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Thyroid Disorders
Figure 1: Iodine Deficiency Evolution of Diagnostic Strategies for
Thyroid Nodules
Several questionnaire studies with European, North American and
Iodine deficiency
H
2
O
2
?
free
radicals?
Australian endocrinologists repeatedly revealed large discrepancies
Impaired
Mutagenesis
in the diagnosis and management of thyroid nodules.
22–25
Among
hormone
synthesis
other discrepancies, a less frequent application of fine-needle
Prolifer
ation
aspiration biopsy (FNAB) and more frequent use of thyroid
Hyperplasia
scintigraphy, thyroid ultrasound calcitonin and thyroid peroxidase
(TPO) antibody determination for the diagnosis of thyroid nodules in
Europe compared with North America and different strategies for
Adaptation by more the treatment of thyroid nodules became apparent. Most of these
efficient iodine
Expansions of cell
clearence, trapping,
clones with questionnaires – and especially those performed in Europe and
metabolism and Goitre and
Goitre with cell
advantageous
increased gene single cells with
clones containing a
mutations leading to
North America – were published in 1999 and 2000; that is, before the
expression somatic mutations
somatic mutations
hot (or cold) nodules
three major society-sponsored guidelines for thyroid diagnosis and
management were published: by the American Association of
Adaptation to Maladaptation to
iodine deficiency
Genetic susceptibility
iodine deficiency
Clinical Endocrinologists/Associazione Medici Endocrinologi (AACE/
AME), the American Thyroid Association (ATA) and the European
5,6
According to current knowledge, the aetiology of thyroid nodules can be summarised as
Thyroid Association (ETA).
26–28
follows: in genetically susceptible individuals with maladaptation to iodine deficiency, the
increased thyroid epithelial cell proliferation and the increased production of H O will lead2 2
to an increased rate of mutagenesis; depending on the gene that is hit, this will lead to small
One survey performed during an interactive symposium at the 32nd
clones of hot or cold thyroid cells, which will then give rise to hot or cold thyroid nodules or,
annual meeting of the ETA in Leipzig, Germany, was carried out to
less frequently, thyroid carcinomas.
5 6
Source: Krohn et al., 2005 and Krohn et al., 2007.
investigate whether these guidelines were able to affect the
divergent management strategies for thyroid nodules that have
Studies on the epidemiology of thyroid nodule function are rare. The previously been documented.
29
This survey showed that for a
scintigraphic evaluation of 60% of the solitary nodules detected by standard patient, i.e. a 40-year-old woman with a recently
ultrasound in a random cohort of probands 41–71 years of age discovered asymptomatic easily palpable, firm, solitary 2.5cm
living in an area with borderline iodine deficiency revealed cold right thyroid nodule with no cervical adenopathy, 90% of the
nodules in 46%, isofunctioning nodules in 44% and hot nodules in European thyroid specialists would perform a thyroid ultrasound. If
6%.
16
In another population study, thyroid nodules were detected by her serum TSH was 0.6mIU/l (normal 0.5–4.5), 45% would obtain a
thyroid palpation of adults 18–64 years of age in only 1.9% in an radioisotope scan, 42% would not obtain one and 12% were
iodine-sufficient area and in 5.1% in an iodine-deficient area. The undecided. Compared with previous European surveys,
23,25,26
these
scintigraphic evaluation of these nodules identified cold nodules in results demonstrate an increased use of thyroid ultrasound and a
87 and 84%, isofunctioning nodules in 0.4 and 0.6% and hot nodules decreased use of scintigraphy by European thyroid experts.
in 8 and 10% in the iodine-sufficient and iodine-deficient areas, Moreover, in evaluating thyroid nodules, ATA members use imaging
respectively.
17
Most hot nodules are easily detected by thyroid- less often than their ETA colleagues, and ATA respondents used
stimulating hormone (TSH) determination; however, in iodine- thyroid scan less frequently and ultrasound more frequently in 2000
deficient areas scintigraphic evidence of thyroid autonomy has compared with 1996.
30
been reported in 40% of patients with euthyroid endemic goitres.
18
Moreover, somatic constitutively activating TSH receptor mutations
have been detected in small 131-iodine (
131
I) hypercaptant areas The high prevalence of thyroid
detected by autoradiography.
19
It is therefore likely that not all hot
nodules requires rational evidence-
nodules – which are much more frequent in iodine-deficient than in
iodine-replete areas
20
– are detectable by determination of TSH. based strategies for their differential
However, if the hot nodule volume surpasses 16ml, a suppressed TSH
diagnosis, risk stratification, treatment
was detectable with a TRH test even with older radioimmunoassay
(RIA) technology.
21
Obviously, the critical threshold volume of hot and follow-up.
nodules that will lead to TSH suppression needs to be re-evaluated
using a third-generation TSH assay.
Concordance between guidelines is very high for both the clinical
The high prevalence of thyroid nodules requires rational evidence- recommendations and the grade of their strength, but the evidence
based strategies for their differential diagnosis, risk stratification, available for recommending ultrasound examination is correctly
treatment and follow-up. These strategies should concentrate on reported only as fair (ATA: grade B; AACE/AME: grade C). Indeed,
the risk of malignancy, hyperthyroidism and symptoms and should although ultrasound is generally appreciated as a diagnostic
be adaptable to the wide spectrum of clinical manifestations of procedure that induces a powerful effect on thyroid outcomes, the
thyroid nodules, ranging from small (<1cm) thyroid incidentaloma quality of evidence-based medicine (EBM) evidence in favour of
to large symptomatic thyroid nodules with progressive growth. clinical use of ultrasound thyroid scan may be rated just as fair due
Moreover, these strategies should also account for the different to the absence of level 1 and 2 clinical evidence.
prevalences of thyroid nodules, hot nodules and the different
subtypes of differentiated thyroid carcinomas in iodine-replete and The examination of the linked references confirms these remarks.
iodine-deficient areas, as well as different healthcare systems. For the thyroid ultrasound issue, the ATA reports three observational
60 EUROPEAN ENDOCRINOLOGY
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