NPB 101: Thyroid Gland & Hormone

thyroid gland location

in the neck over trachea (butterfly-shaped)

follicular cells of thyroid

thyroid hormone secretory cells -- produces T3 and T4

- forms spheres that surround inner lumen (which is acellular - no cells and consists of a colloid (thick fluid))

colloid of thyroid gland

fluid of follicle lumen containing thyroglobulin plus iodine and is precursor to thyroid hormone

Thyroglobulin (Tg)

- a large iodinated glycoprotein with many tyrosines

- from which the active thyroid hormone triiodothyronine (T3) and its precursor, thyroxine (T4) are synthesized

- found in the colloid & it is where TH synthesis occurs

parathyroid and C cells

parathyroid H (PTH) and C cells (secreting calcitonin) are involved with Ca++ homeostasis

thyroid hormone synthesis

1) follicular cells synthesize enzymes and Tg for colloid

2) idodide (I-) is cotransported with Na+ into the cell, specifically to colloid

3) enzymes add iodide (I-) to Tg to make T3 and T4

4) Tg is then taken back into the cell for later usage

5) intercellular enzymes separate T3 and T4 from the Tg protein backbone

6) free T3 and T4 enter circulation

what happens to the colloid and Tg upon release of TH?

- phagocytosis of colloid

- digestion of Tg in lysosomes release T4 (80%) and t3 (20%)

hypothalamic-pituitary-thyroid axis

(-) FB mechanism

- dirunal rhythm + cold (infants) stimulate hypothalamus

- stress inhibits hypothalamus

hypothalamus --> thyrotropin releasing hormone (TRH) --> anterior pituitary --> thyrotropin stimulating hormone (TSH) --> thyroid gland --> T3 and T4

major effects of thyroid hormone

1) increased metabolic rate (determines basal metabolic rate)

- increases rate of O2 consumption

- heat production (thermogenesis)

2) cardiovascular symptoms

- increased heart rate

- increased strength of contractions

(permissiveness for sympathetic nervous system activity)

3) growth (permissive to GH, enables acquisition of GH Rs)

4) development of CNS and special senses (vision and hearing)

thyroid H and target cell action

thyroid H = lipophilic

- follows general lipophilic H mode of action at target cell

- binds to a receptor --> R binds to nuclear element --> transcription --> protein synthesis --> exertion of effects

T3 vs T4

-most of thyroid hormone released from thyroid is in the form of T4

-most of the T4 is then converted in the tissues to T3, which is more active than T4

deiodinase

T4 ---------------> T3

when does thyroid hormone peak?

- at birth

- becomes lower and steady later in life

- coordinated motor movements later in life require steady balance of Hs (pertaining to cerebellum function)

- cerebellum maturation around birth

cerebellum maturation

- around birth

- requires TH

- with TH --> greater cerebellar Purkinje cells compared to without TH

- more of these cells enables greater coordination and movement in life

TH: vision and hearing

peak of TH around birth is essential for color vision and cochlear development

overview of TH disorders in the population as a whole

- 1/10 will be affected

- treatable

- life-long conditions

- if aware of the problem, can lead to serious consequences

------ possibility for miscarriages are even present

hypothyroidism

condition of hyposecretion of the thyroid gland causing low thyroid levels in the blood that result in sluggishness, slow pulse, and often obesity

- decreased BMR

- slower heart rate

- poor cold tolerance (less heat production via decreased BMR)

- increased weight (less fuel metabolism)

- decreased alertness and poor memory

hyperthyroidism

excessive activity of the thyroid gland produces abnormally high levels of thyroid hormone

- Graves' disease

- increased BMR

- increased heart rate

- increased perspiration

- poor heat tolerance (too much metabolic activity and heat production)

- decrease in body weight (quick burning of feul, not stored)

goiter

enlargement of the thyroid gland (can be in both hypo and hyperthyroidism)

caused by...

- thyroid dysfunction

- tumor

- lack of iodine in the diet

- inflammation

occurs with an overstimulation of TSH receptors

- could be due to increased TSH or similar entity (i.e.: antibody)

causes of hypothyroidism

1) primary failure of the thyroid gland

2) autoimmune disease (Hashimoto's)

3) deficiency of TSH, TRH, or both

4) lack of dietary iodine

Hashimoto's thyroiditis

an autoimmune disease in which the body's own antibodies attack and destroy the cells of the thyroid gland

- causes hypothyroidism and hyposecretion of thyroid hormone

- gland destruction

Graves' disease vs Hashimoto's disease

both are autoimmune disorders, but on opposite spectrums

- Graves' disease - causes HYPERthyroidism

- Hashimoto's disease - causes HYPOthyrodism

hypothyroidism in adults

- fatigue

- weight gain

- weak pulse

- cold intolerance (lower BMR, so body does not produce much heat)

- mental sluggishness and depression

hypothyroidism in perinatal period

- cogenital idodine deficiency syndrome

- short stature

- poor motor skills

- moderate to severe intellectual disabilities

(effects on the NS are irreversible is not corrected shortly after birth)

- goiter can occur due to a TH synthesis problem (overstimulation of TSH Rs)

3 causes of thyroid diseases

1) autoimmune (Graves' and Hashimoto's)

2) tumor (leading to hypersecretion of a given H)

3) dietary (lack of iodine - can't make such TH -- hypothyroidism)

what are the consequences of inadequate TH after birth?

- real risk of long-lasting disorders of the brain

- insufficient iodine = low IQ and poor neural development

- disorders are endemic (regional, as some places lack iodine supply)

what is the diagnosis for HYPOTHYROIDISM?

A thyroid function test. If suspecting the following, you should see:

Primary (endocrine gland issue) --> ↓T3 and T4, ↑TSH.

Secondary (hypo. or pit.) --> ↓T3 and T4, ↓TSH.

increase in TSH with low levels of T3 and T4 --> hypothyroidism

Graves' disease

- the most common cause of hyperthyroidism

- an autoimmune disorder in which the antibodies produced by the immune system stimulate the thyroid to produce too much thyroxine (T4)

- the antibodies are like TSH agonists --> they bind to TSH receptors, continously producing TH

**(no (-) FB regulation)**

- overstimulation of TSH Rs ---> goiter

- constant elevated level of TSH and TH

(TSH leads to TH secretion)

Graves' disease symptoms

- Exophthalamos (bulging eyes)

- heat intolerance (high BMR)

- weight loss (high BMR and fuel burning --> no storage)

- rapid heart rate

- hair loss

Treatments of hyperthyroidism

- drugs that inhibit TH synthesis

- surgical removal of thyroid

- destruction of thyroid using radioactive iodine followed by TH supplementation (as hypothyroidism can occur without a functioning thyroid gland)

**basically mechanisms by which the thyroid gland function of producing TH is reduced**