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Head and Neck Imaging |
1 From the Department of Radiology, Helsinki University Central Hospital, Haartmaninkatu 4, PL 380, 00029 HYKS, Helsinki, Finland (A.E.E.B., L.M.K.); and the Departments of Medicine (V.P.V.) and Pathology (J.I.N.), Hyvinkää District Hospital, Finland. Received August 3, 1998; revision requested November 4; final revision received September 15, 1999; accepted September 24. Address correspondence to A.E.E.B. (e-mail: Antti.Brander@huch.fi).
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Abstract |
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 TOP Abstract IntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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MATERIALS AND METHODS: In the original survey, 253 randomly selected adults were screened by means of thyroid US. US abnormalities were detected in 69 subjects (27%). In the follow-up study, 57 (83%) of those 69 subjects who had abnormalities were reexamined by means of thyroid US, fine-needle aspiration biopsy (FNAB), blood tests, and clinical examination.
RESULTS: Of 34 individual nodules, 12 (35%) had grown. Biopsy was performed in 10 of them. Nine were benign. One was equivocal, was excised, and proved to be an adenomatous nodule. Eight nodules (24%) had diminished or disappeared. Seven new focal lesions were found in seven subjects (12%). Biopsy was performed in five of these lesions, and they were benign. At 5-year follow-up, no thyroid malignancies were detected among subjects with echo abnormalities at the primary US screening.
CONCLUSION: Thyroid US abnormalities occurring in a random adult population are predominantly benign and clinically unimportant.
Index terms: Thyroid, biopsy, 273.12985, 273.1261 • Thyroid, neoplasms, 273.34, 273.36 • Thyroid, US, 273.12981 • Thyroiditis, 273.292
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Introduction |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Next to palpation, ultrasonographic (US) examination is currently the basic examination method for patients suspected of having nodular and diffuse thyroid disease. Although US is an appropriate step in evaluating palpable nodules, the role of US is uncertain for detection or follow-up of nonpalpable abnormalities. High-frequency (7–10-MHz) US provides excellent resolution and enables detection of focal thyroid lesions 1–2 mm in diameter (9). The frequency of abnormalities at thyroid US in the adult population is consequently much higher than the frequency of palpable nodules and approaches that at autopsy studies (10–12). The natural history and attendant clinical importance of individual lesions detected at US screening are unknown, as no studies with detailed extensive follow-up exist, to our knowledge.
The present study is based on previous US screening aimed at studying the frequency of abnormalities at thyroid US in a random adult population (11). By means of a 5-year follow-up study, we wanted to clarify the natural history of the lesions detected at thyroid US in a random adult population.
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MATERIALS AND METHODS |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Abnormal US findings were detected in 69 subjects (27%). Women had significantly more echo abnormalities than men (P < .01), and in both sexes abnormalities increased with age. Fine-needle aspiration biopsy (FNAB) was performed in 32 lesions in 30 subjects. No unequivocal malignancies were detected. Since the original survey, two subjects had undergone surgery—one for a solitary lesion with suspicious cytologic findings (class 3; defined later in Materials and Methods), which proved to be a Hürthle cell adenoma, and the other one for a cytologically benign large nodule causing local symptoms, which proved to be an adenomatous nodule. The original study has been reported in detail elsewhere (11).
Subjects with any abnormality differing from the homogeneously hyperechoic echo pattern compared with that of the adjacent muscles in the original study were recruited for a follow-up examination 5 years later. The subjects were informed of the follow-up study in advance by letter, and the examinations were scheduled by telephone. A reminder was mailed if a subject could not be contacted by telephone. It was emphasized that participation in the follow-up study was voluntary and that FNAB and blood tests in some cases would be offered to participants with new lesions or growth of an old lesion.
Of a total of 69 subjects of the original study with abnormal US findings, 57 (83%) participated in the follow-up study. Of the 12 nonparticipants, two had died. The cause of death in both was unrelated to thyroid disease. The present address of two was not found in the council registry; five could not be reached by telephone, although the address was known. Three refused to participate. Omitting the two deceased subjects, participation in the follow-up study was 85%. The mean duration of follow-up was 5.18 years (range, 4.93–5.65 years).
All participants underwent thyroid US examination performed with the use of a real-time scanner equipped with a 7.5-MHz linear transducer (SAL-77A; Toshiba, Tokyo, Japan). All US examinations were performed by the same radiologist (A.E.E.B.). The technique and equipment were similar to that used in the original study. In almost all examinations, an anechoic stand-off pad (Kretztechnik, Zipf, Austria) was used as an aid. The thyroid lobes were screened for the level of echogenicity compared with that of adjacent muscles and any focal abnormalities. A level of echogenicity distinctly higher than that of the muscles was considered normal. All focal lesions were characterized for echogenicity and measured with electronic calipers. The neck was surveyed for enlarged lymph nodes. Comparison was made with the results of the earlier examination, because we aimed to perform biopsy in lesions that had increased in size during the 5-year follow-up, as well as in any new lesions.
