Cost-effectiveness comparison between palpation- and ultrasound-guided thyroid fine-needle aspiration biopsies
© Can; licensee BioMed Central Ltd. 2009
Received: 29 October 2008
Accepted: 16 May 2009
Published: 16 May 2009
The aim of this study is to perform a cost-effectiveness comparison between palpation-guided thyroid fine-needle aspiration biopsies (P-FNA) and ultrasound-guided thyroid FNA biopsies (USG-FNA).
Each nodule was considered as a case. Diagnostic steps were history and physical examination, TSH measurement, Tc99m thyroid scintigraphy for nodules with a low TSH level, initial P-FNA versus initial USG-FNA, repeat USG-FNA for nodules with initial inadequate P-FNA or USG-FNA, hemithyroidectomy for inadequate repeat USG-FNA. American Thyroid Association thyroid nodule management guidelines were simulated in estimating the cost of P-FNA strategy. American Association of Clinical Endocrinologists guidelines were simulated for USG-FNA strategy. Total costs were estimated by adding the cost of each diagnostic step to reach a diagnosis for 100 nodules. Strategy cost was found by dividing the total cost to 100. Incremental cost-effectiveness ratio (ICER) was calculated by dividing the difference between strategy cost of USG-FNA and P-FNA to the difference between accuracy of USG-FNA and P-FNA. A positive ICER indicates more and a negative ICER indicates less expense to achieve one more additional accurate diagnosis of thyroid cancer for USG-FNA.
Seventy-eight P-FNAs and 190 USG-FNAs were performed between April 2003 and May 2008. There were no differences in age, gender, thyroid function, frequency of multinodular goiter, nodule location and diameter (median nodule diameter: 18.4 mm in P-FNA and 17.0 mm in USG-FNA) between groups. Cytology results in P-FNA versus USG-FNA groups were as follows: benign 49% versus 62% (p = 0.04), inadequate 42% versus 29% (p = 0.03), malignant 3% (p = 1.00) and indeterminate 6% (p = 0.78) for both. Eleven nodules from P-FNA and 18 from USG-FNA group underwent surgery. The accuracy of P-FNA was 0.64 and USG-FNA 0.72. Unit cost of P-FNA was 148 Euros and USG-FNA 226 Euros. The cost of P-FNA strategy was 534 Euros and USG-FNA strategy 523 Euros. Strategy cost includes the expense of repeat USG-FNA for initial inadequate FNAs and surgery for repeat inadequate USG-FNAs. ICER was -138 Euros.
Universal application of USG-FNA for all thyroid nodules is cost-effective and saves 138 Euros per additional accurate diagnosis of benign versus malignant thyroid nodular disease.
There are two thyroid nodule management guidelines with global recognition: first is the management guidelines for patients with thyroid nodules and differentiated thyroid cancer by American Thyroid Association (ATA) Guidelines Taskforce and the second one is the American Association of Clinical Endocrinologists (AACE) and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. After identification of a thyroid nodule that is more than 10–15 mm, ATA recommends measuring serum TSH level. If TSH is low, a thyroid scan is next. For a hot thyroid nodule, evaluation and treatment for hyperthyroidism is recommended. If the nodule is not hot, the algorithm points to diagnostic ultrasonography. The flowchart directs again to diagnostic ultrasonography for euthyroid and hypothyroid patients with thyroid nodules. If a nodule is ultrasonographically confirmed, a cytological evaluation is next. ATA recommends ultrasound-guided thyroid fine-needle aspiration biopsy (USG-FNA) for nodules with more than 50% cystic component and for nodules located in posterior parts of the thyroid gland. Otherwise either palpation-guided (P-FNA) or USG-FNA is next . In contrast, as indicated in the abstract of their guideline, AACE recommends universal application of USG-FNA for all thyroid nodules ≥ 10 mm, except for subjects with a low serum TSH level and a hot nodule, in whom FNA is not indicated . Except for minor changes in the sequence of diagnostic steps, ATA and AACE thyroid nodule management guidelines differ only in the utilization of ultrasound guidance. All previous studies show that USG-FNA has higher sensitivity, specificity and accuracy than P-FNA [3–11]. A barrier for universal recommendation of USG-FNA might be its higher initial cost . The aim of this report is to compare cost-effectiveness between palpation- and ultrasound-guided thyroid fine-needle aspiration biopsies from a perspective of ATA versus AACE thyroid nodule management guidelines.
