PHAR 255 > PHAR 255 - Thyroid > Flashcards

PHAR 255 - Thyroid Flashcards

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1
Q

Anatomy of the Thyroid Gland

A

Butterfly-shaped endocrine gland in the front of the neck
Colloid - Storage of building blocks to produce T3/T4 and store T3/T4
Follicular Cells - Transport building blocks into colloid and secrete T3/T4
Parafollicular Cells - Secrete calcitonin

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2
Q

Role of the Thyroid Gland

A

Responsible for synthesis, storage, and secretion of the 2 thyroid hormones (T3 and T4) which is controlled by thryoid stimulating hormone (TSH) which is controlled by thyrotropin-releasing hormone (TRH)

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3
Q

How are T3 and T4 Synthesized?

A

Requires Iodide, thyroglobulin, and tyrosine
1. Iodide binds with tyrosine attached to thyroglobulin = mono or di-iodotyrosine (MIT or DIT)
2. MIT + DIT = T3 or DIT + DIT = T4
3. Secretes into circulation
4. Some T4 is converted to T3 in peripheral tissue (kidney/liver)

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4
Q

What is the Physiologic Ratio of T4:T3?

A

~13:1

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5
Q

Actions of T3 and T4

A

Heart - chronotropic and ionotropic
Adipose tissue - catabolic
Muscle - catabolic
Bone - developmental
Nervous system - developmental
Gut - metabolic
Other tissues - calorigenic

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6
Q

T4 in circulation is ___% from thyroid

A

100%

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7
Q

T3 in circulation is ___% directly from thyroid

A

20%

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8
Q

Is T3 or T4 More Potent?

A

T3 is ~4x more potent than T4

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9
Q

___% of T4 is converted to inactive T3

A

45%

*The rest of T4 and T3 circulate in active free form or protein-bound inactive form

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10
Q

Thyroid Hormone Release is Regulated by a Negative Feedback Loop and Hormone Release is Promoted by…

A
  • Thyroid Stimulating Hormone (TSH) - release of TSH stimulated by Low circulating T3/T4 levels
  • Low serum iodide (short-term)
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11
Q

Thyroid Hormone Release is Regulated by a Negative Feedback Loop and Hormone Release is Inhibited by

A
  • High circulating T3/T4 levels
  • Lithium
  • Iodide excess (short-term)
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12
Q

What is Hyperthyroidism?

A

Disease caused by the excess synthesis and secretions of thyroid hormones

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13
Q

Hyperthyroidism:

Common Causes Of Hyperthyroidism

A
  1. Toxic diffuse goiter (Graves Disease)
  2. Toxic multi-nodular goiter (Plummers Disease)
  3. Acute phase of thyroiditis
  4. Toxic adenoma
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14
Q

Hyperthyroidism:

What is Toxic Diffuse Goiter (Graves Disease)?

A

Autoimmune disorder where the immune system creates antibodies against the TSH receptor
- Can result in hyperplasia of thyroid gland leading to a goiter
- Most common cause of hyperthyroidism
- Most common in younger female patients (20-50yo)

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15
Q

Hyperthyroidism:

What is Toxic Multi-Nodular Goiter (Plummers Disease)?

A

Nodules grow on the thyroid gland producing excess thyroid hormones commonly due to iodine deficiency
- Second most common cause of hyperthyroidism
- Develops slowly over several years
- Most common in older female patients (>50)

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16
Q

Hyperthyroidism:

What is Acute Phase of Thyroiditis?

A

Inflammation and damage to the thyroid gland, that causes excess hormone to be released (Trauma, Infection, Pregnancy)
- Eventually leads to hypothyroidsim once T3/T4 stores are exhausted

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17
Q

Hyperthyroidism:

What is Toxic Adenoma?

