Gynecological Endocrinology

ISSN: 0951-3590 (Print) 1473-0766 (Online) Journal homepage: http://www.tandfonline.com/loi/igye20

Advanced thyroid carcinoma in pregnancy: case

report of two pregnancies

Raquel Guerrero-Vázquez, Eduardo Moreno Reina, Noelia Gros Herguido,

María Asunción Martínez Brocca & Elena Navarro González

To cite this article: Raquel Guerrero-Vázquez, Eduardo Moreno Reina, Noelia Gros Herguido,
María Asunción Martínez Brocca & Elena Navarro González (2015): Advanced thyroid
carcinoma in pregnancy: case report of two pregnancies, Gynecological Endocrinology, DOI:
10.3109/09513590.2015.1018165

To link to this article: http://dx.doi.org/10.3109/09513590.2015.1018165

Published online: 29 Sep 2015.

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ISSN: 0951-3590 (print), 1473-0766 (electronic)

Gynecol Endocrinol, Early Online: 1–4

! 2015 Taylor & Francis. DOI: 10.3109/09513590.2015.1018165

CASE REPORT

Advanced thyroid carcinoma in pregnancy: case report of

two pregnancies
Raquel Guerrero-Vázquez1, Eduardo Moreno Reina2, Noelia Gros Herguido1, Marı́a Asunción Martı́nez Brocca1,
Elena Navarro González1
1
Department of Endocrinology and Nutrition, Virgen del Rocio University Hospital, Seville, Spain, and 2Department of Gynecology and Obstetrics,
Virgen del Rocio University Hospital, Seville, Spain

Abstract Keywords
Downloaded by [University of Otago] at 05:48 01 October 2015

Differentiated thyroid carcinoma is one of the most frequently diagnosed cancers during Fetal monitoring, pregnancy, prognosis,
pregnancy, second only to breast cancer. Therefore, it would be of value to determine if there thyroid carcinoma
are pregnancy-related physiological effects that impact long-term prognosis for patients with
this disease. Hormone effects attributable to b-human chorionic gonadotropin and estrogens History
seem particularly likely. We present a case of a 40-year-old woman with thyroid follicular
carcinoma with accompanying bone metastases. The cancer was discovered immediately after Received 6 December 2014
childbirth and the woman became pregnant again when the disease was in an advanced stage. Accepted 26 January 2015
We describe the cancer evolution and present the maternal and fetal results. Pregnancy in Published online 25 September 2015
women with advanced thyroid carcinoma could affect long-term prognosis. However, more
studies are needed to evaluate this hypothesis. In this unique case, there were two pregnancies
and the second occurred in an advanced state of the disease. We evaluated how these
pregnancies could affect short-term prognosis of the disease.