This is a secondary data analysis of a study registered to ClinicalTrials.gov with Identifier NCT00571090. The aim of the study was to identify ultrasonographic features that predict malignant thyroid nodules. The primary data from this study has not been published. Data relevant to cost-effectiveness comparison are reported here. FNAs were performed as an outpatient procedure in Gayrettepe and Şişli Florence Nightingale Hospitals, two private hospitals affiliated with Istanbul Science University and authors' private medical office in Şişli, all located in Istanbul. Turkish Cardiology Foundation owns and operates Istanbul Science University and Group Florence Nightingale Hospitals in Istanbul. These health care facilities are secondary care centers for thyroid disorders, not tertiary care referral centers.
The clinical information and cytology results of all consecutive patients who underwent FNA biopsy of thyroid nodules in above-mentioned outpatient endocrinology clinics were instantaneously recorded in a computerized database on the day of the FNA biopsy. This study was not a retrospective chart review. All patients were examined by ASC, an endocrinologist who also performed all thyroid FNA biopsies between April 2003 and May 2008. Thyroid function tests and thyroid ultrasonography were routinely obtained. Subjects were classified into euthyroid, hypothyroid (TSH>4.20 μIU/ml) and hyperthyroid (TSH<0.27 μIU/ml) categories according to the results of thyroid function tests. The location, three dimensional diameters, echo structure (solid, mixed or cystic), echogenecity (hypoechoic, isoechoic or hyperechoic) and other ultrasonographic features of thyroid nodules were recorded. A nodule was classified as cystic, if its area was 90–100% cystic. Thyroid scintigraphy with Technetium99m was obtained for subjects with a low TSH level. All subjects consented to FNA biopsy in accordance with the hospital bylaws. Institutional Review Board approval from Istanbul Science University Ethics Committee was asked and granted in July 2007 (Number 2007/006). As thyroid FNAs were performed in routine clinical care without any investigational procedure, the Ethics Committee did not ask for signed informed consent for subjects enrolled prior to approval of the study. Subjects admitted after July 2007 signed informed consent for the study.
Each thyroid nodule was counted as a case in this report. Three-hundred and thirty-nine FNAs were performed between April 2003 and May 2008. Nineteen FNAs for nonpalpable nodules and 16 FNAs for nodules <10 mm were excluded. There were 19 nodules with a low TSH level but without a thyroid scintigraphy and these were also excluded. ATA designates cystic nodules as an indication for USG-FNA . AACE recommends USG-FNA for all nodules, including cystic ones . As there was no disagreement on the utility of ultrasound guidance for cystic nodules between guidelines, 17 cystic nodules were excluded from the analysis. There were 268 thyroid nodules for comparison. One-hundred and ninety USG-FNAs were performed to palpable thyroid nodules with a SonoSite 180 plus hand-carried ultrasound system and a L38/10-5 MHz transducer between March 2004 and May 2008, starting with the acquisition of the ultrasound system. Both the ultrasound system and the transducer were manufactured by SonoSite Incorporation, located in Bothell, WA, USA. A published standard technique was used for USG-FNA . Seventy-eight P-FNAs were performed to palpable thyroid nodules with a previously published technique  between April 2003 and February 2008, at times when the ultrasound system was not available for FNA biopsy. Allocation to P-FNA and USG-FNA groups was not random. The FNAs were done by palpation-guidance until the ultrasonography system was purchased. Then USG-FNA was routinely performed. P-FNA was still performed after the acquisition of ultrasonography system, at times when the ultrasonography machine was temporarily unavailable in the above-mentioned outpatient endocrinology clinics. On-site microscopic adequacy was not determined. Local anesthesia with 2% lidocaine was routinely administered for both P- and USG-FNAs. All FNA biopsies were performed with either 22 or 26 gauge needles. Twenty-two gauge needles are long; 26 gauge needles are short. If the nodule is located anteriorly or in the isthmus a 26 G needle, if posteriorly a 22 G needle was used. Two needle aspirations were carried out for each nodule. If no material was seen on the slides to plain eye without using an optical instrument, up to four aspirations were performed. Half of the smears were air-dried and stained with May-Grünwald-Giemsa and the other half were alcohol-fixed and stained with Hematoxylene-Eosine or Papanicolaou. Cytological diagnoses were categorized as malignant, benign, indeterminate and inadequate [1, 14]. Six clusters of benign cells in at least two slides constituted adequate material for cytological diagnosis. Each cluster was composed of at least 15 cells. The smears that do not meet these criteria were assigned into inadequate category. Indeterminate samples included a pattern of follicular or Hurthle cell neoplasm or aspects of atypia suggestive, but not conclusive of the presence of a malignant neoplasm .
