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The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 11 5145-5149
Copyright © 2003 by The Endocrine Society

Color Doppler Ultrasonography: Diagnosis of Ectopic Thyroid Gland in Patients with Congenital Hypothyroidism Caused by Thyroid Dysgenesis

Hisashi Ohnishi, Hirokazu Sato, Hiromasa Noda, Hiroaki Inomata and Nozomu Sasaki

Department of Pediatrics, Funabashi Central Hospital (H.O., H.N.), Chiba 273-8556; Department of Pediatrics, Saitama Medical School (H.S., N.S.), Saitama 350-0459; and Department of Pediatrics, Ichihara Hospital, School of Medicine, Teikyo University (H.I.), Chiba 299-0111, Japan

Address all correspondence and requests for reprints to: Hirokazu Sato, M.D., Department of Pediatrics, Saitama Medical School, Morohongo 38, Moroyama, Iruma-gun 350-0495, Japan. E-mail: shiroka{at}saitama-med.ac.jp.


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Discussion
 References
 
The etiology of congenital hypothyroidism (CH) may play an important role in determining disease severity, outcome, and, therefore, its treatment schedule. Radionuclide imaging (RI) is currently the most precise diagnostic technique to establish the etiology of CH. Conventional ultrasound can identify an athyrotic condition at the normal neck position and has gained acceptance for the initial evaluation of CH; however, its ability in delineating ectopic thyroid is limited.

We used color Doppler ultrasonography (CDU) to assess blood flow and morphology in the detection of ectopic thyroid in 11 CH patients disclosed by neonatal screening; thyroid glands were undetectable at the normal location by gray-scale ultrasonography (GSU). The patients studied consisted of two infants for initial investigation and nine children for reevaluating the cause of CH. All of the patients underwent GSU, CDU, RI, and magnetic resonance imaging (MRI) investigation. We set RI as the defining diagnostic test for detecting ectopic thyroid and compared the imaging of CDU with those of GSU and MRI. The results of RI showed 10 ectopic thyroids and one athyreosis. In the patients with ectopic thyroid, the sensitivity of CDU, GSU, and MRI for detecting ectopic thyroid was 90, 70, and 70%, respectively. We conclude that CDU is superior to GSU and MRI for detecting ectopic thyroid and that CDU may be adopted as the diagnostic tool for the initial investigation of suspected CH.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Discussion
 References
 
CONGENITAL HYPOTHYROIDISM (CH) causes irreversible mental retardation without T4 replacement from early life. Since the implementation of newborn screening programs for CH, early diagnosis and treatment begins the first weeks of life, resulting in a dramatic improvement in the outcomes of intellectual potential and linear growth of affected infants (1, 2, 3). Permanent primary CH affects about one newborn in 3500. Eighty to ninety percent of infants with CH have developmental defects of the thyroid gland (thyroid dysgenesis); approximately two thirds are caused by incomplete or aberrant migration (ectopic thyroid), and the other one third are attributable to a complete absence of thyroid tissue (athyreosis) (4). Thyroid dysgenesis is primarily sporadic, resulting from as yet unknown mechanisms. The remaining 10–20% of infants with CH have functional defects transmitted by an autosomal recessive mode of inheritance (2, 4, 5). The transient form of hypothyroidism is attributable to antithyroid antibodies, and antithyroid drugs from the mother, iodine excess, and iodine deficiency are also detected in infants by the newborn screening program for CH. The etiology of CH may be important in determining disease severity, outcome, and treatment schedules, with higher treatment doses and close monitoring particularly early in life in patients with athyreosis (2, 6).

Radionuclide imaging (RI) is currently the most precise diagnostic technique to establish the etiology of CH (7, 8); a high TSH level and undetectable thyroglobulin levels indicate athyreosis. By the late 1970s, the standard gray-scale ultrasonography (GSU) was recognized as a sensitive method for evaluating the anatomy of the thyroid grand (9, 10). GSU has recently gained acceptance in evaluation of the etiology of CH and has the advantage of ready availability, noninvasiveness, and low cost; however, its ability in identifying ectopic thyroid is not as satisfactory (7, 11) nor as reliable as RI (7, 12, 13, 14, 15). Although magnetic resonance imaging (MRI) may provide a diagnosis of lingual thyroid (16), its clinical usefulness in the diagnosis of patients with CH has not been evaluated.

Color Doppler ultrasonography (CDU) provides not only the standard gray-scale image, but also a color display of blood flow and, hence, permits the evaluation of thyroid vascularity. Fobbe et al. (17) and others have described the appearance of various thyroid diseases with CDU. Nevertheless, CDU for detecting ectopic thyroid has not been reported.

