Lecture 11 - Thyroid Flashcards
1
Q
Describe the thyroid hormone loop (slide 3)
A
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
2
Q
TRH
A
thyrotropin releasing hormone
3
Q
TSH
A
thyroid stimulating hormone
4
Q
T4 is also known as _______
A
levothyroxine
5
Q
T4 splits up into ??
A
T3 and rT3
6
Q
What is the half-life of T4 (levothyroxine)?
A
7 days
7
Q
What is the half-life of T3?
A
1 day
8
Q
Describe the metabolism of T4 (levothyroxine)?
A
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
9
Q
T4 and T3 have a negative feedback relationship on ___
A
TSH
10
Q
Normal range for T4?
A
64-142 nM
11
Q
Normal range for T3?
A
1.5-2.9 nM
12
Q
Normal range for TSH?
A
0.3-5 mU/L
13
Q
Normal range for Serum Thyroglobulin?
A
<40 ng/mL
14
Q
Hypothyroid range for T4?
A
low
15
Q
Hyperthyroid range for T4?
A
high
16
Q
Hypothyroid range for T3?
A
normal or low
17
Q
Hyperthyroid range for T3?
A
high
18
Q
Hypothyroid range for TSH?
A
high
19
Q
Hyperthyroid range for TSH?
A
low
20
Q
Hypothyroid range for Serum Thyroglobulin?
A
low
21
Q
Hyperthyroid range for serum Thyroglobulin?
A
high
22
Q
Children have higher ___ than adults
A
T3
23
Q
Hypothyroidism is a ___% incidence
A
0.6
24
Q
Hypothyroidism is more common in _____
A
women
25
______ ______ is an autoimmune disorder
Hashimoto's Thyroiditis
26
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
27
What is the cause of Hashimoto's thyroiditis?
Antibodies against thyroid peroxidase and/or thyroglobulin gradually destroy thyroid gland follicles
28
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
29
What is Hashimoto's thyroiditis often misdiagnosed as ?
depression or anxiety, sometimes even as bipolar disorder
30
How do we detect Hashimoto's thyroiditis?
- Presence of specific antibodies is diagnostic
| - Also see increased TSH and often lymphocyte invasion of thyroid gland
31
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
32
What do thyroid hormones do?
Increase adrenergic receptor sensitivity to catecholamines:
| -Normal adrenalin/Noradrenalin, hyper response
33
Do thyroid hormones cross the placenta?
Not in clinically meaningful amounts
34
Pregnant patients with hypothyroidism is ______
difficult
35
Pregnant patients with hyperthyroidism causes _____
abortion
36
If pregnant, must carefully monitor dose regiment because of _____
stimulation
37
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
38
Prevalence of hyperthyroidism?
- most common between 20-60 years of age
| - more prevalent in females
39
What is grave's disease?
- most common form of hyperthyroidism
| - activating Ab to TSH receptor causes increased T3 and T4 levels
40
Diagnosis of hyperthyroidism of patients less than 40?
mainly nervous system effects
41
Diagnosis of hyperthyroidism of patients more than 40?
mainly CV effects
42
Another diagnostic criteria for hyperthyroidism?
catecholamine response
43
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
44
Radioiodine contraindications?
CI in pregnancy and in children
45
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!!!
46
List 3 Antithyroid drugs
- Propylthiouracil
- Methimazole
- Carbimazole
47
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
48
Propylthiouracil inhibits conversion of ______?
T4 to T3
49
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
50
Methimazole:
| Half life ?
6 hours
51
PTU:
| Half life ?
1 hour
52
Methimazole:
| Protein binding ?
Nil
53
PTU:
| Protein binding ?
High
54
Antithyroid drug therapy adjusted and/or reduced every _____ weeks
4-6
55
Methimazole:
| Maintenance dose ?
5-10 mg/day
56
PTU:
| Maintenance dose ?
50-100 mg/day
57
PTU is used for what?
fast decrease in T3 due to peripheral effects - feel better faster
58
In pregnancy, ____ is preferred
PTU
* crosses placenta less
* no teratogenic reports
* only 1/10 crosses into breast milk
59
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
60
____ changes with thyroid status
WBC
| *therefore, routine monitoring not recommended
61
When should you stop thioamide drug therapy
Stop drug therapy at first sign of a sore throat and/or fever
*Then determine WBC status
62
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
63
Describe a thyroid storm
- Greatly increased blood temperature
- Shortness of breath
- Anxiety
- Sweating
- Tachycardia
- Chest pain
- MI
64
Describe how propranolol works?
- It is used to ameliorate CV symptoms/toxicity
| - Some suppression of T4 to T3
65
Dexamethasone:
| MOA
inhibits T4 to T3
66
Lithium:
| MOA
inhibits secretion and degradation in peripheral tissue
67
Sulfonamides:
| MOA
interfere with organification of iodine
68
```
Sodium nitroprusside (long term):
MOA
```
thiocyanate accumulation inhibits iodine uptake by the thyroid
69
Amiodarone:
| MOA
contains lots of iodine
70
SCN (found in some foods) and ClO4-:
| MOA
block iodide uptake
71
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.
72
_________ for replacement therapy
Levothyroxine (T4)
73
______ for hyperthyroidism except in women of child-bearing age
Radioiodine
74
______ and ____ for hyperthyroidism
Methimazole and PTU
75
____ is the drug of choice in pregnancy for hyperthyroidism
PTU
76
List a few other agents with antithyroid action
- amiodarone
- lithium
- sulfonamides
