This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bennedbæk, F. N. Articles by Hegedüs, L. Search for Related Content PubMed PubMed Citation Articles by Bennedbæk, F. N. Articles by Hegedüs, L.

Management of the Solitary Thyroid Nodule: Results of a North American Survey¹

Department of Endocrinology, Odense University Hospital, DK-5000 Odense C, Denmark

Address all correspondence and requests for reprints to: Finn Noe Bennedbæk, M.D., Ph.D., Department of Endocrinology, Odense University Hospital, DK-5000 Odense C, Denmark. E-mail: finn.bennedbaek{at}ouh.dk

	Abstract

Top Abstract Introduction Materials and Methods Results Discussion References

 
The present survey evaluated current trends in the management of the nontoxic solitary thyroid nodule by expert endocrinologists in North America and compared their results with a similar European Thyroid Association survey. A questionnaire was circulated to all clinical members of the American Thyroid Association. An index case (a 42-yr-old woman with a solitary 2 x 3-cm thyroid nodule and no clinical suspicion of malignancy) and 11 variations were provided to evaluate how each alteration would affect management. One hundred and seventy-eight members replied and 142 responses were retained for analysis, corresponding to a response rate of 43% of clinically active members. Based on the index case, basal serum TSH was the routine choice of 99%, and serum T₄ and/or free T₄ were included by 61% of the respondents. Thyroid peroxidase antibodies and serum calcitonin were included by 30% and 5%, respectively. Thyroid scintigraphy was used by 23% (¹²³I, 63%; ^99mTc, 31%; ¹³¹I, 6%), and ultrasonography was used by 34%. Fine needle aspiration biopsy was routinely used by all and was guided by palpation in 87%. Based on the individually chosen diagnostic tests indicating a benign solitary thyroid nodule in a euthyroid subject, L-T₄ treatment was advocated by 47%, no specific treatment and follow-up was advocated by 52%, and surgery was advocated by 1%. Clinical factors suggesting thyroid malignancy (e.g. rapid nodule growth and a large nodule of 5 cm) lead a significant number of clinicians (40 - 50%; P < 0.00001) to disregard biopsy results and to choose a surgical strategy. Nevertheless, North American endocrinologists heavily rely on fine needle aspiration biopsy results. Compared to the European Thyroid Association survey, North American endocrinologists use imaging [scintigraphy, 23% vs. 66% (P < 0.0001); ultrasonography, 34% vs. 80% (P < 0.0001)] and serum calcitonin (5% vs. 43%; P < 0.0001) less frequently. A nonsurgical strategy prevails in North America, and despite controversies on the effect of L-T₄, this treatment is supported by more than 40% in both Europe and North America.

	Introduction

Top Abstract Introduction Materials and Methods Results Discussion References

 
ALTHOUGH THYROID nodules are common, less than 5% prove to be malignant (1, 2). Physicians responsible for the care of patients with thyroid nodules are increasingly aware of the need for safe, expedient, and cost-effective management of this common disorder. The optimal evaluation and management, however, are still controversial. Early referral of patients with suspected thyroid nodules to an endocrinologist results in significant savings in both cost and patient’s time as well as increased precision of diagnosis (3). On the other hand, experts disagree on the predictive value of clinical factors supporting suspicion of a malignant thyroid neoplasm and whether to operate regardless of benign cytological findings (4, 5).

A recent European survey [European Thyroid Association (ETA)] demonstrated major differences in diagnostic approach and treatment in patients with a solitary thyroid nodule (6). We chose to conduct a similar survey within the U.S. and Canada. The objectives were: 1) to determine which in vitro and in vivo tests are currently being used; 2) to determine trends for the recommended treatment in an index patient with a benign-appearing nodule; 3) to determine the impact of different clinical variations on management; and 4) to compare results with the recent ETA survey (6).

