Thyroid Disorders Flashcards
Function of the Thyroid
-Iodine uptake
-Thyroglobulin production
- Hormone secretion
T3 (triiodothyronine) T4 (thyroxine)
- Metabolism
- Temperature homeostasis
- Heart rate
- Body Tissue
Growth
Development
Function
Maintenance
Thyroid Physiology
- Iodide transported into thyroid cell
- Thyroid peroxidase oxidizes iodide
- Binds to iodinated tyrosine residue on thyroglobulin
- Combine to form iodothyronines
Thyroxine (T4) (80%) Triiodothyronine (T3) (20%) Triiodothyronine (IT3) (inactive) - T4 further breakdown to produce majority of T3
T3 and T4 Thyroid Hormones
- 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
Thyroid Function Tests
Free T4- 0.8- 2.7 Free T3- 230- 420 Total T4- 4.8- 10.4 Total T3- 60- 181 TSH- 0.4- 4
Hyperthyroidism Disorders
Graves’ Disease
Multi-nodular Toxic Goiter (Plummer’s Disease)
Thyrotoxicosis
Hypothyroidism Disorders
Primary
Hashimoto’s thyroiditis
Iatrogenic
Secondary
Pituitary disease
Hypothalamic diseaseDrugs Affecting Serum TGB
↑ Serum thyroxine binding globulin (TGB) Estrogen Tamoxifen Heroin Methadone Mitotane Fluorouracil
↓ Serum thyroxine binding globulin(TBG) Androgens Anabolic steroids Slow release nicotinic acid Glucocorticoids
Drugs that Decrease TSH secretion
Dopamine
Glucocorticoids
Octreotide
Drugs that decrease Thyroid Secretion
Lithium
Iodide and iodine preparations
Radiocontrast dyes
Amiodarone - Can ↑↓ Thyroid hormone secretion
Epidemiology of Hyperthyroidism
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’ DiseaseGraves Disease
Stimulating TSH receptor antibody (TSH-R stim) causes excessive TSH production
Multinodular Goiter
Becomes thyrotoxic without ab due to exogenous iodine administration
Nodule become autonomous
Tumors or adenomas
Causes of Goiter
due to organic (KI) or inorganic (amiodarone) sources
- thyroid nodule goes rogue from TSH regulation and synthesizes excess T4
Signs/Symptoms of Hyperthyroidism
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
Diagnostic Criteria for Hyperthyroidism
Low TSH
Elevated free and total T3 and T4
Increased radioactive iodine uptake
Treatments for Hyperthyroidism
Anti-thyroid medications Radioactive Iodine (RAI) Thyroidectomy Symptomatic treatment Beta- blockers
Anti-Thyroid Medications
Preferred: methimazole, propylthiouracil (PTU)
Methimazole: first line
PTU: thyroid storm or 1st trimester
Less common: iodine, lithium
Thioamides Predictor of successful therapy
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
Predictors of Remission (means you would choose thioamides)
Small goiter
Mild disease
Low or negative thyroreceptor antibody titer
Thioamides MOA
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
Thioamides Pregnancy and Lactation
Crosses placenta
Increased TSH and Decreased T4 in fetus
PTU preferred
Compatible with breastfeeding
Methimazole preferredMethimazole Dosing
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 dosesPropylthiouracil (PTU) Dosing
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 disappearPharmacokinetics and Dynamics of Thioamides
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)Attaining Remission
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
Minor Adverse Effects of Thioamides
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
Agranulocytosis
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
Hepatotoxicity
Higher risk with PTU FDA safety alert Treatment d/c therapy Gradually resolves on own Long term therapy: monitor LFTs
Monitoring for Thioamides
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
Iodides MOA
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
Iodide Use in Thyroid Disease
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
Iodide Products
Saturated solution (SSKI)
50mg of iodide per drop
Lugol’s solution
8 mg of iodide per drop
Initial dose of Iodides
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
Adverse Effects of Iodide
Rash
GI upset
Paresthesia
Immune hypersensitivity reactions
Salivary gland swelling
Iodism
Burning in mouth or throat
Metallic taste
Sore teeth and gums
Cold symptomsLithium
Not recommended in ATA/AACE guidelines