In 17 subjects, FNAB of the thyroid was performed with a 22–23-gauge needle by using US guidance, and biopsy of an enlarged lymph node was performed in one subject. All the biopsies were performed by the same radiologist (A.E.E.B).
The aspirates were fixed in alcohol and stained with Papanicolau stain (Danbritt [Schandon], Hampshire, England). All cytologic samples were examined by the same pathologist (J.I.N.) and graded according to Papanicolau into classes 0–5 (13). According to this classification scheme, class 0 indicates inadequate sample; class 1 indicates absence of atypical or abnormal cells; class 2 indicates atypical cytologic findings but no evidence of malignancy; class 3 implies cytologic findings suggestive of, but not conclusive of, malignancy; class 4 cytologic findings are strongly suggestive of malignancy; and class 5 cytologic findings are conclusive for malignancy.
In 49 subjects, tests were performed for determination of thyroid function. The serum levels of thyroxine, or T4 (reference value, 60–160 nmol/L); triiodothyronine, or T3 (reference value, 1.30–2.30 nmol/L); thyrotropin, or TSH (reference value, 0.2–5.0 mIU/L); and thyroglobulin (reference value, 0–50 µg/L), as well as of thyroid antibodies (reference value, <0.4 kIU/L), were determined. The results of the blood tests were interpreted, and 47 subjects were examined clinically by the same internist (V.P.V.). The study design was accepted by the ethical committees of both hospitals (Helsinki University Central Hospital and Hyvinkää District Hospital, Finland) involved. Informed consent was obtained from all subjects.
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RESULTS |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Anechoic lesions other than macrofollicles.—Seven anechoic lesions other than macrofollicles (Fig 2) originally were found in seven subjects. Two lesions had grown, one from 7 to 11 mm and the other from 7 to 13 mm, and their echo structure had changed so that it could be classified as either mixed echoic or hypoechoic. In both lesions, the cytologic finding was benign both originally and at follow-up (Table 2). In two subjects, the lesion had disappeared; in one, it was unchanged. Two subjects were lost to follow-up.
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Two subjects originally had a total of three isoechoic lesions. The subject with two lesions was lost to follow-up. In the other subject, the isoechoic lesion was no longer perceptible (Table 2).
Hypoechoic lesions.—Twelve subjects originally had 16 focal hypoechoic lesions (Figs 3, 4), and one subject had an enlarged left lobe without individually definable nodules but with a nodular hypoechoic echo structure.
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In two subjects, the US finding was unchanged. One subject had undergone surgery for a lesion with class 3 cytologic findings that proved to be a Hürthle cell adenoma. In three subjects, five lesions, four of which initially had benign FNAB findings, had shrunk. Two subjects, one with three lesions and the other with one lesion, were lost to follow-up.
Mixed echoic lesions.—Three subjects initially had a total of three mixed echoic lesions (Fig 5, Table 2). Two lesions had grown, one from 13 to 18 mm and the other from 12 to 20 mm, but in both lesions the cytologic finding was class 1 both originally and at follow-up. One subject had undergone surgery for a large lesion with local symptoms; it proved to be an adenomatous nodule.
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New lesions.—Seven new focal lesions were detected in seven subjects (Table 3). Biopsy was performed in five of them, and the cytologic finding was class 1 in all. Biopsy was not performed in the remaining two lesions, mainly because they were small and the subjects preferred follow-up to biopsy; one lesion was a 7-mm isoechoic nodule, and the other was a 3-mm hypoechoic nodule.
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Associated cervical lymphadenopathy.—Enlarged cervical lymphatic nodes were found in one subject who had diffusely abnormal thyroid echo structure. The cytologic finding of the node in which biopsy was performed was consistent with class 1. In 52 subjects, no lymphadenopathy was found. The status of lymphatic nodes was missing in the US report in four subjects.
Laboratory and Clinical Findings
Forty-nine subjects underwent blood tests for serum levels of thyroxine, thyrotropin, triiodothyronine, thyroglobulin, and thyroid autoantibodies. The mean level of thyroxine was 98 nmol/L ± 19 (SD; range, 68–163 nmol/L), the mean level of triiodothyronine was 1.92 nmol/L ± 0.39 (range, 1.10–3.20 nmol/L), and the mean level of thyrotropin was 1.6 mIU/L ± 1.1 (range, 0.3–6.5 mIU/L). The thyroid autoantibody level was elevated (>0.4 kIU/L) in 11 subjects. The mean thyroglobulin level was 110 µg/L ± 126 (range, 3–622 µg/L). Eighteen subjects had elevated thyroglobulin levels (>100 µg/L).
Forty-seven subjects underwent clinical examination by an internist (V.P.V.). Results of thyroid palpation were abnormal in 12 subjects and normal in 35. Results of palpation were classified as abnormal if any deviation (diffuse enlargement or nodularity) from normal was present.
