Application of thermography in the diagnostic investigation of ...

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Application of thermography in the diagnosticinvestigation of thyroid nodulesCharbel Pereira Damião1), José Ramón Gonzalez Montero2), Maira Beatriz Hernandez Moran2), MariaEugênia de Oliveira Marçal e Silva Carvalho1), Camila Grotta de Farias1), Izadora Bighetti Brito1), MariaAuxiliadora Nogueira Saad1), Cristina Asvolinsque Pantaleão Fontes3), Claudio Fainstein4), ManoelFernando Oliveira Rodrigues4), Aniello Palombo4), Aura Conci2), Rubens Antunes da Cruz Filho1) andGiovanna Aparecida Balarini Lima1)

1) Department of Internal Medicine, Universidade Federal Fluminense (UFF), Niterói, RJ, Brazil2) Department of Computer Science, Universidade Federal Fluminense (UFF), Niterói, RJ, Brazil3) Department of Radiology, Universidade Federal Fluminense (UFF), Niterói, RJ, Brazil4) Department of General and Specialized Surgery, Universidade Federal Fluminense (UFF), Niterói, RJ, Brazil

Abstract. Thyroid nodules (TN) are common in the general population, and the clinical importance of diagnosing thyroidnodules is based on excluding the possibility of thyroid cancer, which occurs in 7–15% of cases. The thyroid gland, owing toits superficial location, is easily accessible via thermography, a noninvasive method of recording body temperature thatmeasures infrared radiation emitted by the body surface. Therefore, this study aimed to evaluate the temperature differencesbetween benign and malignant TN by using thermography. We conducted a cross-sectional study where 147 TN were dividedinto two groups: the first group included 120 benign nodules and the other included 27 malignant nodules. All the noduleswere subjected to ultrasound, fine needle aspiration biopsy, and thermography. On analyzing the thermography results, thebenign nodules had a higher temperature at the beginning of the thermography evaluation, and the malignant nodules showeda higher temperature in the middle and at the end (Ft). Using the relationships, it was observed that the temperature delta (ΔT),ΔT nodule/ΔT healthy, ΔT nodule minus ΔT healthy, and nodule Ft minus Ft of the healthy region were higher in malignantnodules. The ROC curve analysis of ΔT demonstrated a cutoff point of 2.38°C, with a sensitivity of 0.963 and specificity of0.992. Malignant nodules have higher temperatures than benign nodules on thermographic evaluation. This finding suggeststhat thermography can be a useful tool in the diagnosis of thyroid nodules.

Key words: Thermography, Thyroid, Thyroid Nodule, Thyroid Neoplasms

doi:10.1507/endocrj.EJ20-0541

THYROID NODULES (TNS) are common in the gen‐eral population. According to population-based studies inadults living in iodine-sufficient areas, approximately 4–7% of women and 1% of men have palpable TNs [1].However, the prevalence of nodules on ultrasound is sub‐stantially higher, occurring in ~68% of the population[2].

Current guidelines recommend that all patients withpalpable TNs undergo ultrasound examination [3, 4].Although most TNs are benign, malignancy must beexcluded. Thyroid cancer accounts for 7–15% of all TNs

Submitted Aug. 28, 2020; Accepted Dec. 15, 2020 as EJ20-0541Released online in J-STAGE as advance publication Jan. 21, 2021Correspondence to: Charbel Pereira Damião, Department of Inter‐nal Medicine, Universidade Federal Fluminense (UFF), HospitalUniversitário Antônio Pedro, Av. Marquês do Paraná, 303-Centro,Niterói-RJ, 24033-900, Niterói, RJ, Brazil.E-mail: [email protected]

[5]. The American Cancer Society’s most recent estimatefor thyroid cancer in the United States in 2020 was~52,890 new cases (12,720 in men and 40,170 inwomen) [6]. Factors that increase the risk of thyroidcancer include a history of childhood head and neckradiation therapy or ionizing radiation exposure; historyof thyroid carcinoma in the family or a first-degree rela‐tive; and rapid nodule growth or hoarseness [4].

