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PR3152 Finals > Thyroid > Flashcards

Thyroid Flashcards

1
Q

What are the physiological functions of thyroid hormones?

A

related to development, growth, metabolism

  • Body temperature
  • CNS
  • Cardiac function
  • GI functions
  • Menstrual cycles
  • Increase lipid metabolism
  • Increase uptake and utilization of glucose
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2
Q

Describe the negative feedback mechanism of thyroid levels in the body when THs are low

A
  • 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
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3
Q

Is the TSH levels high or low in:
- Primary hyperthyroidism
- Primary hypothyroidism

A
  • Hyper: low
  • Hypo: high
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4
Q

What is the ratio of T4 to T3 in the circulation?

A

4:1

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5
Q

Is T4 or T3 more potent?

A

T3

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6
Q

How is T4 converted to T3?

A

Peripheral conversion by deiodination (via deiodinases)

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7
Q

What’s the half life of T4 and T3?

A

T4: 6-7 days
T3: 2 days

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8
Q

Are T4 and T3 usually plasma protein bound?

A

> 99% bound

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9
Q

To evaluate thyroid status, which hormone levels will be generally useful?

A

Free T4 and TSH

T3 has a erratic half-life and thus is not routinely ordered

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10
Q

What can cause elevation of thyroxine binding globulin (TBG)?

A

Pregnancy or on synthetic estrogen

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11
Q

What is the consequence of elevated TBG?

A

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

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12
Q

What are some antibodies that are related to thyroid diseases?

A

ATgA: thyroglobulin antibodies
TPO: thyroperoxidase antibodies
TRAb: TSH (thyrotropin) receptor IgG antibodies

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13
Q

Routine screening of thyroid status is required for?

A

Pediatric patients and pregnant women

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14
Q

What are some compelling indications for screening of thyroid status?

A
  • 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
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15
Q

What are causes of primary hypothyroidism?

A
  • Hashimoto’s disease
  • Iatrogenic: thyroid resection or radioiodine ablative therapy
  • Iodine deficiency
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16
Q

What are causes of secondary hypothyroidism?

A
  • Central hypothyroidism (hypothalamus or pituitary malfunction)
  • Drug induced
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17
Q

How is Hashimoto’s disease diagnosed?

A

Positive ATgA and TPO antibodies
Signs of hypothyroidism (may have initial hyperthyroidism)
Increased TSH, and decreased FT4 (not in the early stage)

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18
Q

What are signs and symptoms of hypothyroidism?

A
  • Cold intolerance
  • Dry skin
  • Fatigue
  • Weight gain
  • Bradycardia
  • Slow reflexes
  • Coarse skin and hair
  • Periorbital swelling
  • More frequent and heavier menses
  • Goiter
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19
Q

What are some clinical manifestations of hypothyroidism?

A

Increased lipids –> increased risk of atherosclerosis and MI
Increased creatine phosphokinase levels
Increased miscarriage risk
Impaired fetal cognitive development

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20
Q

How do you diagnose central hypothyroidism?

A

Symptoms of hypothyroidism
Low FT4 and low TSH

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21
Q

What are pharmacotherapy options for hypothyroidism?

A
  • Levothyroxine (first line, synthetic T4)
  • Liothyronine (synthetic T3)
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22
Q

What is the initial dosing of levothyroxine in young and healthy adults?

A

1.6 mcg/kg/d (usually can start at 100 mcg/day)

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23
Q

What is the initial dosing of levothyroxine in healthy patients of 50-60 years of age?

A

50 mcg daily

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24
Q

What is the initial dosing of levothyroxine in patients with CVD?

A

12.5 to 25 mcg daily

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25
Q

How should you titrate up levothyroxine dose?

A

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

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26
Q

Counselling points for administration of levothyroxine

A
  • 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
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27
Q

What lab parameters will be useful for monitoring of central hypothyroidism?

A

FT4

TSH not useful cause it will be low

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28
Q

What is the general target for TSH in primary hypothyroidism?

A

0.4 to 4 mIU/L

Different target for pregnant women

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29
Q

How long does it take for levothyroxine to exert its effect?

A

2-3 weeks for symptomatic relief
4-8 weeks for lab parameters normalization

30
Q

How can lab parameters be used to hint non-adherence?

A

Normalization of FT4 levels with consistently high TSH levels

31
Q

What is the upper limit of normal TSH in older adults?

A

Controversial
>70 yo, TSH can still be WNL up to 6.9 mIU/L

32
Q

What are S/E or signs of over replacement of thyroid hormones?

A

Cardiac abnormalities, risk of fractures, signs of hyperthyroidism

33
Q

After a euthyroid state is achieved, how often should you monitor thyroid panel?

A

every 6 months to 1 year, TFT recommended in non-pregnant adult patients

34
Q

What is liothyronine’s starting dose in normal adults? elderly? CVD?

A

25 mcg
elderly or CVD pts 5 mcg

35
Q

Why is liothyronine not first line treatment for hypothyroidism?

