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Errors in the treatment of highly differentiated thyroid cancer as a multidisciplinary problem
https://doi.org/10.21886/2219-8075-2021-12-2-92-95
Abstract
Highly differentiated thyroid cancer is a common endocrine neoplasm with a favorable prognosis. However, errors in the treatment of this pathology can significantly worsen the patient’s quality of life.
Patient V., 65 years old, underwent an operation for papillary thyroid cancer with an injury to the recurrent laryngeal nerve in 2015. Only 6 months later, RAI therapy was performed with an insufficient dose of RI, and levothyroxine was prescribed at a thyrotoxic dose, which led to the development of AF. Throughout the entire period after surgical treatment, biochemical remission could not be achieved, and in 2019, a control ultrasound scan revealed lymphadenopathy of the anterior cervical lymph nodes and metastases in the lungs.
For citations:
Volkova N.I., Merenkova M.D. Errors in the treatment of highly differentiated thyroid cancer as a multidisciplinary problem. Medical Herald of the South of Russia. 2021;12(2):92-95. (In Russ.) https://doi.org/10.21886/2219-8075-2021-12-2-92-95
Thyroid cancer (TC) is a malignant epithelial tumor that develops from the thyroid gland follicular or parafollicular cells. TC has five histological types: papillary (80–85% of cases), follicular (10–15%), medullary (5%), poorly differentiated (1%), and anaplastic (0.1–0.2%) [1]. The first two are classified as well-differentiated types of TC, inclusive of their biological nature (from A- or B-cells), as well as cardinal differences from other types in clinical progression, management tactics, and prognosis. Based on these features, the Russian Association of Endocrinologists in 2020 issued clinical guidelines devoted exclusively to well-differentiated TC. These guidelines set out the principles of diagnosis, treatment, and subsequent prophylactic medical examination of patients with well-differentiated TC. These clinical guidelines have clear guidelines for endocrinologists, oncologists, and surgeons in choosing the most correct therapeutic approach and follow-up for this patient population. This clinical case demonstrates that ignoring a clear algorithm for treating patients with well-differentiated cancer, even despite a favorable prognosis, can significantly worsen the patient's quality of life.
Clinical case. Patient V., 68 years old, turned to the surgical department with complaints of a nodular mass in the thyroid gland in 2015. It was also known from the case history that she had had a nodular mass since June 2015. Objectively: palpation of the thyroid gland revealed a nodular lesion of a densely elastic consistency up to 2 cm in size. The patient was examined in the outpatient setting. Diagnostic findings:
- TSH (thyroid-stimulating hormone) – 3.53 mIU/ml;
- Ultrasound of the thyroid gland – nodular lesion of the right lobe (21 × 19 × 23 mm), extra organ nodular lesion at the right lobe lower pole (17 × 21 × 24 mm), with color Doppler imaging, mixed type of blood flow, structural problems in the anterior cervical lymph nodes on the right (8 × 3 to 21 × 8 mm size);
- fine-needle aspiration of thyroid nodules – the cytological picture corresponded to a malignant tumor of the thyroid gland (papillary cancer);
- puncture of the anterior cervical lymph node on the right – among lymphocytes of various degrees of maturity, there were atypical cells, separately and in the form of complexes;
- spiral computed tomography (CT) of the chest organs – CT image of small calcifications in the lung parenchyma, a single small lesion in the middle lobe of the right lung (without specific CT signs). Fibrotic changes in the basal segment of the lungs.
