Patients undergoing endocrine consultation and first diagnosis of nodular disease: Indications of thyroid ultrasound and completeness of ultrasound reports

To evaluate reasons for performing ultrasonography (US) and completeness of US reports in patients undergoing endocrine consultation with the first diagnosis of nodular disease. Since January 1 to June 30, 2021, we prospectively collected patient data (age and thyroid-stimulating hormone concentrations), reasons for performing thyroid US, and completeness of reports regarding the description of the thyroid gland and nodules. In the case of multiple nodules, we considered the nodule suspected of malignancy and the largest one. To evaluate the accuracy of thyroid nodule description, we referred to the five characteristics suggested by the ACR TI-RADS system. A total of 341 patients with thyroid nodules received endocrine consultation (female, 78%). The most frequent reasons for performing thyroid US were unrelated to a suspected thyroid disease (31.7%), followed by incidentaloma (23.5%), dysfunction or positivity for thyroid antibodies (19.1%), symptomatic or visible nodules (17.6%), and family history of any thyroid disease (8.2%). Gland texture was not reported in 41.9%. The depth of the lobes was the dimension reported most frequently (42.2%), but any diameter was not reported in 57.8% of the cases. As regards the description of the most relevant nodule, length was reported more frequently (75.9%). Margins and echogenicity were more frequently described (54.5% and 44.3%, respectively) than other characteristics (composition: 27%; shape: 8.8%; echogenic foci: 6.7%). No reports had indicated the malignancy risk stratification. The results of the study demonstrate that in patients undergoing endocrine consultation with first detected thyroid nodules, US was mostly performed in asymptomatic cases, US reports were incomplete, and no risk stratification system was reported.


Introduction
Thyroid disease represents the most relevant part of endocrine clinical practice, and among thyroid diseases, a nodular disease is more common. Historical studies have shown that the prevalence of a nodular disease is significantly greater when detected by ultrasound (US) (up to approximately 50%) than by palpation (about 5%), palpation may detect nodules of at least 10 mm, and palpable solitary nodules are associated with the presence of other nodules in 50% of the cases [1][2][3]. More recent studies have shown that the frequency of nodules increases with aging and such an increase is more marked in women than in men [4][5][6]. Indeed, the widespread use of thyroid US has led to an epidemic of thyroid nodules and contributed to an expanded detection of nonpalpable nodules [7]. Another contributing factor to this expanding pool of thyroid nodules is the incidental detection of nodules via computed tomography, magnetic resonance imaging, and positron emission tomography. For instance, studies have reported that thyroid incidentalomas detected by CT accounted for 5-17% of the cases [8][9][10][11][12].
The increasing use of imaging has also induced an increased demand for consultations, fine-needle aspiration (FNA), and surgical procedures [13]. Consequently, the diagnosis of thyroid cancer has progressively increased, which is mostly attributable to microcarcinomas [14][15][16]. However, this unintended screening, rather than a planned screening as observed in Korea, did not decrease the mortality rate [16]. The screening program started in Korea in 1999 until 2011, resulted in a cancer prevalence of 64 in 100,000 people; however, the mortality rate remained unchanged, and thyroid cancer was considered the leading cancer type, whereas it is at 11th place in the United States [16,17].
US represents a pivotal point in the diagnostic and therapeutic process of nodular diseases, and one of its main objectives is to avoid unnecessary diagnostic procedures such as FNA with a negligible number of missed cancer. In relation to this objective, critical points must be considered, mainly represented by the use of a shared lexicon, completeness of US report, experience of the operator, and use of classification systems to stratify the risk of malignancy [18][19][20][21]. With this aim, over the years, endocrine and radiologic societies have published guidelines for the proper execution of thyroid US with relative malignancy risk stratification [22][23][24][25][26]. In this setting, real data about the use by radiologists of a proper lexicon, a complete report, and a risk stratification system are scarce [27].
Thus, this study aimed to evaluate in patients undergoing endocrinological consultation with the first detection of a nodular disease (a) the reasons for performing a thyroid US and (b) the completeness of radiologists' reports, specifically the category risk stratification.

Methods
From January 1 to July 30, 2021, we prospectively collected the data of patients who were referred for endocrine consultation at the Division of Endocrinology of "V. Fazzi" Hospital, Lecce (Italy) with first detection of nodular disease by US. The following data were recorded: [1] patients' age and sex, [2] thyroid-stimulating hormone (TSH) concentrations, [3] reason for US, and [4] completeness of the radiologist's US report regarding the description of the thyroid gland and nodules. The radiologists who performed the US could be from the same institution or from another institution, both public or private, and was not aware of the study. In the case of multiple nodules, we considered the nodule suspected of malignancy, and in absence of malignancy, we considered the largest nodule. We choose to evaluate a single and the most relevant nodule, assuming that in case of multiple nodules, the description made by the radiologist could be more accurate for the most relevant nodule or at worst, similar for less relevant nodules in the same patient. To evaluate the accuracy of thyroid nodule description, we referred to the five characteristics suggested by the ACR TI-RADS system [25]. This is an observational study. The "V. Fazzi" Hospital Research Ethics Committee has confirmed that no ethical approval is required. Informed consent was obtained from all the study participants.

