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Pharm- DM and Thyroid > Thyroid Disorders > Flashcards

Thyroid Disorders Flashcards

1
Q

Function of the Thyroid

A

-Iodine uptake
-Thyroglobulin production
- Hormone secretion
T3 (triiodothyronine) T4 (thyroxine)
- Metabolism
- Temperature homeostasis
- Heart rate
- Body Tissue
Growth
Development
Function
Maintenance

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2
Q

Thyroid Physiology

A
  1. Iodide transported into thyroid cell
  2. Thyroid peroxidase oxidizes iodide
  3. Binds to iodinated tyrosine residue on thyroglobulin
  4. Combine to form iodothyronines
    Thyroxine (T4) (80%) Triiodothyronine (T3) (20%) Triiodothyronine (IT3) (inactive)
  5. T4 further breakdown to produce majority of T3
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3
Q

T3 and T4 Thyroid Hormones

A
  • T3 and T 4 are secreted to the thyroid cell cytoplasm via exocytosis and then cross the capillary membranes into the blood stream
  • 99.8% (T3) and 99.98% (T4) plasma protein bound
    Albumin
    Thyroxine-binding globulin (TBG)
    Tranthyretin
  • Only free hormone is physiologically active
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4
Q

Thyroid Function Tests

A 
Free T4- 0.8- 2.7
Free T3- 230- 420
Total T4- 4.8- 10.4
Total T3- 60- 181
TSH- 0.4- 4
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5
Q

Hyperthyroidism Disorders

A

Graves’ Disease
Multi-nodular Toxic Goiter (Plummer’s Disease)
Thyrotoxicosis

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6
Q

Hypothyroidism Disorders

A 
Primary
     Hashimoto’s thyroiditis
      Iatrogenic
Secondary 
    Pituitary disease
    Hypothalamic disease
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7
Q

Drugs Affecting Serum TGB

A 
↑ Serum thyroxine binding globulin (TGB)
Estrogen
Tamoxifen
Heroin
Methadone
Mitotane
Fluorouracil 
↓ Serum thyroxine binding globulin(TBG)
Androgens
Anabolic steroids
Slow release nicotinic acid
Glucocorticoids
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8
Q

Drugs that Decrease TSH secretion

A

Dopamine
Glucocorticoids
Octreotide

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9
Q

Drugs that decrease Thyroid Secretion

A

Lithium
Iodide and iodine preparations
Radiocontrast dyes
Amiodarone - Can ↑↓ Thyroid hormone secretion

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10
Q

Epidemiology of Hyperthyroidism

A 
Peak incidence between 40-60 years old
More common in women 
     1:5 -1:10 (Male:Female) 
Prevalence: 0.5%  in United States
     60-80% is Graves’ Disease
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11
Q

Graves Disease

A

Stimulating TSH receptor antibody (TSH-R stim) causes excessive TSH production

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12
Q

Multinodular Goiter

A

Becomes thyrotoxic without ab due to exogenous iodine administration
Nodule become autonomous
Tumors or adenomas

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13
Q

Causes of Goiter

A

due to organic (KI) or inorganic (amiodarone) sources

- thyroid nodule goes rogue from TSH regulation and synthesizes excess T4

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14
Q

Signs/Symptoms of Hyperthyroidism

A 
Nervousness 
Palpitations/↑HR
Irritability 
Fatigue 
Menstrual disturbances
Heat intolerance 
Weight loss with increase in appetite 
Flushed moist skin
Exophthalmos/ Proptosis (Graves’ disease)
Thinning hair
Enlarged thyroid
Brittle nails
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15
Q

Diagnostic Criteria for Hyperthyroidism

A

Low TSH
Elevated free and total T3 and T4
Increased radioactive iodine uptake

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16
Q

Treatments for Hyperthyroidism

A 
Anti-thyroid medications
Radioactive Iodine (RAI)
Thyroidectomy
Symptomatic treatment
Beta- blockers
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17
Q

Anti-Thyroid Medications

A

Preferred: methimazole, propylthiouracil (PTU)
Methimazole: first line
PTU: thyroid storm or 1st trimester
Less common: iodine, lithium

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18
Q

Thioamides Predictor of successful therapy

A

High likelihood of achieving remission
Elderly with low life expectancy and high surgical risk
Nursing home or long term care resident or unable to follow radiation safety guidelines
Lack of access to experience surgeon
h/o neck surgery/radiation
h/o Graves’ opthalompathy

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19
Q

Predictors of Remission (means you would choose thioamides)

