THYROTOXICOSIS IN PREGNANCY - PowerPoint Presentation

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THYROTOXICOSIS IN PREGNANCY

A Amouzegar MD

Endocrine Research Center

Research Institute For Endocrine Sciences

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OutlinesCauses of hyperthyroidism

Consequences of hyperthyroidism

Consequence of poor control

The treatment of

choice in GD planning pregnancy

Treatment of GD during pregnancy

Withdraw thyroid drugs

Conclusion

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What are the causesof thyrotoxicosis in pregnancy?

Autoimmune GD (The most common cause )

Less common non-autoimmune causes include :

TMNG

Toxic adenoma

SAT painful or painless

TSH-secreting pituitary adenoma

Struma

ovarii

Functional thyroid cancer metastases

Germline

TSH receptor mutations

Overtreatment with or factitious intake of thyroid hormone

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Consequence of poor control of thyrotoxicosis

Pregnancy loss

Pregnancy induced hypertension

prematurity

Low birth weight

Intrauterine growth restriction, stillbirth

Thyroid storm

Maternal congestive heart failure

May program the offspring to develop diseases Such as seizure disorders and neurobehavioral disorders in later life

Obstet

Gynecol

1994 84:946–949

Clin

Endocrinol

(

Oxf

) 2015 83:751–758

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Fetal risks in women with previous or current Graves’ hyperthyroidism

(a) Fetal hyperthyroidism

(b) Neonatal hyperthyroidism

(

c)

Fetal hypothyroidism(d

)

Neonatal hypothyroidism

(

e

) Central hypothyroidism

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Indications for ordering a TRAb test in pregnant women

with GD include

(a)

Mothers

with untreated or

ATD-treated hyperthyroidism

in

pregnancy

(b)

A

previous history of

GD with

past treatment with radioiodine or total

thyroidectomy

(c) a previous history of delivering an infant with

hyperthyroidism

Eur

J

Endocrinol

1998 139:584–586

.

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Cont

(d)

If the patient requires treatment with ATDs for GD through

mid pregnancy

, a repeat determination of

TRAb is recommended at weeks 18–22Strong recommendation, moderate-quality

evidence

(e) Should

again be performed

in weeks 30–34

to evaluate the need for neonatal and postnatal

monitoring

Strong recommendation, high-quality evidence

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GD planning pregnancy

In all women of childbearing age who are

thyrotoxic

,

the possibility

of future pregnancy should be discussedWomen with GD seeking future pregnancy should be counseled regarding

the complexity of disease

management during future gestation(birth defects

with ATD

use)

Review

the risks and benefits of all treatment options

and the

patient’s desired timeline to

conception

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How should women with GD seeking future pregnancy be counseled?

Pregnancy should be postponed until a stable euthyroid state is reached

2 sets of TFT within the reference range, at least 1 month apart, and with no change in therapy between tests, can be used to define a stable euthyroid state

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Case 1GD+ euthyroidism

A 26 year-old woman with history of GD since 1 year ago has a plan to become pregnant

She is clinically euthyroid now

PHMx

: mild goiter, PR: 76 /min, No GO

She is taking MMI 5 mg daily,T4 9 µg/dl and TSH 0.8

mIU

/L,

TRAb

4 IU/L

TFT showed euthyroid state one month ago

What do you do before conception?

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Cont

a. Patients could consider definitive therapy before

they become pregnant

b. Patients could switch to PTU before trying to

conceive

c. Patients could switch to PTU as soon as pregnancy is diagnosed

d.

The patient

could withdraw

from ATD

therapy as soon as pregnancy is

diagnosed

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ContThe evidence is insufficient to give universal guidance

on how

to choose among these

options

The potential risks

and benefits of each option should be discussed with the patient Patient values and preferences should be taken

into

account

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Advantages and disadvantages of

antithyroid

drugs

Disadvantages

Advantages

Therapy

Medication adverse effects (mild 5%–8%; severe

0.2%)

Birth defects associated with use during pregnancy

(MMI 3%–4%; PTU 2%–3% though

less severe)

Relapse after drug withdrawal likely in 50%–70%

Effective treatment to euthyroid state within

1–2 months

Often induces gradual remission of

autoimmunity

(decreasing antibody titers)

Easily discontinued or modified

Treatment

easy to take

Relatively inexpensive

Antithyroid

drugs

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Advantages and disadvantages of radioactive

iodine

Disadvantages

Advantages

Therapy

Repeat therapy at times necessary

Rising antibody titers following treatment may

Contribute to worsening

orbitopathy

or fetal

risk

Lifelong need of levothyroxine therapy

following ablation

A subset of young patients with severe GD

may not become stably euthyroid within the first year after

131I therapy

Conception should be delayed 6 months and

until a stable euthyroid state is reached after ablation and

initiation of LT4 replacement therapy

Easy oral administration

Reduction in goiter size

Future relapse of hyperthyroidism very rare

Radioactive

iodine

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Advantages and disadvantages of Thyroidectomy

Disadvantages

Advantages

Therapy

Life-long need for levothyroxine

Surgical complications occur in 2%–5%

Healing and recovery from surgery

Permanent neck scar

Definitive therapy of hyperthyroidism

Stable euthyroid state easily achieved on replacement

levothyroxine therapy

Post surgery, gradual remission of autoimmunity occurs

Goiter disappears

Thyroidectomy

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Case 2Hyperthyroidism planning pregnancy

The patient is a 28-year-old- women with history of GD since 14 months ago , is taking MMI 10 mg daily, physical examination shows PR 99/min, goiter, T4=19 µg/

dL

TSH = 0.01

mIU

/L

TRAb

= 40 IU/L

She has a plan to become pregnant in near future

What is the best choice for her?

