Lect 31 & 32 Flashcards
thyroid is bilaterally located under the larynx. similar in size to one another
Thyroid gland
* ________ endocrine organ
* Lies _______ to the first __ tracheal rings
Histology
1. ___________ (__ cells)
- these cells produce _________
- also transport of _____
- Secretion of thyroid hormones
2. ________ epithelial cells
- these cells produce _____ (____ fluid material seen on histo)
- thyroid hormones ?
Thyroid gland
* Bilobed endocrine organ
* Lies bilaterally to the first 5 tracheal rings
Histology
* Parafollicular (C cells)
- these cells produce Thyroglobulin
- also transport of iodine
- Secretion of thyroid hormones
* Follicular epithelial cells
* these cells produce colloid (pink fluid material seen on histo)
* thyroid hormones T3 & T4
Thyroid Hormone
* Synthesis and secretion are REGULATED by _____
* Two major hormones produced: ?
1. thyroxine (T4) : 100% Synthesized by the _______
2. Triiodothyronine (T3): More _______ than T4
* 30-40% of T3 synthesized by the _____
* 60-70% of T3 created by cells _____
* Metabolizes _____
* Removes _____ → T3, rT3
Thyroid Hormone
* Synthesis and secretion are REGULATED by TSH
* Two major hormones produced: 1) thyroxine (T4) & 2) triiodothyronine (T3)
1. thyroxine (T4) : 100% Synthesized by the thyroid
2. Triiodothyronine (T3): More potent than T4
* 30-40% of T3 synthesized by the thyroid
* 60-70% of T3 created by cells systemically
* Metabolizes T4
* Removes iodine → T3, rT3
Thyroid Hormone Synthesis
* More T__ is synthesized than T__
- Most of T3 is produced ______ of the thyroid from ________ of T4
- ______ amounts of reverse T3 (rT3) also produced
* T3 is more _____ than T4 on _____ cells
* 99.9% of T4 and 99% of T3 circulate bound to ______ (2?)
* ~0.1% of T4 and ~1% of T3 are ___/______ (E.g.?; biologically _______) and can diffuse into _____ cells
Thyroid Hormone Synthesis
* More T4 is synthesized than T3
* Most of T3 is produced outside of the thyroid from deiodination of T4
* Small amounts of reverse T3 (rT3) also produced
* T3 is more active than T4 on target cells
* 99.9% of T4 and 99% of T3 circulate bound to proteins (albumin, thyroid-
binding globulin)
* ~0.1% of T4 and ~1% of T3 are free/unbound (free –> fT4 and fT3 biologically inactive)
* These are the biologically active forms of the hormones that can diffuse
into target cells
Thyroid Hormone Synthesis: controlled by _____ Axis;
- Initial stimulation via Thyrotropin releasing hormone (trh).
- Signals anterior pituitary to release tsh, whihc stimulates the thyroid to produce primarily t4 with smaller amt of t3. To rpevent uncontrolled prod of T3 and T4, fT3 feedsback primarily on pituitary and suppresses TSH production. Lower plasma tsh concentration –> reduced production of t3 and t4 by thyroid–> decrease in t3 and t4.
High metabolic demand –> peripheral tissues increase t4 uptake and conversion of t4 and t3. This decreases the circulation concentration of free T43 stimulating the TSH production by the pituitary which increases free T4 and T3 by thyroid gland. Continues communication with peripheral tissues.
* Negative feedback loop on the
pituitary and hypothalamus created
by fT3 and fT4
Thyroid Hormone Synthesis: controlled by HPT Axis; initial stimulation via trh. Signals anterior pituitary to release tsh, whihc stimulates the thyroid to produce primarily t4 with some t3. fT3 feedsback primarily on pouitarya dn suppresses TSH production. Lower plasma tsh concentration –> reduced production of t3 and t4 –> decrease in t3 and t4. High metabolic demand –> peripheral tissues increase t4 uptake and conversion of t4 and t3. Decreases ciruclation concentration of free T43 stimulating the TSH production by the pituitary which incrases free T4 and T3 by thyrdoi gland. Continues commmunication with peripherla tissues.