Statistics
Statistical analyses were performed using the R package. Fisher's exact test was used to analyze the associations between qualitative variables. Univariate and multivariate analyses were used as appropriate. The level of statistical significance was set at 5%.
The most frequent reason for undergoing thyroid US was unrelated to a truly suspected thyroid disease (e.g., for a socalled "check" without any specific reason or for feeling a neck clamp due to anxiety), followed by incidentalomas, dysfunction or positivity for thyroid antibodies, symptomatic or visible nodules, and family history of any thyroid disease (dysfunction, nodules, cancer) ( Fig. 1).
In all cases, the lymph nodes were described. However, in all patients, the risk malignancy stratification system used was not reported. Endocrine consultation was suggested in 46 (13.5%) and FNA in 14 (4.1%) cases.

Discussion
In this study, the first point to emphasize is the reason for undergoing thyroid US. Approximately 30% of the patients underwent US for reasons unrelated to suspected thyroid disease, and the second most frequent reason is represented by an incidentaloma. A symptomatic or visible nodule accounted just for 17.6% of the evaluated patients. These findings clearly show the effects of the increasing demand for imaging examinations by patients and the widespread use of US, resulting in increased detection of asymptomatic nodules [30]. The low number of patients referred for symptomatic nodules appears to contrast with literature finding a symptomatic nodule in 27%-40% of the cases, clearly indicating that, at least in our area of interest, a relevant nonvoluntary screening is taking place [30,31].
The second point that emerges from the data analysis is the incompleteness of US reports, as in approximately 60% of the cases, no lobe diameter was reported, diameters of three nodules were reported in just 15%, and gland texture was not reported in >40% of the cases.
As regards the characteristics of the nodules, the length is the most frequently reported parameter; however, other characteristics were poorly described. That the risk of  Fig. 1 Reasons for undergoing thyroid ultrasound malignancy is positively associated with nodule size is a controversial issue. Two meta-analyses have reported that the risk of malignancy increased in nodules >3.0 cm (but without distinction between follicular and papillary carcinomas) [32,33]. In the retrospective study by Kamran et al., a lower prevalence of malignancy was found in nodules <2.0 cm; the prevalence of malignancy was greater, but steady in nodules >2.0 cm. This trend was suitable to papillary cancer but not to follicular cancer, in which the malignancy rate increased with size [1.0-1.9 cm, 6%; 2.0-2.9 cm, 7%; 3.0-3.9 cm, 12%; >4 cm, 16% (P < 0.01)] [34]. Moreover, the role of the nodule size appears relevant above all in solid and isoechoic nodules with defined margins and without microcalcifications, which may be typical of follicular adenomas and follicular carcinomas [35]. In this setting, it is reasonable to think that follicular carcinomas, which may not show clear features of malignancy, are subjected to FNA later than papillary carcinomas and that in such cases, size is a relevant factor to consider [36,37]. Structural nodule characteristics, more than the size, are decisive when considering whether a further assessment by FNA is necessary. Indeed, as clearly acknowledged, routine FNA, regardless of the nodule characteristics, turns out inappropriate and increases the need for surgical procedures [38,39]. Well-known literature data showed the importance of nodule characteristics detected by US for malignancy risk stratification [40]. Some characteristics are more associated with benignity, whereas some others with malignancy, but each characteristic taken singularly is never decisive; thus, their combinations have been successfully categorized in several risk stratification systems [22][23][24][25][26]. These risk stratification systems adopting different dimensional thresholds are characterized by nonidentical sensitivity and specificity, but are globally effective in reducing inappropriate FNA while leaving undiagnosed a negligible number of cancers [41][42][43][44][45].
Notwithstanding consistent evidence in the field, nodule characteristics were incompletely described in our cohort, and the use of any of the established risk stratification systems was disregarded. However, at least one Italian study showed that among affiliates of the Italian Society of Radiology and the Italian Society of Ultrasonography, 99.6% claimed familiarity with ACR TI-RADS, and 53.3% reported that ACR TI-RADS was routinely used [46]. Our data are not different from those published in a Canadian study, where <30% indicated a risk stratification, none reported all the five nodules characteristics, less than half reported at least one characteristic, and none gave a clinical suggestion (FNA or follow-up) [27].
All US reports used free text instead of a structured template, which may be a point of consideration, as studies demonstrated that a structured template reduces mistakes, reduces the rate of unnecessary FNA, and increases the malignant/benign cytology ratio [47][48][49].
A potential limitation of the study is that we considered just a single nodule for each patient (the most relevant in terms of malignancy risk or dimension). In making this choice, we assumed that in case of multiple nodules, the description of the most relevant nodule made by the radiologist would have been more accurate than a less relevant nodule, or at worst, similar to that of a less relevant nodule. This assumption is indirectly confirmed by the evidence that the quality of nodules' description, i.e. the number of ACR TI-RADS characteristics is not related with uni-or multinodular goiter in multivariate analysis.
In conclusion, the results of this study demonstrate that in patients undergoing endocrine consultation with the first detection of thyroid nodules, (a) US was mostly performed in asymptomatic cases, and (b) US reports were incomplete and no risk stratification systems were used. Conceivably, the use of a structured template and adoption of a risk stratification system would ameliorate the appropriateness of endocrine consultations, reducing unnecessary FNA and surgical procedures. The observed results are not extensible to other regions. Programs for clinical management of a disease may differ by regions or may be totally absent. However, even considering this point, our data highlight the usefulness of a targeted training for radiologists aiming at the use of a structured/complete report and suggest further investigations rather than follow-up.
Author contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by R.N., G.G. The first draft of the manuscript was written by R.N. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.