ENI - The thyroid gland Flashcards
What is the embryological origin of the thyroid gland?
- Downgrowth from pharyngeal endoderm of developing tongue (follicular cells)
- C cells are from ultimobranchial body
Describe the structure of the thyroid glands
- Thyroid follicles
- Single layer of follicular cells around lumen filled with protein rich colloid where hormones are stored
- Microvilli on colloid side
- Cell cells large, pink cytoplasm, interspersed between follicular cells
- Lots of contact with capillaries on basal side
- Tight junctions between neighboruing cells
What is the function of the parafollicular cells?
- Connective tissue near follicles
- secrete calcitonin
What is the colloid?
- Stored within follicles
- Primarily thyroglobulin
- T3 and T4 bound to thyroglobulin
- Normally only 10% of tyrosines in thryroglobulin are iodinated
What is the function of iodine in the body?
Thyroid hormone synthesis, this is its only role
Describe the synthesis of the thyroid hormones
- Iodide pumped from blood into follicular cells using secondary active transport with sodium, down sodium concentration gradient (is against iodine gradient)
- Stimulates by TSH
- Once iodide in, diffuses through cell to colloid end
- Thyroperoxidase (TPO) at colloid end
- Golgi in cell produce thyroglobulin (with 120 tyrosine residues), transported into colloid via exocytosis
- Thyroperoxidase catalyses iodination of thyroglobulin using the iodide
- Iodide oxidised to iodine as H2O2 is reduced
- Iodine added to tyrosine within thyroglobulin, catalysed by iodinase enzyme
- This coupling reaction produces monoiodotyrosinase or diiodotyrosinase
How are T3 and T4 produced from monoiodo and diiodotyrosinase?
- Mono and diiodo combine to form T3
- 2x diiodo to form T4
Describe the process of thyroid hormone secretion
- Get from colloid to basal membrane and into capillary network
- Endocytosis for colloid uptake
- Intracellular vesicles fuse with lysosomes
- Lysosomal enzymes split thryoid hormones from thyroglobulin
- Hormones diffuse across basal plasma membrane into interstitium (lipid soluble so bound to thyroid hormone binding globulin or albumin)
Compare the blood concentrations of the thyroid hormones
- 50-60 times higher blood levels of T4 compared to T3 in circulating blood concentrations
- Very small amount of free hormones (0.03% T4, 0.3% T3)
- Equilibrium between bound and free
Describe the deiodination of thyroxine
- Deiodinated to triiodothyronine within cells of many tissues, esp liver and kidneys
- Free hormones enter cells
- Can be converted to T3 or rT3
- Therefore deiodination pathways are mechanism for regulation
- Active T3 using 5’-deiodinase
- rT3 using 5-deiodinase
- Different position of iodine removed
What is the function of rT3?
- No action and so will slow metabolism
- Adaptation to starvation or illness
How are thyroid hormones excreted?
- Catabolised by liver and kidney
- Further deiodinated to diiodotyrosine and monoiodotyrosine
- Produces conjugated excretory products
- Iodide either recycled or excreted via urine
What are the actions of thyroid hormones?
- Development and growth
- Increase metabolic actions
- Increase breakdown of glycogen in MSK system
- Increased efficiency of oxygen delivery to tissues
- Respiratory system effects
- Maintain normal function of adult nervous system
- Reproductive system
- Gastrointestinal system
What are the effects of thyrotropin hormone (TSH)?
- Increased endocytosis and proteolysis of thyroglobulin from colloid
- Increased activity of Na+/I- symport
- Increased iodination of tyrosine
- Increased size and secretory activity of thyroid follicular cels
- Increased number of follicular cells
- Goitre (enlarged from TSH stimulation)
Describe the regulation of TSH and TRH
- Hypothalamus secretes TRH
- Stimulates TSH release from anterior pituitary (water soluble)
- Acts on thyroid gland
- Adenyl cyclase signal transduction pathway
- Negative feedback from thyroid hormones in long and short loops
Where is most T3 produced?
In the tissues, by deiodination of T4
Which of the thyroid hormones is the primary biologically active hormone?
T3
What are the effects of thyroid hormones on development?
- Required in foetal period and first few months
- Lack leads to reduced development and maturation of brain cells (permanent, cretinism in humans)
What are the effects of hypothyroidism on growth?
