A Case Report :

WOMAN WITH
HYPEREMESIS
GRAVIDARUM AND
HYPERTHYROIDISM

Irma Permata Sari

A.Makbul Aman
 INTRODUCTION
• Hyperemesis gravidarum (HG) : a condition in
early pregnancy that is characterized by
persistent nausea and vomiting that can lead
to dehydration, electrolyte disturbances,
decline in nutritional status, psychological
disorders and even to termination of
pregnancy.
• The prevalence of HG : 1,5% of all pregnancy
• Persistent nausea and vomiting in HG occurs
between weeks 4 and 10 of gestation, and will
be improved at week 15 and 20 of gestation.
• HG manifestasion : Weight loss > 5% of body
weight before pregnancy, severe dehydration,
and the presence of ketonuria.
• Hyperthyroidism: a form of thyrotoxicosis as a
result of the synthesis and secretion of excessive
thyroid hormone by the thyroid gland.
• Etiology : Graves’ disease, toxic multinodular
goiter, and toxic adenoma.
• Regulation of the production of thyroid
hormones (thyroxine / T4, and triiodothyronine /
T3) played by thyroid stimulating hormone (TSH)
through a negative feedback mechanism.
• Pregnancy can induce physiological disorders
of thyroid function  hyperstimulation of the
thyroid gland is common in early pregnancy 
diagnosis of hyperthyroidism in pregnancy is a
challenge. Etiology of
Hyperthyroidism
in pregnancy

Graves’ Gestational
disease hyperthyroidism
• Gestational hyperthyroidism is generally
asymptomatic, are influenced by the
concentration of hCG, in the 1st trimester of
pregnancy.
• hCG has an α subunit identical to the α subunit of
TSH, and also the beta subunit is homologous to
one another.
• Thyrotropic activity of hCG found to be higher in
women with HG  FT3 and FT4 concentration
increases (25-75% of cases)
CASE REPORT
 HYSTORY TAKING
• ♀, Mrs.F, 35 y.o. , a civil servant, was entered Hasanuddin
University Hospital on June 16th 2015, MR: 007.107. Patient
was counseled from the Department of Obs-Gyn to
Subdivision of Endocrinology and Metabolism at June 22,
2015, with a D/ Hyperemesis Gravidarum level II and
hyperthyroidism.
• Patient with chief complaints of vomiting experienced since
± 2 months before admission and worsening in the last 1
month. Frequency of vomiting ± 10x/day, every time when
she eats. The vomiting is consists of water and food residue,
the color is yellowish. A history of vomiting with blood, ± 2
weeks ago, but now is not experienced.
 HISTORY TAKING
• Patient also complained pain in the neck, tasted sour in
the mouth and heartburn. Currently, the patient is
pregnant for the 4th time, gestational age ± 2 months.
A history of similar complaints had experienced during
her first pregnancy (2007).
• Patient has gone to the gynecologist frequently and
was hospitalized for these complaints. Currently,
patient has gotten a multivitamin, anti-vomit and ulcer
drug. No history of frequent consumption of
analgesics, antibiotics, or herbal medicine.
 HISTORY TAKING
• Patient had less food intake since the last 2 months.
The patient's weight decreased by 4 kg in the 1st
month of pregnancy. A history of palpitations
sometimes perceived, no chest pain or shortness of
breath. There was no history of fever and excessive
sweating.
• Currently, the patient has not defecate for 5 days. No
history of frequent diarrhea or black stool before.
Decreased urination, and the color resembles a
concentrated tea.
 OBSTETRIC HISTORY
YEAR CONDITION
2007-2008 1st pregnancy, miscarriage

2008-2009 2nd pregnancy, miscarriage

2009-2010 3rd pregnancy, a child born through Cesaria

section (SC) for the indication of bleeding
and premature rupture of fetal
membranes (PROM) at gestational age 7½
months. Currently, children suffering from
cerebral palsy.

2015 - now Current pregnancy

 PHYSICAL EXAMINATION
• Moderate illness, undernutrition, consciousness.
Weight 37 kg (previously 41 kg), height 155 cm, BMI
15.4 kg / m2.
• BP: 110/70 mmHg; P : 84x/min, regular, strong lift;
RR: 20x/min; T axillary : 37 °C.
• Head : slightly pale conjunctiva, no jaundice sclera,
concave eyes, no exophthalmos, dry lips.
• Neck : no goitre and enlarged lymph nodes.
 PHYSICAL EXAMINATION
• Chest : symmetrical, no tenderness, VF left =
right, resonant percussion, heart lung boundary
ICS VI right anterior, vesicular breath sounds, no
added sounds.
• Heart : heart sound I / II regular, no murmurs.
• Abdominal : flat, follow the motion of breath,
increased peristalsis, tenderness in the epigastric
region, liver and spleen not palpable, percussion
timpani.
• Extremities : no edema and fine tremors.
 LABORATORY RESULTS
• Hb : 10,8 gr/dl • Na : 136 mmol/l
• WBC : 6.650/ uL • K : 3,2 mmol/l
• Cl : 111 mmol/l
• PLT : 241.000/uL,
• FT4 : 1,76 ng/dL (0,93-1,71)
• MCV : 76,2 fL • TSHS : 0,010 uUl/ml (0,27 – 4,2)
• MCH : 26,8 pg Urinalisa:
• MCHC : 35,2 g/dL • Color : turbid yellow
• SGOT : 29 U/L • pH : 7,0
• Protein : (-)
• SGPT : 68 U/L
• Keton : (+) 10 mg/dL
• Albumin : 3,3 gr/dl • Eritrosit : 0-2/LPB
• RBG : 104 mg/dl • Leukosit : 1-3/LPB.
• Ureum : 25 mg/dL
• Creatinin : 0,6 mg/dL.
 ECG

