hyperthyroidism during pregnancy

Dr. M.MoshfeghiOBS&GYN

fellowship of perinatology

RUYAN INSTITUTE

Overt hyperthyroidism

low TSH

elevated free thyroxine [T4]

and/or [T3]

uncommon during pregnancy,

0.1 to 0.4 % of pregnancies

The diagnosis of hyperthyroidism

pregnant women

but presents some unique

problems.

THYROID PHYSIOLOGY DURING NORMAL PREGNANCY

increased metabolic needs

(TBG) excess

high serum total T4 and total T3

not high serum free T4 or free T3

●High (hCG) during early pregnancy

HCG higher in hyperemesis

gravidarum or multiple pregnancies

transient subclinical or overt

hyperthyroidism

nonspecific symptoms

with pregnancy

similar to those with

hyperthyroidism,

tachycardia,

heat intolerance,

increased perspiration.

Anxiety

hand tremor, weight loss

despite a normal or increased appetite.

Specific findings

goiter

ophthalmopathy

suggest Graves'

increased rates of the following

Spontaneous abortion

Premature labor

Low birth weight

Stillbirth

Preeclampsia

Heart failure

Subclinical hyperthyroidismlow TSH,

with normal free T4 and T3 using trimester-specific normal reference ranges or

total T4 and T3 that are less than 1.5 times the nonpregnant range

no evidence of adverse pregnancy outcomes

lower incidence of spontaneous abortion

a higher risk of preeclampsia

Free T4 in the upper-normal quintile

normal free T4 in the upper

quintile

normal TSH

LBW

maternal HTN

not APO

Laboratory findings

— significant overt hyperthyroidism in the first trimester

TSH below that which is seen in asymptomatic healthy pregnant women (ie, <0.01 mU/L),

elevated free T4 and/or free T3

(or total T4 and/or total T3) exceeds the normal range during pregnancy

Transient subclinical hyperthyroidism

subnormal TSH

total or free T4 and T3 in the normal

range

normal physiologic

finding.

not typically associated with APO

not require therapy.

, the lower limit for TSH in healthy pregnant

women

first trimester

0.03 to 0.1 mU/L

Total T4 and T3 levels 1.5-fold higher than

in nonpregnant

When clinical

suspicion

TSH measure.

TSH <0.1 mU/L,

free or total T4 should be

obtained.

If the free or total T4 is in the normal

range

, a total T3 should also

be measured.

suppressed (<0.1 mU/L)

or undetectable (<0.01 mU/L)

TSH value free T4

and/or free T3 (or total T4 and/or total T3)

exceeds the normal range

Dx

causes of hyperthyroidism

Graves' disease (0.1 to 1 % of all pregnancies)

(hCG)-mediated hyperthyroidism due to gestational transient thyrotoxicosis (1 to 3 %)

silent or subacute thyroiditis, toxic adenoma, toxic multinodular goiter, less common during pregnancy

Our approach

differentiate

Graves' disease

hCG-mediated hyperthyroidism.

based upon clinical findings and laboratory tests.

, ultrasound with measurement of thyroidal blood flow can aid in the diagnosis of Graves' disease.

clinical symptoms are similar

Graves' disease

• goiter or ophthalmopathy

• less severe during the later stages of pregnancy

HCG mediated hyper th

• Goiter is not a classical

• transiently in the first half of gestation

• less severe than Graves' disease

Laboratory evaluation

TRAbs confirms DX of Graves' disease

96 to 97 percent of

Graves' disease

TRAbs TSH receptor antibody

Imaging

–thyroid ultrasound with

Doppler flow

Graves' disease

high blood flow

from painless or postpartum thyroiditis

low blood flow

utility in diagnosing hCG-

mediated hyperthyroidism

is unknown.

radionuclide imaging

is contraindicated

in pregnant women.

Graves' disease

• hyperthyroidism, ±• goiter,

• eye disease (orbitopathy),

• dermopathy -pretibial or localized myxedema.

• Graves' disease≠hyperthyroidism

• some patients may have orbitopathy but no hyperthyroidism

the most common feature of Graves

Hyperthyroidism

caused by TRAbs

activate the receptor

stimulating thyroid hormone synthesis

secretion

thyroid growth (causing a diffuse goiter).

