THYROID DISORDERS &

PREGNANCY

Dr. Harefa, SpPD

Bagian Penyakit Dalam
RSUD M Zein Painan
 THYROID PHYSIOLOGY IN
NORMAL PREGNANCY
Pregnant women will have high human chorionic
gonadotropin (hCG) level that stimulates the TSH
receptor.

increase in thyroxine (T4) and triiodothyronine

(T3) production.

which results in inhibition of thyroid-stimulating

hormone (TSH) in the first trimester of pregnancy.
Why higher thyroxine requirements in
pregnancy?
A large plasma volume and thus an
altered distribution of thyroid hormone
increased thyroid hormone metabolism,
increased renal clearance of iodide,
higher levels of hepatic production of
thyroxine-binding globulin (TBG) in the
hyperestrogenic state
- fetal thyroid in humans is histologically
developed and can synthesize thyroid hormone
by the 10th to 12th week of gestation
- thyroid maturation takes longer, and it is not
until midgestation that substantial amounts of
thyroid hormone are produced by the fetal
thyroid gland.
Maternal hypothyroidism during the first
trimester can thus have deleterious effects
on fetal neurodevelopment, which is largely
dependent on maternal thyroxine.
 Epidemiologic and prospective evidence
suggests that early-gestation maternal
hypothyroidism can result in mental and
motor delay in children when assessed at 1
and 2 years of age, and in some cases may
even lead to profound mental retardation
and cretinism
 The National Health and Nutrition
Examination Survey (NHANES 1999
2002) indicates that 3.1% of women of
reproductive age in the United States may
have hypothyroidism.
The prevalence of overt hypothyroidism
in pregnancy is estimated to be between
0.3% and 1.5% in different studies
- In Indonesia the most common cause of
maternal hypothyroidism worldwide is iodine
deficiency
- but in developed countries autoimmune thyroid
disease or Hashimotos thyroiditis is more
prevalent.
The WHO recommends that pregnant and
lactating women have an iodine intake of 250 mg
per day, which is 100 mg above that
recommended for nonpregnant adults
1. increased thyroxine requirements
2. increased renal iodine losses
3. increased fetal iodine requirements in
pregnancy
 Some studies
Thyroid autoimmunity is an important
marker for subsequent development of
hypothyroidism
The measurement of antibody levels may
be helpful in determining the frequency of
monitoring thyroid function during the
remainder of gestation.
 when euthyroid pregnant women with
TPO-Ab positivity were treated with
levothyroxine (low dose 0.51.0 mg/kg/d) to
normalize serum TSH, the rate of
miscarriage was similar to antibody negative
women (3.5% vs 2.4%)
whereas untreated TPO-Abpositive
pregnant women had a significantly higher
TSH and a higher miscarriage rate of 13.8%.
 A TSH level above 6 mU/mL was associated
with a fourfold increase in fetal death in one
population-based study of more than 9000
pregnant women.
A large cohort of TPO-Abnegative
pregnant women showed that those with a
TSH of 2.5 mU/mL or less in the first
trimester had a lower rate of spontaneous
pregnancy loss (3.6%) than women with a
TSH between 2.5 and 5 mU/mL (6.1%).
 A cohort of more than 17,000 women
found that pregnancy in those with
subclinical hypothyroidism was 3 times
more likely to be complicated by placental
abruption and had twice the risk of
preterm delivery.
The rate of miscarriage was 17% in
women with positive thyroid antibodies
compared with 8.4% in autoantibody-
negative women.
This observation suggests that the
upper limit of normal for TSH in the
first trimester of pregnancy should be
2.5 mU/mL.
 Screening for thyroid disease in
pregnancy
The Endocrine Society recommend targeted
case- finding in pregnant women with:
a personal history of thyroid disease,
a positive family history,
type 1 diabetes mellitus or other
autoimmune disorders
infertility
history of miscarriage or preterm delivery
clinical signs or symptoms of thyroid disease
that would classify them as high risk.
In women with a prior history of hypothyroidism
the preconception and first-trimester TSH level
should not exceed 2.5 mU/mL.

In the second and third trimesters, a TSH of less

than 3.0 mU/mL is desirable.

