Term
| Which thyroid hormone is more biologically active? |
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Definition
fT3 is 3-5x more active than fT4
**99% of thyroid hormones are bound to plasma proteins and are not biologically active |
|
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Term
| Which thyroid hormone is produced exclusively in the thyroid gland? |
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Definition
T4 (thyroxine)
**only 10-40% of T3 is produced in the thyroid gland (from thyroglobulin), the rest is produced in peripheral cells via deiodination of T4 |
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Term
| How are thyroid hormones (T3, T4) excreted? |
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Definition
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Term
| How do plasma [fatty acid] affect [fT4] in people? |
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Definition
increased [FA] --> falsely increased [fT4]
FA displace T4 on binding proteins |
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Term
| What species has the lowest [total T4] in health? |
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Definition
Dogs (compared to cats, horses, and people)
** so total T4 assays in dogs must have lower detection limits to accurately measure normal and decreased [total T4] |
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Term
| What is the effect of thyroxine autoantibodies on [total T4] via RIA? |
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Definition
Falsely increased [total T4]
RIA used to measure T4 is a competitive binding assay in which the patient's T4 and radioactively labled T4 compete to bind with a limited number of anti-T4 antibodies on a coated tube (decreased radioactivity = increased patient T4).
In the presence of T4AA, radioactive T4 can bind to T4AA and be washed out resulting in falsely decreased radioactivity and falsely increased T4 |
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Term
| Do thyroglobulin autoantibodies (TGAA) have an effect on [total T4] measured via RIA? |
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Definition
NO
*however, if the serum contains TGAA, it may also contain T4AA which can falsely increased [total T4] via RIA |
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Term
| The human assay for which thyroid hormone can be used in dogs and cats? |
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Definition
total T3
**remember, dogs have much lower [total T4] in health compared with humans and other animals, so most human assays underestimated [total T4] in dogs |
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Term
| Describe some of the limitations associated with measuring canine [TSH] |
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Definition
The canine assay lacks sufficient analytical range to document decreased [TSH]
Also human TSH assays don't cross reactive with canine |
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Term
| What is the most common cause of increased [total T4] in cats? |
|
Definition
thyroid adenoma
*occurs uncommonly in dogs and rarely in horses |
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Term
| Why might [total T4] be WRI in a hyperthyroid cat? |
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Definition
[tT4] can fluctuate and may be WRI in a random sample
nonthyroidal illness can lower [tT4]
*T3 suppression test can confirm presence of hyperfunctional thyroid tissue, or repeat sampling may confirmed [tT4] above RI |
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Term
| What conditions, other than thyroid adenoma, may cause hyperthyroidism in cats? |
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Definition
mutations in TSH receptor resulting in constituitive activation and thyroid hormone production (rare)
thyroid carcinoma (2% of hyperthyroid cats) |
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Term
| How often is thyroid neoplasia (carcinoma or adenoma) functional in dogs? |
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Definition
| ~25% of canine thyroid neoplasia produces enough T4 to cause clinical signs of hyperthyroidism |
|
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Term
| What cells undergo malignant transformation in dogs with multiple endocrine neoplasia (type II)? |
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Definition
APUD cells (amine precursor uptake and decarboxylation)
results in development of thyroid medullary carcinoma (calcitonin), pheochromocytoma, parathyroid hyperplasia/neoplasia, and may also result in T4 secreting thyroid neoplasia |
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Term
| Which thyroid autoantibody test has the greatest diagnostic sensitivity for canine lymphocytic thyroiditis? |
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Definition
| TgAA (thyroglobulin autoantibodies) **damaged thyroid gland exposes antigens from immunologically privileged sites so that the immune system produces autoantibodies including TgAA, T4AA, T3AA, and TpAA |
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Term
| How are [tT4] different in kittens vs. adult cats? |
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Definition
| [tT4] in kittens is 2-3x greater than in adult cats |
|
|
Term
| in what dog breed has congenital hypothyroidism been reported? |
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Definition
|
|
Term
| In what cat breeds has congenital hypothyroidism been reported? |
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Definition
| Abyssinian, Japanese cats, DSH |
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Term
| What are two potential causes of secondary hypothyroidism (i.e. TSH deficiency)? |
