Intern Med 2000 Nov 7;133(9):696-700 [Texto
Usefulness of Ultrasonography in the Management of Nodular Thyroid
Marqusee E, Benson CB, Frates MC, Doubilet PM, Larsen PR, Cibas ES,
Thyroid Division, Brigham and Women's Hospital, Harvard Institutes of
Medicine, 77 Avenue Louis Pasteur, Boston, MA 02115.
BACKGROUND: Fine-needle aspiration biopsy is the standard diagnostic test
for evaluating possible malignancy in a thyroid nodule. OBJECTIVE: To
evaluate the role of routine ultrasonography in the management of nodular
thyroid disease. DESIGN: Retrospective chart review. SETTING:
Multidisciplinary thyroid nodule clinic (endocrinology and radiology).
PATIENTS: Patients with suspected nodular thyroid disease or suspected
recurrent thyroid cancer referred between October 1995 and March 1997. All
patients had thyroid ultrasonography and ultrasonography-guided
fine-needle aspiration biopsy of nodules at least 1 cm in maximum
diameter. MEASUREMENTS: Medical records, ultrasonography findings,
cytology reports, and histologic reports were reviewed. Ultrasonography
findings were compared with the referring physician's findings on physical
examination. RESULTS: 223 patients were seen in the clinic. A total of 209
fine-needle aspiration biopsies were performed on 156 patients. Among 50
of 114 patients referred for a solitary nodule, ultrasonography detected
additional nonpalpable nodules at least 1 cm in diameter in 27 and
determined that no nodules required aspiration in 23. Of 59 patients
referred for a diffuse goiter or a multinodular gland, ultrasonography
detected discrete nodules at least 1 cm in diameter that required
aspiration in 39 and determined that aspiration was unnecessary in 20.
CONCLUSIONS: Ultrasonography altered the clinical management for 63% of
the patients (109 of 173) referred to the thyroid nodule clinic after
abnormal results on thyroid physical examination.
J Clin Endocrinol Metab 2000 Jul;85(7):2493-8
Management of the solitary thyroid nodule: results of a North American
Bennedbaek FN, Hegedus L
Department of Endocrinology, Odense University Hospital, Denmark.
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% ((123)I, 63%; (99m)Tc, 31%; (131)I,
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.
An Med Interna 2000 Feb;17(2):99-101
[Levothyroxine treatment of the solitary thyroid nodule].
Almodovar Ruiz F, Maldonado Castro G, de Luis D, Lahera M, Varela da
Servicio de Endocrinologia y Nutricion, Hospital Ramon y Cajal, Madrid.
The aim of this study was to review all published randomized clinical
trials evaluating the efficacy of suppressive therapy with levothyroxine
for solitary thyroid nodules. No significant differences were observed in
reducing the volume of benign solitary cold thyroid nodules between the
placebo and levothyroxine groups.
Medicine (Baltimore) 2000 Jan;79(1):9-26
Assessing the effects of thyroid suppression on benign solitary thyroid
nodules. A model for using quantitative research synthesis.
Csako G, Byrd D, Wesley RA, Sarlis NJ, Skarulis MC, Nieman LK, Pucino
Clinical Pathology Department, Clin. Ctr., NIH, Bethesda, MD 20892-1508,
Systematic review of the available information with a modified, largely
quantitative method of research synthesis disclosed that an initial trial
of thyroid hormone suppression therapy leads to clinically significant
(> or = 50%) reduction of nodule size or arrest of nodule growth in a
subset of patients with benign solitary thyroid nodules. In fact, in
addition to objective improvements due to decreasing nodule size, L-T4
suppression therapy may benefit patients by reducing perinodular thyroid
volume. Consequently, both pressure symptoms and cosmetic complaints may
improve (9, 68). Additional studies for the assessment of the risks versus
benefits of supraphysiologic doses of L-T4, the optimal level of thyroid
suppression and the dose needed to achieve this magnitude of reduction,
the optimal length of the initial trial, and the conditions for the
continuation of L-T4 thyroid suppression therapy, as well as the
identification of markers for patients most likely to respond to this
therapy, are warranted. Finally, quantitative assessment of available
evidence as described here may be applicable to the review of other
controversial issues as well.
