Introduction
Recently, at the 44th Annual Meeting of the European Thyroid Association (ETA2021), Professor Laszlo Hegedüs from the Department of Endocrinology of the University Hospital of Odense in Denmark and Professor Carla Gambale from the Department of Endocrinology of the University Hospital of Pisa, Italy, made wonderful speeches on "The Application of Ultrasound in the Treatment of Thyroid Diseases".
From redundant to indispensable? Forty years after sound became an image
The origin of ultrasound
Professor Laszlo Hegedüs first introduced the origins of ultrasound. Until the mid-1960s, thyroid disease was diagnosed primarily by palpation, X-rays, and iodine isotope scintillation scans. In the mid-1960s, clinicians first performed ultrasound tomographies of patients, using echoes (black and white) to show anatomy. Ultrasonic (US) grayscale technology emerged in the mid-1970s, providing better resolution.
Physiological knowledge of the normal thyroid gland
Thyroid volume increases with weight (lean body mass), and due to weight differences, the thyroid gland in men is usually larger than in women. Thyroid volume is affected by the seasons, with winter being larger than summer (about 25%).
Use of ultrasound in thyroid diseases
Ultrasound is often used for morphological evaluation of thyroid disease to diagnose goiter. Professor Laszlo Hegedüs stressed that attention should be paid to observer bias when ultrasound assessment and false positive or false negative results should be avoided. Ultrasound-guided fine needle aspiration (FNA) histological biopsy can be used to distinguish benign and malignant thyroid nodules. In addition, ultrasound is the basis of the grading standard of thyroid imaging reporting and data system (TIRADS), and there are currently six types of TIRADS: Kwak TIRADS (Kwak-TIRADS), European TIRADS (EU-TIRADS), South Korea TIRADS (K-TIRADS), American Radiological Association TIRADS (ACR-TIRADS), American Thyroid Association TIRADS (ATA-TIRADS), China TIRADS (C-TIRADS). Due to the criteria used by clinicians across countries, changes in the same shape, edge, echo, and calcification are not consistent in terms of TIRADS scores, which in turn may affect the probability of FNA in patients. Professor Laszlo Hegedüs spoke of the suspicious US characteristics defined by EU-TIRADS as being less common in follicular thyroid cancer (FTCs) than thyroid papillary carcinomas (PTCs) and medullary thyroid cancers (MTCs).
Figure 1 Crude incidence and age-adjusted [IR(W)] incidence of papillary microcarcinomas in Denmark, 1996-2008.
The future of thyroid ultrasound therapy
Professor Laszlo Hegedüs pointed out that the future application of ultrasound to the diagnosis and treatment of thyroid diseases first needs to improve its resolution and availability, reduce costs, and combine new radiofrequency fusion technology with other departments (such as radiology, oncology, surgery/OTOL).
summary
Finally, Professor Laszlo Hegedüs concluded that the use of ultrasound has given us an in-depth understanding of physiology, improved phenotypic classification, enabled doctors to make tissue diagnosis, facilitated doctor-patient communication, and strengthened guided interventions for disease diagnosis, which is a prerequisite for a variety of non-surgical treatment options and a priority measure for the diagnosis of many diseases. At the same time, ultrasound also has some shortcomings, such as TIRADS is not uniformly defined, limited by time and economy, affected by observer bias, limited technology, etc.
The role of ultrasound features and risk stratification systems in the identification of medullary thyroid cancer
At the conference, Professor Carla Gambale gave a wonderful speech on the topic of "The Role of Ultrasonic Features and Hazard Layering Systems in Identifying MTC".
Previously, some scientific associations developed the Ultrasound (US) Risk Stratification System (RSS) to guide the examination of thyroid nodules to determine which nodules should undergo fine needle aspiration cytology (FNAC). For example, "European Thyroid Association Guidelines for Risk Grading of Adult Thyroid Nodule Ultrasound Malignancies: EU-TIRADS", "2015 American Thyroid Association Guidelines for the Management of Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer", "ACR Thyroid Imaging, Reporting and Data System (TI-RADS): ACR TI-RADS Committee White Paper", "Ultrasound Diagnosis and Imaging-Based Treatment of Thyroid Nodules: Revised Consensus Statement and Recommendations of the Korean Thyroid Radiology Society". However, these systems were developed for PTC, and there is little data on their role in identifying MTC. Therefore, Professor Carla Gambale's team studied the role of ultrasound signatures and hazard stratification systems in identifying MTC.
