Endocrine Pathology

associated with
pregnancy

dr. Yunus Tanggo Sp.PD. PhD

Department of Internal Medicine, Universitas Kristen Indonesia
General Hospital, Jakarta, Indonesia

HYPER and HYPOTHYROIDISM

DURING PREGNANCY

INTRODUCTION
Thyroid diseases are more prevalent in women
relatively common in pregnancy
Pregnancy may affect the course of thyroid
disorders
conversely..
Thyroid diseases may affect the course of pregnancy
Thyroid disorders & their management
may affect the mother & fetus

Control of Thyroid Function

By a negative-feedback loop:
The hypothalamus releases TRH
TRH acts on the pituitary to release TSH
TSH acts on the thyroid gland to release
T3 and T4 , that regulate metabolism
TRH and TSH concentrations are
inversely related to the level of T3 & T4
99% circulating T3 & T4 is bound to
TBG. 1% circulate in the Free form,
(only the free forms are biologically
active)

NORMAL CHANGES IN THYROID

FUNCTION ASSOCIATED WITH
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.
The high circulating hCG levels in the first trimester may
result in a slightly low TSH.
TSH 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.

Thyroid function in normal

pregnancy

Following
conception,
circulating total T4 (TT4) and
T4 binding globulin (TBG)
concentrations increase by 68
weeks and remain high until
delivery.

The high circulating hCG levels

in the first trimester may result
in a slightly low TSH

Levels of T4,and T3 gradually

increase in the fetus between
the second and third trimester,
reflecting
the
rising
contribution of the fetal thyroid

Results of Thyroid Tests

in Different Clinical Situations
Anti-

TT4 TT3 FT4 FT3 TSH TPO TSI

Nonpregnant

(-)

Normal pregnancy

(-)

Hyperthyroidism

( +)

Gestasional Transient
Thyrotoxicosis (GTT)

(-)

Hypothyroidism

( +)

Subclinical hypothyroidism

( +)

Chronic thyroiditis

( +)

Anti-TPO = antithyroid peroxidase antibodies; FT3 = free triiodothyronine; FT4 = free thyroxine;
TSH = thyroid stimulating hormon; TSI = thyroid stimulating immunoglobulins; TT4 = total thyroxine

THYROTOXICOSIS &
PREGNANCY
Causes:

Graves disease
TMNG, toxic adenoma
Thyroiditis
Hydatiform mole
Gestational hCG-asscociated Thyrotoxicosis

Hyperemesis gravidarum hCG

60% TSH, 50% FT4
Resolves by 20 wks gestation
Only Rx with ATD if persists > 20 wk

SIGNS AND SYMPTOMS OF

HYPERTHYROIDISM
Nervousness
Irritability

Difficulty Sleeping

Hoarseness or
Deepening of Voice
Persistent
Sore or Dry Throat
Difficulty Swallowing
Rapid or Irregular Heartbeat

Bulging Eyes/Unblinking Stare

Swelling (Goiter)

Infertility

Menstrual Irregularities or

Weight Loss

Light Period

Heat Intolerance

Frequent Bowel Movements

Warm, Moist Palms

Increased Sweating
First-Trimester Miscarriage
Family History of

Excessive Vomiting in Pregnancy

Thyroid Disease
or Diabetes

THYROTOXICOSIS &
PREGNANCY
Risks:
Maternal:
Maternal stillbirth, preterm labor,
preeclampsia, CHF, thyroid storm during labor
Fetal:
Fetal SGA, possibly congenital malformation
(if 1st trimester thyrotoxicosis), fetal
tachycardia, hydrops fetalis, neonatal
thyrotoxicosis

Measure:
TSH, FT4, FT3, T4, T3, thyroid antibodies?
Examine: goitre? orbitopathy? pretibial
myxedema?

Pregnant & Suppressed TSH

TSH < 0.1

TSH 0.1 0.4

Recheck in 5 wks

FT4, FT3, T4, T3

Thyroid Abs
Examine

Still suppressed

Normalizes

Hyperemesis Gravidarum

Very High TFTs:

TSH undetectable
very high free/total T4/T3 Dont treat with PTU
hyperthyroid symptoms
no hyperemesis
TSH-R ab +
Abnormal TFTs past 20 wk
orbitopathy
goitre, nodule/TMNG
pretibial myxedema
Treat Hyperthyroidism (PTU)

TREATMENT GUIDELINES FOR GRAVES'

DISEASE
DURING PREGNANCY
Monitor
Pulse, weight gain, FT4 , TSH every 2-4 weeks
Titrate ATD as necessary
ATD:
PTU is usually preferred to MTZ, but both types can be used.
Use the lowest dosage of that will maintain the patient in a
euthyroid or mildly hyperthyroid state.
Usually the ATD dose can be adjusted downward after 1st trim.
often discontinued during the 3rd trimester
ATD will often need to be reinstituted or increased after
delivery.

