Thyroid Flashcards
What is the general anatomy of the thyroid gland?
It is a butterfly-shaped endocrine gland in the front of the neck
What is the function of the thyroid?
Responsible for synthesis, storage and release of the two thyroid hormones (T3 and T4)
What is the most significant difference between T3 and T4?
T3 contains 3 iodines (more potent)
T4 contains 4 iodines (less potent)
What are the main cell types of the thyroid?
- Colloid (storage for the building blocks (iodine, tyrosine, thyroglobulin) and finished product (T3 and T4)
- Follicular cells (bring materials into and out of the colloid cells)
- Parafollicular cells (responsible for Ca2+ balance via calcitonin (reduce Ca2+)
What is the impact of thyroid resection on calcium levels?
No impact, despite loss parafollicular cells
What hormone controls T3 and T4 production?
It is controlled by TSH, which is controlled by thyrotropin-releasing hormone
What are the building blocks for T3 and T4?
MIT + DIT = T3
DIT + DIT = T4
What is the utility of T4 if it is less potent and more energetic?
It is a storage molecule and can allow for rapid changes in thyroid activity
What is the physiological ratio of T4:T3 (but normal can vary between people and different times)?
It is 13:1
What are the processes involved in thyroid introduction?
- Thyroglobulin synthesis
- Iodide trapping
- Oxidation of iodide
- Iodination of tyrosine
- Coupling of MIT and DIT
- Secretion of hormones
What are some actions of thyroid?
- Heart (chronotropic and inotropic)
- Adipose tissue (catabolic)
- Muscle (catabolic, helps eventually build muscle)
- Bone (development)
- Nervous system (developmental)
- Gut (metabolic)
- Other tissues (calorigenic)
What are the actions of T3 and T4?
- Heart (chronotropic and inotropic)
- Adipose tissues (catabolic)
- Muscle (catabolic)
- Bone (developmental)
- Gut (metabolic)
- Other tissues
What proportion of T4 is produced by the thyroid?
T4 in circulation is 100% from thyroid
What proportion of T3 is produced by the thyroid?
20% directly from thyroid (the rest is produced from conversion of T4 to T3)
What is the thyroid release feedback loop?
Low T3/T4 levels promote release of TSH, which promotes T3/T4
What inhibits TSH release?
- High circulating T3/T4
- Lithium
- Iodide excess (inhibition of the organification of iodide)
What is the prevalence of thyroid disorders?
10% of Canadians have overactive or underactive thyroid glands (more than 50% are undiagnosed)
Do more men have thyroid disorders?
No, more than 80% with thyroid disease are women
What is hyperthyroidism?
Disease caused by excess synthesis and secretion of thyroid hormone
What are some causes of hyperthyroidism?
1, Toxic diffuse goiter (Graves disease)
2. Toxic multi-nodular goiter (Plummers disease)
3. Acute phase of thyroiditis
4. Toxic adenoma
What are some characteristics of toxic diffuse goiter (Graves disease)?
Auto-immune disorder (most common cause of hyperthyroidism, antibodies against the TSH receptor)
More common in younger, female patients
Hyperplasia of thyroid gland (leads to a goiter)
What are some characteristics of toxic multi-nodular goiter (Plummers disease)?
Common cause in older females
Second most common cause of hyperthyroidism
Triggered by iodine deficiency (reduced T4 production, )
Develops slowly over several years
What are the common cause of acute phase of thyroiditis?
- Causes inflammation and damage to the thyroid gland
- Damage causes excess hormone to be released
- Eventually leads to hypothyroidism once T3/T4 stores exhausted
What are some common causes of toxic adenoma?
- Benign tumours growinf on thyroid gland
- Become active and act just like thyroid cells, secreting T3/T4?
What is the clinical presentation of hyperthyroidism?
- Tremor in hands
- Diarrhea
- Heat intolerance
- Unintentional weight loss
- Weakness
- Tachycardia
- Amenorrhea
What are some toxic diffuse goiter specific presentation?
- Exophthalmos (or proptosis)
- Peri-orbital edema
- Diplopia (double vision)
- Diffuse Goiter
- Pre-tibial myxedema (rash on skin)
What is the specific presentation of toxic multi-nodular goiter?
- Same general hyperthyroidism symptoms
- Individual thyroid nodules may be palpable
Review slide 22 for diagnostic lab tests
What drugs can induce hyperthyroidism?
- 1st gen antipsychotics (Increases TSH secretion)
- Amiodarone & iodine (Increases synthesis and release of T3/T4)
- Androgens & Glucocorticoid (Decreases Thyroxin binding globulin)
What are the treatment options for hyperthyroidism?
Drugs
- Thioamides
- Beta-blockers
Radioactive iodine (RAI)
Surgery (thyroidectomy)
What are the types of thioamides used in treatment of hyperthyroidism?
- Methimazole (MMI)
- Propylthiouracil (PTU)
What are some specific indications for thioamides?
- Toxic diffuse goiter
- Toxic multi-nodular goiter
- Pre-treatment before radioactive iodine
What is the goal of therapy for acheiving remission of hyperthyroidism with thioamides?