	Materials and Methods

Top Abstract Introduction Materials and Methods Results Discussion References

 
Survey methods

The questionnaire was initially distributed to all American Thyroid Association (ATA) members participating in the 71st Annual Meeting of ATA in Portland, OR, September 16–20, 1998, and was also sent to members not participating in the meeting. Subsequently, one reminder was sent by air-mail to all nonresponders identified from the membership list.

Structure of the questionnaire

The questionnaire was based on a well defined case: "A 42-year-old Caucasian woman is seen in your hospital/clinic due to a palpable mass in the left thyroid lobe. It is clinically judged to be a solitary 2 x 3 cm mobile nodule. There is no lymphadenopathy and no symptoms of thyroid dysfunction or anterior neck pain. The nodule has been present for 3 months and the patient reports moderate local neck discomfort. There is no family history of thyroid disease and no positive information of previous external irradiation." The questions asked related to the diagnostic investigations (in vitro and in vivo tests) and the choice of therapy. The basic treatment advocated was based on the premise that the preceding (individually chosen) in vitro and in vivo investigations were indicative of a benign condition in a euthyroid subject, and that if chosen, scintigraphy showed a cold nodule. Furthermore, it was assumed that the decision of therapy was left entirely to the clinician.

In the second part of the questionnaire, 11 variations of the initial case report were listed, but only 1 variable was changed in each case (Table 1). The clinicians were then asked to indicate whether the management plan would alter given each variation and to detail the altered diagnostic procedures and treatment.

Results are predominantly given as frequencies. McNemar’s test was employed in each variation to compare the altered therapeutic attitude with the basic treatment advocated, e.g. P = 1 means that the therapeutic attitude was unchanged, given that particular variation. The ² test was used to test for differences between the present survey and the ETA survey. P < 0.05 was considered significant. All variables were registered in a computer-operated database (Paradox 5.0, Borland International), and the statistical software used was SPSS 8.0 (SPSS, Inc., Evanston, IL).

	Results

Top Abstract Introduction Materials and Methods Results Discussion References

 
Survey response

The questionnaire was initially distributed to 568 North American members of the ATA. Fifty-eight responses were received at the meeting in Portland. We then identified 307 nonresponding, supposedly clinically active, ATA members from the membership list, all of whom were sent a reminder. A total of 178 responses were received. Thirty-six originated from nonclinicians, clinicians who had retired, or clinicians who had not regularly seen patients with nodular thyroid disease. The remaining 142 responses, corresponding to a response rate of 43% (142 of 365) of clinically active North American ATA members, were retained for analysis. There was no significant difference between respondents and nonrespondents with regard to type of practice or state in which they practiced. The 142 responses represented clinicians (endocrinology, 90.9%; surgery, 6.3%; nuclear medicine, 2.8%) from the U.S. (133, 93.7%) and Canada (9, 6.3%) who had diagnosed and treated more than 50 (41%) or less than 50 (59%) patients with nodular thyroid disease within the last 6 months. The vast majority (96.5%) stated that their patients live in an area of iodine sufficiency.

In vitro diagnostic procedures (Table 2)

The index patient was investigated as an out-patient by all respondents. Serum TSH was the routine choice of 99.3%. 49.3% added free T₄ (direct measurement or based on T₃ resin uptake), and only 12.0% and 9.2%, respectively, would measure total T₄ and total T₃ (Table 2). Serum thyroid peroxidase antibodies or microsomal antibodies were determined routinely by 35.9%, and calcitonin was included by 4.9%. Thirty-seven percent of the clinicians indicated the routine use of one test only (TSH), whereas 42% used 2 or 3 tests, and the remaining 21% used 4 or more tests. A combination of TSH and free T₄ and/or total T₄ was used by 53%.

