Thyroid Disorders Flashcards
Explain how the negative feedback loop works for low TH
Hypothalamus senses low TH and releases TRH (thyrotropin releasing hormone), which signals the pituitary gland to releaae TSH, which stimulates the thyroid gland to release TH
How are TSH levels like in primary hypothyroidism?
High because they are released in response to low TH but unsuccessfully stimulate TH release
How are TSH levels like in primary hyperthyroidism?
Low because of negative feedback
Which thyroid hormone is the more active one
T3
What are the 7 compelling indications for screening for thyroid disorders?
- Presence of autoimmune disease in another organ (eg. T1DM, cystic fibrosis)
- First-degree relative with autoimmune thyroid disease
- Psychiatric disorders (thyroid abnormalities can induce mood, anxiety and psychiatric issues)
- Patients taking amiodarone or lithium (these drugs affect thyroid hormones)
- History of head or neck radiation for malignancies
- Symptoms of hypothyroidism or hyperthyroidism
- Routine screening for pediatric patients and pregnant women
What are the causes of hypothyroidism? (4)
iodine deficiency, hashimoto disease, iatrogenic, drug-induced
What are the s/sx of hypothyroidism?
cold intolerance, dry skin, fatigue, lethargy, weakness, weight gain, bradycardia, slow reflexes, coarse skin and hair, periorbital swelling, menstrual disturbances (more bleeding) and goiter
How are TSH and T4 levels like in primary and central hyperthyroidism?
Primary - high TSH, low T4
Central - low TSH, low T4
How should levothyroxine be dosed?
- Initial dosing for young healthy adults is 1.5mcg/kg/day
- For patients 50-60 years of age with no cardiac issues, limit to 50 mcg daily
- For those with CVD risk, start much lower at 12.5 - 25 mcg/day and titrate up
How should levothyroxine be administered?
30-60 minutes before breakfast or 4 hours after dinner on an empty stomach (including being empty of other medications)
pay special attention to milk, calcium or iron supplements and antacids (space 2h apart)
When should thyroid response be assessed during levothyroxine therapy?
4-8 weeks after initiating/changing dose
What is the TSH target in levothyroxine therapy? How long does it usually take
0.4 - 4.0 mIU/L
2-3 weeks for symptomatic relief
2-3 months for labs to normalise
What are 3 adverse effects of levothyroxine?
- Cardiac abnormalities like tachyarrhythmias, angina, MI
- Risk of fractures
- Signs of hyperthyroidism hints towards over-replacement
When can liothyronine be used
Myxedema coma (or give IV levo)
How should pregnant mother’s levothyroxine dose be adjusted?
Increase by 30-50% to maintain euthyroid status
What is subclinical hypothyroidism?
elevated TSH, normal T4 (result of hashimoto’s disease)
When should treatment be started for subclinical hypothyroidism?
When TSH > 10 mIU/L
or
TSH 4.5 - 10 mIU/L and pt has sx of hypothyroidism, history of CVD or HF
What are the s/sx of hyperthyroidism/
Weight loss or increased appetite, heat intolerance, goiter, fine hair, heart palpitations or tachycardia, nervousness, anxiety, insomnia, menstrual disturbances (lighter or more infrequent or amenorrhea), sweating and warm moist skin, and exophthalmos in Graves disease
What can be used to diagnose hyperthyroidism? (5)
- Presence of signs and symptoms
- Elevated FT4 serum concentrations and suppressed TSH concentrations (except in TSH-secreting adenomas)
- Radioactive iodine uptake (RAIU) can be used for better etiology
- Presence of TRAb, ATgA or TPO
- Biopsy
What are the 4 broad treatment options in hyperthyroidism?
- Surgical resection
- RAI ablation
- Thyroidectomy
- Antithyroid pharmacotherapy (thionamides, iodides, NSBBs)
How to thionamides (carbimazole, PTU) work?
They inhibit the iodination and synthesis of TH
PTU also blocks T4/T3 conversion in periphery at high doses
What are the adverse effects of thionamides? (4)
- fever
- agranulocytosis early in therapy
- rash (high risk for SJS)
- hepatotoxicity (black box warning for PTU)
How is the onset of action like for thionamides?
Slow, 4-6 weeks
(20-30% remission, remission being normal TSH and T4 after 1 year of discontinuing therapy)
What are the two sx hinting towards hyperthyroidism in pregnancy
Failure to gain weight despite having a good appetite
Tachycardia
What drugs should be given for hyperthyroidism in pregnancy
1st trimester give PTU (lesser congenital malformation risk)
2nd and 3rd give carbimazole (lower hepatotoxicity risk)
How to NSBBs work?
Block hyperthyroidism manifestations mediated by beta-adrenergic receptors
May also block T4 conversion to T3 when used at high doses
How does Lugol’s solution (concentrated KI) work?
inhibits the release of stored THs with a minimal effect on hormone synthesis, helping to decrease vascularity and gland size
When should iodides be used? (2)
7-10 days before surgery (to shrink the gland),
3-7 days after ablative therapy
When should iodides not be used?
Before ablative RAI
What is subclinical hyperthyroidism?
Low TSH, normal T4
What 2 drugs can cause thyroid disease?
Amiodarone and lithium
How does amiodarone cause disease
Contains iodine and affects iodine uptake, secretion and production
How does lithium cause disease
Inhibits TH secretion and release, hence signalling an increase in TSH and resulting in goiter development or thyroiditis
Explain the MOA for levothyroxine
The T4 analogue enters cells and is converted to T3 by deiodinases, which enters the nucleus and binds to TH receptors, activating genes responsible for metabolism
What enzyme does carbimazole inhibit?
Thyroid peroxidase (which normally iodinates T3 to give T4)
