014 article, the researchers found that the flavonoid quercetin can act as a thyroid disruptor which inhibits thyroid function and decreases the expression of the main thyroid-restricted genes involved in thyroid hormone synthesis.

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Symptoms

It is most unfortunate that by the time most clinical signs of hypothyroidism appear, as much as 75% of the dog's thyroid gland may have been irreversibly destroyed.

The result causes physical changes in the cavalier, including weight gain without any change in diet, skin infections, hair loss, temperament changes, lethargy, mental dullness, joint disease, ligament damage, and aggression towards human family members.

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Diagnosis

CavalierHealth.org Copyright © 2007 Blenheim CompanyEarly diagnosis from classic symptoms is extremely difficult because so much damage to the gland already would have occurred before clinical signs normally appear.  Also, a definitive diagnosis can be very difficult because reduced thyroid function can produce any of a number of symptoms which may mimic those of other causes.

Therefore, owners -- especially breeders -- should have a complete baseline thyroid antibody profile of their cavalier conducted before any symptoms appear, followed by annual profiles thereafter. Thyroid testing for genetic screening purposes should start after the cavalier has reached its sexual maturity, and females should not be tested for screening until they are between their first and second heats.

A complete thyroid antibody profile includes levels of T3AA (the active form of the hormone), T4AA (the inactive form created to circulate in the bloodstream), and serum TgAA, and not just freeT4, and administering the thyroid stimulating hormone (TSH) response test. It is reported that the presence of elevated TgAA levels usually confirms thyroiditis.

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Treatment

Veterinarians treat hypothyroidism by prescribing a supplemental thyroid hormone -- usually thyroxine (T4) or levothyroxine and/or liothyronine -- which must be administered to the cavalier daily for the rest of its life. Once the supplemental hormone has stabilized the thyroid-hormone levels within a normal range, the dog should be examined at least every six months.

FDAThyro-Tabs Canine (levothyroxine sodium tablets) is the only FDA-approved levothyroxine drug for hypothyroidism in dogs. In a January 2016 news release, the U.S. Food and Drug Administration (FDA) reports that it has issued warning letters to six manufacturers of unapproved levothyroxine sodium drugs for hypothyroidism in dogs. These unapproved products have not been reviewed by the FDA for safety and effectiveness. FDA issued warning letters to manufacturers of the following unapproved levothyroxine products:

Thyrosyn
Soloxine
Levocrine
Thyromed
Thyroid Chewable Tablets
Thyrokare
Thyroxine L
Thyrovet
Canine Thyroid SupportLeventa

Unless and until these levothyroxine products are approved by FDA, they are deemed to be "unsafe" and "adulterated". Introduction of an adulterated drug into interstate commerce is prohibited under by federal law. Dog owners and veterinarians can report to the FDA any adverse events, including ineffectiveness, in dogs that received approved or unapproved hypothyroidism products. Information on reporting adverse events can be found here. 

A general thyroid support supplement often recommended by holistic veterinarians is Canine Thyroid Support by Standard Process (right).

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Breeders' Responsibilities

The Canine Inherited Disorders Database advises that no dog suffering from autoimmune thyroiditis or hypothyroidism should be bred.  All cavalier breeding stock and their close relatives should be blood-tested and cleared for autoimmune thyroiditis at least annually, the closer the examination to the breeding the better.

The Orthopedic Foundation for Animals (OFA) maintains a Thyroid Registry which is useful for breeders attempting to choose dogs free of hypothyroidism in their breeding programs.  However, OFA's Thyroid Registry only requires a limited thyroid panel and by itself is not sufficient for the early detection of genetic autoimmune thyroiditis.

Antech Diagnostics, the largest veterinary diagnostic laboratory, also recommends that even dogs with negative screening results not be bred before age three years.

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Research News

January 2016: US's Food & Drug Administration warns drug manufacturers to not market levothyroxine sodium drugs unapproved by FDA. FDAIn a January 2016 news release, the U.S. Food and Drug Administration (FDA) reports that it has issued warning letters to six manufacturers of unapproved levothyroxine sodium drugs for hypothyroidism in dogs. These unapproved products have not been reviewed by the FDA for safety and effectiveness. Thyro-Tabs Canine (levothyroxine sodium tablets) is the only FDA-approved levothyroxine drug for hypothyroidism in dogs. FDA issued warning letters to manufacturers of the following unapproved levothyroxine products:

Thyrosyn
Soloxine
Levocrine
Thyromed
Thyroid Chewable Tablets
Thyrokare
Thyroxine L
Thyrovet
Leventa

Unless and until these levothyroxine products are approved by FDA, they are deemed to be "unsafe" and "adulterated". Introduction of an adulterated drug into interstate commerce is prohibited under by federal law. Dog owners and veterinarians can report to the FDA any adverse events, including ineffectiveness, in dogs that received approved or unapproved hypothyroidism products. Information on reporting adverse events can be found here.

