Transcript Thyroid Disease in Pregnancy

Thyroid Disease in Pregnancy
Chantarojanasiri T. ,MD.
OUTLINE
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Normal physiology& changes during pregnancy
Hyperthyroid
Hypothyroid
Postpartum thyroid disease
Thyroid cancer
Euthyroid with autoimmune thyroid disease
Practice guidelines
Normal physiology
• The hypothalamic pituitary axis
• Thyrotropin-releasing hormone (TRH)
– Produced in a tonic fashion in the paraventricular
nucleus of the hypothalamus.
• TSH has an α and β subunit;β subunit confers
specificity.
• TSH secretion regulated by negative feedback
from circulating thyroid hormone, dopamine, and
somatostatin.
• TSH then stimulates the thyroid gland to
produce, as well as secrete, thyroxine(T4) and
triiodothyronine (T3).
• The rate-limiting
step is iodide
trapping
– mediated by TSH.
• nonpregnant
state, 80 mg/d to
100 mg/d of
iodine taken up
• 20% of the intake
is cleared by the
thyroid gland;
remainder renally
Physiologic adaptation during pregnancy
• increase in thyroid-binding globulin
– secondary to an estrogenic stimulation of TBG
synthesis and reduced hepatic clearance of TBG ;two
to threefold
– levels of bound proteins, total thyroxine, and total
triiodothyronine are increased and resin
triiodothyronine uptake (RT3U) is decreased
– begins early in the first trimester, plateaus during
midgestation, and persists until shortly after delivery
– decrease in its hepatic clearance,estrogen-induced
sialylation
• free T4 and T3 increase slightly during the first trimester
in response to elevated hCG. decline to nadir in third
trimester
• human chorionic gonadotropin (hCG)
– intrinsic thyrotropic activity
– begins shortly after conception, peaks around
gestational week 10,declines to a nadir by about
week 20
– directly activate the TSH receptor
– partial inhibition of the pituitary gland (by crossreactivity of the α subunit)
• transient decrease in TSH between Weeks 8 and 14
• mirrors the peak in hCG concentrations
– 20% of normal women, TSH levels decrease to less
than the lower limit of normal
TSH
hCG
• A decrease in basal TSH of 0.1 mU/L was
observed for every 10,000 IU/L increment in
hCG
• reduction in plasma iodide
– fetal :monodeiodinase types II and III in the placenta
– increased maternal glomerular filtration rate-increased renal clearance of iodide throughout
pregnancy
• transplacental passage of T4 and iodide and
placental metabolism of iodothyronines
– stimulate the maternal thyroid ; depleting the maternal
circulation of thyroid hormone and its precursors
• Hypothyroid;25% to 47% average dosage
increase during pregnancy
• increased serum thyroid stimulating hormone
(TSH) and thyroglobulin concentrations, relative
hypothyroxinemia, and occasional goiter
formation
– Esp. from area with borderline iodine sufficiency
• associated with increase in thyroid gland size in
15%
EFFECTS OF PREGNANCY ON THYROID
PHYSIOLOGY
Physiologic Change
Thyroid-Related Consequences
↑ Serum thyroxine-binding globulin
↑ Total T4 and T3; ↑ T4 production
↑ Plasma volume
↑ T4 and T3 pool size; ↑ T4
production; ↑ cardiac output
D3 expression in placenta and (?) uterus
↑ T4 production
First trimester ↑ in hCG
↑ Free T4; ↓ basal thyrotropin; ↑ T4
production
↑ Renal I- clearance
↑ Iodine requirements
↑ T4 production; fetal T4 synthesis during
second and third trimesters
↑ Oxygen consumption by fetoplacental
unit, gravid uterus, and mother
↑ Basal metabolic rate; ↑ cardiac
output
Hyperthyroidism and pregnancy
• 0.2% of pregnancies
• prevalence 0.1% to 0.4%, with 85% Graves’
disease
– Single toxic adenoma, multinodular toxic goiter, and
subacute thyroiditis
– gestational trophoblastic disease,viral thyroiditis and
tumors of the pituitary gland or ovary (struma ovarii)
• TSH is depressed and fT4 and fTI are increased.
