Endocrine Flashcards
Explain the structure of the thyroid gland
Note the thyroid follocles which are cuboidal epithelial cells surrounding colloid.
C-cells are also present (responsible for calcitonin secretion)
Highly vascularised
Outline thyroid hormone synthesis
- Iodine enters the thyroid gland, co-transported with sodium via NIS
a - The concentration gradient for sodium is generated via ATPase - Iodine diffuses through the cell and into the colloid mediated by counter-transport with chloride through pendrin (Chloride-iodide anti porter)
- Iodine is coupled to thyroglobulin, a glycopeptide containing tyrosine residues produced by the sER/Golgi
- Iodide is oxidised by thyroid peroxidase using H2O2
- Organification (coupling of Iodine to tyrosine) occurs mediated by thyroid peroxidase
- Pinocytosis into the cell occurs and proteases breakdown the colloid droplet to allow active thyroid hormones to be released into the blood.
- Deiodinases release tyrosine and iodine from inactive products to allow recycling of these compounds
Outline the different stages of thyroid iodination and number of iodine residues for each molecule
What is the majority of thyroid hormone bound to in the blood?
Thyroxine binding globulin, it can also bind to pre-albumin and albumin
Why does T4 likely have a longer duration of action than the more potent T3?
It takes longer for T4 to unbind from binding proteins in the blood.
How does thyroid hormone expert its effect?
Through binding to nuclear thyroid hormone receptors which combine with the retinoid x receptor and then bind to thyroid response elements.
What are the effects of TSH on thyroid production (5 points)
- Increased proteolysis of TG
- Increased NIS activity
- Increased iodination of tyrosine
- Thyroid hypertrophy
- Increased number of thyroid cells
What is the effect of ACTH on the adrenal cortex that results in increased steroid hormone production?
It enhances the activity of cholesterol desolate which is the first step in steroid synthesis converting cholesterol to pregnenolone.
Which steps of the steroidogenic pathway does trilostane have an effect on?
3B hydroxysteroid dehydrogenase
What is the role of 11BHSD?
It converts cortisol, which has some MC activity, into cortisone (which does not) and is present in the renal epithelium. This is why cortisol, in health, does not have a significant MC effect.
Note that 11 beta-HSD 1 has the opposite effect
What food item may inhibit 11BHSD2?
Licorice, as it contains glycorrhetinic acid
Outline the effects of MC activation and drugs that may impact on some of these effects?
- Aldosterone binds to the MR which then stimulates production of NA/KATPase, ENaC and ROMK.
- Spironolactone inhibits the MR
- Ameloride prevents Na entry into renal cells by antagonising ENaC
Factors and hormones leading to increased vs. decreased insulin secretion
At what level of serum phosphate is all filtered PO4 re-absorbed by the kidney?
<1mmol/L
What treatments have been used/described for the management of hyposomatotropism in dogs/cats?
Use of porcine or human GH products but a problem with these treatments is that antibody development may occur.
Progestin use to stimulate mammary GH production has not been effective in cats.
What is the prevalence of hypersomatotropism in diabetic cats?
18 - 32%
What is the gold standard for diagnosis of HS in people?
Oral glucose administration followed by GH measurement - this has not been described in cats. The normal response is a suppression of GH secretion in response to testing.
Testing, other than GH/IGF-1 that may be used in diagnosis of fHS?
PIIIP - serum type III pro collagen polypeptide, may be up to 5x higher in fHS DM cats compared to DM cats
Gherlin - as a GH secretagogue it is lower in fHS than in healthy cats but may not be lower that DM cats. It has also been shown to increase in response to radiation therapy even when IGF-1 does not change.
GHRG stimulation/SST suppression tests (dogs)
- 1mcg/kg GHRH will NOT stimulate GH release if it is mammary driven (discriminatory test between these types)
- 10mcg/kg SST should suppress GH production in normal animals
What drug may reduce polyphagia in fHS cats?
Fluoxitine
In what scenario is gherlin an important secretagogue for GH release?
Possibly more important in young animals, compared with GHRH
What phase of reproduction is GH secreted from mammary epithelium in dogs?
dioestrus, more often 3 - 5 weeks following oestrus
Treatment for canine acromegaly?
MAMMARY DRIVEN:
OVH
Aglepristone
PITUITARY
As for cats
Pegvisomant (GH receptor antagonist)
Which canine breed is predisposed to pituitary dwarfism? What other hormonal deficiencies are noted in this clinical scenario?
GSD - autosomal recessive
Will typically have combined GH, TSH and PRL deficiency, however, ACTH production is preserved
Other breeds:
- Czechoslovakian wolfdog
- Karelian Bear Dog
- Lapland reindeer dog
- Lapponian herder
- Saarloos Wolfdog
- Tibetan Terrier
- White Swiss Shepherd
Clinical presentation of hyposomatotropism in dogs
Morphological Abnormalities
* Proportionate growth retardation
* Coat changes:
○ Retention of secondary (languno) hairs
○ Lack of primary guard hairs
○ Truncal alopecia (due to loss of languno hairs), sparing trunk and extremities.
○ Hyperpigmentation
○ Scale
○ Secondary bacterial infections
* Pointed muzzle
* LHX3 gene also associated with atlantoaxial joint malformation +/- instability
Reproductive Abnormalities
* Cryptorchidism (due to impaired gonadotrophs)
* Failure to ovulate
Other
May develop reduced demeanour at 2-3 years old due to hypothyroidism and impaired renal function.