Transcript Transient thyrotoxicosis of pregnancy

Thyrotoxicosis in pregnancy
Dr Hashemipour.S
QUMS
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.
Racial differences
• In some studies (Yeo et al., 2001) the
frequency of transient gestational hyper
thyroid-ism reached 11% for Asian women
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
De Groot et al. JCEM 2012, 2543–2565,
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.
HCG level and thyrotoxicosis:
Trophoblastic thyrotoxicosis
The reported prevalence of hyperthyroidism in
patients with hydatidiform mole is 25–64%
.However, most patients with hydatidiform mole
have either none or very few clinical signs of
excess thyroid hormone secretion despite elevated
levels of thyroxine (T4) and triiodothyronine (T3)
It has been reported that about 5% have clinical
hyperthyroidism
Role of HCG quality
• Elevations of thyroid hormone and
suppression of TSH are not entirely
correlated with hCG levels
• An increase in acidic forms of hCG have
demonstrated in hyperemesis gravidarum .
unusual glycosylation patterns of hCG are
common in hydatidiform moles which
frequently present as hyperemesis
gravidarum
mutation of the TSHR
In1998 Cases have been reported about
family in which at least two women
experienced hyperthyroidism , and
hyperemesis gravidarum , during several
pregnancies
Cont
Hyperthyroidism continued throughout
pregnancy. Graves disease was diagnosed
based on duration of hyperthyroidism.
Surprisingly enough, the `Graves' disease
improved in the post-partum period
allowing for discontinuationof antithyroid
drugs. The following pregnancy was also
complicated by hyperemesis and
hyperthyroidism, which required treatment
with antithyroid drugs, and was followed by
recovery of a normal thyroid function postpartum, without any relapse later.
Cont
The daughter had a similar story .She had a
small diffuse goitre, no Graves‘
ophthalmopathy, no thyroperoxidase or
thyroglobulin antibodies,and no TSHR
antibodies. The absence of antibodies,
occurrence of hyperthyroidism only during
gestation and improvement in the postpartum period suggested that Graves'
disease was unlikely
Cont
HCG concentration was within the normal
range during gestation.
Abnormal hCG, with increased thyrotrophic
activity, was hypothesized but ruled out by
in vitro tests.
TTG: TSH receptor mutation
Rodien et al. Human Reproduction Update,2004, 95-105
Hyperemesis gravidarum and
hyperthyroidism
Definition of HG
• Hyperemesis gravidarum, defined as severe
vomiting in early pregnancy that causes
more than 5% weight loss, dehydration, and
ketonuria
prevalence
Frequency ranges from 0.15 %to 1% of
pregnancies. Variation in frequency is
dependent on definition some authors
define hyperemesis gravidarum as severe
vomiting requiring hospitalization which
leads to a higher frequency (up to 1.5%),
whereas others apply a more stringent
definition which includes hydroelectrolytic
disorders, ketosis, and weight loss >5% of
non-pregnant weight
Prevalence (cont)
One puzzling feature of hyperemesis
gravidarum is its variable frequency in
different ethnic groups occurring at a much
higher frequency in the Asian population.
This suggests, at least,a common
predisposing genetic background, if not a
unique disease
Hyperemesis gravidarum
Typically occurs between the 4th and the 10th
week of gestation, with resolution by 20
weeks of gestation. In approximately10% of
HG patients, symptoms will persist
throughout pregnancy.
During the first trimester, the severity of morning
sickness correlates positively with serum free T4
and the concentration of plasma hCG and
negatively with the level of serum TSH
Pathophysiology of HG
The mechanisms of hyperemesis gravidarum
are poorly understood. The syndrome is
favored by hypersecretion of hCG although
normal concentrations of hCG have also
been reported, there is no clear threshold,
since the normal range of hCG
concentration is extremely large.
Prevalence of thyrotoxicosis in
hyperemesis gravidarum
Gestational transient thyrotoxicosis has
been observed in up to two thirds of
women suffering from hyperemesis
gravidarum
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
De Groot et al. JCEM,2012: 2543–2565
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 for your
attention