• The RT3U that normally is decreased in
pregnancy is increased in hyperthyroidism.
Hyperthyroidism and pregnancy
• serum TSH value <0.01 mU/L and also a high
serum free T4 value
• may be difficult to determine the cause
– thyroid radionuclide imaging is contraindicated in pregnant
women.
• Measurement of thyrotropin receptor antibody (thyroid
stimulating immunoglobulins)  Graves' disease during
pregnancy
• transient hyperthyroidism in hyperemesis gravidarum
and gestational transient thyrotoxicity (GET)
Hyperthyroidism and pregnancy
• Severe maternal hyperthyroidism
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increased risk of stillbirth
preterm delivery
intrauterine growth restriction
Preeclampsia
heart failure
spontaneous abortion
Fetal thyroid hyperfunction or hypofunction caused by
TSHRAbs
Fetal goiter from excessive antithyroid drug treatment
Neonatal thyrotoxicosis
Increased perinatal and maternal mortality
Decreased IQ of offspring because of excessive use
of antithyroid drugs
Transient hyperthyroidism during pregnancy &
gestational transient thyrotoxicity (GET)
• hyperemesis gravidarum
– severe nausea and vomiting leading to a 5% loss of body weight,
dehydration, and ketosis.
– absence of goiter and ophthalmopathy, and absence of the common
symptoms and signs of hyperthyroidism
– higher serum hCG and estradiol concentrations
– 60% have a subnormal serum TSH level (< 0.4 mU/L),50% have
an elevated serum free T4 concentration
– Severity positively correlated with maternal free T4 levels but not
to thyroid function.
• 12% elevated free T3 index
– believed to be related to hCG stimulation of the thyroid gland
– Normalization of T4 levels by midgestation.
– Treatment is supportive care
• GET
– first trimester
– related to hCG stimulation of the thyroid gland
– symptoms of hyperthyroidism and elevated free T4
levels.
– The thyroid gland usually is not enlarged
– resolution of symptoms parallels the decline in hCG
levels
– usually resolves spontaneously by 20 weeks’
gestation
– beyond 20 weeks,repeat evaluation for other causes
Trophoblastic hyperthyroidism
• hydatidiform mole (molar pregnancy) &
choriocarcinoma.
– high serum hCG concentrations and abnormal hCG
isoforms
• 55 to 60 percent had clinically evident
hyperthyroidism
• normal thyroid gland and few symptoms of
thyroid hormone excess.
• some :findings of hyperthyroidism and a diffuse
goiter
– ophthalmopathy is not present
• Nausea and vomiting may predominate
subclinical hyperthyroidism
• associated with osteoporosis,
cardiovascular morbidity, and progression
to overt thyrotoxicosis and thyroid failure.
• not associated with adverse pregnancy
outcomes
• does not warrant treatment.
Graves’ disease
• 95% of thyrotoxicosis during pregnancy.
• activity level fluctuate during gestation, with
– exacerbation during the first trimester
– gradual improvement during the latter half.
– exacerbation shortly after delivery
• clinical scenarios.
– stable Graves’ disease receiving thionamide therapy
with exacerbation during early pregnancy.
– in remission with a relapse of disease.
– without prior history diagnosed with Graves’ disease
de novo during pregnancy.
Graves’ disease
• Diagnosis
– difficult :hypermetabolic symptoms in normal
pregnancy
– thyroid examination: goiter (with or without bruit)
– suppressed serum TSH level and usually elevated
free and total T4 serum concentrations.
– TSH receptor antibodies
• complications related to the duration and control
of maternal hyperthyroidism
• autoantibodies mimic TSH can cross the
placenta and cause neonatal Graves’ disease
Graves’ disease
• Pregnancy outcome
• preterm labor
– untreated (88%)/partially treated(25%) /adequately treated (8%) [
• preeclampsia
– untreated twice
• stillbirth
– untreated (50%) /partially treated (16%) /adequately treated (0%)
• small for gestational age
• congenital malformations unrelated to thionamide therapy
• Mother may have thyroid-stimulating hormone-binding inhibitory
immunoglobulin (TBII),
– cause transient neonatal hypothyroidism
– fetal bradycardia, goiter,and growth restriction
Graves’ disease
• Neonatal thyrotoxicosis :
– 1% of infants
– occur in euthyroid mother or has had surgical or
radioactive 131I treatments before pregnancy
– fetal ultrasound to exclude evidence of fetal
thyrotoxicosis (eg, an anterior fetal neck mass) or
fetal tachycardia.
