Tiroid dan Reproduksi Wanita

The thyroid gland is a small butterfly

shaped gland with two lobes. It is
situated in the front of your neck, just
below the Adams Apple. The two lobes
are joined together by tissue called the
isthmus.

The thyroid gland is one of the glands of

the endocrine system.

The thyroid gland has two main

functions: the first function is to control
metabolism. Metabolism is the rate at
which all the chemistry of the body
works. The second function is to control
growth in early life.
Thyroid Stimulating Hormone
• Human TSH is a glycoprotein. It
stimulates the thyroid gland to
produce thyroxine, which is a
hormone that has wide spread
implications for metabolism in the
body.

Absence of thyroxine is incompatible

with life. Patients with pituitary
problems, who lose the function of
TSH, have to have thyroxine
replacement life-long.

Thyroid hormone or thyroxine

increases mental alertness, heart rate,
motion of the gastrointestinal tract,
breathing drive, as well as brain
development and skeletal maturation
in the foetus.
The normal thyroid
produces a number
of different
hormones.

The main hormones are

called thyroxine (T4) and
triiodothyronine (T3).

The thyroid produces

approximately 80% T4
and 20% T3.

T4 is generally
considered to be a pro-
hormone because it is
inactive and only
becomes active when
converted to T3.

T3 is an active hormone
and does all the work of
regulating the body's
metabolism.
• The tissues are unable to use T4, so an enzyme called 5'-
deiodinase converts it to T3.

• This conversion takes place in the body's cells and tissues,

mainly in the liver.

• Problems with the liver can upset/affect the body's conversion of

T4 to T3 and can cause problems for the thyroid.

5'-deiodinase
 The thyroid needs iodine to make thyroid
hormone.

Iodine is found in fish, shellfish, cereals and

grains and vegetables (although levels vary
depending on the amount of iodine in the soil
where the plants are grown). There is also iodine
in cow's milk.

Your body also needs different amino acids to

make thyroid hormone (amino acids are the
building blocks of protein), especially the amino
acid, Tyrosine.

Tyrosine is found in soy, chicken, turkey, fish,

peanuts, almonds, avocados, bananas, milk,
cheese, yoghurt, cottage cheese, lima beans,
pumpkin seeds, and sesame seeds.

Selenium is needed for conversion of T4 to T3. If

your diet does not contain enough selenium, you
may have poor conversion of T4 to T3. Selenium
can be found in meat, fish and nuts.
 Fisiologi tiroid normal
Sintesa hormon tiroid tgt pd suplai iodin yg
adekuat dalam diet

diet (iodin)
Monoiodotirosin
+
diiodotirosin
usus halus (iodida)
TSH
Tiroksin (T4)
Kelenjar tiroid
oksidasi
iodida elemen tirosin Triiodotironin (T3)
 Algoritme skrining kelainan tiroid
[TSH] : 0.45- 4.5mIU/L

meningkat normal menurun

[FT4] : 0.8 – 2.3 ng/dl

meningkat normal menurun

[FT3] : 0.13 – 0.55 ng/dl hipotiroid

hipertiroid
meningkat normal
 The thyroid produces more This is called
Hyperthyroidism (Low thyroid hormone than it hyperthyroidism, an
TSH, High T3) should which causes the overactive thyroid or Graves'
metabolism to run too fast. disease.
 Grave’s disease
Gejala khas, triad:
Hipertiroidism
Eksoftalmus
Miksedemia pretibial

Etiologi : autoantibodi

Pada reproduksi

Ggn. Menstruasi

Amenore-oligomenorea-siklus normal
 The thyroid
produces less This is called
thyroid hormone hypothyroidism,
Hypothyroidism than it should myxoedema or an
which causes the underactive
metabolism to run thyroid.
too slow.
 Thyroid Hormones, PCOS and the Reproductive System
Thyroid hormones have various
effects on the reproductive
system of the human female.
Hypothyroidism and PCOS are
often accompanied by increased
serum free testosterone,
luteinizing hormone (LH) and high
cholesterol. When the ovaries of
hypothyroid women with PCOS
are viewed with an ultrasound an
increase in ovarian volume and
the appearance of bilateral
multicystic ovaries are often
visible.
Alteration in thyroid function,
particularly hypothyroidism, can
cause ovulatory dysfunction and
lead to impaired female fertility.
When thyroid hormone
replacement therapy is initiated,
in addition to stabilizing thyroid
hormone levels, ovarian cysts
regress and ovarian volume is
reduced.
Thyroid Hormone Replacement and Menstrual Irregularities
• Hypothyroid women commonly suffer from menstrual irregularities and
impaired fertility attributed to annovulation and/or luteal phase defect.

• The present study showed that the women with hypothyroidism (with or
without polycystic ovaries) had significantly larger ovaries when
compared with controls, suggesting that thyroid dysfunction has a
profound effect on ovarian size, and may also produce ovarian cysts.

• Research in animals has shown that hypothyroidism causes collagen

deposition within the ovarian intracellular matrix. In humans,
hypothyroidism is characterized by deposition of mucopolysaccharides
(hyaluronic acid and chondroitin sulfate) within the connective tissue of
various organs.

