COMMENTS ON THYROID DISEASE
BY DR. THOMAS
One of the
simplest and least expensive tests to have done, which could possibly reduce or stop
seizures, is a test for low thyroid function or hypothyroidism. I have found from
experience that thyroid testing is very important in every case of canine epilepsy.
Dr. William Thomas, a board-certified neurologist, had this to say about thyroid testing:
1. Thyroid testing should be considered in any dog with recurrent seizures. Although the
relationship between hypothyroidism and recurrent seizures is unclear, thyroid testing is
relatively inexpensive and carries little risk to the patient.
2. In general, any dog that is diagnosed with hypothyroidism by appropriate testing should
be treated with thyroid replacement therapy. This applies to all dogs, whether or not they
suffer seizures. If the seizures improve with thyroid therapy, then great! If not, the
patient should still be treated because hypothyroidism can cause many other health
problems.
3. Thyroid replacement therapy is not indicated in dogs with seizures if the patient has
*not* been diagnosed with hypothyroidism. There are potential risks associated with any
therapy, so subjecting the patient to unnecessary treatment is rarely a good idea. On the
other hand, appropriate use of thyroid medication is one of the more safe and effective
treatments available in veterinary medicine.
4. Many illnesses as well as some drugs, including Phenobarbital, will lower the level of
certain thyroid hormones (for example, T4) without causing clinically significant
hypothyroidism. Thyroid replacement therapy is not indicated in these instances.
Measurement of a T4 concentration alone does not allow discrimination between true
hypothyroidism and the effects of drugs and illnesses. In these patients diagnosis of
hypothyroidism requires measurement of several different parameters of thyroid function
("thyroid panel").
Sincerely,
WB Thomas DVM
Dipl.ACVIM(Neurology)
University of Tennessee
Knoxville, TN
wthomas@utk.edu
INTERVIEW WITH DR. DODDS
Based on Dr. Thomas'
recommendations, I sat down with Dr. Jean Dodds for an overview on
hypothyroidism which follows.
W. Jean Dodds, DVM, is a nationally and internationally recognized authority
on blood and
immune disorders, thyroid disease and nutrition. Dr. Dodds is the president of Hemopet/Pet
Lifeline, the first national nonprofit animal blood bank and greyhound rescue/adoption
program serving North America. Hemopet also conducts nonprofit clinical research studies.
Dr. Dodds has
always been available to those with questions about hypothyroidism, blood and immune
disorders, and nutrition.
I hope all of this is helpful...
Joanne and Asia
Joanne Carson, Ph.D.
Dr. Joanne Carson: Dr.
Dodds, why should a dog with seizures have a thyroid panel done to test for low thyroid
function or hypothyroidism?
Dr. Jean Dodds: Because thyroid dysfunction can precipitate or aggravate existing seizure
disorders. The mechanism is unknown, but may relate to the vital role of thyroid hormones
in cellular metabolism of the central nervous system. In some cases the seizures are related to thyroid dysfunction and when placed on
appropriate thyroid medication the seizures may no longer occur or are reduced in severity
or frequency.
Dr. Carson: What are some of the classic symptoms of hypothyroidism?
Dr. Dodds: There are more than 50 different symptoms of hypothyroidism. Classical signs
include chronic skin disease, hair loss, weight gain, lethargy and slow
metabolism,
although behavioral changes (aggression, hyperactivity, poor concentration, passivity,
phobias, anxiety or neuromuscular events such as seizures), and many other signs of
metabolic imbalances also can occur. This condition can mimic other disorders.
Dr. Carson: How many symptoms would a dog need to have to suspect hypothyroidism and have
a thyroid panel done?
Dr. Dodds: Only one symptom may be present to suspect low thyroid function. Seizures can be
a symptom of thyroid imbalance, which warrants performing a full thyroid panel.
Thyroid dysfunction in dogs is nearly always caused by low levels of thyroid hormones.
(i.e., HYPOthyroidism). The rare exception would be in thyroid cancer which
may, but not
always, produce signs of HYPERthyroidism. As the
thyroid gland controls all metabolic functions, symptoms of hypothyroidism are many and
can mimic a variety of other conditions. Affected dogs can show only one, or several or
even many classical symptoms, which begin in subtle
ways and then usually progress to more obvious signs as the disease process that destroys
thyroid tissue becomes more advanced. This can take months to years. Occasionally symptoms
disappear without treatment and the gland recovers.