A

Small goiter
Mild disease
Low or negative thyroreceptor antibody titer

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20
Q

Thioamides MOA

A

Inhibits thyroid hormone synthesis

PTU only: inhibits peripheral T4 to T3 conversion within in hours of dosing

In vivo effect: depletion of stored hormone and prevention of new hormone synthesis

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21
Q

Thioamides Pregnancy and Lactation

A 
Crosses placenta
Increased TSH and Decreased T4 in fetus 
          PTU preferred
Compatible with breastfeeding 
          Methimazole preferred
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22
Q

Methimazole Dosing

A 
Initial 
      Continue x 4-8 weeks then taper 
      Mild: 15 mg/day
      Moderate: 30-40 mg/day
      Severe: 60 mg/day 
Maintenance
       5-30 mg/ day in 1-3 divided doses Initial 
       1-3 divided doses
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23
Q

Propylthiouracil (PTU) Dosing

A 
Initial
     1-3 divided doses
     300-450 mg/day 
Maintenance
      100-150 mg/day 
Thyrotoxic crisis
      200 mg Q4-6 hours on Day 1
      Taper to maintenance once symptoms disappear
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24
Q

Pharmacokinetics and Dynamics of Thioamides

A 
Absorption
       Well absorbed from GI tract 
       Peak: 1 hour 
Distribution
       Concentrates in thyroid
        Protein binding: 80% (PTU)
Metabolism
       Liver
Elimination 
      Renal, mostly as metabolites
      Half life: 5-13 hours (methimazole), 1-2 hours (PTU)
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25
Q

Attaining Remission

A

Continue x 12-18 months
Then taper or d/c if euthyroid at that time
20-30% of patient achieve remission after initial therapy
Remission: normal TSH, FT4, and T3 one year after d/c of antithyroid medication
Follow-up
Re-test every 1-3 months for 6-12 months after initial remission and d/c of methimazole
Failure to maintain remission
Radioactive iodine or thyroidectomy

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26
Q

Minor Adverse Effects of Thioamides

A

GI upset
Arthralgia
Rash, urticaria, pruritis
5-6% of patients
Severe reactions: treat with 1 mg/kg/day prednisone and d/c therapy
Mild: symptoms likely to resolve on own

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27
Q

Agranulocytosis

A 
Severe Adverse Effect of Thioamides
More likely in
First 2 months 
Higher doses 
Age >40 yo
0.2-0.5% incidence
Granulocyte count <250/mm3
Fever, sore throat, bleeding , bruising, malaise, stomatitis
Stop drug, administer broad spectrum antibiotics
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28
Q

Hepatotoxicity

A 
Higher risk with PTU
FDA safety alert 
Treatment
d/c therapy
Gradually resolves on own
Long term therapy: monitor LFTs
29
Q

Monitoring for Thioamides

A

Free T4 levels
4 months after starting therapy
Every 4-8 weeks until normalized, then every 2-3 months
WBC
Onset of febrile illness or pharyngitis
LFTs
Patients on PTU with signs of liver damage: jaundice, joint pain, abdominal pain, light stool, dark urine, GI upset or fatigue

30
Q

Iodides MOA

A 
Inhibits thyroid hormone release
Decrease thyroid hormone synthesis
Decrease thyroid gland vascularity
Initial effect within 24 hours, max in 10-15 days of continuing therapy 
Improvement in symptoms in 2-7 days
31
Q

Iodide Use in Thyroid Disease

A

Reduce vascularity prior to thyroid surgery
Prepare patients with Graves Disease for surgery
Decrease thyroid iodine accumulation in thyrotoxic crisis
Prevent thyroid uptake of radioactive iodine

32
Q

Iodide Products

A

Saturated solution (SSKI)
50mg of iodide per drop
Lugol’s solution
8 mg of iodide per drop

33
Q

Initial dose of Iodides

A

50-500 mg orally in water or juice
To prepare for surgery: administer 10-14 days preoperatively
As adjunct to RAI, use 3 to 7 days after RAI treatment
Radioactive iodine will concentrate in the thyroid

34
Q

Adverse Effects of Iodide

A 
Rash
GI upset
Paresthesia
Immune hypersensitivity reactions
Salivary gland swelling
Iodism
     Burning in mouth or throat 
     Metallic taste
     Sore teeth and gums
     Cold symptoms
35
Q

Lithium

A

Not recommended in ATA/AACE guidelines

Adverse effects
Tremor, polyuria, renal failure, seizure, arrhythmia, bradycardia, suicide, toxicity

