You are on page 1of 58

Journal Reading

Thyroid Function Tests in


Pregnancy

Hendra Moslem Nurdin, dr


Pembimbing :
Dr. dr. Adityawarman, SpOG (K)
FACTORS AFFECTING
MATERNAL THYROID FUNCTION

BETA HCG
URINARY IODIDE EXCRETION
THYROXIN BINDING GLOBULIN

INCREASE
MATERNAL THYROID DEMAND
Physiologic Changes in Thyroid Function
During Pregnancy
Thyroid binding globulin (TBG) increases due to
reduced hepatic clearance and estrogenic stimulation
of TBG synthesis
The test results that change in pregnancy are
influenced by changes in TBG concentration
Plasma iodide levels decrease due to fetal iodide use
and increased maternal clearance leads to notable
increase in gland size in 15% of women
hCG in early pregnancy (~TSH) T4 , TSH

T3 : Triidothyronine, T4 : tyroxine
Pregnancy Placental transfer
TBG +
TT4, TT3 minimal
FT4, FT3 ++
TSH
Iodide ++
Antithyroid ++
peroxidase antibody

Levothyroxine minimal
PTU or methimazole ++

Berghella, 2011; Cunningham et al, 2010.


Physiologic Changes in Thyroid Function
During Pregnancy

Maternal TSH Free T4 Free


Thyroxine
Total T4 Total T3

Status **initial Index


screening (FTI)
test**
Pregnancy No No No Increase Increase
change change change

Hyperthyroidism Decrease Increase Increase Increase Increase


or no
change

Hypothyroidism Increase Decrease Decrease Decrease Decrease


or no
change
Aetilogy
Hyperthyroidism Hypothyroidism

Graves disease(most Hashimotos (chronic


common = 95%) thyroiditis )
Subacute thyroiditis
Other causes: not associated with goiter
Gestational Thyroidectomy
trophoplastic disease Radioactive iodine
Hyperfunctioning
thyroid adenoma treatment
Toxic goiter Iodine deficiency (most
Subacute thyroiditis common worldwide; rare in
US)
Clinical Finding

Hyperthyroidism Hypothyroidism

Rapid pulse Slow pulse

Increased metabolism Decreased metabolism

Hyperactive reflexes Sluggish reflexes

Emotional lability Placid and phlegmatic

GI effect: diarrhea GI effect: constipation

Warm, moist skin Cold, dry skin


Fetal & Neonatal Effects

Hyperthyroidism Hypothyroidism
Associated with preterm Higher incidence of LBW
delivery, low birth weight, (due to medically indicated
fetal loss preterm delivery, pre-
Fetal thyrotoxicosis eclampsia, abruption)
(related to disease itself or
treatment) Iodine deficient
Risk of immune-mediated hypothyroidismcongenital
hypo/hyperthyroidism (due cretinism (growth failure,
to antibodies crossing the mental retardation, other
placenta, esp. in Graves or neuropsychological deficits)
chronic autoimmune
thyroiditis)
ACOG Recommendations
Screening of all pregnant women with a
personal history, physical examination,
or symptoms of a thyroid disorder.
Results
In the case-finding group, 454 (19.9%)met the
criteria for high risk, whereas 1828 (80.1%) were
low risk. In the universal screening group, 482
(21.1%) would have been classified as high risk
and 1798 (78.9%) as low risk. This difference was
not significant were seen in adverse outcome ( P
= 0.31]
( Negro et al, 2010)
Algorithm for Thyroid Function ( selective case)

( Royal Hospital for Women, Sidney 2013)


If trimester-specic reference ranges for TSH are not
available in the laboratory, the following reference ranges
are recommended:

rst trimester, 0.12.5 mIU/L;


Second trimester, 0.23.0 mIU/L;
third trimester, 0.33.0 mIU/L (ATA, 2011)
Trimester Specific Reference

( Demer LM, Spencer CA, 2003)


Treatment
Hyperthyroid :
PTU is preferred for the treatment of
hyperthyroidism in the rst trimester. Patients on
Metamizole should be switched to PTU if
pregnancy is conrmed in the rst trimester.
Following the rst trimester, consideration should
be given to switching to Metamizole.
Hypothyroid :
- Levothyroxyne
THANK YOU
BETA HCG

THYROID STIMULATING ACTIVITY

B-HCG TSH

BETA CHAIN ALPHA CHAIN BETA CHAIN

IDENTICAL

LH AND TSH RECEPTOR HOMOLOG


Anti-thyroid autoantibodies (or simply anti-
thyroid antibodies) are autoantibodies targeted
against one or more components of the thyroid.