Fine needle aspiration biopsy (FNAB) is the goldstandard diagnostic tool for TNs. Although the specific‐ity of FNAB is >95%, indeterminate FNAB results wereobtained in 15–30% of cases including follicular lesionsof unknown significance and follicular lesions or neo‐plasms [7]. These indeterminate results put the patientand the surgeon in a treatment dilemma. Therefore, thedevelopment of other preoperative diagnostic techniquesfor such cases can prevent unnecessary diagnosticsurgery.

Endocrine Journal Advance Publication Endocrine Journal Advance Publication

The thyroid gland, owing to its superficial location, iseasily accessible via several diagnostic methods such asscintigraphy, ultrasound, thermography, and FNAB [8].Thermography is a noninvasive, non-contact system forrecording body temperature by measuring the infraredradiation emitted by the body surface. Typically, the thy‐roid does not appear on the thermogram. However, thethyroid gland is a superficial gland that emits heat easilydetectable through the skin when it presents nodular ordiffuse hypermetabolism [9].

Thermography can detect changes in temperature gen‐erated by malignant tumors, since the malignant tumorsrequire nutrients during growth, resulting in the develop‐ment of new blood vessels. This process, known asangiogenesis, leads to an increase in blood supply [10,11]. An increased metabolic rate and angiogenesis intumors can cause an increase in local temperature. Inaddition, the increased levels of nitric oxide producedowing to the proliferation of malignant cells results inlocal vasodilation, subsequently leading to heat emission[12].

As the thyroid is a superficial gland [8] and malignanttumors have a higher temperature than the surroundingarea [12], the use of thermography may help in the detec‐tion of these tumors.

The objective of the current study was to compare thetemperatures of benign and malignant TNs by using ther‐mography.

Materials and Methods

Study designThis was a cross-sectional study conducted at a public

university hospital.

Study populationThe patients were recruited from the Endocrinology and

Surgery outpatient clinics of the Hospital UniversitárioAntônio Pedro, Universidade Federal Fluminense,between November 2016 and February 2020. A total of128 patients were recruited and 113 were included in thestudy. Of the patients included, 34 contributed with morethan one nodule, since they met the inclusion criteria ofthe study. Accordingly, sampling was performed, inwhich pairing was done according to the proportion ofmalignant and benign nodules in the population. Thesample was divided into two groups: malignant nodules(n = 27) and benign nodules (n = 120). See Fig. 1.

Patients of either sex were included if they were aged≥18 years and showed the presence of ≥1 TN with a size≥10 mm and a TSH within the normal reference range.Patients with fever and active inflammatory/infectiousprocesses in the cervical region were excluded. In addi‐tion, patients with nodules >4 cm or nodules with a highsuspicion of malignancy according to the American Thy‐roid Association (ATA) criteria were included only ifthey presented two FNAB with Bethesda Category IIresult [7].

Patients were included after signing an informed consentform. The study was approved by the Research EthicsCommittee of the Universidade Federal Fluminense(CAAE, registered at Brazilian Ministry of Health underproject number 57078516.8.0000.5243).

MethodsAfter being included in the study, all the patients

underwent clinical and laboratory evaluations and cervi‐cal ultrasound, FNAB, and thyroid thermography. Whenpatients showed surgical indications, they were referredfor surgery.

Fig. 1 Flowchart showing the selection of study participantsATA, American Thyroid Association; FNAB, Fine needle aspiration biopsy

2 Damião et al.


Thyroid nodules were classified as benign or malig‐nant according to the cytopathological results obtainedon FNAB (for benign nodules) and by the histopatholo‐gical result (for malignant nodules). The nodules wereclassified according to the Bethesda System [7]. Thosewith Category II results were allocated to the benignnodule group. Nodules treated with surgery and with hi‐stopathological results of malignancy were allocated tothe malignant nodule group.

