1
Q
How are TH regulated (2 ways)
A
- Negative feedback
- Peripheral conversion of T4 to T3
2
Q
How does Thyroxine Binding Globulin (TBG) affect TH levels
A
- Elevated TBG (pregnant women or on estrogen)
- Increased binding of T3 and T4 to TBG –> reduced levels of FT3 and FT4
- Negative feedback where TSH will be released for thyroid gland to secrete more TH to return FT3 and FT4 levels back to normal –> new equilibrium is achieved
3
Q
Which antibody is used for confirming Grave’s disease?
A
TRAb
4
Q
Indications for screening
A
- Pregnancy and pediatric patients
- Presence of autoimmune diseases (T1DM, cystic fibrosis)
- First-degree relative with history of autoimmune Thyroid disorder
- Psychiatric disorder
- Patients on amiodarone and lithium
- History of head/ neck radiation from malignancies
- Symptoms of hyper-/ hypothyroidism
5
Q
Possible causes of hypothyroidism
A
- Iodine deficiency
- Hashimoto disease (positive ATgA and TPO antibodies; women more affected)
- Post-thyroid resection or radioiodine ablative therapy (RIA) for hyperthyroidism
- Central hypothyroidism (anterior pituitary unable to secrete TSH or hypothalamus unable to secrete TRH)
- Drug use (amiodarone and lithium)
6
Q
Signs and symptoms of hypothyroidism (10)
A
- Cold intolerance
- Dry skin
- Fatigue, lethargy, weakness
- Bradycardia
- Slow reflexes
- Coarse hair and skin
- Menstrual disturbances (heavy menstrual bleeding)
- Periorbital swelling
- Goiter
- Weight gain
7
Q
Clinical manifestation of hypothyroidism
A
- Hyperlipidemia (elevated LDL, cholesterol, TG)
- Increase atherosclerosis and MI risk
- Elevated Creatine phosphokinase (CPK) levels
- Increase miscarriage risk
- Impaired fetal development
8
Q
What will you expect TSH levels to be for primary hypothyroidism?
A
Elevated
9
Q
What are the pharmacological agents used for hypothyroidism?
A
- Levothyroxine (synthetic T4)
- Liothyronine (synthetic T3)
10
Q
What are the dosings for levothyroxine?
A
Young healthy adults (<50yo): 1.5µg/kg daily
Adults (50-60yo) no cardiac issues: 50µg daily
Patients with CVD: 25µg daily and titrate up (increase by 25µg/day increments)
11
Q
Counseling for Levothyroxine administration
A
- Take 30-60 mins before breakfast or 4 hrs after dinner on an empty stomach (includes other medications)
- Space at least 2 hrs apart from other calcium or iron-containing products/ supplements (ie. antacids)
12
Q
How long does it take for Levothyroxine effects to be felt? And what to monitor?
A
2 – 3 months. Monitor TSH levels after 2-3months.
Monitor T4 if patient is experiencing central hypothyroidism instead.
13
Q
What does normal FT4 and elevated TSH while using Levothyroxine suggest?
A
Non-compliance
14
Q
Adverse effects associated with levothyroxine
A
- Cardiac abnormalities (eg. tachyarrhythmias, angina, MI)
- Risk of fracture
- Hyperthyroidism (weight loss, anxiety, diarrhea, hair loss, difficulty sleeping)
15
Q
Contraindications of Levothyroxine
A
- Patients with heart problem (start at 25µg and titrrate upwards)
- Epilepsy
- Hyperthyroidism
16
Q
Why is Levothyroxine the drug of choice for hypothyroidism?
A
- Good adverse effect profile
- Low cost
- Lack of antigenicity
- Uniform potency
17
Q
Scenario that warrants Liothyronine? (3)
A
- When patient needs to go for diagnostic therapy and has to discontinue Levothyroxine (due to its long half-life). Can substitute with Liothyronine first which can be stopped 1-2 days before the test in the meantime (shorter half-life) before restarting Levothyroxine after the diagnostic test.
- Combination with levothyroxine if TSH is normalized but symptoms of hypothyroidism still persist
- Considered in Myxedema coma (IV Levothyroxine can also be used)
18
Q
Dose adjustment of Levothyroxine for pregnancy
A
If the mother is on Levothyroxine pre-pregnancy, increase the dose by 30-50% to maintain euthyroid state when pregnant (due to increase TBG)
19
Q
What does subclinical hypothyroidism mean?
A
Normalized T4 but elevated TSH (often the result of early Hashimoto’s disease)
20
Q
When should you treat subclinical hypothyroidism? (25-75µg daily)
A
- TSH >10mIU/L
- TSH 4.5-10mIU + Sx of hypothyroidism or TPO antibodies present or Hx of CVD/ HF
- if left untreated, screen regularly
21
Q
Possible causes of hyperthyroidism?
