Ultrasonography of the Fetal Thyroid

Transcription

1 Article Ultrasonography of the Fetal Thyroid Nomograms Based on Biparietal Diameter and Gestational Age Angela C. Ranzini, MD, Cande V. Ananth, PhD, MPH, John C. Smulian, MD, MPH, Michelle Kung, Anita Limbachia, RDMS, Anthony M. Vintzileos, MD Objective: To describe gestational age-dependent and -independent nomograms for fetal thyroid size. Methods. Two hundred fetuses were evaluated between 16 and 37 weeks gestation in this crosssectional study. Results. Nomograms of fetal thyroid size were created by using the 5th, 10th, 50th, 90th, and 95th percentiles based on biparietal diameter and gestational age. A second-order polynomial fit for biparietal diameter and a linear fit for gestational age best described thyroid circumference measurements. Variations in thyroid circumference measurements increased with both larger biparietal diameter and advancing gestational age. There was no intraobserver or interobserver variability in thyroid circumference measurements (P >.20). Conclusions. Both biparietal diameter and gestational age serve as good predictors of fetal thyroid circumference. When the biparietal diameter is difficult to measure, gestational age can be used to assess thyroid size. Key words: fetus; thyroid; ultrasonography; prenatal diagnosis; fetal goiter; fetal thyroid. Abbreviations BPD, biparietal diameter; LMP, last menstrual period Received December 4, 2000, from the Division of Maternal-Fetal Medicine (A.C.R., J.C.S., M.K., A.L., A.M.V.) and Section of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology, and Reproductive Sciences (C.V.A.), University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School/Saint Peter s University Hospital, New Brunswick, New Jersey. Revision requested December 27, Revised manuscript accepted for publication February 7, Dr Ananth was supported in part by Robert Wood Johnson Foundation grant , awarded to The Center for Perinatal Health Initiatives. Address correspondence to Angela C. Ranzini, MD, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School/Saint Peter s University Hospital, 254 Easton Ave, Medical Office Building, Fourth Floor, New Brunswick, NJ Women who have Graves disease or who are treated with medications for thyroid disease during pregnancy are at increased risk of having a fetus with a goiter. For these patients, the fetal thyroid can be imaged during pregnancy. If a fetal goiter is present, in utero testing is available to determine whether thyroid dysfunction is present in these fetuses. 1 Successful in utero treatment for both hyperthyroidism and hypothyroidism is possible. 2 5 When assessing the fetal thyroid, many sonographers rely on a subjective impression of increased thyroid size. The presence of fetal head extension as an adjunct for diagnosing enlargement of the fetal thyroid has been used, but this is present only in fetuses with very large goiters. 6 To diagnose lesser degrees of fetal thyroid enlargement, a nomogram is necessary. Several nomograms for fetal thyroid size have been published, 7 9 but all of them have limitations. These include sample size (31 patients), 7 a complicated formula for volume estimation, 8 and thyroid size estimation performed by only by the American Institute of Ultrasound in Medicine J Ultrasound Med 20: , /01/$3.50

2 Ultrasonography of the Fetal Thyroid observer. 9 In addition, only gestational agebased data have been presented previously, which require reliable gestational age dating. Therefore, the present study was designed to generate gestational age-dependent and -independent nomograms for fetal thyroid measurements in a large population so that a fetal goiter can be diagnosed in an objective manner in those at risk for fetal thyroid enlargement. We also determined whether a circumference or width nomogram was more reliable for thyroid size estimation and assessed interobserver and intraobserver variations in thyroid size. Materials and Methods This study was a cross-sectional study and was approved by the Institutional Review Board at Saint Peter s University Hospital. Patients undergoing ultrasonographic evaluation who had gestational dating based on a reliable last menstrual period (LMP), which was consistent with ultrasonographic evaluation, were eligible for inclusion in this study. Ultrasonographically determined dates were judged to be consistent with LMP if the crown-rump length was within 5 days of LMP in the first trimester or the composite gestational age was within 1.5 weeks gestation in the second trimester or within 2 weeks in the third trimester. Gestational age was based on LMP. Patients were specifically excluded if there were fetal malformations, known chromosomal abnormalities, or multiple gestation. A maternal history of thyroid disease was obtained. Patients were not excluded if there was a maternal history of hyperthyroidism or hypothyroidism, because such patients are part of the normal patient population evaluated at our center. None of the fetuses examined had an obvious goiter. Images of the fetal thyroid were obtained at the time of ultrasonographic examination by experienced perinatal sonographers or maternalfetal medicine specialists using ATL Ultrasound (Bothell, WA) HDI 3000, HDI 5000, and Ultramark 9 equipment. Measurements of the fetal thyroid were obtained in a transverse view through the fetal neck at its maximum circumference after visualizing the carotid arteries. Thyroid circumference was measured by using the ellipse feature, and thyroid lateral width was measured with standard electronic calipers. These measurements included the area of the fetal trachea 7,8 (Fig. 1). Up to 3 measurements were averaged to obtain the thyroid circumference and thyroid width. Interobserver and intraobserver variations in thyroid measurements were assessed for a subgroup of 20 fetuses, each measured twice by 2 examiners. Data from each fetus were used only once in the construction of the nomogram. Standard fetal measurements, including biparietal diameter (BPD) measured at the level of the thalami, were also obtained. Before constructing the nomograms, thyroid circumference and thyroid width measurements were checked for outliers, and their distributions were examined. Separate regression models for the mean and SDs of thyroid circumference and thyroid width were fit on the basis of BPD and gestational age. Thyroid circumference was superior to thyroid width in all equations tested for both the BPD and gestational age models; therefore, only the nomograms for thyroid circumference measurements are presented. The regression model for the mean was best fit by allowing a polynomial term (second order) for BPD and a linear term for gestational age. A linear term for both BPD and gestational age best fit the model for SD. The models for the mean and SD were then combined to derive percentiles of thyroid circumference. The models for SD were weighted by the number of thyroid measurements at each BPD and gestational age. These models implicitly assume that thyroid circumference measurements are normally distributed at each BPD and gestational age. The raw and standardized residuals were examined to assess the fit of the regression models. 10 Finally, the derived nomo- Figure 1. Transverse view of a fetal neck at 37 weeks gestation. The thyroid gland is located within the region of the ellipse. The trachea (T) is shown in the middle of the gland. Carotid arteries (C) are lateral, and the spine (Sp) is posterior. 614 J Ultrasound Med 20: , 2001

