Incidental thyroid nodule: patterns of diagnosis and rate of malignancyAuthors: Jin J, Wilhelm SM, McHenry CRJournal: The American Journal of Surgery 2009; 197: 320–324Centre: Case Western Reserve University, School of Medicine, Cleveland, Ohio, United States

BACKGROUND

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 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 rate of malignancy.”

IN SUMMARY Thyroid incidentaloma

Work up for metastatic disease

Investigations for other medical

problemsNumber of incidentalomas 88 62

Mean size of nodule 2.1 cm (0.4 - 8 cm)

Number submitted to FNAC 125 (82%)

FNAC - "benign" 62

FNAC - "indeterminate" 49

FNAC - "malignant" 9

FNAC - "non-diagnostic" 5

Number submitted to thyroidectomy 65

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.

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

© Dr Arjun Rajagopalan

EBM-O-METER

Evidence level Overall rating Bias levelsDouble blind RCT

TrashLife's too

short for this

Swiss cheese

Full of holes

SafeHolds water

News-worthy

“Just do it”

Sampling

Randomized controlled trial (RCT) Comparison

Prospective cohort study - not randomized Measurement

Case controlled study Interesting l | Novel l | Feasible l Ethical l | Resource saving lCase series - retrospective

RESEARCH QUESTION

Population

Patients referred for evaluation of incidentally detected thyroid nodules during work up for metastatic disease or investigation of other medical problems.

Indicator variable

Thyroid nodule detected on a radiological imaging study.

Outcome variable

Finding of histologically confirmed thyroid cancer in the nodules.

Comparison

Historical controls. Cancer in the two subsets that constituted the study.

OBSERVATIONAL

27 April 2009DissectionsDissectionsEvidence-based Medicine for Surgeons

SAMPLING Sample type Inclusion criteria Exclusion criteria Final score card

Simple random Patients referred to an endocrine surgical unit with a thyroid nodule detected during imaging for metastatic disease or other medical conditions

Previous history of thyroid cancer, previous thyroid surgery, or a known history of nodular thyroid disease

Study

Stratified random Target ?

Cluster Accessible ?

Consecutive Intended 150

Convenience 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.

© Dr Arjun Rajagopalan

COMPARISON Randomized Case-control Non-random Historical None

Controls - detailsAllocation 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

Device suited to task

Y ? N

Rep

etitio

n

Gol

d st

d.

Trai

ning

Prot

ocol

s

Sco

ring

Blin

ding

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.