The Assessment of the Hypothalamic-Pituitary-Adrenal Axis After Oncological Treatment in Pediatric Patients with Acute Lymphoblastic Leukemia

Objective: Oncologic treatment can affect the adrenal glands, which in stressful situations may lead to life threatening adrenal crisis. The aim of the study was to assess adrenal function in pediatric acute lymphoblastic leukemia (ALL) survivors and to identify the best markers for this assessment. Methods: Forty-three ALL survivors, mean age 8.5±3.6 years and 45 age and sex-matched healthy controls were recruited to the study. ALL patients were assessed once within five years following oncological treatment completion. Fasting blood samples were collected from all participants to measure: fasting blood glucose (FBG); cortisol; aldosterone; plasma renin activity (PRA); dehydroepiandrostendione-sulfate (DHEA-S); and adrenocorticotropic hormone (ACTH). Moreover, diurnal profile of cortisol levels and 24-hour urinary free cortisol (UFC) were assessed. ALL survivors underwent a test with 1 ug of synthetic ACTH. Results: The study revealed lower level of PRA (1.94±0.98 ng/mL/h vs 3.61±4.85 ng/mL/h, p=0.029) and higher FBG (4.6±0.38 mmol/L vs 4.41±0.39 mmol/L, p=0.018) in the ALL group compared to controls. UFC correlated with evening cortisol (p=0.015, r=0.26), midnight cortisol (p=0.002, r=0.33), and DHEA-S (p=0.004, r=0.32). UFC also correlated with systolic and diastolic blood pressure (p=0.033, r=0.23 and p=0.005, r=0.31, respectively). The ACTH test confirmed impaired adrenal function in 4/43 ALL survivors (9%). Two of the patients who needed permanent hydrocortisone replacement had low UFC, midnight cortisol and DHEA-S levels. Conclusion: These results highlight the importance of reviewing adrenal gland functionality after chemo/radiotherapy in ALL survivors. DHEA-S proved to be a good marker to assess the adrenal glands after oncological therapy. Post-treatment disturbances of the adrenal axis could be associated with metabolic complications.

Assessment of the function and morphology of the thyroid gland in paediatric patients treated with enzyme replacement therapy due to selected storage diseases - preliminary results of our own research and a review of the literature.

INTRODUCTION: Some storage diseases, caused by a deficiency of a specific enzyme, which results in the systemic accumulation of non-metabolized substances, can be treated with enzyme replacement therapy (ERT), which can protect many organs, including the endocrine system. AIM: The aim of the study was to assess the function and morphology of the thyroid gland in children with storage diseases treated with ERT, and to review the literature. MATERIAL AND METHODS: Eight patients were included in the study: 3 with Fabry disease (age: 17; 9.9; 10 years), 3 with Hunter's disease (12.3; 4.1; 9,3), and 2 with Pompe disease (6.8; 9,5). Thyroid function and morphology were assessed in each patient during ERT, and 4 of them were reassessed 27 months later. RESULTS: One patient with Fabry disease had been treated for hypothyroidism due to autoimmune thyroiditis diagnosed before the study. The remaining patients had normal thyroid tests and negative anti-thyroid antibodies at first and second evaluation; however, in all reassessed patients a decrease in TSH value was noted. Among the remaining patients with Fabry disease, one had normal and a second had heterogeneous echogenicity of the thyroid during first assessment. In the second patient, normalisation of echogenicity was observed at reassessment. Both patients with Pompe disease assessed once had slightly heterogeneous thyroid echogenicity. In 3 patients with Hunter's disease in the first ultrasound examination, no abnormalities were found. In re-evaluation, 2 of them showed heterogeneous thyroid echogenicity. CONCLUSIONS: We conclude that patients with storage diseases should undergo assessment of thyroid function and morphology before and during ERT.

Assessment of adrenal function in pediatric cancer survivors.

