Chapter 49 Thyroid

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Chapter 49 Thyroid
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Chapter 49 Thyroid

• Affects 5-15 of the population
• 31 FM
• Two active thyroid hormones T3 (triodothyronine)
  and T4 (thyroxine) produced by thyroid in
  response to TSH (thyroid stimulating hormone)
  released from pituitary (negative-feedback system)

3
Thyroid continued

• T4 converted to T3 by deiodination in the
  pituitary and peripherally as well
• T3 is 4x as potent as T4
• T3 concentration lt T4
• DRUGs and diseases affect conversion, Table 49-1
• 99.97 of T4 is bound (70 to thyroxin binding
  globulin, 15 to thyroxine-binding pre-albumin,
  and albumin)

4
Thyroid continued

• 0.03 T4 is Free
• extensive binding results in long 1/2 life
• (5-10 days)
• T3 - 99.7 bound (less than T4)
• 0.3 of T3 is Free (shorter 1/2 life (1.5 days)
  and increased potency

5
Hypothyroidism

• Deficiency of thyroid hormone
• 1.4-2 in females, 0.1-0.2 in males
• gt60 yo - 6 in females, 2.5 in males
• Primary hypothyroidism - problem with thyroid
  gland
• secondary hypothyroidism
• hypothalamic- pituitary malfunction
• table 49-2
• (primary more common than secondary)

6
Hypothyroidism continued

• Hashimotos thyroiditis - (autoimmune) most
  common cause of primary hypothyroidism.
• Can present with hypothyroidism and goiter
  (thyroid gland enlargement) or without goiter, or
  euthyroid with goiter.
• Clinical and lab findings
• Table 49-3

7
Hypothyroidism continued

• Myxedema coma-end-stage hypothyroidism- 60-70
  mortality
• hypothemia,confusion, stupor,coma, CO2 retention,
  hypoglycemia, hyponatremia, ileus
• Older patient with hypothyroidism can present
  with minimal or atypical symptoms (weight loss,
  deafness, tinnitus, carpal tunnel syndrome)
• mild/subclinical hypothyroidism may have few or
  no symptoms

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Drug Therapy of hypothyroidism

• Levothyroxine is preferred
• DOSING Table 49-4
• myxedema coma- large doses of levothyroxine (400
  mcg) are necessary - saturates empty thyroid
  binding sites
• subclinical hypothyroidism controversial whether
  to give T4 or not (lab values are normal)

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Drug Therapy of Hypothyroidism continued

• Goal of therapy- reverse signs and symptoms of
  hypothyroidism and normalize TSH and thyroxine
  levels
• Improvement can be seen in 2-3 weeks of therapy
• Excessive replacement (low TSH) associated with
  osteoporosis and cardiac changes

10
Drug Therapy of hypothyroidismcontinued

• Optimal dosage continued for 6-8 weeks (to reach
  steady state) then Retest thyroid function tests.
• After euthyroid state reached then test q 3-6
  months for 1 year, then yearly thereafter
• Dont administer interacting medications (eg.
  Iron, aluminum, calcium, cholesterol resin
  binders, raloxifene) at same time as thyroid
  preparation.

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Hyperthyroidism (thyrotoxiois)

• Hypermetabolic syndrome
• excessive thyroid hormone
• 2 females, 0.1 males
• causes- Table 49-5
• GRAVES disease - most common cause
• autoimmune
• 1 or more of following hyperthryroidism, diffuse
  goiter, ophthalmopathy (exophthalmos),
  dermopathy, acropachy (thickening of fingers or
  toes)

12
Hyperthyroidism continued

• IgG or thyroid receptor antibodies -
• TSH- like ability to stimulate hormone.
• Peak incidence 30-40 years old
• Clinical and lab findings
• Table 49-6
• Elderly patient- usual symptoms may be absent,
  pt. may present as apathetic

13
Hyperthyroidism continued

• Consider hyperthyroidism in elderly patient with
  new or worsening cardiac findings (eg. a fib.)
• untreated can lead to thyroid storm - exaggerated
  thyrotoxicosis symptoms and high fever

14
Treatment

• Antithyroid drugs (thioamides), radioiodine,
  surgery
• Radioactive iodine - older patients, patients
  with cardiac disease, ophthalmopathy, toxic
  nodular goiter
• surgery - preferred if obstructive symptoms,
  malignancy is suspected
• Pregnant patients- thioamides, surgery,
  radioactive iodine contrainidicated.