3 Ranzini et al grams were superimposed on the scatterplot of the observed thyroid circumference measurements. Results Two hundred patients were evaluated. Fourteen patients had a history of maternal thyroid disease; however, none of these had an obvious goiter. Gestational age at the time of thyroid measurement ranged from 16 to 37 weeks (median, 25 weeks). There was no significant intraobserver (mean ± SD, ± cm; P >.3) or interobserver (0.042 ± cm; P >.2) variability (percent difference) in thyroid circumference. The percentiles for thyroid size based on BPD were derived by modeling the mean and SD separately and by combining the following regression models to derive the percentiles. The regression equations were mean = (BPD) (BPD 2 ); R 2 = 0.71; and SD = (BPD). Similarly, the regression equations for thyroid circumference based on gestational age were mean = (gestational age); R 2 = 0.67; and SD = (gestational age). The 5th, 10th, 50th, 90th, and 95th percentiles of thyroid circumference measurements based on BPD and gestational age were then derived by using the relationship of mean ± z (SD), where z is the standard normal deviate with values of ±1396 for the 95th percentile, ±1.28 for the 90th and 10th percentiles, and 0 for the 50th percentile. Scattergrams with superimposed regression lines based on the 5th, 10th, 50th, 90th, and 95th percentiles of thyroid circumference based on BPD are shown in Figure 2, and those based on gestational age are shown in Figure 3. With the use of these equations, the predicted thyroid circumferences for the 5th, 10th, 50th, 90th, and 95th percentiles were derived and are reported in Tables 1 and 2. Discussion Fetal thyroid goiter most commonly occurs as a result of maternal ingestion of goitrogenic drugs, including propylthiouracil, methimazole, and iodine in large doses. Fetal goiter may also occur as a direct result of fetal hyperthyroidism and thyrotoxicosis. Untreated fetal hyperthyroidism may cause intrauterine growth restriction, 3 oligohydramnios, 3 fetal neck hyperextension resulting in fetal malpresentation during delivery, 6 neonatal tracheal obstruction, and death. 11 Other reported complications include delayed perceptual-motor, visual-spatial, and language development. 12 There are several published nomograms of fetal thyroid size. 7 9 Comparison of the thyroid circumference nomogram between ours and those previously published 7 9 reveals some differences; variations in study design, methods of data analysis, and patient profiles (racial and ethnic composition) are the likely reasons for this disparity. The nomogram of Bromley et al 7 included patients between 20 and 40 weeks gestation and was based on a single thyroid measurement of the thyroid circumference and thyroid width, with a superimposed 95th percentile line. They found that fetal thyroid measurements of both thyroid circumference and thyroid width were linearly related to gestational Figure 2. Fetal thyroid measurement percentiles (5th, 10th, 50th, 90th, and 95th) based on BPD. Figure 3. Fetal thyroid measurement percentiles (5th, 10th, 50th, 90th, and 95th) based on gestational age. J Ultrasound Med 20: ,

