Therapeutics II > Block 4: Thyroid Disorders > Flashcards

Block 4: Thyroid Disorders Flashcards

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1
Q

Who are more at risk for thyroid problems?

A

Women

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2
Q

Undiagnosed thyroid disease increases the risk of?

A
  1. CVD
  2. Osteoporosis
  3. Infertility
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3
Q

How is TH formed?

A

Active uptake pumps concentrate iodiDe

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4
Q

What TH has a shorter half-life and stronger affinity to receptors?

A

T3

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5
Q

TH ratio in a normal thyroid gland?

A

T4: 80%
T3: 20%

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6
Q

Difference between bound and unboud TH?

A

TH is higly bound, howeverer is not active. TH is only active in free form

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7
Q

How is TH regulated?

A
  1. Low T3 and T4 levels signal hypothalamus to release thyroid releasing hormone (TRH)
  2. TRH signals anterior pituitary to release thyroid stimulating hormone (TSH)
  3. TSH signals thyroid to release T3 and T4
  4. High levels of T3 and T4 decreases production of TRH and TSH by a negative feedback loop
  5. Disruption of any one of these regulator mechanisms can cause abnormal levels of T3 and T4 leading to thyroid disease
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8
Q

TFT values?

A
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9
Q

Whar is thyrotoxicosis?

A

Inappropriately high thyroid action when those tisses are exposed to to excessive levels of T4, T3, or both

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10
Q

Signs and sx of thyrotoxicosis?

A
  1. Fine hair
  2. Lid lag
  3. Weight loss with an increased appetite
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11
Q

What is hyperthyroidism and what are the types?

A

A form of thyrotoxicosis due to INCREASED synthesis and secretion of thyroid hormones by the thyroid and the overproduction of TH
1. Primary
2. Secondary

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12
Q

What is a common cause of hyperthyroidism?

A

Graves Dx

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13
Q

Whar are sx of Graves?

A
  1. HYPERthyroidism—results from action of thyroid-stimulating antibodies (TSAbs)
  2. Goiter
  3. Exophthalmos
  4. Pretibial myxedema
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14
Q

What is a goiter?

A

Swollen neck due to diffuse enlargement of the thyroid gland may require surgery

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15
Q

What is exophthalmos?

A

Graves’ ophthalmopathy: autoimmune related protruding eyeball

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16
Q

What is Pretibial myxedema?

A

Localized lesions and thickening of skin resulting from depositions of hyaluronic acid usually but not always on the pretibial area)

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17
Q

Tx for Graves?

A

antithyroid drugs (ATD), surgery, or radioactive iodiNe (RAI)

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18
Q

Tx for toxic multinodular goiters?

A

RAI or surgery

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19
Q

Tx of toxic agnoma?

A

RAI or surgery

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20
Q

Tx for postpartum thyroiditis?

A

Beta blockers (propranolol or metoprolol) may help with adrenergic symptoms

ATDs are NOT indicated. They do not decrease the release of preformed thyroid hormone

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21
Q

Pharm tx for hyperthyroidism?

A

Thioureas/Anti-thyroid Drugs (ATD)
1. Methimazole (Tapazole; MMI)
2. Propylthiouracil (PTU)

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22
Q

Nonpharm for hyperthyroidism?

A
  1. Surgery (Thyroidectomy)
  2. Irradiation with Radioactive iodiNe (RAI: sodium iodiNe 131I)
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23
Q

Adjunctive tx for hyperthyroidism?

A
  1. b-blockers
  2. IodiDe containing compounds
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24
Q

Initial tx for hyperthyroidism is dependent on…?