TRAbs + orbitopathy distinguishes the disorder from other causes of hyperthyroidism.

hCG-mediated hyperthyroidism

During normal pregnancy

(hCG) rise soon after fertilization and peak at 10 to 12 w, after which time

the levels decline.

, hCG has weak TSH activity and may cause

hyperthyroidism during the period of highest serum

hCG concentrations.

Gestational transient thyrotoxicosis

peak hCG

(10 to 12 weeks),

total T4 and T3 increase.

free T4 and T3 increase slightly

TSH reduced

subclinical or mild overt

hyperthyroidism

slightly low serum TSH

high-normal or mildly elevated serum free T4

gestational transient

thyrotoxicosis

occurs near the end of the first

trimester,

subside as hCGproduction falls

(14 to 18 w).

Hyperemesis gravidarum

• weight loss of 5 percent or more during early pregnancy

• serum hCG estradiol

• hCG has more thyroid-stimulating activity

• TSH lower than those in normal pregnant

• serum free T4 ,

• overt hyperthyroidism.

transient hyperthyroidism of hyperemesis gravidarum

• vomiting,

• NO goiter and ophthalmopathy,

• NO symptoms and signs of hyperthyroidism

• free T4 minimally elevated

• serum T3 may not be elevated

• not require treatment,

• mild and subsides

• as hCG production falls

Trophoblastic hyperthyroidism

In the past,

55 to 60 %

clinically evident hyperthyroidism

between 2005 and

2010,

biochemical hyperthyr 7 %

clinical hyperthyr2 percent

molar pregnancy

Choriocarcinoma

high serum Hcg

requires treatment of the hyperthyroidism

goals of antithyroid drug (ATD) therapy

maintain persistent mild

hyperthyroidism

to prevent fetal hypothyroidism

Overtreatment with

thionamide

• cause fetal goiter

• and primary hypothyroidism

• .

fetal thyroid is more sensitive to the action of antithyroid drugs

the goal of mild hyperthyroidism

• serum free thyroxine (T4) should be maintained at or just

above the tri-spec .normal range

• if the trimester-specific reference range is not available the total T4 and (T3)

should be maintained at 1.5 times above the nonpregnant reference

range.

• TSH should be below the reference range for pregnancy (goal TSH 0.1

to 0.3 mU/L), using the lowest possible dose of medication

these goals requires

Assess

thyroid function

at four-week intervals

with appropriate adjustment of

medication

Indications for treatment

symptomatic,moderate to severe,

overt hyperthyroidism due to Graves', toxic

adenoma, toxic multinodular goiter,

or GTD

TSH <0.05 mU/L

elevations in trimester-spec. free

T4

and/or total T4 and T3 >1.5 times the upper

limit of normal for nonpregnant Pt

Treatment of hyperthyroidism is not required

Transient, subclinical hyperthyr.

(NL total or free T4 and T3 & a

subnormal TSH) in the first tri.

physiologic finding not require TX

hCG-mediated, overt hyperthyr.

gestational transient

thyrotoxicosis.

Hyperemesis gravidarum-associated hyperthyr.

falls by 16 to 18 w

Subclinical and mild,

asymptomatic, overt

hyperthyroidism due to Graves' disease, toxic

adenoma, or toxic multinodular goiter.

Therapeutic options

Limited

for hyperthyroid pregnant women

potential adverse fetal effects of the available TX

. thionamides.

Thyroidectomy in the second

trimester

option for women who are unable to take thionamides.

Beta blockers

metoprolol or propranolol (but not atenolol),

TX tachycardia and tremor.

primary TX for Pt with hydatidiform mole or GTN

who cannot wait for 3-6 w for thionamides to control hyperthyroidism prior to surgery.

avoided long-term TX with beta blockers (>2-6W) in pregnant women

IUGR and hypoglycemia, especially with atenolol

Control of symptoms

beta blockers

start with metoprolol

25-50 mg /d

Propranolol, 20 mg /

6-8h

weaned as soon as the hyperthyroidism is controlled by thionamides

IUGR

hypoglycemia, RDS ,

bradycardia

have been reported after maternal administration

Decrease thyroid hormone synthesis

moderate to severe

hyperthyroidism due to Graves' disease, toxic

adenoma, or toxic multinodular

goiter,

thionamides

first choice to decrease thyroid

hormone synthesis.