Dr. Carson: What kind of thyroid tests are important and why?
Dr. Dodds: Because the diagnosis of hypothyroidism is often complicated, we need to run
complete thyroid profiles (i.e., T3, T4, free T3, free T4, T3 and T4 auto antibodies, plus
thyroglobulin auto antibody and TSH where indicated) rather than just one or two analytes
(e.g., T4, TSH, free T4) We need to look at the whole picture along with the clinical
history of the seizing animal, breed and family history for likelihood of seizure disorder
and thyroid disease. When I interpret profiles and make recommendations, I take all these
factors, including drugs being given, into consideration.
Dr. Carson: If a dog is diagnosed with low thyroid function, how soon after starting on
thyroid medication should thyroid re-testing be done and why?
Dr. Dodds: After 6 to 8
weeks on thyroid supplementation given twice daily, at the appropriate dose for the dog's
age, breed and weight, the thyroid levels should be retested to determine whether the
current dose is correct This sample needs to be drawn 4 to 6 hours after the morning pill
was given. IMPORTANT: Correct therapeutic ranges at that time should be at the upper 1/3
to 25% above the upper limits of the lab reference ranges (except for geriatric dogs or
sight hounds where mid-range is adequate).
Dr. Carson: If thyroid medication raises the metabolism, is it possible that Phenobarbital
and potassium bromide levels could change? If so, when should these levels be tested after
starting on thyroid supplementation?
Dr. Dodds: Yes, drug metabolism and drug clearance from blood and tissues can be altered
when body metabolic function is raised, such as with thyroid supplement. This could result
in raising or lowering Phenobarbital and potassium bromide levels in individual dogs,
depending upon their liver function and effectiveness of drug binding/clearance
mechanisms. Other drugs, chemical and toxic exposures, or stress situations present in
these dogs could also alter metabolism of thyroid and anticonvulsant medications.
Dr. Carson: I've heard that Phenobarbital can cause a low thyroid reading. Is this true
hypothyroidism and should a thyroid medication be used?
Dr. Dodds: Drug effects on thyroid binding proteins and thyroid levels do not produce true
hypothyroidism, and so treatment with thyroid supplement is unadvisable. However, many
dogs with seizure disorders have thyroid dysfunction independent of Phenobarbital use, and
so significantly lowered thyroid levels---especially of free T4---indicate the likely
benefits of thyroid treatment for assisting in seizure control and any other metabolic
symptoms of hypothyroidism that also may be present (e.g., chronic skin disease, weight
gain, lethargy).
It is well known that Phenobarbital and some other drugs, such as potentiated sulfonamides
can affect blood levels of thyroid hormones. With the sulfonamides, after long-term use, a
clinically hypothyroid state can be produced. Regardless, it is typically the total T4
level that is most affected, with the free T4 being affected much less and temporarily,
depending to some extent on how it was measured.
Dr. Carson: Quite a few vets use only a TSH test to test for low thyroid function on epi's
taking Phenobarbital. Is this an accurate test?
Dr. Dodds: TSH is NOT a reliable assay when used by itself in the dog, and generally has
poor sensitivity and predictive value in the dog. This is in contrast to the use of
endogenous TSH assays in people which work very well.
Here are four very recent studies that support the fact that using endogenous canine TSH
as the sole assay is unreliable for diagnosing canine hypothyroidism.
JAVMA, Vol 212 1998 - Effect of time of sample collection on serum thyroid-stimulating
hormone concentrations in euthyroid and hypothyroid dogs. - Bruner, Scott-Moncrieff,
Williams.
CONCLUSIONS:
This study demonstrates the limitations of the current c-TSH assay. In the present study,
serum c-TSH was supportive of hypothyroidism in only 37% of the samples obtained from
spontaneously hypothyroid dogs. A normal serum
c-TSH concentration does not exclude hypothyroidism as a diagnosis. Current c-TSH assays
are often unnecessary for the diagnosis of hypothyroidism. (J Am Vet Assoc 1998,-
212:1572-1575)
Vet Clin Pathol 1999
28:16-19 - Biological Variation of Canine Serum Thyrotropin (TSH) Concentration - Iversen,
Lundord-Jensen, Holer, Aaes
PUBLISHED
STUDY: 77% OF DOGS WITH SEIZURES HAVE LOW THYROID SEE TABLE 2 BEHAVIORAL
CHANGES ASSOCIATED WITH THYROID DYSFUNCTION IN DOGS W.