Patient data selected for analysis were sex, age,thyroid stimulating hormone (TSH) values, history ofhead and neck irradiation, thyroid antibodies (anti-thyroperoxidase and anti-thyroglobulin), ultrasono‐graphic characteristics of TNs such as nodule size (small,<2 cm, medium, 2–4 cm, and large, >4 cm), Chammasclassification on Doppler ultrasonography [13], FNABresult of TNs by the Bethesda classification and histopa‐thological results of TNs.

Thermographic imagingThe thermographic images were obtained using a

FLIR Thermal Camera SC 620 [14]. The sensitivity ofthe camera is <0.04°C, and the images had dimensions of640 × 480 pixels.

Images were acquired by the following protocol. Ini‐tially, the physical conditions of the environment wereassessed; the temperature in the examination roomshould be maintained between 21°C and 25°C, and thereshould be no heat source close to the procedure area.Doors and windows should be closed during the exami‐nation to avoid uncontrolled airflow in the room. In addi‐tion, there should be no objects that generate any thermalinterference. Then, the parameters of the thermographiccamera were configured: the camera should be posi‐tioned on the tripod and then turned on, waiting 10minutes for its calibration. The following parameterswere set before the procedure: emissivity (fixed valueequal to 0.98 due to the emissivity of human skin), objecttemperature (axillary temperature of the patient mea‐sured with a digital thermometer), distance from thepatient (about 0.6 meters, depending on the width andlength of the patient’s neck), atmospheric temperature,and relative humidity (measured with the thermo-hygrometer). Recommendations were provided to thepatient: should not eat or drink in the last 30 minutesbefore the procedure, and should not have makeup,cream, perfumes, ointments, or any substance in the neckarea. In addition, the patient was asked to remove ear‐rings and any adornment on the neck before the exami‐nation. The neck area and upper chest should beexposed. Finally, the patient should remain seated in theexamination room for 10 minutes before the procedure toachieve thermal balance.

For capturing thyroid images with thermography, thefollowing steps were performed: after measuring thepatient’s axillary temperature and checking the ambienttemperature and humidity, these parameters were enteredin the camera software. The patient was asked to sit in achair in front of the camera, with the head tilted back andresting on the head support. The examiner combined thecenter of the Camera System Box tool with the promi‐nence of the larynx and checked whether the area ofinterest was in the center of the screen and the camerawas parallel to the patient. The patient’s neck area wascooled evenly with a flow of air from a ventilator untilthe temperature indicated by the toolbox reached 31.5°C.The camera was configured to capture an image every 15seconds for 5 minutes, resulting in a total of 20 images.The patient was asked not to move during the procedure.

After obtaining the thermographic images, the locationof the nodule in the images was performed with informa‐tion from the thyroid ultrasound.

Subsequently, a temperature variation in 30 points wasanalyzed in the region of interest. A total of 15 of themwere chosen randomly from healthy regions of the neck(anterior cervical) symmetrically opposite to the noduleand the other 15 were chosen randomly from the regionsidentified as the nodule (Fig. 2). The images were ana‐lyzed temporally considering their initial temperature (It)[nodule and healthy region] in image 1, the medium tem‐perature (Mt) [nodule and healthy region] in image 10,and final temperature (Ft) [nodule and healthy region] inimage 20.

Statistical analysisFor a test power of 80%, 147 TNs were selected, of

which 120 were benign and 27 were malignant. Quanti‐tative data were expressed as the median with interquar‐tile range (IQR), and qualitative data were expressed asthe percentage. The age, TSH level, temperature parame‐ters, nodule size, and Chammas classification were com‐pared between patients with malignant and benignnodules by using the Mann-Whitney test. The same testwas used to compare the temperature parameters of thenodules according to sex. Categorical variables werecompared using the chi-square or Fisher’s exact test.Using the Spearman correlation test, the associationbetween the size of the nodule, age, TSH level and thetemperature parameters were analyzed. The ROC curvewas used to assess the sensitivity and specificity of thetemperature delta. The level of significance was set at0.05. All data were analyzed using IBM SPSS Statisticssoftware version 20.0 (SPSS, Inc. Chicago, IL, USA).

