Lecture 11 - Thyroid Flashcards
Describe the thyroid hormone loop (slide 3)
Hypothalamus releases TRH and it goes to the anterior pituitary.
Anterior pituitary releases TSH to the thyroid.
T3 and T4 then release tissue effects.
*T4 and T3 has negative feed-back inhibiton on the anterior pituitary
TRH
thyrotropin releasing hormone
TSH
thyroid stimulating hormone
T4 is also known as _______
levothyroxine
T4 splits up into ??
T3 and rT3
What is the half-life of T4 (levothyroxine)?
7 days
What is the half-life of T3?
1 day
Describe the metabolism of T4 (levothyroxine)?
20% inactivated
80% converted to T3
(35% to T3, 45% to rT3)
- glucuronidation and salvation in the liver
- excretion in urine and bile
- conjugates reconverted to T4 in lower GIT
T4 and T3 have a negative feedback relationship on ___
TSH
Normal range for T4?
64-142 nM
Normal range for T3?
1.5-2.9 nM
Normal range for TSH?
0.3-5 mU/L
Normal range for Serum Thyroglobulin?
<40 ng/mL
Hypothyroid range for T4?
low
Hyperthyroid range for T4?
high
Hypothyroid range for T3?
normal or low
Hyperthyroid range for T3?
high
Hypothyroid range for TSH?
high
Hyperthyroid range for TSH?
low
Hypothyroid range for Serum Thyroglobulin?
low
Hyperthyroid range for serum Thyroglobulin?
high
Children have higher ___ than adults
T3
Hypothyroidism is a ___% incidence
0.6
Hypothyroidism is more common in _____
women
______ ______ is an autoimmune disorder
Hashimoto’s Thyroiditis
Describe the presentation of hypothyroidism
Slowing of body functions:
-Heart, mental acuity, strength, response to catecholamines, cold and scaly skin, sparse hair, puffiness (myxadema), droopy eyelids, saddle nose thickened lips
What is the cause of Hashimoto’s thyroiditis?
Antibodies against thyroid peroxidase and/or thyroglobulin gradually destroy thyroid gland follicles
Symptoms of Hashimoto’s thyroiditis?
Slower metabolism, reduced CNS activity - weight gain, fatigue, depression, bradycardia, constipation, muscle weakness, memory loss, infertility, hair loss
**NOTE - HT can also cause reactive HYPERthyroidism (inflammation), and thus mania, tachycardia, panic attacks. Mania due to HT is called Prasad’s Syndrome
What is Hashimoto’s thyroiditis often misdiagnosed as ?
depression or anxiety, sometimes even as bipolar disorder
How do we detect Hashimoto’s thyroiditis?
- Presence of specific antibodies is diagnostic
- Also see increased TSH and often lymphocyte invasion of thyroid gland
Describe the Diagnosis of Hashimoto’s Diagnosis
- Enlargement of the thyroid, known as a goiter
- High levels of antibodies against thyroglobulin (TG) and thyroid peroxidase (TPO), detected via blood test
- Fine needle aspiration of the thyroid (also known as a needle biopsy), which shows lymphocytes and macrophages
- A radioactive uptake scene, which would show diffuse uptake in an enlarged thyroid gland
- Ultrasound, which would show an enlarged thyroid gland
What do thyroid hormones do?
Increase adrenergic receptor sensitivity to catecholamines:
-Normal adrenalin/Noradrenalin, hyper response
Do thyroid hormones cross the placenta?
Not in clinically meaningful amounts
Pregnant patients with hypothyroidism is ______
difficult
Pregnant patients with hyperthyroidism causes _____
abortion
If pregnant, must carefully monitor dose regiment because of _____
stimulation
What is the treatment for hypothyroidism?
*If due to iodine deficiency, then add iodine to the diet (elderly/poverty)
- For gland failure, levothyroxine (T4) is the treatment of choice:
- Long half life
- Lag before effects are observed
- Given at birth to prevent cretinism
- Body then converts T4 (levothyroxine) to T3 as required
Prevalence of hyperthyroidism?
- most common between 20-60 years of age
- more prevalent in females
What is grave’s disease?
