MCQ

1. 28 years old women with gravies disease in the 18th

week of pregnancy on carbimazole referred for

medication adjustment .

What of the following set of laboratory result is within the

recommended targets for this patient?

Total t3

70:220ng/dl

Freet4

(0.8;1.8ng/dl

Tsh

(0.5;5)

4002.10.05A

3501.80.1B

3301.51.5C

2801.32.5D

2101.03.5E

2. A 24 years old woman in the first trimester of pregnancy

present with heat intolerance , palpitation and failure to

achieve expected weight gain. she has no prior history of

thyroid disease and takes only prenatal vitamins. on

examination , her pulse is 112beat /min. she has no proptosis or

periorbital soft tissue changes her thyroid is slightly enlarged , and

she has resting hand tremors . free t4 is 25.7(normal 10.3-23.2

pmol/l)and serum TSH is 0.05 MIU/l Which one of the following

laboratory stuties is the most useful in determining the etiology of

this patient’s thyrotoxicosis?

A. TSH receptor antibody testing

B. Thyroid perioxidase antibodies.

C. Serum HCG level.

D. Free t3:freet4 ratio

E. RAIU usin I131

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video

Dr. Mohammed Ibrahim Youssef

Family Medicine Specialist

Albassam Diabetic Center .KSH

Objective:

Give an overview on updated clinical practice guidelines

(Published august.2012) for the management of thyroid dysfunction during pregnancy and postpartum .

Will be reviewed august 2015.

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Objective:

What are the normal physiological changes during

pregnancy?

How can we make interpretation of TFT in the context of

these changes?

hypothyroidism, or hyperthyroidism, how managed what's

our target?

Thyroid autoimmunity ! is it risky ?

Thyroid nodules & caner , how to manage?

Screening of thyroid dysfunctions ! with or against?

Thyroid problems during pregnancy.

1. Hypothyroidism.

2. Hyperthyroidism.

3. Gestational transient hyperthyroidism.

4. Autoimmune thyroid disease.

5. Thyroid nodules and cancer.

6. Iodine nutrition during pregnancy.

7. Postpartum thyroiditis.

8. Screening for thyroid dysfunction during pregnancy.

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Introduction..why guidelines.?

Pregnancy may affect the course of thyroid

Disorders, and conversely, thyroid diseases may affect

both the pregnant woman and the developing fetus.

Pregnant women may be under the care of multiple

health care professionals, including obstetricians,

nurse midwives, family practitioners, endocrinologists,

and/or internists, making the development of

guidelines more imporatant.

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Estrogen

TBGx2

TT4

TT3

HCG=TSH

TSH

TT3&TT4

FT4&FT3

Thyroid physiology

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Increase in serum thyroxine-binding globulin (TBG) concentrations .

Estrogen effect.

2 fold increase.

Total t4 and t3 rise during the first half of pregnancy, plateauing at

approximately 20 weeks of gestation

Stimulation of the thyrotropin (TSH) receptor by human chorionic

gonadotropin (HCG).

Homology between the beta-subunit of HCG &TSH.

HCG &TSH are glycoprotein hormones.

Peak at 10 to 12 weeks gestation

Total (T4 and T3 )concentrations increase.

Free t4 and t3 increase slightly, usually within the normal range.

TSH reduced

Thyroid physiology

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Hypothyroidism

1. Hypothyroidism: maternal and

fetal aspects

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Hypothyroidism

Overt hypothyroidism occurs in 0.3–0.5% .

Subclinical hypothyroidism 2–3%.

Thyroid autoantibodies are found in 5–15% of women during childbearing age.

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Hypothyroidism

Hypothyroid women have an increased prevalence of infertility, abortion,anemia, gestational hypertension, placental abruption,and postpartum hemorrhage .