In vivo diagnostic procedures (Table 3)

Initial diagnosis in the index patient included imaging by 43.6% of the respondents, whereas 56.4% would leave out diagnostic imaging (Table 3). Thyroid scintigraphy and ultrasonography (US) were used by 23.2% and 33.8%, respectively, and 13.4% would employ both imaging modalities. ¹²³I was used by 62.5%, and ^99mTc (technetium pertechnetate) was used by 31.3%, whereas 6.2% preferred ¹³¹I. A radioiodine uptake measurement was performed by 34.4% of the clinicians, and a suppression test was performed by 9.4%. Timing of uptake varied with the isotope used. US was used for determination of thyroid/nodule size by 81.3%, for specification of morphological characteristics (Gray scale) by 72.9%, and for Doppler investigations by 18.8% of the 48 clinicians using thyroid US.

Fine needle aspiration biopsy (FNAB) was advised by all respondents and was performed guided by palpation in 86.6% and by US in 13.4%. Most often it was performed by endocrinologists (68.3%), and 16.2% stated that two or more specialties attended to this function. In 6.3% of the cases a cytopathologist performed the biopsy, and less frequently a radiologist did so (2.1%). In the institutions of 35.9%, 23.9%, and 32.4% of the respondents, the biopsies were performed by one to three, four or five, and six or more persons, respectively. Large needle biopsy was recommended by none. Of those clinicians who had performed scintigraphy, all would perform FNAB given a single nodule without uptake, whereas 97% of the respondents chose this option in the case of a single nodule without uptake in a multinodular gland. In the case of a single nodule with uptake equaling the rest of the gland, 73% would perform FNAB. Only 3% would suggest FNAB in the case of an autonomously functioning nodule.

Therapeutic choices (Table 4)

In the index patient, the majority of physicians (52.1%) refrained from treatment, but suggested follow-up (surveillance) in the patient’s own clinic/institution (50%) or by the primary care physician (2.1%; Table 4). L-T₄ treatment was recommended by 46.5%. Surgery was chosen by only two respondents (1.4%). L-T₄ treatment with the intention to treat symptoms and arrest further growth was recommended by 62.1% and by another 18.2% also as evidence of benign pathology. The initial dose recommended varied considerably, but aimed at a suppressed serum TSH level just below the normal range (60.6%) or low, but still within the normal range (18.2%). Only 9.1% aimed at total or near-total suppression of serum TSH. US was used routinely by 34.8% during follow-up. L-T₄ treatment for 12 months or less was the choice of 54.6%, and 21.2% would treat for years or indefinitely.

Clinical variations: altered management (Table 5 and Fig. 1)

Suppressed serum TSH (variation 1) most frequently resulted in an altered diagnostic approach (Table 5). Some 61.1% of clinicians, by whom a free T₄ had not been performed in the index case, would recommend that this test be performed, and 9.2% and 13.2%, respectively, would include TSH receptor antibodies and thyroid peroxidase antibodies. Furthermore, 80.7% by whom a radionuclide scan was not obtained initially would now perform this test.

View larger version (63K): [in this window] [in a new window]   Figure 1. Percentage choosing surgery () or nonsurgical treatment (surveillance, LT4, radioiodine, and sclerotherapy) () in the index case as well as in variations 1–11. Each variant was compared statistically with the index case using McNemar test.

In variations 6–9, where clinical information favored thyroid malignancy, medical treatment was changed to surgery by 14–50% (P < 0.000001). The preferred surgical technique was hemithyroidectomy (55.6%, 41.7%, 56.3%, and 66.7% in variations 6, 7, 8, and 9, respectively). Approximately one third (31.3–36.1%) would use L-T₄ postoperatively in variations 6–9.