* Negative feedback loop on the
pituitary and hypothalamus created
by fT3 and fT4
Thyroid hormone functions
* Maintain _____ metabolic rate (BMR)
* Related to _____ consumption (basal ____ concentration), ____, ______ metabolism
* Required for proper development of the __________ system and most organs in _______
* Essential for normal _______ actions (4? signaling)
* Enables ______ _____ activity for lipolysis
* Maintain normal ______ and ______ gland activity
* Maintains normal neural signal ________
Thyroid hormone functions
* Maintain basal metabolic rate (BMR)
* Related to oxygen consumption (basal RBC concentration), GFR, glucose metabolism
* Required for proper development of the musculoskeletal system and most
organs in juveniles
* Essential for normal catecholamine actions (skeletal, smooth, and cardiac
muscle signaling)
* Enables lipoprotein lipase (LPL) activity for lipolysis
* Maintain normal haircoat and sebaceous gland activity
* Maintains normal neural signal transduction
What baseline tests can we use to assess thyroid gland function?
- T4 and fT4
- Endogenous TSH
- T3 and fT3
- T3 suppression test
These tests are performed on serum and are not typically part of a routine Biochem panel.
What does the thyroid panel for dogs include?
What does the thyroid panel for cats include?
Thyroxine (T4) Testing
- Measures ?
- There are 2 common Assays:
1. Radioimmunoassay (RIA) = Gold Standard
2. Snap ELISA test kits
- Not reliable for diagnosing hypothyroidism
- Reliable for normal [T4]
Some medications can falsely decrease the value:
1. Glucocorticoids
2. Sulfonamides
3. Phenobarbital, etc.
In ~10% of hypothyroid dogs, anti-T4 antibodies will confound results, most commonly causing a false increase
Thyroxine (T4) Testing
* Measures total circulating T4 (protein-bound & free)
* 2 common Assays:
* 1. Radioimmunoassay (RIA) = Gold Standard
* 2. Snap ELISA test kits
* Not reliable for diagnosing hypothyroidism
* Reliable for normal [T4]
Some medications can falsely decrease the value:
* Glucocorticoids
* Sulfonamides
* Phenobarbital, etc.
In ~10% of hypothyroid dogs, anti-T4 antibodies will confound results, most commonly causing a false increase
Free Thyroxine (fT4) testing measures unbound circulating T4 (free)
There are 2 common Assays:
1. Equilibrium Dialysis (ED) = Gold Standard test
2. Radioimmunoassay (RIA)
- Underestimates FT4 in dogs
- Preferred over total T4 (T4) for assessing thyroid status (as fT4 is the biologically active form), but expensive and time-consuming so less commonly done
** Result can be affected by medications, but not as much as T4.
Free Thyroxine (fT4) testing measures unbound circulating T4 (free)
There are 2 common Assays:
1. Equilibrium Dialysis (ED) = Gold Standard test
2. Radioimmunoassay (RIA)
- Underestimates FT4 in dogs
- Preferred over total T4 (T4) for assessing thyroid status (as fT4 is the biologically active form), but expensive and time-consuming so less commonly done
** Result can be affected by medications, but not as much as T4.
T3 and fT3 testing
- In dogs, more falsely increased or decreased results than T4 due to
greater prevalence of T3 autoantibodies
- Useful in sight hound breeds (Greyhounds, Whippets) FYI
- May have lower T4 and fT4 levels than other dogs but comparable T3
Thyroid Stimulating Hormone (TSH) testing
* Measures concentration of TSH
* 3 types of assays (basically the same)
* 1. Immunoradiometric*
2. Chemiluminescent
3. ELISA
*Differentiates normal from increased TSH concentration , Cannot detect low concentration of TSH (<37 mU/L)
TSH stimulation test
* Considered to be the single ____ standard test by which to measure thyroid status
* But it is important to remember that this test is ______ and very ____-consuming, so not typically
done
–> Principle:
* Measure ?
