Efficacy of Therapy for Endemic Goiter in Children (Data of Longitudinal Follow-up)

The dissertation is devoted to the evaluation of the efficacy of therapy for endemic goiter in children based on long-term follow-up observation. The work addresses questions of treatment and prevention of iodine-deficiency diseases among pediatric and adolescent populations, analyzes various therapeutic and preventive regimens, including the use of potassium iodide and combined therapy (levothyroxine + potassium iodide). Special attention is given to the role of family-hereditary factors in the formation, course, and recurrence of endemic goiter, as well as to the level of awareness and compliance of parents with recommended methods of treatment and prevention.

Iodine deficiency and iodine-related health disorders continue to remain one of the most common forms of non-infectious diseases among the pediatric and adolescent population of our country [7, 31, 48, 50]. In recent years, the results of numerous national and international studies have made it possible to formulate the basic principles concerning the mechanisms of development of iodine-deficiency disorders, the natural course of endemic goiter, and the principles of rational diagnosis, prevention, treatment, and monitoring of these socially significant conditions [115, 116, 195]. It is obvious that under such conditions one should expect the virtually complete elimination of iodine insufficiency in large populations within a relatively short period of time [58, 127, 185].

However, the results of implementing mass iodine prophylaxis programs in a number of countries worldwide indicate that the actual effect is achieved within 5-10 years and only under the condition of regular consumption of iodized salt by no fewer than 90% of the country's residents [8, 128, 235]. Foreign experience shows that only through the enactment of a law on universal salt iodization can actual consumption reach the required level within a minimal period of time (approximately one year) [164, 175]. The next several years will be required for the correction of existing, including latent, health disorders in individuals [46, 171].

To date, the real political and economic prerequisites for adopting such a law are virtually absent in the Russian Federation; therefore, the need arises to justify alternative, possibly surrogate approaches to universal salt iodization for organizing therapeutic and preventive measures among residents of endemic regions, first and foremost among children and adolescents, who constitute the reproductive potential of the nation [13].

The body of a child and adolescent is most sensitive to the deficiency of essential microelements. In this regard, insufficient iodine intake is dangerous not only for the development of manifest psychosomatic diseases but also causes an overall slowing of growth and development in children [63, 70].

Relative consensus among most authors is observed regarding preventive measures, whereas the treatment regimens for this disease continue to be actively debated to the present day [3, 8]. The available literature contains virtually no scientific works devoted to long-term observation of the course of endemic goiter in children and adolescents receiving various treatment regimens.

Normalization of thyroid volume in a patient during treatment is perceived by the child's parents and, unfortunately, sometimes by medical personnel as recovery, which naturally no longer requires constant monitoring and preventive measures, leading sooner or later to recurrence of the disease. Furthermore, to this day, iodized salt is not regarded by a significant portion of the population as a highly effective means of preventing the development of endemic goiter and, due to various circumstances, is not always used regularly. Although, undoubtedly, high compliance of the population with recommended treatment and prevention methods is of great importance for the success of iodine deficiency correction programs.

Endemic goiter is a multifactorial pathology with the undeniably leading role of dietary iodine insufficiency. There exists an opinion regarding differing thresholds of individual sensitivity to iodine insufficiency and regarding family-hereditary predisposition to goiter formation [60, 61]. From the standpoint of clinical genetics, the influence of environmental factors dominates in the pathogenesis of the disease; however, the frequency of occurrence and severity of clinical manifestations substantially depend on hereditary predisposition, both at the individual and group levels [6]. However, the contribution of hereditary factors to the dynamics of the disease course, as well as to the efficacy of treatment and prevention of thyroid pathology among residents of endemic regions, remains unstudied.

Aim of the Study: Based on long-term follow-up observation and genealogical investigation, to determine the drug-induced, temporal, and family-hereditary risk factors for the formation, course, and recurrence of endemic goiter in children.

Tasks of the Study:

1. To study the long-term follow-up history of the course of endemic goiter in children. To determine the degree of efficacy and prognostic significance of various therapeutic and preventive regimens in preventing disease recurrence during long-term patient observation.

2. To establish the contribution of family-hereditary factors to the formation of endemic goiter in children.

3. To evaluate the efficacy of iodine prophylaxis of endemic goiter in children with a family history burdened by thyroid pathology.

4. To determine the level of awareness and compliance of parents as factors affecting the efficacy of treatment and prevention of iodine-deficiency diseases in children.