A pregnant woman receiving an established,

stable dose of levothyroxine will likely need a
30% to 50% dose augmentation by the fourth
through sixth week of gestation
 ATA recommendation
The goal of LT4 treatment is to normalize
maternal serum TSH values within the
trimester-specific pregnancy reference range
- first trimester, 0.12.5 mIU/L;
- second trimester, 0.23.0 mIU/L;
- third trimester, 0.33.0 mIU/L).
 Euthyroid women with TPO-Abs are
believed to be at high risk for developing
hypothyroidism later in pregnancy, and
should be monitored for TSH elevation
and receive prenatal counseling; however,
treatment with thyroid hormone is not yet
recommended in this population
 Monitoring of thyroid function tests in
pregnant women with hypothyroidism
should occur frequently,
- every 2 to 4 weeks throughout midgestation

- 4 to 8 weeks in the second half of pregnancy,

Thyroid Evaluation
Signs and symptoms provide the best
indication to request thyroid tests
Signs and symptoms of thyroid disease
Hypothyroidism Hyperthyroidism

High Suspicion Goitre Goitre

Delayed reflexes Thyroid bruit
Lid lag
Proptosis

Intermediate Fatigue Fatigue

Suspicion Weight gain/difficulty losing weight Weight loss despite increased appetite
Cold intolerance Heat intolerance/sweating
Dry, rough, pale skin Fine tremor
Constipation Family history
Family history Increased bowel movements
Hoarseness Fast heart rate/palpitations
Staring gaze

Low Suspicion Coarse, dry hair Nervousness

Non specific Hair loss Insomnia
Muscle cramps/muscle aches Breathlessness
symptoms Depression Light or absent menstrual periods
Irritability Weight loss
Memory loss Muscle weakness
Abnormal menstrual cycles Warm moist skin
Decreased libido Hair loss
Possible explanations for various result
combinations
High T4 Normal T4 Low T4

High TSH Irregular use of thyroxine Subclinical hypothyroidism Primary hypothyroidism

Amiodarone T4 under replacement
Pituitary hyperthyroidism (TSH-
producing pituitary tumour -
rare)
Thyroid hormone resistance (very
rare)

Normal As above Normal Some drugs

Some drugs (steroids, beta- (anticonvulsants,anti-T3,
TSH blockers, NSAIDS) anti-T4)
Non-thyroidal illness Pituitary or hypothalamic
T4 replacement (sometimes hypothyroidism,
stablises with normal TSH and Severe non-thyroidal illness
FT4)

Low TSH Primary hyperthyroidism Subclinical hyperthyroidism Pituitary or hypothalamic

Subtle T4 over replacement hypothyroidism,
Non-thyroidal illness Severe non-thyroidal illness
 HYPERTHYROIDISM
causal :
1. autoimmune thyroid disease(eg, Graves
disease, hashitoxicosis),
2. toxic adenoma or goiter,
3. transient thyroiditis (eg, subacute
thyroiditis, silent thyroiditis),
4. iodine-induced hyperthyroidism,
5. a pituitary adenoma secreting TSH or
thyroid hormone resistance
6. Additional consideration of hCG-mediated
hyperthyroidism including gestational
transient thyrotoxicosis (GTT) and its
association with hyperemesis gravidarum
becomes very important.
7. Postpartum thyroiditis
The most common cause of hyperthyroidism
in pregnancy, as in all women of reproductive
age, is autoimmune Graves disease with
circulating TSH receptor antibodies (TRAbs)
stimulating the thyroid gland and TSH
receptor.
Graves disease may be challenging to
diagnose in the hypermetabolic state of
pregnancy because of similar symptoms in
both conditions.
Features suggestive of Graves hyperthyroidism in
normal pregnancy include:
1. diffuse goiter,
2. evidence of ophthalmopathy,
3. TRAb or thyroid-stimulating immunoglobulin
(TSI) positivity, and a family history of autoimmune
thyroid disease.
4. The extent of elevation of thyroid function tests
typically is higher in Graves disease than in
hyperemesis gravidarum.
5. The immune-tolerant state of pregnancy is
associated over time with a decrease in TRAb titers,
thus the hyperthyroidism secondary to Graves
disease may subside in severity as gestation progresses
Gestational Transient Thyrotoxicosis

- GTT differs from Graves disease in that

it is a self-limited, nonautoimmune form
of hyperthyroidism with negative TRAbs.
- it is related to the elevation of hCG,
which can then cross-react with the TSH
receptor and induce thyroidal
iodothyronine secretion
Gestational Transient Thyrotoxicosis
- Women have a TSH in the low to normal range
for pregnancy or is frequently undetectable,
- Elevated free T4 and free T3 levels, and
prolonged abnormally high hCG in the first and
second trimesters,
-These patients present with symptoms of
hyperthyroidism in about 50% of cases, and the
emesis or symptoms from thyrotoxicosis may be
severe enough to require hospitalization.
Hyperemesis gravidarum
characterized by excessive nausea and
vomiting, which causes a greater than 5%
weight loss, dehydration, and ketonuria in
early pregnancy, is a milder form of GTT
in that women have subclinical or very
mild overt hyperthyroidism in one-third
to two-thirds of cases.
 pregnant women with uncontrolled
hyperthyroidism:
- Preeclampsia,
- congestive heart failure,
- placental abruption and
- cesarean delivery,
- thyrotoxic periodic paralysis.
 Fetal risks of maternal thyrotoxicosis
include:
- spontaneous abortion,
- premature labor and
- low birth weight,
- stillbirth,
- congenital abnormalities
 TREATMENT
PTU had been the drug of choice during
pregnancy

