Thyroid Flashcards
What are the physiological functions of thyroid hormones?
related to development, growth, metabolism
- Body temperature
- CNS
- Cardiac function
- GI functions
- Menstrual cycles
- Increase lipid metabolism
- Increase uptake and utilization of glucose
Describe the negative feedback mechanism of thyroid levels in the body when THs are low
- Hypothalamus detects low TH
- Hypothalamus releases TRH (thyrotropin releasing hormone)
- TRH binds to pituitary glands and stimulates release of TSH (thyroid stimulating hormone aka thyrotropin)
- TSH binds to thyroid gland and stimulates secretion of thyroid hormone
- Thyroid hormone in the blood reaches normal levels and the hypothalamus stops releasing TRH
Is the TSH levels high or low in:
- Primary hyperthyroidism
- Primary hypothyroidism
- Hyper: low
- Hypo: high
What is the ratio of T4 to T3 in the circulation?
4:1
Is T4 or T3 more potent?
T3
How is T4 converted to T3?
Peripheral conversion by deiodination (via deiodinases)
What’s the half life of T4 and T3?
T4: 6-7 days
T3: 2 days
Are T4 and T3 usually plasma protein bound?
> 99% bound
To evaluate thyroid status, which hormone levels will be generally useful?
Free T4 and TSH
T3 has a erratic half-life and thus is not routinely ordered
What can cause elevation of thyroxine binding globulin (TBG)?
Pregnancy or on synthetic estrogen
What is the consequence of elevated TBG?
FT3 and FT4 will go down as more of them gets bound to TBG
This will cause a negative feedback to increase the secretion of TH from the thyroid to reach a new equilibrium
This process might be affected if the thyroid gland is not functioning well
What are some antibodies that are related to thyroid diseases?
ATgA: thyroglobulin antibodies
TPO: thyroperoxidase antibodies
TRAb: TSH (thyrotropin) receptor IgG antibodies
Routine screening of thyroid status is required for?
Pediatric patients and pregnant women
What are some compelling indications for screening of thyroid status?
- Presence of autoimmune disease
- First degree relative with autoimmune thyroid disease
- Psychiatric disorders (as thyroid malfunction can manifest as such)
- Taking amiodarone or lithium
- History of head/neck radiation for malignancies
- Symptoms of hypo/hyperthyroidism
What are causes of primary hypothyroidism?
- Hashimoto’s disease
- Iatrogenic: thyroid resection or radioiodine ablative therapy
- Iodine deficiency
What are causes of secondary hypothyroidism?
- Central hypothyroidism (hypothalamus or pituitary malfunction)
- Drug induced
How is Hashimoto’s disease diagnosed?
Positive ATgA and TPO antibodies
Signs of hypothyroidism (may have initial hyperthyroidism)
Increased TSH, and decreased FT4 (not in the early stage)
What are signs and symptoms of hypothyroidism?
- Cold intolerance
- Dry skin
- Fatigue
- Weight gain
- Bradycardia
- Slow reflexes
- Coarse skin and hair
- Periorbital swelling
- More frequent and heavier menses
- Goiter
What are some clinical manifestations of hypothyroidism?
Increased lipids –> increased risk of atherosclerosis and MI
Increased creatine phosphokinase levels
Increased miscarriage risk
Impaired fetal cognitive development
How do you diagnose central hypothyroidism?
Symptoms of hypothyroidism
Low FT4 and low TSH
What are pharmacotherapy options for hypothyroidism?
- Levothyroxine (first line, synthetic T4)
- Liothyronine (synthetic T3)
What is the initial dosing of levothyroxine in young and healthy adults?
1.6 mcg/kg/d (usually can start at 100 mcg/day)
What is the initial dosing of levothyroxine in healthy patients of 50-60 years of age?
50 mcg daily
What is the initial dosing of levothyroxine in patients with CVD?
12.5 to 25 mcg daily
How should you titrate up levothyroxine dose?