J Clin Endocrinol Metab 1999 Dec;84(12):4566-9
Changes in thyroid nodule volume caused by fine-needle aspiration: a
factor complicating the interpretation of the effect of thyrotropin
suppression on nodule size.
Gordon DL, Flisak M, Fisher SG
Department of Medicine, Loyola University of Chicago, Maywood, Illinois
60153, USA. DGORDON@luc.edu
The effectiveness of TSH suppression therapy for thyroid nodules remains
controversial. Prior studies have assumed that the fine-needle aspiration
biopsy (FNAB), used to confirm a benign condition before the establishment
of control and treatment groups, has no effect on nodule volume. Seventeen
untreated euthyroid patients with clinical solitary thyroid nodules that
were solid (on high-resolution ultrasound) and a colloid goiter (on
cytologic examination) had ultrasound measurements of nodule volume before
a FNAB, immediately thereafter, and 1 month and 6 months later. Size
differences and individual variability at each time period were analyzed.
No significant difference in mean thyroid nodule volume was present at any
point after the FNAB; however, the changes in nodule volume were quite
marked and bidirectional among patients masking the cumulative effect. The
variability of the change in individual nodule volume was statistically
significant when comparisons were made across time (P = 0.0032). FNAB of
thyroid nodules results in significant individual changes in volume after
the procedure. Studies, such as the effect of TSH suppression on thyroid
nodule volume, that incorporate the FNAB in both control and treatment
arms of the experimental design, need to take these changes into account,
less erroneous conclusions result.
Cancer 1999 Oct 25;87(5):299-305
Ultrasound-guided fine-needle aspiration biopsy of the thyroid.
Tambouret R, Szyfelbein WM, Pitman MB
Department of Pathology, Massachusetts General Hospital, Boston,
Massachusetts 02114, USA.
BACKGROUND: We reviewed the Massachusetts General Hospital experience with
ultrasound-guided fine-needle aspiration biopsies (FNABs) of the thyroid
to determine the indications, rate of unsatisfactory smears, correlation
with excisional biopsy results, and verification of efficient use of
personnel time. METHODS: All radiologically guided FNABs of the thyroid
from January 1993 through June 1997 were reviewed. As a measure of
efficient use of technologist time, a sample of times spent by the
technologist during the procedure for 20 cases in 1993 and 1997 was
compared with that of an equal number of random nonthyroid image guided
FNABs. RESULTS: Two hundred-ninety FNABs were identified in 251 patients,
representing 12% of all thyroid FNABs and 11% of all radiologically guided
FNABs. Indications in the 251 patients included multiple nodules (78),
solitary nodules (61), complex nodules (39), prior failed FNAB (39),
thyroid bed abnormalities post-thyroidectomy (21), difficult access (7),
and investigation of recurrent tumor in residual thyroid lobe (6).
Available records indicated 118 lesions were palpable and 45 were
nonpalpable; the physical examination characteristics of the remainder
(88) were not stated. Diagnoses included 44 unsatisfactory cases (15%),
103 macrofollicular lesions, 20 microfollicular lesions, 26 mixed
macro/microfollicular lesions, 5 oxyphilic lesions, 1 trabecular pattern,
15 nonspecific follicular cell pattern, 9 follicular cell atypia, 30
cysts, 11 thyroiditis, 23 malignant tumors, and 3 other (1 parathyroid, 2
lymph node). Eighty-nine FNABs from 76 patients had subsequent surgical
biopsy. Excisional biopsies in 14 unsatisfactory FNABs were benign. In the
remaining 75 FNABs from 67 patients, 18 malignancies on FNAB were
correctly diagnosed, but 3 other papillary carcinomas were only qualified
as atypical follicular cells on cytology. No false-positive cases
occurred. Of 15 macrofollicular lesions on cytology, 10 were adenomas on
excision, only 2 of which were microfollicular adenomas, and 4 were
adenomatous nodules. An aspirate of a parathyroid adenoma was
misinterpreted as a macrofollicular lesion of the thyroid. Three
microfollicular lesions on FNAB proved to be nodular hyperplasia on
excision, and the other 11 were adenomas, 5 of them microfollicular.