Adverse effects
Tremor, polyuria, renal failure, seizure, arrhythmia, bradycardia, suicide, toxicity
Beta Blocker Use
- Symptomatic treatment of palpitations, tachycardia, tremor, heat intolerance
- Thyrotoxicosis
- Recommended for symptomatic elderly, postpartum women, children, any patient with resting HR> 90 or CVD
- Preoperatively adjunct to potassium iodide, radioactive iodine or antithyroid drugs for Graves’ disease or toxic nodules
- Thyroid storm
- Monotherapy for thyroiditis
Beta Blocker MOA
Blocks beta adrenergic receptors to mitigate adrenergic symptoms of thyrotoxicosis
Propranolol and nadolol may decrease conversion of T4 to T3
Beta Blocker Dosing
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
Radioactive Iodine MOA
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
RAI Contraindicated
Contraindicated
Pregnancy: test 48 hours prior to procedure
Lactation
Thyroid cancer
RAI indications and Benefits
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
RAI Monitor
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
RAI Adverse Effects
Dysphagia
Thyroid tenderness
Thyroid Storm Causes
Stress from surgery, anesthesia, thyroid manipulation in patients with undiagnosed or uncontrolled thyrotoxicosis
Abrupt d/c of antithyroid medication
What is a Thyroid Storm
Thyrotoxic crisis
Life threatening
20-30% mortality
Symptoms of Thyroid Storm
High fever (often
>103*F)
Tachycardia
Atrial fibrillation
Congestive heart failure
Tachypnea
Dehydration
Delirium
Coma
Nausea/vomiting/ diarrheaTreatment of Thyroid Storm
Aggressive treatment recommended
Identify and treat cause
Antithyroid medications
Give BEFORE iodide
Inorganic iodide
Supportive care
Fluids, cooling blankets, acetaminophen
Beta blockade
Corticosteroid therapy4 main Drugs used to Treat Thyroid Storm
*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
Subclinical Hyperthyroidism
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/LPrimary Types of Hypothyroidism
MC= Hashimoto’s thyroiditis
Autoimmune disease
Genetic predisposition
Iatrogenic
Drugs
Radiation
Surgery
Other: endemic iodine deficiency, congenitalSecondary Types of Hypothyroidism
Pituitary disease
Hypothalamic disease
Drug Induced Hypothyroidism
Amiodarone Sunitinib Lithium Interferon Thalidomide Bexarotene Ethionamide Rifampicin Anti thyroid medications : PTU, methimazole
Complications of Hypothyroidism
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
Symptoms of Hypothyroidism
Dry skin Cold intolerance Weight gain Constipation Weakness Lethargy Depression Fatigue/loss of ambition & energy
Signs of Hypothyroidism
Coarse skin and hair Cold or dry skin Periorbital puffiness Bradycardia Slow, hoarse speech
Lab Findings for Hypothyroidism
↑ TSH, ↓ Free thyroxine (FT4)
Lab Findings for Hashimotos Thyroiditis
+ Antithyroglobulin antibody (ATgA)
+ Thyroid peroxidase antibody (TPOS ab) [aka antimicrosomal antibody (AMA)]
+ blocking TSH receptor antibody (TSH-R block)
↑ Cholesterol, LDH, AST, ALT, CPK
Thyroid Supplementation Options
Natural
Desiccated thyroid and thyroglobulin
Synthetic
Levothyroxine
Liothyronine
LiotrixTreatment Guideline for Hypothyroidism
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
Natural Thyroid Hormone
Desiccated thyroid
Compounded from hog, beef or sheep thyroid gland
Levothyroxine
First line, synthetic
L-thyroxine (T4)
Brand and branded generic available
Synthroid, Levoxyl
Pharmacokinetics of Levothyroxine
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 daysLevothyroxine Administration
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
Liothyronine (T3)
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
Liotrix
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 rationaleDosing Recommendations (Synthetic Formulation)
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
Pregnancy Considerations
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)
Adverse Effects for Synthetic Formulations
Allergic ReactionsArrhythmia Acute myocardial infarction Infertility Weight loss Heat intolerance
Monitoring for Synthetic Formulation
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
