Background . medullary thyroid carcinoma (mtc) produces serum markers including calcitonin (ct) and carcinoembryonic antigen (cea). The measurement of ct in fine-needle aspirate washout fluid (FNA-CT) improves the cytological diagnosis of mtc. However, no data are available about cut-off values for FNA-CT using currently immunoassay. The measurement of cea in the needle washout fluid (FNa-cea) in mtc has not been studied. Objective: to assess the diagnostic value and propose cut-off values for FNA-CT and FNacea in the thyroid nodule to diagnose mtc. Material and Methods. We conducted a retrospective analysis of 164 samples of fine-needle aspirate washout fluid collected from 92 patients with thyroid nodules, who underwent FNa followed by cytological examination and measurement of FNA-CT. seventeen cases with mtc and 41 with non-mtc nodules were histologically verified. one hundred and six nodules identified as non-mtc by cytology were not operated on. FNa-cea was additionally studied in 29 samples. The cut-off value was determined by Roc analysis. Results. The FNA-CT level was >2000 pg/ml in all mtc nodules, except for one, in which the FNA-CT level was 638 pg/ml. In non-mtc nodules, the FNA-CT levels were <10 pg/ml and <100 pg/ml in 81 % and 90 %, respectively, however, it was >500 pg/ml in 5 %, and >1000 pg/ml in 2 %. At a cut-off value of 590 pg/ml, the sensitivity and specificity of FNA-CT were 100 % and 96 %, and at a cut-off of 1721 pg/ml, the corresponding values were 94 % and 99 %. The false positive FNA-CT values were 3.7 % and 1.2 % at the cut-off values of 590 pg/ml and 1721 pg/ml, respectively. The median levels of FNa-cea in mtc and non-mtc nodules were 59.3 ng/ml and 1.5 ng/ml, respectively. At a cut-off value of 7.5 ng/ml, the sensitivity of FNa-cea was 86 % and specificity was 100 %. Additional measurement of FNa-cea prevented all false-positive results of FNA-CT, but did not detect 2 mtcs with low FNa-cea levels (false-negative rate of 6.9 %). Among samples with FNA-CT value of >590 pg/ml and negative cytology (n=9), FNa-cea differentiated mtc with 100 % sensitivity and specificity. Conclusion . The maximum sensitivity of FNA-CT in the thyroid nodule was at a cut-off value of 590 pg/ml (100 %), the maximum specificity was at a cut-off value of 1721 pg/ml (99 %). Risk of false positive result is the major challenge of FNA-CT. to reduce false-positive results, we recommend to measure FNa-cea in the nodules with negative cytology and high level of FNA-CT. At a cut-off value of 7.5 ng/ml, FNa-cea allows the false-positive FNA-CT to be excluded.

