Project Hope and Hypothyroidism

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Hope after successful treatment for hypothyroidism

Project Hope

New fund dedicated to detecting hypothyroidism in rescue dogs

Hope, the first dog taken into NGWPR foster care, remained in long term foster care with a loving family until her death. When first evaluated, she was hairless, lethargic, and near death with undiagnosed and untreated thyroid disease. She was also was extremely fearful. With loving, patience, and good medical care, she lived a wonderful life, and while in some situations still shy, the fear dissipated with treatment. Hope’s remarkable transformation served to educate many about this devastating disease.

As many rescue dogs may suffer from this illness, the National German Wirehaired Pointer Rescue organization believes that we are responsible to screen dogs at high risk before offering them for adoption.

Due to generous donations from Chuck Casanova and Robin K Nelson, DVM and Brian and Leslie R Dye, MD to begin funding for this project, these foundational contributions and additional donations will allow us to test all male rescues, aged 2–4 years and any dogs with symptoms (the groups at highest risk) with antibody testing. The cost of testing can be up to $200 with shipping, as only specialized laboratories offer the testing.

Canine Hypothyroidism: Anything New?

Robin K. Nelson, DVM

This article is reproduced from the Fall 2020 issue of Wire News with permission from Wire News and the author, Robin Nelson, DVM. Please find take home points at the end of the article.

Background

Hypothyroidism is arguably the most commonly diagnosed endocrine disease in dogs. The true incidence isn’t known. Confusion and inconsistencies make it difficult to establish a definitive diagnosis, so canine hypothyroidism tends to be one of the most over-diagnosed and therefore over-treated diseases in the dog. The term hypothyroidism needs to be reserved for the end stages of thyroid disease when the dog’s thyroid gland is proven to no longer produce sufficient hormones to sustain clinical health.

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The thyroid gland is a small gland located in the neck region on both sides of the trachea or windpipe. It produces two hormones. Thyroxine (T4) is the protein-bound reservoir hormone that maintains a steady concentration of free hormone. Triiodothyronine (T3) is the unbound hormone which is able to penetrate cell membranes, bind to receptors, and result in biologic activity. These two hormones are responsible for metabolism (the process of turning food into fuel) at the cell level. Thyroid hormones are involved in a wide variety of metabolic processes so virtually every organ in the body is affected when thyroid hormone is low. Hypothyroidism can be life-altering, but typically not life-threatening. Low thyroid hormone levels result in a constellation of clinical signs and laboratory abnormalities. Multiple hormone tests are required to make a diagnosis. Once the diagnosis is confirmed, it is fairly inexpensive and easy to provide life-long treatment.

Canine hypothyroidism occurs in young to middle-aged dogs. Large breed dogs have an earlier onset of development than small breed dogs and dogs with autoimmune disease tend to develop hypothyroidism at a younger age. 90- 95% of cases of canine hypothyroidism are primary and due to acquired immune-mediated destruction of the thyroid gland or idiopathic atrophy of the thyroid gland. Autoimmune thyroiditis, the heritable disease, is characterized histologically (under the microscope) by diffuse infiltration of lymphocytes, plasma cells, and macrophages in the thyroid gland. Antibodies interact with the follicular colloid or thyroglobulin antigens activate cell-mediated toxicity causing a progressive destruction of hormone-producing follicles and a secondary fibrosis. This process can eventually lead to failure of thyroid hormone production. No sex predisposition has been recognized regarding canine hypothyroidism. Idiopathically reduced thyroid function rarely occurs. Its cause is unknown, with no suspicion this is a heritable trait. The functional thyroid gland tissue is replaced by fat, therefore smaller amounts of thyroid tissue remains to produce thyroid hormone. There are no autoantibodies destroying the thyroid gland (TGAA NEG). Secondary forms of hypothyroidism include TSH deficiency, pituitary neoplasia, and Cystic Rathke’s pouch. Congenital cases have also been reported in dogs.