A
  1. Age
  2. Concurrent physiology
  3. Comorbidities
  4. Convenience
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25
MOA of thioamides?
1. Inhibits thyroid peroxidase enzyme (TPO) 2. PTU inhibits the peripheral conversion of T4 to T3 (MMI does NOT have this effect)
26
Place is therapy for thioamides?
1. Preferred treatment in children, adolescents, and pregnancy 2. Useful in elderly patients, patients with a limited life expectancy, and patients with poor surgical risk 3. Initial treatment in severe cases or to prepare for RAI or surgery
27
ADR of thioamides?
1. Hepatotoxicity 2. Agranulocytosis (more likely in PTU)
28
How do you monitor and maintain thioamides?
Sx diminish after 4-8 weeks and circulating TH levels return to normal: 1. Beta blockers may be used during this time to reduce adrenergic symptoms 2. After response, start tapering. Change doses monthly to allow endogenously produced T4 to reach a new steady state concentration 3. Therapy should continue for 12 to 24 months 4. If euthyroid after one year D/C ATD 5. If relapse occurs, RAI is preferred over a second course of ATD **Monitoring:** TFTs every 4 weeks
29
What are the advantages and disadvantages of using thioamides?
**Advantages:** 1. Non invasive 2. Low cost 3. Low risk of permanent hypothyroidism 4. Possible remissionbs due to immune effects **Disadvantages:** 1. Low cure rate 2. ADR 3. Drug compliance
30
MMI is a drug of choice for paitents with ATD except?
1. Pregnancy (1st trimester) and lactation 2. Thyroid storm 3. Refuse RAI/surgery after a minor reaction to MMI You would use PTU
31
When would PTU be a drug of choice?
Thyroid Storm, the 1st trimester of pregnancy and lactation
32
When should surgery be considered? When should it be avoided?
1. Large goiters 2. Severe Graves ophthalmopathy 3. Lack of remission on ATD 4. Graves 5. 2nd trimester 6. Refusal for RAI therapy 1st and 3rd trimester
33
Complications of surgery?
1. Laryngeal nerve damage 2. Hypothyroidism
34
How do you prepare for thyroidectomy?
1. MMI until euthyroid 2. Add iodides (500 mg/day) for 10 to 14 days prior to surgery to decrease vascularity of the gland and during the immediate post operative period 3. Propranolol for several weeks before surgery and 7 to 10 days after surgery
35
Tx after surgery?
1. MMI should be stopped at the time of the thyroidectomy 2. Beta blockers should be tapered off after surgery 3. L-thyroxine should be started at 1.6 mcg/kg daily 4. TSH checked 6 to 8 weeks post-op
36
What are the advantages and disadvantages of surgery?
**Advatnages:** 1. Rapid, effective treatment, especially patients with large goiters 2. Useful when coexisting ssuspicioius nodule present **Disadvantages:** 1. Most invasive 2. Least costly in long-term after quality of life adjustment 3. Permanent HYPOthyroidism 4. Pain 5. Scarring
37
Place in therapy for radioactive iodine 131?
1. Permanent tx for hyper 2. Best for toxic nodules and multinodular goiters
38
CI of RAI?
1. Graves’ ophthalmopathy (RAI may worsen) 1. Thyroid Cancer 1. Women planning pregnancy in the next 4-6 months 1. Patients who are unable to comply with radiation safety guidelines 1. Pregnancy Risk X
39
Counseling of RAI?
1. Double flush toilet 2. Wash hands often 3. No close contact with children or pregnant women for 48 -72 hours
40
How do you prepare for RAI use?
Administered as PO solution or capsule 1. Pretreat with beta blockers prior to RAI in asymptomatic patients who are elderly or with comorbidities 2. Pretreat with MMI prior to RAI in patients at risk of complications from worsening HYERthyroidism (Discontinue 2-3 days prior to RAI, Resume 3-7 days after RAI) 3. Avoid excess iodine intake/seaweed for 7 days prior to treatment
41
Why do most patient acquire hypothyroid are RAI?
destruction of the thyroid tissue within 3 months and require lifelong thyroid hormone supplementation
42
What are the advantages and disadvantages of RAI?
**Advantages:** 1. Cure of hyperthyroidism 2. Lowest cost before quality of life adjustment **Disadvantages:** 1. Permanent hypothyroidism 2. Worsen Graves opthalmopathy 3. Pregnancy deferred 6-12 months 4. No lactation 5. Small potential risk of exacerbation of HYPERthyroidism
43
Beta blockers place in therapy?
1. Control of adrenergic sx 2. Adjunctive therapy with ATDs, RAI, or iodides 3. Primary therapy for thyrotoxicosis associated with thyroiditis 4. All patients with symptoms especially elderly and patients with HR > 90 beats/minute or CV disease
44
When would beta blockers be considered a drug of choice?
1. Propranolol or non-selective is preferred 2. Caution in pts with asthma and COPD
44
Iodide Place in therapy?