July 2012: Anesthesia for Thyroid Gland Disease. In a July 2012 article in NAVC Clinician's Brief, by Dr. Khursheed Mama advises that dogs with clinical signs of hypothyroidism may have lower anesthetic requirements and may also have prolonged anesthetic recoveries. He recommends that body temperature be monitored, especially since hypothermia is common in hypothyroid patients.

April 2011: Dr. Jean Dodds publishes new book.  The Canine Thyroid Epidemic: Answers You Need for Your Dog. by W. Jean Dodds, Diana Laverdure, to inform both the average dog owner and animal health care professionals about the ways in which thyroid disorders occur, can be prevented and treated. 

July 2006: Participants needed for dog behavioral study. Dr. Nicholas Dodman of the Animal Behavior Clinic at Tufts Cummings School of Veterinary Medicine in North Grafton, Massachusetts, and Dr. Jean Dodds, are seeking participants for a study concerning the efficacy of supplementing low, or borderline low, thyroid levels as a treatment for owner-directed aggression.  If you have a dog that is aggressive towards human family members and is not currently being treated for hypothyroidism, please contact Nicole Cottam, telephone 508-887-4802, email nicole.cottam@tufts.edu to find out more about the study. You do not have to visit Tufts in order to participate.

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Related Link

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Veterinary Resources

Control of Canine Genetic Diseases. Padgett. G.A., Howell Book House 1998, pp. 198-199, 222.

Hereditary Hypothyroidism: Understanding the disease process. Jerold S. Bell. AKC Gazette. Aug. 2001. Quote: "Canine hypothyroidism is frequently misunderstood, misdiagnosed, and mistreated. Historically, it has been thought that 50 percent of cases of canine hypothyroidism are caused by autoimmune thyroiditis, and the rest are caused by idiopathic hypothyroidism. What the experts now understand is that almost all primary hypothyroidism in dogs is caused by thyroiditis (autoimmune destruction of the thyroid gland), and that this is a genetic disorder. Primary idiopathic hypothyroidism, if it exists at all, is a rare condition. The confusion comes from looking at blood test 'snapshots' of hypothyroid dogs, and not understanding the whole 'moving picture' of thyroid disease. ... There are metabolic, infectious, endocrinologic, and cancerous illnesses that have no autoimmune components but which can nonetheless cause low thyroid-hormone values. This problem, which occurs less frequently is generally referred to as secondary hypothyroidism. It is not a hereditary thyroid disorder. There is some controversy as to whether environmental toxins or vaccines cause autoimmune thyroiditis. These act as stresses on a dog's body and could possibly affect the onset or severity of autoimmune thyroiditis. However, Dr. W. Jean Dodds, founder of the animal blood bank Hemopet, states that only dogs that have the genetic potential can develop autoimmune thyroiditis. Therefore, any dog that has significant levels of blood-thyroid autoantibodies is considered genetically affected with hypothyroidism, and to carry a gene (or genes) that cause the disorder. Dr. Dodds also reports that thyroid supplementation may be protective to dogs with thyroid autoantibodies even before their thyroid hormone levels drop. ... Studies on the mode of inheritance of hereditary hypothyroidism/autoimmune thyroiditis in dogs have been inconclusive to date. What has been established is that some breeds have a much greater likelihood of developing autoimmune thyroiditis than do others, while some breeds have a below-average risk. These breeds respectively carry a higher or lower genetic load of hypothyroidism causing genes. ... Breeds with the lowest prevalence (<3% affected) of hypothyroidism (Data from the endocrinology lab at Michigan State University): ... Cavalier King Charles Spaniel ... ."

Guide to Congenital and Heritable Disorders in Dogs.  Dodds WJ, Hall S, Inks K, A.V.A.R., Jan 2004, Section II(166).

The Thyroid Dilemma.  Antech Diagnostics News Lab Tips, October and November 2005.

How to Test, Interpret Thyroid Function. W. Jean Dodds, DVM. Veterinary Practice News. April 12, 2011.

Anesthesia for Thyroid Gland Disease. Khursheed Mama. NAVC Clinician's Brief. July 2012.

Thyroid Disease and Autoimmune Thyroiditis. W. Jean Doods. Hemopet.org December 2013.