Jean Dodds, DVM and Linda P. Aronson, DVM In
North America, the principal reason for pet euthanasia stems not from disease,
but undesirable behavior. While this abnormal behavior in dogs and cats
can have a variety of medical causes, it also can reflect underlying problems of
a psychological nature. Inheritance
has been shown to play an important role in the behavior of both animals and
humans. The role of inheritance in behavior was reviewed by Plomin (Science
248:183-188, 1990), who pointed out that the genetic influence on behavioral
disorders rarely accounts for more than half of the phenotypic expression of
behavioral differences. Each of the multiple genes involved has a small
effect on behavior. Development and application of newer techniques in
molecular biology offers the promise of identifying the DNA marker sequences
responsible for behavioral variation. However, behavior is the most
complex phenotype because it reflects not only the functioning of the whole
organism but also is dynamic and changes in response to environmental
influences. With respect to animal behavior, applied behavioral genetics
was first studied several thousand years ago because animals were bred and
selected for their behavior as much as their conformation. The results can
be attested to by the dramatic differences in behavior and physique among
various dog breeds. Today these breeds have a great range of genetic and
behavioral variability. Many
investigators in recent years, have noted the sudden onset of behavioral changes
in dogs around the time of puberty. Most of the dogs have been purebreds
or crossbreds with an apparent predilection for certain breeds. For a
significant proportion of these animals, neutering does not alter the symptoms
and in some cases the behaviors intensify. The seasonal effects of
allergies to inhalants and ectoparasites such as fleas, followed by the onset of
skin and coat disorders including pyoderma, allergic dermatitis, alopecia, and
intense itching, have also been linked to changes in behavior. Another
interesting association which as been increasing in frequency is the link
between thyroid dysfunction and aberrant behavior. Typical clinical signs
include unprovoked aggression towards other animals and/or people, sudden onset
of a seizure disorder in adulthood, disorientation, moodiness, erratic
temperament, periods of hyperactivity, hypo-attentiveness, depression,
fearfulness and phobias, anxiety, submissiveness, passivity, compulsiveness, and
irritability. After the episodes, a majority of the animals were noted to
behave as if they were coming out of a trance- like state and were unaware of
their previous behavior. A
similar association between behavioral and psychologic changes and thyroid
dysfunction has been recognized in humans since the 19th century, and more
recently has been noticed in cats with hyperthyroidism. In a recent human
study, 66% of patients with attention deficit-hyperactivity disorder were found
to be hypothyroid, and supplementing their thyroid levels was largely curative. The
mechanism whereby diminished thyroid function affects behavior is unclear.
Hypothyroid patients have reduced cortisol clearance, and the constantly
elevated levels or circulating cortisol mimic the condition of an animal in a
constant state of stress, as well as suppressed TSH output and production of
thyroid hormones. In humans and seemingly in dogs, mental function is
impaired and the animal is likely to respond to stress in a stereotypical rather
than a reasoned fashion. Chronic stress in humans has been implicated in
the pathogenesis of affective disorders such as depression. Major
depression has been shown in imaging studies to produce changes in neural
activity or volume in areas of the brain which regulate aggressive and other
behaviors. Dopamine and serotonin receptors have been clearly demonstrated
to be involved in aggressive pathways in the CNS. Hypothyroid rats have
increased turnover of serotonin and dopamine receptors, and an increased
sensitivity ot ambient neurotransmitter levels. In dogs with aberrant
aggression, a large collaborative study at Tufts University has shown a
favorable response to thyroid replacement therapy within the first week of
treatment, whereas it took about three weeks to correct their metabolic
deficit. Dramatic reversal of behavior with resumption of previous
problems has occurred in some cases if only a single dose is missed. A
similar pattern of aggression responsive to thyroid replacement has been
reported in a horse. Tables
1 and 2 summarize results of complete thyroid diagnostic profiling on 634 canine
cases of aberrant behavior, compiled by the authors in collaboration with Drs.
