Case report
Thyrotoxicosis: a rare presentation of
1
Department of Internal
Medicine, The George
Washington University Hospital,
Washington, District of
Columbia, USA
2
Department of Endocrinology
and Metabolism, The George
Washington University Hospital,
Washington, District of
Columbia, USA
Correspondence to
Dr Eison De Guzman;
​icydeg1@​gmail.​com
Accepted 14 June 2021
© BMJ Publishing Group
Limited 2021. No commercial
re-­use. See rights and
permissions. Published by BMJ.
To cite: De Guzman E,
Shakeel H, Jain R. BMJ Case
Rep 2021;14:e242131.
doi:10.1136/bcr-2021-
242131
molar pregnancy
Eison De Guzman ‍ ‍,1 Hira Shakeel,2 Rohit Jain2
SUMMARY
A 49-­year-­old woman, G8P7, presented with 1 week of
worsening vaginal bleeding and abdominal cramps in the
setting of a recently discovered unplanned pregnancy.
Vaginal ultrasound findings and a significantly elevated
human chorionic gonadotropin (hCG) level were
concerning for molar pregnancy. She developed signs
of hyperthyroidism on the night of admission, for which
the endocrinology team was consulted. Laboratory
data were consistent with hyperthyroidism. The patient
was believed to have thyrotoxicosis secondary to molar
pregnancy with concern for impending thyroid storm.
Her mental health disorder and bacteraemia made
taking care of her further challenging. She was started
on a beta-­blocker, antithyroid agent and intravenous
corticosteroids. She underwent an uncomplicated suction
dilation and curettage (D&C), with resolution of her
symptoms a few days after. At a follow-­up appointment,
the patient continued to be asymptomatic and was
feeling well.
BACKGROUND
Molar pregnancy is a relatively rare complication
of gestation with an incidence reported in the USA
to be 121 per 100 000 pregnancies.1 This compli-
cation occurs when there is an abnormal prolifera-
tion of trophoblastic tissue, resulting in a non-­viable
mass that often resembles grape-­like structures. The
major risk factors for molar pregnancy are prior
gestational trophoblastic disease and increased
maternal age, especially greater than age 45.1
The most common presenting symptom of molar
pregnancy is vaginal bleeding. Hyperemesis grav-
idarum is a classic association, but presents less
frequently than vaginal bleeding.2 An even rarer
complication of molar pregnancy is thyrotoxi-
cosis. Although increased thyroid function is often
reported in gestational trophoblastic disease, only
5% of these cases show symptoms of hyperthy-
roidism. It is believed that an elevated hCG level
>200 000 IU/L for several weeks is necessary for
the development of thyrotoxicosis.3 Treatment is
necessary to alleviate the patient’s symptoms and
to prevent progression into thyroid storm. Thyroid
storm is a lethal condition that, even when treated,
has a mortality rate as high as 50%.4
We report a case of molar pregnancy in which
the patient subsequently developed thyrotoxicosis.
This case highlights the rare complications of molar
pregnancy, and the importance of monitoring for
clinical hyperthyroidism in this patient population.
The case demonstrates how effective treatment
of thyrotoxicosis in molar pregnancy not only
De Guzman E, et al. BMJ Case Rep 2021;14:e242131. doi:10.1136/bcr-2021-242131
alleviates the patient’s symptoms, but also helps to
prevent progression into the highly lethal thyroid
storm.
CASE PRESENTATION
A 49-­ year-­
old woman, G8P7, with asthma and
bipolar disorder presented to her primary care
provider with nausea, vomiting and bilateral breast
tenderness. At the visit, a qualitative urine preg-
nancy test was positive, revealing an unplanned
pregnancy. The patient then began to experi-
ence intermittent vaginal spotting that eventually
increased to soaking multiple pads throughout the
day. This was associated with abdominal cramps
that prompted her visit to the emergency room. She
had seven uncomplicated vaginal deliveries in the
past, the most recent of which was 10 years ago.
She has no personal or family history of fibroids,
cervical cancer or molar pregnancy.
On admission, the patient was haemodynami-
cally stable with generalised abdominal tenderness
on examination. According to her last menstrual
period, the estimated gestational age was 15 weeks.
She was admitted to the obstetrics and gynecology
(OBGYN) team. Later that night, she developed a
fever of 39.4°C associated with sinus tachycardia,
diaphoresis and tremors in her extremities. On day
2 of admission, she was found to have laboratory
data consistent with hyperthyroidism at which
point the endocrinology team was consulted.
