PHRM 825 Lecture 37- Thyroid Hormones

thyroid hormone produced by follicular cells

most common thyroid hormone

thyroxine (T4)

more potent thyroid hormone

Triiodothyronine (T3)

what are the growth and development effects of thyroid hormones

essential for brain development

promote protein synthesis- anabolic at normal levels

what are the metabolic effects of thyroid hormones

increase basal metabolic rate; increase O2 consumption

what are the thermogenesis effects of thyroid hormones

increase resting heat production

what are the cardiovascular effects of thyroid hormones

increase catecholamine sensitivity

how does iodide get into the cells

Na+- I- symporter (NIS)

what is iodinated by thyroid peroxidase at one or two positions and what is this mechanism called

Thyroglobulin- iodide organification

explain the hypothalamus pituitary thyroid axis

hypothalamus releases TRH--> anterior pituitary releases TSH --> stimulates thyroid gland to release T4 and T3

used for synthesis of thyroid hormones

iodine

an enlargement of the thyroid gland due to a persistent rise in TSH

goiter

severely stunted physical and mental growth

cretinism

what transports thyroid hormones

thyroxine binding globulin (TBG)

transthyretin (TTR)

albumin

which has a longer half life, T4 or T3?

T4- serves as a storage pool

what converts T4 into T3 in the cytoplasm?

Deiodinase

where are inactive thyroid hormones excreted from

the bile

symptoms of hypothyroidism

decrease in metabolic rate

defective thermoregulation

thyroid enlargement

dwarfism and mental retardation

end state of untreated hypothyroidism; water intoxication, shock, and death

Myxoedema coma

causes of hypothyroidism

Hashimoto's thyroiditis

destruction or removal of the gland

iodine deficiency

congenital

TSH deficiency (secondary)

most common cause of hypothyroidism; autoimmune disease that destroys the thyroid gland

Hashimoto's thyroiditis

symptoms of hyperthyroidism

excessive metabolism- poor thermoregulation and weight loss

increased heart rate and cardiac output

most common cause of hyperthyroidism; autoimmune; thyroid stimulating IgG; enlargement of the entire thyroid gland (diffuse toxic goiter)

Grave's disease

cause of hyperthyroidism

adenoma producing excess T3; occur mostly in older women

Toxic uninodular goiter and toxic multinodular goiter

cause of hyperthyroidsm

viral infection of the thyroid gland; transient release of stored thyroid hormones

back to normal when infection is gone

Subacute thyroiditis

pale, cool, puffy

drooping of eyelids

bradycardia

lethargy

decreased appetite

decreased BMR

hypothyroidism

warm, moist, sweating

retraction of upper eyelids

tachycardia

nervousness

increased appetite and BMR

hyperthyroidism

thyroid hormone replacement therapy

desiccated thyroid and thyroglobulin (bovine and porcine)

variable T4/T3 blood levels due to inconsistencies in sources

natural thyroid hormone preparations

thyroid hormone replacement therapy

converted to T3 intracellularly

slow onset, long half life, 6-8 weeks to reach steady state levels

levothyroxine (T4)

thyroid hormone replacement therapy

rapid onset, short duration of action (24h)

greater risk of cardiotoxicity

Liothyronine (T3)

Thyroid hormone replacement therapy

4:1 mixture of T4 and T3

discontinued

Liotrix

thioamides

antithyroid agents for hyperthyroidism

methimazole

propylthiouracil

how do thioamides work and how long does it take

inhibit thyroid peroxidase and blocks iodine organification

slow onset (3-4 weeks)

treats hyperthyroidism

radioactive iodine emitting B particles and y rays

localized destruction of thyroid particles

131-I

problems with 131-I

hypothyroidism occurs in 80%

increase in certain cancers

radiation thyroiditis

how does iodide work to treat hyperthyroidism

large dose of I- inhibits its own uptake, iodine organification, release of thyroid hormones, and decreases vascularity of the thyroid gland

clinical uses of iodide

preparation for thyroidectomy

severe thyrotoxicosis

protection from radioactive iodine fallout

what forms does iodide come in when used for treatment

Lugol's solution

KI