Both methimazole and (PTU)

probably cross the placenta

similar effects on the fetal thyroid

Thyroidectomy during pregnancy

–rarely necessary an option for who

cannot tolerate thionamides

allergy or agranulocytosis.

Plasmapheresis rapidly control

hyperthyroidism

Pretreatment evaluation

— Prior to initiating thionamides,

complete blood count

liver profile (bilirubin and transaminases).

We do not use thionamides in

neutrophil count <1000 cells/microL

Choice of thionamide

PTU and methimazole.

depends upon which trimester the drug is

being initiated.

Methimazole is preferred to PTU except

during the first trimester of pregnancy.

Dx prior to pregnancy

–who are taking high doses of methimazole to maintain a euthyroid state.

Elect definitive therapy with surgery or radioiodine prior to pregnancy.

postpone pregnancy until become euthyroid following definitive tx and on replacement therapy.

Switch to PTU before trying to

conceive.

reasonable in younger women

with normal periods

who are expected to conceive within

one to three months.

for older women and women having difficulty conceiving

Switch to PTU as soon as the

pregnancy test is confirmed

It is recommended that a pregnancy test be obtained

weekly.

for women who have already been treated with methimazole for 12 to 18 months,

normal TSH

on low-dose therapy,

(TRAb) negative.

Discontinue methimazole

monitoring TFT(weekly in first trimester, then

monthly).

If hyperthyroidism recurs after DC,

PTU (if relapse in the first trimester)

or methimazole (if relapse occurs after the first trimester).

Diagnosed during the first trimester

symptomatic, moderate to severe hyperthyroidism

should take PTU.

may continue PTU for the remainder of pregnancy

or switch back to methimazole at 16 weeks.

switching

may increase the risk of maternal or fetal hypothyroidism.

switching to methimazole reduces the exposure to PTU,

which has more serious hepatotoxicity than methimazole,

Diagnosed after the first trimester

should take methimazole

observed with maternal use of methimazole and carbimazole but not PTU

aplasia cutis, scalp defect

tracheoesophageal fistulas,

patent vitellointestinal duct,

choanal atresia,

omphalocele, and omphalomesenteric duct anomaly

have also been mild birth defects, including preauricular sinuses and cysts and urinary tract abnormalities, have been observed after PTU

Gestational weeks 6 to 10

Gestational weeks 6 to 10 is the period of

highest risk for birth defects.

PTU is preferred during the first trimester.

reports of severe PTU-related liver failure have raised concerns about the routine use of PTU

Methimazole associated with liver disease

typically due to cholestatic dysfunction

less likely to cause liver failure than PTU.

Initial dosing lowest dose of thionamide

To minimize the risk of hypothyroidism in the fetus,

• lowest dose of thionamide

●Carbimazole 5 to 15 mg daily

●Methimazole 5 to 10 mg daily, or

●PTU 50 mg two to three times daily

Graves' hyperthyroidism

worsens postpartum.

Monitoring thyroid function tests throughout pregnancy

maternal hyperthyroidism in the third trimester

increase the risk of low birth weight

TRAB

if elevated, again at 18 to 22 w & at 30 to 34 W.

TRAb should be measured

who will be taking thionamides,

hyperthyroidism during pregnancy

Disappearance of TRAb

indicates potential remission of Graves'

dose of thionamides can be reduced and potentially discontinued.

High TRAb levels in late pregnancy

an increased risk of fetal and neonatal hyperthyroidism

Adverse effects

– PTU-associated liver failure

at any time during treatment,

sudden onset

rapidly progressive course.

routine monitoring of LFT is not suggested

Patients should be advised to stop their medication and contact their clinician if they develop weakness, malaise, nausea and vomiting, jaundice, dark urine, or light-colored stools.

Some clinicians and their patients prefer

monitor liver function every four weeks

when blood is being drawn to assess thyroid function.

PTU should be discontinued if serum transaminases are greater than three times the upper limit of normal.

This approach has not been shown to reduce the risk of PTU-associated liver failure.