Определение тиреоглобулина (ТГ) в смыве из пункционной иглы рекомендовано для диагностики метастазов дифференцированного рака щитовидной железы (ДРЩЖ), однако метод не стандартизован и отсутствуют единые рекомендации по пороговому значению, что затрудняет интерпретацию результатов. ЦЕЛЬ: провести анализ ТГ в смыве при пункции образований на шее различной природы и определить оптимальное пороговое значение ТГ в смыве для диагностики метастазов ДРЩЖ. МАТЕРИАЛЫ И МЕТОДЫ: под контролем УЗИ пунктировано 1258 образований на шее у 591 пациента, из которых 566 больных с подтвержденным ДРЩЖ. Игла после пункции промывалась в 1 мл физраствора, в котором затем исследовали концентрацию ТГ. Результат ТГ в смыве сравнивали с гистологическим заключением (n=522) или цитологическим заключением, если операция не проводилась. Пороговое значение ТГ в смыве определено с помощью ROC анализа. РЕЗУЛЬТАТЫ: метастазы ДРЩЖ в лимфоузлы выявлены в 577 пунктатах. В 9 случаях пунктат получен из метастазов рака щитовидной железы (РЩЖ), не экспрессирующего ТГ (недифференцированный РЩЖ, низкодифференцированный РЩЖ, РЩЖ из столбчатых клеток). В 22 случаях - из метастазов других злокачественных новообразований в лимфузлы шеи (рак легкого, яичника, пищевода, опухоль мягких тканей, меланома, нейроэндокринная опухоль). У 6 – другие опухоли шеи (лимфома, аденома паращитовидной железы, невринома). В 26 случаях при пункции получена нормальная тиреоидная ткань, оставшаяся после тиреоидэктомии, в 37 – послеоперационная серома/гранулема, 1 – боковая киста шеи. В 578 пунктатах – гиперплазия лимфоузла, 2 - саркоидоз. Уровень ТГ в смыве из метастаза ДРЩЖ и тиреоидного остатка значимо отличался от образований нетиреоидной природы (p<0,0001). Исключив из ROC анализа пунктаты тиреоидного остатка, AUC=0,975 [95%ДИ 0,966-0,984]. При пороговом значении 7,8 нг/мл чувствительность в диагностике метастазов ДРЩЖ - 94%, специфичность – 95%. При пороговом значении 20 нг/мл чувствительность – 90%, специфичность - 98%. Ложноотрицательные результаты получены при пункции ДРЩЖ с плоскоклеточной метаплазией или малом количестве опухолевых клеток в пунктате. Ложноположительные результаты получены чаще при пункции образований уровня VI и IV по сравнению с другой локализаций (7,6% против 3,6%, p=0,04). Не выявлено различий в количестве ложноположительных результатов у больных до тиреоидэктомии и после тиреоидэктомии (р=0,17), но у больных после тиреоидэктомии с сывороточным уровнем ТГ >200 нг/мл количество ложноположительных результатов ТГ в смыве было значимо выше, чем при меньшем значении сывороточного ТГ (28% vs 3%, р=0,0004). При сравнении информативности цитологии и ТГ в смыве выявлено преимущество ТГ в смыве в диагностике кистозных метастазов, а цитологии – в диагностике микрометастазов и опухолей, не экспрессирующих ТГ. Определение ТГ в смыве повышало чувствительность цитологии на 8%. Совместное применение двух методов выявило метастазы ДРЩЖ у 100%. ВЫВОДЫ: определение ТГ в смыве является полезным дополнением к цитологическому исследованию, повышающее информативность последнего, главным образом, за счет лучшего выявления кистозных метастазов ДРЩЖ. Оптимальным пороговым значением ТГ в смыве предлагается 20 нг/мл, при котором меньшее количество ложноположительных результатов.

Introduction . Measurement of thyroglobulin (Tg) in a washout after fine-needle aspiration (FNA) is recommended for the diagnosis of metastases of differentiated thyroid cancer (DTC), but the method is not standardized and there is no recommended threshold value of Tg washout, which makes it difficult to interpret the results. Aim . To analyze Tg in the washout after FNA of lesions of different origin on the neck and to determine its optimal cutoff for the diagnosis of DTC metastases. Materials and methods . Ultrasound-guided FNA was performed in 1258 neck masses from 591 patients, 566 of them with confirmed DTC. In 1023 lesions, FNA was performed after thyroidectomy, 22 – after lobectomy, 213 – with preserved thyroid gland. The needle after FNA was washed in 1 ml of saline, in which the concentration of Tg was then examined. The level of Tg in the washout was compared with the histological (n = 522) or cytological diagnosis if no surgery was performed. The cut-off for Tg washout was determined by ROC analysis. Results . DTC lymph node metastases detected in 577 specimens. Nine specimens were obtained from metastases of thyroid cancer (TC) that does not express Tg (anaplastic TC, poorly differentiated TC, columnar-cell variant DTC), 22 – from neck metastases of other malignancy (lung cancer, mucinous soft tissues tumor, ovarian cancer, esophageal cancer, melanoma, neuroendocrine tumor), 6 – from other tumors of the neck (lymphoma, parathyroid adenoma, neurinoma). In 26 cases, the specimen was regarded as normal thyroid tissue left after thyroidectomy, 37 – postoperative seroma or granuloma, 1 – cyst of the neck, 578 – lymph node hyperplasia, 2 – sarcoidosis. The level of Tg washout from DTC metastasis and thyroid remnant significantly differed from that of non-thyroidal origin (p <0.0001). At the cut-off of 7.8 ng/ml, the sensitivity and specificity of Tg washout in the diagnosis of DTC metastases is 94 and 95 %, and at the cut-off of 20 ng/ml, 90 and 98 %, respectively. False-negative results were obtained from DTC with squamous metaplasia or sparse tumor cells in a specimen. False-positive results were obtained more often from lesions of level VI and IV compared with other localizations (8 % versus 4 %; p = 0.04). There were no differences in false positive rate in patients before and after thyroidectomy (p = 0.17), but in patients after thyroidectomy with a serum Tg >200 ng/ml, the false positive rate of Tg washout was significantly higher than that with a lower level of serum Tg (28 % versus 3 %; p = 0.0004). When comparing diagnostic performance of cytology and Tg washout, the advantage of the latter is in the diagnosis of cystic metastases, and the former is in the diagnosis of micrometastases and tumors that do not express Tg. Thyroglobulin in the washout increased the sensitivity of the cytology by 8 %. The combined use of these methods detected DTC metastases in 100 % of patients. Conclusion . Measurement of Tg in the washout is a useful addition to the cytology, increasing the diagnostic performance of the latter, mainly due to better detection of cystic metastases of DTC. The optimal suggested cut-off for Tg washout is 20 ng/mL, at which there are fewer false positives.

