Functional State of the Pituitary-Thyroid-Adrenal System in Children with Cardiomyopathies and Cardiac Rhythm Disorders

The dissertation is devoted to a comprehensive study of the functional state of the pituitary-thyroid-adrenal system in children suffering from cardiomyopathies and cardiac rhythm disorders. The investigation includes an assessment of the levels of free thyroxine, total triiodothyronine, thyroid-stimulating hormone, and cortisol in the serum blood, as well as the determination of the morphometric parameters of the thyroid gland and adrenal glands by means of ultrasonographic investigation. The work was performed on a clinical material of children with various forms of cardiomyopathies and arrhythmias and makes it possible to identify patterns of alteration in the hormonal status depending on the type and severity of the cardiac disease.

During the investigation, it was established that alterations in the content of triiodothyronine, thyroid-stimulating hormone, and cortisol correlate with the degree of disease severity and the stage of circulatory insufficiency. The obtained data attest to the role of thyroid gland hormones and cortisol in the pathogenesis of cardiomyopathies and cardiac rhythm disorders in children, as well as to the influence of antiarrhythmic therapy (amiodarone) on the functional state of the endocrine system. The results are of significance for the differential diagnosis and prognostic assessment of diseases in pediatric patients.

Relevance of the Problem. Diseases of the cardiovascular system occupy a significant place in the structure of morbidity among children and adults, notably cardiomyopathies (CMP) [11, 13, 90, 91] and cardiac rhythm disorders (CRD) [80, 111]. The heightened interest of clinicians in these diseases is attributable to their considerable prevalence [16, 176], severity of clinical course, unfavorable prognosis associated with the development of congestive heart failure (CHF), the danger of sudden cardiac death, and the deterioration of patients' quality of life [24, 174, 182].

Clinical investigations in adult patients with CHF have revealed that a low level of triiodothyronine (T3) is an independent predictor of an unfavorable life prognosis [6, 154].

The administration of triiodothyronine to such patients was well tolerated, clinically significant arrhythmias were absent, systemic vascular resistance decreased (vasodilatory effect), and cardiac output increased [154].

There are scant data on alterations in the functional activity of the thyroid gland in adults with dilated cardiomyopathy (DCMP) [171]. Pilot studies involving the use of triiodothyronine in the treatment of children with CHF have appeared [123, 128].

In adult patients with hypertrophic cardiomyopathy (HCM), an elevation of the pituitary-thyroid gland function was identified.

These same authors also revealed a decrease in the content of adrenocorticotropic hormone (ACTH) and cortisol in these patients [118].

A detailed investigation of the functional state of the pituitary-thyroid-adrenal system in children with cardiomyopathies and cardiac rhythm disorders has not been conducted to date. The literature presents isolated studies carried out mainly in adult patients, which determines the relevance of the present investigation.

Objective of the Investigation:

To study the functional state of the pituitary-thyroid-adrenal system in cardiomyopathies and cardiac rhythm disorders in children.

Tasks of the Investigation:

1. To examine the content of free thyroxine (FT4), total triiodothyronine (T3), thyroid-stimulating hormone (TSH), and cortisol in the serum blood in cardiomyopathies and cardiac rhythm disorders in children.

2. To analyze the interrelationships between the levels of the studied hormones and the clinical and paraclinical parameters of the patients. On the basis of the obtained results, to establish diagnostic and prognostic criteria for alterations in hormone levels in children with the specified diseases.

3. To identify features of the morphometric parameters of the thyroid gland and adrenal glands in children with cardiomyopathies and cardiac rhythm disorders upon ultrasonographic investigation of these endocrine glands.

Scientific Novelty of the Investigation

For the first time, on a sufficient clinical material, results have been obtained confirming the participation of thyroid hormones, thyroid-stimulating hormone, and cortisol in the pathogenesis of cardiomyopathies and cardiac rhythm disorders in children.

