Thyroid Gland Physiology Flashcards
Prohormone and active hormone
The Thyroid follicle
C-cells
T4 = prohormone T3 = active hormone
Functional unit of thyroid (filled with colloid
Parafollicular cells —secrete calcitonin
Where are thyroid hormones made
In the follicular lumen (colloid)= new synthesized Thyroid H. Attached to thyroglobulin
Follicle= surrounded by epithelium
These follicular epithelial cells make TH.
How TH is made
New TH-thryroglobulin is released into the lumen (colloid)
IODINE absorbed from the ECF into the thyroid gland and into the colloid is iodinated on thyroglobulin
= T3 and T4 (MORE T4)
Thyroglobulin leaves when TH gets Iodinated
T4—>T3 where
Outer ring deiodination by DEIODINASES
80-90% converted in the periphery
10% converted in the Thyroid Gland
T3 = active and taken up by tissues that need it
How T4–> T3 is lowered
Fasting
Medical/surgical stress
Catabolic disease
TH synthesis detailed version
- Tyrosine ——> Tyroglobulin + ER/Golgi modifications (epithelial cell) goes to the colloid exported out of epithelial cell
- I —> NIS——> Pendrin into the colloid
- Tyroglobulin gets Iodinated (peroxidased)
- TSH stimulates pinocytosis of tyroblobulin-iodinated to back in to the follicular epithelial cell
- Proteases break it down to Tyrosine and T3 and T4
- T3 and T4 are exported out to the circulation
I trap
I enters the epithelial thyroid cell with 2 Na+ ions with the NIS transporter, from the blood
When there is low I
T3 is favored
Deiodinase deficiency
Low T3 and T4 made from tyroblobulin
PENDRIN mutation
Cl-/I pump
(I use NIS to get into epithelial cell——>Pendrin to get into colloid)
Gene SLC26A4= PDS = I can’t get to colloid
=Hypothyroidism + Goiter
=sensorineural hearing loss in cochlea
Wolff-Chaikoff effect
High levels of [I] ———I Thyroid hormones synthesis
Hypothyroidism
PTU
TX: for hyperthyroidism
Inhibits NIS, Pendrin, Peroxidases
T3 and T4 circulate in the blood how
99% bond to plasma proteins 1. Thyroxine-binding globulin (TGB)-made in liver 2. Transthyretin (TTR) 3. Albumin 1% free
How to test TH levels
T4 has higher affinity for TBG
TEST: TBG(most bond to T4) + T3 rein uptake (antibody for T3)
RESULTS
High T4, T3 resin uptake
Hyperthyroidism
RESULTS
LOW T4, T3 resin uptake
Hypothyroidism
RESULTS
HIGH T4,
LOW T3 resin uptake
HIGH TBG
RESULTS
LOW T4,
HIGH T3 resin uptake
LOW TBG
RESULTS
HIGH TBG
LOW T3 resin uptake
Pregnancy
(Low amount of free T3 and T4)———> HIGH stimulation to synthesize T3/T4 (negative feedback)
= HIGH T3/T4 levels, however, NORMAL free T3/T4 -physiologically active
=CLINICALLY EUTHYROID
RESULTS
LOW TBG
HIGH T3 resin uptake
Hepatic Failure
More free T3 and T4 found) ———I synthesis of T3/T4 (negative feedback
Control and regulation of TH synthesis and secretion
T4/T3 ———I AP (TSH) + HYPO paraventricular Nucleus(TRH)
TSH———> secretion of T3/T4 + growth of thyroid gland (trophic effect)
TSH is secreted at a steady rate
LOW TSH
Goiter and Thyroid grows to large = Hypothyroidism
Because TSH ——> Thyroglobulin-iodinated(stored in colloid) to pinocytosis into follicular cells to breakdown and release T4/T3
NoTSH= increased storage in colloid
Factors that increase T3/T4 secretion
TSH
Thyroid- stimulating Igs
High TBG (pregnant women)
Factors that decrease T3/T4 secretion
LOW I, TBG
X: deiodinase
EXCESSIVE I = Wolff-Chaikoff effect
Perchorate Thiocynate——I NIS
PTU———I Peroxidase enzymes
THYROID HORMONES (T4/T3) FUNCTIONS in other organs
NA+/K+ ATPase Transport/ structural proteins B1 receptors (adrenergic) -E Myosin Lypolysis/gluconeogenesis/gycogenolysis/O2 consumption Protein synthesis/ heat production GROWTH, bone maturation Other key metabolic enzymes
Thyroid H.s increase what in metabolism
BMR
Due to increased Na+/K+ = high O2 consumption and heat made
(Long-lasting effect)
Hyperthyroidism = HIGH BMR Hypothyroidism = LOW BMR
T3/T4 on Lipid metabolism
Fat mobilization = HIGH FA oxidation
Lowers cholesterol and TAG (lowers fat)
Carotene——> VIT A (eyes)
make free glucose (gluconeogenesis/glycogenolysis)+ increase glucose storage by insulin
Hypothyroidism= high cholesterol levels, blindness and jaundice