- Required for normal growth
- In young animal: growth retardation, smaller, shorter bones, dealyed closured of physes
Describe the role of thyroid hormones in carbohydrate metabolism
- Stimulate glucose metabolism
- Increase glucose uptake into cells
- Insulin sensitivity
- Insulin secretion
- Glycolysis in liver and skeletal muscle
- Gluconeogenesis
Describe the role of thyroid hormones in fat metabolism
- Enhances fat metbaolism
- Mobilise lipids fom adipose stores
- Accelerate oxidation of lipids to produce energy (by increasing size and number of mitochondria as this is where beta-oxidation takes place)
Describe the role of thyroid hormones in basal metabolic rate
- Increase BMR in all tissues except brain, gonads nad spleen
- Increase heat production
- Increase oxygen consumption
What is the effect of hyperthyroidism on basal metabolic rate and body weight?
- BMR twice normal level
- Weight loss
What is the effect of hypothyroidism on basal metabolic rate and body weight?
- BMR 50% of normal
- Weight gain
Describe the effect of hypothyroidism on the musculoskeletal system
- Reduced muscle tone, changes in fibre type
- Not seen clinically, very little cahnge in MSK system seen
Describe the effect of hyperthyroidism on the musculoskeletal system
- Protein depletion
- AAs used for gluconeogenesis
- Muscle tremors
What are the normal physiological effects of the thyroid hormones on the cardiovascular system?
- Increased blood flow and cardiac output
- Increased heart rate
- Increased contractility
- Aims to increase oxygen supply to the body
What are the effects of hypothyroidism and hyperthyroidism on the cardiovascular system?
Hypo: bradycardia
Hyper: tachycardia
What is the normal action of the thyroid hormones on the respiratory system?
- Increased basal metabolic rate
- Increased demand for oxygen thus increased excretion of carbon dioxide (increased ventilation)
What are the effect of hypo and hyperthryoidism on respiration rate?
- Hypo: little change seen
- Hyper: increased respiration rate
What is the normal action of the thyroid hormones on the nervous system?
- Development
- Enhances sympathetic nervous system (increases epinephrine receptors)
- Needed for optimal nerve conduction
What is the effect of hypothyroidism on the nervous system?
- Slower reflexes
- Lethargic
- Mentally slower
- Require more sleep
What is the effect of hyperthyroidism on the nervous system?
- Hyperexcitable
- Tired becuase of increased nerovus and muscular activity, but difficulty sleeping
What is the effect of hypothyroidism on the reproductive system
- Reduced sexual drive
- Reduced sperm production
- Irregular or absent cycling
What is the normal action of the thyroid hormones in the gastrointestinal system?
- Increases appetite and feed intake
- increases secretion of pancreatic enzymes
- Increases motility
What are the effects of hypo and hyperthyroidism in the gastrointestinal system?
- In humans, not always the case in animals, may be seen in some but not others
- Hypo: constipation
- Hyper: diarrhoea
What is the normal role of the thyroid hormones in the integument?
Initiates and maintains anagen phase of hair growth
What is the effect of hypothyroidism in the integument?
- Arrests hair growth, hair retained in telogen phase
- Alopecia or failure to regrow after clipping
What are the different types of hypothyroidism with respect tothe HPT axis?
- Primary
- Secondary
- Tertiary
Outline primary hypothyroidism
- Disease of thyroid gland itself
- Lack of functional thyroid tissue
- Most common form
- Can be acuired, iatrogenic or congenital
What are the potential causes of acquired primary hypothyroidism?
- Lymphocytic thyroiditis ~50% (autoimmune)
- Idiopathic follicular atrophy
- Secondary to neoplasia (least likely)
- Clinically unimportant to kow which one of these as long as can tell if is neoplasia or not
What are the potential causes of iatrogenic primary hypothyroidism?
- Surgery, radioactive iodine therapy, anti-thyroid medications
- Treatment of hyperthyroidism is common cause
What are the potential causes of congenital primary hypothyroidism?
- Rare, cretinism and early death
- Thyroid gland agenesis or dysgenesis
- Thyroid peroxidase deficiency
- Deficient dietary iodine, ingestion of goitrogens
What is secondary hypothyroidism?
- Disease of pituitary affecting the thyroid (no TSH)
- Uncommon
- Acquired
What are potential causes of acquired secondary hypothyroidism?
- Neoplasia
- Pituitary suppression e.g glucocorticoid administration
- Illness, malnutrition
What are potential causes of congenital secondary hypothyroidism?