Is there a role for iodine as primary therapy for hyperthyroidism? —

insufficient evidence to recommend routine iodine for the primary treatment of pregnant women with Graves' disease.

Therapies not recommended

●Radioiodine

is absolutely contraindicated

during pregnancy

Fetal thyroid tissue begins to function

by 10 to 12 weeks

can be ablated by radioiodine.

radioiodine before

8 to 10 weeks

does not cause fetal hypothyroidism or

birth defects

FETAL OR NEONATAL HYPERTHYROIDISM—

1 to 5 %of mothers with hyperthyroidism (active or treated) have fetuses or neonates with hyperthyroidism

rare, but severe (even life threatening)

effects on neural development.

FHR (>160),

fetal goiter,

advanced bone age,

poor growth,

craniosynostosis

. Cardiac failure and hydrops may occur with severe disease

Measurement of maternal antibodies

(TRAb)

during the third trimester

(24 to 28 weeks)

predict

infants

at higher risk for Graves'

TRAb is > > three to five times the upper

limit of normal.

fetus or infant is more likely to have Graves' hyperthyroidism

TRAb >>>> three times the upper limit of normal, monitoring is necessary.

Fetal monitoring—

All fetuses of women with

Graves' disease should be

monitored for signs of fetal

thyrotoxicosis

●Fetal heart rate

●Fetal growth rate

Breastfeeding

(PTU)-associated hepatotoxicity,

suggest methimazole

rather than PTU for nursing mothers.

Methimazole should be administered

following a feeding in divided doses.

مراجعه کردند اقدامات ۷معادلTSHساله سه ماه قبل از بارداری۲۵بیمار خانم ❑

و بعد از زایمان حوالی زایمانسه ماهه اولمادر قبل از بارداریلازم در این

چگونه میباشد

نا درمانجهتمعادل سه و نیمTSHساله با سابقه نازایی۴۰خانم ❑

اقدامات در مورد تیروئید چگونه استمراجعه کردندباروری

اقدامات قبل از بارداریTSH ۳دوبار سقطباسابقهسال۳۵خانم ❑

Thionamidesprimary treatment of

hyperthyroidism

due to Graves' disease, toxic adenoma, or toxic

multinodular goiter during pregnancy.

PTU or methimazole

Low thyroid function at birth

one-half of neonates whose mothers received during

pregnancy who had normal T4

were normal

(IQ) scores of children who exposed to thionamides in utero

(but were euthyroid at birth)

Ultrasound — Fetal thyroid ultrasound monitoring should be

performed in pregnant women with active Graves' hyperthyroidism and/or

women with serum TRAb levels greater than two to three times the

upper limit of normal

Fetal blood sampling — Because of the potential risk of fetal loss, we

suggest not performing umbilical vein sampling routinely in pregnant women with Graves' disease.

• Monitoring and dose adjustments — Graves' disease frequently ameliorates in the third trimester. Whenever possible, based on thyroid function tests and assessment of TRAb measurements, thionamides should be tapered and potentially discontinued during the third trimester.

• Toxic adenoma and toxic multinodular goiter are unlikely to remit during pregnancy, and therefore, women with hyperthyroidism due to these disorders are usually maintained on thionamides throughout pregnancy.

• TRAb –

• hyperthyroidism during pregnancy

• who will be taking thionamides,

• serum TRAb should be measured at diagnosis

• if elevated, again at 18 to 22 weeks and at 30 to 34 weeks of gestation.

• Disappearance of TRAb indicates potential remission of Graves' disease, and the dose of thionamides can be reduced and potentially discontinued.

• High TRAb levels in late pregnancy are associated with an increased risk of fetal and neonatal hyperthyroidism

• , the risks to the fetus were dependent upon the timing of exposure during pregnancy [45]. Spontaneous miscarriage was more likely when exposure (100 mGy) occurred during the first two weeks (prior to implantation). Exposure during organogenesis (from two weeks gestation) may result in birth defects. After fetal thyroid has developed the capacity to capture iodine (12 to 14 weeks), there is a risk of fetal thyroid ablation and the attendant effects on neurocognitive development. If treatment is given during pregnancy, there needs to be full disclosure. Depending on the couple's wishes, termination of pregnancy might be considered, but the limited data that are available suggest normal outcomes, if the exposure is in the first trimester.