Tanitra Tantitamit,MD

Introduction
Thyroid disease is the second most common
cause of endocrine dysfunction in childbearing
age woman

Rapidly absorbed
dietary iodide

Colloid
droplets by
pinocytosis

Lysosomal exopeptidases
break the binding between
thyroglobulin and T4 (or T3).

Iodide trap

RER synthesises
a thyroglobulin

I - attached to
L-thyrosine in
thyroglobulin form
DIT or MIT

MIT and DIT are

deiodinated,

Thyroid synthesis and secretion are controlled by TRH and negative feedback

Maternal Thyroid Physiology

Three series events occur at different time point of gestation.
1. First half of gestation continuing until term
TBG ( from estrogen ) FT3 FT4 stimulating HPT axis.

2. The second event takes place transients during first trimester

When hCG peak ,TSH lowest and FT4 highest
hCG 10000IU/L increment of associate with basal TSH 0.1mu/liter

3. Alteration of thyroid metabolism occur through pregnancy but more

prominent in second half
Placental deiodinase Type I : not significant modified
Type II : maintain T3 producction
Type III : conversion T4 rT3 ,T3 T2
( low T3 and high rT3)

Maternal Thyroid Physiology

Free H

Placental Deiodenase
Type II : T4 toT3
Type III : T4 to rT3

Bound H

T4 T3
EST

TBG
TBG

hCG

Laboratory evaluation during pregnancy

FT4(pmol/L)
FT3(pmol/L)
TSH(mIU/L)

Not
pregnant

First
trimester

Second
trimester

Third
trimester

11-23
4-9
<4

10-24
4-8
0-1.6

9-19
4-7
1-1.8

7-17
3-5
7-7.3

TSH FT4 : Best way to evaluate thyroid function

In early FT3 FT4 can be high normal ,TSH can be low
(Because hCG effect), then FT3 FT4 fall but not below lower limit

Placentalfetal thyroid physiology

Gestation age

Physiology

7wk
8-9 wk
10-12wk

Thyroid gland form

Bilateral shape form ,TRH is detectable
Pituitary portal circulation is function
Excess iodine cause fetal goiter and hypothyroidism
Increase iodine uptake ,TBG and T4 level
Smaller increase T3 and FT3

18-20wk

(because availability of placenta type III deiodinase )

Fetal tissue depend on T3 for brain development

Placentalfetal thyroid physiology

Maximum growth velocity development of brain
First phase
occur during second trimester
The supply thyroid hormone is maternal origin
If low T4 irreversible neurological defect,
when occur later partially reversible

Second phase
occur during trimester to 2-3 wk postnatally
The supply is fetal origin.

Placentalfetal thyroid physiology

Placental transfer and thyroid function
TSH , TBG does not cross placenta
TRH and T3 (inactive form) crosses placenta,
The small but effective transfer T4,
important to fetal growth esp. brain development
Agents :Iodine ,thioamides
B blocker , Somatostatin
Exogenous TRH
Dopamine agonist and antagonist
Thyroid stimulating immunoglobulin

Hyperthyroidism
Prevalence 0.05%- 0.2% of pregnant woman ,
95%of these have a diagnosis of Graves
disease

Graves disease
Cause by thyroid stimulating Ab (TSAb) ,IgG class
bind to TSH receptor stimulate follicular cell.
TSAb may cross placenta cause fetal
hyperthyroidism, however placenta act as partial
barrier ,so only high titer are affected

Gravesdisease
Complication in uncontrolled
The two most serious ; CHF and thyroid storm
Thyroid storm is medical emergency with MR 25%
CHF ,the more common, is caused by the long term
myocardial effects of T4

Others
Miscarriage , Growth restriction , Premature labor
Placenta abruption ,Preeclampsia ,Infection

Graves disease
Diagnosis
Mimicked hypermetabolism of normal pregnancy
fatigue ,heat intolerance, diaphoresis, tachycardia
More reliable symptoms
PR>100bpm , weight loss , diffuse goiter
Grave opthalmopathy

Laboratory
Increase FT4 FT3 TSAb
Decrease TSH

Management; prepregnancy
Establish the diagnosis of hyperthyroidism
Avoid conception until 4 mo after completion of
radioiodine therapy
Should be euthyroidism for 3 months before
conception

Prenatal management
The goal of treatment
Maintain a euthyroidism and minimal effect of drug
FT4 at the upper normal limit
Provide symptomatic relief