Adverse fetal &neonatal outcomes including premature birth, low birth weight, and neonatal respiratory distress

Low IQ

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Trimester-specific reference ranges

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Hypothyroidism

FREE T4 INDEX

TOTAL T4 ASSAY

X (1.5)

FREE T4 ASSAY

0.3 to 3

3rd

trimester

0.2 to 3.0

2nd

trimester

0.1 to 2.5

1st

trimester

TSH Reference

range

MIU/L

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King Saud Hospital

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If hypothyroidism diagnosed before pregnancy, adjust of

the preconception thyroxine dose to reach TSH target ≤ 2.5 MIU/Liter.

thyroxine dose usually needs to be increased (30:50)% mostly during first trimester. (C)

Hypothyroidism

If hypothyroidism diagnosed during pregnancy, thyroid

function tests should be normalized as rapidly as possible.

maintain the target TSH ≤ 2.5 MIU/liter in the first

trimester (or 3MIU/liter in second and third trimesters) .

Thyroid function tests should be remeasured within 30–40

d and then every 4–6 wk

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Hypothyroidism

Euthyroid women with thyroid autoimmunity (TPO ab &thyroglobulin ab) are at risk of developing hypothyroidism and should be monitored for elevation of TSH every 4–6 wk.

After delivery, most hypothyroid women need to

Decrease the T4 dosage to the prepregnancy dose.

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Hypothyroidism

T4 replacement is recommended to women with SCH

(high TSH + normal free t4) regardless thyroid

peroxidase antibody status.(either positive or

negative).

(Normal TSH +Low FT4) treat or not??

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controversial and requires further study.

partial replacement therapy may be initiated with continued monitoring

Hypothyroidism

FridayThurs.WednesdayTuesdayMondaySundaySaturday

50+5050+505050505050

TSH ≤(2.5)

Thyroxine dose30%:50%

7 tab to 9 tabWeekly

Hypothyroidism

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Monitor frequently

Return back to prepregnancy dose

Anti TPO+ve

2. Hyperthyroidism

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HCG mediated hyperthyroidism

Hyperthyroidism

Gestational transient

thyrotoxicosis

Gestational trophoblastic

disease

Hyperemesis gravidarum

Graves disease

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prevalence of hyperthyroidism ranges from 0.1 to 0.4%.

Graves’ disease accounting for 85% of cases.

Graves’ disease may fluctuate during pregnancy, with exacerbation during the first trimester(high levels of HCG) and improvement by late gestation.

The presence of a goiter, especially with bruit or thrill, may point to true graves’ disease.

2. Hyperthyroidism….

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: ;

.

Maternal hyperthyroidism:Medically indicated preterm delivery, intrauterine growth restriction and low birth weight, preeclampsia,

Congestive heart failure, and fetal death.

Iatrogenic fetal hypothyroidism.

Central congenital hypothyroidism.

Fetal hyperthyroidism: intrauterine growth restriction,

Fetal tachycardia,

Fetal goiter,

Advanced bone age,

Fetal hydrops,

Preterm delivery, and

Fetal death

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2. Hyperthyroidism….

Recommendations.

Normal physiology Gestational

thyrotoxicosis

Overt hyperthyroidism

Must be distinguished from both normal physiology of pregnancy and gestational thyrotoxicosis.

Differentiation is supported by the presence of clinical evidence of autoimmune thyroid disease (typical goiter, and presence of thyrotropin receptor antibody (TRAb).

TPO-Ab may be present in either case. (B)

TSH in healthy pregnant women during the first trimester may be as low as 0.03 to 0.1 mU/L

Significant hyperthyroidism(gravies disease) in the first trimester will have a serum TSH <0.01 mU/L) associated with elevated free T4 and/or free T3 (or total T4 and/or total T3) measurement.

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freeT4 at the upper limit

(12 _ 22)pmol/l

Recommendations.

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For hyperthyroidism due to graves’ disease or thyroid nodules,

ATD therapy should be either:

Initiated (new diagnosis) or

Adjusted (for those with a prior history) to:

Maintain the maternal thyroid hormone levels for

free T4 at the upper limit of the non pregnant reference range. (B)

Recommendations.

