5 - Thyroid

Question 1

Causes of primary hypothyroidism

Answer 1

• Autoimmune thyroiditis (Hashimoto’s)
• Congenital
• Iodine deficiency
• Infiltrative disease (viral, bacterial)
• Drugs (lithium, amiodarone, interferons, tyrosine kinase inhibitors)

Question 2

Describe hormone trends

Answer 2

• Primary hyperthyroidism = high T3 and T4, low TSH; primary = target organ (thyroid gland) is damaged
• Primary hypothyroidism = low T3 and T4, high TSH
• Secondary hyperthyroidism = high T3, T4, and TSH (dysfunction is at pituitary gland)
• Secondary hypothyroidism = low T3, T4, and TSH

Question 3

Describe the function of thyroid hormones

Answer 3

• Affect the function of virtually every organ system
• Important for normal growth & dev’t in children
• Maintain metabolic stability in adults

Question 4

Clinical manifestation (signs and sx) of thyroid disorders

Answer 4

• Hypothyroidism = weakness, fatigue, poor concentration/ memory, bradycardia, constipation, weight gain w/ poor appetite
• Hyperthyroidism = hyperactivity, irritability, dysphoria, tremor, tachycardia, diarrhea, goiter (enlarged thyroid gland -> swelling of neck)

Question 5

Describe the role of TSH, T4, and T3

Answer 5

• TSH releases T4 & T3 (T4»_space;> T3)
• Majority protein bound = inactive
• Biologically most active = free T3
• T4 converted to T3 in periphery by 5’-deiodinase

Question 6

Why isn’t T3 used as a drug? (levothyroxine = T4)

Answer 6

T4 is converted to T3 & we don’t want to lose the body’s ability to perform this conversion & T4 has longer t1/2 (almost like a pro-drug)

Question 7

How do autoimmune thyroid diseases occur? What is the tx?

Answer 7

• Infiltration of thyroid w/ sensitized T lymphocytes (WBC)
• Acute inflammation of thyroid -> damage to gland -> release of T3 & T4
• Initially pt is hyperthyroid (high T3 & T4) but may become hypothyroid (in weeks to months)
• Chronic autoimmune thyroiditis (Hashimoto’s thyroiditis)
• Most common initial presentation = enlargement of thyroid gland (goiter)
• Tx = exogenous T4

Question 8

Describe a goiter

Answer 8

• Generalized (diffuse) enlargement
• Caused by continuous stimulation by TSH
• Hashimoto’s – goiter eventually disappears due to progressive destruction of thyroid

Question 9

Describe thyroid nodules

Answer 9

• Enlargement in 1 part of the gland (asymmetrical)
• Caused by benign/ malignant nodule
• Rarely associated w/ destruction of gland & hypothyroidism

Question 10

Describe Graves’ disease

Answer 10

• Common cause of primary hyperthyroidism in adults & children
• Autoimmune, familial disposition
• Thyroid stimulating antibodies (TSAb) or thyroid stimulating immunoglobulins (TSI) mimic TSH -> autoimmune stimulation
• Continuous stimulation => high T3/T4; increase thyroid size
• Specific to Graves’ disease = opthalmopathy (pathogenesis unclear) & dermopathy (deposition of mucopolysaccharide; shin most common)

Question 11

How are thyroid disorders classified?

Answer 11

• Hypothyroidism diagnosed when TSH is high & FT4 is less than population reference range
• Subclinical hypothyroidism
• • Mild to moderate increased TSH, but total & FT4 normal
• • If TSH very high (> 10) tx may be offered as these px may be at higher risk of CV complications
• TSH is the most reliable therapeutic endpoint for tx of hypothyroidism b/c most sensitive marker for monitoring

Question 12

Lab monitoring for L-thyroxine tx

Answer 12

• FT4 is measured instead of FT3 b/c FT3 can be affected by other sources, so FT4 is more reliable
• After initiating or changing dose, re-measure FT4 & TSH 1 month later; want to measure levels in the morning

Question 13

Factors that alter thyroxine & triiodothyronine binding in serum

Answer 13

• Increased TBG (T4-binding globulin) – estrogens, methadone, perphenazine, SERMs
• Decreased TBG – androgens, anabolic steroids, glucocorticoids
• Binding inhibitors – salicylates, furosemide, phenytoin, carbamazepine, NSAIDs, heparin

Question 14

Consequences of untreated hypothyroidism

Answer 14

• Increased CV mortality
• Impaired intellectual function, depression, slowed speech, memory loss in elderly
• Anovulation, impaired fertility, increased rate of spontaneous abortion
• Myxedema coma (hypothermia, hypotension, hypoventilation, hyponatremia, bradycardia) – medical emergency

Question 15

Dosing levothyroxine

Answer 15

• Healthy, young adults (< 50 y/o), children, older adults recently diagnosed w/ hypothyroidism, older adults recently treated for hyperthyroidism – initial 100-150 mcg/day titrated by 25 mcg q4-6weeks
• Adults > 50 y/o w/o cardiac disease, adults < 50 y/o w/ cardiac disease – 25-50 mcg/day titrated by 12.5-25 mcg q4-6weeks
• Adults > 50 y/o w/ cardiac disease – 12.5-25 mcg/day titrated by 12.5-25 mcg q4-6weeks
• Sx improvement in 2-3 weeks; maximal sx improvement in 4-6 weeks

Question 16

Drug interactions w/ levothyroxine

Answer 16

• TUMS, ranitidine, multivitamin – reduce absorption
• Metformin – decrease TSH secretion, increase levothyroxine requirements, & hypo/hyperthyroidism has effect on insulin sensitivity (hyper = increased sensitivity & vice versa)
• Carbamazepine – increases levothyroxine clearance

