Chapter 49 Thyroid 1

8/9/2019 Chapter 49 Thyroid 1

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Chapter 49 Thyroid


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Chapter 49 Thyroid

Affects 5-15% of the population

3:1 F:M

Two active thyroid hormones T3

(triodothyronine) and T4 (thyroxine)

produced by thyroid in response to TSH

(thyroid stimulating hormone) released frompituitary (negative-feedback system)


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Thyroid continued

T4 converted to T3 by deiodination in the

pituitary and peripherally as well

T3 is 4x as potent as T4 T3 concentration < 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)


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Hypothyroidism

Deficiency of thyroid hormone

1.4-2% in females, 0.1-0.2% in males

>60 yo - 6% in females, 2.5% in males

Primary hypothyroidism - problem with

thyroid gland

secondary hypothyroidismhypothalamic- pituitary malfunction

table 49-2

(primary more common than secondary)


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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


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Hypothyroidism continued

Myxedema coma-end-stage

hypothyroidism- 60-70% mortality

hypothemia,confusion, stupor,coma, CO2retention, hypoglycemia, hyponatremia, ileus

Older patient with hypothyroidism can

present with minimal or atypical symptoms

(weight loss, deafness, tinnitus, carpaltunnel 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 controversialwhether 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


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Drug Therapy of hypothyroidism

continued 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

autoimmune1 or more of following: hyperthryroidism,

diffuse goiter, ophthalmopathy (exophthalmos),

dermopathy, acropachy (thickening of fingers

or toes)


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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 beabsent, pt. may present as apathetic


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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


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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 havesymptoms 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) thanPTU (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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TFT

Thyroid 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


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TFT continued

FT4I and FT3I - indirect estimate of free T4

and T3 when TBG binding is altered - FT4

and FT3 are preferred.


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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 bealtered and TT3 can be low (eg. Older pts,

acute/chronic nonthyroid illness)


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TSH Test of hypothalamic-

pituitary Thyroid Axis Thyroid stimulating hormone (TSH) also

called thyrotropin

most sensitive test to evaluate thyroidfunction

TSH can be abnormal even when FT4 is

WNL (TSH is specific for individual setpoint) FT4 appears normal but low for that

individual


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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)


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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-thyroidillness?


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Question 2 continued

Which TFT is useful to determine euthyroid

state in sick pt?

When should TSH be repeated (in sickpatient) 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 syntheticT4 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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When should T4 be taken in relation to

meals?

NOTE: since publication of text, many T4products 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 8

What is usual replacement dose (using

patient weight)?

What can happen if we administer excessiveT4?

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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How was T4 started in MW? And when was

testing performed?

In general, how should T4 dosingadjustments 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 oflevothyroxine be decreased in relation to

PO doses?

When is once-weekly IM levothyroxineinjection 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 isuntreated 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 forfailure?

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 withcaution 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 symptomsof 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 BetaBlockers?


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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 riskpatient?


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Question 22

NOTE: the treatment of subclinical

hypothyroidism (ie no symptoms of

hypothyroidism with elevated TSH) iscontroversial; 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 ofhypothyroidism (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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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 diseasespontaneously 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 tocontrol?

What activity does propranolol have in

addition to B-Blocking effects (that other B-blockers do not have)?


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What are effective alternatives when B-

blockers are contraindicated?

What is reasonable start dose of metoprololand 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 beavoided 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 inhyperthyroid 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- inducedhyperthyroidism occur?

Chapter 49 Thyroid 1

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