INVESTIGATIONS
Prior to the endocrinology consultation, the patient
underwent a vaginal ultrasound that revealed an
enlarged and irregular cystic-­ appearing endo-
metrium without an intrauterine gestational sac
(figures 1 and 2). β-hCG level was disproportion-
ately elevated to 414 600 IU/L given the gestational
age. These findings were concerning for molar
pregnancy. Her thyroid studies showed an undetect-
able Thyroid-­stimulating hormone (TSH) (<0.015
μIU/mL; first trimester reference range 0.60–3.40),
elevated free T4 (3.73 ng/dL; first trimester refer-
ence range 0.8–1.2) and elevated free T3 (10.0 pg/
mL; first trimester reference range 4.1–4.4). Blood
cultures from the day she spiked a fever eventually
grew Salmonella species. CT chest/abdomen/pelvis
did not reveal a source of the infection, nor did it
show evidence of metastases.
DIFFERENTIAL DIAGNOSIS
The patient’s presentation and workup were consis-
tent with molar pregnancy (nausea, vomiting,
vaginal bleeding, ultrasound with no intrauterine
1
 Case report
Figure 1 Transvaginal ultrasound showing lack of intrauterine sac and
abnormal placental tissue with fluid-­filled cysts in longitudinal view.
sac but with cystic appearance, and significantly elevated
hCG). Her laboratory studies showed a new hyperthyroid state
(compared with baseline normal Thyroid function tests (TFTs)
obtained a few years ago during psychiatric evaluation), and
she experienced symptoms of tachycardia, heat intolerance,
diaphoresis and tremors. Therefore, the leading differential was
thyrotoxicosis secondary to molar pregnancy, as stimulation of
TSH receptors by the beta subunit of hCG can cause increased
production and release of thyroid hormones.5
Other causes of hyperthyroidism were also considered but
deemed less likely clinically. The patient lacked a goitre, pretibial
myxoedema, exophthalmos or lid lag to suggest Graves’ disease,
although TSH receptor and thyroid peroxidase antibodies were
not collected during the admission. She has no history of any
thyroid disorders in the family. There was no preceding viral
upper respiratory tract infection or neck tenderness to indicate
subacute thyroiditis. Fibrinogen was mildly elevated to 558 mg/
dL in the setting of concurrent salmonella bacteraemia. In pain-
less (silent) thyroiditis, T4 is usually disproportionately elevated
compared with T3, which was the opposite in this case.6 The
patient’s home medications were reviewed, and no medications
were found that are classically linked to thyroiditis. She does
have a history of bipolar disorder, but it has been managed with
olanzapine and fluoxetine without prior lithium use. There was
no recent iodinated contrast media exposure prior to the devel-
opment of her symptoms. A thyroid ultrasound was not obtained
prior to her emergent intervention.
Infection, such as endometritis, was also on the differential
before the blood cultures turned positive, given the fever and
Figure 2 Transvaginal ultrasound showing lack of intrauterine sac and
abnormal placental tissue with fluid-­filled cysts in transverse view.
2 De Guzman E, et al. BMJ Case Rep 2021;14:e242131. doi:10.1136/bcr-2021-242131
tachycardia. Although bacteraemia could explain these abnormal
vital signs, it does not account for her other symptoms of heat
intolerance and tremors. Besides an enlarged endometrium,
the vaginal ultrasound did not show signs of endometritis. The
patient also lacked productive cough or dysuria to suggest other
infectious aetiologies.
Lastly, the patient had multiple admissions in the past with
tachycardia that spontaneously resolved. Her tachycardia then
was attributed to excessive caffeine consumption (drinking 4–6
cups of coffee in the morning), as well as frequent use of her
albuterol inhaler. However, the patient currently only drinks
one cup of coffee a day and has not used her albuterol inhaler
in over 2 weeks. She also did not have significant anaemia or
decreased urine output to suggest hypovolaemia as a cause of
the tachycardia.
TREATMENT
After reviewing the patient’s case, the endocrinology team
reached a consensus that the patient was suffering from thyro-
toxicosis secondary to her molar pregnancy. The patient was
scheduled for a suction dilation and curettage to evacuate the
mole and remove the ultimate source of the β-hCG. On day
2 of admission, she was started on propranolol (not adminis-
tered due to hypotension) and propylthiouracil (PTU) (500 mg
loading dose, followed by 100 mg every 8 hours) to decrease
sympathetic hyperactivity and thyroid hormone production,
respectively. Although methimazole has a more rapid onset
and better side effect profile than PTU, this patient also had
significantly elevated free T3 levels, so PTU was chosen for its
ability to prevent T4 to T3 conversion.7 After discussion with
the OBGYN team, there was initially low suspicion for infection
(before blood cultures resulted), so the patient was also started
on intravenous hydrocortisone (300 mg loading dose, followed
by 100 mg every 8 hours). The decision to start steroids was
based on concern of thyroid storm occurring in the periopera-
tive period. At the time the endocrinology team was consulted,
the patient had a Burch-­Wartofsky Point Scale score of 40, which
suggests impending thyroid storm.4 Furthermore, steroids also
help decrease conversion of T4 to the more active T3 hormone.8
Overnight, the patient became hypotensive and persistently
tachycardic. Due to concerns of sepsis, the OBGYN team
performed an emergent suction D&C early on day 3 of admis-
sion. Specimen was collecting during the procedure, and
pathology revealed diploidy with negative p57 immunohisto-
chemistry stain, consistent with a complete hydatidiform mole.
