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BIOM 4030 > Thyroid Axis > Flashcards

Thyroid Axis Flashcards

1
Q

Hormone Synthesis

A
  • uptake of iodide by thymocytes
  • synthesis of the protein, thyroglobulin by the thyrocytes
  • Exocytosis of Tg to the follicular lumen
  • Iodination of the Tg in the lumen
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2
Q

Hormone release

A
  • endocytosis of iodinated Tg (TgI)
  • proteolysis of the TgI, releasing the thyroid hormones
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3
Q

2 oxidation steps occurs in the lumen — both use TPO!

A

Step 1: TPO iodinates tyrosine residues in the Tg to form mono- and diiodinated tyrosine residues [(MIT) and (DIT); mono- and diiodotyrosines]

Step 2: TPO causes the condensation of MIT and DIT residues to form triiodothyronine (T3) and tetraiodothyronine (T4)
• These iodinated thyronine residues remain as part of the Tg molecule

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4
Q

Thyroid regulation by TSH

A
  • TSH receptors are G-protein linked
  • Some are αs and some αq; activation of both lead to cAMP and IP3/DAG production
  • Combined actions of the two receptor types regulate almost all aspects of thyroid hormone synthesis and release
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5
Q

Regulation of Secretion

A

Pulsed secretion of TRH; highest between 10AM-2PM (Circadian)

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6
Q

Wolff-Chaikoff Effect (auto regulation)

A

an excess of iodide (>2 mg/day) inhibits iodide “trapping”

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7
Q

Humans/dogs secrete T4:T3 at _____ ratio; more ____ secreted only in hyperfunction

A

4:1; T3

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8
Q

_____________ of T3 produced by peripheral conversion from T4 in the liver and kidneys (& brain)

A

60-75%

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9
Q

T4:T3 ratio in plasma 20:1 — why?

A

Boils down to elimination — 1/2 life! (T3 is eliminated much faster than T4)

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10
Q

Transport of TH’s

A
  • > 99% of thyroid hormones in blood circulation bound to thyroxin-binding globulin (TBG) (small!)
  • Only free fractions of thyroid hormones biologically active
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11
Q

T3 binds to hormone receptors in the __________ of target cells and regulates the expression of various genes

A

Nucleus

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12
Q

T4 may bind to ___________________ on the cell membrane and activates intracellular events that bring about rapid responses

A

G-protein coupled receptors

*activated receptors may enhance or suppress gene expression

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13
Q

Four isoforms of the TR’s are known…

A
  • alpha 1 and 2; beta 1 and 2

*distribution is tissue specific and age dependent
* can form dimers w/ one another and still activate the gene

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14
Q

T4 1/2 life __________; T3 1/2 life ________

A

6-7 days; 1 day

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15
Q

Deiodination of thyroid hormones occurs in _______, ________, __________ and ___________; sequential removal of iodide to form thyronine

A

Liver; kidney; brain; muscle

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16
Q

Conjugation of thyroid hormones occurs in the _________, excretion (to prevent hyperthyroidism) via ________ and via the _____________

A

Liver; bile; kidney

17
Q

Physiologic Action

A
  • permissive; collaborate with other hormones
  • Involved in the synthesis of other hormones
  • Enhances the effects of GH
  • Regulate metabolic rate and thermogenesis
  • Essential for normal cardiac function
18
Q

Maternal Hypothyroidism

A
  • may lead to congenital hypothyroidism or cretinism
  • stunted physical and impaired mental development due to untreated prenatal deficiency of thyroid hormones
  • Mental retardation, swelling of the skin, loss of water and hair, bone thinning, delayed puberty; female ovulation issues and infertility
19
Q

____ is essential from normal development of bones and CNS of growing fetus

A

T3

20
Q

Thyroid hormone-dependent development of the brain begins ____________, completed after birth

A

In utero

21
Q

T4 is delivered to the ______________ where it is converted to T3

A

Fetal brain

22
Q

Hypothyroidism

A
  • abnormally low serum levels of thyroid hormone
  • slows metabolic processes throughout the body
  • May cause fatigue, slow heart rate, and dry skin
23
Q

T3 regulates…
T3 is needed for…
T3 substantially increases…

A
  • dendritic and axonal growth
  • myelin formation
  • synapsis formation
  • neuronal migration
  • normal hematopoiesis
  • normal gonadal development and function, including seasonality of reproduction in seasonal breeders
  • K+/Na+ pump activity
  • # and activity of mitochondria
  • ATPase activity
24
Q

Causes of Hypothyroidism

A
  • Insufficient dietary iodide (main cause)
  • Anti-thyroid factors in diet (goitrogens)
  • Mutant TSH-R or TRH-R (genetic)
  • TSH deficit
  • Mutant TH transport proteins
  • Impaired TH synthesis
  • Peripheral resistance to TH
  • Thyroiditis (Hashimoto)
25
Q

Hyperthyroidism and its symptoms

A
  • a condition in which the levels of thyroid hormones in the blood are excessively high

• Weight loss
• Nervousness
• Excessive sweating; anxiety
• Increased heart rate and blood pressure
• Protruding eyes (exophthalmia); eyelid retraction
• Goiter
• Diarrhea
• Hand tremors
• Insomnia

26
Q

Hypersecretion of thyroid stimulating hormone (TSH) is most often caused by…

A

A pituitary adenoma
Thyroid cancer*
Inflammation of the thyroid gland (thyroiditis)
Graves’ disease* (thyrotoxicosis)
- Thyroid stimulating immunoglobulins recognize and bind to the TSH receptor; mimics the TSH and activates the secretion of thyroxine (T4) and triiodothyronine (T3)

*associated w/ goiter formation

27
Q

Which causes of hypothyroidism are associated with goiter formation

A
  • Insufficient dietary iodide (main cause)
  • Anti-thyroid factors in diet (goitrogens)
  • Impaired TH synthesis
28
Q

Euthyroid Sick Syndrome (ESS)

A
  • a non-thyroidal condition where there is low circulating T3 and T4 and high rT3
  • Altered conversion of T4 to T3 due to altered activity of deiodinases and/or problems with T4 transport
  • No benefit in supplementing T4
29
Q

ESS: Diagnosis

A
  • History + Symptoms + Plasma Hormones
    + Blood
  • MRI/tomography; biopsy
  • TRH/TSH stimulation (1° vs. 2° vs. 3° )
  • I131 uptake
  • Differential: ESS; adrenal hyperfunction (all metabolic hormones!)
30
Q

ESS: Treatment

A
  • Surgery (e.g., hemithyroidectomy)
    -Hormone supplementation (start with low doses; why?)
  • Radiation therapy/chemotherapy (cancer)
  • Blockers (thiouracil derivatives, a.k.a. thiocarbamides: ~ iodination and T4>13)
  • Stimulants (furosemide; T T4→Т3)
  • Diet, electrolyte infusions, e.t.c.

TREATMENT MAY BE FOR LIFE!

BIOM 4030 (6 decks)

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