Signs and Symptoms of Hypothyroidism

Symptoms of canine hypothyroidism are often insidious and nonspecific. They can mimic other diseases leading to an incorrect diagnosis. Common clinical signs include lethargy, weight gain or obesity, exercise intolerance, and lack of desire to work or play. Chronic, recurring skin conditions such as seborrhea, pyoderma (skin infection), alopecia (hair loss often involving tail or collar region), puppy-like coats, or failure of hair to regrow after clipping are common. Hypothyroid dogs may present with chronic otitis (ear infection) or with lipid deposits in the corneas or dry eyes (keratoconjunctivitis sicca). Hypothyroid dogs may have irregular or absent estrus cycles, low libido, infertility, and litters with low birth weight puppies. Without adequate thyroid hormone, nerves cannot conduct electrical impulses normally. Neurological signs such as general weakness, poor coordination, seizures, or even unexplained, non-painful lameness can suggest hypothyroidism. Focal nerve problems associated with hypothyroidism include facial paralysis presenting clinically as a droopy eye or lip and vestibular disease, a sudden-onset disorder where the dog presents clinically with a head tilt, bizarre eye motion, and balance disruption.

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Hope before treatment

Hypothyroidism can affect the heart causing bradycardia (slow rate) or an abnormal rhythm. Other conditions suspected of being associated with hypothyroidism include megaesophagus (digestive tract problem causing regurgitation) and laryngeal paralysis (difficulty breathing). In moderate to severe cases of hypothyroidism, obvious thickening of the skin occurs secondary to accumulation of glycosaminoglycansan resulting in an obviously puffy appearance and thickened skin folds above the eyes. This puffiness, together with slight drooping of the upper eyelid, gives some hypothyroid dogs a very distinct “tragic” facial expression. A rare syndrome in the extreme expression of hypothyroidism is myxedema coma.

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A rare syndrome int eh extreme expression of hypothyroidism is myxedema coma

Hypothyroidism is suspected of causing aggression or abnormal behavior in German Wirehaired Pointers. In one retrospective study performed at MSU, there was actually a negative correlation between a history of aggression and hypothyroidism translating to…dogs with a history of aggression were LESS likely to be hypothyroid. Michigan State University states there have been anecdotal reports of canine hypothyroidism resulting in aggression which may be the effects of hypothyroidism making a dog “irritable.”

Some dogs show few, if any, signs of hypothyroidism other than behavioral problems

In human medicine, a wide variety of behavioral symptoms have been reported in hypothyroid patients including: reduced cognitive function and concentration, impaired short-term memory, visual and auditory hallucinations, and fear ranging from mild anxiety to frank paranoia. Mood swings and aggression have also been reported in hypothyroid human patients.

More signs and symptoms

These dogs may even be underweight and hyperactive not the typical lethargic and obese. Some dogs present with a sudden onset of aggression-usually owner directed or intraspecific (other dogs). Canine hypothyroidism has been confirmed as an underlying condition in some of these aggressive dogs. Dogs that are fearful and show nervousness early lead behaviorists to suggest anticipatory fear and anxiety leads to the aggression placing less emphasis on the thyroid disease. More research needs to be done to pursue aggressive behavior in dogs and underlying hypothyroidism.

Possible seizures, manifested as dangerous episodes of aggression, have been speculated about for decades. Terms used over the years to describe dangerous aggression include: limbic seizures, psychomotor seizures, rage syndrome, episodic dyscontrol, mental lapse aggression, and sudden onset idiopathic aggression.( SOIA) Sadly, the link between seizure activity and aggressive behavior in dogs also remains poorly investigated. There is very little information in the literature. These dogs may or may not have underlying thyroid disease. Episodic dyscontrol or rage syndrome was diagnosed using clinical history, electroencephalographic findings, and response to treatment with phenobarbital in a few dogs. Clinical features included a mood change, possible irritability heralding aggressive outbursts directed at people or objects, and a post- aggression phase characterized by lethargy and lack of responsiveness. At some point, the mood changes are so extreme and the behavior so different that another explanation is sought to replace the original more typical “dominance-related aggression” label. Owners become able to detect these mood changes in their dogs prior to aggressive outbursts of growling, barking, and biting. Aggression is more likely to occur when the dog is tired and can sometimes be triggered by loud noises. Eyes become glazed, pupils dilated, and the dog enters a “trance-like” state.