• While additional collagen in the lips or to reduce the appearance of

wrinkles can be a good thing, increased collagenic material in the
ovaries creates problems with ovarian function and may dysregulate
hormone synthesis.
 Association of thyroid-stimulating hormone with insulin resistance
and androgen parameters in women with PCOS.
Dittrich R1, Kajaia N, Cupisti S, Hoffmann I, Beckmann MW, Mueller A.
Author information
Abstract

There is a relationship between thyroid function and insulin sensitivity and alterations in lipids and metabolic
parameters.

The association between thyroid-stimulating hormone <2.5 mIU/l and > or =2.5 mIU/l with insulin resistance
and endocrine parameters in 103 women with polycystic ovary syndrome was studied.
Clinical, metabolic and endocrine parameters were obtained and an oral glucose tolerance test was
performed with calculation of insulin resistance indices.
Women with thyroid-stimulating hormone > or =2.5 mIU/l had a significantly higher body mass index (P =
0.003), higher fasting insulin concentrations (P = 0.02) and altered insulin resistance indices (P = 0.007),
higher total testosterone (P = 0.009) and free androgen indices (P = 0.001) and decreased sex hormone-
binding globulin concentrations (P = 0.01) in comparison with women with thyroid-stimulating hormone <2.5
mIU/l.
Generally, all of these parameters correlated significantly (P < 0.05) with thyroid-stimulating hormone only in
women with thyroid-stimulating hormone > or =2.5 mIU/l. Women with polycystic ovary syndrome and with
thyroid-stimulating hormone > or =2.5 mIU/l had significantly altered endocrine and metabolic changes.
 HIPOTIROID

Dari wanita yg
berkunjung ke
Sekunder poliklinik geriatrik,
terhadap reaksi 2-4% tampak
autoimun menderita gejala
hipotiroid secara
klinik

Bila terbentuk
goiter dis:
Hashimoto’s
thyroiditis
 HIPOTIROID

Gejala hipotiroid meningkat dengan

meningkatnya usia & lebih sering pada
wanita

Oleh karena itu penting dilakukan skrining

bahkan pada wanita usia tua tanpa
keluhan.

Rekomendasi: setiap 5 tahun dimulai pd

usia 35 tahun, setiap 2 tahun setelah usia
60 tahun atau dg tampakan keluhan.
 Keluhan hipotiroid

Haid tidak teratur

Amenorea
dan perdarahan

Konstipasi,
intoleran terhadap
dingin, retardasi
psikomotor, Sering tanpa
sindrom karpal keluhan
tunnel dan
toleransi latihan
menurun
 Diagnosis Hipotiroid

Gagal tiroid secara Kadar hormon tiroid

primer yg beredar turun

Merangsang
hipofisis anterior TSH meningkat, T4
untuk meningkatkan rendah
pengeluaran TSH
 Hipertiroid

2 penyebab primer :
• Grave’s disease (toxic diffuse goiter)
• Plummer’s disease (toxic nodular goiter)

20% pdrt usia > 60 th

25% penderita usia lebih tua keluhannya

apatetik atau sindroma atipikal
Tirotoksikosis
Keluhan klasik:

Cemas

Intoleransi panas

Hilangnya berat badan

Berkeringat

Palpitasi

Diare
 Tirotoksikosis

Pemeriksaan
fisik:
Tremor

Kulit
Lidlag Takikardia
berminyak

Proptosis

Panas

Goiter
Hormone Changes.

A normal pregnancy results in a number of important

physiological and hormonal changes that alter thyroid function.

These changes mean that laboratory tests of thyroid function

must be interpreted with caution during pregnancy.
Thyroid function tests change during pregnancy due to the
influence of two main hormones: human chorionic gonadotropin
(hCG), the hormone that is measured in the pregnancy test and
estrogen, the main female hormone.
HCG can weakly turn on the thyroid and the high circulating
hCG levels in the first trimester may result in a slightly low TSH
(called subclinical hyperthyroidism).
When this occurs, the TSH will be slightly decreased in the first
trimester and then return to normal throughout the duration of
pregnancy
Estrogen increases the amount of thyroid hormone
binding proteins in the serum which increases the total
thyroid hormone levels in the blood since >99% of the
thyroid hormones in the blood are bound to these
proteins.

However, measurements of “Free” hormone (that not

bound to protein, representing the active form of the
hormone) usually remain normal.

The thyroid is functioning normally if the TSH, Free T4

and Free T3 are all normal throughout pregnancy.
 What is the interaction between the thyroid
function of the mother and the baby?

For the first 10-12 weeks of pregnancy, the baby is

completely dependent

on the mother for the production of thyroid

hormone.

By the end of the first trimester, the baby’s thyroid

begins to produce thyroid hormone on its own.

The baby, however, remains dependent on the

mother for ingestion of adequate amounts of iodine,
which is essential to make the thyroid hormones.

The World Health Organization recommends iodine

intake of 200 micrograms/day during pregnancy to
maintain adequate thyroid hormone production.
What are the risks of Graves’ Disease /
hyperthyroidism to the mother?