Graves' disease and Hashimoto's thyroiditis are


commonly associated with the presence of anti-
thyroid autoantibodies.
Patogenesis
The production of antibodies in Graves' disease is
thought to arise by activation of CD4+ T-cells,
followed by B-cell recruitment into the thyroid. These
B-cells produce antibodies specific to the thyroid
antigens. In Hashimoto's thyroiditis, activated CD4+
T-cells produce interferon-, causing the thyroid cells
to display MHC class II molecules. This expands the
autoreactive T-cell repertoire and prolongs the
inflammatory response.
Anti-TPO antibodies
Anti-thyroid peroxidase (anti-TPO) antibodies are specific
for the autoantigen TPO, a 105kDa glycoprotein that
catalyses iodine oxidation and thyroglobulin tyrosyl
iodination reactions in the thyroid gland
TSH receptor antibodies
The thyrotropin receptor (TSH receptor) is the antigen for
TSH receptor antibodies (TRAbs). It is a seven
transmembrane G protein coupled receptor that is involved
in thyroid hormone signalling
Thyroglobulin antibodies
Thyroglobulin antibodies are specific for thyroglobulin, a
660kDa matrix protein involved in the process of thyroid
hormone production. They are found in 70% of Hashimoto's
thyroiditis, 60% of idiopathic hypothyroidism, 30% of
Graves' disease, a small proportion of thyroid carcinoma and
3% of normal individuals
AntiNa+/ I symporter
Anti-Na+/I- symporter antibodies are a more recent discovery
of possible thyroid autoantibodies and their role in thyroid
disease remains uncertain. They are present in approximately
20% of Graves' disease and 24% of Hashimoto's thyroiditis
Antithyroid antibody studies are used to evaluate for
autoimmune thyroid problems.
The reference ranges for antithyroid antibodies are as
follows:
Thyroid peroxidase antibody (TPOAb): Less than 35
IU/mL
Thyroglobulin antibody (TgAb): Less than 20 IU/mL
Thyroid-stimulating immunoglobulin antibody (TSI):
Less than 140% of basal activity
Thyroid-stimulating hormone (TSH) receptor binding
inhibitor immunoglobulin (TBII)/TRAb: 1.75 IU/L or
less
Hyperthyroidism
Occurs in 0.2% of Look for:
pregnancies; Graves -Nervousness
disease accounts for 95% of -Tremor
cases
-Tachycardia
-Frequent stools
-Sweating
-Heat intolerance
-Weight loss
-Goiter
-Insomnia
-Palpitations
-Hypertension
-Lid lag/lid retraction
-Pretibial myxedema
Fetal & Neonatal Effects of
Hyperthyroidism
Associated with preterm delivery, low birth weight, fetal
loss
Fetal thyrotoxicosis (related to disease itself or
treatment)
Risk of immune-mediated hypo/hyperthyroidism (due to
antibodies crossing the placenta, esp. in Graves or
chronic autoimmune thyroiditis)
Antibodies in Graves disease can be either stimulatory or
inhibitory
Neonates of women with Graves who have been
surgically/radioactively treated are at higher risk, b/c not taking
suppression
Causes & Diagnosis of
Hyperthyroidism
Most common cause of hyperthyroidism is Graves