– fetal goiter, advanced bone age, poor growth, and
craniosynostosis, Cardiac failure and hydrops
– Fetal blood sampling — Fetal blood for thyroid
function tests by percutaneous umbilical vein
sampling after 20 weeks of gestation
• High maternal TSH receptor-stimulating antibody levels Fetal
signs suggestive of thyroid disease History of a prior baby
with hyperthyroidism
Thyroid storm
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obstetric emergency
extreme metabolic state
10% of pregnant women with hyperthyroidism
high risk of maternal cardiac failure.
fever, change in mental status, seizures, nausea,
diarrhea, and cardiac arrhythmias.
• inciting event (eg, infection, surgery, labor/delivery) and
a source of infection
• treatment immediately, even if serum free T4, free T3,
and TSH levels are not known.
• untreated thyroid storm can be shock, stupor, and coma.
Guidelines for clinical management of maternal
hyperthyroidism during pregnancy
• 1. Use the lowest dosage of thionamide
(preferably PTU) to maintain maternal total T4
concentrations in the upper one third of normal
to slightly elevated range for pregnancy.
– Normal range of total T4 during pregnancy is
estimated to be 1.5 times the nonpregnant state
• 2. Monitor maternal total T4 serum concentration
every 2–4 weeks, and titrate thionamide as
necessary.
– Monitoring serum TSH may become useful later.
Shane O. LeBeau, Endocrinol Metab Clin N Am
35 (2006) 117–136
Guidelines for clinical management of maternal
hyperthyroidism during pregnancy
• 3. Measure TSH receptor antibodies (thyroidstimulating immunoglobulins or TSH receptor
binding inhibitory immunoglobulins) at 26–28
weeks to assess risk of fetal/neonatal
hyperthyroidism.
– TSH receptor antibody measurement is crucial in
hypothyroid levothyroxine-treated women with a prior
history of Graves’ disease, who do not appear
thyrotoxic.
• 4. Perform fetal ultrasound at weeks 26–28 to
assess potential fetal response to thionamide
treatment and effect of TSH receptor antibodies
on fetal thyroid function
Guidelines for clinical management of maternal
hyperthyroidism during pregnancy
• 5. Consider thyroidectomy if persistently high
doses of thionamide (PTU > 600 mg/d or MMI >
40 mg/d) are required,or if the patient cannot
tolerate thionamide therapy.
• 6. β-Adrenergic blocking agents and low doses
of iodine may be used perioperatively to control
hyperthyroid state.
• 7. Check fetal cord blood at delivery for TSH and
T4.
Treatment
• Thionamides
• propylthiouracil (PTU) and methimazole(MMI)
• Both cross the placenta with equal transfer
kinetics.
• Both can cause fetal goiter and hypothyroidism,
usually mild and transient & dose-dependent
• median time to normalization of maternal thyroid
function
– 7 weeks with PTU and 8 weeks with MMI
• PTU more highly bound to albumin
– theorize that MMI crosses the placenta in higher
concentrations
Treatment
• Thionamides
• maternal :rash
• rare birth defects in MMI: aplasia cutis, choanal
atresia,esophageal atresia, and minor dysmorphic
features
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Low thyroid function at birth ½ neonates whose mothers received PTU or
MMI and had serum T4 concentrations within the normal (non-pregnant)
range
– normal IQ scores
• Graves’ disease may ameliorate
– thionamide discontinued in 30% during the final weeks
– fall in serum TSH receptor-stimulating antibody concentrations and a
rise in TSH receptor-blocking antibodies.
• Graves' hyperthyroidism can worsen postpartum
• do not recommend the use of T4 with thionamide therapy during
pregnancy.
