Dissections OBSERVATIONAL

27 April 2009
Evidence-based Medicine for Surgeons

Incidental thyroid nodule: patterns of diagnosis and rate of malignancy

Authors: Jin J, Wilhelm SM, McHenry CR
Journal: The American Journal of Surgery 2009; 197: 320–324
Centre: Case Western Reserve University, School of Medicine, Cleveland, Ohio, United States
A thyroid "incidentaloma" is defined as an unsuspected, focal thyroid lesion discovered by a
radiographic imaging modality or at the time of a nonthyroid neck surgery in a patient without
BACKGROUND history of thyroid disease. It has been suggested that thyroid incidentalomas have a higher rate
of thyroid malignancy than the previously reported rate of 5% for palpable thyroid nodules
Authors' claim(s): “...an incidental thyroid nodule is associated with a high
RESEARCH QUESTION rate of malignancy.”

Population
IN SUMMARY
Patients referred for evaluation of
Thyroid incidentaloma
incidentally detected thyroid
nodules during work up for Work up for metastatic Investigations for
metastatic disease or investigation disease other medical
of other medical problems. problems
Indicator variable Number of incidentalomas 88 62
Thyroid nodule detected on a Mean size of nodule 2.1 cm (0.4 - 8 cm)
radiological imaging study.
Number submitted to FNAC 125 (82%)
Outcome variable FNAC - "benign" 62
Finding of histologically confirmed FNAC - "indeterminate" 49
thyroid cancer in the nodules.
FNAC - "malignant" 9
Comparison
FNAC - "non-diagnostic" 5
Historical controls. Cancer in the
Number submitted to thyroidectomy 65
two subsets that constituted the
study. Thyroid cancer on HPE 21
Microcarcinoma 6
Prevalence of thyroid cancer 15/150 (10%)

THE BOTTOM LINE

As the authors themselves admit, there is a very large selection bias. The majority of patients (88 of 150) were known to
have a pre-existing malignancy and the thyroid nodules were detected on imaging studies carried out for metastatic
disease. The remainder were also patients with other medical complaints who were being worked up. This cannot be
seen in any way as a representative sample of a normal population. The sample population is highly skewed. There is no
attempt to construct a fair control. Despite that, the prevalence of thyroid cancer was 10% (excluding the
microcarcinomata). Considering the small sample size and the skewed sample, this is not likely to be significantly higher
than the quoted 5% in the literature. Interestingly, the mean size of the nodules was 2.1 cm: large enough to be clinically
palpable. Are they really "incidentalomas" if this large? The danger in this paper lies in its being used as the rational for
ordering imaging studies in a thoughtless fashion.

EBM-O-METER
Evidence level Overall rating Bias levels
Double blind RCT Sampling
Randomized controlled trial (RCT) Comparison
Trash Swiss Safe News-
Prospective cohort study - not randomized cheese worthy Measurement
Life's too Holds water
short for this Full of holes “Just do it”
Case controlled study
Interestingl | Novel l | Feasible l
Case series - retrospective  Ethical l | Resource saving l

The devil is in the details (more on the paper) ... 

© Dr Arjun Rajagopalan
 SAMPLING
Sample type Inclusion criteria Exclusion criteria Final score card
Simple random Patients referred to an Previous history of Study
endocrine surgical unit thyroid cancer,
Stratified random Target ?
with a thyroid nodule previous thyroid
Cluster detected during surgery, or a known Accessible ?
imaging for metastatic history of nodular
Consecutive disease or other thyroid disease  Intended 150
Convenience medical conditions  Drop outs 25 (18%)
Judgmental Study 125

 = Reasonable | ? = Arguable |  = Questionable

Sampling bias: The study was carried out on patients who were undergoing work up for metastatic disease (88) or
other medical problems (62). This is not representative of a normal population of individuals. The sample is highly
biased. Twenty five patients (18%) of the referrals underwent no evaluation.

COMPARISON
Randomized Case-control Non-random Historical None

Controls - details
Allocation details All patients underwent US examination of the thyroid gland. Fine-needle aspiration (FNA)
biopsy was performed for all incidentally discovered thyroid nodules with abnormal
sonographic features. Thyroidectomy was recommended for all patients with a malignant,
indeterminate, or persistently nondiagnostic cytologic result.
Comparability Patients were analyzed as two groups: those whose nodules were discovered on imaging for
metastatic disease (88) and those who were studied as part of other medical problems (62).
There is no mention of the basic features of either group or of the comparability.
Disparity The disparity between the two groups and between the whole sample and a general
population, though not stated, is obvious and large.

Comparison bias: The study is deeply flawed in terms of the comparison. Both groups are non-representative.
There is no baseline, disease-free, presumably normal population to serve as a control. All comparisons are against
historical controls.

MEASUREMENT
Measurement error
Device used Device error Observer error
Gold std.

Device suited to task

Training

Scoring

Blinding
Repetition

Protocols

Y ? N

1.Ultrasound assessment of nodule Y N Y N N N N

2.FNAC of suspicious nodules Y N Y N Y N N
3.HPE of thyroidectomy tissue Y - Y N N - -

Measurement bias: Histopathological examination of the excised thyroid is the only gold standard for confirmation
of the presence of malignancy in the nodule. Only 65 of the 150 patients had such confirmation. Admittedly, it is
impossible to submit all patients for thyroidectomy and some sort of screening process is required. This makes the
need for a good control group even more essential - something that this study lacks in entirety.

© Dr Arjun Rajagopalan