Average technologist time was significantly longer for thyroid FNABs than
nonthyroid FNABs in 1993, but in the 1997 sample no significant difference
was identified. CONCLUSIONS: Radiologically guided FNAB of the thyroid is
a clinically useful procedure with a high correlation between benign
lesions not needing excision (macrofollicular), and lesions that need
excision (microfollicular/oxyphilic cell or malignant). Technologist time
needed for immediate evaluation tends to decrease with increasing operator
experience. Cancer (Cancer Cytopathol) Copyright 1999 American Cancer
J Clin Endocrinol Metab 1998 Nov;83(11):3881-5
Suppressive therapy with levothyroxine for solitary thyroid nodules: a
double-blind controlled clinical study and cumulative meta-analyses.
Zelmanovitz F, Genro S, Gross JL
Endocrine Division, Hospital de Clinicas de Porto Alegre, RS, Brazil.
Levothyroxine suppressive treatment of solitary thyroid nodules is
controversial. A 1-yr prospective randomized placebo-controlled trial was
conducted to evaluate the effect of T4 on nodule volume and bone mineral
density, and meta-analyses were performed to examine the quantitative
synthesis of data from similar designed controlled trials. Forty-five
euthyroid patients (42 females, age range: 19-73 yr) with single, colloid
nodules were randomized to T4 (21 patients, 2.7 +/- 0.3 microg/kg, TSH
< 0.3 microIU/mL) and placebo. Ultrasonography and densitometry were
performed at baseline and repeated after treatment. Mean nodule volume or
bone mineral density did not change. Nodule reduction more than 50% was
observed in 6 of 21 treated patients and 2 of 24 placebo patients (P =
0.12). This study and another 6 prospective controlled trials (minimum 6
months, ultrasonographic nodule evaluation) were included in cumulative
meta-analyses (risk-difference method). Nodule volume decreased more than
50% in a significantly higher percentage of patients in the T4 groups
(risk difference, 16.7%; 95% confidence intervals, 5.8-27.6%). Four trials
evaluated nodule growth with homogeneous results (Q = 0.42). Nodule volume
increased more than 50% in a significantly smaller percentage of patients
treated with T4 (risk difference, 9.7%; 95% confidence intervals,
2.0-17.4%). In conclusion, T4 treatment is associated with decreased
nodule volume in 17% of patients and may inhibit growth in another 10%.
Randomized controlled trial
Thyroid 1998 Aug;8(8):647-52
Published erratum appears in Thyroid 1998 Nov;8(11):1079
Thyroid nodules in Graves' disease: classification, characterization,
and response to treatment.
Carnell NE, Valente WA
Department of Medicine, University of Maryland School of Medicine,
Thyroid nodules in patients with Graves' disease are common and raise
concern about coexistent thyroid malignancy. Alternative etiologies for
such nodules are more frequent, and separation from thyroid malignancy is
important for rational management. To characterize the types of thyroid
nodules present in patients with Graves' disease, evaluate the response of
these nodules to treatment, and stratify the risk of thyroid malignancy,
we report on a retrospective single center study in an ambulatory setting
of 468 Graves' patients ages (12-75) followed for 1-31 years (mean = 5.1)
treated with radioiodine (n = 345), near total thyroidectomy (n = 19),
thionamide antithyroid drugs (n = 88) or observation (n = 18). Sixty
patients (12.8% of the total) had nodules and were classified as: (1)
Graves' disease with a solitary hypofunctional nodule (n = 27, 5.8%); (2)
Graves' disease with multiple nodules (n = 21, 4.5%); (3) Graves' disease
with autonomous nodule (n = 4, 1%); or (4) patchy Graves' disease (n = 8,
1.7%). Six patients (1.3% of total or 10% of nodule patients) had cancer:
5 in group 1 and 1 in group 4. Based on the response to therapy or
surgical and fine-needle aspirate pathology, the remaining patients
demonstrated pseudo-nodules of autoimmune thyroid disease, autonomous
nodules of Marine-Lenhart syndrome, colloid goiter, hyperplastic
