Endocrinology 2 Hypoadrenocorticism The thyroid gland Flashcards

1
Q

Hypoadrenocorticism
- common name
- what is it
- onset? presentation?
- breeds?

A
  • 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
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2
Q

Hypoadrenocorticism
- signalment
- PE findings
- hematology
- biochem
- urinalysis

A
  1. Signalment: Young to middle-aged, female
  2. Physical exam: “ill”, hypovolemic, hypotensive, bradycardia
  3. Hematology: lack of ‘stress leukogram’
  4. Biochemistry: electrolyte abnormalities, prerenal azotemia, hypercalcemia, hypoglycemia
  5. Urinalysis: inadequate concentration in face of hypovolemia
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3
Q

Hypoadrenocorticism
- screening test

A

Na/K ratio:
- healthy dogs = 27:1 to 40:1
- hypoadrenocorticism = <23:1
- suggestive of hypoadr. =27:1to23:1

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4
Q

Hypoadrenocorticism
- confirmatory test

A

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

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5
Q

what products is t4 converted into? where does this generally happen?

A

intracellulary:
- 5’-monodeiodinase > T3
- 5-monodeiodinase > rT3

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6
Q

Thyroid gland
- secretes what? what regulates secretion?
- feedback loops?

A
  • 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
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7
Q

Thyroid hormones
- free proportion
- bound to what?
- what form exerts effects?
- active form?

A
  • 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
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8
Q

Thyroid hormones
- how they work under normal conditions to have effects?
> where does T3 come from?
- changes during illness?

A
  • 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
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9
Q

Thyroid hormones Actions:

A
  • carbohydrate and lipid metabolism
  • protein synthesis
  • enzymatic activity
  • metabolism of other hormones
  • tropic effects on heart
  • fetal development
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10
Q

Canine hypothyroidism
- what do glands look like?
- homeostatic attempts to respond?

A
  • thyroid gland is small and atrophied
  • little amount of T4, T3 in the body tells pituitary to secrete more TSH, but to no avail
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11
Q

Canine hypothyroidism
- most common etiology
- when do we see clinical disease?
- cause?

A
  • 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?
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12
Q

Diagnostic approach for canine hypothyroidism
- clinically suspicious indicators

A

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

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13
Q

Confirm canine hypothyroidism - tests

A

a. Total T4 concentration
b. Free T4
c. Endogenous TSH concentration

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14
Q

Canine hypothyroidism diagnosis - Total T4 concentration
- what do we do?
- interpretation?

A
  • 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
    <><><>
    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
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15
Q

Drugs affect serum T4 concentration
- which increase?
- which decrease?

A

Increased T4:
- Narcotic analgesics
- Halothane
- Prostaglandins
- Insulin
<><><>
Decreased T4:
– Glucocorticoids
– NSAIDS
– Phenobarbital
– Androgens
– Sulfonamides

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16
Q

Testing of dogs treated with thyroid hormone supplementation?
- timing

A
  • 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.
17
Q

diagnosing canine hypothyroidism - Free T4
- what we do
- interpretation

A
  • 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
    <><><>
    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.
18
Q

diagnosing canine hypothyroidism - Endogenous TSH concentration
- rationale
- interpretation

A
  • 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
19
Q

Tests not useful for diagnosis of hypothyroidism:

A
  • Serum T3 concentration
  • Serum fT3 concentration
  • Serum rT3 concentration
  • Thyrotropin releasing hormone (TRH) stimulation test
20
Q

Thyrotropin (TSH) stimulation test
- what is it? history
- use

A
  • 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.
21
Q

Thyroid antibodies
- where have they been found
- effects

A
  • 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.
22
Q

Goiter, causes

A

= enlarged thyroid
- Many potential causes
* Lack of iodine
* Interference with thyroxine synthesis

23
Q

How to diagnose hypothyroidism in dogs:

A
  1. The dog “looks” hypothyroid and has no major illness: Measure total serum T4
  2. If T4 is < 10 nmol/L = hypothyroid
  3. If T4 is >10 nmol/L - measure serum free T4 and
    cTSH.
  4. If free T4 is <9 pmol/L and TSH is >0.70 ng/ml =
    hypothyroid
    Also reasonable to run all 3 tests concurrently.
24
Q

Feline hyperthyroidism
- how common? age?
- forms?
- causes?

A
  • 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?
25
Q

Feline hyperthyroidism - diagnosis
- history, signs

A

Weight loss, polyphagia
* Skin changes, excessive grooming, alopecia
* PD/PU
* Diarrhea, vomiting
* Bulky stools
* Hyperactivity
* Heat intolerance

26
Q

Feline hyperthyroidism
- PE findings

A
  • Palpable cervical mass – 90% of affected cats (mass may be near thoracic inlet)
  • Tachycardia
  • Hyperactivity
  • Small kidneys
27
Q

Feline hyperthyroidism
- lab evaluation

A
  • Elevated hematocrit (~25% of cats)
  • Stress leukogram
  • Azotemia
  • Hyperphosphatemia
  • Elevated ALT and ALP
  • Steatorrhea
28
Q

Feline hyperthyroidism
- ways to confirm diagnosis

A

a. Total T4 concentration
b. Free T4 concentration
c. Imaging studies
d. T3 suppression test

29
Q

Feline hyperthyroidism diagnosis - Total T4 concentration

A
  • T4 concentration is elevated in > 90% of
    hyperthyroid cats
  • healthy cats T4 (AHL) 13-55 nmol/L
  • hyperthyroid (likely) >75 nmol/L
30
Q

Feline hyperthyroidism diagnosis - Free T4 concentration

A
  • Specific and sensitive assay in cases of “borderline” total T4 concentrations.
  • AHL reference range for healthy cats = 15-50 pmol/L
31
Q

Feline hyperthyroidism diagnosis - imaging studies

A
  • Radioactive technetium - see dark thyroid
32
Q

Feline hyperthyroidism diagnosis - T3 suppression test
- how it works
- protocol

A
  • 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.
    <><><><>
    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
33
Q

Feline hyperthyroidism - diagnosis summary

A

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

34
Q

Unusual thyroid conditions for cats and dogs

A
  1. Canine hyperthyroidism:
    - essentially always associated with thyroid carcinoma
    <><><><>
  2. Feline hypothyroidism:
    - almost always secondary to treatment for
    hyperthyroidism
    - rarely primary disease
35
Q

Uncommon thyroid condition for horse
- what is it?
- test?

A

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

36
Q

Equine hyperthyroidism
- who gets it?
- signs?
- cause

A
  • Disease of older horses
  • Emaciation, tachycardia, polyphagia, polydipsia
  • Due to thyroid adenoma or adenocarcinoma