Thyroid disorders (including Pharmacology) Flashcards
State the populations that should be routinely screened for thyroid disorders
Pediatric patients and pregnant women
What are some compelling indications for thyroid disorder screening (6 total)
1) Presence of autoimmune disease (e.g. T1DM, cystic fibrosis) -> High risk of developing autoimmune disease in another organ
2) First degree relative with autoimmune thyroid disease
3) Psychiatric disorders
* Thyroid abnormalities can induce mood swings, anxiety psychosis
4) Taking amiodarone or lithium
* Affect thyroid hormone levels
5) History of head / neck radiation for malignancies
* Predisposed to thyroid conditions
6) Symptoms of hypothyroidism / hyperthyroidism
What thyroid protein is affected by certain conditions (e.g pregnancy, estrogen therapy)?
Thyroxine Binding Globulin (TBG)
Tests for autoantibodies in thyroid screening test for which antibodies?
1) ATgA: Thyroglobulin antibodies
2) TPO: Thyroid peroxidase antibodies
3) TRAb: Thyrotropin receptor IgG antibodies
Which antibody is specific and confirmatory for Graves Disease?
TRAb
State the respective lab trends for Primary hypothyroidism vs Central hypothyroidism
Primary Hypothyroidism
o ↑TSH, ↓ T4
o Positive antibodies (TPO, ATgA)
Central Hypothyroidism (pituitary is the issue)
o ↓ TSH, ↓ T4
State how you would initiate and subsequently titrate Levothyroxine in a young, healthy adult.
Initiation: 1.6 mcg/kg/day (can remember as 1.5mcg/kg)
Titration: titrate up/down by 25mcg/day
State how you would initiate Levothyroxine in a patient who is 50-60 years old who has no cardiac issue
50 mcg/day
How would you initiate Levothyroxine in a patient with CVD
12.5-25 mcg/day and titrate up
State how you would counsel a patient who is starting Levothyroxine.
1) Take this 30-60 minutes before breakfast or 4 hours after dinner (take on empty stomach/ when you just wake up) Space apart from foods containing metal cations by at least 2 hours (e.g milk and tofu)
2) Space apart from all other medications especially calcium or iron supplements and antacids (metal cations) need to space at least 2 hours apart
What are the side effects of Levothyroxine?
1) Cardiac abnormalities (tachyarrhythmias, angina, myocardial infarction, Atrial fibrillation)
2) Risk of fractures
3) Signs of hyperthyroidism (e.g diarrhea, anxiety, increased appetite, insomnia)
4) Hair loss
State the monitoring parameters for someone with primary hypothyroidism, including frequency of monitoring
TSH levels
4-8 weeks after initiation/titration. Once thyroid hormone levels stable, once semi-annually to once annually
State the monitoring parameters for patient with Central hypothyrodism, including frequency of monitoring
Free T4 levels (recall: pituitary spoil in central hypothyroid)
4-8 weeks after initiation/titration. Once thyroid hormone levels stable, once semi-annually to once annually
When would Liothyronine use be considered? (3 situations)
1) Normalisation of TSH but still having symptoms of hypothyroidism
2) Myxoedema coma
3) Going for diagnostic procedure and needs to stop Levothyroxine but still need short term control of hypothyroidism (Liothyronine can be stopped 1-2 days before procedure, start Levo again after procedure)
State how you would adjust Levothyroxine therapy for pregnant women and why this adjustment may be needed
May need a 30-50% increase in pre-pregnant dosage to maintain euthyroid status (due to TBG ↑-> lower free T3 and T4)
What is the definition of subclinical hypothyroidism?
Elevated TSH with normal T4. Often the result of early Hashimoto disease
In general, when would treatment of subclinical hypothyroidism be considered?
1) TSH > 10mIU/L (widely accepted)
2) TSH 4.5-10 mIU/L AND
o I. Symptoms of hypothyroidism OR
o II. TPO antibody present OR
o III. History of cardiovascular disease, heart failure, or risk factors for such
What are the signs and symptoms of hyperthyroidism? (9 total)
1) Weight loss or increased appetite
2) Heat intolerance
3) Goiter
* Not as common compared to hypothyroidism; goiter is more due to the fact that nodules get bigger and bigger
4) Fine, weak hair
5) Heart palpitations or tachycardia
6) Nervousness, anxiety, insomnia
7) Menstrual disturbances (lighter or more infrequent menstruation, amenorrhea)
* High T3, T4 -> higher metabolism of estrogen + higher progestin
8) Sweating or warm, moist skin
9) Exophthalmos in Graves disease
What are the usual indications for pharmacological treatment of hyperthyroidism? (4 total)
1) Those awaiting ablative therapy or surgical resection (Minimizes risk of post-ablation hyperthyroidism caused by thyroiditis by depleting thyroid stores)
2) Not ablative or surgical candidates / failed to normalize thyroid [e.g: pregnant (give drug until give birth) or too young, too old, cannot be temporarily isolated (patient will not be able to interact with people for awhile)]
3) Mild disease / small goiter / low or negative antibody titers / women (tend to respond better to drugs)
4) Limited life expectancy
What is the MOA of Thionamides (Carbimazole and Propylthiouracil)?
(C+P): Inhibits thyroid peroxidase (TPO) which normally iodinates tyrosyl residues in thyroglobulin (Tg-Tyrosine) to give precursors of T3 and T4 (MIT and DIT). Inhibition of iodination step leads to gradual ↓ of T3 and T4 synthesis
P: PTU can additionally block T4/T3 conversion in the periphery at high doses
What are the adverse effects of Thionamides? (7 total)
1) Rashes
2) Joint pain
3) Nausea
4) Hepatotoxicity (one sign is Jaundice; PTU > Carbimazole)
5) Hypothyroidism (due to overtreatment)
6) Agranulocytosis (rare)
7) Fever
What lab values are used to titrate Thionamide treatment?
