Choice of Optimal Treatment Method for Autoimmune Thyroiditis, Thyroid Cancer, and Thyroid Lymphoma Based on Clinico-Immunomorphological Studies (Clinico-Laboratory Study)

The dissertation is devoted to a clinico-immunomorphological investigation of three interrelated thyroid pathologies — chronic autoimmune thyroiditis (Hashimoto's thyroiditis), thyroid cancer, and thyroid lymphoma — with the aim of determining optimal treatment methods. The research was conducted on the material of patients from the Rostov Oblast, where, due to ecological and geographic features, an elevated frequency of these diseases is observed. A comprehensive analysis of demographic, clinical, hormone-serological, sonographic, and anatomo-morphological data of three clinical groups of patients and a control group was carried out. Associative and cause-and-effect associations between Hashimoto's thyroiditis and the development of thyroid cancer and thyroid lymphoma were identified. Approaches to screening, diagnosis verification, and the choice of therapeutic strategy were substantiated, including indications for surgical intervention and principles of dispensary observation. The scientific novelty consists in the specification of diagnostic and prognostic criteria, as well as in the substantiation of optimal extents of surgical treatment. The practical significance of the work is expressed in the implementation of developed algorithms for managing patients with Hashimoto's thyroiditis in the practice of surgical endocrinology.

According to WHO statistics, thyroid diseases account for a significant proportion in the structure of not only endocrine pathology but also morbidity as a whole. For many decades, thyroidopathies have collectively constituted no less than 10% of total morbidity. Moreover, a steady tendency toward an increase in the frequency of thyroid pathology is observed almost universally. The unfavorable trend is attributed by specialists to global ecological problems, the demographic shift toward an aging population, and, of course, the expanded diagnostic capabilities of modern thyroidology. This epidemiological trend applies fully and, in particular, to chronic autoimmune thyroiditis (Hashimoto's thyroiditis) and, unfortunately, to thyroid cancer. On average, regardless of age and sex, the population frequency of Hashimoto's thyroiditis currently ranges from 5–7% [49; 158]. However, for women aged 30 to 50, this indicator is several times higher, reaching 50% and even 85% [44, 69; 76, 104, 153]. As for the frequency of thyroid cancer, according to WHO data, over the past 20 years the incidence of thyroid cancer has nearly doubled everywhere, reaching 5–6 cases per 100,000 [89, 124]. Although the proportion of thyroid cancer in the structure of oncological pathology is small, not exceeding 0.5% [13, 19, 23, 193, 266]; nevertheless, thyroid cancer remains the most common oncological pathology of the endocrine glands.

It must be acknowledged that when comparing data from 20–30 years ago with publications of recent years, the views on the relative frequency of Hashimoto's thyroiditis and thyroid cancer, and especially the interpretation of their interrelationship, differ substantially. If earlier researchers doubted and even denied such a connection [19, 42, 150, 192, 276], now the majority of authors speak of a dominant cause-and-effect relationship, particularly between Hashimoto's thyroiditis and thyroid lymphoma [29, 45, 80, 81, 135, 188]. Such an evolution of views can be explained, in part, by natural variations of ethnic, demographic, geochemical, and ecological nature, substantial differences in methodological approaches, first and foremost the advent of immunohistochemical analysis, as well as other features and discrepancies in modern research developments, which is fully characteristic of thyroidology, distinguished by a vast arsenal of research tools and methods [34, 55, 159].

With respect to the situation that has developed in recent years in our country, the listed circumstances are extremely relevant, first and foremost, in connection with the enormous and uncontrolled migration of the population from endemic goitrous regions, as well as taking into account the consequences of the Chernobyl disaster. These events and circumstances have affected most of all the southern part of Russia, including the Rostov Oblast, due to its proximity to Central Asia, Kazakhstan, and Ukraine. It is therefore obvious that, according to recent data, the frequency of thyroid cancer in the Rostov Oblast constitutes more than 1% of all oncological morbidity [46], which is approximately twice the comparable indicator for other regions of Russia [36, 67, 72, 89]. In this regard, questions of epidemiology, clinico-laboratory-morphological diagnosis, and the choice of therapeutic strategy in Hashimoto's thyroiditis and thyroid cancer have acquired exceptional relevance for the Rostov Oblast. This determined the goal and objectives of our research.

Goal and Objectives of the Research

Goal of the Research:

To improve the treatment outcomes of patients with Hashimoto's thyroiditis, thyroid cancer, and thyroid lymphoma based on hormone-serological, morphological, and clinical investigations, as well as to identify possible cause-and-effect interrelationships and develop recommendations for screening and therapeutic strategy.

Objectives of the Research:

• To conduct a cross-correlation and factor-dispersion analysis of demographic, clinical, sonographic, hormone-serological, and anatomo-morphological data in patients with Hashimoto's thyroiditis, thyroid cancer, and thyroid lymphoma, to clarify the interrelationships of the corresponding characteristics and their diagnostic informativeness;

• To establish demographic, anamnestic, clinical, laboratory-intrasurgical, and anatomo-morphological markers by which a risk group can be identified with respect to the development of thyroid cancer and thyroid lymphoma in patients with Hashimoto's thyroiditis;

• To improve screening, diagnosis verification, and therapeutic strategy in Hashimoto's thyroiditis, taking into account the possible risk of developing thyroid cancer and thyroid lymphoma;

• To clarify the choice of optimal method and extent of surgical intervention in patients suffering from thyroid cancer combined with chronic autoimmune thyroiditis, and in patients suffering from autoimmune thyroiditis (nodular form) with signs of malignancy.