Comparison with ETA survey (Table 6)

European endocrinologists perform a larger number of laboratory tests in the index patient [3.5 (2;5.25) vs. 2 (1;3); median (quartiles); P < 0.0001] compared to North American endocrinologists (Table 6). The percentage of clinicians using only one laboratory test (TSH) was 9% in the ETA survey compared to 37% in the ATA survey (P < 0.0001). Most strikingly serum calcitonin was included routinely by 43% in the ETA survey compared to only 5% in the ATA survey (P < 0.0001). Imaging, i.e. radionuclide scan, US, or both, was used more frequently in Europe than in North America (see Table 6 for details). Surgery was the basic treatment recommended by only 1% in the U.S. and Canada compared to nearly one in four in Europe (P < 0.0001). In the case of clinical factors favoring thyroid malignancy, e.g. a large nodule of 5 cm (variation 9), more than 90% of ETA members disregarded biopsy results and chose a surgical approach compared to half of the ATA members (P < 0.0001) (1).

	Discussion

Top Abstract Introduction Materials and Methods Results Discussion References

Variations in imaging were evident. In the initial diagnosis one in three and one in four, respectively, routinely included US and radionuclide scan. On the other hand, the majority (at least two of three) would leave out imaging in the work-up of the index patient, in concordance with North American guidelines recommending radionuclide scan depending on FNAB results and US in selected patients only, e.g. to guide biopsy and in cystic nodules. However, only 6% of the respondents who did not recommend US in the index case would add this technique given a cystic nodule (variation 11). Only in the case of suppressed TSH would the vast majority recommend a radionuclide scan, with ¹²³I being the preferred isotope. Compared to the previous ATA survey from 1996, significantly fewer would include a thyroid scan (23% vs. 56%) (7), possibly as a consequence of the publication of management guidelines (10, 11).

FNAB has become the initial diagnostic test in the evaluation of nontoxic solitary thyroid nodules, based on the fact that FNAB has proved to be a better predictor of thyroid malignancy than radionuclide scan; the latter provides little additional information about cytological findings (12). All respondents included a FNAB in the initial diagnosis. Furthermore, FNAB results are heavily relied upon, as evidenced by the fact that an additional diagnostic surgery was recommended by only 1% of physicians for the index patient. In the case of clinical factors raising the suspicion of malignancy, still less than 50% resorted to surgery.

Once malignancy was excluded or determined to be improbable, the preferred strategy was that of surveillance, in accordance with the existing guidelines (10, 11). However, despite controversies regarding L-T₄ suppressive treatment (13) and ambiguous recommendations on its use in the above-mentioned guidelines (10, 11), it was preferred by a large number of clinicians (47%). Despite regional differences, with more frequent use of L-T₄ in some states, the treatment is widely distributed throughout North America. Furthermore, when surgery was recommended (variations 6–9), routine postoperative L-T₄ treatment in the euthyroid patient was recommended by approximately one third of the physicians, although evidence of an effect on recurrence rate is questioned (14).

Compared to European endocrinologists, ATA members use fewer laboratory tests and less frequently perform imaging (radionuclide scan and/or US) in the index patient. ¹²³I is preferred, in contrast to the situation in Europe, where ^99mTc is the preferred isotope. FNAB is the cornerstone in the initial diagnosis, but whereas North American endocrinologists heavily rely on FNAB results, European endocrinologists perform supplementary testing, primarily diagnostic imaging and serum calcitonin measurement, and turn to surgery in the case of clinical factors favoring thyroid malignancy despite benign FNAB results. A strategy of surveillance, implying careful follow-up of the patient with a benign-appearing nodule, was recommended by the majority of ATA members compared to less than one in three ETA members. The fact is, however, that L-T₄ treatment is supported by more than 40% of physicians in both North America and Europe, although evidence of its effect is lacking, at least in iodine-sufficient regions (15).

Thus, even though a patient with a solitary thyroid nodule is managed differently by North American endocrinologists, a cost-effective diagnostic approach seems, in general, to prevail and largely reflects implementation of the recommendations in the official guidelines (10, 11).

	Acknowledgments

 
We thank the executive committee of the ATA for supporting the implementation of the survey, as well as all the members of the ATA who participated in this survey. The help of Martin I. Surks, who critically reviewed the manuscript, is gratefully acknowledged. The Agnes and Knut Mørk Foundation is thanked for sponsoring the distribution of the questionnaire.