Thermography and thyroid nodules 3


Results

Participant characteristicsA total of 113 patients were included, and 147 nodules

were analyzed (120 benign TNs and 27 malignant TNs);most of the participants in both the groups were female(95.8% vs. 70.4%), with no history of radiation (0% vs.0%) and nodules <4 cm (100% vs. 85.1%). Only thegroup of malignant nodules had large nodules (>4 cm).

The patients were younger in the malignant nodulegroup (41 years vs. 58 years, p < 0.0001), had higherTSH values (2.376 mU/L vs. 1.488 mU/L, p < 0.0001),and had a higher Chammas classification (3–4 vs. 2–3, p< 0.0001). There was a trend towards a higher frequencyof thyroid antibodies (anti-thyroperoxidase and anti-thyroglobulin) positivity in the malignant group of TNwhen compared with the benign group (22.2% vs. 9.16%,p = 0.0885). On the other hand, there was a trendtowards a higher frequency of the cyst component in thegroup of benign nodules (18.3% vs. 3.7%, p = 0.059).The characteristics of the participants in the benign andmalignant TN groups are shown in Table 1.

Among the malignant nodules, the histological types

Fig. 2 Thermography of the anterior cervical region of a patientwith a thyroid nodule. Marking of 15 points within thenodule (a) and 15 points in the healthy region of the neck(anterior cervical) symmetrically opposite the nodule (b)

were papillary carcinoma (PTC) in 19 cases (70.4%), fol‐licular carcinoma (FTC) in 5 cases (18.5%), and medul‐lary carcinoma in 3 cases (11.1%).

Temperature analysisThe It was higher in the benign nodule group than in

the malignant nodule group; however, the Mt, Ft, andtemperature delta (ΔT) were higher in the malignantnodule group (Fig. 3). The It, Mt and Ft of the healthyregion were higher in the benign group than in the malig‐nant group.

The ΔT of the nodule divided by the ΔT of the healthyregion as well as the ΔT of the nodule minus the ΔT ofthe healthy region and the nodule Ft minus the Ft of thehealthy region were higher in the malignant nodulegroup. The comparison of the temperatures of the benignand malignant nodule groups is shown in Table 2.

When separating the benign and malignant nodulesaccording to size categories (<2 cm, 2–4 cm and >4 cm),the differences in the temperature parameters found inthe comparison of the whole group of benign and malig‐nant TN persisted (Table 3). However, analyzing thebenign and the malignant group of TN, no significantcorrelation was found between the size of the nodulesand the temperature parameters. Specifically, no correla‐tion was found between the size of the nodules and It (rs

= 0.00008, p = 0.924), Mt (rs = 0.050, p = 0.289), Ft (rs =0.053, p = 0.211), ΔT nodule (rs = 0.054, p = 0.236), ΔTnodule/ΔT healthy (rs = 0.040, p = 0.282), ΔT nodule -ΔT healthy (rs = 0.048, p = 0.241), It nodule - It healthy(rs = 0.001, p = 0.982) and Ft nodule - Ft healthy (rs =0.062, p = 0.143).