disease
Document elevated FT4 or elevated FTI with suppressed TSH,
in absence of goiter/mass
Most patients have antibodies to TSH receptor, antimicrosomal,
or antithyroid peroxidase antibodies, but measurement of these
is not required (though some endocrinologists recommend
measuring TSI, which are stimulatory antibodies to TSH
receptor)
Other causes:
Excess TSH production, gestational trophoplastic disease,
hyperfunctioning thyroid adenoma, toxic goiter, subacute
thyroiditis, extrathyroid source of TH
Treatment of Hyperthyroidism
Goal is to maintain FT4/FTI in high normal range using
lowest possible dose (minimize fetal exposure)
Measure FT4/FTI q2-4 weeks and titrate
Thioamides (PTU/methimazole) -> decrease thyroid
hormone synthesis by blocking organification of iodide
PTU also reduces T4->T3 and may work more quickly
PTU traditionally preferred (older studies found that
methimazole crossed placenta more readily and was associated
with fetal aplasia cutis; newer studies refute this)
Treatment of Hyperthyroidism
Effect of treatment on fetal thyroid function:
Possible transient suppression of thyroid function
Fetal goiter associated with Graves (usually drug-induced fetal
hypothyroidism)
Fetal thyrotoxicosis due to maternal antibodies is rare -> screen
for growth and normal FHR
Neonate at risk for thyroid dysfunction; notify pediatrician
Breastfeeding safe when taking PTU/methimazole
Treatment of Hyperthyroidism
Beta-blockers can be used for symptomatic relief
(usually Propanolol)
Reserve thyroidectomy for women in whom thioamide
treatment unsuccessful
Iodine 131 contraindicated (risk of fetal thyroid ablation
especially if exposed after 10 weeks); avoid
pregnancy/breastfeeding for 4 months after radioactive
ablation
Hypothyroidism
Symptoms: fatigue, constipation, cold intolerance,
muscle cramps, hair loss, dry skin, slow reflexes,
weight gain, intellectual slowness, voice changes,
insomnia
Can progress to myxedema and coma
Subclinical hypothyroidism: elevated TSH, normal
FTI in asymptomatic patient
Associated with other autoimmune disorders
Type 1 DM -> 5-8% risk of hypothyroidism; 25%
postpartum thyroid dysfunction
Hypothyroidism: Fetal &
Neonatal Effects
Higher incidence of LBW (due to medically
indicated preterm delivery, pre-eclampsia,
abruption)
Iodine deficient hypothyroidism ->
congenital cretinism (growth failure, mental
retardation, other neuropsychological
deficits)
Causes & Diagnosis of
Hypothyroidism
Causes:
Hashimotos (chronic thyroiditis; most common in developed
countries) & iodine deficiency -> both associated with goiter
Subacute thyroiditis -> not associated with goiter
Thyroidectomy, radioactive iodine treatment
Iodine deficiency (most common worldwide; rare in US)
Treatment of Hypothyroidism
Treat with Levothyroxine in sufficient dose
to return TSH to normal
Adjust dosage every 4 weeks
Check TSH every trimester
FTI