PTU is the first line during the first trimester.

PTU may be associated with severe liver toxicity.

Liver toxicity may appear abruptly with PTU.

Monitor liver function in pregnant women on PTU every 3–4 wk .(C)

MMI (carbimazol)in 2nd and 3rd trimester.

MMI may be associated with specific congenital abnormalities . (B)

agranulocytosis

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PTU

Recommendations.

Choanal atresiaAplasia cutis

Hepatotoxicity

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Subtotal thyroidectomy may be indicated optimally

during the Second trimester if: severe adverse reaction to ATD therapy;

persistently high doses of ATD are required (over 30 mg/d of MMI or 450 mg/d of PTU)

patient is nonadherent to ATD therapy and has uncontrolled

hyperthyroidism. (c)

Recommendations.

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Radioactive iodine should not be given to a woman who is or may be pregnant. (A)

No data for or against termination of pregnancy after RAI exposure. (I)

Recommendations.

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No evidence that treatment of subclinical hyperthyroidism improves pregnancy outcome. It could potentially adversely affect fetal outcome. (C).

Subc l in ica l hyperthyroid ism

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Gravies disease

HCG mediated

TSH

FT4

FT3

TT3

SIGNS

TRAB

B.blockers

High normal ft4

Side effects SUBCLINICAL

HYPERTHYROIDISM

RAI

SURGERY SECOND

TRIMESTEER

ATD

BB

Hyperthyroidism

(Fetal aspects)

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Fetal (TSH) appears during the 10th to 12th week of gestation.

Fetal thyroid secretion increases gradually after 18th to 20th week.

Maternal thyroid hormones can cross the placenta??

TSH-receptor antibodies can cross the placenta and cause cause either fetal hyperthyroidism or hypothyroidism

Hyperthyroidism (Fetal aspects).

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Fetal& neonatal hyperthyroidism occurs in (1:5)% of neonates born to women with graves disease.

All fetuses of women with graves' disease should be monitored for fetal thyrotoxicosis .

Hyperthyroidism (Fetal aspects).

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HOW ?

TSH-receptor antibodies(TRAB) should be measured by 22wk gestation in:

Current graves’ disease.

History of graves ’ disease treated with RAI or thyroidectomy before pregnancy.

Previous neonate with graves’ disease.

Previously elevated TRAb.

Negative TRAb have very low risk of fetal or neonatal thyroid dysfunction. (B)

Recommendations.

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TRAb or( thyroid-stimulating Ig) elevated at least (2-3) folds

Fetal thyroid dysfunction should be screened for during the fetal anatomy ultrasound (18th-22 nd wk)

And TFT

Fetal thyroid enlargement.

growth restriction. Hydrops.

Tachycardia.cardiac failure.

MMI or PTU should be givenwith frequent clinical, laboratory, and

ultrasound monitoring.Umbilical blood

sampling

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2.HCG mediated hyperthyroidism

Gestational transient

thyrotoxicosis

Hyperemesis gravidarum

Trophoblastic hyperthyroidism

Familial gestational hyperthyroidism

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Gestational transient hyperthyroidism

Limited to the first half of pregnancy,

Elevated serum free T4 .

Suppressed or undetectable serum TSH.

Absence of thyroid autoimmunity.

Typically associated with hyperemesis gravidarum.

Thyroid stimulation is due to HCG itself, or molecular variant proteins related to HCG.

Hydatidiform mole or choriocarcinoma with very high elevations of HCG may be associated with clinical hyperthyroidism.

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Diagnosis:

Thyroid function tests and TRAb should be measured in patients with hyperemesis gravidarum and clinical features of hyperthyroidism.

Suppressed TSH, and elevated free T4.

Treatment:

Do not require ATD treatment(A).it remit spontaneously.

In women who appear significantly thyrotoxic or who have high serum total T3 . Clinical judgment should be followed .

