Thyroid disorders and pregnancy

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Thyroid disorders and pregnancy

• Medical Complications
• November 23, 2007
• Jill Newstead-Angel, MD FRCPC

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Objectives

• Discuss the normal physiology of the thyroid
  gland during pregnancy
• Discuss hyperthyroidism and pregnancy
• Diagnosis
• Treatment
• Discuss hypothyroidism and pregnancy
• Diagnosis
• Treatment
• Discuss thyroid nodules in pregnancy

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Case 1

• 24 yr old G2P1 presents at 9 weeks GA for first
  prenatal visit
• Part of screening blood work was TSH
• TSH 0.5 mU/L
• Clinically and on history - no evidence of
  thyroid disease

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What should be done?

• Book the patient for a radioactive iodine uptake
  scan
• Start PTU at 100 mg bid
• Do nothing at all
• Check FT4 and FT3

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Normal thyroid physiology in pregnancy

• Fetal thyroid and fetal hypothalamic-pituitary-thy
  roid axis develop independently of maternal
  thyroid
• Starts to function after 10 weeks GA
• 11-12 weeks GA, fetal thyroid concentrates
  iodine and FT4 and TSH are present in fetal
  circulation

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• Increase in thyroid binding globulin due to
  increase in estrogen (stimulation of hepatic
  production and decreased degradation)
• Increase in total T4 and T3
• Increase in GFR leads to increase in renal iodine
  clearance

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• HCG has similar properties to TSH therefore has
  intrinsic thyroid stimulating activity
• increase FT4 and FT3 levels during first
  trimester

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Increase frequency in goiters?

• In iodine replete areas there is not an increased
  frequency of goiters during pregnancy
• If there is a palpable goiter - should be further
  investigated as underlying thyroid disease is
  present 50 of the time

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Hyperemesis Gravidarum

• High levels of HCG
• Associated biochemical evidence of
  hyperthyroidism
• Does not need treatment
• Follow patients out of first trimester to ensure
  not true hyperthyroidism

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What should be done?

• Book the patient for a radioactive iodine uptake
  scan
• Start PTU at 100 mg bid
• Do nothing at all
• Check FT4 and FT3

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Case 2

• 33 year old G5P4 presents at 13 weeks GA for
  first prenatal
• Complaining of palpitations, heat intolerance,
  and tremors
• Clinically tachycardia, tremor and palpable
  thyroid with bruit

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• TSH lt0.01
• FT4 33
• FT3 9

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Hyperthyroidism and pregnancy

• Prevalence 0.1 to 0.4
• Graves is the most common cause
• Other causes
• Functioning adenoma
• Toxic mutlinodular goiter
• Thyroiditis
• Excessive thyroid hormone intake
• Gestational transient thyrotoxicosis

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• Diagnosis difficult in pregnancy because of the
  hyper dynamic state of pregnancy
• Eye signs, tremor, weight loss, marked
  tachycardia more suggestive of hyperthyroidism
• Laboratory
• low TSH with elevated FT4 and FT3
• TSH receptor antibodies
• TPO and TBG antibodies

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Pregnancy outcome

• Depends on treatment and control
• Worse pregnancy outcomes with no treatment or
  partial treatment
• Preterm labor
• Preeclampsia
• Stillbirth
• Small for gestational age

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Treatment

• Antithyroid medications
• PTU
• partially inhibits the conversion of T4 to T3
• Crosses the placenta less
• Dose 100 600 mg
• Methimazole
• Aplasia cutis
• Dose 10 40 mg
• Transient leukopenia develops 10 women treated
• Beta blockers
• Propranolol - may be useful in those with marked
  tachycardia

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• Surgery
• Second trimester best
• Reserved for those that fail medical treatment
• Radioactive iodine treatment
• Contraindicated in pregnancy
• Over all goal
• treat maternal disease while limiting potential
  for fetal hypothyroidism

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Back to case

• Send off blood work for Thyroid stimulating
  antibodies
• Start PTU 100 mg tid
• Start propanolol 10 - 20 mg bid
• Repeat TSH in 2 weeks
• Titrate medications to keep FT4 within higher
  limits of normal

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Sub-clinical hyperthyroidism

