Lect. 6 - Canine hypothyroidism Flashcards
Where to palpate thryoid gland?
the healthy thyroid gland is not palpable in dogs and cats
endocrine cell types found in the thyroid gland?
thyroid follicular cells (thyroglobulin; T4 & T3)
parafollicular C-cells (calcitonin)
parafollicular C-cells are derived from?
neuroectoderm
thyroid follicular cells are derived from?
pharyngeal endoderm
where are C-cells located?
C-cells are located adjacent to the thyroid follicles and reside in the connective tissue.
are large with pale staining cytoplasm compared to the follicular cells
what is thyroglobulin
Thyroglobulin glycoprotein precursor to the thyroid hormones. It acts as a substrate for the synthesis of thyroxine and triiodothyronine as well as the storage of the inactive forms of thyroid hormone and iodine.
calcitonin opposes the effects of…?
of PTH
calcitonin acts to reduce blood Ca2+ level and PTH does the opposite.
where is thyroglobulin synthesized?
in the rough endoplasmic reticulum of the thyroid follicular cells
how does iodine move from blood to follicular cell interior?
by using a Na+/Iodine symporter in the cell membrane. this is active transpot.
The symporter co-transports two sodium ions along with one iodide, with the transmembrane sodium gradient serving as the driving force for iodide uptake.
Iodide is the ionic state of iodine.
Iodide is
the ionic state of iodine.
What happens to Iodide in the thyroid colloid?
It is oxidized to iodine by an enzyme called thyroid peroxidase. Iodine is very reactive and reacts with the thyroglobulin.
Conjugation occurs. Then it re-enters the follicular cell via endocytosis. Proteolysis occurs next.
Canine thyroid neoplasia is
uncommon.
May result in:
euthyroidism 55%,
hypothyroidism 40%
or hyperthyroidism 5%.
Endocrine tumors maybe either
functional or non functional.
But size of tumor does not typically relate to functionality of the tumor.
More than what percentage of canine thyroid tumors are malignant?
more than 80-90%
what percentage of canine thyroid tumors are bilateral?
10%
thyroid carcinomas in cats
are uncommon, prevalence less than 4%.
most cats that are diagnosed with thyroid carcinoma - are hyperthyroid.
INfrequently the carcinoma remains nonfunctional with the cat remaining euthyroid.
nature of follicular tumors in cats usually?
and are called what…?
they are usually benign.
called adenomatous hyperplasia.
about 95% of cats with thyroid adenomatous hyperplasia are…?
hyperthyroid.
most are also bilateral.
most common endocrine disorder in dogs?
hypothyroidism
(note: this is very rare in cats)
What types of hypothyroidism is common and what is rare?
primary is common (95% of clinical cases)
secondary (<5% of cases), tertiary and congenital are all rare.
describe the pathogensis of Primary hypothyroidism
gradual destruction of the thyroid gland by autoimmune lymphocytic thyroiditis or idiopathic atrophy.
2 causes of Primary hypothyroidism:
- Lymphocytic thyroiditis
- Idiopathic necrosis and atrophy
How much thyroid tissue must be lost in thyroiditis, to cause sufficient depression of T3 & T4 levels to be noticed (clinical signs)?
35%
Usually takes at least a 1 year for this to occur.
Lymphocytic thyroiditis involves intense infiltration of the thyroid by what cell type?
cytotoxic T cells
+ autoantibodies attack thyroglbulin etc.
The diagnosis of immune related thryoid destructions requires…?
the confirmation of autoantibodies against thyroid products
what is DLA?
dog leukocyte antigen
DLA is a part of the major histocompatibility complex (MHC) in dogs, encoding genes in the MHC.
The DLA and MHC system are interchangeable terms in canines. The MHC plays a critical role in the immune response system and consists of three regions: class I, class II and class III.
clinical signs of primary hypothyroidism in dogs
thick, in elastic skin
drooping of the upper eyelids / ptosis
weight gain
lethargy
stiff gait
Secondary hypothyroidism is typically divided into
congenital and aquired
causes of aquired secondary hypothyroidism (4)
Pituitary neoplasia
Head trauma
Hypophysectomy
Lymphocytic adenohypophysitis
causes of congenital secondary hypothyroidism (2)
cretinism (only thyroid is deficient)
but with GH deficiency, is pituitary dwarfism
what is tertiary hypothyroidism caused by?
is exteremely rare in dogs, 1 case reported.
