Thyroid Disease in Pregnancy

By La Lura White MD
Maternal Fetal Medicine

 A normal pregnancy
results in a number of
important reversible
physiological and
hormonal changes
that alter thyroid
structure and more
importantly function.

 Understanding these
change are important
to interpreting,
identifying and
managing of thyroid
disease in pregnancy.

 The thyroid gland is located
in the anterior neck below
the hyoid bone.
 Consist of two lobes
connected by an isthmus.
 Each lobe is divided into
lobules that contain 20-40
follicles each.
 Follicles consist of follicular
cells which surround a
glycoprotein material
(colloid).
 Thyroid hormone is produced
by the follicular cells.

 The production of thyroid hormone
functions on a negative feedback
loop.
 The hypothalamus releases
thyrotropin-releasing hormone (TRH)
from paraventricular nucleus.
 Stimulates the anterior pituitary
gland to secrete thyroid-stimulating
hormone (TSH).
 This in turn causes the thyroid gland
to produce and release thyroid
hormone.
 The thyroid gland produces thyroxine
(T4), deiodinated primarily by the
liver to its active form,
triiodothyronine (T3).
 The thyroid gland also produces a
small amount of T3 directly.

 Increase in dietary iodine from 80-100 mcg/d to
200 mcg./day.
 Dietary iodine uptake by thyroid gland is reduced
to iodide.
 This is the rate limiting step for hormone
synthesis.
 Iodide binds to thyroglobulin catalyzed by
thyroid peroxidase to produce monoidotyrosine
(MIT) or di-iodotyrosine (DIT).
 T4: coupling 2 DIT.
 T3: coupling DIT+MIT.
 Stored bound to thyroglobulin as a colloid.

 Under TSH control, thyroglobulin is digested and
T3 30 mcg/d) and T4 (90 mcg./d) released into
capillary circulation.
 T4(thyroid origin) and T3(T4 deiodinated by liver
and kidneys to T3, only 20% thyroid production)
 99% hormone bound mostly to thyroxine-binding
globulin (TBG).
 Other binding proteins include thyroxine-binding
pre-albumin and albumin.

Physiological Changes in Thyroid
Structure

 20% increase in thyroid gland size due to hyperplasia and
increased vascularity.
 T4 production increases approximately 50% starting in
early pregnancy.
 Rarely thyroid gland enlargement causes goiter unless
iodine-deficient.
 Plasma iodide levels decrease as a result of fetal iodide
use, placental losses and increased maternal renal
clearance resulting in a deficit.

 Physiological Changes in Thyroid
Function:
 Influenced by two hormones: hCG and
estrogen.

 hCG:
Shares some structural homology with
thyrotropin (TSH).

Binds to thyroid gland TSH receptors,
exhibit weak thyrotropic stimulation
with subsequent hormone production,
especially first trimester.

 Week from the Last Menstrual
Period Amount of HCG in
mIU/ml
 3 5 -50
 4 3 - 426
 5 19 - 7,340
 6 1,080 - 56,500
 7-8 7,650 - 229,000
 9 - 12 25,700 - 288,000
 13 - 16 13,300 - 254,000
 17 - 24 4,060 - 165,400
 25 - 40 3,640 - 117,000

 Peaks end first trimester and
then declines.

 Increased hCG will
stimulate thyroid hormone
production and produce a
negative feedback,
suppress and decrease
levels of thyroid
stimulating hormone
(TSH) in the first
trimester.
 Serum TSH drops to
undetectable levels in up
to 15% of normal
pregnancies.
 Mistakenly diagnose
hyperthyroidism with
physiologic decrease in
TSH and increase in
thyroid hormone.
 By the second trimester,
serum TSH levels return to
normal

 Estrogen

 Stimulates the liver to produce thyroid binding
proteins, especially (TBG), major transport protein
for thyroid hormone and extend its half-life.
 Significant increase in secretion TBG (levels ~200 %).
 Results in lower free thyroid hormone and stimulate
positive feedback H-P-T axis.
 Reduced peripheral TBG degradation rate.
 80% TBG (greater affinity) 15% TBPA (greater
binding).
 Increase in total but not free thyroid hormone which
remains within normal limits.