Basic Propositions for Defense:

A distinctive feature of endocrine morbidity in the Rostov Oblast population is an elevated frequency of diffuse goitrous hyperplasia of the thyroid gland, against the background of which Hashimoto's thyroiditis is frequently detected.

The increase in thyroid cancer morbidity is associated with the frequency of development of Hashimoto's thyroiditis and is primarily due to a number of aggravating factors, such as advanced patient age and hypothyroidism.

Patients suffering from the nodular form of Hashimoto's thyroiditis and entering the risk group for transformation of this nosology into thyroid cancer should undergo surgical treatment in the extent of subtotal thyroidectomy according to E.S. Dratsinsky.

Patients with Hashimoto's thyroiditis without signs of malignant transformation should be under long-term dispensary observation with the prescription of suppressive doses of thyroid hormones, with periodic hormone-serological investigations.

Scientific Novelty of the Work:

Epidemiological, hormone-serological, and anatomo-morphological markers of Hashimoto's thyroiditis, thyroid cancer, and thyroid lymphoma have been specified, along with their etiopathogenetic differences.

It has been demonstrated that between the etiopathogenetic, clinical, and anatomo-morphological characteristics of Hashimoto's thyroiditis, thyroid cancer, and thyroid lymphoma, there exist two forms of interrelationship: associative and cause-and-effect. The structure of these interrelationships in Hashimoto's thyroiditis and thyroid cancer largely coincides, which provides grounds for considering Hashimoto's thyroiditis, including Hashimoto's thyroiditis, as a risk factor for thyroid cancer.

Immunological factors in the pathogenesis of Hashimoto's thyroiditis, thyroid cancer, and thyroid lymphoma are diverse, ambiguous, and variable, which makes the correction of corresponding disturbances with immunomodulators and other, currently known, immunotropic therapy problematic.

It has been shown that patients suffering from Hashimoto's thyroiditis with signs of transformation into thyroid cancer should undergo surgical treatment. The procedure of choice in these cases should be considered subtotal thyroidectomy according to E.S. Dratsinsky, as the most adequate, from an oncological standpoint, surgical procedure.

Practical Significance:

Scientifically grounded criteria for choosing two tactical variants of managing patients with Hashimoto's thyroiditis have been proposed: the method of passive dispensary observation with replacement therapy and "suppressor therapy" with thyroid hormone preparations.

A complex of diagnostic measures and an algorithm for their conduct during long-term dispensary observation of patients with Hashimoto's thyroiditis has been developed.

Anamnestic, demographic, laboratory, and anatomo-cytological markers that allow establishing the degree of risk of developing thyroid cancer and thyroid lymphoma in patients with Hashimoto's thyroiditis have been clarified.

Indications for surgical treatment of Hashimoto's thyroiditis have been clarified, including in terms of thyroid cancer prevention.

An optimal method and extent of surgical intervention have been selected for the nodular form of autoimmune thyroiditis (Dratsinsky's operation), as well as for combined autoimmune thyroiditis with differentiated unilateral thyroid cancer (total-subtotal thyroidectomy with paratracheal lymphadenectomy).

Implementation in Practice:

The developed diagnostic, prognostic criteria, and principles of managing patients with Hashimoto's thyroiditis have been implemented in the practice of the surgical endocrinology departments of GUZROKB №1 and MONIKI named after M.F. Vladimirsky. The dissertation materials are used in the educational and pedagogical process at the faculty of postgraduate education at MONIKI named after M.F. Vladimirsky and at the Department of Surgical Diseases №4 of the Faculty of Advanced Training and Professional Retraining of the State Educational Institution of Higher Professional Education "Rostov State Medical University".

Publications:

Based on the dissertation materials, 9 printed works have been published.

Defense of the Work:

The dissertation materials were reported at the Annual Conference of Young Scientists of MONIKI named after M.F. Vladimirsky (November 2003), the departmental conference of the Department of Surgery №4 of the Faculty of Advanced Training and Professional Retraining of the State Educational Institution of Higher Professional Education "Rostov State Medical University" (minutes of meeting №40 dated 12.04.2005), the joint meeting of staff of the surgical endocrinology department, the therapeutic endocrinology department of GUZROKB №1, the pathology department of ROPAB, and the Department of Endocrinology of the Faculty of Advanced Education at MONIKI named after M.F. Vladimirsky.

Volume and Structure of the Dissertation:

The dissertation materials are presented across 117 pages. The dissertation consists of an introduction, a literature review, a chapter describing clinical observations and research methods, a chapter with the results of original research, a discussion of research results (conclusion), conclusions, and practical recommendations. The bibliography contains 127 domestic and 157 foreign sources.