Question 17

Monitoring for hypothyroidism

Answer 17

• TSH (primary hypo) or FT4/FT3 (central hypo) – 6-8 weeks until TSH normal, then q1year
• Signs & sx of hypo – weekly by pt (improve in 2-3 weeks; skin change 3-6 months)
• If clinical manifestations not resolved or re-appear –> check TSH level; consider drug/meal interactions or malabsorption

Question 18

Hypothyroidism tx during pregnancy

Answer 18

• T4 requirements increase to maintain euthyroid state (onset 4-6 weeks gestation; increases until week 16-30 then remains constant until delivery)
• Newly pregnant & receiving LT4 -> increase dose by 25-30% in first trimester (if once daily, increase to 9 doses/week)
• TSH is most accurate indication of thyroid status
• • Measure q4weeks in 1st half of pregnancy, then q1week in week 26-32
• Following delivery –> reduce LT4 dose, then check TSH 6 weeks postpartum

Question 19

Pt counseling tips for thyroid replacement therapy

Answer 19

• Levothyroxine should be taken in the AM on empty stomach; important to take same time each day
• Do not take antacids, iron preparations, calcium supplements w/in 4 h of thyroid medication (decreased absorption)
• Try not to change brands (less fluctuation in TFT if using the same brand – “interchangeability” province-dependent)
• Signs & sx to report = chest pain, rapid HR, palpitations, heat intolerance, excessive sweating, increased nervousness, agitation, lethargy

Question 20

Describe liothyronine/ cytomel (T3)

Answer 20

• Used in some px monotherapy or in combo w/ levothyroxine (T4) to control hypothyroidism
• Long-term benefit of combo therapy remains unknown

Question 21

Consequences of untreated hyperthyroidism

Answer 21

• CV –> A fib, angina, HTN, peripheral edema, heart failure
• Ocular –> double vision, corneal damage, vision loss
• Skeletal –> hypercalciuria, mild hypercalcemia, slight increased fracture risk
• Thyroid storm – medical emergency

Question 22

Hyperthyroidism tx. Describe SE, duration, and monitoring

Answer 22

• Antithyroid medications (propylthiouracil, methimazole)
• • PTU & MMI inhibit thyroid peroxidase (TPO) –> block iodination of tyrosine
• • PTU inhibits 5’ deiodinase –> block peripheral conversion of T4 to T3
• Radioactive iodine to destroy gland
• • Used in Graves’ disease, not used in thyroiditis
• Surgery to remove gland
• Sx relief w/ beta blockers
• SE –> maculopapular rash (responds to antihistamines), arthralgia, transient fever, GI intolerance
• • Low risk of permanent hypothyroidism in the long-term
• • Risk of cross-sensitivity between PTU & MMI is 50%
• Response in 4-8 weeks; max response in 4-6 months
• Duration = ~1-2 years
• Monitor q4weeks until euthyroid (CBC, PT, TFT, INR); after remission monitor q6-12months

Question 23

Pt counseling tips for radioactive iodine

Answer 23

• Concentrates in gland & destroys thyroid tissue
• SE  mild thyroidal tenderness/ dysphagia; permanent hypothyroidism
• Differ pregnancy 6-12 months post RAI; no breastfeeding (okay for future pregnancies)
• Most cost effective
• Have the potential to contaminate close contacts via saliva, urine, or radiation emitting from their neck => don’t kiss, exchange saliva, or share food/eating utensils for 5 days; wash dishes in dishwasher if available
• Avoid close contact w/ infants, young children (< 8 y) & pregnant women for 5 days (can be in the same room, stay 2 m away)
• Flush toilet twice after urinating & wash hands thoroughly

Question 24

Radioactive iodine & SSKI

Answer 24

• SSKI = saturated solutions of potassium iodide
• Don’t use SSKI pre-RAI b/c RAI needs to concentrate in thyroid
• MOA = saturates iodide transport system, decreases size & vascularity of gland
• Efficacy – reduced sx x 2-7 days (quick onset), reduce T3 & T4 in weeks

Question 25

Beta blockers for thyroid disorders

Answer 25

- Propranolol & nadolol partially block T4 -> T3 conversion (but this is a small effect on tx) - Role = adjunctive therapy w/ ATD (anti-thyroid drugs), RAI, iodides, surgery, thyroid storm, Graves or toxic nodules for sx management - SE = N/V, anxiety, insomnia, bradycardia - Verapamil, diltiazem may be considered if BB’s aren’t tolerated or CI

Question 26

Euthyroid sick syndrome

Answer 26

- Abnormal thyroid function in px w/ nonthyroidal illness - Natural human response to getting sick - Common in ICU px w/ no thyroid problem - Reduced conversion of T4 -> T3 by T4-5’-deiodinase - Thyroid function shouldn’t be assessed in seriously ill px unless there is a strong suspicion of thyroid dysfunction - Tx not recommended – studies showed tx doesn’t improve survival

Question 27

Thyroid function in non-thyroidal illness

Answer 27

1. Sick – T3 drops first (ex: hospital inpatient) 2. TSH drops but not to zero (transient central hypothyroidism, low TBGs) 3. Sickest – T4 drops (low T4 = poor prognosis)

Question 28

Hypothyroidism in the elderly

Answer 28

- Elderly px may have fewer sx than younger adults - - Memory loss, confusion, weight gain, dry skin, sleepiness - Specific signs in elderly = ataxia, non-joint pain/ muscle ache, falling

Question 29

When to treat thyroid disorders

Answer 29

- Overt hypothyroidism - Subclinical hypothyroidism if symptomatic, presence of anti-thyroid antibodies, or CV disease - TSH target range = 0.45 – 4.12 mIU/L - Dose according to pt response (sx improvement) & TSH tests - Few px require doses > 200 mcg/day