Therapeutic modality
Thionamide
Beta blockers

Iodide
Surgery
Radioactive iodine

Prenatal management
Thionamide
Methimazole and Propylthiouracil
Inhibit thyroglobulin synthesis
Some physician prefer PTU,

PTU also inhibit peripheral conversion

Placental transfer and transfer to breast milk less than MMI
No aplasia cutis/ MMI embryopathy
Disadvantage of PTU ; shorter acting ,more pills require

Prenatal management
Thionamide
Dose :
Initially , PTU 300-450 mg/ MMI 30-45 mg daily for 4-6 wk,
Once euthyroidism , taper dose with further reduction
When take low dose (PTU< 100mg/d MMI10mg/d x 4wk)
should discontinue by 32-36 week

Prenatal management
Thionamide
Adverse effect
Rash or urticaria 5%, pruritis ,hepatitis ,
lupus like syndrome, bronchospasm, leukopenia
Agranulocytosis ; Uncommon 0.1% but Severe
Common in older patient with higher dose
In women with sore throat and fever :
stop drugs and obtain WBC count (improve over day or week)
idiosyncratic with PTU but dose related with carbimazole

Prenatal management
Thionamide
Adverse effect
MMI increase risk of cutis aplasia, scalp deformity
and embryopathy (choanal atresia ,tracheoesophageal
fistula ,facial anomalies) usually dose 20mg/> per day
High doses may cause fetal hypothyroidism
but rarely cause goiter

Prenatal management
Beta blocker
Control adrenergic symptoms
Also reducing peripheral conversion of T4 toT3
Propanolol 20-40 mg/d or Atenolol 50-100 mg/d,
three times daily
Prolong treatment associate IUGR ,bradycardia and
hypoglycemia

Prenatal management
Iodide
Limited to preoperative use.
Long term use results in fetal goiter and hypothyroidism
and not adequate control of thyrotoxicosis

Prenatal management
Radioactive iodine (Iodide 131)
Absolute contraindication in pregnancy
Concentrate in fetal thyroid after 12wk , causing fetal
and neonatal hypothyroidism
Pregnant who inadvertently receive I131,
SSKI should be given immediately along with PTU
within 7-10 day of exposure

Prenatal management
Surgery
Reserved for patients who do not response
and cannot tolerate the medication
2 wk of iodine preoperative to decrease gland
vascularity and prevent thyroid storm
Best in second trimester
Risk of anesthesia ,hypoparathyroidism(1-2%) ,
recurrent laryngeal nerve palsy(1-2%)

Prenatal management
Fetal wellbeing
Recommended for
poorly controlled ,
high TSAb titer even euthyroidism .

Serial USG for dating and growth evaluation

Intrapartum management
Not increase risks in adequately treated
thyrotoxicosis
Labor and delivery may precipitate thyroid storm
in poorly treated thyrotoxicosis.

Intrapartum management
Thyroid storm
Extreme symptoms of hyperthyroidism
Fever is progressive ,begin few hours after a stressful
event and may exceed 40C
Mental status is commonly altered
Severe diarrhea, nausea vomiting and abdominal pain
If severe, high cardiac output failure ,increase PP but
normal BP, shock may ensue with prolong duration

Intrapartum management
Thyroid storm
Difficult to diagnosis because result of biochemical test
may not differ from who have thyrotoxicosis without
thyroid strom.
If suspect, treatment should not be delayed.
The goal of treatment
Decrease hormone production and effect
Provide supportive therapy and treat the underlying disease

Intrapartum management
Treatment Thyroid storm
PTU

600-800 mg
then 150-200mg
SSKI 2-5 drop orally
NaI
0.5-1.0g IV
Lugols solution 8 drop

every 8 hr orally ,NG or rectally

every 4-6 hrs
every 8 hrs or
every 8 hrs or
every 6 hrs

Initiated 1-2 h after thionamide therapy

Attemp to block thyroid release from colloid space

Propanolol
40-80 mg orally every 4-6 hours or 1mg/min IV

Intrapartum management
Treatment Thyroid storm
Dexamethasone 2mg IV or IM every 6 hrs x 4 doses
Phenobarbital 30-60 mg orally every 6-8 hrs
as needed for extreme restlessness
Supportive therapy
Control blood volume , glycemic level, temperature and
electrolyte.