–> Test Steps:
1. Administer ______ (_____ or recombinant ______ ____)
* Re-measure T__ ____ hours after _____ administration
* Should see minimal ______ in ____ following ____ administration in hypothyroid dogs
TSH stimulation test
* Considered to be the single gold standard test by which to measure thyroid status
* But it is important to remember that this test is expensive and very time-consuming, so not typically
done
–> Principle:
* Measure baseline T4
* Administer TSH (bovine or recombinant human TSH)
* Re-measure T4 6 hours after TSH administration
* Should see minimal increase in T4 following TSH administration in hypothyroid dogs
Canine Hypothyroidism
–> Two major disease syndromes:
1. _______ Hypothyroidism = “Canine ______-Onset Hypothyroidism”
2. ________ Hypothyroidism = is Rare: ____ is not synthesized or secreted; Usually associated with a Pituitary gland: ______, ______ malformation, _______ or ______
- ______ clinical signs
- ______ findings on CBC and Chemistry
–> DDx: - _______ sick syndrome
- ________ changes
Canine Hypothyroidism
–> Two major disease syndromes:
1. Primary Hypothyroidism = “Canine Adult-Onset Hypothyroidism”
2. Secondary Hypothyroidism = Secondary hypothyroidism is Rare: TSH is not synthesized or secreted; Usually associated with a Pituitary gland: Neoplasia, Congenital malformation, Trauma or surgery
- Similar clinical signs
- Similar findings on CBC and Chemistry
–> DDx: - Euthyroid sick syndrome
- Spurious changes
Canine Hypothyroidism is the ____ common Thyroid disorder in dogs (~95% is _______ hypothyroidism)
* ★ ________ DISEASE ★ IMPORTANT
* ________ thyroiditis (_______ attacking thyroid glands)→ _______ thyroid ______ (reduce in ____ and ______)
* ________ auto-antibodies (TGAA)
* Cells seen on histo: ________ and _______
* ________ tissue replacing thyroid gland
Canine Hypothyroidism is the most common Thyroid disorder in dogs (~95% is acquired hypothyroidism)
* ★ AUTOIMMUNE DISEASE ★ IMPORTANT
* Lymphocytic thyroiditis (lymphocytes attacking thyroid glands)→ idiopathic thyroid atrophy (reduce in size and function)
* Thyroglobulin auto-antibodies (TGAA)
* Lymphocytes and macrophages
* Fibrous tissue replacing thyroid gland
Canine Hypothyroidism
–> Signalment:
* ______ age dogs, usually ____-breed (not always)
–> Clinical signs
- ________ metabolic rate
- Lethargy, inactivity, mental dullness
- Weight ____
- ______, often ______ –> “___ tail”
- _____, _____ hair coat
- __________
- Myxedema – drooping ______
Apparent when <___% thyroid tissue
_________ onset
Systemic hormone → many systems affected
Canine Hypothyroidism
–> Signalment:
* Middle age dogs, usually pure-breed (not always)
–> Clinical signs
- Decrease metabolic rate
- Lethargy, inactivity, mental dullness
- Weight gain
- Alopecia, often symmetrical –> “rat tail”
- Dry, brittle hair coat
- Seborrhea (red, itchy scalp)
- Myxedema – drooping eyelids
Apparent when <25% thyroid tissue
Gradual onset
Systemic hormone → many systems affected
Canine Hypothyroidism Chemistry Panel IMPORTANT
A.CBC
- ______: mild to moderate
- _____-Regenerative (50% of cases)
- ________, ____________
- __________ Metabolic rate –> ________ oxygen Demand –> DEC ________
- _________ seen in blood smears
B.Chemistry
- Fasting ______cholesterolemia (75%) b/c of decreased cholesterol catabolism by the ______
- Fasting ______triglyceridemia (88%)
Canine Hypothyroidism Chemistry Panel IMPORTANT
A.CBC
* ANEMIA: Mild to moderate
* Non-Regenerative (50% of cases)
* Normocytic, normochromic
- DEC Metabolic rate –> DEC oxygen Demand –> DEC EPO
* Codocytes seen in blood smears
B.Chemistry
- Fasting hypercholesterolemia (75%) b/c of decreased cholesterol catabolism by the liver
- Fasting hypertriglyceridemia (88%)
Canine Hypothyroidism
c. Thyroid function testing tests ____, ____, and elevated _____.
In cases of Hypothyroidism, you will see a ________ TT4, __________ fT4, ___________ TSH
1. TT4 DEC
- Not _________ for hypothyroidism
- IMPORTANT If ______, strongly indicates dog does not have hypothyroidism
- Cell r/o ________ sick syndrome
- r/o _______
2. fT4 DEC
* Usually not affected by _____-thyroid illness
3. TSH INC
* Use as a confirmatory test in combination with _____ and ______
* IMPORTANT If elevated in combination with _____ T4 and fT4, this is ____________ for
hypothyroidism
* IMPORTANT ~20% of hypothyroid dogs may have ________ TSH
Canine Hypothyroidism
c. Thyroid function testing tests TT4, fT4, and elevated TSH.
