Thyroid cancer is the most common endocrine malignancy. It affects persons of all
ages, but the prognosis is worse for elderly patients. A total of 16,100 cases were
projected in 1997, with 11,400 occurring in women.
19
Well-differentiated thyroid cancer occurs predominantly in young women, and the age
at diagnosis is an important prognostic variable. The female predominance of thyroid
cancer makes its occurrence during pregnancy not uncommon. About 10% of thyroid cancers
occurring during the reproductive years are diagnosed during pregnancy or in the first
year after birth.Thyroid nodules in women are common. Two percent of women of childbearing age have
a thyroid nodule. Fortunately, most are benign. The prevalence of cancer in a solitary
nodule ranges from 10% to 20%.
18
Most nodules are discovered by the patient or by the physician at a routine prenatal
examination. The discovery of any abnormality during pregnancy causes much anxiety
for the patient and her physician. Any evaluation or diagnostic procedure must take
into account the pregnant state of the patient and the fetal concerns to decrease
any potential risks.Single clinically detected thyroid nodules are three to four times more common in
women than in men, with a peak incidence during the reproductive years. This distribution
of thyroid nodules suggests a possible role for hormonal stimulation in their development.
8
,
25
Occult microcarcinomas are found approximately equally in men and women, but clinically
detectable disease is more common in women during the childbearing years of hormonal
function, suggesting a role for hormonal influences in the growth of thyroid malignancies.
Walker and Doherty
8
,
26
report an increase in nodular thyroid disease during pregnancy. Mazzaferri
16
reports an 8% to 17% incidence of malignancy in thyroid nodules overall; however,
Doherty and Rosen
8
,
21
,
22
report that 39% to 43% of nodules discovered in association with pregnancy are malignant,
suggesting an increased incidence of thyroid cancer during pregnancy. Most nodules
discovered during pregnancy are benign thyroid cysts or colloid (adenomatous) nodules.
Those found to be malignant are usually slow-growing differentiated thyroid cancers.
These are usually papillary or follicular carcinomas with a good prognosis in this
age group. Variants of papillary thyroid cancer associated with a poorer prognosis
are columnar cell, tall cell, and diffuse sclerosing types.
18
These mainly occur in older patients. The virulent, medullary, and undifferentiated
or anaplastic thyroid carcinomas are rare during the childbearing years, with the
highest incidence in the fifth and sixth decades.
18
These nodules have an extremely poor prognosis regardless of stage or treatment.
The discussion that follows focuses on the more common differentiated thyroid cancers.The changes in thyroid function brought about by pregnancy are well-known.
3
,
20
There is a marked increase in the production of thyroid-binding globulin by the liver
as a result of the elevated estrogen. Thyroid-binding globulin doubles by the end
of the first trimester. Total concentrations of triiodothyronine (T3) and thyroxine (T4) also double; however, free T4 declines slightly but remains in the normal range. Thyroid-stimulating hormone declines
to the lower limit of normal. Thyroid stimulation during pregnancy is thought to be
caused by the high levels of beta human chorionic gonadotropin (β-HCG), which also
has known thyroid-stimulating activity.
15
The thyroid gland may undergo a 20% to 30% increase in volume during pregnancy. In
areas of low iodine intake such as Scotland, 71% of pregnant patients show goiter
formation.
20
The work-up of a thyroid nodule discovered in the pregnant patient is similar to that
in the nonpregnant patient except for the fact that radionuclide scans are contraindicated.
A history of rapid recent growth or of prior head and neck radiation exposure increases
the suspicion that a thyroid nodule may be malignant. A history of treatment of Graves'
disease with radioactive iodine does not increase the risk for thyroid cancer because
doses greater than 5000 cGy ablate the gland completely. A complaint of a painful
thyroid gland suggests thyroiditis, and a family history of Hashimoto's thyroiditis
may be discovered. Radiation exposure increases the incidence of thyroid nodules to
a range of 20% to 30%, and also increases the chance of malignancy in these nodules
to 30% to 50%.