Treatment
• β-Adrenergic blockers
• weaned as soon as the hyperthyroidism is controlled
• occasional cases of neonatal growth restriction,
hypoglycemia, respiratory depression, and bradycardia
• increased frequency of first-trimester miscarriages
• avoiding in the first trimester
• Iodides
• past reports of neonatal hypothyroidism after exposure
to iodine
• low-dose potassium iodide may be considered
– Preparation for thyroidectomy
– thionamide-intolerant patients refusing surgery.
Treatment
• Surgery
• Subtotal thyroidectomy :
– persistently high dosages of thionamides (PTU > 600 mg/d, MMI > 40
mg/d) are required to control maternal disease
– allergic or intolerant of both thionamides
– noncompliant with medical therapy
– compressive symptoms
• second trimester, before gestational week 24
• prepared with a β-adrenergic blocking agent and a 10- to 14-day
course of potassium iodide
Treatment
• Radioactive iodine therapy
• contraindicated
• fetal thyroid gland begins to concentrate iodine after
gestational week 10, Fetal thyroid tissue is present by 10
to 12 weeks
– predisposing to congenital hypothyroidism
• Nursing
• Breast feeding in mothers taking PTU or MMI is safe
• Thyroid function in newborn infants is unaffected
• PTU is preferred because it is less concentrated in
breast milk
Hypothyroidism in pregnancy
• elevated serum TSH concentration:2.5%
of pregnancies
• In iodine-sufficient environment
– Hashimoto’s thyroiditis
– prior radioactive iodine treatment
– surgical ablation of Graves’ disease
– less common causes: overtreatment of hyperthyroidism with
thionamides, transient hypothyroidism owing to postpartum
thyroiditis, medications that alter the absorption or metabolism of
levothyroxine, and pituitary/hypothalamic disease)
Hypothyroidism in pregnancy
• diagnosis
• Symptoms masked by the hypermetabolic state of
pregnancy.
• 20% to 30% overt hypothyroidism develop symptoms
• weight gain, lethargy, decrease in exercise capacity, and
intolerance to cold,constipation, hoarseness, hair loss,
brittle nails, dry skin, goiter, or delay in the relaxation
phase of the deep tendon reflexes
• Elevated serum TSH concentration
• Central hypothyroidism do not manifest an elevated
serum TSH level
Hypothyroidism in pregnancy
• Pregnancy outcome
• depends on the severity of disease and adequacy of
treatment
• Gestational hypertension in overtly hypothyroid women
(36%) vs subclinical disease (25%) or the general
population (8%)
• Overt hypothyroid vs subclinical disease,
– increased use of cesarean section because of fetal distress
– placental abruption, anemia, andpostpartum hemorrhage
increased rates of miscarriage, preeclampsia,placental
abruption, growth restriction, prematurity and stillbirths
• fetuses are at risk for impaired neurologic development
low-birth-weight neonates
Hypothyroidism in pregnancy
• TSH can be elevated with or without suppressed levels
of free T4.
• antithyroid autoantibodies (eg, antithyroglobulin,
antithyroid
• peroxidase) are present
• elevated creatine phosphokinase, cholesterol, and liver
function tests
• 5% to 8% prevalence of hypothyroidism in type I
diabetes
• mellitus and women who have type I diabetes have a
25% risk of developing postpartum thyroid dysfunction
Causes of hypothyroidism
• Worldwide, the most common is iodine deficiency.
• impaired neurologic development; severe mental
retardation, deafness,
• muteness, and pyramidal or extrapyramidal syndromes;
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Hashimoto’s thyroiditis
Idiopathic hypothyroidism; atrophic thyroid gland
and absent antithyroid antibodies.
131I treatment for Graves’ disease and thyroidectomy
Drugs interfere with the metabolism of thyroid hormones
Subclinical hypothyroidism
• normal free T4 level
• elevated TSH above the upper limit of reference
range (4.5–10.0mIU/L)
– thresholds based on gestational age.
• TSH in the first half of pregnancy is 3.0 mIU/L
• prevalence of subclinical hypothyroidism 2–5%
• increased risk of placental abruption and
preterm birth
• important to monitor TSH and free T4 levels.