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Thioamides

• Methimazole (tapozole), propylthiouracil (PTU)
• primary therapy for hyperthyroidism
• prevent hormone synthesis - does not affect
  existing stores of thyroid hormone
• hyperthyroid pt. will continue to have symptoms
  for 4-6 weeks after starting thioamide (need to
  use B-blockers)

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Thioamides continued

• PTU works more quickly than methimazole because
• PTU also inhibits T4 to T3 conversion
• PTU preferred in thyroid storm
• PTU not secreted in breast milk
• Methimazole easier to take (daily) than PTU
  (2-3xD)

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Thioamides continued

• Generally used for 1 to 1-1/2 yrs and hope
  spontaneous remission after D/C . (unfortunately
  not so common)
• ADV effects - Skin rash, GI complaints,
  agranulocytosis, hepatitis
• Other options - surgery, radioactive iodine
• other considerations - malignancy

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TFTThyroid function Tests

• TSH, (thyroid stimulating hormone) , FT4 (Free
  T4), TT4 (total T4), TT3 (Total T3), FT3 (free
  T3), radioactive iodine uptake (RAIU),
• Table 49-7
• FT3- expensive, difficult, unnecessary
• calculated FT3- correlates well with FT3

19
TFT continued

• FT4I and FT3I - indirect estimate of free T4 and
  T3 when TBG binding is altered - FT4 and FT3 are
  preferred.

20
TT4 and TT3

• TT4 total thyroxine and TT3 total
  triiodothyronine - measure of FREE and BOUND
  DRUGS
• falsely elevated - common in euthyroid pregnant
  woman
• peripheral conversion of TT4 to TT3 can be
  altered and TT3 can be low (eg. Older pts,
  acute/chronic nonthyroid illness)

21
TT4 and TT3 continued

• TT3 helpful to detect relapse of Graves disease
  and to confirm hyperthyroidism despite normal TT4
  level.

22
TSH Test of hypothalamic-pituitary Thyroid Axis

• Thyroid stimulating hormone (TSH) also called
  thyrotropin
• most sensitive test to evaluate thyroid function
• TSH can be abnormal even when FT4 is WNL (TSH is
  specific for individual set point) FT4 appears
  normal but low for that individual

23
TSH test continued

• High TSH - hypothyroid
• Low TSH - hyperthyroid
• TSH can be abnormal in euthyroid patients (with
  nonthyroid illness or pt recv. Drug interfere
  with TSH secretion - dopamine agonists and
  antagonists)

24
Test of gland function

• RAIU - radioactive iodine uptake - measure of
  iodine utilization by gland and indirect measure
  of hormone synthesis.
• Used to calculate dose of radioactive iodine for
  treatment of Graves disease.

25
Test of Autoimmunity

• TPO (thyroperoxidase) and ATgA (antithyroglobulin)
  antibodies-indicate autoimmune process
• 60-70 patients with Graves disease and 95 of
  patients with Hashimotos thyroditis have positive
  antibodies
• 5-10 patients without disease have antibodies

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Test of Autoimmunity continued

• TRAb (thyroid receptor antibodies)
• IgG immunoglobulins - in all pts with Graves
• can stimulate thyroid to produce hormone
• useful in select situation (pg. 49-8)
• expensive, not helpful in typical Graves patient

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Question 2

• What is euthyroid sick syndrome?
• How often can this syndrome be found in
  chronically ill or hospitalized patients?
• What are usual changes seen in TFT?
• How valuable are T4 and T3 measurements in
  patients with significant non-thyroid illness?

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Question 2 continued

• Which TFT is useful to determine euthyroid state
  in sick pt?
• When should TSH be repeated (in sick patient) to
  confirm euthyroidism?

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Question 3

• How do anticonvulsants alter serum thyroid
  hormone levels? And by what mechanism?
• What happens to TSH in these patients?

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Question 4

• Under what conditions can a patient have
  increased TT4 and decreased resin uptake and
  normal TSH and FT4?
• What is the reason for this?
• How long after oral contraceptive D/C will it
  take for TFT to return to normal?

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Question 5

• How does Amiodarone affect TFT?
• Can amiodarone cause hyper or hypothyroidism?
• What occurs with dopamine agonists (eg. Dopamine,
  bromocriptine, levodopa) and TSH?
• What occurs with dopamine antagonists
  (metoclopromide) and TSH?

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Question 7

• Is initiation of dessicated thyroid in a
  hypothyroid patient justified? Why not?
• What is approximate equivalent synthetic T4 to 60
  mg of dessicated thyroid?
• What is thyroid replacement of choice?
• Why can we dose T4 once daily?
• What is usual absorption of T4?

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Question 7 continued

• When should T4 be taken in relation to meals?
• NOTE since publication of text, many T4 products
  are now AB rated to each other which means they
  are considered interchangeable by FDA
• why is triiodothyronine not recommended for
  routine thyroid replacement?

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Question 7 continued

• What have small studies found with combination of
  T4 and small dose of T3?
• What are other disadvantages to T3?
• What is primary use of T3?
• What is liotrix?

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Question 8

• What is usual replacement dose (using patient
  weight)?
• What can happen if we administer excessive T4?
• How often should TSH be checked in pt stabilized
  on T4?
• What are some risk factors for cardiotoxicity
  that require careful dosage titration?

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Question 8 continued

• How was T4 started in MW? And when was testing
  performed?
• In general, how should T4 dosing adjustments be
  handled?

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Question 9

• Why should we wait 6-8 weeks after initiation of
  T4 to check TFT?

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Question 10

• Which lab values are best indicators of
  euthyroidism in patients treated with
  levothyroxine?
• TFT should be done at trough levels, this is
  because one study found that..?

