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Keratoconjunctivitis sicca in the dog: a review of two hundred cases. Jane Sansom, K.C. Barnett. J.Sm.Anim.Pract. March 1985; 26(3):121-131. Quote: Two hundred consecutive referred cases of keratoconjunctivitis sicca [KCS] in the dog were examined over a 9 year period [including 11 cavalier King Charles spaniels]. The clinical signs are described and the cases discussed in sections relating to the aetiology and in particular, the age and sex incidence in the West Highland White Terrier. The suitability of this animal as a model for Sjögrens syndrome in man is discussed. ... Hypothyroidism: The association between KCS and hypothyroidism has already been suggested (Peruccio, 1982) and a further two cases in this series supported this theory although the hypothyroidism had not previously been suspected. Nine other cases were sampled but radioimmune assay of serum samples for thyroxine (T4) revealed normal levels. Both dogs were male, a 5-year-old Cavalier King Charles Spaniel and a 7-yearold Shetland Sheepdog. Both showed clinical signs of hypothyroidism in that they were obese and lethargic with a dry coat and soft, pendulous testicles. Blood samples revealed hypercholesterolaemia and low T4 values and both dogs showed a marked improvement in condition when treated with thyroid fed by mouth. The Cavalier King Charles had an extremely painful left eye with blepharospasm and photophobia, marked conjunctival congestion and thick mucopurulent discharge, an oedematous cornea with vascular fringe and a central deep ulcer. The Schirmer tear test reading was zero. The other eye had a slightly tacky discharge with a Schirmer reading of 8 mm of wetting per minute.

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.

Breed influence on canine thyroid reference intervals and age-related thyroid decline. Olivia Barnard-Jones, Kent Refsal, Peter Graham. BSAVA Congress 2019 proceedings; pp. 438. Quote: Objectives: Hypothyroidism is a common canine condition which can be difficult to diagnose. Misdiagnosis can result in unnecessary life-long treatment. One complicating factor may be variation in thyroid hormone reference intervals between breeds, previously shown to be diagnostically important in sighthounds. Increasing age is associated with decreasing thyroxine and increasing TSH serum concentrations, but breed influence on this effect has not previously been explored. This projects aimed to investigate whether more, non-sighthound, breed-specific reference intervals would be appropriate and to discover whether breed influenced age-related thyroid changes. Methods: The study explored total and free, thyroxine and 3-5-3’-triiodothyronine (TT4, FT4, TT3, FT3), and thyrotropin (TSH) in 81,985 euthyroid dogs from 214 breeds using a database of serum thyroid profile results. Breed reference intervals (2.5 to 97.5 percentile) were created for 77 breeds with more than 140 cases. Results: Breed-specific reference limits differed; the lower limit for TT4 ranged from 7 (Sharpei) to 17 nmol/L (Cavalier King Charles Spaniel; CKCS) and the upper TSH limit from 0.44 (Soft Coated Wheaten Terrier) to 0.63 ng/ml ( Keeshond). There was a breed effect on age-related thyroid hormone decline and TSH increase. TT4 decline ranged from –0.021 (Basenji) to –1.324 (CKCS) nmol/L/yr. TSH increase ranged from 0.00097 (Bulmastiff) to 0.0137 (CKCS) ng/ml/yr. Statement (Conclusions): Breeds other than the sighthound group would benefit from their own breed-specific thyroid reference intervals, such as CKCS, as they differed significantly from all-breed intervals with a consequent risk of misdiagnosis. Some breeds also have quicker “thyroid-axis-ageing” than others.