Can increase or decrease (depending on response) every 4 to 8 weeks, in increments of 12.5 to 25 mcg daily or 10-15% of weekly dose
Counselling points for administration of levothyroxine
- Take on empty stomach, 30-60 mins before breakfast or 4 hours after dinner (and other medications)
- Space 2 hours apart with calcium, iron supplements or antacids
What lab parameters will be useful for monitoring of central hypothyroidism?
FT4
TSH not useful cause it will be low
What is the general target for TSH in primary hypothyroidism?
0.4 to 4 mIU/L
Different target for pregnant women
How long does it take for levothyroxine to exert its effect?
2-3 weeks for symptomatic relief
4-8 weeks for lab parameters normalization
How can lab parameters be used to hint non-adherence?
Normalization of FT4 levels with consistently high TSH levels
What is the upper limit of normal TSH in older adults?
Controversial
>70 yo, TSH can still be WNL up to 6.9 mIU/L
What are S/E or signs of over replacement of thyroid hormones?
Cardiac abnormalities, risk of fractures, signs of hyperthyroidism
After a euthyroid state is achieved, how often should you monitor thyroid panel?
every 6 months to 1 year, TFT recommended in non-pregnant adult patients
What is liothyronine’s starting dose in normal adults? elderly? CVD?
25 mcg
elderly or CVD pts 5 mcg
Why is liothyronine not first line treatment for hypothyroidism?
High incidence of adverse effects, shorter half-life, expensive
When should combination of levothyroxine and liothyronine be used?
In patients with normalized TSH but still has symptoms of hypothyroidism
In which condition will liothyronine be used?
Myxedema coma
What are some effects of hypothyroidism in pregnant women?
Miscarriage, spontaneous abortion
Congenital defects, impaired fetal cognitive development
Why does hypothyroidism in pregnant women causes congenital defects?
Maternal THs provides fetus with THs for up to 12 weeks before the fetus forms their own thyroid gland
(THIS I INFER, DK CORRECT OR NOT, BUT HELP TO RMB)
What needs to be done for patients on thyroid replacement when they get pregnant?
To increase pre-pregnant dosage at about 30-50%
Due to increasing TBG as pregnancy progresses
What is the target TSH for pregnant women?
1st trimester: <2.5 mIU/L
2nd trimester: <3.0 mIU/L
3rd trimester: <3.5 mIU/L
more TSH is needed as compared to normal population to stimulate more TH, as there are less free TH due to increasing TBG levels
What is subclinical hypothyroidism?
Asymptomatic
Elevated TSH with normal FT4
Often result of early Hashimoto disease
When would treatment of subclinical hypothyroidism be considered?
TSH > 10 mIU/L due to risk of coronary heart disease
TSH 4.5 - 10 mIU/L AND
- symptomatic
- TPOAb present
- history of CVD, HF
What is the initial dose of levothyroxine for treatment of subclinical hypothyroidism?
25-75 mcg daily
What are the causes of hyperthyroidism?
- Graves disease
- Pituitary adenoma
- Toxic adenoma
- Toxic multi-nodular goiter (Plummer’s disease)
- Drug induced
- Subacute thyroiditis (due to infection, drug, early Hashimoto’s disease)
What are the signs and symptoms of hyperthyroidism?
- Weight loss or increased appetite
- Heat intolerance
- Warm moist skin
- Goiter
- Fine hair
- Palpitations
- Nervousness, anxiety, insomnia
- Lighter or infrequent menstruation
- Exophthalmos (in Graves disease)
How does radioactive iodine uptake test help to differentiate the etiology of hyperthyroidism?
Elevated uptake –> gland is actively secreting TH ie. Graves disease, adenoma, multinodular goiter
Suppressed uptake –> thyroiditis or cancer
What are the tests that are useful to diagnose hyperthyroidism?
- FT4 (elevated)
- TSH (suppressed)
- Presence of TRAb, ATgA, TPO
- Biopsy
- RAIU test
What are the treatment options for hyperthyroidism?