Cystic Rathke’s pouch (accompanied by other pituitary hormone deficiencies e.g. ADH)
Outline tertiary hypothyroidism
- Disease of hypothalamus affecting the thyroid (no TRH)
- Lack of RH in hypothalamic supraoptic and paraventricular nuclei
- Very rare
Describe the signalment for hypothyroidism
- Breed disposition: Doberman Pinschers, Golden retriever, Cocker spaniels, Irish setters, terriers
- No sex or neutering predisposition
- Peak incidence 4-6
Describe the clinical signs of hypothyroidism
- Vague, diffuse gradual onset
- non-pathognomic
- Most commonly dermatological and metabolic signs
- Cardiovascular, neurological and reproductive signs
Describe the metabolic signs of hypothyroidism
- Dullness
- Lethargy
- Obesity without history of polyphagia
- Exercise intolerance
- Cold intolerance
- Tragic appearance
Describe the dermatologic signs fo hypothyroidism
- Bilaterally symmetrical alopecia on areas of wear/pressure points flanks, down backs of limbs, non-pruritic
- Seborrhea, lichenification, comedones
- Hyperpigmentation of alopecic areas
- recurrent infections
- Dry skin and haircoat
- alopecia on bridge of nose and “rat tail” on dogs
- Myxedema: excess mucopolysaccharides and hyaluronic acid in dermis leading to skin folds and haning(tragic) facial expression
Describe the clinical cardiovascular signs of hypothyroidism
- Sinus bradycardia
- Weak apex beat
- Electrocardiograph: ow voltage complexes
- Echocardiogram: decreased fractional shortening
- Decreased contractility
Describe the clinical neurologic abnormalities of hypothyroidism
- Segmental demyelinisation and nerve conduction
- Peripheral neuropathy: knuckling, paresis, hearing impairment
- Myopathy (paresis, slow gait)
- Myxednea coma
Describe the clinical reproductive signs of hypothyroidism
- Female: infertility, shortened oestrus, prolongeed oestrual bleeding, prolonged anoestrus
- Male: infertility, testicular atrophy
Outline the complete blood count results for hypothyroidism
- Nomocytic, normochromic anaemia (non-regenernative)
Outline the biochemistry profile in hypothyroidism
- Increased parameters of lipid metabolism: cholesterol, lipids, triglycerides (TAGs)
- Mild-moderately increased hepatic enzymes
- Fasting hypercholasterolemia
What is euthyroid sick syndrome?
- Non-thyroidal illnesses suppress T4 and T3
- Patient not truly hypothyroid
- Mechanisms: decreased protein binding of T4 and T3, decreased T4 to T3 conversion, decreased TSH release
What tests are used to diagnose hypothyroidism?
- Free and total T4
- TSH
- Total T3
Describe total T4 measurements in hypothyroidism diagnosis
- Measure protein bound and free T4
- Good screening test
- Hypothyroid have low or low-normal total T4
- tT4<6nmol/l = very likely
- tT4>20nmol/l = very unlikely
- Normal total T4 can exclude hypothyroisim
- Good for ruling out, but low specificity due to daily fluctuations, euthyroid sick syndrom, drug (e.g. glucocorticoids, antibiotics)
What will the tests results for total T4 and TSH be if euthyroid sick syndrome is occuring?
Low tT4, low-normal TSH
What will the test results be for total T4 and TSH in hypothyroidism?
Low tTH, high TSH
- For diagnosis use all 4 tests together
Describe free T4 test in diagnosin hypothyroidism
- Only free/unbound T4 can enter cells
- Concentration of fT4 reflects thyroid status at tissue level
- Less affected by external factors
- 90% accuracy in hypothyroidism diagnosis
Describe total T3 in diagnosing hypothyroidism
- Does not reflect thyroid gland function
- Most will be from deiodination of T4 at extra thyroidal sites
- Will be conserveed in hypothyroid states and so is not that clinically useful
Describe baseline TSH in diagnosing hypothyroidism
- 90% specificity
- Lower sensitivity
- Low or high Sh depends on primary or secondary hypothyroidism
- Primary: high TSH, no negative feedback
- Secondary: low TSH leading to decreased T4 production
In order to accurately diagnose hypothyroidism, what is required?
- All 4 tests: tT4, free T4, free T3, baseline TSH
- Compatible clinical signs
- Response to therpeutic trial
- Usually see: total T4 low to low-normal (<6nmol/L)
- TSH>0.5ug/L with low T4
What is the most common cause of hyperthyroidism?
Adenomatous hyperplasia of the thyroid glands
- Small number of thyroid carcinoma
What is the histological appearance of a hyperthyroid gland?
- Lots of small follicles and extra tissue between them
- Looks like “normal” tissue but a lot more of it and bigger
- Can be cystic
What is the effect of hyperthyroidism on the HPT axis?
- Increased production of thyroid hormones
- Negative feedback, decrease TSH production
What is the signalment for feline hyperthyroidism?