|
Definition
1. pituitary is damaged (neoplasia, malformations, surgery, radiation, trauma etc.) and doesn't secrete TSH --> atrophy of thyroid follicular cells and decreased T4/T3 production
2. thyroid neoplasm that produces abnormal thyroid hormones that cannot stimulate physiologic responses in cells but DO suppress pituitary secretion of TSH |
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Term
| Has tertiary (lack of hypothalamic TRH (thyrotropin releasing hormone)) been reported in domestic animals? |
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Definition
|
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Term
| congenital hypothyroidism has been reported in which dog breed in associated with deficiency in what enzyme? |
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Definition
| congenital hypothyroidism has been reported in toy fox terriers as a result of deficiency in thyroid peroxidase (normally involved in iodination of thyroglobulin in thyroid gland to produce T4/T3) |
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Term
| What defect in dogs has been associated with hypothyroidism due to defective T4 production by the thyroid gland? |
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Definition
| iodine organification defect |
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Term
| What are three mechanisms that can be associated with decreased [tT4] in non-thyroidal illness? |
|
Definition
1. decreased protein-bound T4 due to decreased affinity of binding proteins
2. inhibition of TSH secretion
3. inhibition of T4 production |
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|
Term
| Describe the pathogenesis of decreased [tT4] in dogs that have Cushings, or are receiving exogenous glucocorticoids? |
|
Definition
** [tT4] is more consistently decreased in dogs with Cushings than those receiving glucocorticoids
glucocorticoids reduce pituitary secretion of TSH, decrease sensitivity of thyroid glands to TSH, and reduce conversion of T4 to T3 in peripheral tissues |
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|
Term
| What drugs are associated with decreased [tT4] in dogs? |
|
Definition
glucocorticoids, TMS*, phenobarbitol, clomipramine
*sulfonamides interfere with iodination of thyroid hormones by inhibiting thyroid peroxidase activity so [TSH] may be increased |
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|
Term
| What drugs are associated with decreased [tT4] in horses? |
|
Definition
| phenylbutazone and glucocorticoids |
|
|
Term
| What dietary related facts are associated with lower [tT4] in horses? |
|
Definition
Diets high in energy, protein, copper or zinc
ingestion of endophyte-infected fescue grasses
food deprivation (at least 4 days) |
|
|
Term
| What plant, when ingested by cattle, is associated with decreased [tT4] and clinical hypothyroidism? |
|
Definition
|
|
Term
| What are some reported differences in [tT4] between dog breeds? |
|
Definition
lower [tT4] in sighthounds
lower [tT4] in large and medium sized dogs compared to small breed dogs |
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Term
| What pattern of [tT4] and [fT4] are sometimes observed in euthyroid sick cats? |
|
Definition
| decreased to normal [tT4] and increased [fT4] |
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|
Term
| Do T4AA affect [fT4] by equilibrium dialysis? |
|
Definition
No
**T4AA can falsely increased [tT4] via solid phase radioimmunoassays |
|
|
Term
| What conditions are expected to have decreased [tT4] AND decreased [fT4] |
|
Definition
| disorders associated with decreased production of T4 (primary hypothyroidism (destruction of thyroid gland), secondary hypothyroidism (destruction of pituitary-TSH deficiency), defective thyroxine production (e.g. iodine deficiency, iodine organification defect, congenital thyroid peroxidase deficiency in toy fox terriers)) **but also nonthyroidal diseases (e.g. cushings, inflammation) and drugs (e.g. cortisol, sulfonamides, phenobarb) can also be associated with low [tT4] and [fT4] |
|
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Term
| Why is [tT4] and [fT4] preferred over [T3] for diagnosing hypothyroidism? |
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Definition
| T3 is less sensitive for diagnosing hypothyroidism compared with T4 and provides littles useful additional information over [tT4] and [fT4] |
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Term
| What are the major uses for measuring [tT3]? |
|
Definition
monitoring therapeutic concentrations (e.g. supplementing hypothyroid dogs)
assessing owner compliance with T3 suppression test (should be higher than baseline [T3] if administered appropriately)
**T3AA can affect results (positive or negative interference) depending on the assay used |
|
|
Term
| In what conditions is [TSH] expected to be increased? |
|
Definition
Primary hypothyroidism in dogs (but not always- increased [TSH] in 60-75% of affected dogs)
**some dogs with compensated hypothyroidism can maintain [T4]/[T3] WRI but only with greater TSH stimulation of remaining functional thyroid tissue |
|
|
Term
| When might you see increased [TSH] in cats? |
|
Definition
After thyroidectomy or chronic methimazole therapy
**the canine assay is used and there is not 100% cross reactivity, however, these differences should be reflected in the reference interval. Also the lower reference limit in cats is 0- so the assay cannot detect decreased [TSH] |
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|
Term
| How should you interpret the presence of TgAA (thyroglobulin autoantibodies)? |
|
Definition
indicative of thyroid gland disease (NOT dysfunction)- likely from when thyroglobulin is released from damaged thyroid and body reacts to it as a 'foreign' protein.