36
Q

Beta Blocker Use

A
  1. Symptomatic treatment of palpitations, tachycardia, tremor, heat intolerance
  2. Thyrotoxicosis
  3. Recommended for symptomatic elderly, postpartum women, children, any patient with resting HR> 90 or CVD
  4. Preoperatively adjunct to potassium iodide, radioactive iodine or antithyroid drugs for Graves’ disease or toxic nodules
  5. Thyroid storm
  6. Monotherapy for thyroiditis
37
Q

Beta Blocker MOA

A

Blocks beta adrenergic receptors to mitigate adrenergic symptoms of thyrotoxicosis
Propranolol and nadolol may decrease conversion of T4 to T3

38
Q

Beta Blocker Dosing

A 
Propranolol 10-40 mg po 3-4x daily
Nadolol 40-60 mg po 1x daily 
Atenolol 25-100 mg po 1-2x daily 
Metoprolol tartrate 25-50mg po 4x daily 
Esmolol 50-100 mcg/kg/min IV in ICU for thyroid storm
39
Q

Radioactive Iodine MOA

A

Sodium iodide 131 aka 131I
Oral solution

MOA
Disrupts hormone synthesis by incorporating into thyroid hormone and thyroglobulin
Over a period of weeks, follicles develop evidence of necrosis, breakdown, destruction of small vessels within gland
Half life- 5 days

40
Q

RAI Contraindicated

A

Contraindicated
Pregnancy: test 48 hours prior to procedure
Lactation
Thyroid cancer

41
Q

RAI indications and Benefits

A

Ablation for Graves disease
Women planning pregnancy greater than 4-6 months in the future
Patients with increased surgical risk or prior neck surgery
Contraindication to antithyroid medication
Benefits:
Well tolerated
Low risk of thyroid storm

42
Q

RAI Monitor

A

T3 and T4 1-2 months after treatment
Hypothyroidism occurs 4 weeks after treatment
Retreat x 1 if minimal response after 3 months or persistent hyperthyroidism after 6 months
T4 replacement
50% of patients require in 10 years

43
Q

RAI Adverse Effects

A

Dysphagia

Thyroid tenderness

44
Q

Thyroid Storm Causes

A

Stress from surgery, anesthesia, thyroid manipulation in patients with undiagnosed or uncontrolled thyrotoxicosis
Abrupt d/c of antithyroid medication

45
Q

What is a Thyroid Storm

A

Thyrotoxic crisis
Life threatening
20-30% mortality

46
Q

Symptoms of Thyroid Storm

A 
High fever (often   
     >103*F)
Tachycardia 
Atrial fibrillation
Congestive heart failure
Tachypnea 
Dehydration 
Delirium 
Coma 
Nausea/vomiting/ diarrhea
47
Q

Treatment of Thyroid Storm

A 
Aggressive treatment recommended
Identify and treat cause
Antithyroid medications
         Give BEFORE iodide
Inorganic iodide 
Supportive care
         Fluids, cooling blankets, acetaminophen 
Beta blockade
Corticosteroid therapy
48
Q

4 main Drugs used to Treat Thyroid Storm

A

*Hydrocortisone - 300 mg loading dose IV Then 100 mg Q8hours

PTU- 500-1000 mg loading dose Then 250 mg Q4 hours

SSKI- 5 drops (0.25 mL or 250 mg) Q6hours

Methimazole- 60-80 mg/day Beta blocker

BETA BLOCKERS 
Propranolol 60-80 mg po Q4 hours
         Blocks T4 to T3 conversion 
Esmolol infusion 
         In heart failure or when po not plausible 
CORTICOSTEROIDS
        Dexamethasone is an alternative 
         Blood pressure stabilization
49
Q

Subclinical Hyperthyroidism

A 
Diagnosis
      Low TSH 
      Thyroid hormone level within normal limits
Clinical Concern
      Atrial fibrillation  (especially in elderly) 
Cause
       Amiodarone induced
Treatment
       Initiate with TSH < 0.1mIU/L
50
Q

Primary Types of Hypothyroidism

A 
MC= Hashimoto’s thyroiditis
        Autoimmune disease
         Genetic predisposition 
Iatrogenic 
     Drugs
     Radiation
      Surgery 
Other: endemic iodine deficiency, congenital
51
Q

Secondary Types of Hypothyroidism

A

Pituitary disease

Hypothalamic disease

52
Q

Drug Induced Hypothyroidism

A 
Amiodarone
Sunitinib
Lithium
Interferon
Thalidomide
Bexarotene
Ethionamide 
Rifampicin
Anti thyroid medications : PTU, methimazole
53
Q

