Thyroid metabolic hormone

What kind cell type are follicular of the thyroid

cuboidal

What is located in the follicular epithelial cells

TSH receptors, Na/I- symporters, thyroglobulin synthesis

what is located in the colloid of the thyroid

thyroglobulin stroage, MIT/DIT, T4/T3

What are the c cells also known as

parafollicular cells

What is located in the c cells

calcitonin

What cancer occurs in the c cells

medullary thyroid

What stimulates the release of TRH

hypothalamic parvocellular neurons

What does the TRH travel through to reach the anterior pituitary

Portal system

What does TRH bind to release TSH

TRHR

Where does TSH bind to release T4 and T3

TSHR of the thymus

Aside from T4 and T3, what does the binding of TSH to TSHR stimulate?

Increased cAMP

What does T4/T3 do?

Increase metabolism

What kind of feedback does T4/T3 stimulate, and what does it stimulate?

Negative: Hypothalamus and pituitary

What does the feedback from T3 and T4 cause?

Decreased TRH and TSH

What inhbits TSH

Somatostatin, do[amine, glucocorticoids

Where do glucocorticoids inhibit TSH

Supraphysiological ranges

What is graves disease

Production of a thyroid stimulating immunoglobin (TSI)

What does Graves disease cause?

Increased TSHR and T4/T3

What is the wolff-chaikoff effect?

Sudden Increase in I- in a normal I- thyroid causes a decreased in T4/T3, via auroregulatory shut-off to prevent hormone excess

What does the wolff-chaikoff effect counter?

Thyroid storm

What is jod-basedow phenomenon

Sudden increase in I- in I- deficient/autonomous thyroid resulting in increased, unregulated T4/T3, and no feedback control

What illnesses can lead to jod-basedow phenomenon?

Toxic adenoma, iodine deficient patients

What is the ratio of iodine consumption to excretion in a typically healthy person

1:1

About how much iodine does the kidney excrete?

About 480 ug

About how much iodine does the stool excrete?

20 ug

How much I- does the thyroid use?

about 120 ug

How much Iodine does the body have as a reserve (iodothyronines)

about 7,500 ug

How much I- is released from the thyroid?

40 ug

How much iodine is used in thyroid hormones?

80 ug/d

Major sources of iodine?

Seafood/shellfish, dairy, eggs

Fortified sources of iodine?

Salt, bread/grains

After TSH binds to TSHR, what occurs?

Increased of Na/I- symporter, Thyroglobulin, pendrin, dual oxidase, and thyroid peroxidase, endocytosis

What exports Iodide to colloid?

Pendrin

Where is Thyroglobulin (TG) made?

ER/Golgi

Where is TG secreted?

Colloid

What amino acid primarily contributes to the TG formation?

Tyrosine

What makes H2O2?

Dual oxidase (DUOX2)

What oxidises I- with H2O2?

TPO

What is the process of combining H2O2 with Iodine called?

Iodination

What does iodination resut in?

Production of monoiodotyrosine (MIT) and Diiodotyrosine (DIT)

What is used to couple MIT and DIT?

H2O2 and TPO

How is T3/T4 released?

TG is endocytosed, and the undergoes lysosomal proteolysis, which cuts out T3/T4, allowing it to go into the blood

What allows the T/T4 to exit?

Monocarboxylate transporter 8 (MCT8)

How are material recycled for T3/T4 synth

MIT/DIT are deiodinated, and I- and tyrosine are reused

What does chronic TSHR stimulation cause?

Goiter, via hyperplasia

What forms T3?

H2O2 + MIT + DIT

What form T4

H2O2 + DIT + DIT

Is Hashimoto’s thyroiditis hypo or hyper?

Hypo

Is Hashimoto’s thyroiditis Primary or secondary?

Primary

Mechanism of Hashimoto’s thyroiditis

Autoimmune destruction of thyroid follicles

What does Hashimoto’s thyroiditis increased and decrease?

More TRH and TSH, less T4 and T3

Clues for Hashimoto’s thyroiditis

Anti-TPO and anti TG bodies

Is iodine deficiency hypo or hyper?

Hypo

Is iodine deficiency primary or secondary

Primary

What is the mechanism of iodine deficiency

Not enough iodine substrate to make thyroid hormones

What does iodine deficiency result in?

More TRH and TSH, less T4 and T3

Clues for iodine deficiency

Impared neurodevelopment

Is congenital hypothyroidism primary or secondary?

Primary

mechanism of congenital hypothyroidism

Infant thyroid is absent/underdeveloped

What is the effect on the body for congenital hypothyroidism

Increased TRH and TSH, decreased T4 and T3

What are clues for congenital hypothyroidism

Accumulation of mucopolysaccharides, and enlarged toungue

Is Sheehan syndrome hypo or hyper

Hypo

Is Sheehan syndrome primary or secondary

Secondary

Mechanism of Sheehan syndrome

Pospartym pituitary hemorrhage resulting in decreased activity.

Physical effects of Sheehan syndrome

Increased TRH, decreased TSH and T4/T3

Symptoms of Sheehan syndrome

Failure to lactate

Is Graves disease Hypo or Hyper

Hyper

Is Graves disease primary or secondary

Primary

Mechanism of Graves disease

TSI antibody stimulate TSH receptor

What increases and decreases due to Graves disease

Decreased TRH and TSH, increased T4/T3

Clues for Graves disease

Exophthalmos (bulging eyes)

Is Toxic Adenoma Hypo or Hyper

Hyper

Is Toxic Adenoma primary or secondary

primary

Mechanism of Toxic Adenoma

Single autonomous thyroid nodule secretes hormone independently

What happens in the body for Toxic Adenoma

Less TRH and TSH, more T4/T3

Clues for Toxic Adenoma

“hot” nodules upon screening

What are the thyroid mechanisms of action

Bone growth, brain maturation, B1 adrenergic effects, Basal metabolic rate, blood sugar, breaking down, baby development

Why is T3 more responsible for the thyroid hormone effects?

It has a higher affinity for binding the nuclear receptors

What makes up the nuclear receptors?

Heterodimer with retinoid x receptor

How does T3 do bone growth

GH and IGF

What is Throtoxicosis in bone growth?

Early epiphyseal closure of plates

How does T3 do brain maturation

Increases diffrentiation, migration, plasticity, deficiency, cretinsim

What does T3 do to B1 adrenergic receptors?

Increases CO, HR, SV

What can thyrotoxicosis resul in for the receptors?

Beta blockade

How does T3 impact basal metabolis rate?

Increases Na/K ATPase, increases O2 use, increases RR and temperature

How does T3 impact blood sugar

Keeps glucose normal while increased glycogenolysis, gluconeogenesis, glycolysis

How does T3 function in breaking down lipids/proteins?

Increases lipolysis, decreases cholesterol, increases proteolysis

How does T3 impact babies

Fetal thyroid synthesizes surfactant

What can babies with impaired T3 present with?

RDS

What is T3/T4 bound to most of the time in the plasma?

TBG

What does T4 bind for CSF transport?

Transthyretin (TTR)

What does TBH, TTR, and albumin function as?

Resevoir

What do active T4 and T3 do?

Feedback, tissue effects, inactivation, excretion

Is T4 a prohormone

Yes

Is T3 a prohormone

No

Is T3 an active hormone

Yes

Why does T4 have a higher half life?

More affinity for TBG

What does T4 ensure?

Stable circulating pool

What does T3 do?

Potent, rapid metabolic effects, feedback control, and quickly cleared

What does rT3 do?

Acts as a break on metabolism in conditions of starvation and illness