Case report with lower limb weakness and bilateral areflexia. She received
steroid and local radiotherapy (10 Gy over five sessions) followed
The patient in this case was a 40-year-old woman with a 10-year
by monthly doses of 4 mg intravenous zoledronic acid and 10 Gy
history of primary infertility. She became pregnant through
local radiotherapy. After these treatments, the thyroglobulin value
in vitro fertilization. During pregnancy, she was diagnosed with a
(Tg) was 5480 ng/mL with suppressive TSH levels (0.01 mU/mL).
thyroid nodule in the left lobe that measured 49  41  47 mm. A
At this stage in her treatment, the patient moved to our city and
fine-needle aspiration sample was cytologically indeterminate,
started continued care at our unit. We performed CT, magnetic
according to the Bethesda classification. During the third
resonance imaging (MRI) of the spinal column, and blood tests
trimester of her pregnancy, the patient presented with severe
for thyroid hormones, Tg, and Tg antibodies (TgAb).
back pain that was attributed to the pregnancy. At 39 weeks of
MRI results were similar to the previous ones (Figure 1).
pregnancy, the patient delivered vaginally a healthy girl weighing
Results of the MRI of the uterus led us to speculate that the
3200 g. Back pain worsened significantly after childbirth. A
patient was pregnant (Figure 2), which was consistent with her
thoracic-abdominal and pelvic computed tomography (CT) was
reported 10-week amenorrhea. Pregnancy was confirmed with a
performed, revealing multiple pulmonary nodules as large as
pregnancy test. We discussed with the patient the maternal and
12-mm diameter in the right lower lobe, and a solid mass of
fetal risks associated with pregnancy in this situation, mainly
65  65 mm area infiltrating the pedicule of lumbar vertebra
related to zoledronic acid exposure (classified as a category D
1 (L1) and thoracic vertebra 12 (T12); this mass also invaded the
drug by the U.S. Food and Drug Administration) and treatment
spinal canal. A biopsy of the lumbar mass was consistent with a
with radioiodine in the months previous to pregnancy. Maternal
follicular thyroid carcinoma. A total thyroidectomy and lymph
risk of spinal cord compression was also explained.
node dissection were performed, revealing a follicular thyroid
Ultrasounds performed at intervals during the pregnancy
carcinoma measuring 5.5 cm in diameter, accompanied by
showed fetal biometry consistent with the length of gestation
angioinvasion and disease-free resection margins. Lymph nodes
and normal total fetal anatomy with regard to the skull, intra-
were free of neoplasia. She received two doses of 131I with
cranial structures, face, spine, neck, chest, heart, abdominal wall,
recombinant thyroid stimulating hormone (rTSH) at a 3-month
nephrourological apparatus, external genitalia, and extremities.
interval. Scans made after 131I treatment indicated a bilateral
The gestation developed without problems. There was no increase
femoral, lumbar, and costal arches uptake. After the first dose of
131 of lumbar pain or symptoms suggestive of spinal cord compres-
I, the patient experienced increased lumbar pain associated
sion. Tg values increased progressively during gestation, peaking
at 2774 ng/mL in the third trimester (Figure 3). Levothyroxine
Address for correspondence: Raquel Guerrero-Vázquez, Department of
requirements during pregnancy did not change, remaining at
Endocrinology and Nutrition, Virgen del Rocio University Hospital, 200 mcg daily. TSH levels were and remained appropriately
Manuel Siurot Avenue sn, 41013 Seville, Spain. E-mail: suppressed throughout gestation. The delivery was scheduled with
raquel.guerrero.sspa@juntadeandalucia.es the consensus and co-operation of a multidisciplinary team of
 2 R. Guerrero-Vázquez et al.
Figure 1. Computed tomography of spinal column. A solid mass
infiltrating thoracic vertebra 12. This mass also invaded the spinal canal.
Downloaded by [University of Otago] at 05:48 01 October 2015
Figure 2. Magnetic resonance imaging (MRI). Embryo sac inside the
uterus.
anesthesiologists, obstetricians, and endocrinologists, all of whom
participated in monitoring the patient during pregnancy. Cesarean
section at 38 weeks gestation was selected to prevent neurological
impairment due to spinal cord compression during labor and
delivery. Cesarean section was performed without incident. A
healthy, 4000 g male was born. The child was breastfed some
time. Upon termination of breastfeeding, intravenous treatment
with 4 mg of zoledronic acid was resumed monthly. TSH levels
remained suppressed (50.1 mU/mL) throughout follow up.
CT and MRI after delivery did not reveal morphological
disease progression. After delivery, the lumbar tumor mass was
surgically removed. The surgery had two purposes. First, we
wished to stabilize the cord. Second, the tumor could represent
problems when 131I treatment was resumed. The presence of
the tumor could reduce the uptake of the radioiodine by bones
and lung lesions. Also, 131I treatment could cause a local
