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Original Studies |
Division of Endocrinology, Diabetes and Metabolism (M.M.), and Department of Internal Medicine (E.L.M.), The Ohio State University, Columbus, Ohio 43210
Address all correspondence and requests for reprints to: Ernest Mazzaferri, 215 Means Hall, 1654 Upham Drive, Columbus, Ohio 43210-1228.
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Abstract |
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Introduction |
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One study from the New Mexico Tumor Registry reported that the survival rate of thyroid cancer in 22 pregnant women, age 18–46 yr, was not significantly different than that in age-matched women with thyroid cancer who were not pregnant (14).
We report here a large cohort of women who were pregnant when a thyroid nodule was discovered that was subsequently found to be malignant, either during or after pregnancy, and compare their clinical features, treatment, and outcomes with those in age-matched women with thyroid cancer who were not pregnant at the time of diagnosis. The main objective of the study was to examine the effect of pregnancy on the prognosis of concomitant thyroid cancer.
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Subjects and Methods |
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The study design, demographic features of the patient cohort, and the characteristics of their tumors, therapy, and outcomes have been reported elsewhere (15, 16, 17). Beginning in 1962, all patients with thyroid cancer under the care of United States Air Force (USAF) physicians were registered in the USAF Central Tumor Registry in San Antonio, Texas. This world-wide system of reporting and following patients gathered pertinent medical records of USAF and other military personnel who had cancer, including all active duty and retired military, their dependents, and others who had been cared for in military medical facilities. The microfilmed medical records containing hospital summaries, operative and pathology reports, recommendations of tumor boards, and follow-up information of all patients were reviewed by one of the original authors, and data were collected as previously reported (16). Patients with thyroid cancer under the care of physicians at The Ohio State University Hospitals on whom comparable records existed were similarly reviewed and added to the study cohort. The computerized database is now maintained at The Ohio State University Cancer Data and Research Service of the Arthur G. James Cancer Hospital and Research Institute.
The study was approved by the Wilford Hall USAF Medical Center Human Subjects Review Board in 1970 and also by The Ohio State University Human Subjects Institutional Review Board in 1993.
Data collection
Sixty-four data elements were recorded for each patient, including age at the time of diagnosis and therapy, demographic information, and details of the patients’ initial presentation, therapy, and outcome. We have previously described the type of information and data that were collected, including the presence or absence of pregnancy when a woman’s malignant thyroid nodule was discovered or when her initial therapy was performed, and the month of gestation according to the hospital records (16). No specific information was collected about the status of the offspring in this study, although whether or not the patient underwent therapeutic abortion or experienced spontaneous abortion was recorded. The clinical features, treatment, and outcome of pregnant women were compared with those in 528 age-matched women in the study cohort who were not pregnant at the time of diagnosis or initial treatment.
Tumor classification
Thyroid carcinomas were classified according to the World Health
Organization (WHO) recommendations (18). Follicular variant of
papillary thyroid cancer was diagnosed in tumors with only a follicular
pattern that had typical cytological features of papillary thyroid
cancer. For the military patients, the diagnosis of thyroid cancer was
confirmed by routine review by the Armed Forces Institute of Pathology.
For The Ohio State University patients, tumors were reviewed by
university pathologists. Tumors were clinically staged according to The
Ohio State University staging system (see Table 3
for details)
(15).
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Thyroid cancer was treated according to the judgment of the attending physician and not according to specific treatment protocols. We retrospectively reviewed the treatment of all patients in the cohort and have previously reported on this patient cohort (15, 16, 17). Treatment with 131I was considered to be ablation of remnant thyroid tissue if the scans disclosed no uptake of 131I outside the thyroid bed and the treating physician’s operative notes and pathology reports made no mention of residual tumor.
Follow-up
Patients were contacted by mail and telephone. Follow-up was also gathered by letters to attending physicians when tumor recurrence or death had occurred. The social security numbers of patients who could not be contacted were submitted to a nationwide search (Eqifax Government and Special Systems Inc., McLean, VA) to identify any who had died in the United States up to the end of September 1993.
Patient status
An individual was considered lost to follow-up if 5 yr or more had elapsed since the last contact and a special effort in 1992 and 1993 failed to locate the patient and the national death records search did not report a match. Patients were considered to have died of thyroid cancer if the death certificate, hospital summary, or attending physician letters indicated this as the cause of death. Cancer was considered to have recurred when it was documented by biopsy in a patient previously considered clinically free of disease for 6 months after initial therapy, or 131I uptake was found at a distant site or in the neck outside the thyroid bed in a patient in whom no 131I uptake was seen 6 weeks or more postoperatively after thyroid hormone withdrawal and adequate TSH stimulation. Some patients were regarded as free of disease if clinical examination alone disclosed no residual tumor, whereas in others this judgment was based on 131I scanning studies. In recent years, serum thyroglobulin measurements have been obtained routinely on most patients but were not used as an indication of recurrence unless confirmed by an imaging study or biopsy.
Statistical analysis
Statistical analyses were done using Stata 4.0 Graphics Data Management (College Station, Texas). Analysis of individual variables was done by Wilcoxon rank-sum test or Kaplan-Meier survival curves with the log-rank statistic. One-way ANOVA was used for multiple comparisons as noted. A two-tailed P value of <0.05 was considered statistically significant. Data are expressed as median or mean values with SEM or with 95% confidence intervals (95% CI) as indicated. Age refers to the patient’s age at the time of diagnosis. All percentages are rounded to nearest integer.