Continuous variables were presented as means ± standard deviations and Student's t test was used for comparison. As maximal nodule diameter had a positively skewed distribution, its logarithmic transformation was used in Student's t test. Categorical variables were presented as percentages and χ2 test was used for comparison. As the expected frequencies of malignant results were less than five in both groups, each cytology category in P-FNA and USG-FNA groups was compared after collapsing the rest of the categories. Fisher's exact test was employed when the expected frequencies were less than five. Benign and inadequate cytology results were categorized into negative tests, as surgery is not recommended for these conditions. Malignant and indeterminate FNA cytology results were categorized into positive tests, as surgery is recommended to patients with such results. Nodules with benign or inadequate cytology and benign surgical histopathology result were classified as true negatives. Nodules with benign or inadequate cytology and malignant surgical histopathology result were classified as false negatives. Nodules with malignant or indeterminate cytology and malignant surgical histopathology result were classified as true positives. Nodules with malignant or indeterminate cytology and benign surgical histopathology result were classified as false positives. The accuracy of the test was calculated by dividing the sum of true positives and true negatives to the sum of true positives, false positives, false negatives and true negatives.
Cost of thyroid fine-needle aspiration strategies
Cost of diagnostic steps recommended by thyroid nodule management guidelines
History and physical exam
Measurement of TSH
Tc99m thyroid scintigraphy
c USG-FNA is the cost of ultrasound-guided thyroid FNA strategy according to AACE thyroid nodule management guideline to achieve a diagnosis for one nodule, c P-FNA is the cost of palpation-guided thyroid FNA strategy according to ATA thyroid nodule management guideline to achieve a diagnosis for one nodule, a USG-FNA is the accuracy of ultrasound-guided thyroid FNA and a P-FNA is the accuracy of palpation-guided FNA.
Comparison of baseline characteristics and cytology results between palpation-guided and ultrasound-guided thyroid fine-needle aspiration biopsies
Nodule number (n)
47 ± 15
47 ± 12
Right lobe (%)†
Log (nodule diameter)*§
1.26 ± 0.18
1.27 ± 0.19
Cross-tabulation of cytology and surgical histopathology results in palpation-guided thyroid fine-needle aspiration biopsies
Cross-tabulation of cytology and surgical histopathology results in ultrasound-guided thyroid fine-needle aspiration biopsies
Cost-effectiveness comparison between palpation- and ultrasound-guided thyroid fine-needle aspiration biopsies with costs from this study and outcomes from previous studies
P-FNA Strategy Cost*
USG-FNA Strategy Cost*
Manipulation of the data with alternatives
If the diagnostic step of hemithyroidectomy (n = 12 for P-FNA and n = 8 for USG-FNA) is excluded from Figures 1 &2, the average cost of P-FNA will be €349 and USG-FNA €399 in this study. As the analyses reported here are subject to substantial changes depending on the variation of costs and FNA outcomes, alternative data sources are used. The first approach is to replace private health care costs that are used in this study (table 1) with state hospitals' costs in Turkey. Turkish Ministry of Health owns and operates state hospitals and licenses and inspects private hospitals. Turkish Ministry of Labor and Social Security manages Turkish Social Security Institution which covers 80% of the population and is the main payer for health care . All state hospitals provide services to patients insured by the Turkish Social Security Institution from the prices that the Institution determines. Turkish Social Security Institution's prices are obtained from the internet  and Ankara University, Faculty of Medicine (Murat Faik Erdogan, MD, email@example.com, e-mail communication, June 10, 2008). These prices were valid for all state hospitals in Turkey in 