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Question 12

• Which is preferred IV or IM administration of
  levothyroxine? And why?
• Why should parenteral doses of levothyroxine be
  decreased in relation to PO doses?
• When is once-weekly IM levothyroxine injection an
  option?

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Question 13

• What can occur to the fetus when the mother has
  inadequately treated hypothyroidism?
• Does thyroid hormone cross the placenta?

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Question 14

• What are early clinical findings of congenital
  hypothyroidism?
• What can happen if hypothyroidism is untreated
  during first three years of life?

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Question 15

• What are possible reasons for RTs therapeutic
  failure?
• What is the most likely explanation for failure?
• What questions/intervention should be suggested?
• What meds can interfere with thyroid
  bioavailability?

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Question 16

• How does hypothyroidism affect cholesterol?

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Question 17

• What is myxedema coma? What are the classic
  features?
• Which medications should be used with caution in
  myxedema coma?
• NOTE treatment of myxedema coma is in text for
  reference

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Question 19

• What are symptoms of myxedema heart?
• NOTE hypothyroidism should be excluded in all
  pts with new or worsening symptoms of CVD.

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Question 20

• How does hypothyroidism aggravate subendocardial
  ischemia during an acute MI?
• How do nitrates precipitate hypotension?
• Why are cardioselective Beta Blockers preferred
  over non-cardioselective Beta Blockers?

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Question 21

• What can occur when initiating T4 in patients
  with longstanding hypothyroidism, CAD, or
  advanced disease?
• NOTE you may want to address cardiac disease (eg
  angina) before T4 therapy
• What dose should be used in at risk patient?

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Question 21 continued

• NOTE some patients may not be able to tolerate
  full T4 replacement dose, in these patients, T4
  dose is balance between prevention of myxedema
  coma and cardiac toxicity.
• Why is T3 theoretically better for use in cardiac
  patients?
• Even so, why is T3 not recommended?

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Question 22

• NOTE the treatment of subclinical hypothyroidism
  (ie no symptoms of hypothyroidism with elevated
  TSH) is controversial see question 22 for
  details.

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Question 23

• What did a randomized, double-blind,
  PCB-controlled determine about T4 supplementation
  in pts with symptoms of hypothyroidism (eg
  fatigue, cold intolerance, dry skin) and normal
  TSH and T4 levels?

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Question 24

• What are symptoms of hyperthyroidism?
• What is the most common arrhythmia in
  hyperthyroidism?
• What arrhythmia is the presenting-symptom in
  5-20 of patients with hyperthyroidism?

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Question 25

• NOTES
• Hyperthyroidism creates an increase in clotting
  factor catabolism (i.e. increased INR)
• Hypothyroidism results in decrease in metabolism
  and synthesis of clotting factors (i.e decreasing
  INR)

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Question 31

• What are 3 major treatment modalities for
  Graves-related hyperthyroidism? Table 49-10
• When are thioamides preferred?
• NOTE Thioamides do not generally cause
  hypothyroidism, unlike surgery and RAI.
• How long are thioamides given for?

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Question 31 continued

• Why should thioamides be given before RAI or
  surgery?
• What are disadvantages of thioamides?
• When is surgery the treatment of choice?
• When is RAI the preferred treatment?

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Question 32

• Why is methimazole preferred over PTU?
• When is PTU preferred over methimazole?

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Question 34

• What lab values should be measured to help
  determine efficacy and toxicity of thioamides?

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Question 35

• How long does thioamide therapy traditionally
  continue?
• How often does Graves disease spontaneously
  remit?

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Question 36

• How does thyrotoxicosis affect diabetes?
• How often does a lupus-like syndrome occur with
  thioamide?
• What are symptoms of this syndrome?

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Question 37

• What adjunctive therapy is used in
  thyrotoxicosis?
• What symptoms do Beta-blockers to control?
• What activity does propranolol have in addition
  to B-Blocking effects (that other B-blockers do
  not have)?

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Question 37 continued

• What are effective alternatives when B-blockers
  are contraindicated?
• What is reasonable start dose of metoprolol and
  goal for treatment?

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• NOTE Thioamides can cause maculopapular rash in
  5-6 of pts. They can also cause transient
  elevation in transaminase in about 30 of pts
  with in 2 months that does not require drug D/C.
• However should D/C if clinical symptoms of
  hepatitis.
• Also, thioamides can cause agranulocytosis in
  0.5-6 of pts

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Question 42

• What is a major reason for adding T4 to PTU
  regimen?

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Question 44

• What antithyroid agents are contraindicated
  during pregnancy?
• Shy should long-term use of propranolol be
  avoided in pregnancy?
• What are treatments of choice for hyperthyroidism
  during pregnancy?

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Question 47

• What is incidence of RAI induced myxedema?

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Question 50

• What are the clinical manifestations of thyroid
  storm?
• What is the incidence of thyroid storm in
  hyperthyroid pts?

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Question 52

• How often does subclinical hypothyroidism occur
  in pts on chronic lithium therapy?

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Question 53

• What can occur following Lithium withdrawal?

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Question 54

• How often does amiodarone- induced hypothyroidism
  occur?
• How often does amiodarone- induced
  hyperthyroidism occur?