Beta blockers (metoprolol) may be helpful and used with obstetrical agreement. (B)

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Gestational transient hyperthyroidism

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4. Autoimmune thyroid disease

4. Autoimmune thyroid disease

TSH every month during the first half of pregnancy

andat least once during the last trimester

Positive association exists between thyroid antibodies (anti TPO)and pregnancy loss.

Universal screening for thyroid antibodies, and possible treatment, cannot be recommended at this time.(like ATA.)

However, monitoring for the development of hypothyroidism was recommended

SO TSH should be measured before pregnancy, as well as during the first and second trimesters of pregnancy.(C)…. How?

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some experts, including some UpToDate editors suggest levothyroxine (50 mcg daily) with carful monitoring :

euthyroid women with TPO ab+ve

in case of recurrent miscarriage.

((Uptodate Jun 19, 2014))

4. Autoimmune thyroid disease

and miscarriage

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5. Thyroid nodules and cancer

Pregnancy may promote the onset of growth of a thyroid

nodule .

No clear evidence that pregnancy worsens the survival

from well-differentiated thyroid cancer .

Some evidence that thyroid cancers discovered during

pregnancy have a greater chance of recurrence.

Evaluation is the same.

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5. Thyroid nodules and cancer

5. Thyroid nodules and cancer

FNA cytology should be performed for

predominantly Solid thyroid nodules greater than 1 cm discovered In pregnancy.

Nodules 0.5 cm to 1 cm in size should be considered for FNA if they have a high-risk history or suspicious findings on ultrasound.

Complex nodules 1.5–2 cm or larger .

During late pregnancy, FNA can be delayed until after delivery.

Ultrasound guided FNA is better. B

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Suspicious findings on ultrasound.

All solid consistency.

Calcifications, especially tiny or microcalcifications.

Really dark appearing or hypoechoic.Irregular margins.

Suspicious neck lymph nodes.

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if malignant or highly suspicious to exhibit rapid growth nodule:

Surgery should be offered in the second trimester.

Papillary cancer without evidence of advanced disease

Can be delayed until the postpartum period for definitive surgery. (B)

5. Thyroid nodules and cancer

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Give thyroxine to achieve suppressed but detectable TSH in pregnant women with

Treated thyroid cancer .

if surgical treatment delayed until postpartum.

keep free t4 or total t4 levels within the high normal range for pregnancy.(I)

RAI should not be given to women who are breastfeeding. (A)

Pregnancy should be avoided for 6 months to 1 year in women

received therapeutic RAI .(B)

5. Thyroid nodules and cancer.

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Surgery

During

2nd trimester

Papillary

carcinoma

follicular

neoplasm

medullary carcinoma

Anaplastic

RAI T4

Nodule0.5-1 cm with suspicious

>1cmFNAC

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6.0. Iodine nutrition during

pregnancy

6.0. Iodine nutrition during pregnancy

Women in the childbearing age should have

an average iodine intake of 150 microgram/day.

As long as possible before and during pregnancy and breastfeeding, iodine intake should be increased their daily to 250 microgram on average. (A)

Breast milk provides 100 microgram iodine per day to the infant.

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During pregnancy and breastfeeding do not exceed twice the recommended daily dose ( 500 microgram iodine per day). (I)

Once-daily prenatal vitamins should contain 150–200 microgram iodine in the form of potassium iodide or iodate.

6.0. Iodine nutrition during pregnancy

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7.0. Postpartum thyroiditis

PPT is the occurrence of

Hyperthyroidism. Or

Hypothyroidism. Or

Hyperthyroidism followed by hypothyroidism

During the first year postpartum in women without clinically evident thyroid disease ??Before pregnancy.

Caused by thyroid autoimmunity.

Exclusively in thyroid antibody positive.