 Gestational Transient Thyrotoxicosis)

 Seen in 10% to 15% of pregnant women during early pregnancy.
 Mildly increased free T4 and suppressed TSH early in pregnancy not due
to intrinsic thyroid pathology.
 Characterized by mild or no symptoms, and resolves spontaneously by the
second half of pregnancy.
 No evidence of thyroid autoimmunity, when evaluating thyroid
antibodies (thyroid peroxidase antibodies ) or immunoglobulin's (thyroid-
stimulating immunoglobulins).
 Associated with hyperemesis gravidarum.
 Also with hydatidiform mole, secondary to high levels of hCG that lead to
TSH receptor stimulation.
 Rarely symptomatic, no treatment with anti-thyroxine medications.

 Fetal thyroid:
 Form as a midline
outpouching of the
anterior pharyngeal
floor, migrates and
reaches its final
position by 7 weeks.
 Lateral contributions
from the 4th and 5th
pharyngeal pouches
give its bilateral
shape by week 8-9.

 Fetal Thyroid

 The fetal thyroid begins concentrating
iodine by 10 to 12 weeks and produces
thyroid hormones (T4 and T3) between 15
and 18 weeks of gestation, with the fetal
pituitary also producing TSH beginning
around this time.
 Although fetal thyroid is functional, it still
depends on adequate amounts of iodide
from mother.
 Placental transfer of maternal T4,T3 is
believed to occur prior to fetal thyroid
hormone synthesis and continue thereafter.
 May be the only source of thyroid hormone
during early fetal life, and it is important to
maintain normal maternal thyroid status for
brain maturation of the developing child.

 Hypothyroidism Normal

 Complicates 1-3/1000
pregnancies.
 Most common cause of
primary hypothyroidism in
women of child-bearing age is
chronic autoimmune
thyroiditis (Hashimoto’s
thyroiditis).
Hashimoto’s thyroiditis
 Painless inflammation with
progressive enlargement of
the thyroid gland (diffuse
lymphocytic infiltration,
fibrosis, parenchymal
atrophy, eosinpohilic
changes).

 Other causes primary hypothyroidism (thyroid gland)
 Endemic iodine deficiency
 Ablative radioiodine therapy
 Thyroidectomy

 Secondary hypothyroidism (pituitary)
 Lymphocytic hypophysitis
 Hypophysectomy

Tertiary hypothyroidism (hypothalamus)
 Rare

Hypothyroid Symptoms: (similar to pregnancy complaints)

 Fatigue  Insomnia
 Constipation  Weight gain

 Cold intolerance  Hair loss

 Muscle cramps  Carpel tunnel
 Voice changes
 Intellectual slowness

 Signs of
hypothyroiddism:

 Peri-orbital edema
 Dry skin
 Goiter
 Prolonged relaxation
phase of DTR’s

 Maternal/Fetal Risk

 Infertility
 Spontaneous abortion
 Pre-eclampsia
 Placental abruption
 Low birth weight
 Prematurity
 Stillbirth

 Fetal Risk: Impaired neurodevelopment

 Initial phase of the fetal brain (neuronal multiplication,
migration, and organization) during the second trimester,
the supply of thyroid hormones to the growing fetus is
almost exclusively of maternal origin.
 During the next phase of fetal brain development (glial
cell multiplication, migration and myelinisation), from the
third trimester up to 2-3 years postnatally, the supply of
thyroid hormones to the fetus is essentially of fetal origin.
 While severe maternal hypothyroidism during the second
trimester will result in irreversible neurologic deficits,
maternal hypothyroxinemia occurring at later stages will
result in less severe, and also partially reversible, fetal
brain damage.

 Diagnosis

 TSH (most sensitive):
 Non-pregnant normal range for TSH (.45-4.5
mIU/ml).
 95% have levels <2.5 mIU/ml., and those with
levels 2.5-4.5 mIU/ml are at greater risk for
overt disease.
 T4: (nl 0.7-1.8 ng/dl)

 For diagnosis of hypothyroidism, elevated TSH
and decreased T4.

 Management:
 Levothyroxine sodium
(Synthyroid)
 1-2 mcg/kg/d (100 mcg/d).
 Measure TSH every 6-8 weeks

(.5-2.5 mIU/L).
 T4 can be helpful to determine
response to treatment.
 Adjust medication dose on
25-50 mcg increments.

 Newly diagnosed hypothyroid patient, a full
replacement dose of levothyroxine should be
instituted immediately, assuming there are no
abnormalities in cardiac function.

 To normalize the T4 pool more rapidly (when
clinically required), therapy may be initiated by
giving for two-three days a levothyroxine dose which
is two-three times the estimated final replacement
daily dose.

 This will allow more rapid normalization of the
circulating T4 levels and a more rapid return to the
euthyroid state.