- Relapses are common
- About 30% remain in remission after 1-2 years of therapy with either drug
What is the mechanism of action for thioamides?
- They interfere with thyroid peroxidase-mediated processes in T3/T4 production
- PTU also inhibits peripheral conversion of T4 to T3
How are thioamides dosed?
It is an initial dose (lower maintenance doses)
Titrate dose if TSH and T4 does not improve in 4-6 weeks
Decrease dose gradually once euthyroid
Review slide 28
Can thioamides be taken without food?
Take with or without food
What is the onset of effect for thioamides?
Symptom improvement in 1-4 weeks
Euthyroid in 2 to 3 months
How long does thioamide therapy for hyperthyroidism last?
12-18 months is common (taper to d/c to see if relapse occurs)
What are some common side effects associated with thioamides?
Higher rates with PTU than MMI
- GI upset
- Rash
- Arthralgia
- Abnormal taste/smell
What are some serious side effects associated with thioamide use?
- Agranulocytosis (0.3-0.4% of patients affected)
- Fever, malaise, sore throat are the most common symptoms
- WBC falls to less than 0.5 x 10^9 - Hepatoxicity (0.1-0.2%)
- MMI (reversible cholestatic jaundice)
- PTU (allergic type hepatocellular damage) - Vasculitis (more common with PTU, like all side effects)
- Damage to vascular tissue causing inflammation and destruction of blood vessels (acute renal dysfunction, arthritis, skin ulcers, respiratory problems)
Review slide 34 for what to counsel patients on about thioamides
What are some drug interactions associated with thioamides?
Warfarin (results in a decrease in INR, often resolved by adjusting warfarin dose)
Digoxin (Increase in digoxin levels)
Methimazole inhibits 2D6. 2C9, 2E1 (very weak interactions, clinically irrelevant)
What are some monitoring tips for thioamides?
Assess TSH, T3, and T4 at 4-6 week intervals until stable, then every 2-3 months for 6-12 months, then every 4-6 months
CBC (baseline and 1 week later for agranulocytosis)
LFTs (baseline and 1 week later for signs of hepatotoxicity)
What should be monitored when discontinuing thioamides?
TSH at 3, 6, 12, and annually
Relapse of hyperthyroidism after thioamide d/c is most likely in the first 3 months
Review slide 38 on differences between thioamides (propylthiouracil and methimazole)
What is the purpose of beta-blockers in hyperthyroidism treatment?
They reduce CV symptoms associated with hyperthyroidism
- Palpitations
- Tachycardia
- Tremors
- Anxiety
- Heat intolerance
What beta-blockers are used in hyperthyroidism treatment?
Choose propranolol (short-acting and easy to titrate) if no other compelling indication for a beta-blocker exists
What is the role of radioactive iodine treatment in hyperthyroidism treatment?
Used commonly
radio-labelled iodine is taken up by the thyroid gland and causes tissue damage and ablation of gland
What are the disadvantages of radioactive iodine therapy in hyperthyroidism therapy?
- Permanent hypothyroidism
- Can trigger thyroid storm/thyrotoxicosis
- Worsen exopthalmous (protruding eyes)
What are some contraindications for radioactive iodine therapy for hyperthyroidism?
- Pregnant women/lactation
- Severe hyperthyroidism/exopthalmous
What happens to thyroid levels immediately after administration of radioactive iodine?
Initial hyperthyroidism exacerbation likely (controlled with thioamide pre-treatment and post-treatment)
How is radioactive iodine therapy for hyperthyroidism initiated?
Pre-treatment with thioamides (used to achieve euthyroidism and prevent thyroiditis). Initiate 4-6 weeks before radioactive therapy, and stop 3 days before
Administer radioactive iodine therapy
Restart thioamides 3 days after administration of radioactive iodine therapy
Taper and discontinue once thyroid hormone levels decline
What are some patient instructions following radioactive iodine therapy for hyperthyroidism?
- Do not kiss, exchange saliva, or share food or eating utensils for 5 days.
- Avoid close contact with infants, young children (under 8 years), and pregnant women for 5 days (patient can be in the same room though)
- No breast-feeding
- Flush toilet twice and wash hands thoroughly
- If sore throat or neck pain develops (take acet or aspirin)
- If increased nervousness, tremors, or palpitations, then call a physician (signs of hyperthyroidism after radioactive treatment)
What is the role of surgery in hyperthyroidism treatment?
It is reserved for the following patient groups:
- Pregnant patients who cannot tolerate medication
- Patients who want curative therapy, but not RAI
- Patients with large goiters (resistant to RAI)
What are some complications associated with surgical resection of the thyroid?
- Hypoparathyroidism (Parathyroid is behind the thyroid, so it can be damaged during thyroid resection)
- Vocal cord paralysis
- Thyrotoxicosis
Should thioamides be used to treat thyroiditis?
No, because thyroiditis is an acute condition and thioamides are used in more chronic presentations
How is thyroiditis managed?