In cases of Hypothyroidism, you will see a decreased TT4, decreased fT4, elevated TSH
1. TT4 DEC
- Not specific for hypothyroidism
- IMPORTANT If WNL, strongly indicates dog does not have hypothyroidism
- Cell r/o euthyroid sick syndrome
- r/o spurious
2. fT4 DEC
* Usually not affected by non-thyroid illness
3. TSH INC
* Use as a confirmatory test in combination with T4 and fT4
* IMPORTANT If elevated in combination with low T4 and fT4, this is confirmatory for
hypothyroidism
* IMPORTANT ~20% of hypothyroid dogs may have normal TSH
Feline Hyperthyroidism is the most ________ endocrine disorder of cats. –> Signalment
- _____ to ______ cats (usually >__ yrs)
* Cats starts to “Act like a ______”
* Etiology: Largely _______
–> Pathogenesis
a-Functional _______ (or _______)
- ~___-___% of hyperthyroid cats
- ______ >or _______ > or ______
b- Thyroid ____________
* ~___-___% of hyperthyroid cats
Feline Hyperthyroidism is the most common endocrine disorder of cats. –> Signalment
- Old to geriatric cats (usually >10 yrs)
* Cats starts to “Act like a kitten”
* Etiology: Largely unknown
–> Pathogenesis
a-Functional adenoma (or hyperplasia)
- ~98-99% of hyperthyroid cats
- bilateral >or unilateral > or ectopic
b- Thyroid adenocarcinoma
* ~1-2% of hyperthyroid cats
What are the clinical signs of Feline Hyperthyroidism?
Clinical signs
* Weight loss and polyphagia, which occurs in 90% of cats
- This is due to an Increased basal metabolic rate and energy consumption
* Vomiting
* Diarrhea
* Aggression in some instances
* Hyperactivity like kittens
* PU/PD
What will you find on physical exam in a hyperthyroid cat?
Feline Hyperthyroidism
Physical exam findings
* 70% of cases: bilateral thyroid slip
- 30% of cases are unilateral
- Tachycardia due to basal metabolic rate being compromised.
- +/- heart murmur
- Poor hair coat
Feline Hyperthyroidism IMPORTANT
A. CBC
1. _____________ (~50%)
* ↑metabolic rate →↑_____ demand →↑_____
* T4 directly stimulates Bone Marrow ________
2. ______-Body Formation
* NOT associated with _____ ______
3. ______ leukogram (~20%)
B. Biochem panel
1. _____ liver enzyme activity (~90%)
- Mild to moderate increases in ____
- Severity correlates with ____ levels
2. Altered ____ metabolism (~20%)
- May contribute to increased ____
3. _______ (>30%) (elevated ____, +/- _______, often ____-renal (~26% of cats)
- Pre-Renal: ________
- Renal: Concurrent ________ renal insufficiency
Masked Azotemia
* _______ GFR due to _______ cardiac output
* _____ muscle mass → lower basal _____
Unmasked with treatment of hyperthyroidism
Feline Hyperthyroidism IMPORTANT
A. CBC
1. Erythrocytosis (~50%)
* ↑metabolic rate →↑oxygen demand →↑EPO
* T4 directly stimulates Bone Marrow erythropoiesis
2. Heinz-Body Formation
* NOT associated with hemolytic anemia
3. Stress leukogram (~20%)
B. Biochem panel
1. Increased liver enzyme activity (~90%)
- Mild to moderate increases in ALT
- Severity correlates with TT4 levels
2. Altered bone metabolism (~20%)
- May contribute to increased ALP
3. Azotemia (>30%) (elevated BUN, +/- Creatinine, often pre-renal (~26 of cats)
- Pre-Renal: Dehydration
- Renal: Concurrent primary renal insufficiency
Masked Azotemia
* Increased GFR due to increased cardiac output
* Less muscle mass → lower basal CREA
Unmasked with treatment of hyperthyroidism
Feline Hyperthyroidism
c. Thyroid Function Testing
1. INC Total T4 (TT4)
- Single and reliable test to Dx hyperthyroidism in cats.