7.0. Postpartum thyroiditis

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Prevalence:

In unselected populations is 7 %

Type 1 diabetes mellitus. 25%

The highest rates occur with

history of postpartum thyroiditis ( 42 %) and

positive antithyroid peroxidase antibodies (40 : 60)%

may occur after pregnancy loss (miscarriage, abortion, ectopic pregnancy), as well as after normal delivery.

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7.0. Postpartum thyroiditis

Insufficient data to recommend screening of all women for postpartum thyroiditis.(I)

Monitor TSH at 6–12 wk gestation and at 6 months postpartum for TPO ab + ve .(a)

Screening by TSH is recommended at 3 and 6 months postpartum in patients with

Type1 diabetes.

Chronic viral hepatitis. (B)

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7.0. Postpartum thyroiditis

PPT has Increased risk of developing permanent primary hypothyroidism in the 5- to 10-yr period after the episode of PPT.

Annual TSH level should be performed. (A)

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7.0. Postpartum thyroiditis

7.0. Postpartum thyroiditis: Treatment.

Asymptomatic hypothyroidismSymptomatic hypothyroidism

TSH less than 10 MIU/liter

Not planning for subsequent pregnancy

No intervention, but should be remonitored in 4–8 wk.

When a TSH above the reference range continues, women should be treated .

women With TSH above normal .

planning for pregnancy.

should be treated with levothyroxine.

Beta blockers. propranolol

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Symptomatic hyperthyroidism

Screening for thyroid dysfunction

during pregnancy

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Universal screening of healthy women for thyroid dysfunctionusing serum TSH before pregnancy is not recommended. (I)

Identify individuals at “high risk” for thyroid illness.

If high risk measure TSH .

IF >2.5 MIU/L repeat to confirm. Give low dose thyroxine to bring TSH below 2.5 mIU/liter.

Thyroxine can be discontinued if the woman does not become pregnant .

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8.0. Screening for thyroid dysfunction before&

during pregnancy

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High risk for thyroid illness:

Age over 30 years.

Family history or autoimmune thyroid disease or hypothyroidism

Goiter

Thyroid antibodies, primarily thyroid peroxidase antibodies

Symptoms or clinical signs suggestive of thyroid hypofunction

Type 1 DM or other autoimmune disorders

Infertility

History of miscarriage or preterm delivery

Prior head or neck irradiation or thyroid surgery

Women currently receiving levothyroxine replacement

Women living in a region with presumed iodine deficiency

Universal screening for anti-TPO antibodies either before or during pregnancy is not recommended.(C)

But if identified, screen for serum TSH abnormalities before pregnancy, as well as during the first and second trimesters of pregnancy (C)

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8.0. Screening for thyroid dysfunction

during pregnancy

for newly pregnant women. Two versions are presented:

Some members recommended screening of all pregnant women by the ninth week or at the time of their first visit. (C)

Others. Strongly support aggressive case finding to identify high-risk women.

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8.0. Screening for thyroid dysfunction

during pregnancy

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Summary

Consider the physiological changes during pregnancy.

Establish trimester specific ranges for TSH &free t4.

Maintain target TSH ≤ 2.5 during treatment of hypothyroidism

Maintain free T4 near upper limit during treatment of hyperthyroidism.

Do not give ATD in HCG mediated hyperthyroidism.

TRAB only with gravies disease.

PPT exclusively in anti TPO +ve.

Surgery for cancer thyroid optimally in 2nd trimester

Iodine requirement during pregnancy is 250 mcg.

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Abbreviations.

ATD, Antithyroid drug.

FNA, fine-needle aspiration.

GH, gestational hyperthyroidism.

HCG, human chorionic gonadotropin.

MMI, methimazole.

PPT, postpartum thyroiditis.

PTU, propylthiouracil.

TG, thyroglobulin.

TPO-Ab, thyroid peroxidase.

TRAb, TSH receptor antibodies.

RAI, radioactive iodine.

SCH, subclinical hypothyroidism.

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Referenes

Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline

Overview of thyroid disease in pregnancy last updated: Jun 19, 2014.

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