Fine needle aspiration biopsy is a routinely used technique to determine the nature of thyroid and parathyroid nodules. The complications and side effects associated with this procedure are minimal. At the same time, the histological alterations resulting from its use are well documented. Their range is quite w, however, from a clinical point of view, the most striking and catastrophic in their consequences are extensive heart attacks and necrosis. Such changes more often than in formations of a different morphological nature occur in tumors from oxyphilic cells. It should be noted that a lot of works devoted to post-biopsy changes are naturally focused on the morphological aspects of this problem, or are presented in the form of a presentation of individual clinical observations. This report presents the observation of necrosis in the parathyroid adenoma, which developed before fine needle aspiration biopsy.

Introduction. The results of the calcitonin (Ctn) study in patients with thyroid nodules are included in the clinical guidelines for the treatment of differentiated thyroid cancer. However, the management of patients with moderately elevated Ctn up to 100 pg/mL is not clearly defined.Materials and methods. The study included 103 patients with thyroid nodules and a Ctn level above the reference, but not more than 100 pg/ml. The Ctn concentration was determined using the Cobas e platform (Roche, Germany) or by the immunoradiometric method (Izotop, Hungary). 45 patients were operated on. The analysis of the incidence of medullary thyroid carcinoma (MTC), other thyroid and nonthyroid pathology in patients with elevated Ctn scan was carried out. The results of additional examination are presented: the serum cancer embryonic antigen, Ctn in wash-out, stimulated Ctn, gene RET mutation testing.The study objective is to evaluate the probability MTC with Ctn level <100 pg/ml, propose management tactics for patients with elevated Ctn and negative cytological results.Results. The incidence of MTC was 22 % (23/103). The maximum probability of mTC was at Ctn above 50 pg/mL (81 %, 13/16), at Ctn 31-50 pg/mL mTC was detected in 38 % (3/8). With Ctn <30 pg/mL and <20 pg/mL, the incidence of MTC was 9 % (7/79) and 6 % (4/64), respectively. In the majority of MTC patients (65 %), the tumor size did not exceed 1 cm. However, 22 % (5/23) had metastases to the neck lymph nodes. postoperative Ctn normalization was achieved in 96 % (22/23). In 26 % (5/19), a RET germ-line mutation was detected, most often p.val804met.Among patients without MTC, other thyroid tumors were found in 35 % (28/80), more often papillary thyroid cancer (25 %, 20/80). 13 % (10/80) had other malignant neoplasms. parathyroid adenoma was detected in 3 % (2/80). The maximum Ctn in this group was in patients with chronic kidney disease and metastatic liver disease with cholestasis and ascites.Cancer embryonic antigen was increased in 53 % of patients with MTC and in 7 % of patients without MTC. Ctn in washout was >2000 pg/mL in mTC and up to 938 pg/mL in patients with histologically confirmed absence of MTC.Conclusion. If the Ctn level is <100 pg/mL and there is no cytological confirmation, the issue of surgery is decided individually, taking into account many factors. After excluding other causes of hypercalcitoninemia (hyperparathyroidism, kidney disease, other tumors), measurement of serum cancer embryonic antigen and Ctn in wash-out is recommended. In some cases, testing for a RET mutation can be helpful.

IV (XXVII) Национальный конгресс эндокринологов с международным участием «ИННОВАЦИОННЫЕ ТЕХНОЛОГИИ В ЭНДОКРИНОЛОГИИ» 22-25 сентября 2021 года РЕЗУЛЬТАТЫ ЛЕЧЕНИЯ РАКА ПАРАЩИТОВИДНОЙ ЖЕЛЕЗЫ Северская Н .В ., Ильин А .А ., Исаев П

