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