Endocrinology 2 Hypoadrenocorticism The thyroid gland Flashcards
Hypoadrenocorticism
- common name
- what is it
- onset? presentation?
- breeds?
- Atrophy and hypofunction of adrenal cortical cells
- Reduced cortisol and aldosterone, clinical manifestations mostly due to aldosterone deficiency
- Insidious onset, often present in crisis
- Some breed predisposition > poodles, westies
Hypoadrenocorticism
- signalment
- PE findings
- hematology
- biochem
- urinalysis
- Signalment: Young to middle-aged, female
- Physical exam: “ill”, hypovolemic, hypotensive, bradycardia
- Hematology: lack of ‘stress leukogram’
- Biochemistry: electrolyte abnormalities, prerenal azotemia, hypercalcemia, hypoglycemia
- Urinalysis: inadequate concentration in face of hypovolemia
Hypoadrenocorticism
- screening test
Na/K ratio:
- healthy dogs = 27:1 to 40:1
- hypoadrenocorticism = <23:1
- suggestive of hypoadr. =27:1to23:1
Hypoadrenocorticism
- confirmatory test
ACTH stimulation test:
* inject 0.25 mg of ACTH/dog
* Measure plasma cortisol after 1
hour
* Dogs with disease usually have <30 nmol/L at baseline and <50 nmol/L cortisol at 1 hour
what products is t4 converted into? where does this generally happen?
intracellulary:
- 5’-monodeiodinase > T3
- 5-monodeiodinase > rT3
Thyroid gland
- secretes what? what regulates secretion?
- feedback loops?
- Secretes predominantly T4, small amount of T3
- Secretion regulated by TSH and in response to excess or insufficient iodine availability
- TSH release is subject to negative feedback of T3 produced through de-iodination of T4 by tissues
Thyroid hormones
- free proportion
- bound to what?
- what form exerts effects?
- active form?
- Less than 1% of T4 and T3 is free in plasma
- Most is bound to thyroid-binding globulin (TBG), transthyretin, albumin, and other proteins
- Only free hormone exerts biological effects > protein-bound hormone acts as a reservoir
- T3 is much more biologically active than T4, while rT3 is inactive
Thyroid hormones
- how they work under normal conditions to have effects?
> where does T3 come from?
- changes during illness?
- Under “normal” conditions free T4 enters cells, and is then de-iodinated to free T3 which exerts the majority of the metabolic effects.
- Therefore, 80 to 90% of cellular T3 is derived from de- iodination of T4.
- During states of illness, starvation, or excessive catabolism, free T4 is preferentially de-iodinated to inactive rT3
Thyroid hormones Actions:
- carbohydrate and lipid metabolism
- protein synthesis
- enzymatic activity
- metabolism of other hormones
- tropic effects on heart
- fetal development
Canine hypothyroidism
- what do glands look like?
- homeostatic attempts to respond?
- thyroid gland is small and atrophied
- little amount of T4, T3 in the body tells pituitary to secrete more TSH, but to no avail
Canine hypothyroidism
- most common etiology
- when do we see clinical disease?
- cause?
- Most commonly “primary” hypothyroidism i.e. failure of the thyroid gland itself
- Progressive destruction of gland > clinical disease once more than 75% of gland is destroyed
- Lymphocytic thyroiditis? Antibody-mediated gland destruction? Degeneration due to unknown cause?
Diagnostic approach for canine hypothyroidism
- clinically suspicious indicators
a. Breed – English Setter, Doberman Pinscher,
Golden Retriever, etc.
b. Age – middle age, earlier in susceptible breeds
c. Clinical signs – highly variable: weight gain, lethargy, dermatopathy (hyperkeratosis, alopecia), weakness, reproductive abnormalities, neuropathy, etc.
- insidious onset of clinical signs
d. Biochemistry – fasting hypercholesterolemia, hyperlipidemia and hypertriglyceridemia are common
e. Hematology – normocytic, normochromic, non- regenerative anemia, increase in target cells – uncommon changes
Confirm canine hypothyroidism - tests
a. Total T4 concentration
b. Free T4
c. Endogenous TSH concentration
Canine hypothyroidism diagnosis - Total T4 concentration
- what do we do?
- interpretation?
- Measure total T4
- Different assays > reference ranges vary from laboratory to laboratory
- Baseline T4 is lower in dogs than in humans – need sensitive assay
- T4 is stable – can use yesterday’s serum sample
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Interpretation - Healthy (euthyroid) 12-50 nmol/L (OVC)
- Hypothyroid (likely) < 10 nmol/L
- Cannot always distinguish between euthyroid, hypothyroid and euthyroid with other illness (“euthyroid sick”) in many cases.
- Degree of change is important to establish an “index of suspicion” in conjunction with clinical diagnostic findings = weight of evidence
Drugs affect serum T4 concentration
- which increase?
- which decrease?
Increased T4:
- Narcotic analgesics
- Halothane
- Prostaglandins
- Insulin
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Decreased T4:
– Glucocorticoids
– NSAIDS
– Phenobarbital
– Androgens
– Sulfonamides
Testing of dogs treated with thyroid hormone supplementation?
- timing
- Treatment with thyroxine results in suppression of endogenous TSH secretion by the pituitary gland and of secretion of T4 and T3 by the thyroid gland.
- Therefore, thyroid gland function cannot be assessed until supplementation has been discontinued for a minimum of 6 weeks, ideally 8 weeks.
diagnosing canine hypothyroidism - Free T4
- what we do
- interpretation
- Assay should incorporate equilibrium dialysis (ED) to separate total T4 from free T4
- Valuable assay for identifying euthyroid sick
dogs - perform dialysis > ,easure hormone in dialysate
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Interpretation: - Healthy dogs 9-26 pmol/L
- Hypothyroid dogs (likely) < 9 pmol/L
- Free T4 concentration is less affected by non-thyroidal illness and drug therapy than total T4.