- Self-limited
- beta-blocker for symptom control
- NSAIDs for pain
- Steroids (for most severe cases)
What is thyroid storm/thyrotoxicosis?
It is a rare, life-threatening condition that is characterized by severe manifestations of hyperthyroidism (liver damage, CV collapse, and shock)
What causes thyroid storm/thyrotoxicosis?
- Thyroid surgery or radioactive iodine therapy
- Trauma
- Infection
- Giving birth
What is the basic cause of hypothyroidism?
Results from a defect anywhere on the HPA axis
What are the types of hypothyroidism?
- Chronic autoimmune thyroiditis (Hashimoto’s)
- Drug-induced
- Iatrogenic disease (thyroidectomy/RAI)
- Post-partum thyroiditis
- Chronic iodine deficiency
- Central hypothyroidism
- Hypopituitarism
What are some characteristics of chronic thyroiditis (Hashimoto’s)?
- Most common cause of hypothyroidism
- Autoimmune disorder where antibodies form and bind to TSH receptors and destroy thyroid cells
- Other antibodies may form that can interfere with T3 and T4 production
What are some drugs that can trigger hypothyroidism?
- Lithium
- Amiodarone
What is the mechanism of action for lithium causing hypothyroidism?
Lithium blocks iodine transport into the thyroid and prevents hormone release
Monitor for hypothyroidism at 3 months, then every 6-12 months
What is the mechanism of action for amiodarone causing hypothyroidism?
Can cause hyperthyroidism (5-25%)
Increased risk if history of thyroid dysfunction
Monitor every month for 3 months, then every 3 months for 6 months, then every 6-12 months
What is the clinical presentation of hypothyroidism?
PNS-like activity
- Slow harse speech
- Puffiness around eyes
- Emotional lability
- Impaired concentration
- Hypothermia
- Confusion
- Hypoglycemia
Review slide 55 for lab results that are significant to diagnosing hypothyroidism?
What substance is elevated in hypothyroidism patients?
TSH
Review slide 56 for a series of drugs that can affect levels of hormones and substances that are used to diagnose hypothyroidism
What are some treatment options for hypothyroidism?
Replacement of thyroid hormone is necessary. The following are options to resolve the deficiency of thyroid hormones:
- Desiccated thyroid
- Liothyronine
- Levothyroxine
- Combined T3/T4
What are some characteristics of desiccated thyroid?
- First agent available
- Prepared from thyroid glands of animals
- Contains T3 and T4
- Causes high peak T3 (and shorter half-life)
- Not well standardized batch to batch
What are some characteristics of Liothyronine?
- Contains T3, no effect on T4
- Short half-life (causes wide flucuations in serum levels)
- Costly
- Higher incidence of cardiac adverse effects
- Try to dose close to physiological ratio of T4:T3 (13:1)
What are some characteristics of Levothyroxine?
- Analogue of T4
- Standard 1st therapy
- Half life of 7 days (potential for weekly dosing)
- Conversion to T3 regulated by body
How is levothyroxine dosed?
Depends on age, weight, cardiac stus, severity, and duration of hypothyroidism (ensure titration is gradual and safe)
Average replacement dose is 1.6mcg/kg/day (100mcg is given empirically to young, healthy patients)
Starting dose: (12.5mcg/day to max weight based dose)
What are some populations that we should be more careful with initiating levothyroxine?
Start low (12.5-25mcg) and titrate up by 12.5-25mcg every 4-6 weeks
- Any CVD
- Rhythm disorders
- More than 50 years old
- Severe, long-standing hypothyroidism
What are some administration instructions for levothyroxine?
Administer on empty stomach, 30 minutes before meals or 1 hours after
Best to take in the morning and stagger from other drugs
What are some side effects associated with levothyroxine?
- Hyperthyroidism symptoms (nervousness, hyperactivity, mood swings)
- Cardiac risk increase
- Aggravate existing CVD
- BMD reduction
What are some drug interactions associated with levothyroxine?
Drugs that reduce absorption of levothyroxine:
- Antacids
- Iron
- Ca2+/mineral supplements
- Cholestyramine
What are some drug interactions associated with levothyroxine?
Potent CYP inducers increase thyroid hormone metabolism:
- Ciprofloxacin
- Phenytoin
- Carbamazepine
- Rifampin
- Pregnancy of arrhythmias
What are some monitoring parameters for levothyroxine?
TSH (aim for low normal value, 2.5mIU/L). Any lower increases risk for cardiac toxicity
Levels can take 4-6 weeks to stabilize with each dose (then monitor TSH every 6-12 months)
Symptom improvement in 2-3 weeks, with max effect in 4-6 weeks
Is subclinical hypothyroid treated in most cases?
No, it is not treated often (only treated if patient develops symptoms, planning pregnancy, heart failure, or a very young patient)
What are some reasons for levothyroxine treatment failure?
- Decreased bioavailability (poor adherance, malabsorption)
- Increased need (recent weight gain, pregnancy, new meds that increase metabolism)
- Other conditions (Addison’s disease, altered HPA)