 Thyroxine requirements of women with preexisting
hypothyroidism increase during pregnancy and about
30-50% will need adjustment of their medication:

 estrogen-induced increased TBG concentrations
 increased volume of distribution
 increased placental T4 degradation and transport

 Check TSH levels on first prenatal visit
 Adjustment of levothyroxine dosage should be
implemented as early as possible during gestation
and certainly within the first trimester.

 Those well-controlled can have TSH levels checked
each trimester.
 Drugs that interfere with levothyroxine:

absorption: (cholestyramine, ferrous sulfate,
aluminum hydroxide antacids)
metabolism: (phenytoin, carbamazepine, rifampin)

 After delivery:
 Levothyroxine dose should progressively be reduced to
its pregestational level.
 TSH concentration rechecked at the 6th-8th week
postpartum visit.
 Patient can breastfeed.

 Subclinical hypothyroidism:(elevated TSH/normal T4)

 Some suggest treat to restore TSH to normal range due
to possible increase in fetal wastage or impaired
neurodevelopment but no consensus or ACOG
recommended.

 Isolated hypothyroxinemia: (normal TSH/lowT4)

 May suggest central hypothyroidism (pituitary
macroadenoma, pituitary surgery or radiation).
 Associated with iodine insuffiency causes autoregulatorty
response that leads to low T4.
 Possible treatment for impaired fetal neurodevelopment
with central hypothydoidism conditions otherwise no
treatment.

 New guidelines of the American Thyroid Association (ATA)
reported online July 25, 2010

 Women who are already receiving thyroid replacement
therapy should increase their dose by 25% to 30% when
they become pregnant.
 Women with subclinical hypothyroidism in pregnancy who
are not initially treated should be monitored for
progression to overt hypothyroidism.
 Serum thyroid-stimulating hormone (TSH) and free
thyroxine (FT4) levels should be measured approximately
every 4 weeks until 16 to 20 weeks' gestation and at least
once between 26 and 32 weeks' gestation.

 In the first trimester, normal range for TSH level
is 0.1 to 2.5 mIU/L; this level increases to 0.2 to
3.0 mIU/L in the second trimester and 0.3 to 3.0
mIU/L in the third trimester.

 During pregnancy and lactation, the minimal
suggested daily recommended allowance for
iodine is 250 μg.
 The risk for fetal hypothyroidism may increase
when total daily iodine intake from diet and/or
supplements is or exceeds 500 μg.

 Congenital hypothyroidism
 Cretinism: "Jonny druitt syndrome"
 Dull look
 Puffy face
 Thick tongue that sticks out
 Choking episodes
 Constipation
 Dry, brittle hair
 Jaundice
 Lack of muscle tone
 Low hairline
 Poor feeding
 Short height
 Sleepiness
 Sluggishness

 Other caues congenital
hypothyroidim:

 Thyroid agenesis, inborn errors of
metabolism, maternal blocking
antibodies, congenital pituitary
and hypothalamic hypothyroidism.
 Neurological impairment if not
treated before 3 months
postnatal.

Neonatal Hypothyroidism

 Hyperthyroidism

 Hyperthyroidism affects 2/1000
pregnancies
 Graves disease (diffuse toxic goiter) is the
most common form of overt
hyperthyroidism.
 Organ-specific autoimmune process where
thyroid stimulating autoantibodies attach
to and activate TSH receptors.
 In some with history of Graves disease,
thyroid stimulating autoantibodies activity
may decrease with chemical remission.
 Other etiologies:
 Functional adenoma or toxic nodular
goiter, thyroiditis or excess thyroid intake.

 Symptoms

 Nausea/Vomiting
 Weight loss
 Nervousness
 Heat intolerance
 Insomnia
 Breathlessness
 Diaphoresis
 Fatigue
 Anxiety

Signs:
 Thyromegaly
 Diffuse goiter
 Exophthalmos
 Pretibial myxedema
 Increased cardiac output
 Systolic flow murmur
 Resting pulse >100
(tachycardia)

 Maternal Risk:

 Congestive heart failure
 Thyroid storm
 Pre-eclampsia

 Fetal Risk

 Early pregnancy loss
(increased risk
congenital anomalies
untreated)
 IUGR
 LBW
 PTB

 Neonatal hyperthyroidism 1-2%
 Thyrotropin receptor-stimulating
antibodies (TSHR-SAb), can cross the
placenta, and cause an overactive
thyroid in the fetus.
 small head circumference, prominent
forehead
 Enlarged thyroid (goiter)
 Difficulty breathing
 High blood pressure
 Tachycardia
 Arrythmia
 Emesis
 Diarrhea