Nicholas Dodman, and Jean DeNapoli of Tufts University School of Veterinary
Medicine, North Grafton, MA. *Ninety
percent (568 dogs) were purebreds and 10% were mixed breeds. *There
was no sex predilection found in this case cohort, whether or not the animals
were intact or neutered. *63%
had thyroid dysfunction as judged by finding 3 or more abnormal results on the
comprehensive thyroid profile *The
major categories of aberrant behavior were: aggression (40% of cases),
seizures (30%), fearfulness (9%), and hyperactivity (7%); some dogs exhibited
more than 1 of these behaviors. *Thyroid
dysfunction was found in 62% of the aggressive dogs, 77% of seizuring dogs, 47%
of fearful dogs, and 31% of hyperactive dogs. *Outcomes
of treatment intervention with standard twice daily doses of thyroid replacement
were evaluated in 95 cases. Of these, 58 dogs had greater than 50%
improvement in their behavior as judged by a predefined 6-point subjective scale
(34 were improved >75%), and another 23 dogs had >25 but <50%
improvement. Only 10 dogs experienced no appreciable change, and 2 dogs
had a worsening of their behavior. When compared to 20 cases of dominance
aggression treated with conventional behavioral or other habit modification over
the same time period, only 11 dogs improved >25% and of the remaining 9
cases, 3 failed to improve and 3 were euthanized or placed in another
home. These initial results are so promising that complete thyroid
diagnostic profiling and treatment with thyroid supplement, where indicated, is
warranted for all cases presenting with aberrant behavior. References Baverman LE, Utiger RD (eds). Werner and Ingbar's The Thyroid: A
Fundamental and Clinical Text, 7th ed. Philadelphia, Lippincott-Raven,
1996. Cameron DL, Crocker AD. The hypothyroid rat as a model of increased
sensitivity to dopamine receptor agonists. Pharm Biochem Behav 37:627-632,
1990 Denicoff KD, Joffe RT, Lakschmanan MC, Robbins J, Rubinow DR.
Neuropsychiatric manifestations of altered thyroid state. Am J Psych 147:94-99,
1990 Dewey CW, Shelton GD, Bailey, CS. Neuromuscular dysfunction in five dogs
with acquired myasthenia gravis and presumptive hypothyroidism. Prog
Vet Neurol 6:117-123, 1995. Dodds,
WJ. Estimating disease prevalence with health surveys and genetic
screening. Adv Vet Sci Comp Med 39: 29-96, 1995. Dodds WJ. What's new in thyroid disease? Proc AM Hol Vet Med
Assoc 1997; pp 82-95. Dodman NH, Mertens PA, Aronson, LP. Aggression in two hypothyroid dogs,
behavior case of the month J Am Vet Med Assoc 207:1168-1171, 1995. Happ GM. Thyroiditis - A model canine autoimmune disease. Adv Vet
Sci Comp Med 39: 97-139, 1995. Hauser P, Zametkin AJ, Martinez, P et al. Attention deficit-hyperactivity
disorder in people with generalized resistence to thyroid hormone. N
Eng J Med 328:997-1001, 1993. Henley WN Chen X, Klettner C. Bullush LL, Notestine MA. Hypothyroidism increases
serotonin turnover and sympathetic activity in the adult rat. Can J
Physiol Parmacol 69:205-210, 1991. Table
1. Canine Aberrant Behavior * *
Mean Age, 3.7 years (Range 0.5-12 years). Median Age, 2.5 years. Table
2. Most Commonly Represented Breeds with Thyroid Dysfunction and Aberrant
Behavior* (63%) (40%) (30%) (9%) (7%) 63% (62%) (77%) (47%) (31%) *
Some dogs had more than 1 abnormal behavior. Numerator = Thyroid
Dysfunction. Denominator - Aberrant behavior Reprinted from Proceedings 1999
American Holistic Veterinary Medical Association Annual Conference, pp. 80-82.
Authors:
W. Jean Dodds, DVM, Hemopet, 938 Stanford Street, Santa Monica, CA 90403 and
Linda P. Aronson, DVM, Tufts University School of Veterinary Medicine, 200
Westboro Road, North Grafton, MA 01536.