adenomatous disease, and Hashitoxicosis. In conclusion, Graves' patients
present with or may develop nodules commonly (12.6%) and the majority of
these are benign expressions of autoimmune changes and coexistent nodular
goiter. Thyroid cancer occurs in 10% of all nodules, 19% of palpable
solitary cold nodules and 1.3% of the total patients. If the fine-needle
aspiration biopsy (FNAB) cytology is benign, it is reasonable to use
nonsurgical therapy. Any single cold nodule that remains or develops after
treatment needs careful re-examination due to the high risk of
Ann Intern Med 1998 Mar 1;128(5):386-94 [Texto
Thyroxine suppressive therapy in patients with nodular thyroid
Gharib H, Mazzaferri EL
Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
PURPOSE: To review evidence about thyroxine suppressive therapy in
patients with thyroid nodules, including the clinical importance and
natural history of nodules and the effects and potential side effects of
thyroxine therapy. DATA SOURCES: English-language articles published from
1986 to December 1996 were identified through searches of the MEDLINE
database, selected bibliographies, and personal files. DATA EXTRACTION:
Randomized, controlled trials and nonrandomized trials of thyroxine
suppressive therapy for solitary and predominantly solid thyroid nodules
were reviewed. In most studies, nodule cytology was evaluated by
fine-needle aspiration biopsy. Therapy was considered suppressive if
suppression was documented by thyroid-stimulating hormone-releasing
hormone tests or sensitive thyroid-stimulating hormone assays. Response
was defined as a decrease of 50% or more in nodule size or volume; most
recent studies measured nodule size by ultrasonography. DATA SYNTHESIS:
The evidence suggests that thyroxine suppressive therapy fails to shrink
most nodules: Only 10% to 20% of nodules responded to this treatment.
Fine-needle aspiration biopsy is more reliable in distinguishing benign
from malignant nodules. Recent studies suggest that spontaneous decrease
in size with complete disappearance of thyroid nodules is not uncommon. No
data show that thyroxine therapy arrests further growth in most existing
nodules or prevents the emergence of new nodules. Postoperative thyroxine
therapy does not seem to prevent recurrence of thyroid nodules except in
patients with a history of radiation therapy. Potential adverse effects of
long-term suppressive therapy include osteoporosis and heart disease.
CONCLUSIONS: Patients with cytologically benign nodules are best followed
without thyroxine treatment. Most benign nodules remain stable in size and
remain benign when monitored for a long time. For nodules that increase in
size, biopsy should be done again or surgery should be performed.
Presse Med 1997 Apr 5;26(11):507-11
[Isolated thyroid nodule. Comparative value of cyto-puncture and
Duquenne M, Rohmer V, Guyetant S, Becouarn G, Dion Barbot N, Saint
Andre JP, Ronceray J, Bigorgne JC
Service d'Endocrinologie, Nutrition, Medicine interne, CHU d'Angers.
OBJECTIVES: Nodular thyroid disease, indicated by the presence of single
or multiple nodules within the thyroid gland is a common clinical problem,
the main question remains the malignancy. Radionuclide scanning,
ultrasonography and fine needle aspiration biopsy have been helpful to
distinguish benign from malignant nodules and to select patients for
surgery. METHODS: We performed a prospective study to assess the
comparative value of fine needle nonaspiration biopsy and thyroid scinti
scan in the management of 412 patients operated for solitary thyroid
nodule. RESULTS: Sensitivity and negative predictive values were the same
for both methods, but specificity of cytology was greater than that of
thyroid scinti scan (80.53% vs. 10.47%, p < 0.001). DISCUSSION: Thyroid
radionuclide scanning remains valuable in the evaluation of a cytological
benign solitary thyroid nodule when TSH value is low, in order to
distinguish toxic adenoma from cold nodule in Graves' disease.