	Footnotes

 
¹ This work was supported by the Agnes and Knut Mørk Foundation. The results were presented in part at the 72nd Annual Meeting of the American Thyroid Association, Palm Beach, Florida, September 29, 1999.

Received January 26, 2000.

Revised March 17, 2000.

Accepted April 4, 2000.

	References

Top Abstract Introduction Materials and Methods Results Discussion References

 

1. Mazzaferri EL. 1993 Management of a solitary thyroid nodule. N Engl J Med. 328:553–559.[Free Full Text]
2. Burch HB. 1995 Evaluation and management of the solid thyroid nodule. Endocrinol Metab Clin North Am. 24:663–710.[Medline]
3. Ortiz R, Hupart KH, DeFesi CR, Surks MI. 1998 Effect of early referral to an endocrinologist on efficiency and cost of evaluation and development of treatment plan in patients with thyroid nodules. J Clin Endocrinol Metab. 83:3803–3807.[Abstract/Free Full Text]
4. Hamming JF, Goslings BM, van Steenis GJ, et al.1990 The value of fine-needle aspiration biopsy in patients with nodular thyroid disease divided into groups of suspicion of malignant neoplasms on clinical grounds. Arch Intern Med. 150:113–116.
5. Woeber KA. 1995 Cost-effective evaluation of the patient with a thyroid nodule. Surg Clin North Am. 75:357–363.[Medline]
6. Bennedbæk FN, Perrild H, Hegedüs L. 1999 Diagnosis and treatment of the solitary thyroid nodule. Results of a European survey. Clin Endocrinol (Oxf). 50:357–363.[CrossRef][Medline]
7. Solomon BL, Wartofsky L, Burman KD. 1996 Current trends in the management of well differentiated papillary thyroid carcinoma. J Clin Endocrinol Metab. 81:333–339.[Abstract]
8. Vierhapper H, Raber W, Bieglmayer C, Kaserer K, Weinhäusl A, Niederle B. 1997 Routine measurement of plasma calcitonin in nodular thyroid diseases. J Clin Endocrinol Metab. 82:1589–1593.[Abstract/Free Full Text]
9. Dunn JT. 1993 Editorial: when is a thyroid nodule a sporadic medullary carcinoma? J Clin Endocrinol Metab. 78:824–825.[CrossRef][Medline]
10. Singer PA, Cooper DS, Daniels GH, et al. 1996 Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer. Arch Intern Med. 156:2165–2172.[Abstract]
11. Feld S. 1996 AACE clinical practice guidelines for the diagnosis and management of thyroid nodules. Endocr Pract. 2:78–84.
12. Sabel MS, Staren ED, Gianakakis LM, Dwarakanathan S, Prinz RA. 1997 Effectiveness of the thyroid scan in evaluation of the solitary thyroid nodule. Am Surg. 63:660–663.[Medline]
13. Gharib H. 1997 Changing concepts in the diagnosis and management of thyroid nodules. Endocrinol Metab Clin North Am. 26:777–800.[CrossRef][Medline]
14. Hegedüs L, Nygaard B, Hansen JM. 1999 Is routine thyroxine treatment to hinder postoperative recurrence on nontoxic goiter justified? J Clin Endocrinol Metab. 84:756–760.[Abstract/Free Full Text]
15. Bennedbæk FN, Nielsen LK, Hegedüs L. 1998 Effect of percutaneous ethanol injection therapy vs. suppressive doses of L-thyroxine on benign solitary solid cold thyroid nodules: a randomized trial. J Clin Endocrinol Metab. 83:830–835.[Abstract/Free Full Text]

This article has been cited by other articles:

				F. Illouz, P. Rodien, J. P. Saint-Andre, S. Triau, S. Laboureau-Soares, S. Dubois, B. Vielle, H. Antoine, and V. Rohmer Usefulness of repeated fine-needle cytology in the follow-up of non-operated thyroid nodules Eur. J. Endocrinol., March 1, 2007; 156(3): 303 - 308. [Abstract] [Full Text] [PDF]