A

Benign tumours growing on the thyroid gland that become active and act just like thyroid cells, secreting T3/T4 but not responding to negative feedback

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18
Q

Hyperthyroidism:

Clinical Presentation and Non-Specific Symptoms of Hyperthyroidism

A

Most Common
- AFib
- Cardiac Murmur
- Decreased weight
- Heat intolerance
- Sweating
- Hyperactivity
- Increased Systolic BP
- Tachycardia
- Diarrhea
- Anxiety
- Hair loss
- Tremors

Less Common
- Amenorrhea
- Onycholysis
- Acropathy
- Sexual dysfunction
- Vitiligo
- Weakness

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19
Q

Hyperthyroidism:

Specific Presentation/Symptoms of Toxic Diffuse Goiter (Graves)

A
  • Exophthalmos (or proptosis) - bulging eyes
  • Peri-orbital edema - swelling around eyes
  • Diplopia - double vision
  • Diffuse Goiter
  • Pre-tibial Myxedema

*Ocular Symptoms

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20
Q

Hyperthyroidism:

Specific Presentation/Symptoms of Toxic Multi-Nodular Goiter (Plummers)

A
  • Same general hyperthyroidism symptoms
  • Individual thyroid nodules may be palpable
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21
Q

Hyperthyroidism:

Diagnosis/Lab Tests: Sub-Clinical Hyperthyroidism

A

Serum TSH: Decreased (< 0.3)
Free T3: Normal
Free T4: Normal

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22
Q

Hyperthyroidism:

Diagnosis/Lab Tests: Toxic Diffuse Goiter (Graves)

A

Serum TSH: Decreased (< 0.1)
Free T3: Increased
Free T4: Normal-Increased

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23
Q

Hyperthyroidism:

Diagnosis/Lab Tests: Toxic Multi-Nodular Goiter (Plummers)

A

Serum TSH: Decreased (< 0.1)
Free T3: Increased
Free T4: Increased

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24
Q

Hyperthyroidism:

Examples of Drug-Induced Hyperthyroidism

A

Amiodarone, Iodine (chronic us): Increases synthesis and release of T3/T4
1st Gen Antipsychotics: Increases TSH Secretion
Androgens, glucocorticoids: Decreased thyroxin binding globulin (TBG)