* The presence of TgAA has been reported in up to 55% of dogs with hypothyroidism (lymphocytic thyroiditis) |
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|
Term
| What autoantibodies are most commonly observed in dogs with hypothyroidism (TgAA, T4AA, T3AA, TpAA [thyroid peroxidase autoantibodies])? |
|
Definition
TgAA are most common but dogs with lymphocytic thyroiditis may also have T4AA and T3AA (~6%), and/or TpAA (~17%)
**however, some dogs will have a negative TgAA and positive T4 or T3AA |
|
|
Term
| What is the role of thyroid peroxidase? |
|
Definition
thyroid peroxidase catalyzes the iodination of tyrosine molecules that are attached to thyroglobulin in colloid and leads to the formation of T4 and T3 bound to thyroglobulin
(T4 and T3 are cleaved from thyroglobulin in thyroid epithelial cells prior to release into the blood) |
|
|
Term
| How good is the TRH response test for identifying hypothyroidism in dogs? |
|
Definition
Crappy! (positive predictive value is only 50%)
TSH response test is much better, but not routinely run because a cost effective source of TSH is not currently available |
|
|
Term
| What response to the TRH response test is expected in hyperthyroid cats? |
|
Definition
No increase in TSH or T4
* in a healthy euthyroid cat serum tT4 would markedly increase in the post TRH sample (TRH causes pituitary release of TSH --> increased production of T3/T4 in the thyroid) |
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|
Term
| What [tT3] and [tT4] are expected in a euthyroid cat following T3 suppression test? |
|
Definition
[tT3] increased above baseline
[tT4] decreased (< 20 nmol/L) |
|
|
Term
| What [tT3] and [tT4] are expected in a hyperthyroid cat following T3 suppression test? |
|
Definition
[tT3] increased above baseline
[tT4] increased (> 20 nmol/L) |
|
|
Term
| How would primary hypothyroidism be expected to affect T4:TSH ratio? |
|
Definition
Decreased ratios would be expected with primary hypothyroidism
**decreased ratios can also occur with secondary hypothyroidism (TSH deficiency due to pituitary disease) because [tT4] may decrease more than detectable [TSH] <-- remember, TSH assays often cannot measure decreased values, esp. in dogs. |
|
|
Term
| What patterns of [tT4], [fT4], [TSH], and TgAA would be expected in dogs with primary hypothyroidism caused by lymphocytic thyroiditis? |
|
Definition
low [tT4]*, [fT4]
high [TSH]
positive TgAA
* [tT4] may be WRI to increased if there is positive interference by T4AA |
|
|
Term
| What patterns of [tT4], [fT4], [TSH], and TgAA would be expected in dogs with primary hypothyroidism caused by thyroid atrophy? |
|
Definition
low [tT4], [fT4]
high [TSH]
negative TgAA |
|
|
Term
| What patterns of [tT4], [fT4], [TSH], and TgAA would be expected in dogs with secondary hypothyroidism caused by pituitary disease? |
|
Definition
low [tT4], [fT4], [TSH] (actually would be within RI because the canine TSH assay lacks sufficient analytical range to measure decreased [TSH]
negative TgAA |
|
|
Term
| What patterns of [tT4], [fT4], [TSH], and TgAA would be expected in a euthyroid sick dog? |
|
Definition
low [tT4]
WRI to increased [fT4], [TSH]
negative TfAA |
|
|
Term
| How can thyroid hormones be used to assess appropriate thyroxine supplementation in hypothyroid dogs? |
|
Definition
measure in a blood sample collected 4-6h post pill
[tT4] should be high normal and [TSH] should be WRI |
|
|
Term
| What is the washout period for reassesment of hypothyroidism in dogs receiving thyroxine supplementation? |
|
Definition
|
|
Term
| How would you interpret an increased [tT4] in a cat? |
|
Definition
strong evidence of hyperthyroidism
* |
|
|
Term
| how would you interpret decreased [tT4] in a cat? |
|
Definition
| probably non-thyroidal illness |
|
|
Term
| how would you interpret decreased to normal [tT4] and increased [fT4] in a cat |
|
Definition
| probably non-thyroidal illness |
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