In tertiary hypothyroidism, the hypothalamus does not release enough thyrotropin-releasing hormone, so the pituitary does not send enough TSH to encourage thyroid hormone (T3 and T4) production.
Tertiary hypothyroidism is rare, but it is often due to a mass or tumor near or on the hypothalamus when it does occur.
Name some Major functions of thyroid hormones
– Increase anabolism at physiological
concentration and catabolism in excess.
– Increase weight at physiological concentration and decrease weight in excess.
– Increase heart rate
– Increase blood pressure
– Increase body temperature
– Increase gut motility
– Increase CNS activity
– Are required for growth
– Are required for reproduction
Lesser known complications of hypothyroidism in dogs (2)
a wide variety of reproductive issues
myxedema
Name some reproduction related complications of hypothyroidism in dogs (6)
- Increased periparturient mortality
- Low birth weights
- Uterine inertia
- Irregular estrus
- Testicular atrophy
- Low libido/subfertility
Describe Myxedema complications of hypothyroidism in dogs (6)
- Acid and neutral mucopolysaccharides (glycosaminoglycans). Mostly hyaluronic acid. These cause thickening of the dermis.
- Rounding of facial features
- Myxedematous coma
– Life threatening endocrine emergency
ECG abnormalties of hypothyroidism may include
bradycardia
may also include arrythmias and a weak pulse.
Sequence of diagnostic tests in the diganosis of hypothyroidism in dogs.
- Clinical examination always first!
- Hematology
- Blood serum/plasma biochemistry panel (note comorbidities that may affect the funtional test resutls!)
- Functional tests come last.
What change in hematology may present in cases with hypothyroidism?
Mild to moderate normocytic, normochromic,
non regenerative anemia
≈ 30%
Why is Mild to moderate normocytic, normochromic, non regenerative anemia seen in some dogs with hypothyroidism?
What classic serum biochemical abnormality is seen in dogs with hypothyroidism?
The classic serum biochemical abnormality is fasting hypercholesterolemia and Triglyceridaemia, which occurs in ~80% of dogs with hypothyroidism.
What liver marker abnormality is seen in dogs with hypothyroidism?
Mild to moderate increase in ALT&ALP ≈90%
plus – Large amounts of gall bladder sludge.
What renal function abnormality is seen in dogs with hypothyroidism?
– Raised creatine kinase
– Symmetric dimethylarginine (SDMA) –associated with decreased glomerular filtration rate (GFR).
Why not total T4 as a single test?
Low TT4 can be due to more than just hypothyroidism so results can be misleading.
e.g.
2. Breed specific normal variations
3. Drugs
4. „Euthyroid sick“ syndrome
What is „Euthyroid sick“ syndrome?
also known as “nonthyroidal illness syndrome” or “sick euthyroid syndrome,” refers to a condition in which there are abnormal changes in thyroid function tests despite the absence of primary thyroid gland dysfunction (typically low serum thyroid levels).
the thyroid gland itself is not the primary problem, but there can be alterations in thyroid levels that occur in the context of acute or severe systemic illness.
Which is one reason why we do not rely on thyroid functional tests alone in diagnosis of hypothyroidism. Sick dogs with non-thyroidal illness may be falsely diagnosed as being hypothyroid (euthyroid sick syndrome).
Hyperthyroid cats with concurrent illness may be falsely diagnosed as being euthyroid. What is this called?
Euthyroid sick syndrome
Breeds that may present with “normal” low serum TT4 concentrations of thyroid hormones.
Sighthounds:
Sloughi (pictured)
greyhound
whippet
scottish deerhound
irish woflhound
saluki
basenji
Breeds that may present with “normal” low serum T3 concentrations of thyroid hormones.
greyhounds
Common drug therapies affecting thyroid
function tests in dogs.
(clomipranime is a tricyclic antidepressant, The name “tricyclic” refers to the three-ring chemical structure present in these medications. )
Advantages of total T4 measurements for the diagnosis of hypothyroidism
Sensitivity 90-95% (those with low levels detected)
Inexpensive, widely available and easily measured.
Highly sensitive marker for hypothyroidism.