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25
# Hyperthyroidism: **Treatment** **Thioamides:** 2 Drugs
Methimazole (MMI) - Drug of Choice Propylthiouracil (PTU)
26
# Hyperthyroidism: **Treatment** **Thioamides:** Indications
- Toxic Diffuse Goiter - Toxic Multi-Nodular Goiter - Pre-treatment before RAI | **Not used in Treatment of Acute Thyroiditis**
27
# Hyperthyroidism: **Treatment** **Thioamides:** Goal of Therapy
Achieve remission and then consider discontinuing - There is potential for toxicity issues if used long-term so should instead pursue curative options
28
# Hyperthyroidism: **Treatment** **Thioamides:** Mechanism of Action
Interferes with thyroid peroxidase mediated processes in T3/T4 production *PTU also inhibits peripheral conversion of T4 to T3
29
# Hyperthyroidism: **Treatment** **Thioamides:** Dosing and Administration
Start with a High Initial Dose and Lower Maintenance Dose - Titrate dose if TSH and T4 does not improve in 4-6w - Decrease gradually once euthyroid - Take with or without food *MMI (OD) and PTU (BID-TID)
30
# Hyperthyroidism: **Treatment** **Thioamides:** Onset of Effect
- Symptom improvement within 1-4 weeks - Euthyroid in 2-3 months
31
# Hyperthyroidism: **Treatment** **Thioamides:** Duration of Therapy
12-18 months most common, then consider d/c if euthyroid - Test 'thyroid receptor antibodies' (TRAb) and if they are **low or negative values** then the patient is a good candidate to taper and d/c without relapse OR if they are **high values** we should continue treatment and/or prepare for RAI/Surgery as they are at risk of relapse if d/c
32
# Hyperthyroidism: **Treatment** **Thioamides:** Common Side Effects
- GI Upset - Rash - Arthralgia - Abnormal taste/smell *Dose related for MMI, but not PTU, Most side-effects will imporve over 4 weeks, higher rates with PTU
33
# Hyperthyroidism: **Treatment** **Thioamides:** Serious Side Effects
- Neutropenia/Agranulocytosis - Hepatotoxicity - Vasculitis
34
# Hyperthyroidism: **Treatment** **Thioamides:** What Should We Tell Patients About Side-Effects?
- Discuss common side-effects, management strategies, and reassure they usually improve after 1 month - Discuss risk of severe side-effect are low but watch for signs of infection (fever headache, malaise, sore throat) and for PTU watch out for liver related issues (fatigue, weakness, RUQ pain, jaundice, dark urine)
35
# Hyperthyroidism: **Treatment** **Thioamides:** Drug Interactions
- Warfarin - decrease in INR - Digoxin - Increase in digoxin levels *MMI weakly inhibits 2D6, 2C9, 2E1
36
# Hyperthyroidism: **Treatment** **Thioamides:** How Do We Monitor Effectiveness?
- Symptoms: 1-4 weeks for improvement - Assess TSH, T3, T4 at 4-6 week intervals until stable, then q2-3 months for 6-12 months, then q4-6 months ***also test 4-6 weeks after each dose change or significant changes in weight (≥4.5kg)** - Assess thyroid receptor antibodies (TRAb) q1-2 years and before discontinuing - If discontinuing, must watch for relapse TSH at 3 months --> 6 months --> 12 months --> annually *Relapse is most likely within first 3 months of d/c and if TRAb levels are high
37
# Hyperthyroidism: **Treatment** **Thioamides:** Monitoring Safety
**CBCs:** Baseline **LFTs:** Baseline and 1 week later - watch for AST/ALT >3x ULN and symptoms of hepatotoxicity
38
# Hyperthyroidism: **Treatment** **Thioamides:** Use in Pregnancy
PTU is more safe in the 1st trimester and MMI is more safe in the 2nd/3rd Trimester
39
# Hyperthyroidism: **Treatment** **Beta-Blockers:** Use in Therapy
- Most beta-blockers are effective (non-selective are preferred such as propanolol) - Can be started as soon as hyperthyroidism suspected and added to other treatment Reduce Symptoms of Hyperthyroidism: - Palpitations - Tachycardia - Tremors - Anxiety - Heat Intolerance
40
# Hyperthyroidism: **Treatment** **Radioactive Iodine:** When Can it Be Given?
Only give when: - Mild hyperthyroidism - Normal or only slightly enlarged gland - No exopthalmous
41
# Hyperthyroidism: **Treatment** **Radioactive Iodine:** Mechanism of Action
Iodine is taken up by the thyroid in its normal process, but the iodine causes tissue damage and ablation of the gland
42
