Thyroid Disease in Pregnancy

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Thyroid Disease in Pregnancy

• Chantarojanasiri T. ,MD.

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OUTLINE

• Normal physiology changes during pregnancy
• Hyperthyroid
• Hypothyroid
• Postpartum thyroid disease
• Thyroid cancer
• Euthyroid with autoimmune thyroid disease
• Practice guidelines

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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 a and ß subunitß 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).

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• 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

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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

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• 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
  cross-reactivity of the a 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

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hCG
TSH
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• 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

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• Hypothyroid25 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

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EFFECTS OF PREGNANCY ON THYROID PHYSIOLOGY
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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.

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Hyperthyroidism and pregnancy

• serum TSH value lt0.01 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)

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Hyperthyroidism and pregnancy

• Severe maternal hyperthyroidism
• 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

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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 (lt 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

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• 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

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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

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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.

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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.

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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

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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

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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

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Thyroid storm

• 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.

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Guidelines for clinical management of
maternalhyperthyroidism 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 24 weeks, and titrate thionamide as
  necessary.
• Monitoring serum TSH may become useful later.

Shane O. LeBeau, Endocrinol Metab Clin N Am 35
(2006) 117136
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Guidelines for clinical management of
maternalhyperthyroidism during pregnancy

• 3. Measure TSH receptor antibodies
  (thyroid-stimulating immunoglobulins or TSH
  receptor binding inhibitory immunoglobulins) at
  2628 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 2628 to
  assess potential fetal response to thionamide
  treatment and effect of TSH receptor antibodies
  on fetal thyroid function

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Guidelines for clinical management of
maternalhyperthyroidism during pregnancy

• 5. Consider thyroidectomy if persistently high
  doses of thionamide (PTU gt 600 mg/d or MMI gt 40
  mg/d) are required,or if the patient cannot
  tolerate thionamide therapy.
• 6. ß-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.

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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

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Treatment

• Thionamides
• maternal rash
• rare birth defects in MMI aplasia cutis, choanal
  atresia,esophageal atresia, and minor dysmorphic
  features
• 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.

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Treatment

• ß-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.

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Treatment

• Surgery
• Subtotal thyroidectomy
• persistently high dosages of thionamides (PTU gt
  600 mg/d, MMI gt 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 ß-adrenergic blocking agent and a
  10- to 14-day course of potassium iodide

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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

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Hypothyroidism in pregnancy

• elevated serum TSH concentration2.5 of
  pregnancies
• In iodine-sufficient environment
• Hashimotos 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)

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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

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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

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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

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Causes of hypothyroidism

• Worldwide, the most common is iodine deficiency.
• impaired neurologic development severe mental
  retardation, deafness,
• muteness, and pyramidal or extrapyramidal
  syndromes
• Hashimotos 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

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Subclinical hypothyroidism

• normal free T4 level
• elevated TSH above the upper limit of reference
  range (4.510.0mIU/L)
• thresholds based on gestational age.
• TSH in the first half of pregnancy is 3.0 mIU/L
• prevalence of subclinical hypothyroidism 25
• increased risk of placental abruption and preterm
  birth
• important to monitor TSH and free T4 levels.
• 25 progress to overt hypothyroidism each year

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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

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Guidelines for clinical management of
maternalhypothyroidism 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 lt 10 mU/L,
  initial dose of 0.1 mg/d may be sufficient.
• 3. For previously diagnosed hypothyroid women,
  monitor serum TSH every 34 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 34
  weeks after every dosage adjustment. When
  levothyroxine dosage achieves equilibrium, resume
  monitoring TSH alone

Shane O. LeBeau, Endocrinol Metab Clin N Am 35
(2006) 117136
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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 lt 10 mU/L, increase 0.05 mg/d.
• 2. TSH 1020 mU/L, increase 0.075 mg/d.
• 3. TSH gt 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

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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

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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)

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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

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• 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.

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Postpartum thyroiditis

• antithyroids no role.
• Hypothyroid may require treatment and some
• significant rate of residual hypothyroidism
• Recommendmaintain 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

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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.

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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,ultrasonograp
  hy 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.

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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.

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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 antibodypositive
  women
• maintain the TSH concentration at 2.5 mU/L or
  less.

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CLINICAL PRACTICE GUIDELINEManagement of Thyroid
Dysfunction during Pregnancyand Postpartum An
Endocrine Society ClinicalPractice 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 46 wk gestation
  and 3050 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 3040 d.

Abalovich et al. Guideline Thyroid Dysfunction
during and after Pregnancy J Clin Endocrinol
Metab, August 2007, 92(8) (Supplement)S1S47
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• 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

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• 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

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• 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.

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• 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

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• 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.

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• 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

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• 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.

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• 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.

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• 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.

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• 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 48 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.

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• 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.

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• 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.

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References

• 1. LeBeau Mandel.Thyroid Disorders During
  Pregnancy.Endocrinol Metab Clin N Am 35 (2006)
  117136.
• 2. Neale et al. Thyroid Disease in Pregnancy.Clin
  Perinatol 34 (2007) 543557.
• 3. Abalovich et al. Guideline Thyroid
  Dysfunction during and after Pregnancy. J Clin
  Endocrinol Metab, August 2007, 92(8)
  (Supplement)S1S47.
• 4. Kronenber Williams Textbook of Endocrinology,
  11th ed.
• 5. Up To Date ver.15.1