Do not attempt to normalize serum TSH -- TSH 0.1 - 0.4 mU/L are appropriate
Communicate regularly with obstetric providers,
Especially fetal pulse & growth in the 2nd half of gestation

THYROTOXICOSIS & PREGNANCY

TREATMENT
PTU
Start 100 mg tid, titrate to lowest possible dose
Monitor qmos on Rx: T4, T3, FT4, FT3
TSH less useful (lags, hCG suppression)

Aim for high-normal to slightly elevated hormone

levels
T4 150-230 nM, T3 3.8-4.6 nM, FT4 26-32 pM

3rd trimester: titrate PTU down & d/c prior to delivery if

TFTs permit to minimize risk of fetal goitre
Consider fetal U/S wk 28-30 to R/O fetal goitre

If allergy/neutropenia on PTU: 2nd trimester

thyroidectomy

HYPOTHYROIDISM IN
PREGNANCY
MAY BE DIFFICULT TO DIAGNOSE
Signs and symptoms (weight gain, fatigue)
can overlap with common pregnancy
complaints
Among pregnant hypothyroid patients:
1/3 have few or no symptoms
1/3 have moderate symptoms
1/3 have classical presentation of
hypothyroidism

LABORATORY TESTS
Because symptoms does not reliably distinguish
hypothyroidism from normal pregnancy
Lab test are the standard for diagnosis
Overt Hypothyroidism: Subclinical hypothyroidism:
symptomatic patient
asymptomatic
TSH level
TSH
FT4 & FT3.
normal FT4 & FT3

RISK FACTORS FOR

HYPOTHYROIDISM
IN PREGNANT WOMEN
Previous therapy for
hyperthyroidism
Previous external neck irradiation
Goiter , Autoimmune disorder
Family history of thyroid disease

FETAL THYROID FUNCTION

During early gestation
The Fetus needs T4 for brain / neurologic development
Fetal Thyroid development begin at 10 -12 ws,
Fetus does not produce its own T4 until 12 ws,
Fetus relies on Maternal T4 : Exclusively (until 12 ws)

By 20 weeks gestational age

The fetal thyroid is fully responsive to
Thyroid stimulating immunoglobulin (TSI)
Antithyroid drugs
Maternal T4, T3 & TSH pass across the placenta in small
and decreasing amounts as gestation progress,

but TSI, Iodides are readily transferred to the fetus

CONSEQUENCES OF
HYPOTHYROIDISM
IN PREGNANCY
Miscarriage
Preterm delivery
Anemia
Placental abruption
Fetal complications

The impact -- depends on the severity of the condition.

CONSEQUENCES OF
HYPOTHYROIDISM
IN PREGNANCY

Congenital cretinism:
Growth failure,
Mental retardation,

Other neuropsychologic deficits

If cretinism is identified & treated in the first 3 months of life:

near-normal growth and intelligence can be expected.
newborn screening for congenital hypothyroidism !!

THERAPY OF
HYPOTHYROIDISM
Choice of medication
Adjustment of therapy
Follow-up care

L-Thyroxine :

Adjustment of therapy : careful

titration
Follow-up care

Clinical evaluation
Laboratory monitoring (TSH)

GESTATIONAL DIABETES
This diagnosis is given when a woman, who
has never had diabetes before, gets diabetes
or has high blood sugar, when she is pregnant.
In pregnant women not previously known to
have diabetes, screen for GDM at 24-28 weeks
gestation, using a 75-g OGTT
It occurs in about 5% of all pregnancies
(200,000 cases each year)
If not treated, gestational diabetes can cause
health problems for the mother and the fetus.

