Thyroid Flashcards
Primary Thyroid Disease
Affects Thyroid Gland (T4 and T3 secretion)
Secondary Thyroid Disease
Affects Pituitary Gland (TSH Secretion)
Tertiary Thyroid Disease
Affects Hypothalamus (TRH Secretion)
T4 vs T3
- Which is the main hormone secreted
- Which one is biologically active
- Which one is more protein bound
- Which one has the longer half life
- Which one is more potent
T4 (Thyroxine)
- Main hormone secreted
- Biologically Inactive
- 99.96% protein bound
- Half Life = 7 days (Longer half life due to being more protein bound than T3)
T3 (Triiodothyronine)
- 80% converted in periphery from T4
- Biologically Active
- 99.5% protein bound
- Half Life = 1-2 days
- 3x more potent at inhibiting TSH
Hyperthyroidism
- How much thyroid hormone
- Effect on metabolism
Too much thyroid hormone
Metabolism speeds up
Hypothyroidism
- How much thyroid hormone
- Effect on metabolism
Too little thyroid hormone
Metabolism slows down
TSH
- Value in Hyperthyroidism vs Hypothyroidism
TSH is low in Hyperthyroidism
TSH is high in Hypothyroidism
TSH
- Fluctuations in value
Will be at its highest around midnight
Will be at its lowest in late afternoon
Values are different in pregnancy and old age
When to use TSH
When screening for thyroid dysfunction
When screening for thyroid hormone replacement
Not good for pituitary diseases
- Use free T4 instead
When to use Free T4
TSH is low (Sign of hyperthyroidism)
- Use free T4 to evaluate thyrometabolic status
Use to confirm hyper/hypothyroidism
- Used as second test after TSH
When to use Free T3
Generally not used for hypothyroidism
- As T3 is usually low in absence of thyroid disease
Used to differentiate between different kinds of hyperthyroidism
- Ordered when TSH is low but T4 is normal/low
Who should be screened for Thyroid Disorders
Do not screen asymptomatic non-pregnant patients
Screen:
- Symptomatic patients
- Patients at increased risk
Patients at increased risk of thyroid disorders
Women older than 45
Postpartum Women
Patients taking lithium or amiodarone
Patients with auto immune disease
- Type 1 Diabetes
- Strong Family History
Tests for screening Primary Thyroid Disorders
TSH first
Do not use free T3 or free T4 for screening hypothyroidism or to adjust doses for patient with diagnosed primary hypothyroidism
- T3 and T4 are mostly protein bound so the amount in blood will normally be low
Hypothyroidism
- 2 Kinds
Subclinical:
- TSH high
- T4 normal
Overt:
- TSH high
- Free T4 is low
Hypothyroidism
- Signs and Symptoms
Similar to Hyperthyroidism:
- Hoarseness of Deepening of Voice
- Swelling (Goiter)
- Persistient Dry/Sore throat
- Difficulty Swallowing
- Infertility
Different from Hyperthyroidism
- Puffy Eyes
- Cold Intolerance
- Weight Gain
- Elevated Cholesterol
- Tiredness
- Forgetful/Slower thinking
- Depression
- Muscle weakness/cramps
- Slower heartbeat
- Constipation
Hypothyroidism
- High risk populations
- Women (postpartum) - 3x more risk
- Prior history of graves diseease
- Increasing age (especially after 60)
- Family history of autoimmune thyroid disease
- Other autoimmune endocrine conditions (Type 1 diabetes)
- Other autoimmune non-endocrine conditions (Celiac disease, Pernicious anemia)
Hypothyroidism
- Primary
Primary (99%)
- Hasimoto’s Disease
- Iatrogenic Hypothyroidism
- Iodine Excess/Deficiency
- Drugs
- Congenital
Hypothyroidism
- Secondary/Tertiary
Secondary/Tertiary (1%)
- Pituitary Disease
- Hypothalamic Disease
Hashimoto’s Disease
Primary Hypothyroidism
- Elevated Thyroid Peroxidase Antibody, attacks and impairs Thyroid Peroxidase
—> Lowers amount of thyroid hormone
Iatrogenic Hypothyroidism
Radiated Iodine
- Destroys thyroid gland
Thyroidectomy
What drugs cause hypothyroidism
Lithium
Amiodarone
Antithyroid drugs
Effect of Excess Iodine on Thyroid
Causes a surge in thyroid hormone
- Then causes white blood cells to infiltrate thyroid and impairs it from producing thyroid hormone