				K. Boelaert, J. Horacek, R. L. Holder, J. C. Watkinson, M. C. Sheppard, and J. A. Franklyn Serum Thyrotropin Concentration as a Novel Predictor of Malignancy in Thyroid Nodules Investigated by Fine-Needle Aspiration J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4295 - 4301. [Abstract] [Full Text] [PDF]

				M Niedziela Pathogenesis, diagnosis and management of thyroid nodules in children. Endocr. Relat. Cancer, June 1, 2006; 13(2): 427 - 453. [Abstract] [Full Text] [PDF]

				T. Watt, M. Groenvold, A. K. Rasmussen, S. J. Bonnema, L. Hegedus, J. B. Bjorner, and U. Feldt-Rasmussen Quality of life in patients with benign thyroid disorders. A review. Eur. J. Endocrinol., April 1, 2006; 154(4): 501 - 510. [Abstract] [Full Text] [PDF]

				A. N. Khalid, C. S. Hollenbeak, S. A. Quraishi, C. Y. Fan, and B. C. Stack Jr The Cost-effectiveness of Iodine 131 Scintigraphy, Ultrasonography, and Fine-Needle Aspiration Biopsy in the Initial Diagnosis of Solitary Thyroid Nodules. Arch Otolaryngol Head Neck Surg, March 1, 2006; 132(3): 244 - 250. [Abstract] [Full Text] [PDF]

				S. R. Steele, M. J. Martin, P. S. Mullenix, K. S. Azarow, and C. A. Andersen The Significance of Incidental Thyroid Abnormalities Identified During Carotid Duplex Ultrasonography Arch Surg, October 1, 2005; 140(10): 981 - 985. [Abstract] [Full Text] [PDF]

				S. J. Mandel A 64-Year-Old Woman With a Thyroid Nodule JAMA, December 1, 2004; 292(21): 2632 - 2642. [Full Text] [PDF]

				L. Hegedus The Thyroid Nodule N. Engl. J. Med., October 21, 2004; 351(17): 1764 - 1771. [Full Text] [PDF]

				A. Lyshchik, V. Drozd, S. Schloegl, and C. Reiners Three-Dimensional Ultrasonography for Volume Measurement of Thyroid Nodules in Children J. Ultrasound Med., February 1, 2004; 23(2): 247 - 254. [Abstract] [Full Text] [PDF]

				F. N. Bennedbaek and L. Hegedus Treatment of Recurrent Thyroid Cysts with Ethanol: A Randomized Double-Blind Controlled Trial J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5773 - 5777. [Abstract] [Full Text] [PDF]

				L. Hegedus, S. J. Bonnema, and F. N. Bennedbaek Management of Simple Nodular Goiter: Current Status and Future Perspectives Endocr. Rev., February 1, 2003; 24(1): 102 - 132. [Abstract] [Full Text] [PDF]

				H. Dossing, F. N. Bennedbaek, S. Karstrup, and L. Hegedus Benign Solitary Solid Cold Thyroid Nodules: US-guided Interstitial Laser Photocoagulation— Initial Experience Radiology, October 1, 2002; 225(1): 53 - 57. [Abstract] [Full Text] [PDF]

				D. S. Ross Nonpalpable Thyroid Nodules--Managing an Epidemic J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 1938 - 1940. [Full Text] [PDF]

				S. J. Bonnema, F. N. Bennedbak, P. W. Ladenson, and L. Hegedus Management of the Nontoxic Multinodular Goiter: A North American Survey J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 112 - 117. [Abstract] [Full Text] [PDF]

				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]

This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bennedbæk, F. N. Articles by Hegedüs, L. Search for Related Content PubMed PubMed Citation Articles by Bennedbæk, F. N. Articles by Hegedüs, L.