Impression : Sinus rythme, HR : 81x/menit, Normoaxis

WNL
 USG THYROID
• The right lobe: The size within normal limits.
Hypoechoic lesions appear spherical shape, well
defined, regular edges size 0.12 cm. Looks
hypervascularization the thyroid parenchyma.
• Left lobe: The size and parenchymal echo within
normal limits. Does not seem pathological lesions.
Looks hypervascularization the thyroid parenchyma.
• Isthmus is not thickened. There does not appear
cervical lymphadenopathy region.

Impression: right lobe of thyroid nodules (TIRADS 2).

 USG OBSTETRIC

• Impression: Pregnant
live single, ± 10-11
weeks gestation, FHR
(+) 173x / minute, NT:
1,2 mm
• Based on history, physical examination and
investigations were obtained, the patient was
diagnosed with:

Hyperemesis gravidarum level II (G4P1A2) +

hyperthyroidism + anemia hypochromic + mild
hypokalemia+ undernutrition.
 MANAGEMENT
Obstetric & Gynecology Dept. Endocrinology & Metabolism Div.
• Intake/oral stopped for 24 h • Propylthiouracil (PTU) 100
• IVFD RL : D5  1:2 28 mg 1 tablet/24 h/oral.
drop/min • Plan for evaluation of
• Aminofluid : KAEN Mg3  1:1 thyroid function 1-2 weeks
40 drop/min later.
• Mixed capsule (CPZ 10mg + • Thyroid function pursued in
B6) 1 caps/8 h/oral
the high normal range.
• Ondancetron 8 mg/ 8h/iv
• Pantoprazole 40 mg/24 h/iv
• Consult to clinical nutrition
dept.
• After treatment for 8 days, the patient's
condition improved and was discharged on
June 24, 2015.
• Patients are encouraged to return control of
thyroid function on June 29, 2015.
DISCUSSION
• Nausea and vomiting (emesis) is a natural
phenomenon and common in the 1st
trimester of pregnancy, approximately 60-80%
in primigravida and 40-60% on multi gravida.
• About 1 to 20 among a thousand pregnancies,
these symptoms become more severe.
• HG is defined as frequent vomiting during
pregnancy with onset before 13 weeks'
gestation.
• The condition is caused by increased levels of
the hormone estrogen and hCG in serum 
effect on the central nervous system or the
emptying of the stomach is reduced.
 GRADE OF HG

Level I

HG

Level II Level III

Patient w/ 10 wk
gestation :
• Persistent vomitting HYPEREMESIS
• 4 kg weight loss in a GRAVIDARUM
month. GR II
• sign of dehydration
• Ketonurin.
• No encephalopathy
Exclusion the secondary
causes of HG :
Hyperthyroidism
work up : Multiple pregnancy, molar
pregnancy, cholecystitis,
Sign & symptoms
pyelonephritis, hepatitis, &
FT4 HYPERTHYROIDISM
TSHS
• The Endocrine Society in 2007 recommended to check
thyroid function in all patients with HG (5% weight loss,
dehydration and ketonuri).
• In addition, for all pregnant patients suspected
hyperthyroidism to examined TSH, FT4, FT3 and TRAb.
• In this patient, we found :
 Symptoms and signs of thyrotoxicosis in patient is
not so clear : No drastic weight loss before
pregnancy, excessive sweating, heat intolerance,
increased appetite, frequent diarrhea, tachycardia,
exoftalmos, goitre diffuse and fine tremor; although
sometimes patients feel palpitations.
 Lab : decreased levels of TSHS and mild increase of
FT4  hyperthyroidism.
QUESTIONS

What is the cause of

hyperthyroidism in this
patient ???

Does the patient should

receive antithyroid drug
therapy ???
Regulation Of Thyroid Function During
Normal Pregnancy
Increase in thyroid-binding globulin.

Increases in total T4 and T3.

Thyroid stimulation by hCG.

Increase in renal iodide clearance

Increase in serum thyroglobulin.