Postnatal management
Lactation
Consider safe if PTU total doses 150mg ,MMI 10mg
Only 0.07% of maternal PTU dose is excreted in breast
milk, with higher dose for MMI (10%)
Perform TFT on cord blood and in neonate in woman
who are breast feeding
Should take medication after BF ,3-4h interval before
lactation again

Postnatal management
Symptoms may worsen ,especially if medication
dosage was reduced
If TSAb titer is high, screen for neonatal
thyrotoxicosis on day 3-4 and day 7-10 of life.
Observe the neonate for signs of hypothyroidism if
maternal taking medication

Fetal and neonatal thyrotoxicosis

Cause by transplacental passage of TSAb

Occur in 1%-17% of baby born to GD woman
These Ab exert an effect on the fetal thyroid at 20 wkGA.
Fewer cases are diagnosed in utero than in neonatal period

Fetal and neonatal thyrotoxicosis

Fetal thyrotoxicosis
Suspected in persistent tachycardia (>160 beats/min),
May lead to premature delivery(90%) ,
fetal craniosynostosis ,exophthalmos, hydrop fetalis
,hepatosplenomegaly ,thrombocytopenia, goiter and
growth restriction

Fetal and neonatal thyrotoxicosis

Neonatal thyrotoxicosis
Jaundice, poor feeding, poor weight gain ,irritability
MR may as high as 25%
Usually transient ,lasting 2-3 months after delivery and
may be delayed up to 2 weeks if mother take ATD until
delivery (TSAb are cleared slowly than medication)

Fetal and neonatal thyrotoxicosis

Prediction
Test Maternal TSH receptor autoAb in early pregnancy
to predict fetal thyrotoxicosis
If high titer or if level does not decrease
fetal thyrotoxicosis should be anticipate
Recommended USG to assess fetal growth ,HR and goiter

Test again in late pregnancy to predict neonatal disease

If Ab are detected in late pregnancy
cord blood and neonatal TSH and FT4 should be perform

Fetal and neonatal thyrotoxicosis

Treatment
In utero most cases are treated by PTU given to mother
Subsequence maternal hypothyroidism can be treated
with thyroxine , which does not cross placenta
Cordocentesis ,percutaneous fetal blood sampling may
play a role for monitoring treatment

Transient hyperthyroidism
Seen in most pregnant women (66%)
The most likely etiology is thyroid stimulation by hCG
(or hCG subfractions).
Patients with this condition have no previous history o
f thyroid disease, no palpable goiter,
no S&S of hyperthyroidism except for tachycardia,
Women with early pregnancy with weight loss, tachycardia,
vomiting and laboratory may be difficult to DDX from early,
true thyrotoxicosis.

Transient hyperthyroidism
Thyroid antibodies are negative.
TSH ,T3, T4 but T3 is lower than true hyperthyroidism.
The degree of thyroid function abnormalities correlates with
the severity of vomiting.
The time to resolution is widely variable (110 weeks).
Treatment is symptomatic, and antithyroid medication is not
recommended.

Introduction
Rare because of menstrual disturbance and
frequency anovulatory.
(1/1600-2000 of deliveries)

Diagnosis
Symptoms
Insidious ,can be masked by hypermetabolic
stage of pregnancy
Lethargy ,cold intolerance , weight gain,
constipation, hoarseness, hairless ,brittle nail ,dry
skin

Signs
Goiter ,bradycardia, thyroidectomy scar, delay
relaxation of DTR

Diagnosis
Laboratory
TSH ,FT4 : Overt hypothyroid
TSH , normal FT4 : Subclinical hypothyroid
Positive thyroid autoantibody ; may cross placenta
Lipid, CPK, Liver enzyme may elevate
Antiperoxidase Ab (TPO Ab)
Antimicrosomal Ab (AMA Ab)
Antithyroglobulin Ab (ATG Ab)

Differential diagnosis
Hashimotos thyroiditis
Most common autoimmune disease
8-10% of reproductive women

Present antithyroid Ab
Almost have Antithyroidperoxidase Ab elevate 50-70% of pregnancy

Goiter form
Diffuse enlarge painless infiltrated by lymphocyte and plasma cell
Many patients are euthyroid but can subsequently develop
hypothyroidism

Atropic form
Idiopathic hypothyroidism and negative Ab
Less common than Goiter form

Differential diagnosis
Post I131 ablation, thyroidectomy
10-20% develop hypothyroid within 6 months after
I131 ablation , 2-4% develop each year thereafter

Subacute viral thyroiditis

Secondary to hypotha;roid or Pituitary disease

Differential diagnosis
Drug induced
Inhibit synthesis ;
Inhibit T4 T3 ;

Thoinamide ,I2,Li
Amiodarone

Inhibit clearance ;
CBZ ,Phenytoin, Rifampin
Interfere intestinal absorption ;
AlOH3 , Cholestyramine, FeSO4, Sucralfate, Calcium

Implication of hypothyroidism
Higher pregnancy complication rate

Miscarriage
Preeclampsia
Placental abruption
Low birth weight
Prematurity
Stillbirth

Frequently associated with type I DM

T4 replacement treatment can increase in insulin
requirement.