Influence of medications on thyroid function in dogs: An update. Timothy A. Bolton, David L. Panciera. J. Vet. Intern. Med. July 2023; doi: 10.1111/jvim.16823. Quote: Erroneous thyroid function test results can occur because of drugs that alter thyroid hormone physiology in one or more aspects, including synthesis, secretion, distribution, and metabolism. Research since publication of the last review in the Journal of Veterinary Internal Medicine (JVIM) 20 years ago has evaluated the effects of amiodarone, zonisamide, inhalant anesthetics, clomipramine, trilostane, and toceranib on thyroid function tests in the dog. In addition, recent work on the effects of glucocorticoids, sulfonamides, phenobarbital, and nonsteroidal anti-inflammatory drugs will be reviewed. Awareness of these effects is necessary to avoid misdiagnosis of hypothyroidism and unnecessary treatment. ... The list of drugs studied and found to alter thyroid function test results in dogs has increased over the last 20 years. In general, dogs receiving glucocorticoids, phenobarbital, NSAIDs (eg, aspirin), sulfonamides, inhalant anesthetics, clomipramine, toceranib, amiodarone, and trilostane should have thyroid function test results interpreted with caution. For some drugs, such as glucocorticoids and sulfonamides, drug dosage and treatment duration dictate whether a clinically relevant impact on thyroid function will occur. If feasible, dogs given medications known to affect thyroid function should not even have thyroid testing performed because it is likely to result in inaccurate test interpretation and potentially unnecessary treatment. If thyroid function testing is performed, interpretation of abnormal test results in the context of history and physical examination findings is crucial. Knowledge of the drugs that affect thyroid function test results in dogs and the duration of drug withdrawal, if known, needed for resolution of such effects are required for accurate interpretation of thyroid test results.

Assessment of the likelihood of hypothyroidism in dogs diagnosed with and treated for hypothyroidism at primary care practices: 102 cases (2016-2021). Victoria Travail, Carolina Fernandez Sanchez, Jose M. Costo, Nicola Valentine, Megan Conroy, Venessa Lee, Dimitrios Bouziopoulos, Kathryn Bateman, Emma Gatehouse, Judith Cruzado-Perez, Danica Pollard, Valerie Lamb, Florence Juvet, Darren Kelly. J. Vet. Intern. Med. February 2024; doi: 10.1111/jvim.16993. Quote: Background: There is a possibility that an incorrect diagnosis of hypothyroidism could be made in euthyroid dogs, and the prevalence of hypothyroidism in the dog population remains unknown. Objectives: To retrospectively assess the percentage of dogs diagnosed with, and treated for, hypothyroidism at first opinion practice which are likely to be hypothyroid and require levothyroxine supplementation. Animals: One hundred two client-owned dogs were included in this study. ... Of the 102 included dogs, Of the 102 included dogs, there were ... 10 Labrador retrievers (9.8%), 9 Border collies (8.8%), 8 English springer spaniels (7.8%), 6 German shepherd dogs (5.8%), 5 Cocker spaniels (4.9%), 4 Golden retrievers (3.9%), 4 Boxers (3.9%), 4 Staffordshire bull terriers (3.9%), 3 Schnauzers (2.9%), 3 Cavalier King Charles spaniels (2.9%), ... Materials and Methods: The computerized databases of 7 first opinion practices were searched to identify dogs treated with levothyroxine supplementation. Three European College of Veterinary Internal Medicine—Companian Animals (ECVIM-CA) diplomates independently assigned 1 of 4 clinical assessments to each case as follows: confirmed or likely hypothyroid, hypothyroidism suspected but not confirmed, hypothyroidism considered unlikely, and no reason to suspect hypothyroidism. They commented as to whether or not they thought levothyroxine supplementation was appropriate. Results: The clinical assessments of “confirmed or likely hypothyroid”; “Hypothyroidism suspected but not confirmed”; “Hypothyroidism considered unlikely”; and “No reason to suspect hypothyroidism” was assigned respectively by Clinician 1 to 38.2%, 5.9%, 3.9%, and 52% of cases, by Clinician 2 to 48%, 22.6%, 22.6%, 6.9% of cases, and by Clinician 3 to 55.9%, 11.8%, 13.7% and 18.6%. Clinician 1, Clinician 2, and Clinician 3 considered levothyroxine supplementation not indicated in 58.8%, 52.9%, and 45.1% of cases, respectively.