1. Prevents peripheral conversion of T4 to T3 1. Short term inhibitor of thyroid hormone release 1. Temporary treatment during Thyroid Storm 1. Used 7-14 days before surgery 1. Should NOT be used before RAI; give 3 to 7 days after RAI treatment, so that the RAI can concentrate in the thyroid
45
Types of iodide containing agents?
1. Lugol’s solution: 6.3mg iodiDe per drop 2. Potassium iodiDe (SSKI): 38 mg of iodiDe per drop * 3-10 gtt QD in water or juice
46
How do you counsel for iodide containing compounds?
1. Mix with milk, juice, or water to prevent GI upset 2. Administer through a straw to prevent discoloration of teeth 3. Inform physician if rash develops 4. Monitor for signs of thyroid storm
47
ADRs of iodide containing compounds?
1. Hypersensitivity rx 2. Salivary gland swellingn 3. Iodism (poisoning) 4. Gynecomastia
48
Tx for HYPERthyroidism in Pregnancy?
PTU: 1st trimester MMI: 2nd and 3rd trimester Use the lowest possible dose to maintain T4 levels in the high normal range * PTU 300 mg tapered to 50 to 150 mg daily after 4 to 6 weeks **RAI is absolutely contraindicated** Surgery: usually NOT recommended (especially during the 1st trimester)
49
Tx in HYPERthyroidism in Neonates?
1. 7-10 days after birth 2. Placental transfer of TSAbs for hyperthyroid mother 3. Treat until the antibodies clear (8 to 12 weeks) * MMI 0.5 to 1 mg/kg/day (MMI is the recommended first line agent) * PTU 5-10 mg/kg/day * Potassium iodiDe may be used the first few days to acutely inhibit hormone release
50
Tx of hyperthyroidism in children?
1. MMI (first line) 2. RAI (avoid in very young children <5YO) 3. Surgery 4. Beta blockers for sx, HR >100bpm
51
Tx of hyperthyroidism in elderly?
1. ATD or RAI is preferred * Thyroid function is usually controlled with ATD before RAI * Beta blockers may be used to control symptoms **Surgery is rarely recommended due to risk**
52
What is thyroid storm?
Abrupt increase in severity of hyperthyroid sx (cardiac) usually due to stressors in a patient when hyperthyroidism is untreated
53
What are the steps to treat thyroid storm?
**Suppression of TH formation and secretion:** 1. Block synthesis: PTU 2. Block release: SSKI 3. Iodides should be administered AFTER the thioamide is initiated. If iodide is administered first, it could serve as substrate to produce even more thyroid hormone. **Block peripheral effects:** 1. Antiadrenergic therapy: Propranolol IV 2. Administration of corticosteroids: Dexamethasone PO/NG **Supportive therapy:** 1. Acetaminophen and cooling blankets 2. Avoid ASA and other NSAIDS 3. Fluids and electrolyte replacement 4. Plasmapheresis and peritoneal dialysis for unresponsive patients
54
What is subclinical hyperthyroidism? When is tx recommended?
TSH and free T3 and T4 should be reassessed in 2 to 4 months 1. ALL patients >65 years of age 2. Patients with: * Cardiac RF * HD * OP * Post menopausal * Hyperthyroid problems
55
Tx for subclinical hyperthyroidism?
ATDs or RAI
56
How should you monitor hyperthyroidism txs?
1. After surgery, ATD, or RAI has been initiated, patients should be evaluated on a monthly basis until they reach euthyroid condition 2. If T4 replacement is initiated, titrate to a free T4 and TSH in the normal range then follow up every 6 to 12 months
57
DDI with amiodarone?
Disrupts thyroid function: 1. Interferes with thyroid hormone synthesis 2. release and decreases thyroid hormone metabolism Obtain TSH before starting amiodarone therapy: Monitor TSH periodically
58
DDI with biotin?
Doses > 5000 mcg/day can interfere with thyroid hormone assays * Falsely Low: TSH * Falsely Elevated: TT4, FT4, and TT3 **Hold Biotin doses for 24 to 48 hours before lab testing**
59
What is hypothyroidism?
DECREASED synthesis and secretion of thyroid hormones often due to autoimmune destruction of the thyroid gland **Underproduction of TH**
60
Common causes of hypothyroidism?
Hashimotos Dx
61
What is Hashimotos? Tx?
1. Antibodies are directed against multiple thyroid sites 2. Inhibits thyroid peroxidase 3. Inhibits the effects of TSH 4. Stimulates thyroid tissue growth Levothyroxine (T4)
62
Drugs that induce primary hypothyroidism?
1. Amiodarone 2. Lithium 3. Thiocyanates 4. PTU 5. MMI
63
Causes of iatrogenic Primary HYPOthyroidism?
1. Thyroid Radiation Therapy 2. Surgical removal of the thyroid gland
64
What is postpartum thyroiditis?
Slef-limiting: hyperthyroid then mildly hypothyroid
65
What is secondary hypothyroidism?
Caused by failure of the pituitary gland -> insufficient TSH release: 1. ↓ T3 and T4 2. ↓ TSH
66
Causes of secondary hypothyroidism?
1. Pituitary tumors 2. Surgery 3. Radiation 4. Necrosis 5. Autoimmune mechansims