• Low TSH with normal FT4
• Affects 1.7 of pregnant women
• During pregnancy not found to be associated
  with any adverse outcomes

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Case 3

• 25 year old G1P1 seen preconception for
  hypothyroidism
• Would like to conceive in the near future
• Currently on Synthyroid 75 mcg per day
• Most recent TSH 4 with normal FT4 and FT3

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Hypothyroidism and pregnancy

• 95 the result of primary disease of the thyroid
• Autoimmune (Hashimotos thyroiditis)
• Less common causes
• Over treatment of hyperthyroidism
• Transient hypothyroidism due to postpartum
  thyroiditis
• Medications
• Pituitary or hypothalamic disease

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Diagnosis

• 20-30 of patients have symptoms
• Elevated TSH
• Patients with central hypothyroidism do not
  manifest elevated TSH during pregnancy

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Complications

• Overt hypothyroidism
• Gestational hypertension (36 of patients
• Placental abruption
• Spontaneous abortion
• Preterm birth
• Postpartum hemorrhage

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• Association between maternal hypothyroidism and
  impaired cognitive function of the offspring

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Thyroid replacement and medications

• Drugs that interfere with absorption
• Prenatal vitamins
• Iron replacement
• Antacids
• Cholestyramine
• Drugs that interfere with metabolism
• Phenytoin
• Rifampin
• Carbamazapine

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Back to case

• Increase her medication to 100 mcg per day to get
  her TSH lt2.5 before conception
• Once she becomes pregnant, check her TSH and
  adjust the dose as necessary
• Monitor q trimester during pregnancy

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Sub clinical hypothyroidism

• Elevated TSH with normal FT4 and FT3
• Prevalence 4-8.5
• Pregnant women 2-5
• Normal TSH 0.3 and 2.5 mU/L
• Levels between 2.5 and 4.0 gray zone
• Values gt4.0 indicative of early thyroid failure
• Treat?
• controversial

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Postpartum Thyroiditis

• Occurs in 5-10 of women
• 25 of patients with DMI

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• Occurs 6-12 weeks postpartum
• Phases
• Hyperthyroid - last 1-2 months
• Hypothyroid - last 6-9 months
• Postpartum depression
• Screen with a TSH as may be cause

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Treatment

• Hyperthyroid phase
• Anti-thyroid medications not effective
• Beta blockers for symptoms
• Hypothyroid phase
• Treat with replacement for 6-12 months and then
  reduce or discontinue dose and recheck TSH in 6
  weeks

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Thyroid nodules and cancer during pregnancy

• Increase in the prevalence of thyroid nodule
  during pregnancy
• Increase in the growth of existing nodules during
  pregnancy
• No evidence to suggest thyroid cancer arises de
  novo more frequently during pregnancy

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Evaluation

• Lab evaluation of thyroid function
• Ultrasound
• FNA
• Benign cytology - observe and follow postpartum
• Malignant cytology - surgery recommended

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• Women with previously diagnosed or treated
  differentiated thyroid cancer require an increase
  in levothyroxine dosage during pregnancy
• TSH of 0.1-0.8 mU/L for papillary or follicular
  cancer
• TSH of lt2.5 mU/L for patients with medullary
  thyroid cancer

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Summary

• Normal physiology of pregnancy is such that the
  TSH will decrease in the first trimester due to
  similarities to HCG
• If initially low, repeat second trimester and
  check FT4 and FT3
• Hyperthyroidism - treat to maintain FT4 in the
  higher range of normal
• Hypothyroidism - goal TSH 0.5 to 2.5 mU/L

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• Postpartum depression - screen for postpartum
  thyroiditis

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Reference

• Casey B, Leveno K. Thyroid disease in pregnancy.
  Obstetrics and Gynecology 2006 108 (5)
  1283-1292
• Hypothyroidism in the pregnant woman. Drug and
  therapeutic bulletin 2005 44 (7) 53-55
• LeBeau S, Mandel S. Thyroid disorders during
  pregnancy. Endocrinology and Metabolism Clinics
  of North America. 2006 35 117-136
• Molitch M. Endocrine disease in pregnancy.
  Principles and Practice of Endocrinology and
  Metabolism 3rd edition.