For first 1-2 years of therapy, look at T4 instead of TSH as marker to titrate
What are some disadvantages of using Thionamides? (3 total)
1) Slow onset in reducing symptoms (weeks). Maximal effect may take 4–6 months
2) Remission rates low: 20%–30%. Remission is defined as normal TSH and T4 for 1 year after discontinuing antithyroid therapy
3) Does not solve root cause (symptomatic treatment)
How is Carbimazole metabolised?
Metabolised by CYP450 and FMO (Flavin-containing monooxygenase) enzymes
What are symptoms of hyperthyroidism in pregnancy? (2 main symptoms)
1) Failure to gain weight despite good appetite
2) Tachycardia
State how you would treat a pregnant woman with Thionamide (which one would you use at which trimester(s) and why)
1st Trimester: Use PTU as Carbimazole have higher risk of congenital malformations
2nd and 3rd Trimesters: Use Carbimazole as PTU have higher risk of hepatotoxicity and yet less potent
Use lowest possible dose; keep T4 at upper-normal limit
What is the MOA of beta-blockers in treating hyperthyroidism?
Blocks many hyperthyroidism manifestations mediated by β-adrenergic receptors; also may block T4 conversion to T3 when used at high dose
What are beta blockers place in therapy for hyperthyroidism?
1) Symptomatic relief (does not solve root cause)
2) Bridging therapy for Thionamides effects to kick in/ before ablation /surgery
o Use to suppress symptoms before Carbimazole starts working
3) PRN for high-risk patients e.g elderly with CVS disease
4) Treatment of thyroiditis, which is usually self-limiting
What is the MOA of Iodides?
Inhibits the release of stored thyroid hormones + Helps decrease vascularity and size of gland.
Minimal effect on hormone synthesis.
When are Iodides typically used?
1) Before Surgery (7–10 days) to shrink the gland
2) After ablative therapy (3–7 days) to inhibit thyroiditis thyroiditis-mediated release of stored TH
3) Thyroid storm
When should Iodides not be used?
1) Limited efficacy after 7–14 days of therapy as TH release will resume
2) Do NOT use before ablative RAI (may reduce uptake of radioactive iodine).
How does Radioactive Iodine treat hyperthyroidism?
Radioactive Iodine gets taken up by thyroid cells and destroys them
What are the absolute contraindications for Radioactive Iodine Ablative Therapy?
Pregnancy
What are the signs and symptoms of hypothyroidism? (10 total)
1) Cold intolerance
2) Dry skin
3) Fatigue, lethargy, weakness
4) Weight gain
5) Bradycardia
6) Slow reflexes
7) Coarse skin and hair
8) Periorbital swelling
9) Menstrual disturbances (more frequent, more blood)
* Low level of T3 and T4 -> estrogen levels are high (doesn’t get metabolised that quickly) and low progestin (cause more painful cramps)
10) Goiter
* Thyroid gets bigger because it cannot get enough iodine to try and absorb iodine
What are clinical manifestations of hypothyroidism?
1) ↑ Total cholesterol, LDL, Triglycerides
2) ↑ CV risk (e.g Atherosclerosis, MI risk, Stroke risk)
3) ↑ Creatine phosphokinase (CPK) levels
* Other drugs that may increase CPK: Statins
o Check for thyroid problems as well if patient on statin and CPK increase
4) ↑ Miscarriage risk
5) Impaired fetal development
State starting dose of Levothyroxine for subclinical hypothyroidism that is required to be treated
25-75mcg/day
What is the definition of subclinical hyperthyroidism?
Low or undetectable TSH with normal T4
What are patients with subclinical hyperthyroidism at risk of?
1) higher risk of AFib in patients > 60 y.o
2) higher risk of fractures in postmenopausal women
What are some drugs that may cause thyroid diseases?
Amiodarone, Lithium, Interferon alfa
What are patients with subclinical hypothyroidism at risk of?
CV problems
How is Levothyroxine metabolised?
1) Liver (major site for T4 deiodination to T3)
- Glucuronidation and sulphation also occur
2) Deiodination in kidney and peripheral tissues
What are some DDIs/DFIs of Levothyroxine?
- Drugs (inducers/inhibitors) affecting pH, absorption, GI motility, plasma protein binding, liver enzyme
- Food: fiber, grapefruits, pomelo
o Fibre -> interfere with absorption of levothyroxine from the GI tract
Explain the negative feedback principle of thyroid hormone regulation
Low [free T3, T4] -> ↓negative feedback signal -> ↑ release of TRH from hypothalamus -> ↑ TSH -> ↑ binding to TSH receptor -> ↑ T3, T4 synthesis -> ↑ negative feedback signal -> ↓ release of TRH and TSH
Is Carbimazole an active or prodrug?
Prodrug. Converted into active Methimazole in serum.
State the 2 ways in which thyroid hormones are regulated
1) Negative feedback
2) Conversion of T4 to T3 in the periphery via 5-deiodinase
Compare and contrast the 2 thyroid hormones (T3 and T4)
T3 more potent but shorter half life (2 days vs T4: 6-7 days)
T3’s shorter half-life is also why its levels are more erratic and hence not usually measured when evaluating thyroid function
What is MOA of Levothyroxine?
Undergoes deiodination by 5-deiodinase to form active T3 -> binds to Thyroid hormone receptors in cell nucleus and exert its effects (activate gene transcription of proteins responsible for metabolism)
What should you do if a patient on thyroid hormone replacement therapy presents with normal T4 but persistently high TSH?
Enquire about adherence