• 2–5% progress to overt hypothyroidism each
year
Isolated maternal hypothyroxinemia
• normal TSH
• free T4 below 0.86 ng/dl.
• In the first half of pregnancy,
– prevalence 1.3%.
• not associated with adverse perinatal
outcome
Guidelines for clinical management of maternal
hypothyroidism during pregnancy
• 1. Check serum TSH level as soon as pregnancy is
confirmed.
• 2. For newly diagnosed hypothyroid women, initial
levothyroxine dosage is based on severity of
hypothyroidism. For overt hypothyroidism, administer 2
mcg/kg/d. If TSH is < 10 mU/L, initial dose of 0.1 mg/d
may be sufficient.
• 3. For previously diagnosed hypothyroid women, monitor
serum TSH every 3–4 weeks during first half of
pregnancy and every 6 weeks thereafter.
• 4. Adjust levothyroxine dosage to maintain serum TSH ≤
2.5 mU/L.
• 5. Monitor serum TSH and total T4 levels 3–4 weeks
after every dosage adjustment. When levothyroxine
dosage achieves equilibrium, resume monitoring TSH
alone
Shane O. LeBeau, Endocrinol Metab Clin N Am
35 (2006) 117–136
Treatment
• 6. Levothyroxine ingestion should be separated from
prenatal vitamins containing iron, iron and calcium
supplements,and soy products by at least 4 hours to
ensure adequate absorption.
• 7. After delivery, reduce levothyroxine to prepregnancy
dosage, and check serum TSH in 6 weeks
• adjusting levothyroxine
– 1. TSH < 10 mU/L, increase 0.05 mg/d.
– 2. TSH =10–20 mU/L, increase 0.075 mg/d.
– 3. TSH > 20 mU/L, increase 0.1 mg/d.
• normal range for total T4 concentrations during pregnancy is 1.5
times the nonpregnant
• iodine :prenatal vitamin 220 mg/day
Postpartum thyroid disease
• Postpartum thyroiditis
– Dx: documenting abnormal TSH (elevated or
suppressed) levels during the first year postpartum in
the absence of positive TSI or a toxic nodule
– hypo- or hyperthyroidism
– classic presentation :
– transient hyperthyroid phase that occurs 6 weeks to 6
months postpartum
– followed by a hypothyroid phase that lasts for up to 1
year postpartum
Postpartum thyroiditis
• autoimmune disorder with a self-limited hyperthyroid phase
• within one year after parturition.
• Presentations
– Transient hyperthyroidism alone
– Transient hypothyroidism alone
– Transient hyperthyroidism followed by hypothyroidism
and then recovery.
• can also occur after spontaneous or induced
abortion
• 3 to 16 percent
– higher, up to 25 percent, in women with type 1 diabetes mellitus
,and in women with positive antithyroid antibodies (normal
thyroid function)
Postpartum thyroiditis
• like painless thyroiditis
– variant form of chronic autoimmune thyroiditis (Hashimoto's thyroiditis).
• high serum concentrations of anti-peroxidase antibodies
• many eventually become hypothyroid or have a goiter
• high serum antithyroid antibody concentrations early in pregnancy
– decline later (as immunologic tolerance increases during pregnancy)
– rise again after delivery
• subclinical thyroid autoimmune disease early in pregnancy and soon
after
• Progression to permanent hypothyroidism
– related to higher TSH concentrations and the antiperoxidase antibody
titer
– maternal age and female sex of the infant
• Postpartum thyroiditis is likely to recur after subsequent pregnancies
• distinguished from Graves' hyperthyroidism,
– hyperthyroidism in postpartum thyroiditis is usually
mild (both clinically and biochemically),
– thyroid enlargement is minimal
– Graves' ophthalmopathy is absent.
– by reevaluation in three to four weeks: postpartum
thyroiditis improved
• lymphocytic hypophysitis,
– TSH normal or low, low free T4
– postpartum thyroiditis, TSH elevated with decreased
FT4.
Postpartum thyroiditis
• antithyroids :no role.
