Thyroid Disease and

Pregnancy
Sheila F. Perillo, MD

Thyroid disease is the second most

common endocrine disease affecting

women of reproductive age

Thyrotoxicosis (thyroid storm)

a generic term referring to a clinical and

biochemical state resulting in over-production

of and exposure to thyroid hormone
Overt hyperthyroidism complicates
approximately 2 in 1,000 pregnancies.

Pregnant women with hyperthyroidism are at

increased risk for:

spontaneous pregnancy loss
congestive heart failure
thyroid storm
preterm birth
Preeclampsia
fetal growth restriction, and
increased perinatal morbidity and mortality

Grave's disease
the most common cause of thyrotoxicosis in

pregnancy
An autoimmune condition characterized by
production of thyroid-stimulating
immunoglobulin (TSI) and thyroid-stimulating
hormone binding inhibitory immunoglobulin
(TBII)
facilitate the thyroid-stimulating hormone

(TSH) receptor in the mediation of thyroid

stimulation and inhibition

 Hyperthyroidism- thyrotoxicosis resulting

from an abnormally functioning thyroid

gland.
Thyroid storm- acute, severe exacerbation

of hyperthyroidism

gestational transient
thyrotoxicosis
associated with hyperemesis gravidarum
can be due to high levels of human chorionic

gonadotropin (hCG) resulting from molar

pregnancy
high hCG levels TSH receptor stimulation and
temporary hypothyroidism
rarely symptomatic
treatment with antithyroxine drugs- not beneficial
expectant management
not associated with poor pregnancy outcomes

Impact of Pregnancy on Thyroid:

Thyroxine (T4), the major secretory product

of the thyroid gland, is converted in

peripheral tissues to triiodothyronine
(T3)
T3- biologically active form
T4- secretion is under the direct control of
pituitary TSH
T4 and T3 are transported in the peripheral
circulation bound to thyroxine-binding globulin
(TBG), transthyretin (formerly called
"prealbumin") and albumin.
Less than 0.05% of plasma T4, and less than
0.5% of plasma T3, are unbound and able to
interact with target tissues

20 weeks' gestation
reduced hepatic clearance
estrogen-induced change in the structure of

TBG that prolongs serum half-life

plasma TBG increases 2.5 folds 25% to
45% increase in serum total T4 (TT4) from a
pregravid level of 5 to 12 mg to 9 to 16 mg

** Total T3 (TT3) increases by about 30% in

the first trimester and by 50% to 65% later

Pregnancy increase in available protein

transient change in free T4 (FT4) and free

thyroxine index (FTI) in the first trimester
(possibly related to an increase in hCG)

Increased concentrations of TSH stimulate

restoration of the free serum T4 level, such

that FT4 and FTI levels are generally
maintained within the normal non-pregnant
range

Ultrasound evaluation of the thyroid

gland during pregnancy
Increase in volume
Echo structure remains unchanged (Plasma

iodide levels decrease in pregnancy due to

fetal use of iodide and increased maternal
renal clearance)
15% to 18% increase in size of the thyroid
gland
enlargement usually resolves after delivery
not associated with abnormal thyroid function

tests

Diagnostic Approach:
The suspicion increases if

Mild hyperthyroidism:
Fatigue
increased appetite
Vomiting
Palpitations
Tachycardia
heat intolerance,
Increased urinary

frequency
Insomnia
Emotional instability

patient has
Tremor
Nervousness
frequent stools
excessive sweating
brisk reflexes
muscle weakness
goiter
Hypertension
weight loss.
Grave's ophthalmopathy

(stare, lid lag and retraction,

exophthalmos)
dermopathy (localized or
pretibial myxedema)

Untreated hyperthyroidism poses considerable

maternal and fetal risks, including preterm

delivery, severe preeclampsia, heart failure,
and thyroid storm

Characteristics of Thyroid Storm:

- a hypermetabolic complication of

hyperthyroidism:
hyperpyrexia (temperature >41C)
cardiovascular compromise (tachycardia out of

proportion to the fever, dysrhythmia, cardiac

failure)
gastrointestinal upset (diarrhea)
central nervous system changes (restlessness,
nervousness, changed mental status, confusion,
and seizures).

Thyroid storm is a clinical diagnosis, and

treatment should be
initiatedbeforeconfirmatory test results
are available.