Source : flipper.diff.org
 DIAGNOSIS
• Based on American Thyroid Association and
American Association of Clinical Endocrinologists
2011 (ATA/AACE)
TSH estimation w/
trimester

TT4 & TT3 FT4 & FT3

adjusted 1,5 X estimation
non-pregnant OR w/ trimester
reference using LC

HYPERTYROIDISM
IN PREGNANCY
 Recommended trimester -specific
reference ranges for Thyroid Function Test
• Non pregnant woman TSH : 0,27 – 4,2 μIU/mL

Trimester Range of TSH

This patient has :
First 0,1 – 2,5 mIU/L TSH = 0,010 μIU/mL ↓
FT4 = 1,76 ng/dL (0,93-1,71)↑
Second 0,2 – 3,0 mIU/L
Third 0,3 – 3,0 mIU/L

• For FT4 : If FT4 measurement by Dx/ HYPERTHYROIDISM

LC/MS is not available
IN PREGNANCY
clinician should use whichever measure or estimate FT4 is
available in their laboratory, being aware of the limitation.
 Etiology of
hyperthyroidisme in
pregnancy

Graves’ disease
(85-90% of case)

Gestational
hyperthyroidism
(40-70% of case)
 Gestational Hyperthyroidism
(Transient Hyperthyroidism of Hyperemesis
Gravidarum)

• THHG covers 30-73% of women with HG.

• Hyperthyroidism diagnosed for the first time
in early pregnancy, transient, without
evidence of thyroid autoimmunity (negative
thyroid Ab), and lack of physical findings
consisting with Graves’ disease.
 In this case...
HG Gr.II
(G4P1A2) No history of
thyroid disease
& clinical
symptoms
were not clear

No signs THHG is most

The of likely, but GD
patient Graves’ couldn’t be
disease
excluded

TSHS ↓
FT4 ↑
Anti-
thyroid
Ab ???
• Women with HG &hyperthyroidism have a
serum hCG levels are higher than normal
pregnant women.
• hCG has thyroid- stimulating activity .
• Mori et al : high levels of hCG in women with
HG. hCG level was positively correlated with
the concentration of FT4, decreased of TSH
and the severity of vomit.
Transient Hyperthyroidism of Hyperemesis
Gravidarum

Goldman AM et al. Journal of Thyroid Research 2011

 MANAGEMENT
Management for HG :
• Supportive therapy : iv fluid for rehidration, correct
electrolyte imbalance, nutrition and antiemetics.
This patient gets :
• Iv fluid RL and D5%, parenteral nutrition.
• CPZ : Dopamine antagonists and inhibit vomiting by
inhibiting the CTZ along with a direct action on the GIT
D2 receptors.
• Vitamin B6 (pyridoxine) : effective in reducing nausea
and vomiting in pregnancy.
 Management for Hyperthyroidism

American Thyroid Association (2011):

• Not recommend ATD in the treatment of
gestational hyperthyroidism and HG, except on
condition of hyperthyroidism due to Graves'
disease and thyroid nodules.
• In situations in which it is difficult to arrive at a
definite diagnosis, a short course of ATDs is
reasonable.
• The Endocrine Society (2012) : ATD treatment in
women with HG were diagnosed with Graves‘
hyperthyroidism (FT4 levels above the normal
value or total T4> 150% upper limit value, TSH
<0.01 mIU / L, and the detection of TRAb).
• The Endocrine Society (2007) : provide ATD in
patients with symptomatic hyperthyroidism and
there is severe increased T4 and / or T3. (T4> 50%
of normal value).
 • Patient was given ATD, PTU 1x100
In this mg for 1-2 weeks with a target
case monitoring thyroid function (FT4)
are in the high normal range.

• Hyperthyroidism can cause negative effects

for mother and fetus.
• Patient with a history of abortion twice
The consecutively and her 3rd children has CP.
reasons • Patient with severe vomiting (HG grade II)
• The definite cause of hyperthyroidism can’t
be established
 Effects of Hyperthyroidism

• the risk of preeclampsia and

eclampsia can be increased.
Mother • spontaneous abortion in the
first trimester

• stillbirth,
• premature birth,
Fetal • low birth weight
• stunted fetal growth
• PTU was elected as ATD in this patients
because of the gestational age of patient is 10
weeks (1st trimester), where the process of
organogenesis takes place.
• PTU less penetrate the placental blood barrier
compared with methimazole  more minimal
teratogenic effects.
• Target of thyroid hormones in pregnant
women is maintained in the high normal
range  FT4 neonate can reach normal
values.
• Fetus is highly dependent on T4 transplacental
from mother.
• Deiodination of maternal T4 by fetal will
generate local production of T3  very
important in neurological development.
 SUMMARY
• Have reported a case of a woman, 35 y.o with a
diagnosis of hyperemesis gravidarum level II with
hyperthyroidism, anemia hypochromic, mild
hypokalemia and undernutrition. On the 6th day
of treatment, the patient consulted to the
subdivision of Endocrinology and Metabolism
and got the PTU 1x100 mg for 1-2 weeks, with
the target of thyroid hormone levels are in the
high normal range. Two days later, the patient's
condition improved and allowed to go home.
THANK YOU