Complications of Hypothyroidism

A

Subclinical hypothyroidism
TSH above normal levels, thyroid hormone within normal limits
Treat with TSH > 10 mIU/L
Myxedema
Associated with coronary artery disease
Treat with caution to avoid precipitating a cardiac event
Myxedema coma
End result of untreated hypothyroidism
Medical emergency
Requires ICU, intubation, IV levothyroxine loading dose

54
Q

Symptoms of Hypothyroidism

A 
Dry skin
Cold intolerance
Weight gain
Constipation 
Weakness 
Lethargy 
Depression 
Fatigue/loss of ambition & energy
55
Q

Signs of Hypothyroidism

A 
Coarse skin and hair
Cold or dry skin
Periorbital puffiness
Bradycardia
Slow, hoarse speech
56
Q

Lab Findings for Hypothyroidism

A

↑ TSH, ↓ Free thyroxine (FT4)

57
Q

Lab Findings for Hashimotos Thyroiditis

A

+ Antithyroglobulin antibody (ATgA)
+ Thyroid peroxidase antibody (TPOS ab) [aka antimicrosomal antibody (AMA)]
+ blocking TSH receptor antibody (TSH-R block)
↑ Cholesterol, LDH, AST, ALT, CPK

58
Q

Thyroid Supplementation Options

A 
Natural 
      Desiccated thyroid and thyroglobulin
Synthetic 
     Levothyroxine
     Liothyronine 
     Liotrix
59
Q

Treatment Guideline for Hypothyroidism

A

ATA/ AACE Guidelines
Initiate treatment
TSH > 10 mIU/L
TSH= 4.5-10 mIU/L- No Consensus
Synthetic L-thyroxine is recommended first line
Consistent use of one formulation/manufacturer
If changed, test TSH in 4-6 weeks
Less data to support desiccated thyroid

60
Q

Natural Thyroid Hormone

A

Desiccated thyroid

Compounded from hog, beef or sheep thyroid gland

61
Q

Levothyroxine

A

First line, synthetic
L-thyroxine (T4)
Brand and branded generic available
Synthroid, Levoxyl

62
Q

Pharmacokinetics of Levothyroxine

A 
Absorption
       40-80% bioavailable
        Increases with fasting
        Decreases with fiber
Distribution
          99% protein bound
           TBG
            Thyroxine binding prealbumin (TBPA)
Metabolism 
       80% hepatic: Active metabolite
      Renal: Deiodination 
        Enterohepatic recirculation 
        Excretion
Renal (80%)
      Fecal (20%) 
      Half life: 6-7 days
63
Q

Levothyroxine Administration

A

Oral
30 minutes prior to breakfast
4 hours after last meal at bedtime
Intravenous
recommend 50% of oral dose
Feeding tube
Crush tablet and create suspension with water
Wait at least 1 hour to restart feeding
Administer as long as possible after stopping feeding

64
Q

Liothyronine (T3)

A

Chemically pure with known potency
Synthetic T3
Half life: 1.5 days
Disadvantages
Higher incidence of cardiac effects
Higher cost
Difficult to monitor with conventional lab tests

65
Q

Liotrix

A 
Synthetic T4:T3
         Ratio is 4:1
Attempt to mimic natural hormone secretion
Chemically stable and pure
Predictable potency 
Disadvantages
       High cost
       Lack of therapeutic rationale
66
Q

Dosing Recommendations (Synthetic Formulation)

A

Dependent on age, sex, weight
Ideal body weight is recommended
Initial dosing
1.6-1.7 mcg/kg/day (full replacement dose)
Requirement may be lower in patients with residual thyroid function
Elderly or CAD: 25-50 mcg/day
Consider lower doses: long standing disease, severe disease, iron deficiency anemia
Adjust every 4-8 weeks based on TSH
12.5-25 mcg/day increments

67
Q

Pregnancy Considerations

A

Euthyroid essential for normal neurocognitive development in fetus
Women being treated for hypothyroidism
↑ rate of metabolism for thyroid hormone/ transplacental transport
Dose of levothyroxine should be increased by 30%
Thyroid function tests should be tested every 2-3 weeks
TSH goal depends on trimester: 2.5 mIU/L, 3 mIU/L and 3.5 mIU/L (1st, 2nd, 3rd trimester respectively)

68
Q

Adverse Effects for Synthetic Formulations

A 
Allergic ReactionsArrhythmia
Acute myocardial infarction
Infertility 
Weight loss
Heat intolerance
69
Q

Monitoring for Synthetic Formulation

A

TSH and T4 should be measured every 4-8 weeks until euthyroid
Normal TSH: 0.4-4mIU/L
Normal FT4: 0.8-1.5ng/dL
Once normalized, should measure TSH and free T4 once every 6-12 months

Pharm- DM and Thyroid (4 decks)

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