A
- Graves disease (positive TRAb that mimics TSH)
- Pituitary adenomas
- Toxic adenoma (hot nodule)
- Toxic multi-nodular goiter (Plummer’s disease)
- Drug induced (amiodarone or Lithium)
- Subacute thyroiditis (release of stored TH)
22
Q
Signs and symptoms of hyperthyroidism (9)
A
- Heat intolerance
- Weight loss
- Goiter (due to nodule growth or Grave’s disease)
- Fine hair
- Tachycardia
- Anxiety, nervousness, insomnia
- Sweating or warm, moist skin
- Menstrual disturbances (lighter or more infrequent menstruation or amenorrhea)
- Exophthalmos in Graves disease
23
Q
Treatment options for hyperthyroidism
A
- Surgical resection
- Radioactive iodine ablation therapy (RAI)
- Thyroidectomy
- Anti-thyroid pharmacotherapy
24
Q
What are the antithyroid pharmacotherapeutic agents?
A
- Thionamides (Carbimazole or PTU)
- Beta-blocker (Propranolol)
- Iodine (Lugol’s solution)
25
When is antithyroid pharmacotherapy considered for use in hyperthyroidism?
1. Those awaiting ablative therapy or surgical resection (to deplete TH stores and minimize risk of thyroiditis)
2. Not ablative/ surgical candidates or failed to normalize thyroid hormones after these processes
3. Mild disease (small goiter/ low or negative antibody titres/ women)
4. Limited life expectancy
26
What are the 2 thionamide drugs?
1. Carbimazole
2. Propylthiouracil (PTU)
27
MOA of Thionamides
1. Inhibition of Thyroid peroxidase (TPO) to inhibit iodination --> inhibit the synthesis of new thyroid hormones
2. PTU can additionally block peripheral conversion of T4 to T3 at high doses
28
ADR associated with thionamides (carbimazole and PTU)
1. Hepatotoxicity (Black Box warning for PTU)
2. Agranulocytosis
3. Rash (risk for SJS)
4. Hypothyroidism (over-treatment)
5. Fever
29
Counselling points for Thionamides
Maximum effect can be felt after 4-6 months
30
What parameters are used to measure efficacy of Thionamides?
T4. monthly dose titration may be required based on T4 levels.
- Total T3 may be used for monitoring early in the therapy but is expensive
31
2 main symptoms of hyperthyroidism in pregnancy
1. Weight loss despite good appetite
2. Tachycardia
32
Concerns of hyperthyroidism in pregnancy
Fetal loss if untreated
33
Use of thionamides for hyperthyroidism in pregnancy
1st trimester: Use PTU > Carbimazole (higher risk of congenital malformations)
2nd and 3rd trimester: Use carbimazole > PTU (Higher risk of hepatotoxicity and less potent)
34
Which non-selective beta-blocker agent is used for hyperthyroidism?
Propranolol
35
MOA of beta-blockers in hyperthyroidism
1. Blocks many hyperthyroidism manifestations mediated by beta-adrenergic receptors (symptomatic management)
2. Decrease peripheral conversion o T4 to T3
3. Used for treatment of thyroiditis
36
Which iodide is used for hyperthyroidism?
Lugol's solution
37
MOA of iodide in hyperthyroidism
1. Inhibits the release of Thyroid hormone stores --> inhibit thyroiditis-mediated hyperthyroidism
2. Helps decrease vascularity and size of thyroid gland
38
When is iodide indicated for hyperthyroidism?
1. Before surgery (7-10 days) to shrink the thyroid gland
2. After ablative therapy (3-7 days after) to inhibit thyroiditis-mediated hyperthyroidism (release of stored thyroid hormones)
3. Thyroid storm
39
Limitations of using iodides for hyperthyroidism
1. Limited efficacy after 7-14 days of therapy as thyroid hormone release will resume again
2. Do not use before Radioactive iodine ablative therapy (RAI) --> decrease the uptake of radioactive iodine
40
Definition of subclinical hyperthyroidism
Low or undetectable TSH levels while T4 are normalized
41
Risk associated with subclinical hyperthyroidism?
1. Atrial fibrillation in patients >60yo
2. Elevated risk of bone fractures in postmenopausal women
42
Treatment for subclinical hyperthyroidism
1. Therapy is indicated if TSH <0.10 mIU/L
2. Non-selective BB should be selected if patient has AFib
3. If untreated, screen regularly for development of overt hyperthyroidism
43
How does amiodarone cause thyroid disorder
1. Iodine contained in its chemical structure --> affects iodine uptake, secretion, production
2. Cause thyroiditis
3. May cause hypo- or hyperthyroidism
44
How does lithium cause thyroid disoder
1. Inhibit thyroid hormone secretion and release --> signaling an increase in TSH and positive goiter development (hypothyroidism)
2. Thyroiditis (hyperthyroidism)
PR3152
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