Radioactive iodine cannot be used

The goal of therapy is to use the lowest
dose of medication to maintain maternal
free T4 in the upper nonpregnant
reference range, as this minimizes the risk
of hypothyroidism to the fetus.
 radioactive iodine administration for
diagnostic scans and treatment is
absolutely contraindicated in pregnant
patients and in women considering
becoming pregnant in the near future,
secondary to adverse effects on the fetus
and the fetal thyroid gland.
Thyrotoxicosis and primary hyperthyroidism
in the neonate is usually transient, and
remits with clearance of maternal TRAbs in
the first 3 to 6 months of life.

Postpartum short-term levothyroxine

administration to the hypothyroid neonate is
recommended, and the hyperthyroidism
should only be treated with antithyroid
agents if the neonate has clinically severe
thyrotoxicosis.
 When the mother is euthyroid after
treatment of Graves disease, is at risk of
recurrence, especially postpartum, and her
thyroid function should be monitored
during pregnancy and after delivery.

If the mother has had thyroid ablation or

surgery she may still be TRAb positive,
and antibodies may cause fetal
hyperthyroidism via passage through the
placenta.
 TRAb titers should be measured before
pregnancy or at the end of the second
trimester in all pregnant women with current
or a history of Graves disease to assess the
risk of neonatal hyperthyroidism in the fetus.

If titers are high, fetal ultrasonography is

necessary to look for growth restriction,
hydrops, goiter, and cardiac failure in addition
to clinical monitoring of the fetus for
hyperthyroidism
 Subtotal thyroidectomy can usually be
performed in the second trimester of
pregnancy, in situations whereby:
- Hyperthyroidism is uncontrolled with ATDs
-Treatment requires persistently high doses of
antithyroid medication (generally thought to be more than
approximately 300 mg of PTU daily)
- If the mother has a serious adverse effect to medical
therapy.
- Women who receive I-131 therapy for
Graves disease should wait at least 6
months before becoming pregnant

-These patients should become hypothyroid

within 2 to 3 months, and it may
subsequently take 1 to 2 months to restore
euthyroidism with exogenous levothyroxine.
 Lactation and Treatment of
Thyroid Dysfunction
Breastfeeding is considered safe in
mothers with hypothyroidism and
hyperthyroidism taking thyroid medications.
Although MMI and PTU both appear in
human milk, it is at very small
concentrations The decision whether to
breastfeed while taking antithyroid agents is
an individual decision that should be
discussed by the patient and her physician.
 Postpartum Thyroid Dysfunction
an autoimmune destructive thyroiditis (PPT)
with a period of thyrotoxicosis,
hypothyroidism, or both, followed by
recovery in the first year after delivery. It is
frequent and occurs in about 8% of women
worldwide, and is strongly associated with
TPO-Ab positivity. PPTD occurs most
frequently at about the fourth month after
delivery, although it can take place any time
between 1 and 12 months postpartum.
 Up to 50% of pregnant women with TPO-
Abs will develop PPTD, and of these about
20% may develop permanent hypothyroidism
over the next several years.
Risk factors for subsequent and permanent
hypothyroidism include a postpartum peak
TSH greater than 20 mU/mL, a high titer of
TPO-Abs, hypoechogenicity on thyroid
ultrasonography, and a hypothyroid phase of
PPTD.
 The hypothyroid phase of PPTD should be
considered for treatment with levothyroxine
at replacement doses, especially when TSH is
10 mU/mL or greater.
stop the medication after approximately 6
to 12 months of treatment to determine if
the hypothyroidism is permanent and then, if
normal, perform periodic monitoring.
 The Endocrine Society recommends
screening for PPTD by measuring TSH at 3
and 6 months postpartum in all women
with TPO-Abs and type 1 diabetes mellitus,
as well as annually in those with a history
of PPTD in prior pregnancy. Mothers who
experience depression in the postpartum
period should also be screened for
hypothyroidism, and treated accordingly.