Hyper/Hypothyroidism Flashcards
The follicular cells have ………………… on the surface next to the colloid to …………………….
microvilli
increase SA
The follicular cells have ………………………. between them
Tight junctions
What hormones do follicular cells produce?
Triiodothyronine (T3)
Thyroxine (T4)
What are the thyroid hormones derived from?
Thyroid hormones are amino acid derivatives (from tyrosine) and consist of linkage of two iodinated tyrosine molecules (iodothyronines)
How many iodines do T3 and T4 have?
T4 has 4 iodines suck to it and T3 has three iodines stuck to it.
90% of thyroid hormone production is …………………..
90%: Thyroxine (T4)
Describe how the thyroid hormones are formed
Active transport of iodide into the colloid cell via a sodium coupled transporter, iodide diffuses to the colloid end of the cell and meets the enzyme TPO (thyroid peroxidase) and this transports the iodide across the membrane and into iodine. TPO attaches the iodine onto the thyroglobulin.
What stimulates Iodide uptake into the follicular cells?
TSH
What is the fate of excess iodide?
Excess iodide excreted via kidneys
Where is thyroglobulin synthesised?
Follicular cells synthesize thyroglobulin
Processed in Golgi apparatus
How many tyrosine molecules are in one molecule of thyroglobulin?
Each thyroglobulin contains 120 tyrosine molecules
How is iodide turned back to iodine?
Iodide (I−) oxidized to iodine (I2) as hydrogen peroxide (H2O2) is reduced
What is stored within the colloid?
Triiodothyronine (T3) and thyroxine (T4) are bound to the thyroglobulin
Triiodothyronine (T3) and thyroxine (T4) are bound to the thyroglobulin
What is the half life of T3 and T4?
T3: 6 hours dog
T4: 12 hours
Are thyroid hormones lipid or water soluble?
lipid
How does T3 –> T4? Where does this occur?
Thyroxine deiodinated to triiodothyronine
Within cells of many tissues
So it doesnt matter that the thyroid secretes mostly T4 as it gets turned into T3 in the cell anyway.
T3 is…
triiodothyronine
T4 is…
Thyroxine
What is the fate of the remaining T4?
Remaining T4 deiodinated to reverse T3 (rT3)
Free T3 is biologically active but rT3 is inactive so this acts as regulation
What enzymes convert T4 to T3 and rT3?
Active T3 produced by 5′-deiodinase and Reverse T3 by 5-deiodinase
Increasing thyroid hormone increases metabolism so how is metabolism reduced?
Achieved by reducing thyroid hormone concentration or action by lowering TSH from pituitary gland
Or alter deiodination by increasing 5-deiodinase activity and Inhibit 5′-deiodinase activity (more rT3)
Excess thyroid hormones undergo Hormone catabolism, what is this and where does it happen?
Further deiodinated into diiodotyrosine and monoiodotyrosine
In the Liver and kidneys
Iodide is either recycled or excreted via the urine
Do intracellular receptors have a higher affinity for T3 or T4?
Much higher affinity for T3 (90% receptor binding with T3) Only 10% receptor binding with T4.
Define Euthyroid
normal thyroid function
Hypothalamus releases thyrotropin-releasing hormone and what does this stimulate?
This stimulates the adenohypophysis (anterior pituitary gland) to secrete thyroid-stimulating hormone (TSH); also called thyrotropin
What intracellular pathway does TSH initiate in the follicular cell?
Adenyl cyclase signal transduction pathway: cyclic AMP (cAMP)
What are the 5 actions of TSH?
- Increased endocytosis and proteolysis of thyroglobulin from colloid*Takes 30 minutes
- Increased activity of the Na+/ I– symport
- Increased iodination of tyrosine
- Increased size and secretory activity of thyroid follicular cells
- Increased number of follicular cells
What effect do T3 and T4 have on development?
Lack can cause Reduced development and maturation of brain cells (permanent) in fetus and young
What effect do T3 and T4 have on growth?
They are Required for normal growth
What effect do T3 and T4 have on carbohydrate metabolism?
Thyroid hormone stimulates glucose metabolism (energy burning):
Glycolysis
Gluconeogenesis
What effect do T3 and T4 have on fat metabolism?
Thyroid hormone enhances fat metabolism (energy burning)
Mobilizes lipids from adipose stores
Accelerates oxidation of lipids to produce energy
Occurs within mitochondria (beta oxidation) so Increase in size and number of mitochondria
What effect do T3 and T4 have on basal metabolic rate?
Increase BMR in all tissues, except the brain, gonads, and spleen
Increased heat production
Increased oxygen consumption
What effect do T3 and T4 have on MSK?