Episodic dyscontrol is described as outbursts of aggressive behavior in children and adults with boys being affected more frequently than girls. By definition, episodic dyscontrol in humans consists of recurrent attacks of uncontrollable rage usually with minimal provocation and often out of character. There is sometimes a family history of violent behavior especially in the case of fathers, suggesting a genetic component. More research is needed to determine if these episodes are due to transient hormonal factors, learned behaviors or some type of aggression threshold breakdown. The most important diagnostic pointer for episodic dyscontrol is the lack of provocation to justify this type of behavior.

During the unpredictable, unprovoked aggression episodes in dogs, the dogs’ eyes are often black and glazed. The speed at which a dog gets out of control is frightening. The dog may not respond to his name or any command, seemingly intent on getting to the face or neck of the perceived target. Episodic dyscontrol or “rage syndrome” is well documented in English Springer Spaniels and can be traced back to a winner at the Westminster Kennel Club dog show who went on to become a top stud (Popular sire effect) supporting possible genetic factors. Other affected breeds include Cocker Spaniels, Border Collies, Rottweilers, and Bernese Mountain Dogs, to name a few. Many dogs display first symptoms of aggression on or around one of the critical learning periods identified in dogs. The genetics of the breed and of the parents in particular, play an important role in how sociable, playful, fearful, excitable, or domineering a puppy becomes. Puppies under three months of age are still developing their social skills and many problem behaviors do not begin to emerge until sexual or social maturity. When a dog is diagnosed with episodic dyscontrol, the condition is rarely treatable, even if an underlying thyroid condition is addressed. There have been minor successes treating individuals with phenobarbital (anti-seizure) medication, but because of the nature of the disorder and its unpredictable violence, often the recommendation is humane euthanasia. The stress of what is happening, the risks and dangers to family and other dogs, friends, neighbors, all need to be considered. Overall quality of life and the hope of or odds of a turn-around are dismal. Attacks cannot be prevented with training because this is a problem the dog cannot consciously control. The attacks often occur without apparent cause although some dogs may seem to have “triggers.” Some dogs show few, if any, signs of hypothyroidism other than behavioral problems.

A German Wirehaired Pointer being considered for a breeding program needs to be tested for thyroid disease.

OFA Rank and Thyroid

The GWPCA has lowered its OFA thyroid profile rank and increased normal thyroid profile numbers by not breeding dogs with immune-mediated thyroiditis.

GWPs ranked 9th in breed statistics for thyroid disease through December 2012 with a total of 385 GWPs tested: 11% were abnormal, 76% normal with the remaining 13% equivocal. Our CHIC Program required an OFA Thyroid profile beginning in 2008. There have been a total of 1033 OFA thyroid evaluations for GWPs from 1974–2019. Increased numbers of OFA thyroid profiles prove our members recognize and test for thyroid disease in our breed. A total of 648 OFA Thyroid profiles have been run in 7 years allowing our GWP rank to drop from 9th to 16th. 80.3% of dogs tested Normal, autoimmune thyroiditis affected 8.5% of GWPs and 10.7% tested Equivocal.