A 40-year-old female taking estrogen in the absence of


intrinsic thyroid disease will have normal free-T4 and TSH
levels. She will, however, have an elevated total-T4 level
due to the increased TBG from estrogen exposure. The
T3RU will be decreased due to the increased availability of
hormone-binding sites on TBG, making less hormone
available for uptake by the resin. Thus, despite an elevated
total-T4 level, the decreased T3RU will keep the FTI within
normal limits.
FREE THYROXINE INDEX
Females
<1.3 suggest hypothyroidism
1.3-3.0 suggest euthyroidism
>3.0 suggest hyperthyroidism

THYROXINE, TOTAL
Females
0-11 months: not established
1-9 years: 6.0-12.5 mcg/dL
10-17 years: 5.0-11.0 mcg/dL
> or =18 years: 5.0-12.5 mcg/dL
Effect of Human reproduction
The presence of anti-thyroid antibodies is
associated with an increased risk of unexplained
subfertility (odds ratio 1.5 and 95% confidence
interval 1.12.0), miscarriage (odds ratio 3.73,
95% confidence interval 1.87.6), recurrent
miscarriage (odds ratio 2.3, 95% confidence
interval 1.53.5), preterm birth (odds ratio 1.9,
95% confidence interval 1.13.5) and maternal
Postpartum thyroiditis (odds ratio 11.5, 95%
confidence interval 5.624).[15]
isoforms
TR-1 (widely expressed and especially high
expression in cardiac and skeletal muscles)
TR-2 (homologous with viral oncogene c-erb-A,
also widely expressed but unable to bind
hormone)
TR-1 (predominately expressed in brain, liver
and kidney)
TR-2 (expression primarily limited to the
hypothalamus and pituitary)
Iodide transfer to folicular lumen (via pendrin)
Oxydation (Thyroid peroxydase) Iodium + Tyrosil
residu (Thyroglobulin) MIT + DIT T3 & T4
secretion by proteolysis
Synthesis of the thyroid hormones, as seen on an individual thyroid
follicular cell:[3]
- Thyroglobulin is synthesized in the rough endoplasmic reticulum and
follows the secretory pathway to enter the colloid in the lumen of the
thyroid follicle by exocytosis.
- Meanwhile, a sodium-iodide (Na/I) symporter pumps iodide (I-) actively
into the cell, which previously has crossed the endothelium by largely
unknown mechanisms.
- This iodide enters the follicular lumen from the cytoplasm by the
transporter pendrin, in a purportedly passive manner.[4]
- In the colloid, iodide (I-) is oxidized to iodine (I0) by an enzyme called
thyroid peroxidase.
- Iodine (I0) is very reactive and iodinates the thyroglobulin at tyrosyl
residues in its protein chain (in total containing approximately 120 tyrosyl
residues).
- In conjugation, adjacent tyrosyl residues are paired together.
- Thyroglobulin binds the megalin receptor for endocytosis back into the
follicular cell.
- Proteolysis by various proteases liberates thyroxine and triiodothyronine
molecules, which enter the blood by largely unknown mechanisms.
Despite being lipophilic, T3 and T4 cross the
cell membrane via carrier-mediated
transport, which is ATP-dependent. The
thyroid hormones function via a well-
studied set of nuclear receptors in the
nucleus of the cell, the thyroid hormone
receptors.
A thyroid adenoma is a benign tumor of the thyroid
gland. Follicular and Papillary
Thyroid follicular adenoma ranges in diameter from
3 cm on an average, but sometimes is larger (up to 10
cm) or smaller. The typical thyroid adenoma is solitary,
spherical and encapsulated lesion that is well demarcated
from the surrounding parenchyma. The color ranges
from gray-white to red-brown, depending upon :
the cellularity of the adenoma
the colloid content.
Toxic nodular goiter involves an enlarged
thyroid gland. The gland contains areas that
have increased in size and formed nodules.
One or more of these nodules produce too
much thyroid hormone. from functionally
autonomous thyroid nodules, which do not
require stimulation from thyroid stimulating
hormone (TSH)
Goiter is an enlargement of the thyroid gland. The gland can be
generally enlarged or have multiple growths (nodules) leading
to enlargement of the whole thyroid gland. The latter is termed
multinodular goiter (MNG). There are two forms of
multinodular goiter: 1) nontoxic MNG and 2) toxic MNG. If
the goiter makes normal amounts of thyroid hormone, it is
known as a nontoxic MNG. If the goiter makes higher than
normal amounts of thyroid hormone leading to a suppressed
TSH, it is known as a toxic MNG. (See Hyperthyroidism) The
exact causes of thyroid nodules or multinodular goiters are
unknown. In general, the development of goiter is due to a
complex mix of genetic and environmental factors. Iodine
deficiency as a cause of goiter is rare in North America and
most of Europe. However, even in areas of iodine deficiency
most patients do not develop goiters.