2008. Following are Turkish State Hospitals' fees: history and physical exam €8, TSH measurement €2.32, thyroid ultrasonography €7.49, Tc99m thyroid scintigraphy €9.65, P-FNA €36.81, USG-FNA €52.14, subtotal hemithyroidectomy €393.76. From a perspective of Turkish Social Security Institution prices and FNA outcomes of this study, P-FNA strategy costs €124 and USG-FNA strategy costs €117 for one thyroid nodule. ICER is -€88, again indicating savings with USG-FNA. The next example is to input other authors' costs to our thyroid FNA outcomes. From a mid-Atlantic academic medical center in the USA, the cost of initial P-FNA was reported as €162, USG-FNA as €263 and hemithyroidectomy as €1733 . These were hospital costs and were not actual billed charges. When these costs are inputted into the last five boxes of Figure 1 and 2, the cost of P-FNA strategy is estimated as €480 and the cost of USG-FNA strategy as €478. ICER is -€25, indicating savings with USG-FNA strategy. The other approach is to use costs in table 1 with inadequate and accuracy rates from the literature. A cost-effectiveness comparison is made by using data from previous studies that report both the accuracy rates and head-to-head comparison of P-FNA with USG-FNA and is illustrated in table 5.
Limitation of the study
A cystic nodule was defined if the cystic component is more than 90% of nodule area in this study. ATA recommends USG-FNA if a nodule is more than 50% cystic . Posterior location of the nodule, an indication for USG-FNA was not recorded and could not be used in the construction of ATA thyroid nodule management guidelines. Another point to remember is that actual costs should be approximately 30% lower in this study, because charges for diagnostic steps, like physical examination or TSH are for per patient, not for per nodule. There were four nodules with medullary thyroid cancer from three patients in the USG-FNA group. A genetic RET screening was requested. It was refused by one subject, the other subject was lost to follow-up and RET analysis is pending in the third subject. The medullary thyroid cancer patients were not from the same family. A single familial cluster of medullary thyroid cancer was not present. The assignment to P-FNA or USG-FNA groups was not affected by the presence of medullary thyroid cancer and there was no bias in the study from that aspect. Our inadequacy rates are high (42% for P-FNA and 29% for USG-FNA). Mehrotra and coworkers reported an inadequacy rate of 47% for P-FNA and 16% for USG-FNA . Our inadequacy rates are not greatly different from Mehrotra's rates. Cytology outcomes of this study reflect everyday clinical practice. This may be an advantage in a cost-effectiveness comparison, because controlled studies may have different outcomes than real-life situations.
From a perspective of ATA and AACE thyroid nodule management guidelines and with costs from Turkish health care system, this study shows that USG-FNA is cost-effective. If universal USG-FNA is used instead of P-FNA, 138 Euros are saved for one additional accurate diagnosis of benign versus malignant thyroid nodular disease.
American Association of Clinical Endocrinologists
Ahmet Selçuk Can (the author of this study)
American Thyroid Association
fine-needle aspiration biopsy
incremental cost-effectiveness ratio
palpation-guided thyroid fine-needle aspiration biopsy
ultrasound-guided thyroid fine-needle aspiration biopsy.
The author thanks to Dr. Kamil Peker and Dr. Kemal Şarman, the pathologists who performed the cytological evaluations for the majority of thyroid FNAs. Kamil Peker and Kemal Şarman are partners in Istanbul Pathology Laboratory and provide services to Group Florence Nightingale Hospitals, other private hospitals and to private medical offices. They employ other pathologists. Drs. Kamil Peker and Kemal Şarman are funded by Group Florence Nightingale Hospitals and by their private practice in Istanbul Pathology Laboratory. Ahmet Selçuk Can is funded by his employer and his private practice.
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