Background. Parathyroid cancer (PC) is extremely rare, usually diagnosed after surgery, there are no clinical recommendations for the treatment of metastatic PC.The study objective is to present the results of a clinical examination and treatment of patients with PC.Materials and methods. Retrospective analysis of 15 PC patients treated from 2001 to 2019. The results of laboratory tests, the surgical approach, the results of treatment, the rate of metastasis and relapse within 19 months (3 months – 11.6 years) after surgery are presented.Results. Tumor size is 35 mm (20–45 mm). Lymph node metastases – 1 (6.7 %), distant metastases – 2 (13 %). The median initial parathyroid hormone (PTH) is 735 pg/mL, calcium 3.22 mmol/L. Severe hyperparathyroidism with osteitis fibrosa cystica – in 6 (40 %). The surgical approach was parathyroidectomy in 10 (67 %), en bloc resection in 5 (33 %). Normalization of PTH and calcium after surgery – 13 (87 %). In two patients with distant metastases, the PTH and calcium remained high. A patient with Th6 vertebral metastasis was successfully operated on, with normalization of PTH and calcium, and 1.5 years was without relapse. A patient with lung and liver metastases received sorafenib after surgery, with decrease in calcium level. She died of progression 12 months after operation. Among patients with normalization of postoperative PTH, one had local relapse after 4 years. The patient was re-operated and 1 year after the second operation without relapse. The remaining patients are without relapse/progression.Conclusion. At the time of diagnosis, lymph node metastases are in 6.7 %, distant metastases – 13 %. Normalization of PTH and calcium after surgery suggests a good prognosis, but does not exclude the recurrence in the future, which requires long-term follow-up. Repeated surgery for local recurrence or solitary distant metastases can provide stable remission. Sorafenib in metastatic PC has managed to control hypercalcemia in the short term, however, antitumor efficacy requires further study.

Hyperparathyroidism is one of the most common endocrinopathies. This disease leads to a violation of phosphorus-calcium metabolism and the washing out of calcium from bone tissue. Breach of the skeleton’s structure in hyperparathyroidism is often mistaken for metastatic bone damage, which leads to incorrect treatment tactics. In this work we present the clinical observation of a patient with an adenoma of the parathyroid gland and a severe bone form of hyperparathyroidism. Multiple lesions of bones with destruction of the cortical layer and the presence of the softtissue component were initially regarded as metastases in the bone. However, the morphological pattern of bone foci, as well as an elevated level of calcium and parathyroid hormone, made it possible to diagnose the bony form of hyperparathyroidism. The search for the cause of hyperparathyroidism revealed a tumor in the projection of the right lower parathyroid gland. Surgical removal of parathyroid adenoma led to the normalization of the level of calcium and parathyroid hormone. The article presents data of laboratory-instrumental methods of research and the results of surgical treatment of a patient.

Hyperparathyroidism is one of the most common endocrinopathies. This disease leads to a violation of phosphorus-calcium metabolism and the washing out of calcium from bone tissue. Breach of the skeleton’s structure in hyperparathyroidism is often mistaken for metastatic bone damage, which leads to incorrect treatment tactics. In this work we present the clinical observation of a patient with an adenoma of the parathyroid gland and a severe bone form of hyperparathyroidism. Multiple lesions of bones with destruction of the cortical layer and the presence of the softtissue component were initially regarded as metastases in the bone. However, the morphological pattern of bone foci, as well as an elevated level of calcium and parathyroid hormone, made it possible to diagnose the bony form of hyperparathyroidism. The search for the cause of hyperparathyroidism revealed a tumor in the projection of the right lower parathyroid gland. Surgical removal of parathyroid adenoma led to the normalization of the level of calcium and parathyroid hormone. The article presents data of laboratory-instrumental methods of research and the results of surgical treatment of a patient.

None of the variants of therapy currently available for patients with differentiated thyroid cancer (DTС) refracted to therapy with radioactive iodine 131I (RAI) is not radical and does not allow to obtain full complete recovery including this is related to traditional chemotherapy regimens increasing toxicity of treatment contribute to improvement of the clinical effect. With the introduction of multicinase inhibitors into clinical practice made it possible to increase improve therapeutic outcomes. In December of 2015 in the Russian Federation was registered lenvantinib for therapy of patients with progressing DTC resistant to RAI therapy, which according to opinion may substantially improve the results of treatment of such patients and has a potential to change current clinical practice. The article deals with description of 5 clinical cases of inoperable patients with DTС refractory to RAI therapy receiving treatment with lenvatinib in the frameworks of the international randomized clinical trial phase III SELECT. The range of therapeutic effects varied from complete regression of the tumour to stabilization.

Возможности эхографии в дифференциальной диагностике фолликулярных опухолей щитовидной железыЖелонкина Н.В., Пойтина А