OUTCOME AND FOLLOW-UP
After suction D&C, the patient was closely monitored for
thyroid storm in the postoperative period, with no worsening of
her symptoms. Four days after the procedure, her tachycardia,
tremors, diaphoresis and heat intolerance finally resolved. Her
thyroid function tests also improved (FT3 3.0 pg/mL, FT4
1.52 ng/dL, TSH 0.016 μIU/mL) (table 1). Her β-hCG level
decreased to 14 744 from 414 600 IU/L. Propranolol and PTU
were discontinued at that time since the patient was no longer
symptomatic. The intravenous steroids were discontinued soon
after the procedure due to the patient’s blood cultures turning
positive and eventually growing Salmonella species. A CT chest/
abdomen/pelvis performed to identify an infectious source was
unrevealing. Per discussion with the infectious disease team, the
Salmonella bacteraemia was likely secondary to bacterial trans-
location from the gastrointestinal tract, and the patient was
discharged with ciprofloxacin (500 mg two times per day) to

Table 1 TFTs and β-hCG (Beta human chorionic gonadotropin)
levels
Admission Discharge 2 weeks
Test value value postdischarge Reference range
TSH <0.015 0.016 0.249 0.4–4.7 μIU/mL
Free T4 3.73 1.52 1.16 0.70–1.80 ng/dL
Free T3 10.0 3.0 2.9 2.8–5.3 pg/mL
Quantitative 414 600 14 744 1060 <10 IU/L (non-­
β-hCG pregnant)
complete a 2-­week course of antibiotics. She was counselled on
molar pregnancy and complications of pregnancy at an advanced
maternal age. The importance of contraception use during this
postoperative period was emphasised, in order to monitor for
a rise in β-hCG that may indicate development of gestational
trophoblastic neoplasia (GTN). Imaging is useful not only in
diagnosing hydatidiform moles, but also in detecting compli-
cations such as GTN metastases, the most common site being
the lung.9 In our patient, a chest x-­ray and CT chest/abdomen/
pelvis did not show any evidence of metastatic disease. Labwork
performed 2 weeks after discharge showed continued improve-
ment of her TFTs and β-hCG levels.
DISCUSSION
Molar pregnancy is part of a spectrum of diseases known as
gestational trophoblastic diseases. It is a complication defined
by abnormal benign or malignant proliferation of trophoblastic
cells which result in markedly elevated β-hCG levels. Gestational
trophoblastic disease can cause secondary hyperthyroidism
as a result of structural homology between β-hCG and TSH.
Hormones such as TSH, Follicle-­stimulating hormone (FSH),
Luteinizing hormone (LH) and hCG are heterodimeric glyco-
protein hormones that have an alpha subunit and a beta subunit.
The alpha subunit is common to all these hormones. More-
over, there is structural similarity between hCG and TSH beta
subunits. Laboratory studies have revealed that normal β-hCG
has weak thyrotropic activity on thyroid TSH receptors.10 One
unit of β-hCG has the reactivity equivalent to 0.0013 uU of TSH.
The level of sialylation of β-hCG determines its bioreactivity on
the TSH receptors: the higher the degree of sialylation, the less
activity β-hCG will have. The β-hCG produced by hydatidiform
moles has greater thyrotropic activity than normal β-hCG due to
its decreased sialylation.11 Moreover, the extent of desialylation
of β-hCG varies with each molar pregnancy. One unit of β-hCG
produced by Gestational trophoblastic disease (GTD) has thyro-
tropic activity range from 3.72 to 46.8 uU equivalents of TSH.12
It is estimated that for every 10 000 IU/L increase in hCG, there
is a 0.1 μIU/mL decrease in TSH and 0.1 ng/dL increase in free
T4.13
Increased levels of β-hCG concentration cause a weak hyper-
thyroid state in a normal pregnancy. The degree of hyperthy-
roidism is exacerbated by molar pregnancy with elevated levels
of β-hCG and decreased levels of sialylation. The extent and
development of hyperthyroidism, thyrotoxicosis, and ultimately
thyroid storm is determined by multiple factors: the levels of
β-hCG, the amount of desialylation, as well as the duration and
type of molar pregnancy.