Scientific Novelty of the Study:

For the first time, a four-year follow-up of endemic goiter in children has been studied. It has been established that treatment of endemic goiter for one year leads to normalization of thyroid gland size in no fewer than 68% of patients. In the absence of iodine prophylaxis over the subsequent three years, disease recurrence develops in nearly one-third of the children.

It has been established that the annual increase in the incidence of endemic goiter in the pediatric and adolescent population in the absence of controlled iodine prophylaxis is 5-6% per year.

For the first time, the significance of treatment of endemic goiter with potassium iodide and combined therapy (levothyroxine + potassium iodide) has been determined from the standpoint of possible disease recurrence. From the standpoint of evidence-based medicine, the greatest advantage of combined treatment has been demonstrated, which ensures a minimum three-year period of maintaining normal thyroid gland size subsequently.

Data have been obtained on the contribution of family-hereditary factors to the development, course, and recurrence of endemic goiter. It has been established that the predisposition to goiter development is inherited, predominantly, through the maternal line.

For the first time, a relationship between family-hereditary factors and the efficacy of therapeutic and preventive measures in children under conditions of iodine deficiency has been identified. Risk indicators and odds ratios for recurrence of endemic goiter have been calculated depending on intrafamily disease frequency.

It has been proven that constant iodine prophylaxis makes it possible to mitigate the negative impact of unfavorable family-hereditary predisposition factors.

Practical Significance of the Study:

It has been shown that the unjustified absence of iodine prophylaxis after completion of the primary course of treatment for endemic goiter in children and adolescents already leads, within three years, to disease recurrence in one-third of the children. Risk indicators for recurrence of endemic goiter have been calculated depending on the medication methods employed.

The appropriateness of combined therapy for endemic goiter as the most effective approach in terms of preventing recurrence has been scientifically substantiated.

The role of family-hereditary factors in the formation of endemic goiter in children has been established, and the intrafamily frequency of thyroid pathology among residents of regions with moderate iodine deficiency has been determined. Therapeutic approaches to the management of patients with endemic goiter in pediatric practice, taking into account family factors, have been formulated.

Data on the awareness of rural residents of an iodine-deficient region regarding the problem of insufficient iodine intake, which determine parental compliance with treatment and prevention of endemic goiter in their children, have been summarized.

The use of recommended treatment and prevention regimens substantially improves the efficacy of therapy for endemic goiter in children, reducing the costs of repeated re-examination and preventing disease recurrence.

Verification of the Study:

The dissertation materials have been presented and discussed at All-Russian conferences and congresses: "Medico-Biological and Extreme Pediatrics" (Moscow, 2000), "Pharmacotherapy and Pharmacogenetics in Pediatrics" (Moscow, 2000), the IX Congress of Pediatricians of Russia (Moscow, 2001), the IV Russian Congress of Endocrinologists (St. Petersburg, 2001), the X National Congress "Man and Medicine" (Moscow, 2003), the III All-Russian Conference on Pediatric Endocrinology (Moscow, 2005); at international congresses: at the symposium "Iodine Prophylaxis — Benefits and Possible Efficacy" (Krakow, Poland, 2001), the 5th European Endocrine Congress (Turin, Italy, 2001), the annual meetings of the European Thyroid Association — the 27th (Warsaw, Poland, 2001) and the 30th (Istanbul, Turkey, 2004); a session of the Saratov Branch of the Russian Association of Endocrinologists (Saratov, 2005).

Fragments of the research were included in the programs of the following competitions for young scientists:

• At the All-Russian Conference "Pharmacotherapy and Pharmacogenetics in Pediatrics" (Moscow, 2000) — the report "Comparative Assessment of the Efficacy of Medication Methods of Treatment and Prevention of Endemic Goiter in Children" — an encouragement prize;

• At the IX Congress of Pediatricians of Russia (Moscow, 2001) — the report "Prognosis of the Course of Endemic Goiter in Children: The Role of Family-Hereditary Factors" — a fourth prize;

• At the X National Congress "Man and Medicine" (Moscow, 2003) — the report "Treatment of Endemic Goiter in Children (An Assessment from the Standpoint of Evidence-Based Medicine)" — the Grand Prix.

Implementation of Research Results:

Seventeen scientific works have been published on the dissertation topic, including four articles (two in central journals, one in a foreign journal, and one in a scientific collection of the Endocrinological Scientific Center of RAMN).

The dissertation materials have been included in the methodological recommendations "Endemic Goiter in Children of the Saratov Region. Prevalence, Diagnosis, Prevention, Treatment" (Saratov, 2006), approved by the Minister of Health and Social Support of the Saratov Region.