hyperthyroidism Flashcards
regulation of thyroid hormones
-Plasma levels of TSH are measured to assess the status of thyroid hormone regulation.
TPO (thyroid peroxidase) is an essential enzyme in organification of
iodide (I-) into thyroid hormones.
Thyroid gland stores large amounts of thyroid hormones bound to thyroglobulin.
T3 is approximately 3-4x more potent than T4. 80% of active T3 is produced by peripheral deiodination of T4
Causes of hyperthyroidism
Graves’ disease
* Autoimmune disease
* Autoantibodies activate TSH receptor to drive increased
thyroid hormone production
Inappropriate TSH production
* TSH-secreting pituitary adenoma
* Pituitary resistance to thyroid hormone
Symptoms of hyperthyroidism
1) Intolerance to heat
- sweat
2) Warm moist palms
3) weight loss
4) irritability, nervousness, difficulty sleeping
5) tremors, muscle weakness
6)bulging eye
7)frequent bowel movement
8)infertility, scant menstrual period.
What drugs are used for hyperthyroidism?
1) Thioamides - carbimazole, propylthiouracil
2)iodides, iodine
3) Radioiodine
Where is thioamides metabolised?
metabolised in liver to active metabolite
thiamazole
MOA of thioamides
inhibit the thyroid peroxidase
(TPO) enzyme preventing thyroid
hormone production
Propylthiouracil (not carbimazole) also inhibits
deiodination of T4 to T3
metabolism of drug during illnesses
Severe liver :
Pro:disease
carb: Normal Decreased
Severe kidney disease:
Normal Normal
Excretion forms for both thioamides
Pro: 35% of the drug is
excreted in the urine, in
intact and conjugated
forms, within 24 hours.
carb: Urine
Adverse effects of thioamides
Agranulocytosis- reversible once discontinued
periodic blood tests and risk of opportunistic infections
mild: purpuric urticaria papular rash
Liver toxicity:
carbimazole: choleostatic jaundice
Propylthiouracil: risk of severe liver injury and acute hepatic failure.
Do not use in children unless of Carbimazole allergy
Which thioamide is preferred over the other?
Carbimazole in view of lower risk of hepatotoxicity and reduced half life allows for once or twice daily dosing
Can thioamides be used during pregnancy?
Thioamides readily cross the placenta:
* Can induce goiter and even cretinism in the developing fetus
* Important that a sufficient, but not excessive, dose be given
* Thyroid dysfunction often diminishes in pregnancy
* Dose reduction may be possible.
* If propylthiouracil is used during pregnancy, or if the patient
becomes pregnant while taking propylthiouracil, the patient should
be warned of the rare potential hazard to the mother and fetus of
liver damage.
* Carbimazole may be associated with the rare development of fetal
abnormalities such as aplasia cutis and choanal atresia
* 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 carbimazole for the second and third trimesters.
MOA of iodide/ iodine
- Suppress thyroid hormone synthesis
- Inhibit thyroid hormone release
- Decrease the size and vascularity of the gland when
given over 1-2 weeks.
Iodide (I-)
Useful in thyrotoxic crisis (thyroid storm) to prevent release of
thyroid hormone stores
Used for 10-14 days pre-operatively in patients scheduled for
thyroidectomy surgery.
Pharmacokinetics of iodide
Administration: Oral
* Onset of action: Hyperthyroidism: 24-48 hours.
* Peak effect: 10-15 days after continuous therapy
* Excretion: Renal clearance
What happens when there are too much iodide?
Iodide is required for thyroid
hormone synthesis but overloading
with iodide triggers shutdown of
thyroid hormone production and
release.
adverse effects of iodide
- Delays onset of effect of thioamide therapy (? by inhibiting the
drug effect on thyroid peroxidase) - Prevents the use of 131I for several weeks (competes for uptake
into thyroid gland) - May produce severe exacerbations of thyrotoxicosis if the
gland “escapes” from iodide block (as iodide is precursor for
thyroid hormone production) - “Iodism” from chronic overuse:
* bleeding disorders, conjunctivitis, fever, inflamed salivary
glands, metallic taste, mucous membrane ulcerations, rash,
rhinorrhoea - Avoid use while breastfeeding and in pregnancy as I- crosses
the placenta and may cause fetal goitre.
Who should try radio iodine?
Radioiodine is
1. Treatment of choice for patients aged >35 years
2. An alternative choice to
i. thioamides (when there is relapse or allergic response),
ii. surgery (in patients unsuitable for surgery e.g., heart disease).
MOA of radio iodine
Thyroid tissue has a unique ability to take up iodine from blood. Like iodine,
radioiodine is taken up and concentrated in thyroid follicular cells via a
membrane sodium-iodide transporter
131I is concentrated in the thyroid gland; this isotope emits both gamma and
beta rays. 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 of 131I disappears after 2 months and its cytotoxic effect
peaks after a further 2 months.
Advantages of radioiodine
- Convenient: Can be administered at outpatient clinic as a single
oral dose of 3-5 mCi - Inexpensive
Disadvantages of radio iodine
- 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 hypothyroidism in
later life.
Contraindications for radio iodine
- Not used in children (risk of genetic damage, carcinogenesis)
- Contraindicated in pregnancy (effect on foetal thyroid) and
nursing mothers (effect on neonatal thyroid).