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DISCUSSION |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Kuma et al (15) reexamined 134 subjects (of 532 initially) with cytologically benign nodules after 9–11 years. One case (0.9%) turned out to be malignant. Measured by means of US, a decrease in size or disappearance was found in 42%–79% of nodules. Among single and multiple nodules, 21%–23% increased in size. The growth potential of solitary colloid nodules has been estimated by means of US in several series in which the effect of thyroxine-suppressive therapy was assessed. Most of these studies include relatively small samples and short follow-up. Gharib et al (16) reported a statistically nonsignificant shrinkage of 25 nodules in the placebo group after a follow-up of 6 months. In the material of Reverter et al (17), with 20 subjects in the placebo group and mean follow-up 10.6 months, the size of the nodules in the placebo group remained the same. Cheung et al (18) studied 37 nodules (mean follow-up, 1.5 years) and reported spontaneous regression in 35% and growth in 19%.
To our knowledge, no studies including US characterization of lesions and extended follow-up periods are available. The aim of our follow-up study was to check the status of the abnormal US findings after 5 years. Cytologic confirmation was obtained originally in less than half of the subjects with abnormalities, in part because most subjects were asymptomatic and in part because the lesions were generally small. We assumed that even without cytologic confirmation, lack of growth of a lesion during an interval of 5 years could be considered an indication of its probably benign character.
Our series represents a longitudinal study of a random group of thyroid echo abnormalities in the general adult population. Although the number of subjects (n = 57) at follow-up was small, participation (83%) was high and rendered selection bias unlikely. Most reported series in which US was used for accurate characterization and measurement of the lesions were smaller than the present series and represented a selected group of nodules unlike the "average" nodule in the "average" adult.
Macrofollicles are considered to represent dilated follicles (19), an expression of normal heterogeneity of follicular response to thyrotropin stimulation. In our study, their number had increased in five subjects, and 10 subjects with no macrofollicles in the previous study had them at follow-up (altogether 26%). Because macrofollicles are mostly too small for reliable FNAB, biopsy was not performed originally or at follow-up. The only way to rule out definitely the possibility of microcarcinomas in lesions 1–5 mm in diameter would, in our opinion, be surgical excision. As far as we know, no malignancies were reported among entirely anechoic lesions.
The distinction between a small anechoic versus a small hypoechoic lesion at thyroid US is sometimes problematic. In only one subject in our series, a larger nodule had developed at the site of a previous macrofollicle. Larger anechoic lesions more than 5 mm in diameter probably represent adenomatous nodules with cystic degeneration rather than true cysts (Fig 2). Among the various US patterns, the hypoechoic nodules (Figs 3, 4) are considered most susceptible for malignancy (20,21). In our original survey (11), biopsy was performed in 12 of 16 focal hypoechoic lesions. Only one had an equivocal cytologic finding and was excised but proved to be a Hürthle cell adenoma. At follow-up, biopsy was performed in five previously detected and one new hypoechoic lesion. One solitary hypoechoic lesion with benign cytologic findings at the performance of two previous biopsies showed clear growth (Fig 3) and equivocal cytologic findings at a third biopsy; the lesion was excised and proved to be an adenomatous nodule (Table 2).
The general growth potential of the hypoechoic nodules during 5 years seemed to be modest—the shrinkage and anechoic change in some of the nodules could be partly due to results of previous performance of biopsy. Our results seem to indicate that the likelihood of malignancy in hypoechoic nodules detected by means of US in an unselected population is lower than that in clinically apparent hypoechoic nodules selected for surgery. However, the results must be interpreted with caution because of the limited number of hypoechoic nodules in the present series. The malignant potential of the mixed echoic (Fig 5) and hyperechoic lesions is usually considered to be lower than that of the hypoechoic ones. Biopsy was performed again in five mixed echoic or hyperechoic lesions showing growth, but cytologic findings were benign in all of them.
The subjects with diffusely abnormal echo patterns and a cytologic finding of chronic inflammation reflect the known prevalence of occult autoimmune thyroid disease in the general population (3). In all subjects with follow-up in whom the diagnosis of autoimmune thyroiditis was confirmed cytologically, the echo pattern remained abnormal (Table 3). None of them developed hypothyroidism. In childhood autoimmune thyroiditis, Rallison et al (22) reported that there is progression to hypothyroidism in one-third of cases, whereas one-third resolve completely and one-third remain unchanged for decades.
In conclusion, after a 5-year follow-up, no malignancies were detected among 57 (83%) of the original 69 (27%) subjects who had abnormal US findings at screening of a random adult population of 253 subjects. Although our series is restricted with a small number of subjects, the results are in concordance with those of other more comprehensive series (4,14), which indicates that in contrast to nodules selected for surgery, most lesions randomly detected at US of the thyroid are benign.
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Footnotes |
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Author contributions: Guarantor of integrity of entire study, A.E.E.B.; study concepts, all authors; study design, A.E.E.B., L.M.K.; definition of intellectual content, all authors; literature research, A.E.E.B.; clinical studies, A.E.E.B., V.P.V., J.I.N.; data acquisition and analysis, A.E.E.B., V.P.V., J.I.N.; manuscript preparation, A.E.E.B.; manuscript editing and review, all authors.
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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