Thyroid Disorders Drugs (Thyrotoxic crisis (Thyroid storm)
Thyroid Disorders Drugs
Levothroxine, aka L-thyroxine allows dose titration with reduced CVS risk
The liver is the main site of T4 deiodination, and along with the kidneys are responsible for about 80% of circulating T3
80% is T3 from peripheral conversion of T4
Normally, about one-third of T4 is converted to T3 and about one-third to rT3 in peripheries. The remainder of T4 is metabolized by different pathways, in particular glucuronidation and sulfation.
Used when a rapid onset of
action is needed.
IV for treatment of myxedema coma (severe hypothyroidism)
Specific state where thyroid gland is responsible for high thyroid hormone production
Risk of liver failure, recommending close monitoring of liver function during its use. Propylthiouracil should not be used in children except in the case of carbimazole allergy
Thought to inhibit the thyroid peroxidase enzyme as they:
• Interfere with iodination
• Inhibit coupling
Carbimazole may be associated with the rare development of fetal abnormalities such as aplasia cutis (absence of skin usually in small circle on scalp) and choanal atresia (back of the nasal passage (choana) is blocked)
• Propylthiouracil is the preferred agent during organogenesis, in the first trimester of pregnancy.
• Given the potential maternal adverse effects of propylthiouracil (e.g. hepatotoxicity), it may be preferable to switch from propylthiouracil to methimazole for the second and third trimesters after organogenesis
Strong iodine solution (Lugol's solution)
• consists of 5% iodine and 10% potassium iodide.
• Iodine is reduced to iodide in the intestine before absorption
• Potassium iodide tablets
Mechanisms of Action:
- Suppress iodination of tyrosine and also coupling of MIT, DIT thus inhibiting thyroid hormone synthesis
- Inhibit the release of T3 and T4 (thus useful in the management of thyroid storm)
- Decrease the size and vascularity of the gland when given over 1-2 weeks. This effect is valuable for patients who are to be treated surgically.
Negative feedback, inhibits organification in the thyroid gland, the formation of thyroid hormones inside the thyroid follicle, and the release of thyroid hormones into the bloodstream
Excess iodide transiently inhibits thyroid iodide organification. In individuals with a normal thyroid, the gland eventually escapes from this inhibitory effect and iodide organification resumes; however, in patients with underlying autoimmune thyroid disease, the suppressive action of high iodide may persist due to impaired escape. The Wolff–Chaikoff effect lasts several days (around 10 days), after which it is followed by an "escape phenomenon," which is described by resumption of normal organification of iodine and normal thyroid peroxidase function. "Escape phenomenon" is believed to occur because of decreased inorganic iodine concentration inside the thyroid follicle below a critical threshold secondary to down-regulation of sodium-iodide symporter (NIS) on the basolateral membrane of the thyroid follicular cell.
- For prophylaxis against endemic goitre (by supplying the iodide that is deficient)
- To reduce the size and vascularity of the thyroid gland by giving pre- operatively (for up to 10 days)
- To treat thyroid storm (by inhibiting hormone release)
Disadvantages of iodides
- Delays onset of effect of thioamide therapy (possibly by inhibiting the drug effect on peroxidase)
- Prevents the use of radioiodine for several weeks due to increase in intraglandular stores
- May produce severe exacerbations of thyrotoxicosis when the gland “escapes” from iodide block, following withdrawal of the iodides, should not be used alone
“Iodism” from chronic overuse:
• bleeding disorders
• inflamed salivary glands
• metallic taste
• mucous membrane ulcerations
Avoid use while breastfeeding and in pregnancy as I- crosses the placenta and may cause fetal goiter.
- Treatment of choice for patients aged >35 years
- An alternative choice to
i. thioamides (when there is relapse or allergic response),
ii. surgery (in patients unsuitable for surgery e.g. heart disease).
While gamma rays pass through the follicular cells, the beta particles (T1/2: 8 days) emit rays with short path-length that irradiate thyroid tissue to a thickness of 1.0 - 2.0 mm, destroying the follicular cells without damaging surrounding tissue.
Radioactivity disappears after 2 months and its cytotoxic effect peaks at 4 months.
- Convenient - can be administered at outpatient clinic as a single oral dose of 3-5 mCi
- Slow onset of cytotoxic effect - begins only after 1-2 months and peaks after a further 2 months
- Major adverse effect is the development of hypo-thyroidism in later life, give levothyroxine
- Not used in children (risk of genetic damage, carcinogenesis)
- Contra-indicated in pregnancy (effect on foetal thyroid)
and nursing mothers (effect on neonatal thyroid).