Causes Hypothyroidism
Effect of Deficiency Iodine on Thyroid
Hypothyroidism
Hypothyroidism Treatment
- Pharmacological
Levothyroxine
Hypothyroidism Treatment
- Pharmacological Dose
Long half life, once a day dosing
Dose depends on:
- Age
- Body weight
- Pregnancy status
- Cardiac Disease
Severity of hypothyroidism
- If subclinical = Lower dose
- If RAI or Thyroidectomy = Higher dose
Hypothyroidism Treatment
- Pharmacological Absorption
Take 30-60 minutes before breakfast with water
Should be take on empty stomach
- Separate by 4 hours with Iron, Calcium, Multivitamins
Levothyroxine Dose
- Healthy Adult
1.6 mcg/kg
Levothyroxine Dose
- Elderly (65 years or above)
1.0 mcg/kg
- Average maintenance dose is 100mcg
- Initiation should be at lower dose and titrated slowly (Start at 12.5-25mcg)
As patient ages dose should decrease
Levothyroxine Dose
- Cardiac Patients (Or at risk)
12.5-25mcg
- Initiate at low dose and titrate slowly
- Avoid cardiac compromise and ischemia (Avoid increasing BP and HR)
Levothyroxine
- Monitoring
Primary Hypothyroidism: Monitor TSH levels
Secondary Hypothyroidism: Monitor Free T4 levels
Monitor every 6-8 weeks after initiation/dose change until euthyroid
- Adjust as needed until values are euthyroid
- Once euthyroid monitor yearly, or until new symptoms appear
Over treatment of Levothyroxine
- Atrial fibrillation and Stroke
- Increased risk of Angina and Myocardial Infarction in Cardiac Patients
- Bone Loss and Fractures
- Anxiety, Sleep Disturbance, Irritability
Under treatment of Levothyroxine
- Increased lipids
- Decreased heart rate and ventricular contractility
- Increased peripheral vascular resistance and diastolic pressure
- Memory loss
- Mood impairment
Levothyroxine in Healthy Patients
- Low Dose vs Full Dose (1.6 mcg/kg)
Full dose is more convenient and cost effective, achieves Euthyroidism faster
Hypothyroidism Treatment
- Desiccated Thyroid
Lower T4:T3 ratio is lower than what is secreted by human thyroid gland
- Supraphysiologic levels of T3
- Animal derivative
Not recommended
Hypothyroidism Treatment
- Liothyronine
Basically synthetic T3
- Short half life, has to be dosed twice a day
- Increases Cardiac Adverse Drug Reaction
Hypothyroidism Treatment
- Combination
Levothyroxine + Liothyronine
- No evidence of benefit
- Small subset of patients do better (Those that remain symptomatic on levothyroxine)
Summary: Consider if patient remains symptomatic on levothyroxine
- Have to carefully monitor
Factors that reduce Levothyroxine Effectiveness
Malabsorption Symptoms
Reduced Absorption
Drugs that increase clearance
Factors that decrease T4 conversion to T3
Factors that reduce Levothyroxine Effectiveness
- Malabsorption Symptoms
Short Bowel
Celiac Disease
Factors that reduce Levothyroxine Effectiveness
- Reduced Absorption
Sucralfate
Food
Ferrous Salts
Calcium Supplements
Aluminum Hydroxide
Cholestyramine
Factors that reduce Levothyroxine Effectiveness
- Drugs that increase clearance
Rifampin
Carbamazepine
Phenytoin
Factors that reduce Levothyroxine Effectiveness
- Decreases T4 conversion to T3
Amiodarone
Hypothyroidism
- Pregnancy
Thyroid function changes in pregnancy
- May have to increase dose
Untreated hypothyroidism can affect cognitive function of child and increase maternal hypertension, preeclampsia, postpartum hemorrhage, spontaneous abortion, fetal death
Hyperthyroidism
- Symptoms
Similar to Hypothyroidism
– Hoarseness of Deepening of Voice
- Swelling (Goiter)
- Persistient Dry/Sore throat
- Difficulty Swallowing
- Infertility
Different from Hypothyroidism
- Budging eyes
- Heat Intolerance
- Weight Gain
- Rapid/Irregular Heartbeat
- Nervousness
- Irritability
- Frequent bowel movements
- Increased sweating
- First trimester miscarriage
Hyperthyroidism
- Etiology
- Graves’ Disease
- Toxic Nodules
- Tumours
- Subacute Thyroiditis
- Hashitoxicosis
- Excessive Dosage of T3 or T4
Graves’ Disease