Compared with partial hydatidiform moles, complete hydatid-
iform moles usually have higher β-hCG levels.14 Therefore, it is
not surprising that complete moles have been associated with
more severe hyperthyroidism. In one Turkish study, patients
with complete moles were found to have significantly lower TSH
De Guzman E, et al. BMJ Case Rep 2021;14:e242131. doi:10.1136/bcr-2021-242131
Case report
levels and higher free T4 levels compared with those with partial
moles.15 The patients diagnosed with complete moles were also
significantly older and of higher gravidity than the patients diag-
nosed with partial moles. Our patient, who was diagnosed with a
complete mole, was 49 years old with seven prior pregnancies. A
recent case report describing thyroid storm in a complete molar
pregnancy also consisted of an older maternal age woman with
multiple pregnancies (G7P3033).16
In the past few decades, physicians have diagnosed molar
pregnancies at earlier gestational ages. One Brazilian study
found that the average gestational age at time of diagnosis
from 1988 to 1992 was 15 weeks, compared with only 10
weeks in 2008–2012.17 This earlier detection is promoted by
the increased utilisation of first trimester ultrasound and β-hCG
levels for screening of prenatal conditions.18 In our patient, the
later diagnosis at 15 weeks gestation was likely due to a delay in
seeking medical care after having missed her period.
Treatment of thyrotoxicosis or thyroid storm is based on
managing the four major elements involved: the precipitating
event; the thyroid gland; the peripheral effects of thyroid
hormone and systemic decompensation, if any. The precipi-
tating event in our case was molar pregnancy with the defini-
tive treatment being evacuation. Thyroid hormone synthesis can
be curbed with PTU or methimazole, and hormone release can
be decrease with iodine. PTU and glucocorticoids can dampen
the peripheral effects of thyroid hormone by decreasing the
rate of conversion of T4 to the more active T3. Beta blockers,
Patient’s perspective
When I found out I was pregnant, I had no idea about a molar
pregnancy. When I realised there was no baby, I was confused.
I’ve never had a miscarriage. All my children were live births, so
this was strange. I knew something was wrong when I started
vomiting so much. I felt like it was killing me. I believe that if I
hadn’t come to the doctor, I would have laid in bed and died. I
knew I had to come see somebody to find out what was going
on with me. I was too sick for a normal pregnancy or even a
miscarriage. It took me a while to accept that there was no baby.
I was a little sad because I felt like I’ve been punished. Im being
honest, I don’t wish this type of pain and illness on anybody.
Constantly throwing up, the stomach pain, I don’t want anyone
to have to go through this. I want people to know about this
disease, so they can avoid what I’ve been through. I am thankful
that the surgery went well. I feel that my health is better now. I
hope I never experience this again, and that nobody else has to
experience it. It’s worse than actually having a baby.
Learning points
►► In patients with molar pregnancies, it is essential to monitor
for rare complications such as thyrotoxicosis.
►► Treatment of thyrotoxicosis in molar pregnancies, especially
those with significantly elevated β-hCG levels and
undetectable TSH levels, is important to prevent progression
to thyroid storm.
►► Counselling patients about the risks associated with
advanced maternal age pregnancy is necessary for the
health of both fetus and mother, and can prevent undesired
complications, such as molar pregnancy and thyrotoxicosis in
this case.
3
 Case report
specifically propranolol and esmolol, can decrease the peripheral
effects of thyroid hormone by blocking the receptors on which
T3 acts. In severe illness, plasmapheresis and charcoal plasma
perfusion can help remove excess hormone.19
In our patient, due to active infection, steroids were discon-
tinued after two doses and propranolol was not administered
given low blood pressure. She essentially received 5 days of
PTU therapy, which was discontinued once her FT4 normalised
before discharge. Given that she had suction dilatation and
curettage done in an appropriate and timely manner, her thyroid
function tests continued to improve following the procedure as
did her clinical status.
Contributors EDG, HS and RJ were directly involved in the patient’s care. EDG and
HS drafted the manuscript under the supervision of RJ, who provided guidance for
the final manuscript. All authors contributed to the final version of the manuscript.
Funding The authors have not declared a specific grant for this research from any
funding agency in the public, commercial or not-­for-­profit sectors.
Competing interests None declared.
Patient consent for publication Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
ORCID iD
Eison De Guzman http://​orcid.​org/​0000-​0001-​8549-​1969
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