• Hypothyroid :may require treatment and some
• significant rate of residual hypothyroidism
– Recommend:maintain thyroxine until childbearing is complete,
with an attempt to wean off medication 1 year after the last
delivery
• Postpartum--signs/symptoms of thyroid dysfunction
– symptoms mimic normal postpartum changes
• TSH, free T4, and antithyroid antibodies levels
• postpartum depression and postpartum thyroiditis
Postpartum Graves’ disease
• 60% Graves’ disease in the reproductive
years; postpartum onset
• euthyroid patients with Graves’ disease
with TSI
– increased risk of developing recurrent Graves’
disease if antithyroid medication was withheld
• TSIs differentiate postpartum Graves’
disease from postpartum thyroiditis with a
hyperthyroid component.
Thyroid cancer
• Thyroid tumors ;most common endocrine neoplasms.
• thyroid cancer accounts for 1% of all cancers. ¾ women; 1/2
reproductive years.
• biopsy ,Serum TSH and free T4 levels,ultrasonography & Fine
needle aspiration
• Radionucleotide scanning is contraindicated during pregnancy
• malignant or suspicious for papillary cancer, surgery at the earliest
safe period
• no evidence that pregnancy causes a reactivation of thyroid cancer
or that exposure to radioactive iodine poses a risk to future
pregnancies
• maintained on thyroid replacement therapy with monitoring of TSH
and free T4 levels every 8 weeks.
Euthyroidism with autoimmune
thyroid disease
• increased risk for spontaneous
miscarriage, subclinical hypothyroidism,
and postpartum thyroiditis
• Increase in serum TSH levels
– most normal
• presence of antithyroid antibodies
– lack of thyroidal reserve in response to the
stimulatory effects of pregnancy.
Euthyroidism with autoimmune
thyroid disease
• recommend initiating levothyroxine therapy in
women with antithyroid antibodies
– before pregnancy
– TSH level greater than 2.5 mU/L.
• Serum TSH should be monitored throughout
pregnancy in all antithyroid antibody–positive
women
• maintain the TSH concentration at 2.5 mU/L or
less.
CLINICAL PRACTICE GUIDELINE
Management of Thyroid Dysfunction during Pregnancy
and Postpartum: An Endocrine Society Clinical
Practice Guideline
• 1. HYPOTHYROIDISM AND PREGNANCY: MATERNAL
• AND FETAL ASPECTS
• 1.1.1. maternal hypothyroidism should be avoided.Targeted case
finding is recommended at the first prenatalvisit or at diagnosis of
pregnancy
• 1.1.2. If hypothyroidism diagnosed before pregnancy, adjust
preconception T4 dose to reach a TSH ≤2.5 U/ml before pregnancy.
• 1.1.3. T4 dose incremented by 4–6 wk gestation and 30–50%
increase in dosage.
• 1.1.4. If overt hypothyroidism is diagnosed during pregnancy, thyroid
function tests should be normalized as rapidly as possible.
– The T4 dosage should be titrated to rapidly ,maintain serum TSH ≤ 2.5
U/ml in the first trimester (or 3 U/ml in the second and third trimesters)
or to trimester-specific normal TSH ranges.
– Thyroid function tests remeasured within 30–40 d.
Abalovich et al. • Guideline: Thyroid Dysfunction during and after Pregnancy
J Clin Endocrinol Metab, August 2007, 92(8) (Supplement):S1–S47
• 1.1.5. Women with thyroid autoimmunity who are
euthyroid in the early stages of pregnancy are at risk of
developing hypothyroidism and should be monitored for
elevation of TSH above the normal range
• 1.1.6. Subclinical hypothyroidism ;associated with an
• adverse outcome for both the mother and offspring.
– T4 treatment - improve obstetrical outcome but has not been
proved to modify long-term neurological development in the
offspring.
– Recommends T4 replacement in women with subclinical
hypothyroidism.
• 1.1.7. After delivery, most hypothyroid women need a
• decrease in the T4 dosage they received during
pregnancy
• 2. MANAGEMENT OF MATERNAL
HYPERTHYROIDISM: MATERNAL (A) AND FETAL (B)
ASPECTS
• 2.1.a.1. subnormal serum TSH
– hyperthyroidism must be distinguished from both normal
physiology during pregnancy and hyperemesis gravidarum
– Differentiation of Graves’ disease from gestational thyrotoxicosis
by evidence of autoimmunity, a goiter, and presence of TRAb.