Total
No. Cases
Purebreds
Mixed
Breeds
Thyroid
Dysfunction
Euthyroid
634
568
66
401
233
Breed
Thyroid
Dysfunction 401/634
Aggression
251/634
Seizures
189/634
Fearful
55/634
Hyperactive
42/634
Golden
Retriever
50/73
12/16
22/30
4/6
1/6
German
Shepherd
34/53
10/22
14/16
3/7
2/2
Akita
27/38
24/33
0/1
0
0/2
Labrador
Retriever
8/30
6/11
12/16
2/15
0/3
Shetland
Sheepdog
14/25
3/6
2/3
2/4
3/3
Collie
8/9
0
7/7
0
0
English
Setter
4/6
1/1
0
1/3
1/2
Other
Purebreds
217/334
89/135
72/93
10/15
5/16
Mixed
Breeds
39/66
11/27
16/23
4/5
1/8
Totals
401/634
156/251
145/189
25/55
13/42
CONCLUSIONS:
The present study was to estimate the between-dog, within-dog and analytical components of
variance for serum thyrotropin (TSH) in healthy dogs. The number of samples required to
determine the true mean value in a single dog
was 40. Comparing a single serum TSH measurement from an individual dog to the
conventional population-based reference range may be too insensitive to detect small but
important changes in the serum TSH level of that particular dog. (Vet Clin Pathol 28:16-19
1999)
JAVMA, Vol 211 No. 11 December 1, 1997- Measurement of serum total thyroxine,
triiodothyronine, free thyroxine, and thyrotropin concentrations for diagnosis of
hypothyroidism in dogs. - Peterson, Melian, and Nichols.
CONCLUSIONS:
Results indicate that measurement of serum free 1 and TSH concentrations is
useful for diagnosis of hypothyroidism in dogs. About a quarter of the dogs with confirmed
hypothyroidism, however, will have serum
TSH concentrations within reference limits (J Am Vet Med Assoc 1997:211;1396-1402)
JAMVA, Vol 212. No. 3, February 1, 1998 - Comparison of serum concentrations of
thyroid-stimulating hormone in healthy dogs, hypothyroid dogs, and euthyroid dogs with
concurrent disease - Scott-Moncrieff, Nelson, Bruner, and Williams
CONCLUSION:
cTSH assay had good specificity for use in the diagnosis of hypothyroidism in
dogs. Because this assay had low sensitivity, a diagnosis of hypothyroidism could not be
excluded on the basis of a serum cTSH concentration that was within the reference range. (
J Am Vet Med Assoc l998:212:387-391)
Dr. Carson: Thank you Dr. Dodds. You have always been a wealth of information and always
accessible for questions.
W. Jean Dodds, DVM
resume'
Dr. Dodds was born on January 4, 1941. She received her D.M.V. in 1964 from the Ontario
Veterinary College. In 1965 she moved to the New York State Health Department is Albany
and began comparative studies of animals with inherited and acquired bleeding diseases.
This work continued full time until 1986 when she moved to Southern California to
establish Hemopet, the first nonprofit national blood bank program for animals.
From l965 to l986, she was a member of many national and international committees on
hematology, animal models of human disease, veterinary medicine, and laboratory animal
science. Dr. Dodds was a grantee of the National Heart, Lung, and Blood Institute (NIH)
and has over 150 research publications. She was formerly President of the Scientist's
Center for Animal Welfare, and Chairman of the Committee on Veterinary Medical Sciences
and Vice Chairman of the Institute of Laboratory Animal Resources, National Academy of
Sciences. In 1974 Dr. Dodds was selected as Outstanding Woman
Veterinarian of the Year, AVMA Annual Meeting, Denver, Colorado; in 1977 received the
Region I Award for Outstanding Service to the Veterinary Profession from the American
Animal Hospital Association, Cherry Hill, New Jersey; in 1978 and 1990 received the Gaines
Fido Award as Dogdom's Woman of the Year; and the Award of Merit in 1978 in Recognition of
Special Contributions to the Veterinary Profession from the American Animal Hospital
Association, Salt Lake City, Utah. In 1984 she was awarded the Centennial Medal from the
University of Pennsylvania School of Veterinary Medicine. In 1987 she was elected a
distinguished Practitioner of the National Academy of Practice in Veterinary Medicine. In
1994 she was given the Holistic Veterinarian of the Year Award from the American Holistic
Veterinary Medical Association, Orlando, Florida. She is a member of numerous professional
societies.
Today, Dr Dodds is actively expanding Hemopet's range of nonprofit services and
educational activities. On behalf of Hemopet, she consults in clinical pathology
nationally and internationally and regularly travels to teach animal health care
professionals, companion animal fanciers, and pet owners on hematology and blood banking,
immunology, endocrinology, (including thyroid) nutrition and holistic medicine. She is also the
editor of "Advances in Veterinary Sciences and Comparative Medicine" for
Academic Press.
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