Hypothalamic - Pituitary - THYROID Flashcards
Outline the overall thyroid axis
Hypothalamic hormone is TRH
Anterior Pituitary is TSH
Endocrine target is the Thyroid Gland which secretes thyroid hormones
Non-endocrine target is many tissues
What is the structure of the thyroid ?
> just below larynx
> on either side of the trachea
> 2 lobes
> connected by isthmus
> largest purely endocrine gland (20-25 grams)
** lateral to first 3-8 trachael wings **
Diagram of the thyroid
Follicles take up I- from the blood & secrete it into the colloid
In the colloid, I- is oxidized & attached to a tyrosine residue on thyroglobulin
Production of thyroid hormones
Thyroglobulin : made by the follicle cells, it is a long peptide chain located in colloid with lots of tyrosine side chains
Iodid (I-) : transported from blood to follicular cells by a sodium-iodide transporter then transported into colloid via pendrin
What are the two ways iodine attaches to thyroglobulin ?
1) attachment of 1 iodine on a tyrosine produces monoiodotyrosine (MIT)
2) attachment of 2 iodines produces diiodotyrosine (DIT)
How do you make thyroid hormones ?
Enzymes in colloid modify structures of MIT and DIT to make the hormones
> MIT + DIT = triiodothyronine (T3)
> DIT + DIT = tetraiodothyronine (T4)
How long does T3 & T4 stay bound to thyroglobulin ?
until hydrolyzed by a small volume of colloid and then they are secreted into the blood
STIMULATED BY TSH
Summary of production of thyroid hormones
Step 1 : enzyme thyroid peroxide (TPO) removes an eledtron from I- to produce I
Step 2 : iodine kinds tyrosine residues to form MIT & DIT
Step 3 : condensation of MIT & DIT residues to form T3 & T4
How does the receptor binding of thyroid receptors work ?
1) T4 and carrier binding protein enters target cell
2) T4 is converted to T3 (biologically active form)
3) T3 uses binding proteins to enter nucleus
4) Hormone-receptor comples binds DNA
5) New mRNA is the product
6) Protein Synthesis occurs making new protein
7) Initiates thyroid hormone response
What is the transportation of thyroid hormones
>99% of thyroid hormones in blood circulation bound to a plasma carrier protein called thryroxine-binding globulin (TBG)
- only free fractions of thyroid hormones biologically are active; therefore has to lose the carrier protein to produce effects in target cell
How is TRH secretion regulated ?
- Pulsed secretion of TRH
- young animals > old animals
- stress/cold increase
Circadian rhythm of thyroid hormones in humans, secretion is highest between 10am & 2pm.. WHY?
acting on basal metabolic rate; resting rate of calorie expenditure
>in mice/rodents, circadian rhythm of thyroid hormones secretion is highest at night because they are nocturnal animals
Physiological action of thyroid hormones
- elevates basal metabolic rate
- needed for normal gonadal development and function
- needed for normal embryonic/fetal development, particularly for the development of the CNS
** thyroid hormone deficiency or excess may therefore have serious consequences
Compare hypo- and hyperthyroidism
Hypothyroid :
abnormally low basal metabolic rate - weight gain
lethargy
Intolerance to cold
Hyperthyroid :
Increased basal metabolic rate - weight loss
muscular weakness
nervousness
protruding eyes (exophtalmos)
What is cretinism ?
Congenital deficiency of thyroid hormones; usually due to materal HYPO-thyroidism
How do you treat Cretinism ?
Treatment with thyroxine (T4) soon after birth (before 1 month) has shwon to (almost) completely restore development of intelligence by age 5
Thyroid Hormones: terminal brain differentiation
Thyroid Hormone-dependent development of the brain beings in utero - completed after birth
Dendritic and axonal growth, myelin formation and synapsis formation
Neuronal migration
Maternal THs first supply the needs of the embryo/fetus
Causes of cretinism
May be due to innate maternal hypothyroidism
Diet deficient in iodine (this deficiency affects many people worldwide)
The causes of hypothyroidism and hyperthyroidism
- Insufficient dietary iodide
- Thyroid gland defect
- Impaired Thyroid Hormone Pathway
- insufficient anterior pituitary TSH
- insufficient hypothalamic TRH
- mutant TSH or TRH receptors (genetic)
- mutant TH transport proteins
- autoimmunity
Goiters & HYPOthyroidism:
Abnormal Growth of Thyroid
Low iodide intake = thyroid cant produce enough thyroid hormones
Clinical signal: low plasma, thyroid hormones, T3, T4
High TRH
High plasma TSH
Stimulates excess growth of thyroid
Graves & HYPERthyroidism
AutoAbs activate thyroid gland
Clinical signal: High plasma, thyroid, T3, T4
Low TRH
Low plasma TSH
Synthetic thyroid medicine and natural thyroid medicine
Synthroid : Levothyroxine = T4
Natural : made from porcine thyroid
Thyroid problems in animals
HYPERthyroid is common in cats
HYPOthyroid is more common in dogs
Primary hypothyroidism (animals)
Most primary hypothyroidism in dogs is from destruction of the thyroid
Common causes, primary:
1) Lymphocytic thyroiditis (immune infiltration)
2) Idiopathic atrophy of the thyroid (thyroid lost and replaced by adipose cells)
Secondary Hypothyroidism (animals)
Common causes, secondary:
1) thyroid destruction secondary to neoplasia
2) congenital hypothyroidism/cretinism/pituitary dwaarf
more than 75% of both lobes must be non-function before development of clinical signs: Myxedema (swelling of tissues) (severe HYPOthyroidism)/stupor/coma
Treatment for thyroid disorders
1) Surgery (hemithyroidectomy)
2) Hormone supplementation (start with low doses)
3) Radiation Therapy (cancer)
4) Blockers (thiouracil derivatives - thiocarbamindes decrease iodionation and conversionof T4 into T3)
5) stimulants (furosemide; increase in conversion of T4 to T3)
6) Diet, electrolyte infusions, etc..
** TREATMENT ME BE FOR LIFE **