18
On physical examination, a hard fixed nodule with cervical adenopathy is a sign of
malignancy. Vocal cord paralysis, hoarseness, and dysphagia are rare but are signs
of advanced disease. A dominate nodule, even of long duration, needs evaluation because
of the slow growth pattern in most differentiated thyroid cancer.
In general, extensive laboratory testing is not helpful.
6
,
18
Mazzaferri
15
,
16
suggests that the level of thyroid-stimulating hormone be obtained to identify unsuspected
thyroiditis. Most patients with a malignant thyroid nodule have normal findings on
thyroid function testing. Although medullary thyroid cancer is rare in young women,
a serum calcitonin level should be obtained when this lesion is suspected. Serum calcitonin
elevations are specific for medullary thyroid cancer. Other clinicians recommend,
in addition to an assay for thyroid-stimulating hormone, determinations of free T3 and free T4, antithyroid antibodies, and serum calcium to rule out a parathyroid lesion.
26
Radionuclide thyroid imaging with 123I or 131I is contraindicated during pregnancy because of the ability of the fetal thyroid
to concentrate iodine. Thyroid imaging does not reliably distinguish malignant nodules
from benign nodules. Malignant nodules do not incorporate iodine as well as normal
thyroid tissue and appear “cold” on the scan. Nodules that concentrate iodine or “hot”
nodules are usually but not always benign. Cold nodules are found to be malignant
16% of the time.
18
Ultrasound is safe in pregnancy but does not diagnose or exclude malignancy. Ultrasound
is an accurate method for measuring a nodule and for determining the presence of more
than one nodule. Ultrasound is accurate in categorizing nodules as cystic or solid.
It has a low specificity for thyroid pathology and is unable to distinguish benign
from malignant nodules. A solid nodule has a greater likelihood of being malignant,
whereas a cystic nodule is more often benign.
18
Ultrasound can be helpful in guiding fine-needle aspiration as well.Fine-needle aspiration is the most important diagnostic tool in the work-up of a thyroid
nodule discovered in the pregnant patient. It is safe, inexpensive, and helps to distinguish
those patients who can be observed safely during pregnancy from those who need surgery.
False-negative results are reported in 1% to 6% of patients with a diagnostic accuracy
of 70% to 97%.
5
,
18
The results of a fine-needle aspiration may be malignant, suspicious, benign, or
indeterminate. Hamburger
9
recommends strict criteria in the interpretation of the findings of fine-needle aspiration
for the exclusion of malignancy. There must be at least six clusters of benign thyroid
cells on two smears from separate aspirates from different parts of the nodule to
exclude malignancy reliably. Biopsy specimens from lesions greater than 4 cm in size
can be obtained with a cutting needle, allowing more accurate histologic analysis.Tan and co-workers
25
report that fine-needle aspiration is a reliable diagnostic tool in pregnant and
nonpregnant patients. Benign findings on a fine-needle aspiration allow for the continued
observation of a nodule until completion of the pregnancy. If the sample is inadequate
to exclude malignancy or has a benign appearance on aspiration cytology, suppression
with thyroxine is warranted. Exogenously administered thyroid hormone will suppress
most benign nodules but not most malignant ones. Unfortunately, successful suppression
does not completely exclude malignancy because some malignant nodules also suppress.
18
Thyroxine is safe during pregnancy, although some physicians defer thyroid treatment
until after delivery for medicolegal reasons.
8
,
9
Levels of thyroid-stimulating hormone should be followed to ensure adequate doses
of thyroxine are given to lower the level. Thyroidectomy for diagnosis is rarely indicated
in the pregnant patient.Mazzaferri
15
suggests proceeding with fine-needle aspiration in all thyroid nodules discovered
prior to 20 weeks' gestation. Fine-needle aspiration is performed after 20 weeks only
in nodules that grow during suppressive therapy. Surgery for indeterminate findings
on fine-needle aspiration can be delayed until after delivery in most patients unless
the nodule is increasing in size. Doherty and co-workers
8
suggest that the work-up of a thyroid nodule should depend on the gestational age.