Introduction to previous studies
Professor Carla Gambale began with a brief introduction to previous research. The study of Valderrabano P et al. showed that the ultrasonic features proposed by ATA worked well in MTC and had good consistency among observers. Studies by Wolinski K et al. have shown that ultrasound signatures, often used as markers of malignancy, can also be used to diagnose MTC. However, patients with MTC tend to be more likely to have suspicious US features than patients with PTC. Lee S et al. show that MTC and PTC may have overlapping ultrasound features of malignancies, and currently accepted ultrasound criteria are available for MTC diagnosis, but MTC tends to be larger and inherently more cystic, and in this series of studies, uniform echo structures in the solid part are more common.
Research design
Professor Carla Gambale then introduced his team's research. The study, which began in January 2014 and ended in September 2020, included a total of 152 patients with sporadic or hereditary MTC, collected preoperative neck ultrasound findings from all patients, and was designed to characterize ultrasound of MTC and evaluate the performance of RSS in recognizing MTC. The average age of the 152 MTC patients was 53 years old, of which 53.3% were women and 46.7% were men. Ret gene mutations occurred in 17.1% of patients.
Research results
The researchers counted the thyroid ultrasound characteristics of 152 patients, and the results showed that most of the nodules were solid components, low echo, and marginal regularity. About half of them showed calcifications, and only one subgroup had microcalcifications. A few nodules are "taller than wide". Only 7.9% of MTC had at least four simultaneous ultrasound features suggestive of malignancy. Specific data as shown in Table 1, thyroid nodule diameter between 1.1-2 is the highest, accounting for 35.5%. Of the 152 patients, 57.9% were polynodal. Solid thyroid nodules account for 92.8%, mixed nodules account for 6.6%, and thyroid cystic nodules account for only 0.7%. Thyroid nodules accounted for 0.7% of echoless, slightly low-echo nodules accounted for 53.9%, pronounced echo nodules accounted for 29%, and isoelic nodules accounted for 16.4%. 67.1% of patients had clear thyroid nodule boundaries and 27.6% had visible halo rings. Thyroid nodules are accompanied by calcifications accounted for 55.3%, of which large calcification of thyroid nodules accounted for 13.1%, peri-thyroid nodule calcifications accounted for 2.4%, thyroid nodules small calcifications accounted for 32.1%, and visible punctate strong echoes in thyroid nodules accounted for 52.4%. Thyroid nodules account for 44.7% without calcification. Thyroid nodules are "taller than wide" in 10.5%.
Table 1 Ultrasound characteristics statistics of the test group
Overall, of the 152 patients, 80.9% had solid thyroid nodules with low echoes, and the remaining 19.1%; 30.3% were solid thyroid nodules with low echo and irregular margins, and the rest accounted for 69.7%,7% were solid thyroid nodules with low echo, edge irregularities, and small calcifications, and the rest accounted for 92.1%. Professor Carla Gambale then showed us ultrasound images of several thyroid nodules.
Fig. 2 Ultrasound images of several thyroid nodules
The researchers also graded the patient's thyroid nodules according to the grading criteria of different thyroid imaging reports and data systems. According to 5 RSS, the risk of ultrasound hyper-malignancy in MTC ranged from 45.4% to 47.4%, indicating that only 48.7% to 63.8% of all MTC required FNAC. Graded according to ATA-TIRADS 2015, benign nodules accounted for 0.7%, very low suspicious malignant nodules accounted for 3.3%, low-degree suspicious malignant nodules accounted for 7.9%, moderately suspicious malignant nodules accounted for 40.8%, and highly suspicious malignant nodules accounted for 47.4%. The results of other grading systems are shown in Table 2.
Table 2 Malignant tumor risk (ROM) results determined according to different grading criteria
Thyroid nodule scores with the same ultrasound features are inconsistent due to different criteria for doctors from country to country, which may affect subsequent treatment. According to EU-TIRADS, FNAC is required in 50% of patients. According to ATA 2015, 61.8% of patients require FNAC. According to AACE/ACE-AME, 48.7% of patients require FNAC. According to ACR-TIRADS, FNAC was required in 48.7% of patients. According to K-TIRADS, 63.8% of patients required FANC.
Finally, Professor Carla Gambale summarized and found that neither a single ultrasound feature nor multiple ultrasound features are unique to MTC. Less than 50% of MTC is correctly identified by RSS. According to existing RSS, about half of MTC patients do not need to undergo FNAC. It is suggested that ultrasound in conjunction with other diagnostic tools is necessary to avoid clinical missed diagnosis and delayed treatment.