inflammation in the tumor that might compress the cord.
Afterwards, the patient was treated with 180 mCi of 131I with
rTSH, without complications. Tracer uptake was demonstrated
in the lungs, in intra-abdominal tissues, in the dorsal spine, and
at the femoral level. Tg levels under rTSH stimulus exceeded
30 000 ng/mL. 2-Deoxy-2-(18F)fluoro-D-glucose tracer followed
by a positron emission topography (18-FDG PET) scan showed
Gynecol Endocrinol, Early Online: 1–4
that there had been uptake by the dorsal spine, lung tissues,
and the liver.
Discussion
It is estimated that 1 out of 1000 pregnancies are complicated by
cancer [1]. Researchers in the USA evaluated five million women
between 1991 and 1999 and estimated that the incidence of
differentiated thyroid carcinoma (DTC) in pregnancy was 14 out
of 100 000. That ranks it the second most frequent cancer during
pregnancy, after breast cancer. In 75% of these cases, the
diagnoses were made after delivery, as in this case [1]. Ten
percent of all DCTs in women of child-bearing age are diagnosed
during pregnancy or shortly after [2].
The role of pregnancy hormones on the prognosis of DCT has
been debated. b-human chorionic gonadotropin (b-HCG) is
structurally similar to TSH and therefore, could participate in
the growth of benign and malignant lesions [3]. High levels of
estrogens could contribute to the growth of benign thyroid lesions
by interacting with a membrane receptor that is expressed in some
thyroid cells [4], suggesting a role for estrogen in tumorigenesis.
Estrogens may stimulate the expression of the estrogen receptor a
(ERa) in cell lines of thyrocytes in vitro [5,6] and, through
binding to its receptor, may activate different intracellular
signaling pathways, in particular the RAS-RAF-MAPK-ERK
signaling pathways. These play an important role in cell
proliferation and tumor growth. Moreover, the activation of
these pathways stimulates phosphorylation of estrogen receptors,
leading to their activation. Other studies have shown that
estrogens can reduce the expression of the sodium–iodine
symporter and stimulate the expression of genes involved in the
production of Tg without stimulating rapid cell proliferation [7,8].
Tg values in healthy women increase during pregnancy [9],
apparently due to a complex interaction between b-HCB, TSH,
and estrogens in thyroid cells. In addition, iodine clearance is
more efficient during pregnancy. However, elevation of Tg does
not seem to correlate with the DCT disease progress in pregnant
women [8]. We observed a progressive increase of Tg levels
during gestation, with maximum values in the third trimester, but
there was no apparent relation to disease progression. Specifically,
there was no evidence of disease progression in the morphological
re-assessment after delivery, although there was a marked
decrease of Tg levels (Figure 3).
The effect of these pregnancy-related hormonal factors on the
prognosis of DCT has been the subject of speculation. In some
early studies, there was no relationship between pregnancy and
the mortality due to DCT or its recurrence [10,11]. However, in a
subsequent study, researchers concluded that women diagnosed
with DCT during pregnancy or in the first year after delivery had
a worse prognosis than nulliparous women or women who had
delivered more than 1 year before diagnosis. This study concluded
that diagnosis during pregnancy was the main predictor of
persistent disease, and suggested that it was related to increased
expression of ERa in the pregnant women compared to control
women [12]. It must be noted that in this work, prognosis was not
associated with time of surgery (during pregnancy or in the first
year after it), nor with the time during which patients received
treatment with 131I. Another recent study [13] does find an
association between pregnancy and the risk of recurrence or
persistence of the disease in women diagnosed with DCT during
pregnancy or in the 2 years immediately following, compared to
two control groups. However, in this study, no differences in the
ERa expression between the pregnant group and control groups
were found, leading the authors to conclude that more studies are
needed to clarify the pathophysiological mechanism by which the
pregnancy may worsen the overall prognosis of DCT [13].
 DOI: 10.3109/09513590.2015.1018165
6000
5000
4000
3000
2774
2000 1890
1806 1763
1000
0
Pregestaonal First trimester Second Third
(July-12) trimester trimester
Figure 3. Thyroglobulin evolution before, during and after pregnancy.
Downloaded by [University of Otago] at 05:48 01 October 2015
It is important to consider that the final variables assessed, and
the methodology used in the aforementioned studies was different,
preventing straightforward comparison between them [10–13].
In more recent studies [12,13], persistence and recurrence of
disease were evaluated with more sensitive methods for disease
detection than those used in previous studies [12–15]. In the
instance of this particular case, the data do not permit us to
evaluate the effect of the pregnancy on the prognosis: there were