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Results |
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Presentation, clinical features, and pathology
The thyroid tumor was initially found by a physician (the others
were discovered by the patient) in 35 (57%) of the pregnant women and
in 103 (22%) of the women who were not pregnant (P <
0.001). The physical findings in the two groups were not significantly
different (Table 1). The presenting
manifestations, however, were significantly different among the two
groups of women, mainly because fewer pregnant women had symptoms
referable to their thyroid nodule, which was more often found
unexpectedly by routine prenatal neck examination (Table 2, P < 0.001). A history
of prior head and neck x-ray treatment was obtained in 5 (8%) of the
pregnant women, and in 31 (7%) of the women who were not pregnant
(P = NS). There were no important differences in the
tumor features in the two groups of women (Table 3
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Time lapse from discovery of the tumor to initial therapy was
similar in the pregnant women and those who were not pregnant [12.7
months (95% CI 7.9–17.4) compared with 10.8 months (95% CI
8.8–12.7), respectively, Table 4]. One
pregnant patient (2%) underwent thyroidectomy during the first
trimester, 12 (20%) were operated on during the second trimester, 1
(2%) underwent surgery early in the third trimester, whereas 47 (77%)
were operated on 1–84 months after delivery of their babies. Some of
these patients were cared for before fine-needle aspiration biopsy was
widely employed, accounting for the long delays in recognizing the
malignant nature of a few thyroid nodules: 12 patients underwent
thyroidectomy 12–84 months after delivery for a thyroid nodule
discovered during pregnancy that later grew or developed other features
suggesting malignancy. The surgical and medical therapy was not
significantly different among pregnant women and those who were not
pregnant (Table 5, P =
0.07 by Wilcoxon rank-sum).
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Cancer recurred in 9 (15%) pregnant women and 107 (23%) women
who were not pregnant (Table 6,
P = NS). Cancer recurred in distant sites in 1 (2%)
pregnant woman and 12 (3%) who were not pregnant (Table 6,
P = NS). No patient who was pregnant at the time the
thyroid tumor was discovered died of cancer, whereas 6 women (1%) who
were not pregnant at the time of diagnosis died of cancer (Table 6,
P = NS). The outcomes were similar in patients operated
after delivery and those who underwent surgery during pregnancy (Table 7).
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Discussion |
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On the basis of the present study, however, we believe that an especially aggressive initial management of thyroid cancer simply based on the fact that a woman is pregnant is not warranted. We believe that both the diagnostic studies and initial therapy may be delayed until after delivery in most patients.
In pregnant women, we found that the malignant thyroid nodule was more than twice as often asymptomatic and discovered by a physician during a routine prenatal exam as compared with women who were not pregnant in whom nodules were more often symptomatic or discovered by the patient. The pregnant women had similar physical findings, tumor pathological features, treatment, and outcomes as women who were not pregnant.
Most agree that the diagnostic paradigm for a thyroid nodule in a pregnant woman should begin with fine-needle aspiration biopsy, similar to women who are not pregnant, but the timing of the work-up remains uncertain (9, 12, 24). Our observations suggest that the work-up can be postponed until after delivery in most patients without an adverse outcome. Because diagnostic radioactive iodine scans must be delayed until after childbirth to avoid fetal complications, a work-up that begins after delivery permits utilization of an 123I scan (25). This is especially important in patients with indeterminate fine-needle aspiration cytology results (i26). Postponing the work-up until the postpartum period thus seems reasonable in most patients but remains problematic in the nursing mother in whom 123I cannot be used and surgery might be delayed even longer. Delaying the diagnosis for more than 1 yr after discovery of a nodule may significantly increase the risk of death from thyroid cancer (15).
Some suggest that surgical treatment can be safely delayed till after delivery (12, 25). There appears to be no compelling reason to routinely perform thyroidectomy during pregnancy, even if the tumor is bulky or is associated with cervical metastases. We found that 41% of the pregnant women had lymph node metastases and that 10% were bilateral, which may increase the risk of cancer mortality (15). Nonetheless, the pregnant women had a favorable outcome, probably as a result of their young age, regardless of whether their surgery was performed before or after delivery: cancer recurrence and distant metastases occurred with the same rates, even in women who had more advanced stages of tumor.
We believe that most pregnant women with a newly discovered thyroid nodule can safely undergo diagnostic studies and therapy after delivery. During the postpartum period surgery can be performed without risk to the fetus and can be followed by diagnostic and therapeutic radioactive iodine as necessary, providing the mother is not breast feeding.
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Acknowledgments |
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Received April 25, 1997.
Revised June 5, 1997.
Accepted June 6, 1997.
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This article has been cited by other articles:
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  S. Kuy, S. A. Roman, R. Desai, and J. A. Sosa Outcomes Following Thyroid and Parathyroid Surgery in Pregnant Women Arch Surg, May 1, 2009; 144(5): 399 - 406. [Abstract] [Full Text] [PDF]
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 Subsection Reports J. Clin. Endocrinol. Metab., August 1, 2007; 92(8_suppl): s8 - s47. [Full Text] [PDF]
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M. Abalovich, N. Amino, L. A. Barbour, R. H. Cobin, L. J. De Groot, D. Glinoer, S. J. Mandel, and A. Stagnaro-Green Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline J. Clin. Endocrinol. Metab., August 1, 2007; 92(8_suppl): s1 - s47. [Abstract] [Full Text] [PDF]
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S. Fatemi and J. S. LoPresti A Consensus Report of the Role of Serum Thyroglobulin as a Monitoring Method for Low-Risk Patients with Papillary Thyroid Carcinoma J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4507 - 4508. [Full Text] [PDF]
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E. L. Mazzaferri and R. T. Kloos Current Approaches to Primary Therapy for Papillary and Follicular Thyroid Cancer J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1447 - 1463. [Full Text]
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