Surgical treatment was recommended to the patient based on her complaints, medical history, physical examination, and examination data. Thyroidectomy with traumatization of the right lower laryngeal nerve, removal of the pretracheal and paratracheal cellular tissue with lymph nodes, right middle and lower jugular lymph nodes was performed. Histology of the surgical specimen: "papillary cancer, invasion of the gland capsule in the surrounding adipose tissue." Histology of the resected lymph nodes: "metastases of papillary carcinoma were found in three lymph nodes." The patient was dismissed from the hospital in satisfactory condition with the recommendations: "Sodium Levothyroxine 100 μg per day, TSH control, free T4 after 3 months, radioactive iodine therapy (without specifying the recommended timing)". In addition, video laryngoscopy and an otorhinolaryngologist’s consultation were not recommended for the patient, which is mandatory for the specified volume of surgery and nerve trauma [2]. Soon the patient developed hoarseness.
This patient belongs to the group of intermediate risk of TC relapse (based on the metastases in the lymph nodes, invasion of the capsule of the gland, and the tumor invasion into the surrounding adipose tissue). TC therapy in patients of this risk group includes the following stages: surgical treatment, radioactive iodine therapy (RIT), and suppressive therapy with levothyroxine. After surgery, patients should be referred for RIT no later than 3–6 weeks after surgery, which increases survival and improves prognosis [3, 4]. However, the patient was referred for RIT only after 3 months. Before therapy, laboratory assessments: TSH – 93 mIU/ml, thyroglobulin (TG) – 34 ng/ml, antibodies (ABs) to TG – 3.12 U/ml. Whole-body scintigraphy (WBS) is a hyper fixation of a radiopharmaceutical agent in the neck area. The results of these examinations (a high level of TG, the presence of ABs to TG, the accumulation of RP (radiopharmaceutical), as revealed by scintigraphy) indicated that not all changed lymph nodes were removed during the surgery; therefore, the RIT effectiveness was significantly reduced. However, the patient underwent this stage of treatment (a dosage of 2.6 GBq, which was an insufficient dose for this patient), recommendations for monitoring laboratory indices, and vague recommendations for increasing the levothyroxine dosage to "125 – 150 μg per day" were given. The patient was not recommended for a target TSH level.
After 5 months, the control WBS did not reveal pathological foci of RP hyper fixation, but the persistently high level of TG (30 ng/ml) and ABs to TG (11.13 U/ml) attracted attention. The patient continued to take levothyroxine at a 125–150 μg dosage every other day, associated with this TSH therapy – 0.01 mIU/ml (therefore, this dose was thyrotoxic for the patient). It should be noted that the TSH target level for patients receiving suppressive therapy is the lower limit of the normal (0.4 mMU/ml) at high normal concentrations of free T4 and free T3 [3]. However, the patient was again not given recommendations for the target TSH level, and the levothyroxine dosage was not reduced.
In 2017, the patient noted the emergence of complaints of palpitations, and "atrial fibrillation, paroxysmal form" was diagnosed as a result of a long-term thyrotoxic dose of thyroid hormone medication. Sotagexal 40 mg 2 times per day was prescribed for atrial fibrillation treatment. Against this background, the patient's dose of levothyroxine was reduced to 75 μg and a consultation with an otorhinolaryngologist was recommended. However, associated with this therapy, TSH was 14.72 mIU/ml, which led to an increase in the levothyroxine dosage to 88 μg. Against the background of this dosage, TSH was 84.79 mMU/ml, as a result of which the patient was recommended to return to a dosage of 125 μg and β-blockers administration. The patient was consulted by an otorhinolaryngologist and diagnosed with "Paresis of the right larynx, dysphonia".
Throughout 2016–2019, the patient retained ABs to TG and various levels of TG were determined, which indicated the insufficient effectiveness of the previous treatment stages. As revealed by the thyroid gland ultrasound and the chest organ CT, the time course was not observed. Biochemical remission was not achieved, but the patient did not receive a recommendation.
In 2019, the patient received levothyroxine at a dosage of 100 μg per day, on top of this therapy with TSH 1.6 mIU/ml. In November 2019, during a control ultrasound of the thyroid bed, lymphadenopathy of a single anterocervical lymph node on the right side was noted. A puncture of this node was performed, and papillary carcinoma metastases were found. According to WBS data, there were no foci of pathological accumulation of RP, which indicated the presence of iodine-resistant metastases.