- Older cats (>10 years)
- No gender difference
- Rare in himalayans and siamese
Outline the common history for a cat with hyperthyroidism
- Wet canned food more likely than dry good
- Fish flavoured more at risk
- Pedigree cats more resistant than domestic shorthairs
- Indoor cats more at risk
- Behavioural changes: hyperactivity, vocalisaion, agitation and restlessness, changes to grooming (over or under), poor thermoregulation
What are the common clinical signs of feline hyperthyroidism?
- Insidious progressive signs
- Weight loss, polyphagia, PUPD are main ones
- Diarrhoea, respiratory abnormalities, vomiting, haircoat changes
- Thin cat
- Cervical nodule/goitre
- Tachycardia(>240bpm) +/- murmur +/- gallop rhythm
- Less commonly: tremors, weakness, dyspnoea, heat and stress intolerance, cardiac disease/failure, systemic hypertension, blindness (due to haemorrhage of retinas)
Outline canine hyperthyroidism
- Rare
- Thyroid carcinomas (only small proportion of thyroid carcinomas are functional)
- Highly metastatic
- Older dogs >10 years
- Golden retrievers, boxers, beagles
How does hyperthyroidism cause weight loss and polyphagia?
- Increased metabolic rate
- Increased catabolism of stores
- Making up for lost stores (may lead to regurgitation as are eating more than are able to digest)
How does hyperthyroidism lead to vomiting?
- Overeating
- Activation of emetic centre
- Concurrent disease
Why does diarrhoea occur in hyperthyroidism?
- Pancreas unable to cope with quantitiy of food
- Food not digested properly due to insufficient pancreatic secretions
- Leads to maldigestion and thus diarrhoea
- Hypermotility and thus malabsorption
How does hyperthyroidism cause the cardiovascular signs seen?
- Sensitisation of cardiactissue to catecholamines (as thyroid hormoens enhance SNS)
- More response to catecholamines leading to tachycardia
- Disturbed cardiac activity and flow
- Hypertrophic cardiomyopathy leading to murmurs
How does hyperthyroidism cause PU/PD?
- Exact mechanism unclear
- Increased cardiac output, glomerular filtration rate and medullary blood flow
- Possibly psychogenic component
- Concurrent renal disease in some cats as is mostly old cat disease
How does hyperthyroidism lead to behavioural changes?
- Interaction with CNS
- Leads to increased SNS activity, thus increased activity in general
- Thermoregulation changes
How does hyperthyroidism lead to hypertrophic cardiomyopathy?
- Direct effect of thyroid hormones on myocytes
- Indirect effect of adrenergic nervous system
- Indirect compensatory changes for altered peripheral perfusion
What tests are used to diagnose hyperthyroidism?
- Baseline hormone concentration (total and free T4)
- Dynamic hormone testing: T3 suppression test, TRH stimulation test
Rank the tests used to diagnose hyperthyroidism in order of preference
- Serum total T4 (usually diagnostic, rare to have other reason for raised hyperthyroidism)
- Repeat T4
- Free T4 by equilibrium dialysis
- T3 suppression test
- TRH response test
- Scintigraphy
What are the limitations of Total T4 testing in diagnosis of hyperthyroidism?
- Daily/hourly fluctuations
- May be normal in early or mild hyperthyroidism
- Depressed by non-thyroidal illness (euthyroid sick mechanism)
- Addition of free T4 may be helpful
Describe the T3 suppression test in hyperthyroidism diagnosis
- Admin of exogenous T3 causes decrease in TSH and thus decrease in T4
- Measure T4: thyroid gland response, in hyper are autonomously producing T4 and TSH already suppressed so more T3 will not lead to further suppression of TSH or T4
- Measure T3 to check T3 has been absorbed/given. If there is no cahnge in T3 then shows it has not been absorbed
Outline the use of thyroid scintigraphy in the diagnosis of hyperthyroidism
- Radioactive marker identifies functional thyroid tissue
- Technetium or iodine isotope
- Specific counts via gamma camera to determine thyroid/salivary gland ratio
- Need specific facilities, not commonly available
- Confirms and localises
- Identifies ectopic tissues and metastatic disease
Decribe the appearance of hyper and hyperthyroid glands on thyroid scintigraphy
- Hyperthyroid darkened more intensely
- Hypothyroid very pale/alnost invisible
Outline the treatment of hyperthyroidism
- Administration of radioactive iodine, will concentrate in thyroid gland to a level where it is able to destroy the thyroid tissue, thus preventing production of T4
- Drugs inhibiting thyroid peroxidase (needed to make iodide into iodine)
- Starving cats of iodine using special diet