Reference interval values suggest hypothyroidism is unlikely.
disadvantages of total T4 measurements for the diagnosis of hypothyroidism
Specificity 70-74%
Advantages and disadvantages of canine TSH measurements for the diagnosis of hypothyroidism in dogs
Should not be interpreted alone.
TSH is only elevated in 65-75% of hypothyroidism cases.
The advantages and disadvantages of free
T4 measurements for the diagnosis of
hypothyroidism in dogs
More expensive than TT4, more sensitive/finicky test anyhow.
What combination of the available thyroid related hormone analyses is diagnostic of hypothyroidism?
decreased total T4 or free T4, with elevated TSH is diagnostic of hypothyroidism with a combined sensitivity of 75% and specificity of 95/98%
Recommendations for routine testing of thyroid function.
(thyroid)(Auto)antibodies are Useful for diagnosis of
autoimmune thyroiditis but are not measures of thyroid functions.
May interfere with the determination of total thyroid hormone concentrations due to the antibody-T4 complexes.
In a hypothyroid dog with T4-autoantibodies, T4 may be falsely elevated into normal range. Why/how?
Standard blood tests for thyroid function typically measure total T4 levels. This measurement includes the T4 that is bound to proteins, including T4-autoantibody complexes.
Since the antibody-bound T4 is included in the measurement, it can lead to an overestimation of the actual free, biologically active T4 levels.
The total T4 levels measured in the blood test may appear to be higher than they actually are. This can create a misleading impression that the thyroid function is normal, even though the dog may be hypothyroid.
False negatives.
Do two step/equilibrium analysis in autoimmune cases.
Some breeds are overrepresented for autoimmune thyroiditis, such as:
– English setter
– Dalmatian
– Basenji
– Old English Sheepdog
– Boxer
– Shetland sheepdog
young-middle aged dogs
What percentage of hypothyroid dogs may have decreased TT4 but TSH within ref range?
20-25%
TT4 is >2 µg/dL*
(25,7 nmol/L)
What do we conclude?
Hypothyroidism unlikely
Reference range basal TT4:
1,3 - 4,5 µg/dL
(16,7-57,9 nmol/L)
TT4 is <2 µg/dL
(25,7 nmol/L)
What do we conclude?
Hypothyroidism possible
Reference range basal TT4:
1,3 - 4,5 µg/dL
(16,7-57,9 nmol/L)
TSH response (stimulation) test evaluates
the reserve function of the thyroid gland.
You test TT4 before and after TSH administration.
This test is considered to be more reliable than any other single individual test for canine
hypothyroidism.
TRH stimulation test is used…?
What is the principle?
used very rarely in practice.
Principle: TRH stimulates synthesis and release of TSH. TSH stimulates production of T4 and T3.
Some healthy dogs do not respond to TRH. Thus the test should only be used to confirm euthyroidism.
Thyroid scintigraphy uses what substance
Radioactive sodium pertechnetate
Thyroid scintigraphy is the Most accurate method for differentiating…?
Most accurate method for differentiating
hypothyroidism from euthyroidism in dogs with
decreased serum T4.
T3 is
the Metabolically active form of T4.
Only ½ of all T3 is secreted by the thyroid gland. ½ is produced by deiodination of T4 in peripheral tissues.
T3 is Primarily an intracellular hormone. Frequently does NOT accurately reflect thyroid
function. In general, not a useful test.
What is the “K value”?
is the Canonical discriminant analysis combining
Baseline T4 & Cholesterol.
“Canonical discriminant analysis (CLIA) is a multi- variate technique which can be used to determine the relation- ships among a categorical variable and a group of independent variables.”
hypothyroidism Prognosis
- Individual variation
- Excellent in most cases of hypothyroidism
- Check-up every ½ year
- With myxedema coma guarded
- Dogs with congenital hypothyroidism may have residual mental retardation and skeletal
abnormalties including degenerative arthropathy
Desired „post-pill“ serum T4 concentration?
Not sufficient clinical response concentration?
Too high concentration?
- Desired „post-pill“ serum T4 concentration
40-70nmol/L* - Not sufficient clinical response
<35 nmol/L - Higher dosage needed
- Too much
90-100 nmol/L or higher..
– Lower the dosage
T4-Autoantibodies may interfere with
the determination of thyroid hormone concentrations.