- Surgical resection
- Thyroidectomy
- RAI ablative therapy
- Pharmacotherapy (thionamides, iodides, NSBB)
What is the first line option of treatment in Graves disease? Are there any contraindications for that option?
RAI ablative therapy (destroys overactive thyroid cells)
Contraindicated in pregnant women
When is pharmacotherapy for hyperthyroidism considered?
- For those awaiting ablative therapy or surgical resection
- For those who are not candidates of ablative or surgical option
- For those with mild disease
- For those with limited life expectancy
What are drug examples of thionamides? What is their MOA?
Carbimazole and propylthiouracil (PTU)
MOA: inhibits iodination and synthesis of thyroid hormones by antagonizing TPO; PTU can additionally block peripheral conversion of T4 to T3
What are adverse effects of thionamides?
- Hepatotoxicity (boxed warning for PTU)
- Rash, risk for SJS
- Agranulocytosis (usually within 3 months of therapy)
- Drug fever
What is the initial dose of carbimazole? And subsequent dose when euthyroid?
15-60 mg daily in 2-3 divided doses
5-15 mg once daily when euthyroid
What is the initial dose of PTU? And subsequent dose when euthyroid?
50-150 mg TDS
50mg BD-TDS when euthyroid
When does thionamides start to reduce symptoms of hyperthyroidism? When is the maximal effect of thionamides seen?
Takes weeks to reduce symptoms
Takes 4-6 months for maximal effect
As the body stores the thyroid hormones and it takes time for it to be depleted
The drug affects synthesis of NEW thyroid hormones
Do you need to take thionamides for life-long?
Remission rates are low at about 20-30%, meaning only 20-30% people who have discontinued the drug can maintain a normal TSH and FT4 for 1 year or more –> so probably yes?
What are the lab parameters used for monitoring efficacy of thionamides?
In early therapy, total T3 may be better marker for efficacy than FT4
TSH may remain suppressed for months after therapy begins, thus might not be ideal for early monitoring
What are the 2 main symptoms of hyperthyroidism in pregnant women?
- Failure to gain weight despite good appetite
- Tachycardia
What is the treatment of choice for hyperthyroidism in pregnant women?
1st trimester: Use PTU (risk of congenital malformations with carbimazole)
2nd and 3rd trimester: Use carbimazole (PTU has higher risk of hepatotoxicity)
DO NOT USE RAI ablative therapy
How does NSBB help with hyperthyroidism?
- Blocks hyperthyroidism manifestations mediated by beta adrenergic receptors (symptomatic relief)
- Block peripheral T4 to T3 conversion when used at high dose
When is NSBB indicated?
Treatment of thyroiditis
Symptomatic relief
Bridging therapy for thionamide effects to kick in
PRN for high risk pts eg. elderly with CVD
What is Lugol’s solution? What is its MOA?
Saturated solution of potassium iodide
MOA: Inhibits the release of stored THs, decrease vascularity and size of thyroid gland
When is Lugol’s solution indicated?
- 7-10 days before surgery to shrink the gland
- 3-7 days after ablative therapy to inhibit thyroiditis-mediated release of stored TH
- Thyroid storm
What is the longest duration you can use Lugol’s iodine for?
14 days
TH release will resume afterwards
When is use of Lugol’s iodine contraindicated?
BEFORE ablative therapy
It can reduce uptake of radioactive iodine, rendering the procedure ineffective
Subclinical hyperthyroidism definition
Asymptomatic
Low or undetectable TSH, normal FT4
What are the risks of subclinical hyperthyroidism?
- Elevated risk of AF in patients older than 60
- Elevated risk of bone fracture in postmenopausal women
When and how should subclinical hyperthyroidism be treated?
More compelling if TSH < 0.10 mIU/L
Same as hyperthyroidism, except use oral therapy as an alternative to ablative therapy in young patients
If AF, use beta-blocker
What drugs can cause thyroid disease?
Amiodarone: hypo or hyper
Lithium: hypo or hyper
Interferon alfa: hyper then hypo
All 3 drugs can cause thyroiditis
