Thyroid hormones Flashcards
Thyroxine (T4) is produced ___ times more than Triiodothyronine (T3)
10x
Triiodothyronine (T3) is more ___
potent
Physiologic effects of thyroid hormones
Growth and development
* essential for ___ development (absent T3 = cretinism)
* Promote skeletal/muscle growth; ___ at the levels of hyperthyroidism
- brain
- catabolic
Physiologic effects of thyroid hormones
Metabolic effects
* ___ basal metabolic rate (BMR); Increase ___ consumption.
* Starvation lowers both ___
hormone and thyroid receptor.
- Increase, oxygen
- T3
Physiologic effects of thyroid hormones
Thermogenesis
* Increase resting ___ production.
* Inability to adjust to environmental temperature
- heat
Physiologic effects of thyroid hormones
Cardiovascular effects
* Increase ___ sensitivity
catecholamine
Steps of thyroid hormone synthesis
- Dietary iodine → ___ in the stomach
- Iodide is actively transported into the cell by ____
- In the follicular cell, iodide passes down its electrochemical gradient and into the follicular colloid (partially through the apical transporter, ___). It is oxidized by ___ to ___ at the apical membrane.
- Iodide-free ___ is transported to the apical membrane.
- Thyroglobulin is ____ at one or two positions, forming the hormone precursors ___, and ___ (iodide organification).
- MIT + DIT = tri-iodothyronine (3,5,3ʹ-__) and DIT + DIT = tetra-iodothyronine (T4) = ___. Coupling is dependent on thyroid peroxidase.
- Thyroid hormone-containing ____ is retrieved back into the cytosol of the follicular cell as colloid droplets by pinocytosis.
- Lysosomal exopeptidases cleave ___
(or T) from thyroglobulin and the 3
hormones are ___ into circulation where T4 can be converted to the more active T
3 by ___.
- I-
- Na-I symporter (NIS).
- pendrin, thyroid peroxidase, I
- thyroglobulin
- iodinated by thyroid peroxidase, mono-iodotyrosine (MIT), di-iodotyrosine (DIT)
- T3, thyroxine
- thyroglobulin
- T4, released, 5’deiodinase
Iodide organification
Catalyzed by ___
thyroid peroxidase
Hypothalamus-pituitary-thyroid axis
Hypothalamus: ___
Anterior pituitary: ___
Thyroid gland: ___
- TRH
- TSH
- T4 and T3
Iodine
- Used for synthesis of ___.
- high amounts in ___
- Goiter – an enlargement of the thyroid gland due to a persistent rise in ___
- ___ – severely stunted physical and mental growth
- Routinely added to ___
- thyroid hormones
- seafood
- TSH
- Cretinism
- table salt
Transport
Transported in plasma by
* ___ (TBG) – primary transport protein
* ___ (TTR)
* Albumin
Transport proteins have greater affinity to T4
* Only 0.04% of T4 is ___.
* T4 has a ___ half life than T3; serves as a storage pool (2 – 3 months)
* T3 has a more ___ onset.
- Thyroxine-binding globulin
- Transthyretin
- free
- longer
- rapid
deiodinase converts T4 to ___
T3
Metabolism
- Deiodination
- Conjugation to form ___ with the phenolic group
- Excreted via the ___.
- Some are hydrolyzed by bacteria; marginal ___ circulation
- glucuronide or sulfate
- bile
- enterohepatic
Hypothyroidism Symptoms
- ___ in metabolic rate – fatigue, mental dullness, lethargy, inattention
- always cold
- May occur with thyroid enlargement (nontoxic ____).
- Dwarfism and mental retardation (____) in infants and children
- ____ coma – end state of untreated hypothyroidism; water intoxication, shock, and death
- Decrease
- Goiter
- cretinism
- Myxoedema
causes of hypothyroidism
- ___’s thyroiditis – most common; autoimmune disease that destroys he thyroid gland
- Destruction or removal of the gland (radiation, X-ray, thyroidectomy)
- ___ deficiency
- Congenital (cretinism)
- Secondary – ___ deficiency
- Hashimoto’s
- iodine
- cretinism
- TSH
Hyperthyroidism Symptoms
- ____ metabolism – always hot and weight loss
- Increased ___ and cardiac output
- excess
- heart rate
Hyperthyroidism Causes
- ___ diseases - Most common; autoimmune; thyroid-stimulating ___;enlargement of the entire thyroid gland (diffuse ___)
- Subacute thyroiditis - ___ infection of the thyroid gland; transient release of stored thyroid hormones
- Grave’s, IgG, toxic goiter
- Viral
T or F: Toxic uninodular goiter and toxic multinodular goiters are adenomas producing excess T3; occuring mostly in older women
True
Hypothyroidism: Thyroid hormone replacement therapy
Natural thyroid hormone preparations
* Desiccated thyroid & thyroglobulin (___ or ___)
* ___ T4/T3 blood levels due to inconsistencies in sources
- bovine or porcine
- variable
Hypothyroidism: Thyroid hormone replacement therapy
Levothyroxine (T4)
* Converted to ___ intracellularly.
* ___ onset, long half-life (____); 6-8 weeks to reach steady-state levels.
- T3
- slow, 7 days
Hypothyroidism: Thyroid hormone replacement therapy
Liothyronine (T3)
* ___ onset, ___ duration of action (24 hr) requiring multiple ___ doses
* ___ risk of cardiotoxicity
* ___ to monitor using conventional laboratory tests.
- rapid, short, daily
- greater
- difficult
Liotrix
* ___ mixture of T4 and T3
* More expensive, but ___ to be more effective than T4 administration alone.
- 4:1
- not shown
Hyperthyroidism: Thioamides
- Antithyroid agents
- Methimazole, propylthiouracil
- Inhibit ___
- Block iodine ___
- Block coupling of the ___
- ___onset (3 – 4 weeks)
- Require depletion of stored ___
.
- thyroid peroxidases
- organification
- iodotyrosines
- Slow
- T4
Hyperthyroidism: I 131
- Radioactive iodine emitting ___ particles and ___ rays
- t1/2= ___ days
- Localized destruction of ___
No surgery and lower cost
- β, γ
- 8 days
- thyroid follicles
Problems of I 131
- ___ occurs in 80% of patients.
- Potential increase in certain ___
- Radiation thyroiditis (in rare cases leading to ____); prevent with pretreatment of ____ drugs
- Contraindications: Not for pregnant women or nursing mothers.
- hypothyroidism
- cancers
- thyroid strom, antithyroid
Hyperthyroidism: Iodide
- Large dose of I- ___ its own uptake, iodine ___ (Wolff–Chaikoff block), release of thyroid hormones, and decreases vascularity of the thyroid
gland. - Beneficial effect is transient and thus not used for ___ management.
- Lugol’s solution - Aqueous solution of elemental I and KI
- Used for preparation for ___, Severe ___, Protection from ___ iodine fallout (nuclear accident or military exposure)
- SE: Hypothyroidism, sensitivity to ___ in some patients (ex. angioedema)
- inhibits, organification
- long term
- thyroidectomy, thyrotoxicosis, radioactive
- iodine
hypothyroidsism vs hyperthyroidism