Arch Intern Med. 1996;156:2165-2172 [Texto
Treatment Guidelines for Patients With Thyroid Nodules and
Well-Differentiated Thyroid Cancer
Peter A. Singer, MD; David S. Cooper, MD; Gilbert H. Daniels, MD; Paul
W. Ladenson, MD; Francis S. Greenspan, MD; Elliot G. Levy, MD; Lewis E.
Braverman, MD; Orlo H. Clark, MD; I. Ross McDougall, MB, ChB, PhD; Kenneth
V. Ain, MD; Steven G. Dorfman, MD
A set of minimum clinical guidelines for use by primary care physicians in
the evaluation and management of patients with thyroid nodules or thyroid
cancer was developed by consensus by an 11-member Standards of Care
Committee (the authors of the article) of the American Thyroid
Association, New York, NY. The participants were selected by the committee
chairman and by the president of the American Thyroid Association based on
their clinical experience. The committee members represented different
geographic areas within the United States, to reflect different practice
patterns. The guidelines were developed based on the expert opinion of the
committee participants, as well as on previously published information.
Each committee participant was initially assigned to write a section of
the document and to submit it to the committee chairman, who revised and
assembled the sections into a complete draft document, which was then
circulated among all committee members for further revision. Several of
the committee members further revised and refined the document, which was
then submitted to the entire membership of the American Thyroid
Association for written comments and suggestions, many of which were
incorporated into a final draft document, which was reviewed and approved
by the Executive Council of the American Thyroid Association.
Arch Intern Med 1995 Dec 11-25;155(22):2418-23
Solitary thyroid nodule. Comparison between palpation and
Tan GH, Gharib H, Reading CC
Division of Endocrinology/Metabolism and Internal Medicine, Mayo Clinic,
Rochester, Minn, USA.
OBJECTIVE: To determine the accuracy of clinical palpation in the
diagnosis of solitary thyroid nodule in comparison with ultrasonographic
findings. METHODS: From a computerized database of 1774 patients with the
diagnosis of nodular thyroid disease made from January 1990 through
December 1991 at our institution, we retrieved and reviewed the medical
records of the 193 patients who underwent ultrasonography of the thyroid
(42 patients with multinodular glands on palpation were excluded). Nodules
were categorized as "solitary" or "dominant nodule of a
multinodular gland." Concordance rates were measured between results
of palpation and ultrasonographic findings. RESULTS: Of 151 patients
included in the study, 78 had solitary nodules on ultrasonography and 73
had multiple nodules. Of those with multiple nodules, 49 had two nodules
and 24 had three or more nodules. Of clinically palpable nodules, 89% were
1 cm or greater in diameter. In 72% of the patients with multiple nodules,
the other nodules not identified on palpation were less than 1 cm in
diameter. The overall concordance rate between the size of the solitary
nodule or the dominant nodule in a multinodular gland estimated with
clinical palpation and the actual size seen on ultrasonography was 72%.
The relationship between multiple nodules and malignancy was not
statistically significant. CONCLUSIONS: Our results suggest that (1) a
palpable solitary nodule represents a multinodular gland in about 50% of
patients, (2) clinical palpation is less sensitive than thyroid
ultrasonography in identifying multiple nodules, and (3) palpation is
reliable only if a nodule is at least 1 cm in diameter. We recommend that
small, occult (impalpable) thyroid nodules not be considered clinically
important; they do not warrant further evaluation unless ultrasonographic
features suggest malignancy or the nodule increases in size.
Lancet 1995 Nov 4;346(8984):1227
Alcohol sclerotherapy for benign solitary solid cold thyroid nodules.
Bennedbaek FN, Hegedus L
Postgrad Med 1995 Aug;98(2):73-4, 77-80
Solitary thyroid nodules. Separating benign from malignant conditions.
Boigon M, Moyer D
Section of General Internal Medicine, Temple University School of
Medicine, Philadelphia, USA.
Although features found on history taking, physical examination, thyroid
function tests, and imaging studies help categorize solitary thyroid
nodules as benign or malignant, fine-needle aspiration biopsy is the
diagnostic test of choice. Nodules found to be malignant on cytologic
examination should be treated with surgery. Benign nodules may be followed
clinically or treated with levothyroxine to suppress their growth.
Intermediate nodules should be excised if there is clinical suspicion of
malignancy. In suspect nodules, levothyroxine therapy with follow-up
ultrasound assessment for size is appropriate. Nodules that do not shrink
significantly within 6 months should be excised.