Although there were significant differences in age,sex, and TSH values between the benign and malignantgroups, no correlation was found between age, TSH val‐ues and temperature parameters. Specifically, no correla‐tion was found between age and It (rs = 0.009, p =0.051), Mt (rs = 0.060, p = 0.053), Ft (rs = 0.077, p =0.062), ΔT nodule (rs = 0.127, p = 0.068), ΔT nodule/ΔThealthy (rs = 0.032, p = 0.151), ΔT nodule - ΔT healthyΔ (rs = 0.067, p = 0.063), It nodule - It healthy (rs =0.003, p = 0.311), Ft nodule - Ft healthy (rs = 0.093, p =0.077). Also, no correlation was found between TSH andIt (rs = 0.002, p = 0.637), Mt (rs = 0.045, p = 0.064), Ft(rs = 0.080, p = 0.081), ΔT nodule (rs = 0.069, p =0.071), ΔT nodule/ΔT healthy (rs = 0.060, p = 0.078), ΔTnodule - ΔT healthy (rs = 0.076, p = 0.091), It nodule - Ithealthy (rs = 0.025, p = 0.147) and Ft nodule - Ft healthy(rS = 0.031, p = 0.063). Finally, no difference in the tem‐perature parameters was found when comparing femalesand males, respectively: It (31.21 vs. 31.27, p = 0.621),Mt (33.43 vs. 33.98, p = 0.106), Ft (33.97 vs. 34.37, p =0.066), ΔT nodule (2.86 vs. 3.22, p = 0.163); ΔT nodule/

4 Damião et al.


ΔT healthy (1.57 vs. 1.57 p = 0.856); ΔT nodule - ΔThealthy (1.09 vs. 1.14, p = 0.621); It nodule - It healthy(0.61 vs. 0.88, p = 0.075) and Ft nodule - Ft healthy(1.70 vs. 2.02, p = 0.067).

Since it is known that FTC has more blood flow thanPTC [15], we compared the temperature parameters ofthe malignant nodules according to the histological typePTC and FTC, and no significant difference was observed.

A ROC curve analysis of ΔT was performed. Theresults demonstrate a statistically significant curve (AUC= 0.967, EP = 0.026; p < 0.0001; 95% CI = 0.916–1,000), and evaluating the coordinates of the ROCCurve, it was noted that the cutoff point that maximizedspecificity and sensitivity was the ΔT of 2.38°C, withsensitivity of 0.963 and specificity of 0.992. Thus, theΔT had a greater capacity to correctly classify those whohad a benign nodule (99.2% of cases) when compared tothose who had a malignant nodule (96.3% of cases). Inaddition, it was noted that the positive predictive valuewas 0.963 and the negative predictive value was 0.992(Fig. 4).

Discussion

In the current study, the malignant nodules had ahigher temperature during the thermografic evaluation.In addition, the ΔT, the ΔT of the nodule divided by theΔT of the healthy region, as well as the ΔT of the noduleminus the ΔT of the healthy region and the Ft nodule

minus the Ft of the healthy region, were higher in themalignant nodule group. The ROC curve analysis of ΔTdemonstrated a cutoff point of 2.38°C, with a sensitivityof 0.963 and specificity of 0.992.

The patients were younger in the malignant nodulegroup than in the benign nodule group (41 years vs. 58years, p < 0.0001). This characteristic is in line with datafrom the literature, such as the study by Lim H et al.(2017) that demonstrated that the median age at diagno‐sis of thyroid cancer was 47 years [16]. In addition, the

Fig. 3 Initial temperature (It), medium temperature (Mt), andfinal temperature (Ft) of the nodules in the benign andmalignant groups

Table 1 Patients’ characteristics in the benign and malignant group of thyroid nodules

Characteristic Benign nodule group(n = 120)

Malignant nodule group(n = 27) p-value

Age (years) 58 (53–64) 41 (35–60) 0.0001**

Sex Female, n (%) 115 (95.8%) 19 (70.4%)

0.0001* Male, n (%) 5 (4.2%) 8 (26.6%)

TSH (mU/L) 1.488 (1.00–2.00) 2.376 (2.00–3.00) 0.0001**

Nodule size (cm) 2.00 (1.5–2.8) 2.00 (1.5–3.2) 0.242

Size classification Small, n (%) 60 (50.0%) 11 (40.7%) Medium, n (%) 60 (50.0%) 12 (44.4%) 0.0001* Large, n (%) 0 4 (14.9%)