67
What are sx of hypothyroidism?
1. Dry skin 2. COurse hair 3. Cold intolerance 4. Weight gain 5. Constipation 6. Weakness 7. Bradycardia 8. Ptosis
68
How do you screen for hypothyroidism?
All adults at age 35 and Q5Y after
69
Brand name of levothyroxine?
Synthroid Lecothroid Levoxyl
70
Why is levothyroxine considered a drug of choice?
Replacement therapy in HYPOthyroidism: 1. chemically stable 1. relatively inexpensive 1. active when orally administered 1. free of antigenicity 1. has uniform potency
71
PK of levothyroxine?
1. Prohormone 2. Half-life of 7 days 3. Should recieve same brand of levo at each med refill
72
Effects of Levothyroxine?
1. Increase in serum T4 within 1 to 2 weeks 1. Therapeutic effects seen within 3 to 4 weeks 1. May take up to 8 weeks to normalize TSH levels
73
Maintenece Dosing of Levothyroxine?
Full replacement dose: 1.6 mcg/kg PO once daily 125 mcg/day is the average dose
74
Initial dosing of Levothyroxine?
1. <50 years of age without cardiac risk factors: Start with full replacement dose of 1.6 mcg/kg/day 2. >50 years of age without cardiac risk factors: Start with 25 to 50 mcg/day, and titrate by 25 mcg monthly PRN 3. Presence of cardiac risk factors or diseases: Start with 12.5 to 25 mcg/day, and titrate by 12.5 to 25 mcg monthly PRN 4. Duration and severity of hypothyroidism
75
Weight based dosing may ___ initial doses in obese patients?
Overestimate
76
What Levo tablet is the least allergenic? Why?
0.05 mg (50 mcg) Synthroid tablet due to lack of dyes and fewer excipients
77
Drugs that inihibit GI absorption of Levo?
1. Antacids 2. BAS 3. Iron sulfate
78
What drugs increase the metabolism of levo?
1. Rifampin 1. Carbamazepine 1. Phenytoin 1. Phenobarbital
79
What drugs displaces levo binding?
1. NSAIDS 1. Salcylcliates >2 gm/day 1. Heparin 1. Phenytoin
80
What drugs decreases conversion of T4 to T3 from Levo?
1. Beta blockers 1. Amiodirone 1. PTU 1. Steroids
81
Patient counseling of hypothyroidism?
1. Take with a sip of WATER only 2. Take on an EMPTY stomach: in the morning at least 30 to 60 minutes BEFORE breakfast OR at bedtime at least 3 hours AFTER dinner 1. 3. SEPARATE dose from any Ca, Iron, or Al containing products 1. Take AFTER bisphosphates 1. Take 1 hour BEFORE or 4 hours AFTER bile-acid binding resins 1. Should be taken in a consistent manner and at the same time of day 1. Monitor for signs of hyperthyroidism 1. Do NOT double up doses if missed previous day
82
How do you monitor hypothyroidism?
Review TSH, free T4 and symptoms 6 weeks following initiation of therapy or dosage adjustments
83
Tx for Hypothyroidism in pregnancy?
1. Increase the risk of stillbirths 2. Thyroid hormone must come from the mother for the first 2 months of gestation 3. Pregnancy increases the T4 dose requirement for 75% of women
84
Tx for Hypothyroidism in Congenital HYPOthyroidism in Children?
1. Initiate with full replacement dose (age and weight based) as soon as possible after birth to improve mental and physical development 1. Target T4 is 10 mcg/dl within 30 days of birth
85
Tx for Hypothyroidism in elderly?
Initiate with lower doses and adjust slowly to avoid cardiac and other problems associated with too much thyroid hormone
86
What is myxedema coma?
From severe/prolonged hypothyroidism that presents as worsening of HYPOthyroid symptoms, hypoxia, HYPOglycemia, and gradual progression to coma if left untreated
87
What are the triggers of myxedema coma?
1. Hypothermia 2. Surgery 3. Infections 4. MI
88
Tx for myxedema coma?
1. All medications must be given parenterally due to GI peristalsis 2. Immediate IV thyroxine (T4) loading dose followed by IV maintenance doses until able to take PO 3. IV hydrocortisone loading dose followed by IV maintenance doses until HPA suppression is ruled out
89
Supportive care for myxedema coma?
1. Vasopressors, glucose, oxygen 2. Diagnosis and treat underlying disorders
90
Tx for subclinial hypothyroidism?
levothyroxine: Dosing: 25-50 mcg/day Titrate to TSH level between 0.3 and 3.0 IU/mL
91
When do you treat subclinical hypothyroidism?
TSH > 10 µIU/mL; start therapy TSH 5-10 µIU/mL in a patient with a goiter or positive anti-thyroid antibodies; start therapy
92
How do you monitor levo replacement therpay?
Clinical symptoms TSH * Elevated TSH indicates under replacement * Suppressed TSH indicates over replacement
93
When do you follow up for levo replacement therapy?
1. Patients should be evaluated on a monthly (4 to 8 weeks) basis until they reach euthyroid condition 2. Titrate to a TSH in the normal range then follow up every 6 to 12 months
Therapeutics II
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