• 2.1.a.2. For overt hyperthyroidism due to Graves’
disease or hyperfunctioning thyroid nodules,
– ATD therapy should be either initiated (for those with new
diagnoses) or adjusted (for those with a prior history)
– maintain the maternal thyroid hormone levels for free T4 in the
upper nonpregnant reference range.
• 2.1.a.3. methimazole may be associated with congenital
anomalies, propylthiouracil should be used as a first-line
drug,
– especially during first-trimester organogenesis.
– Methimazole may be prescribed if propylthiouracil is not
available or if a patient cannot tolerate or has an adverse
response to propylthiouracil
• 2.1.a.4. Subtotal thyroidectomy for maternal Graves’
disease if
– 1) a patient has a severe adverse reaction to ATD therapy,
– 2)persistently high doses of ATD are required
– 3) a patient is not adherent to ATD therapy and has uncontrolled
hyperthyroidism.
– optimal timing of surgery is in the second trimester.
• 2.1.a.5. no evidence that treatment of subclinical
hyperthyroidism improves pregnancy outcome
• 2.1.b.1 TRAb (either TSH receptor-stimulating or –
binding antibodies) freely cross the placenta and can
stimulate the fetal thyroid.
– These antibodies should be measured before pregnancy or by
the end of the second trimester in mothers with current Graves’
disease, with a history of Graves’ disease and treatment with
131I or thyroidectomy, or with a previous neonate with Graves’
disease.
– Women who have a negative TRAb and do not require ATD have
a very low risk of fetal or neonatal thyroid dysfunction.
• 2.1.b.2. 131I should not be given to a woman who is or
may be pregnant.
– radiation danger to the fetus, including thyroid destruction if
treated after the 12th week of gestation.
• There are no data for or against recommending termination of
pregnancy after 131I exposure
• 2.1.b.3. In women with elevated TRAb or in women treated with
ATD, fetal ultrasound should be performed to look for evidence of
fetal thyroid dysfunction
– growth restriction, hydrops, presence of goiter, or cardiac failure.
• 2.1.b.4. Umbilical blood sampling should be considered only if the
diagnosis of fetal thyroid disease is not reasonably certain from the
clinical data and if the information gained would change the
treatment.
• 2.1.b.5. All newborns of mothers with Graves’ disease should be
evaluated for thyroid dysfunction and treated if necessary
• 3. GESTATIONAL HYPEREMESIS AND
HYPERTHYROIDISM
• 3.1. Thyroid function tests should be measured in all
patients with hyperemesis gravidarum (5% weight loss,
dehydration, and ketonuria)
• 3.2. Few women with hyperemesis gravidarum will
require ATD treatment.
• Overt hyperthyroidism believed due to coincident
Graves’ disease should be treated with ATD.
• Gestational hyperthyroidism with clearly elevated thyroid
hormone levels (free T4 above the reference range or
total T4 150% of top normal pregnancy value and TSH
0.1 U/ml) and evidence of hyperthyroidism may require
treatment as long as clinically necessary
• 4. AUTOIMMUNE THYROID DISEASE AND
MISCARRIAGE
• 4.1. universal screening for antithyroid antibodies and
possible treatment cannot be recommended at this time.
• 5. THYROID NODULES AND CANCER
• 5.1. Fine-needle aspiration (FNA) cytology should be
performed for thyroid nodules larger than 1 cm.
– Ultrasound-guided FNA minimizing inadequate sampling.
• 5.2. When nodules are discovered in the first or early
second trimester to be malignant on cytopathological
analysis or exhibit rapid growth,
– surgery should be offered in the second trimester before fetal
viability.
• For papillary cancer or follicular neoplasm without
evidence of advanced disease
– prefer to wait until the postpartum period for definitive surgery
– reassured that most well differentiated thyroid cancers are slow
growing
– surgical treatment soon after delivery is unlikely to adversely
affect prognosis
• 5.3. administer thyroid hormone to achieve a suppressed
but detectable TSH in pregnant women with a previously
treated thyroid cancer or an FNA positive for or
suspicious for cancer and those who elect to delay
surgical treatment until postpartum.
