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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 ++
Hyperthyroidism Hypothyroidism
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)
B-HCG TSH
IDENTICAL
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