Subacute thyroiditis leads to pain and discomfort in the
thyroid gland. Individuals with this condition will also
have symptoms of overactive thyroid and later develop
symptoms of underactive thyroid.
Subacute thyroiditis generally occurs after an upper
respiratory viral infection such as the flu or the mumps.
The mumps is a highly contagious viral infection that
causes inflamed salivary glands. Subacute thyroiditis is
very rare. However, it is slightly more common in middle-
aged women.
Subacute thyroiditis is a self-limited thyroid
condition associated with a triphasic clinical
course of hyperthyroidism, hypothyroidism, and
return to normal thyroid function. Subacute
thyroiditis may be responsible for 15-20% of
patients presenting with thyrotoxicosis and 10% of
patients presenting with hypothyroidism.
Recognizing this condition is important; because it
is self-limiting, no specific treatment, such as
antithyroid or thyroid hormone replacement
therapy, is necessary in most patients.
Hashimoto's thyroiditis or chronic
lymphocytic thyroiditis is an autoimmune
disease in which the thyroid gland is attacked
by a variety of cell- and antibody-mediated
immune processes. It was the first disease to
be recognized as an autoimmune disease.[1] It
was first described by the Japanese specialist
Hakaru Hashimoto in Germany in 1912.
Hashimotos
Enlargement of the thyroid is due to lymphocytic
infiltration and fibrosis rather than tissue
hypertrophy. Physiologically, antibodies against
thyroid peroxidase (TPO) and/or thyroglobulin
cause gradual destruction of follicles in the thyroid
gland. Accordingly, the disease can be detected
clinically by looking for these antibodies in the
blood. It is also characterized by invasion of the
thyroid tissue by leukocytes, mainly T-
lymphocytes. A rare but serious complication is
thyroid lymphoma, generally the B-cell type
Hyperthyroid vs Spontanous abortion
Thyroid dysfunction has also been associated with increased
rates of pregnancy loss (25,180).
Stagnaro-Green and colleagues (181) published the rst paper
that demonstrated an association between pregnancy loss and
thyroid antibodies. In that prospective observational study,
patients who were positive for thyroid antibodies (TPOand Tg)
had a twofold increase in the risk of a pregnancy loss (17% vs.
8.4%, p=0.011).
Iijima and colleagues (182) also reported a nearly twofold
increase in spontaneous pregnancy loss in patients who were
positive for anti-microsomal antibodies.
Glinoer and colleagues (183) reported a fourfold increase in
pregnancy loss (13.3 vs. 3.3 %, p<.001) with the presence of
TPOAb
Hyperthyroid vsPreterm delivery
Medical conditions such as hypertension and diabetes have
been associated with a risk of preterm delivery
The most severe example of uncontrolled hyperthyroidism,
thyroid storm, results in high rates of preterm labor and
delivery
The relationship of thyroid antibodies and preterm delivery
has also been investigated. Glinoer et al.
Negro et al. (28) reported an increased risk of preterm
delivery among euthyroid TPOAb + women compared
with euthyroid TPOAb - women in the only published pro
spective interventional trial to date (22.4% vs. 8.2%,
p<.01).
Hypothyroid and preeclampsia
hypothyroidism being an accepted cause of reversible
hypertension both in the pregnant and in the nonpregnant
population,
Hypothyroidism can cause vascular smooth muscle
contraction both in systemic and renal vessels, which leads
to increased diastolic hypertension, peripheral vascular
resistance, and decreased tissue perfusion
Thyroid dysfunction can be associated with proteinuria,
which is known to result in increased excretion of
thyroxine and thyroid-binding globulins. Rare cases, have
been reported where proteinuria is severe enough to result
in losses of thyroid-binding globulins and thyroxine that
cannot be compensated by the body.
Graves' disease (or Flajani-Basedow-
Graves disease)
is an autoimmune disease. It most commonly affects the
thyroid, frequently causing it to enlarge to twice its size or
more (goiter), become overactive, with related
hyperthyroid symptoms such as increased heartbeat,
muscle weakness, disturbed sleep, and irritability. It can
also affect the eyes, causing bulging eyes (exophthalmos).
It affects other systems of the body, including the skin,
heart, circulation and nervous system.
Graves

The trigger for autoantibody


production is not known.
There appears to be a
genetic predisposition for
Graves' disease, suggesting
some people are more prone
than others to develop TSH
receptor activating
antibodies due to a genetic
cause. HLA DR (especially
DR3) appears to play a
significant role

You might also like