Flashcards in Thyroid Hormones Deck (38):
1
triiodothyronine
T3
2
thyroxine
T4
3
Thyroid hormone preparation of T4
Levothyroxine (given orally, long half life)
4
T3 aka
triiodothyronine
5
T4 aka
thyroxine
6
Thyroid hormone preparation of T3
Liothyronine (more potent, faster acting but short half life, injectable)
7
When do you give T3?
T3 given only when an immediate response is needed (E.g. in myxodema coma)
8
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
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Levothyroxine
T4 hormone prep
10
Effects of Thyroid hormones on growth & development
• Essential for normal physical & mental growth, hence cretinism - mental retardation
11
caloric effects of thyroid hormones
• ↑ BMR and
• ↑ manitain body temperature
12
Liothyronine
T3 hormone prep
13
cardiovascular effects of thyroid hormones
• ↑ HR and
• ↑ peripheral resistance
14
metabolic effects of thyroid hormones
• ↑ blood sugar,
• ↑ synthesis of fatty acids and
• decrease plasma CH and TG levels
15
Use of thyroid hormones
➢ Hypothyroidism caused by:
• Hashimoto’s disease
• Myxedema
• Following surgical ablation of thyroid gland
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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.
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Thyroid Inhibitors:
• Perchlorate,
• thiocyanate,
• goitrin
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Thyroid Hormone Synthesis
1. Uptake of Iodide (iodide trapping)
2. Iodide organification
• (oxidation and iodination)
3. Coupling of MIT and DIT
4. Secretion of thyroid hormones
5. Conversion of T4 to T3
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Ionic Inhibitors
Affects uptake of Iodine
• Perchlorate (ClO4- )
• thiocyanate (SCN- )
➢ No Therapeutic use: only Diagnostic
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Monovalent anions
Affects uptake of Iodine
• Resemble Iodide
• Inhibit transport of iodide into thyroid
➢ No Therapeutic use: only Diagnostic
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Thyroid peroxidase
Oxidizes iodide to iodine
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Thioamides
Antithyroid drug!
➢ Iodine rapidly iodinates tyrosine residues in thyroglobulin forming MIT (mono-iodotyrosine) and DIT (di-iodotyrosine)
• Inhibited by: Thioamides
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Coupling of MIT and DIT
➢ Coupling reaction involves oxidation by:
• Thyroid peroxidase
1. MIT + DIT --> T3
2. DIT + DIT --> T4
➢ Stored in thyroglobulin in colloid matrix
• Inhibited by thioamides -
examples:
• Methimazole
• Propylthiouracil
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Thioamides MOA
➢ Inhibit thyroid peroxidase :
• Block iodine oxidation
• Coupling of MIT and DIT
25
Propylthiouracil MOA
Inhibit peripheral conversion of T4 to T3
• Block synthesis T3 and T4 not release, therefore slow onset of action
26
Thioamides A/E
➢ Relatively low incidence (3 – 12%)
• Maculopapular pruritic rash
• Hypothyroidism
• Gastrointestinal intolerance
• Agranulocytosis (
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Secretion of T4 and T3 Inhibited by:
Iodine and Iodides
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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
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Iodides
➢ Inhibit TH release - thyroid constipation
➢ Decreased size & vascularity of gland
➢ Improvement of thyrotoxic symptoms occurs rapidly – used in thyroid storm
30
Conversion of T4 to T3 Inhibited by
• Propranolol
• Propylthiouracil
• Glucocorticoids (prednisolone)
31
Conversion of T4 to T3:
➢ 80% of T4 converted to T3 in peripheral tissues
• De-iodination of T4 (thyroxine) to active T3 (triiodothyronine)
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Lugol’s Iodine and Na/K Iodide:
• use
• toxicity
Use:
• Preoperatively- thyroidectomy
• Thyroid storm
Toxicity:
• Iodism- rash, rhinorrhoea, ulcers, conjuctivitis
33
Radioactive Iodine
• what
• half life
I-131
➢ Rapidly absorbed (orally)
➢ Concentrated in thyroid
➢ Emits b radiation --> destruction of thyroid gland
• half life (5 days)
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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
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Treatment of Hyperthyroidism
➢ Antithyroid drug therapy
• Propylthiouracil, methimazole
➢ Thyroidectomy
➢ 131Iodine
36
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
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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
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