Thyroid dysfunction dr. mohammed ibrahim youssef (1)(1)

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
23/04/1436 2
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.
23/04/1436 4

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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23/04/1436 9
 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

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 dose
30%:50%
7 tab to 9 tab
Weekly
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 atresia
Aplasia cutis
Hepatotoxicity
23/04/1436 29

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).
Subclinical hyperthyroidism

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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)
23/04/1436 33

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).
23/04/1436 34

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).
23/04/1436 35
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.
23/04/1436 36

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 given
with frequent clinical, laboratory, and
ultrasound monitoring.
Umbilical blood
sampling
23/04/1436 37

2.HCG mediated hyperthyroidism
Gestational
transient
thyrotoxicosis
Hyperemesis
gravidarum
Trophoblastic
hyperthyroidism
Familial gestational
hyperthyroidism
23/04/1436 38

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.
23/04/1436 39

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)
23/04/1436 40
Gestational transient hyperthyroidism

23/04/1436 41
4. Autoimmune thyroid disease

TSH every month during the first half
of pregnancy
and
at 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?
23/04/1436 42

 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))
and miscarriage
23/04/1436 43

23/04/1436 44
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.
23/04/1436 45

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
23/04/1436 46

Suspicious findings on ultrasound.
All solid consistency.
Calcifications, especially tiny or microcalcifications.
Really dark appearing or hypoechoic.Irregular margins.
Suspicious neck lymph nodes.
23/04/1436 47

 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)
23/04/1436 48

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.
23/04/1436 49

Surgery
During
2nd trimester
Papillary
carcinoma
follicular
neoplasm
medullary
carcinoma
Anaplastic
RAI T4
Nodule
0.5-1 cm with suspicious
>1cm
FNAC
23/04/1436 50

23/04/1436 51
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.
23/04/1436 52

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
23/04/1436 53

23/04/1436 54
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.
23/04/1436 55

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.
23/04/1436 56

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)
23/04/1436 57

 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)
23/04/1436 58

7.0. Postpartum thyroiditis: Treatment.
Asymptomatic hypothyroidism
Symptomatic 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
23/04/1436 59
Symptomatic hyperthyroidism

Screening for thyroid dysfunction
during pregnancy
23/04/1436 60

Universal screening of healthy women for thyroid dysfunction
using 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 .
23/04/1436 61
8.0. Screening for thyroid dysfunction before&
during pregnancy

23/04/1436 62
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)
23/04/1436 63
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.
23/04/1436 64
8.0. Screening for thyroid dysfunction
during pregnancy

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.
23/04/1436 66

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.
23/04/1436 67

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.
23/04/1436 68

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