Thyroid Hormones Flashcards
triiodothyronine
T3
thyroxine
T4
Thyroid hormone preparation of T4
Levothyroxine (given orally, long half life)
T3 aka
triiodothyronine
T4 aka
thyroxine
Thyroid hormone preparation of T3
Liothyronine (more potent, faster acting but short half life, injectable)
When do you give T3?
T3 given only when an immediate response is needed (E.g. in myxodema coma)
MOA of thyroid hormones
➢ Thyroid hormones are attached to plasma carrier proteins.
• Hormones dissociate from carrier proteins enter the cell by active transport
➢ Within the cell T4 converted to T3 – enters nucleus- bind to thyroid hormone receptor - localized in the nucleus –> Stimulates transcription of particular genes
Levothyroxine
T4 hormone prep
Effects of Thyroid hormones on growth & development
• Essential for normal physical & mental growth, hence cretinism - mental retardation
caloric effects of thyroid hormones
- ↑ BMR and
* ↑ manitain body temperature
Liothyronine
T3 hormone prep
cardiovascular effects of thyroid hormones
- ↑ HR and
* ↑ peripheral resistance
metabolic effects of thyroid hormones
- ↑ blood sugar,
- ↑ synthesis of fatty acids and
- decrease plasma CH and TG levels
Use of thyroid hormones
➢ Hypothyroidism caused by:
- Hashimoto’s disease
- Myxedema
- Following surgical ablation of thyroid gland
hypothyroidism signs and symptoms
- anemia;
- hyponatremia,
- galactorrhea,
- goiter;
- hard, pitting edema of the lower extremities
- delayed return of deep tendon reflexes
- Any combination of a few or many signs and symptoms may occur at any given time.
- Some signs and symptoms, such as galactorrhea, anemia, and skin changes are seen in individuals in later stages of hypothyroidism.
Thyroid Inhibitors:
- Perchlorate,
- thiocyanate,
- goitrin
Thyroid Hormone Synthesis
- Uptake of Iodide (iodide trapping)
- Iodide organification
• (oxidation and iodination) - Coupling of MIT and DIT
- Secretion of thyroid hormones
- Conversion of T4 to T3
Ionic Inhibitors
Affects uptake of Iodine
- Perchlorate (ClO4- )
- thiocyanate (SCN- )
➢ No Therapeutic use: only Diagnostic
Monovalent anions
Affects uptake of Iodine
- Resemble Iodide
- Inhibit transport of iodide into thyroid
➢ No Therapeutic use: only Diagnostic
Thyroid peroxidase
Oxidizes iodide to iodine
Thioamides
Antithyroid drug!
➢ Iodine rapidly iodinates tyrosine residues in thyroglobulin forming MIT (mono-iodotyrosine) and DIT (di-iodotyrosine)
• Inhibited by: Thioamides
Coupling of MIT and DIT
➢ Coupling reaction involves oxidation by:
• Thyroid peroxidase
- MIT + DIT –> T3
- DIT + DIT –> T4
➢ Stored in thyroglobulin in colloid matrix
• Inhibited by thioamides -
examples:
• Methimazole
• Propylthiouracil
Thioamides MOA
➢ Inhibit thyroid peroxidase :
• Block iodine oxidation
• Coupling of MIT and DIT
Propylthiouracil MOA
Inhibit peripheral conversion of T4 to T3
• Block synthesis T3 and T4 not release, therefore slow onset of action
Thioamides A/E
➢ Relatively low incidence (3 – 12%) • Maculopapular pruritic rash • Hypothyroidism • Gastrointestinal intolerance • Agranulocytosis (
Secretion of T4 and T3 Inhibited by:
Iodine and Iodides
Secretion of T4 and T3
➢ Proteolysis - release of T4 and T3 stored within thyroglobulin (TG)
• MIT and DIT deiodinated; iodine reutilized
➢ Inhibited by Iodine and Iodides
Iodides
➢ Inhibit TH release - thyroid constipation
➢ Decreased size & vascularity of gland
➢ Improvement of thyrotoxic symptoms occurs rapidly – used in thyroid storm
Conversion of T4 to T3 Inhibited by
- Propranolol
- Propylthiouracil
- Glucocorticoids (prednisolone)
Conversion of T4 to T3:
➢ 80% of T4 converted to T3 in peripheral tissues
• De-iodination of T4 (thyroxine) to active T3 (triiodothyronine)
Lugol’s Iodine and Na/K Iodide:
• use
• toxicity
Use:
• Preoperatively- thyroidectomy
• Thyroid storm
Toxicity:
• Iodism- rash, rhinorrhoea, ulcers, conjuctivitis
Radioactive Iodine
- what
- half life
I-131
➢ Rapidly absorbed (orally)
➢ Concentrated in thyroid
➢ Emits b radiation –> destruction of thyroid gland
• half life (5 days)
Use of radioactive iodine
• advantages
• disadvantages
• contraindicated
Use: Hyperthyroidism
Advantage:
• Inexpensive, simple, outpatient basis
• No surgical risk
• Permanent cure
Disadvantage:
• response slow
• Hypothyroidism
Contraindicated:
• pregnancy,
• young patients
Treatment of Hyperthyroidism
➢ Antithyroid drug therapy
• Propylthiouracil, methimazole
➢ Thyroidectomy
➢ 131Iodine
Thyroid Storm
• triggers
• treatment
• what is it
aka thyrotoxic crisis
• high mortality
Triggers:
• Acute illness, surgery, radioiodine in an untreated thyroid.
Treatment:
• Large doses of Propylthiouracil: inhibit the peripheral conversion
• Propranolol - control cardiac manifestations
• Potassium iodide – inhibit release of thyroid hormones
• Glucocorticoids- protect against shock, block conversion of T4 to T3
What is Thyroid Storm
Thyroid storm is a crisis or life-threatening condition characterized by an exaggeration of the usual physiologic response seen in hyperthyroidism.
Whereas hyperthyroidism can cause symptoms such as sweating, feeling hot, palpitations and weight loss - symptoms of thyroid storm are more severe, resulting in complications such as:
- fever
- dehydration
- rapid heart rate
- nausea/vomiting
- diarrhea
- irregular heart beat
- weakness
- heart failure
- confusion/disorientation
- death
Propranolol
beta blocker
➢ Many symptoms of thyrotoxicosis - sympathetic stimulation- palpitation, nervousness, tremors
• b-blockers - Block physiological effects of sympathetic nervous system stimulation