INTRODUCTION: Oncological therapy can temporarily or permanently disrupt adrenal gland function. The aim of our study was to assess the function of adrenal glands in cancer survivors and to find the best diagnostic tools for it. MATERIAL AND METHODS: Sixty patients aged 1.2-14.9 years (mean 8.3 ±3.5) with diagnosed malignancies and 45 healthy children as controls were recruited to the study. Patients were assessed 0-8 years (mean 2.4 ±2.0 years) after the oncological therapy. In all patients fasting blood samples were collected to measure: glucose, sodium, potassium, cortisol, aldosterone, plasma renin activity (PRA), dehydroepiandrostenedione-sulphate (DHEA-S), adrenocorticotropic hormone (ACTH) and antibodies against the adrenal cortex (AAA). Moreover, 24-hour urinary free cortisol (UFC) was assessed. Test with synthetic ACTH was carried out with 250 µg in neuroblastoma and nephroblastoma patients and with 1 µg in other oncological patients. RESULTS: The levels of morning cortisol and sodium were significantly lower and blood glucose were higher in cancer survivors than in controls (p = 0.006, p = 0.043, p = 0.008). Basal laboratory tests confirmed adrenal insufficiency (AI) in 1 patient with neuroblastoma. Low-dose ACTH revealed AI in 3 patients with acute lymphoblastic leukemia. In the study group, UFC correlated with evening and midnight cortisol (p = 0.001, p = 0.006). In the control group UFC correlated with DHEA-S (r = 0.623, p = 0.0001). None of assessed parameters correlated with the time since the completion of oncological therapy. CONCLUSIONS: The study confirmed possibility of developing asymptomatic AI in cancer survivors even several years after therapy. Instead of morning cortisol, classical diagnostic low-dose ACTH test seems to be an optimal tool for adrenal function's assessment.

Psychological Resilience of Volunteers in a South African Health Care Context: A Salutogenic Approach and Hermeneutic Phenomenological Inquiry.

Volunteering in non-Western countries, such as South Africa, is subject to poor infrastructure, lack of resources, poverty-stricken conditions and often conducted by volunteers from lower socio-economic spheres of society. Sustaining the well-being of volunteers in this context is essential in ensuring their continued capacity to volunteer. To do so, it is important to understand the psychological resilience of these volunteers and the resistance resources they employ to positively adapt to their challenging work-life circumstances. The aim of this qualitative hermeneutic phenomenological study was to explore volunteers' psychological resilience from a salutogenic perspective. In-depth interviews were conducted with eight volunteers servicing government-run hospitals. Data were analysed through phenomenological hermeneutical analysis. Findings show a characteristic work-life orientation to be at the root of volunteers' resilience. Their work-life orientation is based on a distinct inner drive, an other-directedness and a "calling" work orientation. It is proposed that this work-life orientation enables volunteers in this study context, to cope with and positively adapt to challenging work-life circumstances and continue volunteering. The elements of their work-life orientation are presented as intrapersonal strength resources fundamental to their psychological resilience. It is suggested that organisations invest in developmental interventions that endorse and promote these intrapersonal strengths.

Anti-tumour necrosis factor α therapy - Does it increase the risk of thyroid disease or protect against its development?

AIM OF THE STUDY: Tumour necrosis factor α (TNF-α) is a cytokine involved in the pathogenesis of many diseases, primarily those associated with auto-immunisation. Anti-TNF-α drugs are used in the therapy of many of them, such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, psoriasis, or inflammatory bowel disease. TNF-α is also a key factor in the pathogenesis of autoimmune thyroid disease (AITD). The incidence of AITD in people with other autoimmune diseases is increased compared to the general population. Therefore, it would be interesting to find out if anti-TNF-α therapy of other autoimmune diseases could influence the possible development or re-gression of thyroid gland dysfunction, especially AITD. AIM OF THE STUDY: The main aim of the study is to assess the effect of anti-TNF-α therapy used in inflammatory and immunological diseases on thyroid function and the development of AITD. CONCLUSIONS: The real impact of anti-TNF-α therapy on the development of AITD remains an open question. The available studies concern the adult population; there are no data regarding this problem in children. Due to the increasing use of anti-TNF-α therapy also in the paediatric population, it seems reasonable to evaluate this subject in this group of patients.

Infliximab Therapy Could Decrease the Risk of the Development of Thyroid Disorders in Pediatric Patients With Crohn's Disease.