Graves’ disease may present initially during the first

trimester or may be exacerbated during this time in a
woman known to have the disorder.

In addition to the classic symptoms associated with

hyperthyroidism, inadequately treated maternal
hyperthyroidism can result in early labor and a
serious complication known as pre-eclampsia.

Additionally, women with active Graves’ disease

during pregnancy are at higher risk of developing
very severe hyperthyroidism known as thyroid storm.

Graves’ disease often improves during the third

trimester of pregnancy and may worsen during the
post partum period.
 What are the risks of Graves’ Disease /
hyperthyroidism to the baby?

The risks to the baby from Graves’ disease are due to one of three
possible mechanisms:

1 Uncontrolled maternal hyperthyroidism :

This has been associated with fetal tachycardia (fast heart

rate), small for gestational age babies, prematurity, stillbirths
and possibly congenital malformations.

This is another reason why it is important to treat

hyperthyroidism in the mother.
2 Extremely high levels of thyroid stimulating immunogloblulins (TSI):

Graves’ disease is an autoimmune disorder caused by the production of antibodies that

stimulate thyroid gland referred to as thyroid stimulating immunoglobulins (TSI). These
antibodies do cross the placenta and can interact with the baby’s thyroid.

Although uncommon (2-5% of cases of Graves’ disease in pregnancy), high levels

of maternal TSI’s, have been known to cause fetal or neonatal hyperthyroidism.

Fortunately, this typically only occurs when the mother’s TSI levels are very high
(many times above normal). Measuring TSI in the mother with Graves’ disease is
often done in the third trimester.

In the mother with Graves’ disease requiring antithyroid drug therapy, fetal
hyperthyroidism dueto the mother’s TSI is rare, since the antithyroid drugs also
cross the placenta.

Of potentially more concern to the baby is the mother with prior treatment for Graves’
disease (for exampleradioactive iodine or surgery) who no longer requires antithyroid
drugs.

It is very important to tell your doctor if you have been treated for Graves’ Disease in the past
so proper monitioring can be done to ensure the baby remains healthy during the pregnancy.
3 Anti-thyroid drug therapy (ATD):

Methimazole (Tapazole) or propylthiouracil (PTU) are the ATDs available in the United
States for the treatment of hyperthyroidism (see Hyperthyroidism brochure).

Both of these drugs cross the placenta and can potentially impair the baby’s thyroid
function and cause fetal goiter.

Historically, PTU has been the drug of choice for treatment of maternal
hyperthyroidism, possibly because transplacental passage may be less than with
Tapazole.

However, recent studies suggest that both drugs are safe to use during pregnancy. It is
recommended that the lowest possible dose of ATD be used to control maternal
hyperthyroidism to minimize the development of hypothyroidism in the baby or
neonate.

Neither drug appears to increase the general risk of birth defects.

Overall, the benefits to the baby of treating a mother with hyperthyroidism during pregnancy
outweigh the risks if therapy is carefully monitored.
 What are the treatment options for a pregnant
woman with Graves’ Disease / hyperthyroidism?

Mild hyperthyroidism (slightly elevated thyroid hormone levels,

minimal symptoms) often is monitored closely without therapy
as long as both the mother and the baby are doing well.

When hyperthyroidism is severe enough to require therapy,

anti-thyroid medications are the treatment of choice, with PTU
being the historical drug of choice.

The goal of therapy is to keep the mother’s free T4 and free T3

levels in the high-normal range on the lowest dose of
antithyroid medication.

Targeting this range of free hormone levels will minimize the

risk to the baby of developing hypothyroidism or goiter.

Maternal hypothyroidism should be avoided.

• In patients who cannot be adequately treated with anti-thyroid medications (i.e. those
who develop an allergic reaction to the drugs), surgery is an acceptable alternative.

• Surgical removal of the thyroid gland is only very rarely recommended in the pregnant
woman due to the risks of both surgery and anesthesia to the mother and the baby.

• Radioiodine is contraindicated to treat hyperthyroidism during pregnancy since it

readily crosses the placenta and is taken up by the baby’s thyroid gland.

• This can cause destruction of the gland and result in permanent hypothyroidism.

• Beta-blockers can be used during pregnancy to help treat significant palpitations and
tremor due to hyperthyroidism.

• They should be used sparingly due to reports of impaired fetal growth associated with
long-term use of these medications.

• Typically, these drugs are only required until the hyperthyroidism is controlled with
anti-thyroid medications.
What is the natural history of Graves’ Disease
after delivery ?
• Graves’ disease typically worsens in the postpartum period,
usually in the first 3 months after delivery.
• Higher doses of anti-thyroid medications are frequently required
during this time.
• At usual, close monitoring of thyroid function tests is necessary.

Can the mother with Graves’ disease, who is being

treated with anti-thyroid drugs, breastfeed her infant?

• Yes. PTU is the drug of choice because it is highly protein bound.

• Consequently, lower amounts of PTU cross into breast milk
compared to Tapazole.
• It is important to note that the baby will require periodic assessment
of his/her thyroid function to ensure maintenance of normal thyroid
status.