Patients without classic

symptoms
Other signs of thyrotoxicosis in any patient

with postpartum congestive heart failure:

tachycardia
severe hypertension
central nervous system (CNS) features, such as

coma after cesarean section or seizures

suggestive of eclampsia
Delay in diagnosis increase the risk of

maternal mortality

 Thyroid storm is usually seen in patients with

poorly controlled hyperthyroidism complicated by

additional physiologic stressors, such as
infection, surgery, thromboembolism,
preeclampsia, and parturition

Laboratory Tests:
CBC (Leukocytosis)

Coagulation studies

Thyroid function test results

are consistent with

hyperthyroidism (elevated
FT4/FT3 and depressed TSH)
but they may not always
correlate with the severity of
the thyroid storm
Baseline electrolyte

(occasionally hypercalcemia)
Glucose
Renal
Liver function testing

(elevated hepatic enzymes)

CT or MRI of the brain

(unconscious patients,
signs of focal CNS signs)
blood, uterine and wound
cultures (as appropriate)
chest x-ray
12-lead electrocardiogram
(ECG) and continuous
cardiac monitoring
Pulse oximetry
blood gas analysis

Management of thyroid Storm

Thyroid storm is a clinical diagnosis based

on severe signs of thyrotoxicosis:

significant hyperpyrexia (>103F or >41C)

neuropsychiatric symptoms
Tachycardia with a pulse rate exceeding 140
beats/min
congestive heart failure
Gastrointestinal symptoms (nausea and
vomiting) accompanied by liver compromise

Obstetric intensive care unit (ICU)/ ICU that

Management of Thyroid Storm:

has continuous fetal monitoring and can

handle an emergent delivery
Therapy is designed to:
Reduce the synthesis and release of thyroid

hormone
Remove thyroid hormone from the circulation and
increase the concentration of TBG
Block the peripheral conversion of T4 to T3
Block the peripheral actions of thyroid hormone
Treat the complications of thyroid storm and
provide support
Identify and treat potential precipitating conditions

Management of Thyroid Storm

Supportive adjunctive care for the patient in thyroid

storm are:
IV fluids and electrolytes
Cardiac monitoring
Consideration of pulmonary artery catheterization
(central hemodynamic monitoring to guide betablocker therapy during hyperdynamic cardiac failure)
Cooling measures: blanket, sponge bath,
acetaminophen, avoid salicylates (risk of increased
T4). Acetaminophen is the drug of choice
Oxygen therapy (consider arterial line to follow serial
blood gases)
Nasogastric tube

Medications:
Reduce synthesis of thyroid hormones:
Thionamides : propylthiouracil (PTU)
Methimazole)

inhibit iodination of tyrosine -- leading to

reduce synthesis of thyroid hormones and block
peripheral conversion of T4 to T3
can reduce the T3 concentration by 75%

 Iodide (Lugol's iodine, SSKI (Strong Solution of

Potassium Iodide), sodium iodide, orografin, or

lithium carbonate)
inhibit proteolysis of thyroglobulin block
the release of stored hormone
**Because one of the side effects is an initial
increase in production of thyroid hormone, it is
therefore very important to start PTU before you
give iodides

 Glucocorticoids

block release of stored hormone (as do

iodides), and peripheral conversion of T4 to T3
(as do thionamides)
They may also bolster adrenal function, and
prevent adrenal insufficiency

Dosage/ Management:
PTU orally or via nasogastric tube, 300-800 mg loading dose

followed by 150-300 mg every 6 hours

One hour after instituting PTU give: Sodium iodide, 500 mg every

8-12 hours or oral Lugol's solution, 30-60 drops daily in divided

doses.
Iodides may be discontinued after initial improvement
Give adrenal glucocorticoids (Hydrocortisone, 100 mg IV every 8

hour, or Prednisone, 60 mg PO every day, or

Dexamethasone, 8 mg PO every day)
Glucocorticoids may be discontinued after initial improvement

Medications to control maternal

tachycardia
Beta-blocker agents - Propranolol can be used to control autonomic symptoms
(especially tachycardia)
Some effect on inhibition of peripheral conversion of T4 to T3, but

will not alter thyroid hormone release nor prevent thyroid storm.
Use with caution: it has a tendency to increase pulmonary

diastolic pressure, and cardiac failure is a frequent

presentation of thyroid storm
Reserved for heart rates of 120 beats per minute or higher
Propranolol, labetalol, and esmolol