4 Ultrasonography of the Fetal Thyroid Table 1. Thyroid Circumference Nomogram (5th, 10th, 50th, 90th, and 95th Percentiles) Based on BPD Thyroid Circumference by Percentile, cm BPD, cm 5th 10th 50th 90th 95th Table 2. Thyroid Circumference Nomogram (5th, 10th, 50th, 90th, and 95th Percentiles) Based on Gestational Age Gestational No. of Thyroid Circumference by Perentile, cm Age, wk Patients 5th 10th 50th 90th 95th age. However, not only was their study limited by the small sample size (31 patients) on which the nomograms were developed, but they also failed to model the mean and overall variability in constructing the nomogram. Ho and Metreweli 9 reported normal values of fetal thyroid volume between 20 and 36 weeks gestation and found a constant ratio between thyroid volume and fetal weight. Unfortunately, the complexity of the calculations reported, as well as the need for measuring thyroid height in addition to thyroid circumference, limits the clinical usefulness of this nomogram. The nomograms by Achrion et al 8 of thyroid width and circumference between 14 and 37 weeks gestation in 193 fetuses of Israeli women revealed a linear relationship. 8 These authors did not account for the variability in thyroid measurements as a function of gestational age. As a result, the 95% confidence interval limits do not widen as gestational age increases, as would be expected of any fetal biometry population. In contrast, we modeled the SD separately and found an increasing variation in thyroid size as both BPD and gestational age increased. Notwithstanding this important but crucial limitation, the overall rate of growth per week of the thyroid circumference was 2.3 mm in the study by Achiron et al, 8 slightly lower than our estimate of 1.7 mm. As a result, the upper limits for normal thyroid size of Achiron et al 8 are slightly higher than ours. Differences in patient profiles, ambient iodine concentrations, and the number of individuals obtaining the reported thyroid measurements are the likely contributors to this finding. One advantage of the data provided in this study is the information on thyroid circumference based on BPD. Such information may be useful in the absence of a well-dated pregnancy or possibly if the fetus is large or small for gestational age. Previously published gestational ageindependent nomograms include BPD as a predictor of fetal age, 13 head circumferenceabdominal circumference ratio, 14 and BPD-long bone ratios for Down syndrome screening. 15 Biparietal diameter- and gestational age-based nomograms may be used to assess fetal thyroid size in patients who are at risk for fetal goiter, enabling the examiner to evaluate the possibility of thyroid abnormality in the fetus and to assess fetal thyroid size after intrauterine treatment. This may assist in determining the timing of 616 J Ultrasound Med 20: , 2001

5 Ranzini et al intrauterine treatments. The BPD is a gestational age-independent measurement, useful for predicting fetal thyroid size. When the BPD is difficult to measure, then gestational age can be used to assess thyroid size. References 1. Thorpe-Beeston JG, Nicolaides KH, McGregor AM. Fetal thyroid function. Thyroid 1992; 2: Abuhamad AZ, Fisher DA, Warsof SL, et al. Antenatal diagnosis and treatment of fetal goitrous hypothyroidism: a case report and review of the literature. Ultrasound Obstet Gynecol 1995; 6: Hadlock F, Deter RL, Harrist RB, et al. Estimating fetal age: computer-assisted analysis of multiple fetal growth parameters. Radiology 1984; 152: Campbell S. Ultrasound measurement of the fetal head to abdomen circumference ratio in the assessment of growth retardation. Br J Obstet Gynaecol 1977; 84: Vintzileos AM, Egan JF, Smulian JC, et al. Adjusting the risk for trisomy 21 by a simple ultrasound method using fetal long bone biometry. Obstet Gynecol 1996; 87: Davidson KM, Richards DG, Schatz DA, et al. Successful in utero treatment of fetal goiter and hypothyroidism. N Engl J Med 1991; 324: Hatjis CG. Diagnosis and successful treatment of fetal goitrous hyperthyroidism caused by maternal Graves disease. Obstet Gynecol 1993; 81: Sagot P, David A, Yvinec P, et al. Intrauterine treatment of thyroid goiters. Fetal Diagn Ther 1991; 6: Romero R, Pilu G, Jeanty P, et al. The neck. In: Prenatal Diagnosis of Congenital Anomalies. Norwalk, CT: Appleton & Lange; 1988: Bromley B, Frigoletto FD, Cramer D, et al. The fetal thyroid: normal and abnormal sonographic measurements. J Ultrasound Med 1992; 11: Achiron R, Rotstein Z, Lipitz S, et al. The development of the fetal thyroid: in utero ultrasonographic measurements. Clin Endocrinol (Oxf) 1998; 48: Ho SSY, Metreweli C. Normal fetal thyroid volume. Ultrasound Obstet Gynecol 1998; 11: Altman DG, Chitty LS. Charts of fetal size: I. Methodology. Br J Obstet Gynaecol 1994; 101: Bongiovanni AM, Eberlein WR, Thomas PZ, et al. Sporadic goiter of the newborn. J Clin Endocrinol Metab 1956; 16: Rovet J, Ehrlich R, Sorbara D. Intellectual outcome in children with fetal hypothyroidism. J Pediatr 1987; 110: J Ultrasound Med 20: ,