- most common form of hyperthyroidism
- activating Ab to TSH receptor causes increased T3 and T4 levels
Diagnosis of hyperthyroidism of patients less than 40?
mainly nervous system effects
Diagnosis of hyperthyroidism of patients more than 40?
mainly CV effects
Another diagnostic criteria for hyperthyroidism?
catecholamine response
Describe Radioiodone
-The treatment of choice at many centres
125I half life = 60 days
131I half life = 8 days (beta particles, kills cells)
123I half life = 0.55 days (would need quick delivery)
- Ionizing radiation destroys the gland
- Caution with other antithyroid drugs as must be concentrated into uptake gland
- Stop for 2 days before and after
Radioiodine contraindications?
CI in pregnancy and in children
Describe some precautions with radioiodine
- Delay in therapeutic response (2-6 months)
- Depending on symptoms, may need other pharm intervention because of delay
- Radiation-induced thyroiditis
- Hypothyroidism - if destroy too much
- Thyroid cancer - discourages some patients, may choose surgery (but also damage risk … i.e. parathyroids)
- Pregnancy!!!
List 3 Antithyroid drugs
- Propylthiouracil
- Methimazole
- Carbimazole
MOA of Thioamide drugs?
Blocks synthesis of thyroid hormones:
- Interferes with organification of iodine - a competitive inhibitor of peroxidase
- Blocks MIT conversion to DIT
- Inhibits coupling of iodinated tyrosines
- Does not affect uptake of iodine or T4 or T4 release
- Onset requires depletion of thyroid hormone stores
Propylthiouracil inhibits conversion of ______?
T4 to T3
Describe Thioamide Drug Disposition
- Concentrated in the thyroid gland (~100 x)
- Potency of methimazole compared to PTU is ~ 100X
- Disposition altered in cirrhosis and in renal failure
- Treatment: methimazole once daily and PTU every 8 hours
Methimazole:
Half life ?
6 hours
PTU:
Half life ?
1 hour
Methimazole:
Protein binding ?
Nil
PTU:
Protein binding ?
High
Antithyroid drug therapy adjusted and/or reduced every _____ weeks
4-6
Methimazole:
Maintenance dose ?
5-10 mg/day
PTU:
Maintenance dose ?
50-100 mg/day
PTU is used for what?
fast decrease in T3 due to peripheral effects - feel better faster
In pregnancy, ____ is preferred
PTU
- crosses placenta less
- no teratogenic reports
- only 1/10 crosses into breast milk
SE of thioamide drugs?
1-5% show fever, rash, arthritis-like symptoms
- Most common = leukopenia (WBC < 4000 mm^3)
- Low cross reactivity between methimazole and PTU
____ changes with thyroid status
WBC
*therefore, routine monitoring not recommended
When should you stop thioamide drug therapy
Stop drug therapy at first sign of a sore throat and/or fever
*Then determine WBC status
Thioamide drugs could also cause Agranulocytosis - what is that?
an acute condition involving a severe and dangerous leukopenia (lowered white blood cell count), most commonly of neutrophils causing a neutropenia in the circulating blood
*rare and usually reversible when drug treatment is stopped
Describe a thyroid storm
- Greatly increased blood temperature
- Shortness of breath
- Anxiety
- Sweating
- Tachycardia
- Chest pain
- MI
Describe how propranolol works?
- It is used to ameliorate CV symptoms/toxicity
- Some suppression of T4 to T3
Dexamethasone:
MOA
inhibits T4 to T3
Lithium:
MOA
inhibits secretion and degradation in peripheral tissue
Sulfonamides:
MOA
interfere with organification of iodine
Sodium nitroprusside (long term): MOA
thiocyanate accumulation inhibits iodine uptake by the thyroid
Amiodarone:
MOA
contains lots of iodine
SCN (found in some foods) and ClO4-:
MOA
block iodide uptake
Iodide (large doses):
MOA
Decreases degranulation of thyroglobulin and gland vascularity.
It is useful prior to surgery but the effect disappears after a few days of intake.
_________ for replacement therapy
Levothyroxine (T4)
______ for hyperthyroidism except in women of child-bearing age
Radioiodine
______ and ____ for hyperthyroidism
Methimazole and PTU
____ is the drug of choice in pregnancy for hyperthyroidism
PTU
List a few other agents with antithyroid action
- amiodarone
- lithium
- sulfonamides