Dosages:
Propranolol,1-2 mg/min IV or dose sufficient to slow heart rate

to 90 bpm; or 20-80 mg PO or via nasogastric tube every 4-6

hourly
Esmolol, a short-acting beta-acting antagonist given IV with a

loading dose of 250 to 500 g/kg of body weight followed by a

continuous infusion at 50 to 100 g/kg/min
Echocardiogram and/or pulmonary artery catheter to help

guide management, especially in cardiac failure

If patient has severe bronchospasm -- give 1-5 mg reserpine

every 4-6 hours or 1 mg/kg orally of guanethidine every 12

hours.

Heart failure due to cardiomyopathy from

excessive thyroxine in women with uncontrolled

hyperthyroidism is more common in pregnant
women
Same treatment as that of thyroid storm
Medical emergency
Give phenobarbital to control restlessness
Phenobarbital: 30 to 60 mg orally every 6-8 hours

as needed
Plasmapheresis or peritoneal dialysis
to remove circulating thyroid hormone
reserved for patients who do not respond to conventional

therapy
Subtotal thyroidectomy (during second-trimester

pregnancy) or radioactive iodine (postpartum)

for unsuccessful conventional therapy

Postpartum Care:
Most asymptomatic women should have a TSH

and free T4 performed approximately 6 weeks

postpartum
PTU and methimazole are excreted in breast milk
PTU is largely protein bound and does not seem to

pose a significant risk to the breastfed infant

Methimazole has been found in breastfed infants of
treated women in amounts sufficient to cause
thyroid dysfunction
at low doses (10-20 mg/d) it does not seem to pose a major

risk to the nursing infant

Teratogenic effects of
Antithyroid Medications:
PTU
first-line treatment for Grave's disease in

pregnancy due to lower risks of teratogenicity

than methimazole.
It crosses the human placenta and associated
with fetal hypothyroidism
Cordocentesis is sometimes recommended to
test fetal thyroid function
does not readily crosses membranes
milk concentrations are quite low

Methimazole (Thiamazole, Mercazole,

Tapazole):
Second-line treatment of Grave's disease
crosses the human placenta and can induce fetal

goiter and even cretinism in a dose-dependent

fashion
commonly associated with fetal anomalies such as
aplasia cutis, esophageal atresia, and choanal atresia
Long-term follow-up studies of exposed children:
no deleterious effects on their thyroid function or physical

and intellectual development with doses up to 20 mg/d

excreted in breast milk

The American College of Obstetricians and

Gynecologists (ACOG) recommends
treatment for women with a systolic blood
pressure higher than 170 mmHg and/or
diastolic blood pressure above 109 mmHg
There is no consensus whether lesser
degrees of hypertension require treatment
during pregnancy because
antihypertensive therapy improves only
the maternal, not the fetal, outcome in
women with mild to moderate chronic
hypertension

Radioactive iodine (iodine-131; I-131):

contraindicated in pregnant women
cost-effective, safe, and reliable treatment for
hyperthyroidism in non-pregnant women
ACOG recommendation: women should avoid
pregnancy for 4-6 months following treatment
Detrimental effects on the thyroid of the
developing fetus as a result of I-131treatment for
thyrotoxicosis of the mother in the first
trimester of pregnancy are reported.
Breast-feeding should be avoided for at least
120 days after treatment

Summary
Thyroid storm

a life-threatening condition, requiring early recognition and

aggressive therapy in an intensive care unit setting.

During gestation, women with hyperthyroidism should have their

thyroid function checked every 3-4 weeks.

Grave's disease represents the most common cause of maternal

hyperthyroidism during pregnancy

Only 0.2% of gestations are complicated by thyroid storm and

more than 90% of cases are caused by Grave's disease

Increased production of thyroid hormone occurs when

autoantibodies (thyroid-stimulating antibody [TSAb] -- formerly

known as LATS [long-acting thyroid stimulator]) against TSH
receptors -- acts as TSH agonists.

Thyroid Storm: Critical Care In Obstetrics

WHEC Practice Bulletin and Clinical

Management Guidelines for healthcare

providers. Educational grant provided by
Women's Health and Education Center
(WHEC).
Published:2 June 2010