The flavonoid quercetin inhibits thyroid-restricted genes expression and thyroid function. Giuliani C, Bucci I, Di Santo S, Rossi C, Grassadonia A, Piantelli M, Monaco F, Napolitano G. Food Chem. Toxicol. April 2014;66:23-29. Quote: Quercetin is the most abundant flavonoid present in a broad range of fruit and vegetables. Furthermore, quercetin is available as dietary supplements that are based on its antioxidant, antiproliferative and anti-inflammatory properties. However, concerns have been raised about the potential toxic effects of excessive intake of quercetin, and several studies have demonstrated that flavonoids, included quercetin, can interfere with thyroid function. In a previous report, we showed that quercetin inhibits thyroid-cell growth and iodide uptake. The latter effect was associated with down-regulation of sodium/iodide symporter gene expression. In the present study, we have evaluated the effects of quercetin on the expression of other thyroid-restricted genes, and we show that quercetin decreases the expression of the thyrotropin receptor, thyroid peroxidase and thyroglobulin genes. We further investigated the inhibitory effects of quercetin on thyroid function in vivo through evaluation of radioiodine uptake in the Sprague-Dawley rat, which was significantly decreased after 14 days of quercetin treatment. These data confirm that quercetin can act as a thyroid disruptor, and they suggest that caution is needed in its supplemental and therapeutic use. Our data show that quercetin inhibits thyroid function and decreases the expression of the main thyroid-restricted genes involved in thyroid hormone synthesis. These effects that we have here demonstrated in vitro, are also confirmed here by inhibition of thyroid radioiodine uptake in normal rats. These data are relevant given the worldwide diffusion of dietary supplements containing high amounts of quercetin, and they should spur on human studies to better define these anti-thyroid effect of quercetin. The data of the present study comes from experiments performed in rats. Therefore, to define quercetin as a thyroid endocrine disruptor even for human, further studies must be conducted in human ingesting quercetin supplements or involved in clinical trials with quercetin. Meanwhile, we also suggest that the use of quercetin in pregnant and lactating women should be avoided, along with its use for patients with hypothyroidism and for candidates for radioiodine administration.

Histological and immunohistochemical evaluation of stroma variations and their 4 correlation with the Ki-67 index and expressions of glucose transporter 1 and 5 monocarboxylate transporter 1 in canine thyroid C-cell carcinomas. Yoshio Kawamura, Hiroko Mizooku, Minoru Okamoto, Kazuya Matsuda, Tetsuo Omachi, Kazuko Hirayama, Tsuyoshi Kadosawa, Hiroyuki Taniyama. J. Vet. Med. Sci. January 2016. Quote: "Canine thyroid C-cell carcinomas (CTCCs) are malignant tumors derived from calcitonin-producing C-cells of the thyroid gland. This study aimed to investigate the histological diversity of CTCCs from the viewpoint of stroma variations and to investigate their components by histological and immunohistochemical analysis including semiquantitative analysis of the density of microvessels (MVs) and α-SMA-positive cell count. Moreover, we examined whether the variations correlated with the Ki-67 index and expressions of glucose transporter 1 (GLUT-1) and monocarboxylate transporter 1 (MCT-1). Three stroma types (reticular, R, nest, N, and trabecular, T) were observed in CTCCs and 21 cases were divided into 3 variations based on their combinations: mixed R and N (R/N) (n=7), simple N (n=7) and mixed T and N (T/N) (n=7). [One cavalier King Charles spaniel: female aged 10 years, tumor diameter: 4 cm., period to surgical treatment: 300 days.] Immuno-histochemically, stroma types depended on morphological features of α-SMA/fibronectin/laminin/collagen type IV-positive stroma cells. The density of MVs in R/N tended to be highest, and the density of those in N was significantly higher than the density of those in T/N (P=0.028). The α-SMA-positive cell count for N tended to be the lowest among the 3 variations. The Ki-67 index for R/N was significantly higher than those of the other variations (vs. N, P=0.007; vs. T/N, P=0.03), and that for T/N tended to be higher than that for N. Although there were no significant differences, GLUT-1 and MCT-1 expressions tended to be low in N. We concluded that stroma variations reflect tumor cell proliferation and expressions of GLUT-1 and MCT-1 in CTCCs."

Cardiogenic Pulmonary Edema in a Dog Following Initiation of Therapy for Concurrent Hypoadrenocorticism and Hypothyroidism. Jooyae Paik, Ji-Houn Kang, Dongwoo Chang, Mhan-Pyo Yang. JAAHA. September 2016. Quote: A 5-year-old intact female cocker spaniel dog weighing 7.8 kg was referred with anorexia, vomiting, and depression. At referral, the dog was diagnosed initially with typical hypoadrenocorticism, and 2 d later, concurrent primary hypothyroidism was detected. Hormonal replacement therapies, including fludrocortisone, prednisolone, and levothyroxine, were initiated, but a few days later the dog became abruptly tachypneic, and thoracic radiographs indicated the development of pulmonary edema. Echocardiography showed that there were abnormalities indicating impaired left ventricular function, although the heart valves were normal. Following treatment with pimobendan and furosemide, the pulmonary edema resolved. The dog had no recurrence of the clinical signs after 10 mo of follow-up, despite being off all cardiac medications; consequently, the cardiac failure was transient or reversible in this dog. The case report describes the stepwise diagnosis and successful treatment of cardiogenic pulmonary edema after initiation of hormonal replacement therapy for concurrent hypoadrenocorticism and hypothyroidism in a dog.

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