# Hyperthyroidism: **Treatment** **Radioactive Iodine:** Downsides/Complications
- Permanent hypothyroidism - Can trigger thyroid storm/thyrotoxicosis - Worsen exopthalmous
43
# Hyperthyroidism: **Treatment** **Radioactive Iodine:** Contraindications
- In pregnancy/lactation - Severe hyperthyroidism/exopthalmous
44
# Hyperthyroidism: **Treatment** **Radioactive Iodine:** Adverse Effects
- Initial hyperthyroidism exacerbation likely - Followed by hypothyroidism symptoms
45
# Hyperthyroidism: **Treatment** **Radioactive Iodine:** Pre-Treatment With Thioamides
Given to achieve euthyroid status and avoid thyroiditis - It is recommended to treat all patients with thioamides first but you must pretreat elderly patients, cardiac disease or severe hyperthyroidism - Initiate 4-6 weeks before RAI - Stop one week prior to RAI - Restart three days after RAI - Taper and discontinue once thyroid hormone levels decline
46
# Hyperthyroidism: **Treatment** **Radioactive Iodine:** Patient Instructions Once RAI is Done
1. Do not kiss, exchange saliva, or share food or eating utensils for 5 days. Your dishes should be washed in a dishwasher, if one is available. 2. Avoid close contact with infants, young children (under 8 years), and pregnant women for 5 days. (You can be in the same room with them.) 3. If you have an infant, no breast-feeding is allowed. 4. Flush the toilet twice after urinating, and wash your hands thoroughly. 5. If a sore throat or neck pain develops, take acetaminophen or aspirin. 6. If you note increased nervousness, tremors, or palpitations, call a physician.
47
# Hyperthyroidism: **Treatment** **Surgery (Thyroidectomy):** When is Surgery an Option?
- Pregnant patients who cannot tolerate medications - Patients who want "curative" therapy but not RAI - Patients with large goiters (resistant to RAI)
48
# Hyperthyroidism: **Treatment** **Surgery (Thyroidectomy):** Complications
- Hypoparathyroidism - Vocal cord paralysis - Thyrotoxicosis
49
# Hyperthyroidism: **Treatment** How do we Treat Subclinical Hyperthyroidism?
TSH < 0.3, normal T3/T4, asymptomatic **If at risk for complications** - Strongly consider treatment, or check levels again in 3 months (then treat if confirmed result) **If at low risk for complications** - recheck levels in 3-6 months unless TSH < 0.1 (then consider treating)
50
# Hyperthyroidism: **Treatment** Acute Thyroiditis Management
- Self-limiting - B-Blocker for symptom control - NSAIDs for pain - Courses of steroids for severe cases
51
# Hyperthyroidism: What is Thyroid Storm/Thyrotoxicosis?
Rare, life threatening condition characterized by severe manifestations of hyperthyroidism (Liver damage, cardiovascular collapse and shock) - Can occur in patients with untreated hyperthyroidism - Often Triggered by an acute event, like Thyroid surgery, RAI, Trauma, Infection, Giving birth
52
# Hyperthyroidism: Treatment of Thyroid Storm/Thyrotoxicosis
- Supportive care (oxygen, ventilator, IV fluids) - Correct electrolyte imbalance - Treat cardiac arrythmias - Control Hyperthermia - Treat underlying conditions Administer: - Beta-Blockers to reduce symptoms - High dose anti-thyroid meds (PTU preferred) - Iodine 1 hour after anti-thyroid meds - Steroids to block conversion of T4 to T3
53
What is Hypothyroidism?
Disease caused by a defect anywhere on the HPT axis resulting in less thyroid hormone release
54
# Hypothyroidism: Common Causes of Hypothyroidism
- Chronic autoimmune thyroiditis (Hashimoto's) - Drug Induced - Iatrogenic Disease (from thyroidectomy/RAI) - Post-partum Thyroiditis - Chronic iodine deficiency - Central hypothyroidism - Hypopituitarism
55
# Hypothyroidism: What is Chronic Autoimmune Thyroiditis (Hashimoto's)?
Autoimmune disorder where antibodies form and bind to the TSH receptors which directly destroy thyroid cells or interfere with the production of T3/T4
56
# Hypothyroidism: What is Drug-Induced Hypothyroidism?
**Lithium** - Blocks iodine transport into the thyroid and prevents hormone release - Patients with a history of thyroid dysfunction are at risk, and elderly - Monitor at 3m then q6-12m if patient is on lithium **Amiodarone** - Can cause hyper (< 5%) or Hypothyroidism (5-25%) - Increased risk if history of thyroid dysfunction - Monitor q1m x3m, then q3m x6m, then q6-12m
57