RISK FACTORS:
for first trimester screening

> 35 yrs
BMI > 30
Previous diagnosis of GDM
Delivery of a mascrosomic baby
Member of a high-risk population
(Aboriginal, Hispanic, South Asian,
Asian, African)
Acanthosis nigricans
Corticosteroid use
PCOS

ADA and WHO Criteria for the

Diagnosis of GDM
ADA
ADA
100-g OGTT
75-g OGTT
Fasting (mg/dl)
126
1-hour (mg/dl)

2-hour (mg/dl)
140
3-hour (mg/dl)
For the ADA criteria, two or

95

WHO
75-g OGTT
95

180

180

155

155

140

more of the values from either the

100- or 75-g OGTT must be met or exceeded to make the
diagnosis of GDM. For the WHO criteria, one of the two values
from the 75-g OGTT must be met or exceeded to make the
diagnosis of GDM

PATHOPHYSIOLOGY (1)
Characterized by progressive insulin resistance that
begins near midpregnancy and progresses through the
third trimester
In late pregnancy, insulin sensitivity falls by until 50%
Two main contributors to insulin resistance include
increased maternal adiposity
insulin desensitizing effects of hormones produced
by the
placenta
Placenta
produces
human
chorionic
somatomammotropin (HCS, formerly called human
placental lactogen), bound and free cortisol, estrogen,
and progesterone

PATHOPHYSIOLOGY (2)
HCS stimulates pancreatic secretion of insulin in
the fetus and inhibits peripheral uptake of glucose
in the mother
In non diabetic pregnant women, the first- and
second phase insulin responses compensate for
this reduction in insulin sensitivity, and this is
associated with -cell hypertrophy and hyperplasia
However, women who have a deficit in this
additional insulin secretory capacity develop GDM
-Cell dysfunction in women diagnosed with
GDM may fall into one of three major categories:
1) autoimmune,
2) monogenic,
3) occurring on a background of insulin resistance
(as is
most common).

PATHOPHYSIOLOGY (3)
The loss of the first-phase insulin response leads to
postprandial hyperglycemia, whereas impaired
suppression of hepatic glucose production is
responsible for fasting hyperglycemia when
present.
Because insulin does not cross the placenta, the
fetus is exposed to the maternal hyperglycemia
The fetal pancreas is capable of responding to this
hyperglycemia
The fetus thus becomes hyperinsulinemic, which in
turn promotes growth and subsequent macrosomia.

Why isnt insulin doing

its job

The placenta is a system of vessels

that passes nutrients, blood, and water
from mother to fetus.
The placenta makes certain hormones
that may prevent insulin from working
the way that it should.
When this condition happens, it is
referred to as insulin resistance.
In order to keep metabolism normal
during pregnancy, the body has to
make three times more insulin than
normal to offset the hormones made
by the placenta.

COMPLICATIONS
Maternal complications
Antepartum morbidity in women with GDM
mostly consists of higher risk for development
of hypertensive disorders and preeclampsia
GDM increases the risk of cardiovascular
disease (CVD)
increased risk of cesarean delivery
GDM have an increased risk of developing
diabetes after pregnancy compared to the
general population

COMPLICATIONS
Fetal complications
Macrosomia
Neonatal hypoglycemia
Perinatal mortality
Congenital malformation
Hyperbilirubinemia,
Polycythemia, hypocalcemia,
Respiratory distress syndrome.

MEDICAL NUTRITION
THERAPY (MNT)
Refer patients for
Goals:
nutritional counseling
Provide a nutritionally
adequate diet for
with registered dietitian
pregnancy
familiar with pregnancy
Achieve normoglycemia
MNT is based on
Target Glucose Levels for
standard nutritional
Normoglycemia3
recommendations during
pregnancy, with
Preprandial glucose
customization based on:
Height
Weight
Nutritional assessment
Level of glycemic
control3,4,5

95 mg/dL (5.3 mmol/L)

1-hour postprandial glucose

140 mg/dL (7.8 mmol/L) or
2-hour postprandial glucose
120 mg/dL (6.7 mmol/L)

1. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30. 2. Kitzmiller JL, et al. Diabetes Care. 2008;31(5):1060-79.
3. Jovanovic L, et al. Mt Sinai J Med. 2009;76(3):269-80. 4. ADA. Diabetes Care. 2004;27(suppl 1):S88-90.
5. National Academy of Sciences, Institute of Medicine, Food and Nutrition Board, Committee on Nutritional Status in Pregnancy and Lactation, Nutrition During Pregnancy:
http://www.iom.edu/Reports/1990/Nutrition-During-Pregnancy-Part-I-Weight-Gain-Part-II-Nutrient-Supplements.aspx, 1990. Accessed: April 26, 2012.