• High-risk patients benefit from a greater degree of TSH
suppression
• free T4 or total T4 levels should ideally not be increased
above the normal range for pregnancy.
• 5.4. RAI administration with 131I should not be given to
women who are breastfeeding.
• pregnancy should be avoided for 6 months to 1 yr in
women with thyroid cancer who receive therapeutic RAI
doses to ensure stability of thyroid function and confirm
remission of thyroid cancer.
• 6. IODINE NUTRITION DURING PREGNANCY
• 6.1. Women of childbearing age ; average iodine intake 150 g/d.
• pregnancy and breastfeeding women should increase intake to 250
g
• 6.2. Iodine intake during pregnancy and breastfeeding should not
exceed twice the daily recommended nutritional intake for iodine, i.e.
500 g iodine per day
• 6.3. To assess the adequacy of the iodine intake during pregnancy
in a population, urinary iodine concentration should be measured in
a cohort of the population.
– Urinary iodine concentration should ideally range between 150 and 250
g/liter.
• 6.4. To reach the daily recommended nutrient intake for iodine,
multiple means must be considered, tailored to the iodine intake
level in a given population.
– 1) countries with iodine sufficiency and/or with a well established
universal salt iodization (USI) program,
– 2) countries without a USI program or an established USI program
where the coverage is known to be only partial, and finally
– 3) remote areas with no accessible USI program and difficult
socioeconomic conditions.
• 7. POSTPARTUM THYROIDITIS
• 7.1. There are insufficient data to recommend screening
of all women for PPT.
• 7.2. Women known to be thyroid peroxidase antibody
positive should have a TSH performed at 3 and 6
months postpartum
• 7.3. The prevalence of PPT in women with type 1
diabetes is 3-fold greater than in the general population.
• Postpartum screening (TSH determination) is
recommended for women with type 1 diabetes mellitus at
3 and 6 months postpartum
• 7.4. Women with a history of PPT have a markedly
increased risk of developing permanent primary
hypothyroidism in the 5- to 10-yr period after the episode
of PPT.
• An annual TSH level should be performed in these
women.
• 7.5. Asymptomatic women with PPT who have a TSH
above the reference range but less than 10 U/ml and
who are not planning a subsequent pregnancy do not
necessarily require intervention but should be
remonitored in 4–8 wk.
• Symptomatic women and women with a TSH above
normal and who are attempting pregnancy should be
treated with levothyroxine.
• 7.6. There is insufficient evidence to conclude whether
an association exists between postpartum depression
and either PPT or thyroid antibody positivity (in women
who did not develop PPT).
• women with postpartum depression should be screened
for hypothyroidism and appropriately treated.
• 8. SCREENING FOR THYROID
DYSFUNCTION DURING PREGNANCY
• 1. Women with a history of hyperthyroid or
hypothyroid disease, PPT, or thyroid lobectomy.
• 2. Women with a family history of thyroid
disease.
• 3. Women with a goiter.
• 4. Women with thyroid antibodies (when known).
• 5. Women with symptoms or clinical signs
suggestive of thyroid underfunction or
overfunction, including anemia,elevated
cholesterol, and hyponatremia.
• 6. Women with type I diabetes.
• 7. Women with other autoimmune disorders.
• 8. Women with infertility who should have
screening with TSH as part of their infertility
work-up.
• 9. Women with previous therapeutic head or
neck irradiation.
• 10. Women with a history of miscarriage or
preterm delivery.
References
• 1. LeBeau& Mandel.Thyroid Disorders During
Pregnancy.Endocrinol Metab Clin N Am 35 (2006) 117–
136.
• 2. Neale et al. Thyroid Disease in Pregnancy.Clin
Perinatol 34 (2007) 543–557.
• 3. Abalovich et al. • Guideline: Thyroid Dysfunction
during and after Pregnancy. J Clin Endocrinol Metab,
August 2007, 92(8) (Supplement):S1–S47.
• 4. Kronenber: Williams Textbook of Endocrinology, 11th
ed.
• 5. Up To Date ver.15.1