It has been demonstrated that the magnitude of alterations in the content of T3, TSH, and cortisol depended on the severity of the disease and the stage of circulatory insufficiency (CI), whereas no dependence of alterations in FT4 content on disease severity and CI stage was observed.

In children with HCM, in contrast to the control group, a decrease in the content of T3 in the serum blood was detected (p < 0.05). No dependence of the content of T3, FT4, TSH, or cortisol on the form of HCM was established.

In children with DCMP, a decrease in the content of T3 in the serum blood was detected for the first time (p < 0.05), depending on the stage of circulatory insufficiency (CI).

In patients with PS and DCMP, reliable correlational connections were established between the levels of T3, FT4, cortisol, and echocardiographic parameters characterizing the development of cardiomyopathies.

It has been established that a low level of T3 is an unfavorable prognostic criterion in children with DCMP.

For the first time, heterogeneity in the content of FT4 in children with DCMP has been noted. Thus, in 20% of children with DCMP, moderate hyperthyroxinemia was observed, and in 35% — hypothyroxinemia. The investigation revealed an elevation of TSH levels in children with DCMP compared with the control group, children with HCM, and children with arrhythmias.

In children with DCMP and CI stage 2B–3, a reliable elevation of the cortisol level in the serum blood is noted compared with the control group, indicating an enhancement of the cortisol-secretory function of the adrenal glands in these children.

In a portion of children with chronic tachycardia (CT), a decrease in the T3 level was identified. In a significant number of children with CT, both hypo- and hyperthyroxinemia were detected. Analysis of the results showed that the decrease in T3 and FT4 content in children with CT was in most cases caused by the administration of amiodarone.

In a significant number of children with sinus node dysfunction, both hypo- and hyperthyroxinemia were identified.

In children with parasystole and atrioventricular blocks, a decrease in the FT4 content and an increase, compared with the control group, in the TSH content were noted.

Upon ultrasonographic investigation of the thyroid gland in children with DCMP, HCM, and cardiac rhythm disorders, alterations in the total thyroid volume (TTV) and the parenchyma of the thyroid gland (in the form of hypoechoic areas) are noted.

Practical Significance

The results of the work are of practical and theoretical interest for pediatricians, pediatric cardiologists, and endocrinologists.

The practical significance of determining the content of iodinated thyroid hormones, pituitary thyroid-stimulating hormone, and cortisol for the differential diagnosis of cardiomyopathies and arrhythmias of hormonal and non-hormonal etiology in children has been established.

In children with dilated cardiomyopathy, an additional criterion of an unfavorable life prognosis has been established (in the form of a low content of triiodothyronine), used in the assessment of the severity of CHF.

It is necessary to take into account that during amiodarone therapy of children with cardiomyopathies, dysfunctions of the pituitary-thyroid-adrenal system occur, manifesting as alterations in the levels of FT4, T3, TSH, and morphometric parameters of the thyroid gland.

Implementation in Practice. The principal provisions of the work have been implemented in the clinical practice of the cardiology, membranology, ultrasonographic diagnostics departments, and in the outpatient practice of the consultative-diagnostic center of the State Educational Institution "Scientific Center for Children's Health" of the Russian Academy of Medical Sciences.

The dissertation materials were reported at the VIII Congress of Pediatricians in Moscow in 2003. Five publications on the dissertation topic have been published in domestic scientific journals.

Dissertation Defense. The dissertation materials were reported and discussed at the joint scientific conference of the departments of cardiology, membranology, functional diagnostics, ultrasonographic diagnostics, and the clinical biochemistry laboratory of the Research Institute of Pediatrics of the State Educational Institution "Scientific Center for Children's Health" of the Russian Academy of Medical Sciences.

Structure of the Dissertation. The dissertation is written on 125 pages of typed text and consists of an introduction, a literature review, three chapters of original observations, a discussion of the obtained results, conclusions, and practical recommendations. The work is illustrated by 49 tables, 5 photographs, and 4 clinical examples. The reference list includes 120 domestic and 89 foreign sources.