Chammas classification 2 (2–3) 3 (3–4) 0.0001**

Positive Antibodies(Anti Thyroperoxidase and AntiThyroglobulin), n (%)

11 (9.16%) 6 (22.2%) 0.0885*

The data are expressed as the median (with interquartile range) for continuous variables and as apercentage for categorical variables (IQR: interquartile range; * p < 0.05 [chi-squared test); ** p <0.05 [Mann-Whitney test]).IQR, interquartile range; TSH, thyroid stimulating hormone



TSH values were higher in the malignant nodule groupthan in the benign nodule group, although the valueswere within the normal range (2.376 mU/L vs. 1.488mU/L, p < 0.0001). Several studies have shown a directcorrelation between serum TSH levels and the risk ofmalignancy of TNs, possibly because TSH stimulatescell proliferation [17-19].

The assessment of intranodular vascularization usingDoppler ultrasonography, by the Chammas classification,demonstrated greater central vascularization in malignantnodules (3–4 vs. 2–3, p < 0.0001), which is in agreementwith data that intranodular vascularization was correlatedwith thyroid malignancy [13, 20].

Regarding the size of the nodules, only the malignantnodule group presented with nodules >4 cm, possiblyindicating the relationship between the nodule size andthe malignancy risk [21]. The histological types observedin our study were papillary (70.4%), follicular (18.5%),and medullary tumors (11.1%), which is in agreementwith the literature [22, 23].

The current study analyzed the use of thermographyfor 27 malignant nodules and 120 benign nodules todetermine whether thermography can be used as an addi‐tional tool for the investigation of TNs, especially thedetection of malignant nodules.

Thermography is a technique in which the temperatureof distant objects without physical contact, by capturinginfrared radiation in the electromagnetic spectrum viathermographic cameras, wherein the radiated energy ofthe object is captured by the camera and later convertedinto temperature values [24].

The analysis of the thermograms showed that the Mt(33.46°C vs. 33.01°C, p < 0.0001), Ft (33.99°C vs.33.38°C, p < 0.0001), and ΔT (2.95°C vs. 1.73°C, p <0.0001) were higher in the malignant nodule group thanin the benign nodule group. Only the It was lower in themalignant nodule group than in the benign nodule group(31.22°C vs. 31.68°C, p < 0.0001). These differencesbetween the Mt, Ft, and ΔT, with higher values amongmalignant nodules, suggest that malignant nodules emitmore heat than benign nodules do.

Angiogenic conversion is a fundamental component ofprimary tumor growth, i.e., the tumor’s ability to pro‐mote the formation of new capillaries from preexistingblood vessels. The pattern of vascular formation inmalignant tumors is anomalous: the vessels are tortuous,dilated, permeable, and branched in various configura‐tions [10, 11]. Owing to increased blood flow, malignanttumors may have a higher temperature than the surround‐ing region [12, 25]; this temperature difference could becaptured via thermography and used to differentiatebetween benign and malignant TNs.

The tendency of a higher frequency of thyroid anti‐bodies (anti-thyroperoxidase and anti-thyroglobulin) pos‐itivity in the malignant group of TN suggests that there isa greater number of patients with autoimmune thyroiditis(AT) in this group. Since vascularization of the thyroidgland may decrease in the later stages of AT [26], thismay explain the lower temperature in the healthy region(It, Mt and Ft) found in this group compared to the groupof benign TN.

