thyroid hormones

what is a follicle?

• the functional unit of a thyroid gland

• made up of follicular cells

• filled with colloid

what is colloid filled with?

a protein rich fluid

where is thyroglobulin synthesized?

• in the ER of the follicle cell, processed by the golgi complex, and then secreted into the lumen of the follicle

what do thyroglobulin molecules contain?

tyrosine (tyrosol) residues, to which iodide will attach in the synthesis of the thyroid hormone

how are thyroid hormones synthesized?

1) iodide is co transported from the blood into the follicle

2) an iodide transporter moves the iodine from the follicle to the colloid

3) conjugation occurs in the colloid, where iodine joins the thyroglobulin and either creates 2 DIT or 1 MIT

4) either 2 DITs are combined or 1 MIT and 1 DIT are combined

5) DIT + DIT is T4 and MIT + DIT is T3

6) T3 and T4 are taken into the cell via endocytosis

7) lysosomes snip and chew up the Tg and T3 and T4

8) . T3 and T4 are diffused into the blood

9) the amino acids are recycled and reused

What is stored in the colloid for reserves?

iodinated TG containing MITs and DITs plus T3 and T4 are stored in the colloid,

• this provides weeks of hormone supply if the body runs low

how much T4 is secreted?

80%

T4 is converted to T3 or rT3 in the peripheral tissues

how much T3 is secreted?

20%

T3 is the most biologically active

how much rT3 is secreted?

less than 1%

it is biologically inactive

how much thyroglobulin molecules are released?

very small amounts

what is the most active thyroid hormone?

T3

What percent of thyroid hormones are bound to protein?

99%

what are the two functions of the binding proteins on thyroid hormone?

• maintains a large circulating reservoir of T4

• prevents thyroid hormone from being filtered in the kidney and excreted in the urine

what do the free T4 and T3 do?

they cross the capillary wall and enter the body’s cells

what does the hypothalamus synthesize and secrete?

Thyrotropin releasing hormone (TRH)

what does the anterior pituitary synthesize and secrete?

thyroid stimulating hormone (TSH)

what is the secretion of TRH and TSH regulated by?

negative feedback of circulating levels of free T3 and T4

what is a sensitive indicator of thyroid gland function?

concentrations of TSH

what other factors contribute to regulation of the hypothal-ant pit- thyroid gland axis?

• iodide availability

• prolonged exposure to cold

• drugs

• disease

if T3 and T4 are lowered what happens to TSH

it increases

if T3 and T4 are high, what happens to TSH?

it decreases

what is the effect of TSH on the thyroid follicular cell?

• anything involved in the synthesis of T3 and T4

• growth and proliferation of thyroid follicular cells

  • stimulation of growth

what is the thyroid hormone action on body’s cells?

• there is bound T4 and T3 in the blood vessel, as well as free T3 and T4

• it diffuses into the cell membrane

• T4 is converted into T3, because T3 is more potent

• T3 binds to the thyroid hormone receptor inside the nucleus on the DNA and results in gene expression

what are the proteins created by the actions of the thyroid hormones?

• sodium potassium pump and atpase

• mitochondrial enzyme, respiratory enzymes, proteins for growth of mitochondia

• B-adrenergic receptors

• gluconeogenic enzymes (make glucose)

• myosin heavy chain

what are the major effects of thyroid hormone on the babies and children?

• growth and development of the fetal brain

  • deficits cause mental retardation

• infants are screened for TSH levels at birth

• growth and development of the child

can low thyroid issues as a child be treated?

• if hypothyroidism is treated within a few days of birth, development can proceed almost normally including mental development

• hormone replacement treatment can help catch up growth during childhood

What is another major function of thyroid hormone?

Basal Metabolic Rate (BMR)

How does thyroid hormone impact BMR?

• thyroid hormone is a major calorigenic hormone, which creates cycles of catabolism/anabolism, increases sodium potassium pump activity and it generates internal heat

if there is a complete lack of thyroid hormone how does the BMR change?

declines to around 40-50% of normal

If there is excess thyroid hormone how does BMR change?

increases to 60-100% above normal

If you have increasing amounts of T3 and T4 does BMR increase or decrease?

increase

what is hyperthyroidism?

• when BMR increases at rest because T3 and T4 is increased

• symptoms: unintentional weight loss, sensitivity to heat

what is hypothyroidism?

• low BMR because Low T3 and T4

• symptoms: fatigue, hair loss, unintentional weight gain bc low energy, sensitivity to cold

what is the permissiveness of thyroid hormone?

potentiates the effectiveness of epi and norepi

what is euthyroid?

normal thyroid function

what are the characteristics of hypothyroidism?

• BMR: decreased

• gluconeogenesis: decreased

• glycogenesis: decreased

• synthesis: decreased

• proteolysis: decreased

• lipogenesis: decreased

• lipolysis: decrease

• BLOOD CHOLESTEROL: INCREASED

• thermoregulation: sensitive to cold

• ANS: normal concentration epinephrine

what are the characteristics of hyperthyroidism?

• BMR: increased

• gluconeogenesis: increased

• glycogenesis: increased

• synthesis: increased

• proteolysis: increased

• lipogenesis: increased

• lipolysis: increased

• BLOOD CHOLESTEROL: DECREASED

• thermoregulation: sensitive to head

• ANS: upregulation of beta adrenergic receptors, therefore elevated sensitivity to epi: resting HR above 100

what is the most common worldwide cause of hypothyroidism?

dietary: iodine/iodide deficiency. TSH levels elevated which stimulates the grwoth of the gland (GOITER)

what is the most common cause of hypothyroidism in the USA?

Hashimoto’s disease: circulating immunoglubulins that destroy the thyroid gland. TSH is elevated. The IG stimulated destruction causes inflammation and swelling (GOITER)

what are the other ways that hypothyroidism is caused?

• radiation: destruction of the thyroid by radiation

• secondary causes: enzyme defects, pituitary problems

what is the most common cause of hyperthyroidism in the USA?

Graves disease: immunoglobulins called Thyroid stimulating antibodies mimics TSH and stimulates the thyroid gland. TSI stimulates the secretion of thyroid hormone, therefore a hyperthyroid state (GOITER)