Thyroid Gland

Hypothyroid + enlarged thyroid (Goiter) can be caused by:

iodine deficiency (thyroid not working as well)

Thyroid gland contains what kind of cells

follicular cells

(these are polarized - specific transporters on apical + basolateral membrane)

Steps for thyroid hormone synthesis:

1. Iodide uptake via NIS - Na+/I+ symptorter) @ basal surface

2. Iodine exits via Pendrin = enters the colloid (where thyroglobulins reside, thyroglobulins contain tyrosine)

3. Iodine is oxidized (TPO)

4. Iodine is attached to tyrosine residues (TPO)

   1. MIT and DIT (T3) and two DITs (T4)

5. Thyroglobulin-T3/T4 complex = endocytosed = T3/T4 enters circulation

MIT vs DIT

M = Mono (one iodine added to tyrosine)

D= di (two iodine added to tyrosine )

T3= MIT + DIT

2 DIT = T4

What is the main enzyme in thyroid hormone synthesis? What roles does it play?

TPO - thyroperoxidase (binds to BOTH: Tyrosine + Iodine!

1. oxidation of iodine

2. Iodination of tyrosine

3. Coupling of iodotyrosine residues (ie. making MIT and DIT)

What stimulates TPO + what type of drugs suppress it?

TSH

Antibodies to TPO = supress its activity = HYPOthyroidism

Thiocarbamide drugs = inhibit TPO

What regulates NIS (Na+/I+ symporter?)

TSH

*congential hypothyroidism occurs when defect in NIS

Effects of EXCESS iodine

Inhibits (3):

• NIS

• TPO (no iodination of tyrosine residues)

• Secretion of hormones

What is Wolff Chaikoff Effect

EXCESS iodine = causes inhibited thyroid hormone secretion

Excess iodine = can induce what type of thyroid disorder

HYPER

• enlarged thyroid

• Tumor in thryoid = can contribute to HYPER

Role of Pendrin + what else does it affect besides the thyroid?

Pendrin = on apical membrane = allows iodine to enter colloid

Pendren Syndrome: hearing loss + HYPO/enlarged thyroid

HYPOTHYROIDISM - iodine can’t enter

Autoantibodies to Pendrin can occur: what diseases are these associated with?

Hashimotos + HYPO

Enzymes in Peripheral Conversion of T4—> T3

Deiodinases:

1 and 2 = primarily involved

D1: liver, kidney, skeletal m., thyroid

Decreased in HYPO

Incr in HYPER (we are making more of the pOTENT T3)

D2: LOCAL conversion

• brain, pituitary, fat, skeletal m.

• INCR in HYPO

• Decr in HYPER (high levels of thyroid hormone = inhibit D2 - ubiquitination)

D3: Degradation (results in inactivation T4 —> rT3)

• DECR IN HYPO

• INCR IN HYPER

D1 and D2 = 5’ monodeiodanse

D1 and D3 = 5 monodeiodinase

Majority of T3/T4 is bound/free

BOUND

yet only free = has physiological effects

what are the major carrier proteins for thyroid hormones (T3/T4)

TBG - thyroxine binding globulin

• Carrier protein concentration = proportional to TOTAL thyroid hormone concentrations (NOT FREE)

• Therefore [TBG] = only affects TOTAL thyroid hormone levels

TSH in hyper vs hypo thyroidism

HYPer: low TSH (T3/T4 = neg feedback/inhibit TRH and TSH)

HYPO: high TSH (no inhibition)

concentration of binding proteins [TBG] in hypo and hyper

normal

TRH is produced through whic pathway (GPcR)

Gq = incr Ca2+ levels

TRH = stimulates syntehsis, conjunction of alpha/beta chains of TsH AND the secretion of TSH

TRH = stimulates an increase in

PROLACTIN

6Bs of thyroid hormones effects on tissues

1. basal metabolic rate (heat generation)

2. Break down of proteins + fats (lipolysis)

   1. incr glucose GI absorption + incr GI motility (diarrhea)

3. Blood glucose levels incr (incr glycogenolysis)

4. Beta-adrenergic receptors increase

   1. incr HR, catecholamine response (EPI, NOR), decr TPR

5. Bone Effects - bone growth (excess = leads to osteoporosis in adults)

6. Brain effects - helps w/ brain maturation (retardation if low)

Thyroid hormone + carotene, effect on skin, + milk secretion

• helps w. conversion of carotene —> vit A

  • If low thyroid hormones = carotene builds up = yellow tint of skin (except sclera!)

• Degrades proteins (buildup in skin = promote water retention = puffy skin/myxedema)

  • thyroid hormones = degrades these proteins = no puffy skin

• Increases MIlk secretion! (dont Q this)

Explain Thyroid antibodies (stimulating vs blocking/antagonizing)

• Antibodies to TPO (thyroid peroxidase)

• Antibodies to Thyroglobulin = alter Tg

• Antibodies to TSH receptor

  • Stimulating: HYPER (Graves disease)

  • Blocking/Antagonizing: HYPO

Symptoms of excess vs low thyroid hormones (HYPER/HYPO)

hyper: heat intol, sweat, weight loss, warm skin, moist skin, vasodilation, incr appetite, incr gi motility (diarrhea), Catacholamine effects (EPI/NOR - tachycardia, palpitations, incr HR), CNS effects - fast reflexes, nervous, anxiety, insomnia, tremors, decreased libido/infertility

Labs: High free T3/T4, low TSH (in primary), decreased LDL, HDL, + cholesterol (due to incr lipolysis)

hypo: opposite - cold, slow breathing, slow metabb, puffy face (due to GAGs/water retention), myxedema, low appetite, weight gain, constipation, bradycardia, low pulse, hypoactive nervous syst, chronic fatigue, cna’t concentrate, delayed reflexes, decreased libido/fertility

Labs: low free T3/T4, Incr TSH (primary), hypercholesterolemia, hyponatremia (due to higher ADH)

Primary, secondary, tertiary hypo vs primary, secondary, tertiary hyper

HYPO:

primary: @ T4

Decr T4 —>

Incr TRH —>

Incr TSH

Secondary @ TSH

Decr TSH —>

Decr T4 —>

Incr TRH

Tertiary - everything low (@ TRH)

HYPER

primary: @T4

high T4—>

low TRH —>

low TSH

Secondary @ TSH

high TSH —>

high T4—>

low TRH

Tertiary (everything high - @ TRH)