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Guideline-oriented Diagnosis of Thyroid Nodules
number of serial sections.
11
Most autopsy studies report incidences Figure 1: Iodine Deficiency
ranging from 6 to 11%.
12–14
A comparison of these papillary
microcarcinoma incidence rates in autopsy studies with the incidence
H O ?
2 2
Iodine deficiency
rates for clinically apparent papillary carcinomas strongly suggests that
free
radicals?
most papillary microcarcinomas will not lead to clinically apparent
Impaired
Mutagenesis
thyroid carcinomas. Moreover, these data suggest that histological
hormone
synthesis
evaluation of resected thyroid tissue will often detect papillary
ation
Prolifer
Hyperplasia
microcarcinomas with an unlikely clinical relevance. A follow-up study of
papillary microcarcinomas over a nine-year period demonstrated no
metastases in patients with tumors <0.8mm.
15
Adaptation by more
Expansions of cell
Studies on the epidemiology of thyroid nodule function are rare. The
efficient iodine
clones with
clearence, trapping,
Goiter with cell
scintigraphic evaluation of 60% of the solitary nodules detected by
advantageous
metabolism, and Goiter and
clones containing a
mutations leading to
increased gene single cells with
ultrasound in a random cohort of probands 41–71 years of age living in
somatic mutations
hot (or cold) nodules
expression somatic mutations
an area with borderline iodine deficiency revealed cold nodules in 46%,
isofunctioning nodules in 44%, and hot nodules in 6%.
16
In another
Adaptation to Maladaptation to
Genetic susceptibility
iodine deficiency iodine deficiency
population study, thyroid nodules were detected by thyroid palpation of
adults 18–64 years of age in only 1.9% in an iodine-sufficient area and
5,6
According to current knowledge, the etiology of thyroid nodules can be summarized as
follows: in genetically susceptible individuals with maladaptation to iodine deficiency, the
in 5.1% in an iodine-deficient area. The scintigraphic evaluation of these
increased thyroid epithelial cell proliferation and the increased production of H O will lead to2 2
nodules identified cold nodules in 87 and 84%, isofunctioning nodules
an increased rate of mutagenesis; depending on the gene that is hit, this will lead to small
clones of hot or cold thyroid cells, which will then give rise to hot or cold thyroid nodules or,
in 0.4 and 0.6%, and hot nodules in 8 and 10% in the iodine-sufficient 5 6
less frequently, thyroid carcinomas. Source: Krohn et al., 2005 and Krohn et al., 2007.
and iodine-deficient areas, respectively.
17
Most hot nodules are easily
detected by thyroid-stimulating hormone (TSH) determination; determination for the diagnosis of thyroid nodules in Europe compared
however, in iodine-deficient areas scintigraphic evidence of thyroid with North America and different strategies for the treatment of thyroid
autonomy has been reported in 40% of patients with euthyroid nodules became apparent. Most of these questionnaires—and especially
endemic goiters.
18
Moreover, somatic constitutively activating TSH those performed in Europe and North America—were published in 1999
receptor mutations have been detected in small 131-iodine (
131
I) and 2000; that is, before the three major society-sponsored guidelines for
hypercaptant areas detected by autoradiography.
19
It is therefore likely thyroid diagnosis and management were published: by the American
that not all hot nodules—which are much more frequent in Association of Clinical Endocrinologists/ Associazione Medici
iodine-deficient than in iodine-replete areas
20
—are detectable by Endocrinologi (AACE/AME), the American Thyroid Association (ATA), and
determination of TSH. However, if the hot nodule volume surpasses the European Thyroid Association (ETA).
26–28
16ml, a suppressed TSH was detectable with a TRH test even with older
radioimmunoassay (RIA) technology.
21
Obviously, the critical threshold One survey performed during an interactive symposium at the 32nd
volume of hot nodules that will lead to TSH suppression needs to be annual meeting of the ETA in Leipzig in Germany, was carried out to
re-evaluated using a third-generation TSH assay. investigate whether these guidelines were able to affect the divergent
management strategies for thyroid nodules that have previously been
The high prevalence of thyroid nodules requires rational evidence-based documented.
29
This survey showed that for a standard patient, i.e. a
strategies for their differential diagnosis, risk stratification, treatment, 40-year-old woman with a recently discovered asymptomatic easily
and follow-up. These strategies should concentrate on the risk for palpable, firm, solitary 2.5cm right thyroid nodule with no cervical
malignancy, hyperthyroidism, and symptoms and should be adaptable adenopathy, 90% of the European thyroid specialists would perform a
to the wide spectrum of clinical manifestations of thyroid nodules, thyroid ultrasound. If her serum TSH was 0.6mIU/l (normal 0.5–4.5),
ranging from small (<1cm) thyroid incidentaloma to large symptomatic 45% would obtain a radioisotope scan, 42% would not obtain one, and
thyroid nodules with progressive growth. Moreover, these strategies 12% were undecided. Compared with previous European surveys,
23,25,26
should also account for the different prevalences of thyroid nodules, hot these results demonstrate an increased use of thyroid ultrasound and
nodules, and the different subtypes of differentiated thyroid carcinomas a decreased use of scintigraphy by European thyroid experts.
in iodine-replete and iodine-deficient areas, as well as different Moreover, in evaluating thyroid nodules, ATA members use imaging
healthcare systems. less often than their ETA colleagues, and ATA respondents used
thyroid scan less frequently and ultrasound more frequently in 2000
Evolution of Diagnostic Strategies for compared with 1996.
30
Thyroid Nodules
Several questionnaire studies with European, North American, and Concordance between guidelines is very high for both the clinical
Australian endocrinologists repeatedly revealed large discrepancies in recommendations and the grade of their strength, but the evidence
the diagnosis and management of thyroid nodules.
22–25
Among other available for recommending ultrasound examination is correctly
discrepancies, a less frequent application of fine-needle aspiration reported only as fair (ATA: grade B; AACE/AME: grade C). Indeed,
biopsy (FNAB) and more frequent use of thyroid scintigraphy, although ultrasound is generally appreciated as a diagnostic procedure
thyroid ultrasound calcitonin, and thyroid peroxidase (TPO) antibody that induces a powerful effect on thyroid outcomes, the quality of
US ENDOCRINOLOGY 113
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