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Whether testing a GWP in a breeding program for immunemediated thyroid disease or screening a dog based on clinical signs of the disease, ALL thyroid profile numbers must be examined in conjunction with clinical evaluation of the animal. An annual chemistry profile which includes a TT4 is an excellent “screening tool” for hypothyroidism if a dog is clinically normal and not being used in a breeding program. Many commercial labs include a TT4 in a metabolic panel for a nominal fee. If the TT4 is low and the panel shows elevated cholesterol levels or a mild non-regenerative anemia, more testing needs to be done. Approximately 75- 80% of hypothyroid dogs have elevated fasting cholesterol levels. A mild non-regenerative anemia is present in 30–40% of hypothyroid dogs and should be pursued with further testing. SDMA, a newer biomarker for kidney disease can also be significantly higher in hypothyroid dogs.

GERMAN WIREHAIRED POINTERS showing clinical signs suggesting thyroid disease or unexplained behavior or aggression should be tested for hypothyroidism

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Testing for Hypothyroidism

  1. Serum Total thyroxine or TT4

The vast majority of dogs with hypothyroidism have a serum T4 below normal, but some NORMAL dogs may have a low T4. In-house testing of TT4 is NOT recommended since 50% of normal dogs have a low serum T4 at some time during the day. A diagnosis of hypothyroidism can be ruled out if the TT4 is in the upper 50% of the lab’s reference range. Autoantibodies to T4 which occur in approximately 10–15% of hypothyroid dogs may falsely elevate the serum T4 concentration from below normal into the normal range so the T4 antibodies need to be interpreted with the TT4.

2. Serum Free T4 (FT4)

Since T4 is highly protein-bound in the circulation and can be altered by many non-thyroid illnesses and by certain drugs, measurement of the inbound or free T4 can provide a more accurate assessment of thyroid function. ***Measurement of fT4 by equilibrium dialysis should be performed when uncommon clinical signs of hypothyroidism are present, the dog is being treated with a drug that may affect thyroid function, when non-thyroidal illness is present, and if autoantibodies to T4 are detected.

3. Serum TSH

Primary hypothyroidism results in a decrease in T4 with decreased negative feedback causing the pituitary gland to secrete more TSH (thyroid stimulating hormone). Serum levels of TSH increase as more thyroid hormone is needed. In the dog, TSH concentration is elevated in 65–75% of cases of hypothyroidism so it cannot be used as a single screening test. ***25–35% of dogs with hypothyroidism have normal TSH.

4. Thyroid Autoantibodies

Antibodies against T4 or T3 or both are sometimes present in dogs with autoimmune thyroiditis. The presence of these antibodies does NOT indicate that the dog is hypothyroid, but suggests that autoimmune thyroid disease is present. ***Autoantibodies frequently cause false elevation of T4 or T3 making it confusing and difficult to interpret these numbers. Dogs with autoimmune thyroiditis have circulating antibodies to thyroglobulin, the primary protein making up the colloid of the thyroid gland. ***TGAA (thyroglobulin autoantibodies) is a measurable marker for the presence of immune-mediated thyroid disease. More than 60–70% of the thyroid tissue needs to be destroyed before changes occur in laboratory measures of thyroid function. The majority of dogs that develop autoantibodies do so by 3–4 years of age. Development of high levels of autoantibodies at any time in a dog’s life is an indication that the dog most likely has the genetic form of thyroid disease. ***In a longterm study at Michigan State University, 20% of asymptomatic, anti-thyroglobulin positive dogs with normal thyroid function progressed to hypothyroidism in one year.

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1. Free T4

The metabolically active fraction of T4 is considered the “gold standard” for assessment of the thyroid’s production and cellular availability of thyroxine. It is less affected by nonthyroidal illness and drugs than TT4. Measurement of fT4 should be done by equilibrium dialysis expecting results to decrease in dogs with thyroid dysfunction due to autoimmune thyroiditis

2. Canine Thyroid Stimulation Hormone (cTSH)

cTSH helps determine the site of the thyroid pathology: autoimmune thyroiditis — the lesion is at the level of the thyroid gland and the pituitary gland in the brain functions normally. cTSH is expected to be elevated in dogs with thyroid atrophy from autoimmune thyroiditis

3. Thyroglobulin Autoantibodies (TGAA)

Elevated TGAA is an obvious confirmation of immune-mediated thyroid disease. Antibodies against thyroglobulin are produced during the disease process of lymphocytic thyroiditis. ***In some animals this process never progresses to cause clinical disease. ***Because of the known hereditary component to the development of thyroiditis, measuring TGAA is used to identify animals predisposed to hypothyroidism prior to breeding before clinical signs have developed.