On comparing the size of the nodules and the tempera‐

Table 2 Comparison of the temperature parameters between benign and malignant nodules

Benign nodule group (n = 120) Malignant nodule group (n = 27) p-value

It nodule (°C) 31.68 (31.36–31.95) 31.22 (30.96–31.53) 0.0001*

Mt nodule (°C) 33.01 (32.56–33.23) 33.46 (33.09–33.93) 0.0001*

Ft nodule (°C) 33.38 (33.11–33.64) 33.99 (33.90–34.48) 0.0001*

ΔT nodule (°C) 1.73 (1.50–1.91) 2.95 (2.74–3.24) 0.0001*

It healthy (°C) 30.79 (30.51–31.22) 30.52 (29.95–30.88) 0.008*

Mt healthy (°C) 32.38 (31.98–32.75) 32.06 (31.74–32.15) 0.007*

Ft healthy (°) 32.90 (32.45–31.14) 32.38 (32.16–32.60) 0.0001*

ΔT healthy (°C) 2.00 (1.66–2.14) 1.94 (1.59–2.22) 0.542

ΔT nodule/ΔT healthy (°C) 0.90 (0.79–1.01) 1.57 (1.46–1.77) 0.0001*

ΔT nodule–ΔT healthy (°C) –0.195 (–0.41–0.02) 1.11 (0.97–1.28) 0.0001*

It nodule–It healthy (°C) 0.78 (0.55–1.04) 0.63 (0.51–0.95) 0.305

Ft nodule–Ft healthy (°C) 0.59 (0.33–0.84) 1.83 (1.59–0.47) 0.0001*

The data are expressed as the median (with interquartile range) for continuous variables. Initial temperature; Ft, finaltemperature; Mt, medium temperature; ΔT, temperature delta* p < 0.05 (Mann-Whitney test).

6 Damião et al.


Table 3 Comparison of the temperature parameters between benign and malignant nodules,according to the size categories of the thyroid nodules