T3/T4 on cardiovascular effects
T4–> T3
T3=
1. Tissue thermogenesis
2. Decrease Systemic vascular resistance
LOWER Diastole BP = decrease Afterload = HIGH CO
LOWER Diastole BP= cause aldosterone to release= increase Preload= HIGH CO
= Increase blood volume
Also makes B1 adrenergic receptors (NE) which cause increase heart myocardial cells constriction
How B1 get effected by TH.s
They make B1 adrenergic receptors (NE) which cause increase heart myocardial cells constriction (sympathetic)
This overtakes the M2 receptors (ACH) which decreases CO and heart contraction (parasympathetic)
T3/T4 effects on Growth
Act with GH to promote growth
Act with somatomedins to promote bone formation
Somatostatin
Inhibits GH and TSH from AP
Inhibits pancreatic Hs. Like insulin and glucagon
Inhibits gastric enzymes from secretion
T3/T4 effects on CNS
Important in prenatal synapse formation and myelination and dendrite formation
Low TH during prenatal= cretinism (learning disability, dumb/foolish)
EXCESS TH on the Metabolism and Bone and CNS
Metabolism:
Heat intolerance (prefers cold)
Weight loss
HIGH BMR
Bone:
Osteoporosis
CNS:
Agitation, anxiety, ADD, Hyperreflexia
DEFICIENT TH on the Metabolism and Bone and CNS
Metabolism:
Cold intolerance (prefer heat)
Weight gain
Low BMR
Bone:
Stunted growth
CNS:
Cretinism, slow movements, impaired memory, low mental capacity, somnolence, listlessness, tiredness
EXCESS TH on Skin, CV system, and GI
Skin:
Sweating
CV:
Tachycardia, palpitations, atrial fibrillations, high CO failure
GI:
Diarrhea
DEFICIENT TH on Skin, CV system, and GI
Skin:
Dry
Myedema
CV:
Bradycardia
Low CO, and contraction
Heart failure
GI:
Constipation
Primary Hyperthyroidism
Thyrotoxicosis Graves Disease (most common)
Secondary Hyperthyroidism
HIGH TSH from AP
Despite the high T3 trying to negative feedback and ——I AP
Graves Disease
Cause
Primary hyperthyroidism
Thyroid Stimulating Ig ——> TSH R. On Thyroid gland
= increases T3/T4 continuously
(T3——I TSH at AP, which does nothing)
LOW TSH
Grave’s Disease
Sx:
Dx:
EXOPHTHALMOS = protrusion of the eyeballs
Periorbital edema
Dx: high T3/T4 free and bonded, TSI (TS Igs)- not tumor in this case
Goiter + ophthalmophaty
High I also found
Graves Disease
Tx:
PTU
Thyroidectomy
High I-
B1 blocking agents
Hypothyroidism
causes
Tx:
- Gland destruction - Hashimoto’s Tyroditis:
- I deficiency——I TH synthesis and release
- Drugs
- Defected enzymes
- Hypothalamic disease or AP disease (Sheehan’s syndrome)
- TH resistance
- Low TSH/TRH
TH replacement therapy
Hypothyroidism
Tx:
T4 replacement (Higher dosage needed in younger patients, since 1/2-life increases with age)
*overprescribing T4 in post-menopause women= osteoporosis
Hashimoto’s Thyroditis
Thyroglobulin can’t make T4/T3
= LOW T3/T4
=HIGH TSH
=growth of thyroid gland GOITER
GOITER
HIGH TSH
Hyperpigmentation
HIGH ACTH
Hypothyroidism congenital
causes
Sx:
X: I
Mom takes anti-thyroid medication
Thyroid gland did not develop
LOW T3/T4
Sx:
Feeding problems, resp. Probs, protruding tongue, ,growth stunted, mental slowness, Jaundice, dry skin, hypotonia
IF I IS LOW ——> hypothyroidism and why
Low T4/T3 made on the Thyroglobulin
= HIGH TSH made
= growth of thyroid gland GOITER
- If normal levels of T4/T3 can still be made with this elevated TSH= EUTHYROID and ASYMPTOMATIC (with goiter)
- If normal levels of T4/T3 can’t be reached despite TSH increase= HYPOTHYROIDISM
Sheehan Syndrome
AP necrosis
X: lactation, hypothyroidism, amenorrhea (no periods) other endocrine dysfunctions,
postpartum hemorrhage can cause it, or other reasons
LOW TSH, T3/T4
GOITER happens during:
- Hyperthyroidism = Grave’s disease, AP tumor in TSH producing area
- Primary Hypothyroidism = low I in diet, autoimmune thyroid disease, Hishimoto’s disease, random cause
Thyroiditis in hyperthyroidism
low I found
High T3/T4
low TSH
Hyperthyroidism
Sx:
Weight loss, sweating, tremor, muscle spasm, hot feeling, Goiter, EXOPHTHALMOS, increased CO, high BMR
Hyperthyroidism causes
Graves’ disease Thyroid neoplasm High TSH Exogenous T3/T4 Defected AP or tumor of the AP