Hypothyroidism – reduced muscle tone and changes in fiber type
Hyperthyroidism – protein depletion; amino acids used for gluconeogenesisis
What effect do T3 and T4 have on CRS?
Increase blood flow and cardiac output
Increase heart rate
Increase contractility
What effect do T3 and T4 have on the nervous system?
Enhances sympathetic nervous system (increase in epinephrine receptors)
What effect do T3 and T4 have on the GI tract?
Thyroid hormone increases appetite and feed intake
Increases secretion of pancreatic enzymes
Increases motility
What effect do T3 and T4 have on the skin and hair?
Thyroid hormone initiates and maintains anagen (growth) phase
What is primary hypothyroidism?
Lack of functional thyroid tissue
What are the two types of primary hypothyroidism?
Acquired - most common
Idiopathic follicular atrophy
Iatrogenic - caused by surgery and antithyroid medications, ingestion of goitogens
What is secondary hypopthyroidism?
Impaired secretion of TSH from the pituitary
What are the two types of secondary hypothyroidism?
Acquired – eg via Neoplasia
Congenital – rare eg. Cystic Rathke’s pouch
What is the signalment for canine hypothyroidism?
Breeds: Doberman Pinschers, Golden Retrievers, Cocker spaniels, Irish setters, terriers
Sex – no predisposition
Age – peak incidence 4 to 6 years
What are the dermatology symptoms for canine hypothyroidism?
Derm signs: Bilateral symmetrical alopecia on the areas of wear (non-pruritic), Seborrhea, lichenification (thickened), Comedones, Hyperpigmentation on alopecic areas and recurrent infections. (Rat tail and bridge of the nose)
What are the cardiovascular symptoms for canine hypothyroidism?
Cardiovascular signs: Sinus bradycardia, Weak apex beat, low voltage complexes and a decrease in contractility
What are the neuro symptoms for canine hypothyroidism?
Neurological signs: From segmental demyelinization and slow nerve conduction, Peripheral neuropathy leads to knuckling and myopathy leads to a slow gait.
What is myxedema?
Excess mucopolysaccharides + hyaluronic acid in dermis gives hypothyroid dogs a tragic facial expression
What is the CBC for a hypothyroid dog like?
Normocytic, normochromic anemia (< 50%)
Leukocytosis if there is infection
What is the biochemistry profile for a hypothyroid dog like?
Increased parameters of lipid metabolism
Mild–moderately increased hepatic enzymes
What are the tests for thyroid function?
Total T4 + free T4
(Total T3) and free T3
TSH
How do we use total T4 in thyroid testing?
Snout test
Low T4 correlates with likelihood of hypothyroidism
It’s such a good test that Normal total T4 can exclude hypothyroidism but it has poor specificity as there are daily fluctuations in individuals and is influenced by non-thyroidal illness and drugs
What does measuring free T3 tell us?
Spin test
Only free / unbound T4 enters the cell
Concentration fT4 reflects thyroid status at tissue level
What does measuring total T3 tell us?
Absolutely bugger all.
Most circulating T3 from deiodination of T4 at extra thyroidal sites
What does measuring baseline TSH tell us?
Spit test
90% specificity If interpreted with total T4 or free T4 results
What us hyperthyroidism?
Hyperthyroidism is Excessive production of thyroxine (T4) caused by adenomatous hyperplasia of the thyroid gland(s)
What are the effects of hyperthyroidism?
Increased metabolic rate
Increased catabolism
Interaction with CNS (sympathetic drive)
What is the signalment of feline hyperthyroidism?
Older cats (> 10 years)
No gender difference
Rarer in himalyans/siamese
What are the clinical signs of feline hyperthyroidism?
Weight loss Polyphagia PU/PD Tachycardia Diarrhoea Vomiting Patchy alopecia Behaviour: Hyperactivity, Vocalisaton, Agitation and restlessness, Obsessive groooming
What are the limitations of total T4?
Daily/hourly fluctuations
May be normal in early or mild hyperthyroidism
Depressed by non-thyroidal illness
Addition of free T4 may be helpful
How can we use a T3 suppression test in hyperthyroid diagnosis?
In normal cats, administration of exogenous T3 causes a decrease in TSH and T4
Minimal decrease in T4 with hyperthyroid cats
Snout test
What is thyroid scintigraphy?
Radioactive marker identifies functional thyroid tissue Confirms diagnosis of hyperthyroidism Localises tissue (unilateral, bilateral) and determines benign or malignant.
Do dogs get hyperthyroidism?
Very rare, but thyroid carcinomas have been recorded in dogs over 10 (Golden retrievers, Boxers, Beagles) and highly metastic