In June 2020, repeated RIT was carried out (without surgical removal of the affected lymph node). Therapy was performed in October 2020 (5.7 GBq dose). To achieve the target TSH level, the levothyroxine dosage was increased to 112 μg per day.
Due to the coronavirus pandemic in January 2021, the patient was remotely consulted by an oncologist, who concluded that surgical removal of the affected lymph node was contraindicated due to the presence of TC metastases in the lungs, according to a chest CT scan. Also in January 2021, TSH was monitored (0.027 mIU/L), which indicated that the levothyroxine dose administrated was still high.
For the present, for this patient, "conservative treatment" was chosen due to metastases in the lungs, which did not increase. The dosage of sodium levothyroxine was reduced to 100 μg, recommendations on control of laboratory findings and their target levels were given (target TSH level – 0.4 mIU/L). The third RIT was considered inappropriate due to the iodine resistance of the existing metastases (most likely, iodine resistance developed as a result of an insufficient dose during the first RIT in 2016); when there is a negative trend, the prescription of targeted therapy will be considered.
Conclusion
Thus, some mistakes at almost every stage of TC therapy led to a significant decrease in the patient's quality of life. Errors in the extent of the operation, ignoring biochemical relapse, later certification for the first RIT, as well as an insufficient dose of radiation, led to the iodine-resistant metastases, which worsened the prognosis for this patient. The prescription of supraphysiologic doses of levothyroxine, the lack of recommendations for target TSH levels, and the resulting maintenance of TSH below the target level resulted in atrial fibrillation. The patient's late referral to an otorhinolaryngologist did not allow timely initiation of rehabilitation after the right lower laryngeal nerve trauma, which resulted in paresis of the right larynx. The patient's referral for repeated RIT without surgical removal of the lymph node in the absence of RP accumulation in the neck (a sign of iodine-resistant metastases) led to an unjustified intervention.
In the treatment of well-differentiated TC, adherence to a strict patient management algorithm is aimed at minimizing the number of errors and, as a result, at more effective patient treatment, avoiding iatrogenic complications of therapy, which eventually will increase the duration and quality of patients’ life.
References
1. Dedova I.I., Mel'nichenko G.A., eds. Endokrinologiya: natsional'noye rukovodstvo. M.: GEOTAR-Media, 2019. (In Russ.)
2. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. // yroid. – 2016. – V.26(1). – P.1-133. DOI: 10.1089/thy.2015.0020
3. Assotsiatsiya onkologov Rossii. Rossiyskoye obshchestvo spetsialistov po opukholyam golovy i shei. Assotsiatsiya endokrinnykh khirurgov. Rossiyskaya assotsiatsiya endokrinologov. Klinicheskiye rekomendatsii. Vysokodifferentsirovannyy rak shchitovidnoy zhelezy. 2020 (In Russ.)
4. Ruel E., Thomas S., Dinan M., Perkins J.M., Roman S.A., Sosa J.A. Adjuvant radioactive iodine therapy is associated with improved survival for patients with intermediate-risk papillary thyroid cancer. // J Clin Endocrinol Metab. – 2015. V.100(4). – P.1529-36. DOI: 10.1210/jc.2014-4332
About the Authors
N. I. VolkovaRussian Federation
Natalya I. Volkova, Dr. Sci. (Med.), Professor, Head of Department of internal diseases №3
Rostov-on-Don
M. D. Merenkova
Russian Federation
Maria D. Merenkova, 2nd year resident, Department of internal diseases №3
Rostov-on-Don
Review
For citations:
Volkova N.I., Merenkova M.D. Errors in the treatment of highly differentiated thyroid cancer as a multidisciplinary problem. Medical Herald of the South of Russia. 2021;12(2):92-95. (In Russ.) https://doi.org/10.21886/2219-8075-2021-12-2-92-95