–> If you have a low Clinical suspicion but inconclusive TT4 (2-10%)
Options:
1. Recheck _____ in 1-2 weeks
2. Treat ______ disease and recheck _____
3. Submit _____ ($)
Feline Hyperthyroidism
c. Thyroid Function Testing
1. INC Total T4 (TT4)
- Single and reliable test to Dx hyperthyroidism in cats.
–> If you have a low Clinical suspicion but inconclusive TT4 (2-10%)
Options:
1. Recheck TT4 in 1-2 weeks
2. Treat underlying disease and recheck TT4
3. Submit FT4 ($)
3-Euthyroid sick syndrome
A. Sick animals have ___TT4
B. Common
- _______ response
- ______ clinical signs for hypothyroidism
- Treatment ____ required
C. Thyroid Function Testing: TT4, FT4, TSH
- TT4 ______
- FT4 _____ to ______
- TSH _____ to _____ … 99% of the time, TSH is _____! <– IMPORTANT: key to recognize and distinguish dz
3-Euthyroid sick syndrome
A. Sick animals have ↓TT4
B. Common
- Adaptive response
- Absent clinical signs for hypothyroidism
- Treatment NOT required
C. Thyroid Function Testing: TT4, FT4, TSH
- TT4 decreased
- FT4 normal to decreased
- TSH normal to increased … 99% of the time, TSH is normal! <– IMPORTANT: key to recognize and distinguish dz
Lab testing Feline hyperthyroidism
1. T3 suppression test
* Used to differentiate hyperthyroid cats from ______ sick cats when ___ is normal
–> Principle:
- Measure baseline ___ and ___
- Client administers ___ to the cat orally several times over 2 days
- Measure ___ and ___ 2-4 hours after the last dose of ___ is administered
–> Interpretation:
* If the final __ or __ is ____ cutoff value –> lack of ______ of both
–> confirms hyperthyroidism
Lab testing Feline hyperthyroidism
1. T3 suppression test
* Used to differentiate hyperthyroid cats from euthyroid sick cats when T4 is normal
–> Principle:
- Measure baseline T4 and T3
- Client administers T3 to the cat orally several times over 2 days
- Measure T4 and T3 2-4 hours after the last dose of T3 is administered
–> Interpretation:
* If the final T4 or T3 is above cutoff value à lack of suppression of T4 or T3
–> confirms hyperthyroidism
Feline Hyperthyroidism
1. Consistent clinical signs of severe weight ____ and ______
2. ______ thyroid tumor
3. _______ TT4 IMPORTANT
4. ______ to therapy
Feline Hyperthyroidism
1. Consistent clinical signs of severe weight loss and polyphagia
2. Palpable thyroid tumor
3. Increased TT4 IMPORTANT
4. Response to therapy
Spurious cases of changes in the thyroid.
1. Daily Variation: TT4 is sporadic and unpredictable. Depending on time of day, thyroid levels change- 8am - Lowest
- 2pm – Highest
2. Age: Progressive decline in TT4, FT4, T3 with age
3. Breed: As animals age, decline in these hormones. Trend to lower TT4
* Medium to large breeds have lower TT4
* Greyhounds and sighthounds have lower TT4
4. Drugs
a. Glucocorticoids
- Mechanism: Changes peripheral metabolism of T4; Inhibits TSH formation
b. Sulfonamides
- Mechanism: Block iodination of thyroglobulin
C tends to be mild to moderate
A
B b/c lower t4 and free t4 and high tsh
A
Hyperadrenocorticism Screening tests: Urine cortisol:creatinine ratio
- High sensitivity (>92%) but low specificity
- If it is normal, hyperadrenocorticism can be ruled out
- Increased value is not specific for hyperadrenocorticism, since the
ratio can be increased in stressed dogs and dogs with non-adrenal
illness
Fasting urine sample collected at home
HAC confirmatory tests: LDDST
Step #1 Look at the 8 hour result.
* Normal dogs: suppress cortisol at 8 hours (ie, cortisol <1.5 μg/dL)
* HAC dog: >90% do not suppress cortisol 8 hours (ie, cortisol >1.5)