We assessed the ability of CDU to establish the presence of ectopic thyroid in patients with CH by comparing with the imaging of RI and compared these findings with those of GSU and MRI.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Discussion
 References
 
Patients

Eleven patients (seven females and four males), who were found to have elevated TSH levels by a neonatal mass screening program and who had absent thyroid glands at the normal neck position by GSU, were enrolled in this study (Table 1Go). None of the patients had a family history of thyroid diseases. Two newly diagnosed infants (patients 1 and 2) were investigated before thyroid replacement therapy. The remaining nine patients whose etiological diagnoses were not defined were investigated 4 wk after withdrawing thyroid hormone replacement. Blood samples were taken, and serum TSH, T4, T3, and thyroglobulin were examined. Serum TSH, T4, and T3 were measured with commercial chemiluminescent immunoassay kits. Serum thyroglobulin was measured with a commercial immunoradiometric assay kit.


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  		TABLE 1. Clinical data at investigation

 
All of the patients underwent CDU, GSU, RI, and MRI investigations. We obtained informed consent from the parents of all patients. At the time of investigation, the investigator (O.H., H.N.) had no knowledge of the etiology of CH, except their family history and serological data. RI was set as the defining diagnostic test for detecting ectopic thyroid (8). The findings on CDU, GSU, and MRI were compared with those of RI, and the sensitivities for detecting ectopic thyroid were calculated. In the cases in which a color signal was identified with CDU, the CDU investigation was repeated after the start or restart of replacement treatment with levothyroxine.

As controls for the CDU investigation, 33 volunteers ranging in age from 1 month to 15 yr (mean, 5.9 ± 4.9 yr) were also examined to determine a baseline pattern of color flow in the tongue area.

Ultrasonography

Ultrasonography was performed with an SSA-370A ultrasound scanner (Toshiba Co. Ltd., Tokyo, Japan) and a 12-MHz linear-array transducer for GSU and a 5-MHz linear-array transducer for CDU in every patient, without sedation with the neck extended. Midline sagittal image and posterior coronal image starting at the level of the hyoid and moving to the base of the tongue were obtained. CDU was also performed at the normal neck position. The imaging of CDU was indicated inversely on the screen. The minimal detectable flow velocity of CDU was 1 mm/sec. At color flow imaging, flow toward the transducer was displayed as red, whereas blue indicated flow in the reverse direction. Two investigators (O.H., H.N.) analyzed the images of ultrasonography independently, and the results were compared. When the result was discordant, agreement was obtained after conjoint reexamination. Color flow signal detected in or around the tongue by CDU was considered abnormal, and its distribution was compared with the corresponding focal concentration detected by RI.

RI

Thyroid RI with either 99mTc-pertecnetate (patients 1 and 2) or 123I-sodium iodine (patients 3–11) was performed using a gamma camera equipped with a parallel hole collimeter. Six patients (patients 1–6) were sedated. Results of RI define the final etiological diagnosis.

MRI

MRI was performed with a 1.5-T superconducting unit (Sigma, St. Louis, MO; GE Medical System, Milwaukee, WI). Six patients (patients 1–6) were sedated. T1-weighted (SE TR400/TE12) and T2-weighted (SE TR400/TE90) images were obtained with sagittal and axial slice series (4-mm slice thickness) without contrast medium.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Discussion
 References
 
Clinical data at the investigation are shown in Table 1Go. The serum TSH levels were elevated in all patients, and serum thyroglobulin in one patient (patient 11) was undetectable. Diagnoses by different diagnostic modalities are shown in Table 2Go. Based on RI findings, 10 patients were finally diagnosed as CH with ectopic thyroid (lingual, patients 1, 3–8; prelaryngeal, patient 2; sublingual, patient 9; lingual and prelaryngeal, patient 10) and the patient with undetectable thyroglobulin as CH with athyreosis (patient 11).


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  		TABLE 2. Comparison of RI, CDU, GSU, and MRI for detecting ectopic thyroid gland

 
CDU findings in the control group in and around the tongue area showed no color flow signal (Fig. 1Go). In contrast, peripheral or internal color flow signal on CDU was depicted clearly in nine patients (Fig. 2Go). The results were found to be identical between two investigators, except one failed to detect color flow signal in the sublingual area (patient 9). The area of the signal imaging detected by CDU corresponded to thyroid tissue found by RI. A decrease of color signal was observed after thyroid replacement therapy in all nine patients (Fig. 3Go). No color flow signal was obtained in the remaining two patients, one with ectopic thyroid (lingual, patient 5) and the other with athyreosis (patient 11). The thyroid gland was not detected by CDU at the normal neck position in every patient.