Hyperthyroidism (Seen in younger female patients)
- Body produces antibodies that activate the thyroid gland
Toxic Nodules
Hyperthyroidism (Seen in elderly)
- Creates lots of T3 and T4
- Does not respond to negative feedback
Tumours
Hyperthyroidism
- Excessive stimulation of thyroid gland
Subacute Thyroiditis
Hyperthyroidism in first phase
- Then white blood cells infiltrate and damage the thyroid gland leading to hypothyroidism
Hashitoxxicosis
Hyperthyroidism in first phase
- Then white blood cells infiltrate and damage the thyroid gland leading to hypothyroidism
Excessive Dosage with T3 or T4
Hyperthyroidism
Autoimmune Endocrine Disorders associated with Graves’ Disease
- Addison’s Disease
- Type 1 Diabetes
- Primary Gonadal Failure
- Hashimoto’s Thyroiditis
Autoimmune Non-Endocrine Disorders associated with Graves’ Disease
- Celiac Disease
- Myasthenia Gravis
- Pernicious Anemia
- Immune Thrombocytopenic purpura
- Rheumatoid Arthritis
Hyperthyroidism
- Treatment
Drugs
Radioactive Iodine
Surgery
Hyperthyroidism
- Beta Blockers initiation
Used to control symptoms, should not be sole therapy
- Can be initiated at presentation before diagnosis
Hyperthyroidism
- Beta blockers For who
Considered for patients with:
- Symptomatic Thyrotoxicosis
- Elderly
- Resting heart rate greater than 90
- Coexistent CV disease
Hyperthyroidism
- Beta blockers which to choose
All are equally effective
- Some may impair T3 to T4 conversion but has not shown to be clinically significant
Hyperthyroidism
- Antithyroid Drugs
Propylthiouracil (PTU)
Methimazole
Hyperthyroidism
- Antithyroid Drugs Mechanism
Inhibits Thyroid Peroxidase and synthesis of thyroid hormone
–> Less thyroid hormone
PTU blocks peripheral T4 to T3 conversion
Hyperthyroidism
- Antithyroid Drugs Response
Higher likelihood of response:
- Older patients (Greater than 40 years old)
- Small goiters
- Short duration of disease
- Small amounts of Thyroid Peroxidase Antibody
Hyperthyroidism
- Antithyroid Drugs Long Term Treatment
Best to use Methimazole
Hyperthyroidism
- Antithyroid Drugs First Line
Methimazole is preferred as first line
- Except 1st trimester of pregnancy where PTU is preferred
PTU vs Methimazole
- Half Life
Methimazole has a higher half life
- Can be dosed less frequently at lower doses
PTU vs Methimazole
- Side Effects
PTU has higher risks of side effects
PTU vs Methimazole
- Pregnancy
Methimazole is not to be used in first trimester of pregnancy
- Use PTU instead
Hyperthyroidism
- Antithyroid Drugs Side Effects
- Skin Rash
- Allergic Reaction
- Agranulocytosis
- Hepatotoxicity (Greater chance in PTU)
Hyperthyroidism
- Antithyroid Drugs Counseling
Stop medication if experiencing rash, fever, jaundice, sore throat
Hyperthyroidism
- Antithyroid Drugs Lab Tests
- Baseline CBC (Include WBC and differential)
- ALT/AST
- Bilirubin
Hyperthyroidism
- Methimazole Monitoring
- Monitor Free T4 at 4 weeks, then every 4-8 weeks (Can also add free T3)
- Once Free T4/T3 is normal, add TSH and monitor every 2-3 months
- Also taper dose by 30-50%
- Continue for 12-18 months
- Taper or discontinue is TSH is normal at this time
Long-term methimazole in Graves’ disease
Hyperthyroidism has less chances to recur with long term treatment
Hyperthyroidism
- RAI Indication
- Patient is unable to get surgery
- Contraindications to ATD
- Not planning to get pregnant
Hyperthyroidism
- RAI Monitoring
Should see Euthyroidism within 6-18 weeks
- 50% chance to cause hypothyroidism after 10 years
Hyperthyroidism
- RAI Pregnancy
Contraindicated in pregnancy
- Crosses placenta and destroys fetal placenta
- Defer pregnancy for 3-6 months after treatment
Hyperthyroidism
- Surgery Indication
- Symptomatic Compression
- Large Goiter (greater than 80g)
- Thyroid malignancy
- Planning pregnancy 4-6 months or less
Hyperthyroidism
- Surgery Recurrence
Total Thyroidectomy: 0% chance of recurrence
Subtotal Thyroidectomy: 8% chance of recurrence at 5 years