 Hyperthyroidism:
 Diagnosis

 Depressed serum TSH (< .45mIU/L)
 Elevated T4 (>1.8 ng/dl)
 Rare T3 thyrotoxicosis (check for if
depressed TSH but normal T4)
 Check TSH receptor antibodies, may be
increased risk neonatal hypothyroidism)

 Antithyroid drugs: inhibit iodination of
thyroglobulin and thyroglobulin synthesis:

 Propylthiouracil(PTU):
 Also some blocking T4 to T3 conversion
 Crosses the placenta less readily
 Initial daily dose 100-600 mg, suggest start 300
mg/d
100-150 mg q 8 hr.
50 mg. qid
150 mg/d
Maintain 50mg bid

 Methimazole :10-40 mg daily dose

 Management:
 Maintain T4 in upper normal range using lowest
possible dose.
 May be able to discontinue 32-34 weeks.
 Improvement in T4 in 4 weeks
 Normalization TSH 6-8 weeks

 Methamizole: ? Aplasia cutis,
esophageal and choanal
atresia
 PTU: severe liver toxicity

 Thiomide Risk:
 Rash, hepatitis,drug fever
 10% transient leukopenia
 .1-0.2% agranulocytosis
(acute onset, not dose
related but others feel
related to higher doses and
increased maternal age)

 Other treatments: (unable to take medication)

 Surgery: subtotal thyroidectomy
after 1st trimester
hypothyroidism
recurrent laryngeal nerve paralysis

 Radioactive iodine ablation is contraindicated
and women should avoid pregnancy for at least 6
months

 Monitor closely after
delivery.
 Can get recurrence or
aggravation of
symptoms first few
months.
 Check TSH and T4 6
weeks postpartum.
 Can breast feed, most
medication protein
bound.

 Acute, life-threatening exacerbation of
thyrotoxicosis
 1-2% of patients with hyperthyroidism progress to
thyroid storm
 Precipitated by a physiologically stressful event,
labor, delivery, C/Section, infections
 If untreated, thyroid storm may be fatal is as
high as 20%

 Fever  Nausea
 Tachycardia  Vomiting
 Tremor  Diarrhea
 Delirium  Dehydration
 Coma

 Tachycardia (out of proportion to the fever)
 Diaphoresis (often profuse)
 Widened pulse pressure
 Congestive heart failure (may be a high
output failure)
 Atrial fibrillation (may be refractory to
attempted rate control with digitalis;
converts after antithyroid therapy in 20-50%
of patients
 Shock

Up to one half of patients presenting to the ED in thyroid storm
report a dramatic weight loss of more than 40 lb.

 1 gm PTU p.o. or crushed in NG tube the continued
200 mg. q. 6 hours or 600 mg. b.i.d.
 One hour later give Sodium iodide 500-1000mg IV q. 8
(block release T3 and T4)
oral 5gtts KI or 10 gtts Lugol’s solution q. 8 hrs.
If hx iodide anaphylaxis, give lithium carbonate 300 mg.
q. 6 hrs.

 Propranolol: 40 mg.p.o q 6 hr. (1-2 mg IV) for
tachycardia >120 bpm.
 Dexamethasone 2 mg q. 6 hrs. X 4 doses (block
peripheral conversion T4 to T3)
 Fluid and nutritional support
 Treat hyperthermia

 Post-partum Thyroditis

 3-6 months postpartum.
 Up to 10% women first year after childbirth.
 Secondary to thyroid autoantibodies.
 Depression, memory impairment, carelessness.

 Risk:
Family hx of thyroid or other autoimmune
diseases, 25% +IDDM will develop disease
 Transient hypo or hyper thyroidism

 Two Phases:
1) 1-4 months post delivery: glandular disruption
leads to hormone release (4% transient
thyrotoxicosis)
abrupt; develop small, painless goiter, fatigue,
palpitations
antithyroid meds ineffective, can give b-
blockers
2) 4-8 months postpartum (2-5% develop
hypothyroidism)
treat with thyroxine 6-12 months

 Most recover within 12 months
 30% permanent hypothyroidism

 Subclinical Hyperthyroidism

 Depressed TSH with normal T4
 1.7% of pregnancies
 More common in iodine deficient areas
 Long-term sequale:

 Osteoporosis, cardiovascular morbidity, overt
thyrotoxicosis, thyroid failure.
 No adverse pregnancy affects

Obstetrix Professor

 www.secondopinion2.com
 info@secondopinion2.com

Thyroid Disease in Pregnancy

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