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  		FIG. 1. Color Doppler sonographic image of the tongue area in a healthy infant. A, Midline sagittal image. B, Posterior coronal image. The images were indicated inversely on the screen. Color flow signal is absent in the tongue area on each scanning. T, Tongue; P, palate; U, uvula; M, mandible.

 


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  		FIG. 2. Color Doppler sonographic image in patient 4. A, Color flow signal is shown as the internal pattern within the base of the tongue on the midline sagittal image. B, Color flow signal is shown as the peripheral pattern within the lesion on the posterior coronal image.

 


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  		FIG. 3. Color Doppler sonographic midline sagittal image in patient 8 before and after the restart of replacement therapy. A, Color flow signal as the peripheral pattern on the midline sagittal scan is delineated clearly at the base of tongue before treatment. B, Decreased color flow signal within the lesion is shown after thyroid replacement therapy.

 
GSU showed seven ectopic thyroids (lingual, patients 1, 3, 4, 6 and 8; prelaryngeal, patient 2; lingual and prelaryngeal, patient 10) as a hypoechoic mass or a hyperechoic mass to the surrounding tissue. GSU failed to detect three ectopic thyroids (patient 5, 7, and 9).

MRI detected ectopic thyroids as rounded masses with higher signal intensity than that of the surrounding tissue in both the T1-weighted and T2-weighted images (Fig. 4Go). A total of seven ectopic thyroids (lingual, patients 1, 3, 4, and 8; prelaryngeal, patient 2; sublingual, patient 9; lingual and prelaryngeal, patient 10) were clearly detected. MRI failed to detect three ectopic thyroids (patients 5–7), like GSU.



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  		FIG. 4. Sagittal T1-weighted MRI in patients 1 (A) and 8 (B). The lingual thyroid gland is shown as a rounded mass lesion in the base of the tongue (white arrow).

 
Regarding the one patient with athyreosis diagnosed by RI (patient 11), none of the remaining three imaging techniques detected her thyroid tissue. The sensitivities of CDU, GSU, and MRI for detecting ectopic thyroid were, therefore, 90, 70, and 70%, respectively.


   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
References
 
CDU permits the assessment of blood flow in addition to the depiction of morphology in thyroid imaging. Our study demonstrated that peripheral or internal color signal in or around the tongue area was clearly depicted in nine of 10 ectopic thyroids by CDU. The distribution of the color signal depicted by CDU corresponded exactly to the focal concentration shown by nuclear scintigraphy (RI). This color sign was not detected in any subjects of the control group. Consequently, CDU may be useful in the detection of ectopic thyroid.

Although the mechanism of increased color flow pattern shown in our patients is not clear, it may be a reflection of the TSH-stimulated hyperfunctional state of the ectopic thyroid despite hypothyroidism in the whole body, because a decrease of color signal was observed after the replacement treatment. Moreover, the same phenomenon was observed in our neonates with CH because of thyroid dyshormonogenesis (data not shown) and also in a fetal goiter with hypothyroidism induced by antithyroid medications (18). In the case, that ectopic thyroid was shown by nuclear scintigraphy (RI) but not depicted by CDU (patient 5), the absence of color signal might have been caused by poor vascularity because of the small size of the gland. Interestingly, ectopic thyroid was also not detected by GSU and MRI in patient 5.

Although RI was set as the defining diagnostic test for detecting ectopic thyroid in this study, we used two kinds of radioisotope. Because 99mTc-pertecnetate and 123I-sodium iodine assess different aspects of thyroid metabolism, it may be possible that the 99mTc-pertecnetate scan could detect thyroid tissue that was not visible by the 123I-sodium iodide scan. However, an elevated TSH level and undetectable thyroglobulin levels also indicated athyreosis in patient 11.

GSU, although only recently gaining acceptance for the evaluation of the etiology of CH, has the advantages of ready availability, noninvasiveness, and low cost, but lower sensitivity in identifying ectopic thyroid (12, 15). In our study, GSU had a 70% sensitivity for detection of ectopic thyroid, which is similar to a previous study (11). Three of the 10 ectopic thyroids might not have been detected by this technique because of their scattered echotexture and echogenicity or small size.

Demonstrations of ectopic thyroid in children and adults by MRI have been reported (16, 19, 20). However, its usefulness in etiological diagnosis of CH has not been studied. MRI showed 70% sensitivity for the detection of ectopic thyroid in our study. Detection failure of the three ectopic thyroids may be attributable to the similar signal intensity to adjacent muscular tissue of the tongue or small size of the thyroid tissue.