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ContA) Increase the dose of MMI to 20- 30 mg daily and continue the drug till pregnancy

B) Increase the drug till euthyroidism then Radioactive iodine therapy

C) Increase the drug till euthyroidism

then thyroidectomy

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The treatment of choice

A hyperthyroid patient who desires future pregnancy

may be

offered

:

Ablative therapy using 131 IThyroid surgeryMedical therapy

Each

therapeutic option carries

advantages and disadvantages

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Back to caseThe patient is not euthyroid

Medication adverse effects with higher doses

The patients with high

TRAb

levels or severe hyperthyroidism may

favor consideration of other therapeutic options such as surgery Radioablation

would not be a good choice

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Case 3

Hyperthyroidism in pregnancy

A 33-year old 7 week- pregnant- woman presented with palpitation ,tachycardia and weight loss ( 4 kg during recent 3 weeks)

Physical exam shows mild active GO, goiter ,

Lab tests: T4 25 µg/

dL

and TSH < 0. 01

mIU

/L

TRAb

10 IU/L

Which therapy is the best choice ?

A) MMI 20 mg in divided dose daily

B) PTU 300 mg in divided dose daily

C) Radioiodine therapy

D)PTU first then surgery after

euthyroism

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Graves’ hyperthyroidism during pregnancy

Thionamides

(

MMI,

carbimazole

, and PTU) : mainstays of treatment

MMI

,

5–30 mg/d

(typical

10–20mg/d)

CM

,

10–40 mg/d

PTU

,

100–600 mg/d (typical 200–400mg/d)

The equivalent

potency of MMI to PTU is approximately

1:20 (e.g

.,

5mg MMI

= 100mg of PTU

)

Because

the half-life of

PTU is

shorter

dosing

should generally be split into

2

or

3 daily doses

MMI :one daily dose

Severe

hyperthyroidism, twice or

three times

may

be of

benefit

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Side effects (mother)

Allergic reactions,

agranulocytosis

and liver

failure are rare The risk of hepatotoxicity in PTUlimiting

the use of PTU to the first trimester of

pregnancy

Monitoring

hepatic enzymes

during administration

of PTU may be

considered

However

,

no showed to be effective

in preventing

fulminant PTU-induced hepatotoxicity

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Potential teratogenic effects

A

‘‘syndrome of

methimazole

/

carbimazole embryopathy’’was described, which also includes

Aplasia cutis

Dysmorphic

facies

Choanal

Esophageal atresia

Abdominal wall

defects including

umbilicocele

Eye, urinary

system, and

VSD

Complications affect

2%–4%

of children

who have been exposed to MMI in early

pregnancy, especially

during gestational weeks

6–10

2%–3% of children exposed to PTU

developed birth

defects

primarily

face and neck cysts

and

urinary tract abnormalities

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Beta-adrenergic blocking agents

propranolol 10– 40mg

every 6–8 hours may be used for controlling

hypermetabolic

symptoms

until patients have become euthyroid In the vast majority the drug can be discontinued in 2–6

weeks

Long-term

treatment with

b-blockers has

been associated with intrauterine growth restriction,

fetal

bradycardia

, and neonatal

hypoglycemia

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ATD administration

ATDs also

effectively

cross the placenta

ATD maternal hyperthyroidism also

modulates fetal thyroid function ATDs tend to be more

potent in the fetus than in the

mother

When

the mother is made euthyroid, the fetus is

often

overtreated

The

aim of treatment is to maintain maternal

TT4/ FT4

values at, or just above the pregnancy-specific upper

limit of normal

The

smallest possible dose

of ATDs

should be used whenever possible

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F/U

TFT should

be measured

:

Every

2–4 ws following initiationEvery 4– 6 ws

after achieving the target

value

When trimester-specific

FT4 values are not available, use of

the reference

range for

nonpregnant

patients is

recommended

TT4

with

reference value

1.5 times

the

nonpregnancy

range may be used in

2nd and 3

rd

trimesters

Overtreatment should be avoided because

of the

possibility of inducing fetal goiter and or fetal hypothyroidism

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Case 4

ATD+ pregnancy

When to withdraw?

32-year-Old

8-week pregnant lady, Graves dis, has been treated with MMI 10 mg daily since 4 month ago

PHx

: mild active Go, goiter

Prepragnancy

TSH

0.1

mIU

/L

Current MMI dose is 10 mg/daily

T4=15 µg/

dL

TSH=0.01

mIU

/L

What do you choose for the patient?

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ContA) Continue MMI 10 mg daily

B) Change to PTU 200 mg daily

C) Change to PTU 200 mg

daily and change to MMI after 16 w

D) withdraw the drug after 1st trimester

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Should antithyroid medication be

withdrawn or modified in early pregnancy?

The

high risk

of rapid relapse

after withdrawal:

Have

been treated for a short

period (<

6months

)

Have

suppressed

or low serum TSH

while

on medication

prepregnancy

Require

>5–10mg of MMI

per day

to stay

euthyroid

Have

active

orbitopathy

Large goiter

Have

high levels of

TRAb

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Cont The risk is considered high, medication should not be

withdrawn, and

PTU should be administered as the drug of

choice

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Conclusion

In all women of childbearing age who are

thyrotoxic

,

the possibility

of future pregnancy should be discussedThyrotoxic women should be rendered stably

euthyroid before

attempting

pregnancy

Several

treatment

options exist

, each of which are associated with risks and

benefits

PTU is recommended for the treatment of maternal hyperthyroidism through 16 weeks of pregnancy

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Cont

MMI should

be switched to PTU as early as

possible

If ATD therapy is required after 16 weeks gestation, it remains unclear whether PTU should be continued or therapy changed to MMI

In women being treated with ATDs in pregnancy, FT4/ TT4

and TSH should be monitored

a every 4

weeks

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