two pregnancies and the second occurred when the disease was
already in an advanced stage.
Despite the commonness of DCT during pregnancy [1], there
are few cases reported of advanced thyroid carcinoma described
in the literature [16–18]. To our knowledge, there is only one
other reported case of a follicular carcinoma with metastatic lung
disease and intra-cranial and bone metastases during pregnancy
[16]. In this case, the patient presented with a differentiated
follicular carcinoma and the diagnosis was made during preg-
nancy. Other cases of DTC with metastatic disease during
pregnancy were papillary tumors [17,18]. In one of them, brain
metastases from papillary carcinoma were diagnosed at 29 weeks
of gestation [17]. In another case, the patient was paraplegic 2 d
after delivery and the diagnosis of lumbar metastatic disease was
a papillary tumor [18].
There are very few reports in the literature of lumbar spinal
metastases, or benign or malignant primary tumors in pregnancy,
and so there is little information available to optimize the
approach in these situations. The majority of the reported cases
are of spinal metastases of trophoblastic tumors [19,20] or other
primary tumors, such as hemangiomas [21] or metastatic breast
cancer [22]. Since these studies are concerned with different
tumors, treatment varies and there is little basis for comparison.
One case similar to ours involves a woman diagnosed during
pregnancy with breast cancer that had spinal metastases. This
patient was treated with chemotherapy, with a positive outcome
for both mother and infant [22].
Monitoring and treatment of advanced thyroid carcinoma
during pregnancy. Due to its rarity, advanced thyroid carcinoma
during pregnancy does not receive special attention in the
published guidelines clinical practice. The American Thyroid
Association makes general recommendations as follows [23]:
(1) Thyroid function should be evaluated as soon as pregnancy is
confirmed. The adequacy of levothyroxine treatment should
Thyroid carcinoma in pregnancy 3
5000
2829
2647
2195
1805
1458
Thyroglobulin (ng/ml)
Early 6 months aer Aer spinal December-13 February-14 July-14
postpartum delivery (March dorsal surgery
-13) (November-13)
be monitored every 4 weeks until 16–20 weeks of gestation
and at least once per trimester thereafter.
(2) The pre-conception level of TSH in women with DCT, which
is determined by risk stratification, should be maintained
during pregnancy.
(3) Ultrasound monitoring is recommended in each trimester
during pregnancy in patients with previously treated DCT
and high level of Tg, or when there was evidence of
persistent structural disease prior to pregnancy.
Pregnancy in this situation requires strict maternal and fetal
monitoring by a multidisciplinary team who communicate
regularly. Treatment should be administered in a center dedicated
to this specialty [24,25]. A detailed study of the risks, benefits,
and potential implications of the pregnancy on the maternal and
fetal well-being is necessary [25]. In this case, the patient and her
partner accepted the risks and decided to continue the pregnancy.
During the pregnancy, we monitored:
(1) Thyroid hormones to guarantee appropriate supply of thyroid
hormone to the fetus and to allow adequate suppression of
TSH, so that its stimulatory effects on the tumor would be
avoided. TSH suppression was maintained throughout gesta-
tion. We did not perform cervical ultrasound quarterly
because there was no structural disease prior to pregnancy.
(2) Monitoring the spine to assess the need for surgical treatment
of vertebral bone in the event of spinal involvement. The
patient was clinically stable during pregnancy, with no
symptoms of spinal compression, making intervention
unnecessary.
(3) Close monitoring and co-ordinated follow-up by a multidis-
ciplinary team of endocrinologists and obstetricians.
(4) Completion of the pregnancy. In the case mentioned above
[22], the delivery was carried out by cesarean section at 33
weeks by breech presentation and oligoamnios. In the case
presented here, there were no complications with the
pregnancy, so the delivery was made at 38 weeks. Cesarean
section was chosen to prevent labor and expulsion, which
could have led to spinal cord compression.
Conclusions
We present a rare case of advanced thyroid carcinoma in a
pregnant woman with clinical presentation during the first
 4 R. Guerrero-Vázquez et al.
pregnancy and in an advanced state during the second pregnancy.
The management of advanced thyroid carcinoma in a pregnant
woman is a unique clinical challenge with no clinical studies or
guidelines. It is unclear what the effect of the pregnancy will be
on the evolution of the disease, although it was recently suggested
that it may adversely affect the prognosis. Follow-up by a
multidisciplinary team during pregnancy is essential, as well as
providing detailed, complete information to pregnant women
about the risks.
Declaration of interest
The authors report no conflicts of interest.
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