THYROID DISEASE IN PREGNANCY

CALIFORNIA AACE CHAPTER MEETING

SEPTEMBER 9, 2017

JONATHAN D. LEFFERT, MD, FACP, FACE, ECNU

PRESIDENT, AACE

DISCLOSURE

• RESEARCH STUDIES- ABBVIE, NOVO NORDISK, SANOFI,

KOWA, BOEHRINGER INGELHEIM,MYLAN GMBH, ASTRA ZENECA, BRISTOL MYERS SQUIBB

• ABIM SUBSPECIALTY BOARD OF ENDOCRINOLOGY, DIABETES AND METABOLISM

OBJECTIVES

• REVIEW THE RECENT GUIDELINES FOR THYROID DISEASE

IN PREGNACY

• TO UNDERSTAND THE PHYSIOLOGY AND

PATHOPHYSIOLOGY OF THYROID DISEASE IN PREGNACY

• REVIEW THE CURRENT DIAGNOSIS AND TREATMENT OF

THYROID DISEASE IN PREGNANCY

TSH IN PREGNANCY

A 28-year-old woman who is 6 weekspregnant has a routine serum TSHlevel of 4.5 mIU/L & FT4 1.3 ng/dL

Q: Is this TSH normal?

TRIMESTER SPECIFIC TSH LEVELS IN PREGNANCY

Guidelines for Serum TSH During Pregnancy

•Trimester-specific reference ranges for TSH, as defined in populations with optimal iodine intake, should be applied

• If trimester-specific reference ranges for TSH are not available, the following references ranges are recommended:1st trimester, 0.1-2.5 mIU/L; 2nd trimester,0.2-3.0; 3rd trimester, 0.3-3.0

T4 in Pregnancy

•FT4 levels with progression of pregnancy

•FT4I = TT4 x T3 uptake; no trimester-specific ranges available

•TT4 is more reliable during pregnancy;measure when FT4 discordant with TSH

•TT4 is x 1.5 pre-pregnancy level

Overt Hypothyroidism in Pregnancy

•0.05% incidence

• If TSH ≥2.5 and FT4 orTSH ≥10 irrespective of FT4

• Increased risk of premature births, low birth weight and miscarriage

•Neurocognitive disturbances likely

Subclinical Hypothyroidism (SCH) in Pregnancy

•2.5-5% incidence

•Defined TSH 2.5-10 with normal FT4

•Variable evidence for risks

•Possible neurocognitive deficits in developing fetus

IODINE STATUS IN PREGNANCY

•Maternal iodine deficiency results in impaired maternal and fetal thyroid hormone synthesis

•Woman planning pregnancy should take a supplement of 150 mcg of iodine daily

•Pregnant women should ingest approximately 250 mcg of iodine daily (dietary and supplement)

Thyroid and Pregnancy

Physiologic consequences for the fetus

• Fetal development – in particular that ofthe brain – is dependent on the thyroid function of the mother

•The thyroid gland is not developed inthe fetus until 12 th week

•Thyroxine (T4) passes placenta, but relatively poorly

Thyroid in Pregnancy

Maternal consequences of the physiologic

changes

•High risk for false estimation of thyroid function tests

• Increase of goiter size may becomeclinically significant

Effect of Hypothyroidism onPregnancy Outcomes

•Maternal-anemia, hypertension, preeclampsia, abruption placenta, postpartum hemorrhage

•Fetal- miscarriage, low birth weight, stillbirth, psychoneurologic impairment

SCH in Pregnancy

A 26-year-old woman desires pregnancy; serum TSH is 4.0 mIU/L and FT4 1.0 ng/dL

Questions:

•Would you measure TPOAb?

•Would you Rx with T4 if TPOAb is positive?

•What if TPOAb is negative?

Autoimmune Thyroid Disease and Miscarriage

• Pregnant women with TSH ≥2.5 mIU/L should be evaluated for TPO antibody status

•All studies show increased miscarriage in women with thyroid antibodies and normal TSH

•Majority of studies demonstrate an association between thyroid antibodies and recurrent miscarriage

•Does T4 therapy miscarriage rate?

THYROID HORMONE USAGE IN TPOAB-POSITIVE PREGANT EUTHYROID WOMEN

WITH SPONTANEOUS OR RECURRENT MISCARRIAGE

• INSUFFICIENT EVIDENCE EXISTS TO CONCLUSIVELY DETERMINE IF LT4 THERAPY DECREASES MISCARRIAGE RISK

• TWO TRIALS IN EUROPE- TABLET TRIAL IN UK, AND T4LIFE TRIAL IN PROGRESS

• TREATMENT WITH LT4 25 OR 50 MCG MINIMAL RISK GIVEN POTENTIAL BENEFITS

IS OVERT THYROID DYSFUNCTION OR SUBCLINICAL HYPOTHYROIDISM TPO AB-

ASSOCIATED WITH INFERTILITY?