# Hypothyroidism: Clinical Presentation and Non-Specific Symptoms of Hypothyroidism
Most Common - Increased Diastolic BP - Bradycardia - Slow hoarse speech - Constipation - Menorrhagia - Fatigue/lethargy - Weight gain - Dry skin/hair loss - Emotional Lability Less Common - Dyslipidemia - Cold intolerance - Eyelid edema - Goiter Advanced Disease - Hypothermia - Confusion - Stupor, coma - Peripheral neuropathy - Hypoglycemia - Hyponatremia
58
# Hypothyroidism: **Diagnosis/Lab Tests:** Sub-clinical Hypothryoidism
**Serum TSH:** Increased (4.5-10) **Free T3:** Normal **Free T4:** Normal
59
# Hypothyroidism: **Diagnosis/Lab Tests:** Hashimoto's
**Serum TSH:** Increased (>10) **Free T3:** Decreased **Free T4:** Decreased
60
# Hypothyroidism: Examples of Drug-Induced Hypothyroidism
**Amiodarone, Glucocorticoids, Metformin:** Decreases TSH **Amiodarone, BB, Glucocorticoids:** Decrease conversion of T4 to T3 **Amiodarone, lithium, iodine (acute use):** Decrease synthesis/release of T3/T4 **Carbamazepine, phenobarbital, phenytoin:** Increases T3/T4 metabolism
61
# Hypothyroidism: **Treatment** Drug Options for Replacement of Thyroid Hormone
- Desiccated thyroid - Liothyronine - Levothyroxine - Combined T3/T4
62
# Hypothyroidism: **Treatment** Desiccated Thyroid
- Prepared from thryoid glands of animals (different ratio of T4:T3 = 4:1) - Contains T3 and T4 - Not well standardized batch to batch - Worse CV outcomes long-term because of T3 overstimulation
63
# Hypothyroidism: **Treatment** Liothyronine
- Contains T3 not effect on T4 (same issues as desiccated thyroid because of high T3) - Short half life - Higher incidence of cardiac adverse effects - Try to dose close to physiologic ratio T4:T3 - May be considered in people who cannot convert T4 to T3
64
# Hypothyroidism: **Treatment** Levothyroxine
- Standard 1st therapy - Analogue of T4 - Half life of 7 days allowing for a stable response - Conversion to T3 is regulated by the body
65
# Hypothyroidism: **Treatment** **Levothyroxine:** Dosing
- Average replacement dose is 1.6mcg/kg/d - Starting dose ranges from 12.5mcg/day to max wt. based - Often give 100mcg empirically to young, healthy patients - If subclinical give 25-50mcg empirically | Higher Baseline TSH usually predicts higher T4 Dose
66
# Hypothyroidism: **Treatment** **Levothyroxine:** When Do you Consider Starting Low and Titrating up?
- Any CVD - >65 years old - Severe, longstanding hypothyroidism Start low (12.5-25mcg) and titrate up by 12.5-25mcg q4-8 weeks (usually 8 weeks)
67
# Hypothyroidism: **Treatment** **Levothyroxine:** Administration
Administer on empty stomach, 30min before meals or 1 hour after, in the morning is best
68
# Hypothyroidism: **Treatment** **Levothyroxine:** Side-Effects
Side-effects are related to over treatment only: - Hyperthyroidism symptoms - Cardiac risk Increase - Aggravate existing CVD - BMD reduction
69
# Hypothyroidism: **Treatment** **Levothyroxine:** Drug Interactions
Absorption Reduction: - Coffee/tea/meals - Antacids/PPIs/H2 blockers - Iron, calcium, mineral supplements Potent CYP inducers increase Thyroid hormone metabolism: - ciprofloxacin - Phenytoin - Carbamazepine - Rifampin - Grapefruit Decreases levels of thyroid hormone: - estrogens - Ritonavir - SSRIs Increases Risk of Arrhythmias: - TCAs - Oral semaglutide | Check labs at 4-6 weeks if on med chronically
70
# Hypothyroidism: **Treatment** **Levothyroxine:** Monitoring
**TSH** - aim for low normal value (< 2.5) and once stable monitor q6-12-24m **Free T4** - normal to slightly elevated **Free T3** - normal **Symptoms** - improvement in 2-3 weeks, maximum effect in 4-6 weeks *Test 4-6 weeks after each dose change, or significant changes to weight (≥4.5kg)
71
# Hypothyroidism: **Treatment** When Do We Treat Subclinical Hypothyroidism?
TSH 4.5-10, normal T3/T4, asymptomatic - Treat if patient develops symptoms, planning pregnancy, heart failure, or very young patients
72
# Hypothyroidism: **Treatment** If Treatment with Levothyroxine Fails, Consider...
**Decreased Bioavailability:** - Poor adherence - Malabsorption - Improper administration **Increased need:** - Recent weight gain - Pregnancy - New meds that increase metabolism of T3/T4 **Other Conditions:** - Addison's disease - Altered HPT axis - Insufficient peripheral conversion of T4-T3
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