Looking at thyroid profiles, certain breeds have normal ranges of thyroid hormones that are different from most other breeds. Few have been specifically evaluated, but Sighthounds (Greyhounds, Scottish Deerhounds, Salukis, Whippets) have serum TT4 and fT4 concentrations that are considered lower than most other breeds. Lower T4 concentrations are also seen in normal Alaskan sled dogs.

When interpreting thyroid profile results, the dog’s clinical presentation and the possibility of Euthyroid Sick Syndrome must be considered. It is well documented that thyroid hormone concentrations can decrease as part of a metabolic response to nonthyroidal illness.

Alternative Explanations for decreases in thyroid laboratory values

Infectious, endocrinologic, and cancerous illnesses can all cause low thyroid values

Seizure medications, prednisone, or other corticosteroids- including topical medications for eyes and ears, NSAIDS or nonsteroidal anti-inflammatory drugs used for injury or arthritis pain like Deramaxx or Rimadyl (carprofen) , separation anxiety medication like clomipramine can all contribute to lower thyroid hormone numbers. Sulfonamide antibiotics, sometimes prescribed for urinary tract disease, can actually trigger a “reversible” hypothyroid state with numbers returning to normal after withdrawing medication. Physiologic adaptations to decreased cell metabolism during periods of illness cause changes in thyroid hormone production, the characteristics of serum protein binding, and the altered metabolism of thyroid hormones which may all contribute to the false low results. Despite low numbers, the dog remains euthyroid or normal at the cellular level and should NOT be treated. More than 60–70% of the thyroid tissue needs to be destroyed before changes occur in laboratory measures of thyroid function. This process can take months or years to cause classic hypothyroidism. *** In some dogs, it may not progress.

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Treatment is usually simple with medication

Treatment for Hypothyroidism

Once a diagnosis has been confirmed, treatment for canine hypothyroidism is fairly simple and inexpensive with daily synthetic thyroid hormone replacement. Levothyroxine is the only hormone that appears necessary for treatment. Studies have shown most dogs can be regulated with once-daily levothyroxine administered on an empty stomach usually initiated at .02mg/kg every 24 hours. In clinical practice, some dogs seem to respond better to twice daily medication, so it is still an option. The bioavailability of thyroxine can range from 13–87% in the same dog from day to day. Most dogs show clinical improvement within the first 1–2 weeks of therapy with increased and more normal activity and improved attitude. Cutaneous manifestations of hypothyroidism may take several weeks to months to resolve. After four weeks of supplemental therapy, blood is collected 4–6 hours post-pill for T4 measurement. The post-pill T4 should be at the upper end of the reference range or slightly above. If a dog has a “questionable diagnosis” and a trial with T4 supplementation is suggested because of a strong clinical presentation consistent with hypothyroidism and non-thyroidal illness has been ruled out, an entire “profile” should be run. An objective case review should be conducted after 6–8 weeks of trial therapy for evidence of clinical improvement. Therapy should be discontinued if clinical signs and thyroid function numbers don’t support the diagnosis. Therapeutic monitoring during treatment is lifelong.