• FOR OVERT THYROID DYSFUNCTION- BOTH HYPER AND HYPO ASSOCIATED WITH INFERTILITY- HYPO TREATED WITH LT4

• FOR SUBCLINICAL WITHOUT POSITIVE TPOAB-DESIRING PREGNANCY- TRIAL OF LT4

• FOR EUTHYROID, NONPREGANT, TPOAB+,DESIRING PREGNANCY INSUFFICIENT EVIDENCE , SO NO RECOMMENDATON

LT4 Therapy in SCH During Pregnancy

•LT4 is recommended when TSH>2.5 and TPOAb+

•LT4 is recommended when TSH ≥10, irrespective of TPOAb

•LT4 is considered when TSH 2.5-10.0 and TPOAb-

•No LT4 is necessary when TSH ≤4.0 and TPOAb-

LT4 Rx During Pregnancy

A 28-year-old woman has been on T4 for hypothyroidism for 5 years, she is now taking LT4 125 mcg daily. She is now pregnant and asks about thyroxine dose.

Q: What is optimal T4 dose and TSH level?

EUTHYROID WOMAN AT RISK FOR HYPOTHYROIDISM ONCE PREGNANT

•EUTHYROID PATIENTS WHO ARE AB POSITIVE

•POST-HEMITHYROIDECTOMY

•POST RADIOACTIVE IODINE TREATED

LT4 Rx in Pregnancy

• Treated hypothyroid women on LT4 who are newly pregnant should T4 dose by 30%, which is usually equivalent to 2 extra pill per week

• Those with OH or SCH not treated previously should be monitored with repeat TSH every 4 weeks until week 20 then at week 30

•Hypothyroid women on LT4 during pregnancy should be targeted to a TSH in the lower half of the trimester specific range and if not available, should adjust T4 dose to keep TSH ≤2.5 mIU/L

Hyperthyroidism in Pregnancy

A 32-year-old woman pregnant 10 weeks presents with nausea, vomiting, and a 5 lb weight loss; her first pregnancy 2 years earlier was uncomplicated

On exam she is a bit dehydrated, euthyroid, without a goiter and has normal eyes

TSH 0.01 (<2.5)FT4 2.1 (0.8-1.8)FT4I 20 (5-12)

Q: Does she require antithyroid Rx?

Hyperthyroidism & PregnancyClinical Clues in DDx

Gestational GD

Sx prepregnancy – ++

Sx during pregnancy

+ +++

N & V ++++ +

Goiter/GD – +

TRAb/TPOAb – +

Diagnosing Hyperthyroidism in Pregnancy

• TSH; FT4

• T3

•Goiter

•TRAb

•RAIU – contraindicated

Hyperthyroidism in Pregnancy

A 32-year-old woman is 8 weeks pregnant; she reports palpitations, anxiety, heat intolerance and an 8 lb weight loss for 6 months

On exam she is nervous, slightly hyperthyroid, has lid lag, and thyroid is x2 enlarged

TSH 0.01FT4 2.8FT4I 16 (5-12)TRAb 75% (<16%)

Q: How do you manage?

Hyperthyroidism in Pregnancy

•Thyroid autoantibodies (TRAb) cross placenta& affect fetal thyroid after week 12

•Fetus can develop intrauterine myxedema or hyperthyroidism even if mother is euthyroid

•Avoid combination T4/ATD Rx

Hyperthyroidism in Pregnancy

• PTU is recommended for maternal hyperthyroidism thru 16 weeks of pregnancy

• Pregnant women on MMI who become pregnant should be switched to PTU

•When shifting from MMI to PTU, use a dose ratio of 1:20

•After week 16, either PTU or MMI can be used

Hyperthyroidism in Pregnancy

•Women treated with ATDs in pregnancy should be monitored with FT4/TT4 and TSH every 4 weeks

•ATDs in pregnancy should be administered at the lowest effective dose , targeting FT4/TT4 to the upper limit or moderately above the reference range

Hyperthyroidism in Pregnancy

•A 28 yo WF with history of Graves Disease on Methimazole 5 mg qd with Free T4 of 1.6, Total T3 of 130, and TSH of 0.03, with positive TRAB calls the office to tell you she has just found out that she is 6 weeks pregnant.

•What is your next step?

Hyperthyroidism in Pregnancy

• In a newly pregnant woman with GD and euthyroidon low dose Methimazole, consider discontinuing all antithyroid medications given potential teratogenic effects

• FT4, TT4, TSH and clinical examination should be performed every 1-2 weeks to assess maternal and fetal thyroid status

•Decision to continue conservative management should be guided by clinical and biochemical assessment of maternal thyroid status

Hyperthyroidism in Pregnancy

•Small but detectable amount of PTU/ MMI found in breast milk of lactating women on ATDS for Graves Disease

•The lowest effective doses of MMI/PTU should be administered ( up to maximal dose of 20 qd of MMI and 450 mg of PTU)

•All breast feeding women should 250 mcg of daily iodine with 150 mcg from oral supplement

Postpartum Thyroiditis (PPT)

•Most common endocrine disease in women

•Worldwide prevalence 1.1-16.7% (mean 7.5%)

•Autoimmune disorder that occurs within 1 yr following delivery

•Typical course is transient hyperthyroidism followed by transient hypothyroidism

Postpartum Hyperthyroidism

•May be due to PPT or GD

•For GD, MMI 20-30 mg/d, is safe for lactating women & their infants

•For PPT, use propranolol at the lowest dose to alleviate Sx – no need for ATD

Postpartum Thyroiditis

•Women with 1 episode of PPT have 70% chance of recurrence with next pregnancy

•TPOAbs are usually positive

•Relation between PPT and pp depression is undefined

•Majority of pt are euthyroid by the end of first pp year

Thank your for your attention

Questions ?