Although scintigraphy can detect ectopic thyroid anywhere in the body, ectopic thyroid outside the neck is considered to be extremely rare (5). We conclude that CDU has an advantage over other techniques such as GSU and MRI in its ability to image ectopic thyroid; it may be adopted as the first choice of a diagnostic tool at the initial investigation for suspected CH.


   Footnotes
 
Abbreviations: CDU, Color Doppler ultrasonography; CH, congenital hypothyroidism; GSU, gray-scale ultrasonography; MRI, magnetic resonance imaging; RI, radionuclide imaging.

Received April 28, 2003.

Accepted August 20, 2003.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 References
 

  1. Van Vliet G 1999 Neonatal hypothyroidism: treatment and outcome. Thyroid 9:74–84
  2. Van Vliet G 2001 Treatment of congenital hypothyroidism. Lancet 358:86–87[CrossRef][Medline]
  3. Sato H, Niimi H 1994 Mental development in children with congenital hypothyroidism detected by neonatal screening in Japan. In: Takasugi N, Naruse H, eds. New trends in neonatal screening. Sapporo, Japan: Hokkaido University Press; 205–208
  4. Devos H, Rodd C, Gagné N, Laframboise R, Van Vliet G 1999 A search for the possible molecular mechanisms of thyroid dysgenesis: sex ratios and associated malformations. J Clin Endocrinol Metab 84:2502–2506[Abstract/Free Full Text]
  5. Weber AL, Randolph G, Aksoy FG 2000 The thyroid and parathyroid glands: CT and MRI imaging and correlation with pathology and clinical findings. Radiol Clin North Am 38:1105–1129[CrossRef][Medline]
  6. Hanukoglu A, Perlman K, Shamis I, Brnjac L, Rovet J, Daneman D 2001 Relationship of etiology to treatment in congenital hypothyroidism. J Clin Endocrinol Metab 86:186–191[Abstract/Free Full Text]
  7. Muir A, Daneman D, Danneman A, Ehrich R 1988 Thyroid scanning, ultrasound, and serum thyroglobulin in the origin of congenital hypothyroidism. Am J Dis Child 142:214–216[Abstract]
  8. LaFranchi S 1999 Congenital hypothyroidism: etiologies, diagnosis, and management. Thyroid 9:735–740[Medline]
  9. Blum M 1975 Enhanced clinical diagnosis of thyroid disease using echography. Am J Med 59:301–307[CrossRef][Medline]
  10. Chilcote WS 1976 Gray-scale ultrasonography of the thyroid. Radiology 120:381–383[Abstract]
  11. Takashima S, Nomura N, Tanaka H, Itoh Y, Miki K, Harada T 1995 Congenital hypothyroidism: assessment with ultrasound. Am J Neuroradiol 16:1117–1123[Abstract]
  12. Pöyhönen L, Lenko HL 1984 Ultrasonography in congenital hypothyroidism. Acta Pediatr Scand 73:523–526[Medline]
  13. Farriaux JP, Dhond JL 1988 Thyroid scanning, ultrasound, and serum thyroglobulin in determining the origin of congenital hypothyroidism. Am J Dis Child 13:103–109
  14. Bruyn RD, Ng WK, Taylor J, Campbell F, Mitton SG, Dicks-Mireaux C, Grant DB 1990 Neonatal hypothyroidism: comparison of radioisotope and ultrasound imaging in 54 cases. Acta Pediatr Scand 79:1994–1998
  15. Ohnishi H, Inomata H, Watanabe T, Wataki K, Sato H, Sanayama K, Noda H, Yasuda T, Niimi H 2002 Clinical utility of thyroid ultrasonography in the diagnosis of congenital hypothyroidism. Endocr J 49:293–297[Medline]
  16. Takashima S, Ueda M, Shibata A, Takayama F, Momose M, Yamashita K 2001 MR imaging of the lingual thyroid. Acta Radiol 42:376–382[Medline]
  17. Fobbe F, Finke R, Reichenstein E, Schleusener H, Wolf K-J 1989 Appearance of thyroid diseases using color-coded duplex sonography. Eur J Radiol 9:29–31[Medline]
  18. Soliman S, Mcgrath F, Brennan B, Glazbrook K 1994 Color Doppler imaging of the thyroid gland in a fetus with congenital goiter: a case report. Am J Perinatol 11:21–23[Medline]
  19. Johnson JC, Coleman LL 1989 Magnetic resonance imaging of a lingual thyroid gland. Pediatr Radiol 19:461–462[CrossRef][Medline]
  20. Spinas GA, Staub JJ, Wey W, Nidecker A 1989 Magnetic resonance imaging for the assessment of lingual thyroid. J Endocrinol Invest 12:429–431[Medline]



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