Thyrotoxicosis in pregnancy

Outline

• Transient thyrotoxicosis of pregnancy

• Graves disease during pregnancy

Changes in thyroid physiology in
pregnancy
Physiologic changes during
pregnancy
Transient thyrotoxicosis of
pregnancy (TTP)
 TTP: Prevalence

• Close to 20% of pregnant women have a

suppressed TSH and normal free T4

• In about 2.4% pregnant women had low

TSH ( less than 0.20 mU/liter) and high
free T4 index concentration.
 Prevalence

Gestational thyrotoxicosis is at least 10-fold

more frequent than hyperthyroid ism due to
graves disease
 Pathogenesis

Human chorionic gonadotropin (hCG) is

a weak TSH agonist

The etiology of thyroid stimulation

during pregnancy is related to hCG
action
 Action of HCG on thyroid cells

In thyroid cells, hCG increases CAMP, iodide

transport , and cell growth and hormone
synthesis.
Mirror curve of TSH and HCG
concentrations

Glinoer et al., 1990,The Endocrine Society

 TTP:
Role of HCG

• In normal pregnancy, when hCG levels are

highest at 10–12 wk gestation, there is
suppression of serum TSH levels,
presumably due to slight increases in free
thyroxine concentration driven by high hCG
values
HCG level and thyrotoxicosis (cont)

These abnormalities are exaggerated in

hyperemesis gravidarum and more so in
gestational Hyperthyroidism , especially if
peak hCG values exceed 75–100,000 IU/ml
with a duration of the peak that exceeds the
normal situation (which is less than 1 wk).
HCG level and thyrotoxicosis (cont)

In twin pregnancies, HCG levels tend to be

higher and suppressed TSH levels are more
frequent and more prolonged.
 Distinction between transient
thyrotoxicosis of pregnancy (TTP) and
Graves' disease
Distinction between TTP and Graves' disease

1.charachteristics of hyperemesis
gravidarum are present in former .
2.Goitre is usually but not necessarily
absent in the former
3.No past history of thyroid disease is
reported by the patient or her family.
4.Ophthalmic examination reveals no
abnormality, in contrast to half of patients
with graves disease. Graves' disease.
5.Gestational age
 Distinction between gestational
transient thyrotoxicosis and
Graves' (cont)

Gestational transient thyrotoxicosis is usually

of short duration and spontaneously
resolves with the decline of hCG. in these
patients freeT4 levels normalized by 15 wk,
whereas TSH remained suppressed until 19
wk gestation
Distinction between gestational transient
thyrotoxicosis and
Graves' disease:TFT

• Antithyroid antibodies are usually absent in

gestational transient thyrotoxicosis. In
particular, TSHR antibodies are absent

• Serum free T3 is elevated less frequently in

GTT compared with graves disease
 Treatment

• Clinical symptoms usually are mild

• Close observation of the course of the
clinical presentation and thyroid hormone
abnormalities is indicated.
• Beta blockers such as metoprolol may be
helpful and may be used with obstetrical
agreement
 Key massges

• Transient thyrotoxicosis of pregnancy should

differentiated from hyperthyroidism solely based
on clinical judgment

• Subjects with TTP should be observed carefully

and treated with appropriate beta blockers if have
sever symptoms of thyrotoxicosis
Graves disease during pregnancy
 Prevalence

• Prevalence of hyperthyroidism in
pregnancy less than 0.1
• About 85% of cases are Graves’disease

De Groot et al. JCEM,2012: 2543–2565

 Clinical course of Graves in
pregnancy
First trimester

 Second and third trimester

Postpartum period
 Clinical manifestations
• Symptoms are non-specific and may be
mimicked by normal pregnancy.

• Significance of goiter

• TFT must be interpreted in the context of

the normal gestational changes of decreased
serum TSH and increased T4and T3 levels
De Groot et al. JCEM,2012: 2543–2565
 Maternal complications of
hyperthyroidism in pregnancy

Manissto etal.JCEM, 2013,

2725-2733
 Fetal complications
• Low birth weight
• Fetal hypothyroidism
(overtreatment of mother)
• Fetal central congenital hypothyroidism
(undertreatment of maternal hyperthyroidism)
• Fetal thyrotoxicosis placental passage of TSI
• Fetal death

De Groot et al. JCEM,2012: 2543–2565

Neonatal Graves
 Treatment:
Goal

• Goal of therapy : maintaining free T4 or FTI

upper limit of the non pregnant reference range.

evidence level :B (1QQEE)

De Groot et al. JCEM 2012, 2543–2565,

 Treatment:
Choosing ATD
• PTU is recommended as the first-line drug for
treatment of hyperthyroidism during the first
trimester of pregnancy
• Monitoring liver function is recommended every
3–4 wk and encourage patients to promptly report
any new symptoms of hepatitis
• MMI may also be prescribed if PTU is not
available or if a patient cannot tolerate or has an
adverse response to PTU.
level: C; evidence, poor (2QEEE)

De Groot et al. JCEM 2012, 2543–2565,

Aplasia cutis
Aplasia cutis
 Treatment:
Choosing ATD
• After switching from PTU to MMI, thyroid
function should be assessed after 2 wk
and then at 2- to 4-wk intervals

( level: B; evidence, fair (1QQEE)

.
De Groot et al. JCEM 2012, 2543–2565,
Treatment
 Thyroidectomy
Indications :
•patients with severe adverse reaction to ATD
therapy
•persistently high doses of ATD are required
over 30mg/d of MMI or 450 mg/d of PTU
• Non adherence to ATD.
Optimal timing of surgery: second
trimaster
level: C; evidence, fair (2QEEE)
De Groot et al. JCEM 2012, 2543–2565,
 Subclinical hyperthyroidism

• No evidence of benefit of treatment of

subclinical hyperthyroidism during
pregnancy

• Treatment could potentially adversely affect

fetal outcome
level: C; evidence, fair (2QEEE)
De Groot et al. JCEM 2012, 2543–2565,
 Key massages
• Goal of treatment in maternal hyperthyroidism is
achieving free T4 or FTI in upper limit normal

• PTU is recommended in firs trimester

• Methimazole is recommended in second and third

trimester

• TFT should be carry out at least monthly and

stepwise decreasing antithyroid drugs during
pregnancy is recommended to achieve above goal
Thank you