<2 cm Benign (n = 60) Malignant (n = 11) p-value

It nodule (°C) 31.66 (31.44–31.93) 31.20 (30.78–31.27) 0.0001*

Mt nodule (°C) 33.00 (32.59–33.26) 33.23 (32.87–33.45) 0.062

Ft nodule (°C) 33.38 (33.14–33.58) 33.95 (33.88–33.99) 0.0001*

ΔT nodule (°C) 1.68 (1.41–1.90) 2.77 (2.70–3.33) 0.0001*

It healthy (°C) 30.77 (30.51–31.17) 30.52 (29.90–30.71) 0.032*

Mt healthy (°C) 32.33 (32.03–32.70) 32.06 (31.73–32.15) 0.075

Ft healthy (°C) 32.85 (32.50–33.08) 32.30 (32.01–32.46) 0.018*

ΔT healthy (°C) 2.01 (1.55–2.14) 1.86 (1.80–2.21) 0.539





2–4 cm Benign (n = 60) Malignant (n = 12) p-value

It nodule (°C) 31.71 (31.26–31.96) 31.20 (30.81–31.51) 0.009*

Mt nodule (°C) 33.02 (32.54–33.32) 33.59 (33.15–34.01) 0.001*

Ft nodule (°C) 33.38 (33.08–33.72) 34.17 (33.89–34.49) 0.0001*

ΔT nodule (°C) 1.78 (1.53–1.93) 3.01 (2.81–3.22) 0.0001*

It healthy (°C) 30.80 (30.55–31.35) 30.61 (29.91–30.88) 0.047*

Mt healthy (°C) 32.46 (31.92–32.81) 32.03 (31.71–32.11) 0.013*

Ft healthy (°C) 32.92 (32.35–33.17) 32.32 (32.16–32.54) 0.004*

ΔT healthy (°C) 1.97 (1.71–2.13) 1.77 (1.56–2.23) 0.934





>4 cm Benign (n = 0) Malignant (n = 4) p-value

It nodule (°C) — 31.55 (34.45–32.06) —

Mt nodule (°C) — 34.05 (33.85–34.65) —

Ft nodule (°C) — 34.69 (34.44–35.06) —

ΔT nodule (°C) — 2.90 (2.72–3.51) —

It healthy (°C) — 30.83 (30.41–31.32) —

Mt healthy (°C) — 32.51 (32.16–32.77) —

Ft healthy (°C) — 32.75 (32.60–32.98) —

ΔT healthy (°C) — 1.97 (1.61–2.20) —

ΔT nodule/ΔT healthy (°C) — 1.57 (1.46–1.75) —

ΔT nodule–ΔT healthy (°C) — 1.09 (0.90–1.36) —

It nodule–It healthy (°C) — 0.85 (0.61–1.05) —

Ft nodule–Ft healthy (°C) — 1.94 (1.53–2.39) —

The data are expressed as the median (with interquartile range) for continuous variables. Initialtemperature; Ft, final temperature; Mt, medium temperature; ΔT, temperature delta* p < 0.05 (Mann-Whitney test).



ture parameters, both in the benign and malignant TNs,there was no significant correlation between the size ofthe nodules and the temperature parameters. A probableexplanation that may justify this finding is the presenceof cystic areas, that have no vascularization. This mayhave contributed to the absence of temperature differenceconsidering the size of the TNs [27]. Nonetheless, therewas no significant difference in the frequency of cysticcomponent when comparing benign and malignant TNgroups.

Among all the thermographic parameters analyzed, theΔT stood out and the ROC curve analysis demonstrated acutoff point of 2.38°C, with a sensitivity of 0.963 andspecificity of 0.992. Thus, the temperature delta could bea parameter with clinical applicability in the differentia‐tion between benign and malignant TN.

Our results, which demonstrated a temperature differ‐ence between malignant and benign nodules, are in linewith the findings of previous studies. In 1972, Samuelsreported that, of the 3 nodules with a histological diagno‐sis of malignancy, 2 were “hot” on thermography; how‐ever, the temperature of these tumors was not described[28]. In 1974, Galli et al. reported 6 cases of histologi‐cally confirmed malignant tumors that demonstrated anevidently increased temperature on the thermogram, withvalues close to those recorded for hyperthyroidism; how‐ever, the temperature was not reported [29]. In a study byKamardin et al., 201 patients with thyroid pathologiesand surgical indications underwent thermography, and

Fig. 4 The ROC curve of the nodule ΔT

the correct diagnosis was made in 59 of the 66 patientswith thyroid carcinoma; however, the parameter used forthermographic differentiation of the nodules was notclear [30]. Another study by D’Arbo et al. in 1988 evalu‐ated the usefulness of thermography for the selection ofTNs for surgery. A difference of 0.9°C was observed onthe thermograms between benign and malignant lesionsof the thyroid [31]. More recently, Aweda et al. evalu‐ated 37 patients with thyroid disease and 16 healthy vol‐unteers. A significant difference was observed in thetemperatures of the malignant nodules (37.63 ± 0.29°C)compared to healthy patients (36.21 ± 0.73°C), althoughthe thermographic parameters were not described again[32].

A limitation of this study was that the thickening ofthe neck fat layer was not evaluated. The surface temper‐ature of the cervical region may be associated with thethickness of the fat layer owing to the thermal insulationeffect of the adipose tissue [33].

Conclusions

The findings of the current study showed thatmalignant nodules have higher temperature than benignnodules on thermographic evaluation. These findingsdemonstrate that thermography could be a useful tool forthe investigation of malignant TNs. However, furtherstudies are needed to prove the effectiveness of thermo‐graphy for the investigation of these nodules.

Declarations

Author disclosure statementNone of the authors have any potential conflicts of

interest associated with this research.

Financial supportThis study was financed in part by the Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior - Brasil(CAPES). This was not an industry-supported study.

Authors’ contributionsCAPF, MANS, AC, RACF and GABL: Conception or

design of the work. CPD, JRGM, MBHM, MEOMSC,CGF, IBB, CF, MFOR and AP: Data collection. CPD,JRGM, AC, RACF and GABL: Data analysis and inter‐pretation. CPD: Drafting the article. RACF and GABL:critical revision of the article. All the authors providedFinal approval of the version to be published.

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