A

High incidence of adverse effects, shorter half-life, expensive

36
Q

When should combination of levothyroxine and liothyronine be used?

A

In patients with normalized TSH but still has symptoms of hypothyroidism

37
Q

In which condition will liothyronine be used?

A

Myxedema coma

38
Q

What are some effects of hypothyroidism in pregnant women?

A

Miscarriage, spontaneous abortion
Congenital defects, impaired fetal cognitive development

39
Q

Why does hypothyroidism in pregnant women causes congenital defects?

A

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)

40
Q

What needs to be done for patients on thyroid replacement when they get pregnant?

A

To increase pre-pregnant dosage at about 30-50%

Due to increasing TBG as pregnancy progresses

41
Q

What is the target TSH for pregnant women?

A

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

42
Q

What is subclinical hypothyroidism?

A

Asymptomatic
Elevated TSH with normal FT4

Often result of early Hashimoto disease

43
Q

When would treatment of subclinical hypothyroidism be considered?

A

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

44
Q

What is the initial dose of levothyroxine for treatment of subclinical hypothyroidism?

A

25-75 mcg daily

45
Q

What are the causes of hyperthyroidism?

A
  • 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)
46
Q

What are the signs and symptoms of hyperthyroidism?

A
  • 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)
47
Q

How does radioactive iodine uptake test help to differentiate the etiology of hyperthyroidism?

A

Elevated uptake –> gland is actively secreting TH ie. Graves disease, adenoma, multinodular goiter

Suppressed uptake –> thyroiditis or cancer

48
Q

What are the tests that are useful to diagnose hyperthyroidism?

A
  • FT4 (elevated)
  • TSH (suppressed)
  • Presence of TRAb, ATgA, TPO
  • Biopsy
  • RAIU test
49
Q

What are the treatment options for hyperthyroidism?

A
  • Surgical resection
  • Thyroidectomy
  • RAI ablative therapy
  • Pharmacotherapy (thionamides, iodides, NSBB)
50
Q

What is the first line option of treatment in Graves disease? Are there any contraindications for that option?

A

RAI ablative therapy (destroys overactive thyroid cells)

Contraindicated in pregnant women

51
Q

When is pharmacotherapy for hyperthyroidism considered?

A
  • 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
52
Q

What are drug examples of thionamides? What is their MOA?

A

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

53
Q

What are adverse effects of thionamides?

A
  • Hepatotoxicity (boxed warning for PTU)
  • Rash, risk for SJS
  • Agranulocytosis (usually within 3 months of therapy)
  • Drug fever
54
Q

What is the initial dose of carbimazole? And subsequent dose when euthyroid?

A

15-60 mg daily in 2-3 divided doses
5-15 mg once daily when euthyroid

55
Q

What is the initial dose of PTU? And subsequent dose when euthyroid?

A

50-150 mg TDS
50mg BD-TDS when euthyroid

56
Q

When does thionamides start to reduce symptoms of hyperthyroidism? When is the maximal effect of thionamides seen?

A

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

57
Q

Do you need to take thionamides for life-long?

A

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?

58
Q

What are the lab parameters used for monitoring efficacy of thionamides?

A

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

59
Q

What are the 2 main symptoms of hyperthyroidism in pregnant women?

A
  • Failure to gain weight despite good appetite
  • Tachycardia
60
Q

What is the treatment of choice for hyperthyroidism in pregnant women?

A

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

61
Q

How does NSBB help with hyperthyroidism?

A
  • Blocks hyperthyroidism manifestations mediated by beta adrenergic receptors (symptomatic relief)
  • Block peripheral T4 to T3 conversion when used at high dose
62
Q

When is NSBB indicated?

A

Treatment of thyroiditis
Symptomatic relief
Bridging therapy for thionamide effects to kick in
PRN for high risk pts eg. elderly with CVD

63
Q

What is Lugol’s solution? What is its MOA?

A

Saturated solution of potassium iodide

MOA: Inhibits the release of stored THs, decrease vascularity and size of thyroid gland

64
Q

When is Lugol’s solution indicated?

A
  • 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
65
Q

What is the longest duration you can use Lugol’s iodine for?

A

14 days
TH release will resume afterwards

66
Q

When is use of Lugol’s iodine contraindicated?

A

BEFORE ablative therapy

It can reduce uptake of radioactive iodine, rendering the procedure ineffective

67
Q

Subclinical hyperthyroidism definition

A

Asymptomatic
Low or undetectable TSH, normal FT4

68
Q

What are the risks of subclinical hyperthyroidism?

A
  • Elevated risk of AF in patients older than 60
  • Elevated risk of bone fracture in postmenopausal women
69
Q

When and how should subclinical hyperthyroidism be treated?

A

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

70
Q

What drugs can cause thyroid disease?

A

Amiodarone: hypo or hyper
Lithium: hypo or hyper
Interferon alfa: hyper then hypo

All 3 drugs can cause thyroiditis

PR3152 Finals (4 decks)

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