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TAKE HOME POINTS for GWP OWNERS:

  • With your veterinarian’s help, learn to read and understand your dog’s OFA Thyroid Profile. Check for TGAA- if present, results suggest thyroid pathology- usually autoimmune thyroiditis, but in older patients, possible thyroid neoplasia (cancer). The absence of TGAA doesn’t exclude the possibility of thyroid dysfunction, but it’s less likely. The OFA Thyroid Profile will help identify dogs that are phenotypically normal for breeding programs. An OFA number is issued to all dogs found to be normal at 12 months of age, but dogs in a breeding program should be re-examined at 2, 3, 4, (6 and 8) years of age. Because of the variable onset of the presence of thyroid autoantibodies, periodic testing is necessary. The majority of affected dogs will have autoantibodies by 4 years of age. ***All data whether normal or abnormal should be submitted to OFA for completeness. A GWP must be 2 years of age for the thyroid profile to qualify under current GWPCA CHIC requirements.
  • Canine hypothyroidism is heritable, so knowing the status of a dog and the status of the dog’s lineage allows breeders to decide which matings are most appropriate for reducing the incidence of autoimmune thyroiditis in GWP offspring. ***Laboratory and pedigree analyses of affected families show a progressive earlier age of onset of thyroiditis and clinical signs of dysfunction, as well as an increased portion of affected vs normal offspring in successive litters.
  • Breeding normal testing dogs that have come from litters which have mostly tested normal is recommended. ***Always retest equivocal results. Testing is not simple or perfect. Discordant test results are common and retesting can be required
  • Ruling out hypothyroidism as a contributing factor to aggression, “irritability”, and abnormal behavior is valuable.
  • It would be interesting to analyze our GWP data checking trends in our TT4, fT4, numbers as a “group.”

Email Robin K Nelson at gwpoint@aol.com with any questions

References:

  1. Brunette, David. Canine Hypothyroidism. Chicago Vet 2019
  2. Hanseltine, Johanna. Canine Hypothyroidism: Diagnosis and Treatment. TVP March/April 2019
  3. Dodman, NH, Miczek, KA, Knowles, K, Thelhammer, JG, Shuster, L. Phenobarbital-responsive episodic dyscontrol (rage) in dogs. JAVMA Vol 201 No 10 Nov 15 1992 1580–3
  4. Aronson, LP, Dodds, W. J. The Effect of Hypothyroid Function on Canine Behavior. Pet Shrink 2008
  5. Landsberg, GM. Is It Medical or Is It Behavioral? Companion Animal Behavior Therapy Study Group 2008
  6. Peterson, M. Hypothyroidism in Animals. Merck Manual 2019
  7. Leviton, D M. Canine Hypothyroidism — Are You Over Treating? Atlantic Coast Veterinary Conference 2016
  8. Horowitz, D, Lansbury, G. Puppy Behavior and Training- Socialization and Fear Prevention. Behavior Pet Services
  9. Shell, L, Rothrock, K. Hypothyroidism, Acquired. Vincyclopedia of Diseases 2018
  10. Please refer to Dr Sharon Albright’s article Spring 2020 Wire~News page 17 for the latest research regarding new test method development for Canine Hypothyroidism.
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About Us

National GWP Rescue is a nationwide rescue program whose volunteers work tirelessly to provide funding, foster homes, medical care and training for GWPs found in shelters, animal control facilities and to those GWPs whose current owners are unable to provide a suitable situation.

Working hand- in-hand with governmental and local shelters, NGWPR provides a safe and responsible home for GWP’s in need. Placed with an experienced GWPCA member, fostered GWPs that have been neglected, untrained or have medical issues quickly blossom as they are readied for their “forever” homes.

Prior to releasing our rescued GWPs for adoption, volunteers provide obedience, manners, and house training. We hold to the philosophy that a mannerly dog has a better chance of fitting into a new household.

NGWPR believes that Wires were designed to hunt and unlike some other rescue programs, we are happy to place dogs with field experience or bird instinct with potential owners who enjoy hunting behind a Wire. However, NGWPR insists that any rescue dog first be a house dog and companion, then a weekend hunting partner.

Please go to our website to learn more.

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We believe that the more we educate people the more likely we are to accomplish our mission of matching homeless GWPs with loving owners.

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