Implication of hypothyroidism
Fetal effect
Mild maternal hypothyroid alone associated with
lower IQ level in the offspring
Not increase frequency of congenital anomalies

Implication of hypothyroidism
Fetal and neonatal hypothyroidism
Severe neurological deficit also occur in children
with congenital deficiency of thyroid hormone
Thyroid hormone deficit from maternal blocking Ab
transferred to fetus
Could more accurately be determined by
cordocentesis than amniotic fluid concentration
measurement
Optimal T4 necessary to correct hypothyroidism

Implication of hypothyroidism
American Association of Clinical Endocrinologists (1999)
Routine TSH measurement before or in early pregnancy are
reasonable
Determined TSH in all pregnancy with
Goiter, Positive thyroid Ab , Hx of autoimmune disease ,
Family history of thyroid disease ,DM type I

Administration thyroxin promptly even if TSH elevation is mild

Women on thyroxin treatment should be monitored during
pregnancy

Treatment
Thyroxin (T4) is drug of choice
Fetal brain unable to use maternal T3
Initiate dose 0.1-0.15 mg/day
Adjust dose accord TSH level every 4 wk until TSH
is in lower end of normal range
If euthyroidism on T4 in early pregnancy
rechecked every 8 wk (during pregnancy increase
requirement)

Treatment
The cause of increase T4 requirement
Renal increased demand
FeSO4 Therapy ,
should be taken at difference time from T4 treatment

After delivery , reduce dose to prepregnancy

levels and check TSH 6-8 wk later

Introduction
Autoimmune thyroid disease, which is
suppressed during pregnancy ,is
exacerbated in postpartum period
Up to 10% of all postpartum pregnancy
Usually lymphocytic thyroiditis thyroiditis
Less frequently in Graves disease

Immune change gradually return to

normal in 12 months postpartum

Postpartum Graves disease

Development of TsAb
Peak of Ab 3-6 months of postpartum
period
Almost all patients with persistent TSI will
develop recurrence of grave disease,
if ATD withdrawn

Postpartum thyroiditis (PPT)

TSH or during first PP year in
negative TSI or toxic nodule
(Exclude GD)
Incidence 6-8%, increase in type I DM
High recurrent rate 64%

Postpartum thyroiditis (PPT)

Clinical, classically
Hyperthyroid phase ;
6wk -6mo PP
TSH , T4 and radioactive iodine uptake

Hypothyroid phase
follows and can last up 1yPP
TSH and Antithyroid Ab , T4

Classical symptom present only 26% ,

hyperthyroidism alone 36% and
hypothyroidism alone 36%

Postpartum thyroiditis (PPT)

Treatment
Hyperthyroid phase ;
blocker for symptomatic treatment,
ATD no role a play

Hypothyroid phase ;
low dose T4 required ,wean off 6mo after
initiation ,some recommended maintain 1y

Postpartum thyroiditis (PPT)

Screening
No cost-benefit analysis
Should screen in high risk
(history of PTT ,DM I) and symptomatic
women

Postpartum thyroiditis (PPT)

Recovery of TFT
Not universal , 77% recover during first
PP year 23% permanent hyperthyroid
Women with history of PPT should be
evaluate TFT annually for possible
develop of hypothyroid

Solitary thyroid nodule

Pregnancy does not affect growth rate CA and
prognosis of CA
Risk of malignancy 5-43% associated with
previous radiation ,growth rate ,Age
Surgery is increase risk of miscarriage, preterm
,death esp. in 1st ,3rd TM
Radiation is contraindication

SINGLE THYROID NODULE

Abnormal TSH

Normal TSH

W/U for
thyroid dysfunction

USG
Solid < 2cm
Cystic < 4cm

Solid > 2cm

Cystic > 4cm
GA < 28wk

GA > 28wk

FNA
Malignant
Surgery in 2ndTM

Observation
Not Malignant

Thyroid
suppression?

Needle biopsy if

F/U PP