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Guideline-oriented Diagnosis of Thyroid Nodules
concluding that re-aspiration is not necessary.
40
On the other hand, Figure 2: Flow Chart for the Diagnostic Evaluation of
Chehade et al. followed 235 patients with benign FNA for an average of
Thyroid Nodules
2.9 years, and on repeat FNA found malignancy in one (0.4%),
concluding that re-biopsy reduces false-negative rates.
41
Patient with thyroid nodule(s)
For the example patient—a 40-year-old woman with a single 2.5cm
Clinical history
nodule that is benign, colloid by FNA, and solid by ultrasound and with
Physical examination of the thyroid and the neck
serum TSH 0.6mIU/l—65% would not recommend T4 suppressive
therapy. Whereas previously most endocrinologists would have used
FT3, FT4, TSH
Neck US
T4 to suppress TSH in this case, current guidelines do not recommend
(TPO Ab)
(solid/mixed)
Calcitonin
this practice. Therefore, it is gratifying that 65% of the European
thyroid specialists agreed with the guidelines and chose not to use T4
Diameter Diameter >1cm Low TSH or
therapy. The AACE/AME guidelines state that routine T4 therapy in
Normal
<1cm or multinodular
TSH
patients with benign thyroid nodules is not appropriate, but it may be
No suspicion <1cm suspicious goiter
considered in iodine deficiency. Only 12% of this group voted to use
Thyroid
T4 if the patient was in an iodine-deficient area. The ATA guidelines do
scan
not recommend suppression therapy for benign nodules. A recent
‘Cold’ or
meta-analysis of nine studies including 596 patients showed that Follow-up FNAC isocaptant
nodule volume decreased significantly in only fewer than 20%
nodule(s)
of the treated group. Moreover, T4 suppressive therapy led to a
Malignant,
non-significant improvement in the rate of response to therapy Benign nodule suspicious, or Surgery
(defined as ≥50% nodule volume reduction by ultrasound): pooled
follicular neoplasm
relative risk (RR) 1.83, 95% confidence interval (CI) 0.9–3.73.
42
In
This figure presents an attempt at an overview that tries to give an integrated view of the
summary, neither the guidelines nor the majority of European thyroid
diagnostic approaches for the diagnostic workup of a patient with a thyroid nodule. FNAC =
specialists recommend T4 to suppress benign thyroid nodules.
fine-needle aspiration cytology; TPO Ab = thyroid peroxidase antibody; TSH = thyroid-stimulating
28
hormone; US = ultrasound. Source: Pacini F, Schlumberger M, Dralle H, et al.
If cytology showed ‘suspicious for malignancy—follicular neoplasm,’ Table 3: Factors Suggesting Increased Risk for Malignancy
80% would recommend surgical excision of the nodule. Management of
a nodule with indeterminate cytology still generates controversy. The
History of head and neck irradiation
cancer risk among these specimens ranges from 15 to 75%, and is
Family history of MTC or MEN2
approximately 15% for follicular neoplasms. Immunohistochemical
Age <20 or >70 years
Male sex
markers have neither regularly nor reliably separated benign from
Growing nodule
malignant lesions.
38
Repeat biopsy is not helpful and can even lead to
Firm or hard consistency
confusion, because if re-aspiration is benign, the clinician has to
Cervical adenopathy
reconcile between a benign and a suspicious result. The AACE/AME
Fixed nodule
guidelines consider surgical excision as the best management; repeat
Persistent hoarseness, dysphonia, dysphagia, or dyspnea
biopsy or large-needle biopsy is not recommended. The ATA guidelines
MEN2 = multiple endocrine neoplasia type 2; MTC = mycobacterium tuberculosis complex.
discourage the use of molecular markers and prefer a radioiodine
26
American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi, 2006.
thyroid scan to rule out nodule hyperfunction when cytology is
suspicious. The ETA guidelines find immuno-cytochemistry neither Hurthle cell neoplasms. For example, Paphavasit et al. report that
sensitive nor specific, believing surgical treatment is the best approach. intraoperative frozen section was correct in 78% of patients, with
sensitivity, specificity, positive predictive value, negative predictive value,
If the cytology is ‘follicular neoplasm’, lobectomy and post-operative and accuracy of 78, 99, 90, 98, and 98%, respectively.
43
It is therefore not
histological review was recommended by 24%, near-total surprising that European experts seem evenly divided between the
thyroidectomy by 34%, and lobectomy and intraoperative frozen surgical options noted above. While there is no majority of opinion here,
section exam by 36% of the European thyroid specialists. The these differences likely represent the availability of surgical and pathology
AACE/AME guidelines recommend surgical treatment but do not expertise available to each participant in his/her clinic or location.
specify the extent of surgery. The ATA guidelines suggest thyroid
lobectomy for an isolated, indeterminate solitary nodule, whereas the For the example patient, 49% of the European thyroid specialists would
ETA recommends lobectomy for a solitary nodule and a near-total measure a baseline serum calcitonin (CT) level, whereas 43% would not.
thyroidectomy for a multinodular goiter when cytology is suspicious. This is in fact the most controversial question. Serum CT is a useful
Moreover, the ETA does not endorse frozen section because of the marker for C-cell disease and correlates well with tumor burden. MTC
high frequency of false-negative results. accounts for only 5% of thyroid malignancies; however, recent reports
show that the prevalence of MTC ranges from 0.4 to 1.4% in unselected
Recent reports suggest that in experienced hands intraoperative frozen patients with nodular thyroid disease. Data from non-randomized,
section can accurately separate benign from malignant follicular or prospective studies, mostly from European countries, suggest that
US ENDOCRINOLOGY 115
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