- Therefore, useful assay for distinguishing euthyroid sick from hypothyroid dogs with total T4 concentrations between ~10 and 20 nmol/L.
diagnosing canine hypothyroidism - Endogenous TSH concentration
- rationale
- interpretation
- Rationale: TSH concentration is increased before T4 secretion from a failing thyroid gland is noticeably decreased.
- Only canine TSH-specific assays are useful
- Interpretation:
> Healthy dogs 0.05 to 0.70 ng/ml
> Hypothyroid dogs (likely) >0.70 ng/ml - This assay is specific, but not as sensitive as tT4
Tests not useful for diagnosis of hypothyroidism:
- Serum T3 concentration
- Serum fT3 concentration
- Serum rT3 concentration
- Thyrotropin releasing hormone (TRH) stimulation test
Thyrotropin (TSH) stimulation test
- what is it? history
- use
- NO LONGER AVAILABLE
- Widely performed in the past, and therefore
prevalent in the literature. - This test was good for distinguishing full-on hypothyroidism from “healthy”, but not sensitive to distinguishing early hypothyroidism from euthyroid sick.
Thyroid antibodies
- where have they been found
- effects
- Antibodies reactive with T3, T4, and thyroglobulin have been found in hypothyroid and euthyroid dogs
- Antibodies may interfere with assay technique and result in unexpectedly high or low total T4 or T3 results.
- Autoantibodies in hypothyroid dogs may indicate an autoimmune process.
Goiter, causes
= enlarged thyroid
- Many potential causes
* Lack of iodine
* Interference with thyroxine synthesis
How to diagnose hypothyroidism in dogs:
- The dog “looks” hypothyroid and has no major illness: Measure total serum T4
- If T4 is < 10 nmol/L = hypothyroid
- If T4 is >10 nmol/L - measure serum free T4 and
cTSH. - If free T4 is <9 pmol/L and TSH is >0.70 ng/ml =
hypothyroid
Also reasonable to run all 3 tests concurrently.
Feline hyperthyroidism
- how common? age?
- forms?
- causes?
- Common disease in aged cats
- Mean age at diagnosis ~12years
- Multinodular is the most common
> adenomatous hyperplasia most common histologic diagnosis - Maybe unilateral or not palpable
- Cause: Goitrogenic substances? Slow glucoronidation of goitrogenic substances? Dietary iodine?
Feline hyperthyroidism - diagnosis
- history, signs
Weight loss, polyphagia
* Skin changes, excessive grooming, alopecia
* PD/PU
* Diarrhea, vomiting
* Bulky stools
* Hyperactivity
* Heat intolerance
Feline hyperthyroidism
- PE findings
- Palpable cervical mass – 90% of affected cats (mass may be near thoracic inlet)
- Tachycardia
- Hyperactivity
- Small kidneys
Feline hyperthyroidism
- lab evaluation
- Elevated hematocrit (~25% of cats)
- Stress leukogram
- Azotemia
- Hyperphosphatemia
- Elevated ALT and ALP
- Steatorrhea
Feline hyperthyroidism
- ways to confirm diagnosis
a. Total T4 concentration
b. Free T4 concentration
c. Imaging studies
d. T3 suppression test
Feline hyperthyroidism diagnosis - Total T4 concentration
- T4 concentration is elevated in > 90% of
hyperthyroid cats - healthy cats T4 (AHL) 13-55 nmol/L
- hyperthyroid (likely) >75 nmol/L
Feline hyperthyroidism diagnosis - Free T4 concentration
- Specific and sensitive assay in cases of “borderline” total T4 concentrations.
- AHL reference range for healthy cats = 15-50 pmol/L
Feline hyperthyroidism diagnosis - imaging studies
- Radioactive technetium - see dark thyroid
Feline hyperthyroidism diagnosis - T3 suppression test
- how it works
- protocol
- Administration of T3 (oral) > suppression of TSH > should decrease serum T4
- T3 not converted to T4 > no interference with T4 assay.
- In hyperthyroid cats T4 secretion by the adenomatous thyroid gland is unresponsive to decreases in TSH concentration.
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1. Baseline T4 and T3 concentration.
2. Owners administer synthetic T3 orally 7x over 3 days.
3. Serum for T4 and T3 concentration 2 to 4 hours after the last dose of T3.
4. T3 measurement to assess owner compliance.
5. Hyperthyroid: T4 concentration does not decrease
Feline hyperthyroidism - diagnosis summary
Usually straightforward diagnosis:
1. Clinical signs + physical exam + screening laboratory tests
2. Total T4
3. If necessary: free T4 (equilibrium dialysis) or T3 suppression test
Unusual thyroid conditions for cats and dogs
- Canine hyperthyroidism:
- essentially always associated with thyroid carcinoma
<><><><> - Feline hypothyroidism:
- almost always secondary to treatment for
hyperthyroidism
- rarely primary disease
Uncommon thyroid condition for horse
- what is it?
- test?
Equine hypothyroidism:
- “response” to thyroxine supplementation ≠ hypothyroidism
- TSH and TRH stimulation tests have been described for horses. The TSH stimulation test appears to discriminate better between baseline and responding values
- free T4 assays for horses are available and of similar usefulness as in other species
Equine hyperthyroidism
- who gets it?
- signs?
- cause
- Disease of older horses
- Emaciation, tachycardia, polyphagia, polydipsia
- Due to thyroid adenoma or adenocarcinoma