They recommend delaying any work-up or biopsy until after delivery in patients first
found to have a nodule beyond 20 weeks' gestation, except in patients with rapidly
growing lesions. Fine-needle aspiration is performed on all patients prior to 20 weeks'
gestation.The timing of surgery for nodules is controversial. Hamburger
9
recommends surgery if the findings of fine-needle aspiration are positive for cancer
but does not state exactly when this treatment should be performed. In pregnant patients
with differentiated thyroid cancer found after 20 weeks' gestation, definitive surgery
is usually delayed until after delivery. Fortunately, undifferentiated cancer is rare
in this age group, and treatment for these aggressive cancers must be individualized
depending on the extent of disease. The prognosis is usually so poor in this situation
that only a palliative procedure may be recommended.
9
For cancer found early in pregnancy, surgery during the second trimester is safe
for the patient and her fetus.
6
,
21
,
22
Cunningham and Slaughter
7
reported on five patients operated on during pregnancy from 1956 to 1967. Three fetal
deaths were attributed to the extent of the surgical procedure; however, more recent
reports note no fetal complications using contemporary monitoring techniques.
6
,
8
,
10
Because nearly all of these malignancies in young women are differentiated thyroid
cancers with an excellent prognosis, delaying surgical treatment until after delivery
for tumors found during the second trimester is advocated.
9
Although reproductive factors have been implicated in the development of thyroid cancer,
there is no evidence that pregnancy worsens the prognosis of thyroid cancer found
during an existing pregnancy or that subsequent pregnancies increase the risk for
cancer recurrence. McTiernan and co-workers
17
reported that pregnancy had little effect on the general incidence of thyroid cancer.
Other investigators have found no difference in recurrence rates in patients treated
for thyroid cancer who subsequently become pregnant.
2
,
12
,
23
Rosen and Walfish
22
reported on 30 patients with thyroid neoplasia during pregnancy. There was a 43%
incidence of cancer and a 37% incidence of adenoma. They concluded that thyroid neoplasia
during pregnancy has a higher incidence of cancer and suggested that its course is
aggravated by pregnancy. Citing no data whatsoever, Asteris and DeGroot
1
proscribe further pregnancy in these patients and recommend therapeutic abortion
for cancers found during the first trimester. Herzon and co-workers
11
reported on 22 patients with thyroid cancer diagnosed at the time of pregnancy. Six
patients underwent successful surgery during pregnancy and delivered uneventfully.
There were two recurrences overall and no deaths in this group of patients. When compared
with nonpregnant patients, there were no differences in survival. Rosvoll and Winship
23
also reported no growth acceleration of thyroid cancers as an effect of pregnancy,
nor did the tumors complicate the pregnancy. They suggested that subsequent pregnancy
is safe in these patients. In contrast, Hod and others
13
,
14
,
21
have reported on cases in which pregnancy did seem to accelerate the growth of a
thyroid cancer. It is speculated that high levels of serum HCG stimulated the growth
of the thyroid cancers through the stimulation of thyroid-stimulating hormone receptors.
14
Subsequent pregnancy after treatment with 131I seems to be safe. Impairment of gonadal function by 131I is temporary and reversible, and there does not seem to be an increased incidence
of adverse pregnancy outcome.
4
,
24
The genetic risks after exposure to therapeutic doses of 131I are low. Casara and co-workers
4
reported on 70 patients who became pregnant after treatment with 131I for thyroid cancer. There was no increase in stillbirths, malformations, early deaths,
or malignancies in the offspring. They empirically recommend the avoidance of pregnancy
for 1 year after the administration of 131I to ensure complete elimination of the radionuclide.To read this article in full you will need to make a payment
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Article info
Footnotes
Address reprint requests to Peter C. Morris, MD, Nebraska Methodist Hospital Cancer Center, 8303 Dodge Street, #200, Omaha, NE 68114
Identification
Copyright
© 1998 W. B. Saunders Company. Published by Elsevier Inc. All rights reserved.