Autoimmune diseases, including autoimmune thyroid diseases (AITDs), may be associated with Crohn's disease (CD). Taking into consideration the role of tumor necrosis factor alpha (TNF-alpha) in the immune-mediated inflammation that underlies both diseases, we evaluated an ultrasound of thyroid gland in pediatric CD patients, naïve, and treated with infliximab (IFX), an anti-TNF-alpha antibody, to assess the risk for AITD and evaluated the usefulness of ultrasonography to diagnose AITD in patients with CD. Sixty-one patients with CD were enrolled in the study, including 36 patients (mean age 14.5 ± 3.5 years) treated with IFX (IFX group) for a mean of 13.9 ± 16.6 months and 25 patients (mean age 14.7 ± 2.3 years) who never received anti-TNF-alpha therapy (control group). An ultrasound examination of the thyroid gland was performed; thyroid function tests and thyroid antibodies were assessed. We found 10-times higher prevalence of decreased thyroid echogenicity in CD and IFX-naive patients compared to IFX-treated group [a significant reduction in thyroid echogenicity in 1/36 (2.8%) patients receiving IFX compared to 7/25 (28%) patients naive to biologic therapy]. The latter showed significantly lower thyroid-stimulating hormone (TSH) levels (p = 0.034) and higher levels of thyroid antibodies (p = 0.042) in comparison to control. Our data suggest the protective role of IFX therapy in the development of thyroid disorders and indicate the usefulness of thyroid ultrasound to identify the risk of probable AITD in pediatric patients with CD.

Circulating chemerin level may be associated with early vascular pathology in obese children without overt arterial hypertension - preliminary results.

Background Elevated chemerin level is observed in patients with arterial hypertension. The aim of the study was to determine the relationship between chemerin level, and parameters of blood pressure and arterial stiffness in children and adolescents with obesity but without arterial hypertension. Methods In 23 children with obesity (13 girls, mean age 9.3, SD 1.9, mean BMI SDS 3.9, SD 1.7) 24 h ABPM (Spacelabs 90,217, USA), common carotids and abdominal aorta intima media thickness measurements (Voluson 730, GE Medical System 8.5 and 3.5 MHz probes), body composition analysis (Tanita BC 418 S MA, Tokyo, Japan) were performed. Glucose, triglycerides, total, LDL and HDL cholesterol, liver enzymes, uric acid, creatinine, sodium, insulin and chemerin levels were assessed in blood sample taken after a 12-h fasting period. Results There was a significant correlation of circulating chemerin level with systolic blood pressure load in ABPM (r=0.5, p<0.05). Conclusion Elevated chemerin level may be associated with increased systolic blood pressure in obese children.

A Comparison of the Impact of Two Methods of Nutrition-Behavioral Intervention on Selected Auxological and Biochemical Parameters in Obese Prepubertal Children-Crossover Preliminary Study.

Obese children are exposed to short and long-term health consequences, such as dyslipidemia, hypertension and diabetes mellitus. For these reasons, the prevention and treatment of obesity in the pediatric population is a challenge for health care professionals. The aim of this study was to evaluate whether an intensive intervention based on diet and physical activity has a better impact on the auxological and biochemical parameters than standard care (intervention). The study included 20 children (six boys, 14 girls), of the mean age 8.9 (SD 1.4) before puberty. The participants were randomly assigned to two groups: Group I (starting treatment with intensive intervention), and II (starting treatment with standard intervention). After three months, the groups were switched. The comparison of the two interventions in the study group indicates a better effectiveness of intensive intervention in the improvement of anthropometric parameters and majority of biochemical ones (except for insulin concentration, HOMA IR index and LDL cholesterol). As the result of intensive intervention, the mean % of weight-to-height excess and hip circumference decreased significantly (p < 0.005). Our results confirm that complex intervention based on systematic control visits, including personalized dietitian counselling and physician care, during the weight reduction process is more effective than a one-off standard visit.

Extrathyroidal congenital defects in children with congenital hypothyroidism - observations from a single paediatric centre in Central Europe with a review of literature.

INTRODUCTION: Patients with congenital hypothyroidism (CH) can have an increased risk of occurrence of extrathyroidal defects compared to the general population, which could influence their development. The abnormalities occur mainly in organ systems whose development and function is dependent on genes that are also responsible for proper organogenesis of the thyroid gland and thyroid hormone synthesis. AIM OF THE STUDY: The aim of the study was to evaluate the frequency of extrathyroidal defects in CH patients, taking into consideration the cause of this co-occurrence and the role of genetic tests. MATERIAL AND METHODS: The study included 54 newborns with positive screening test for CH based on elevated TSH level, in the years 2010-2017, from South-Eastern Poland. The data was retrieved retrospectively from patients' medical records. RESULTS: Twenty of 54 newborns with CH (37%) had congenital defects of other organs. In 10 (18.5%) cardiac defects were found, in 5 (9.25%) abnormal symptoms of the respiratory system, 7 (12.96%) had abnormalities of the gastrointestinal system, five (9.25%) had genitouri-nary abnormalities, 3 (5.55%) had abnormalities of the nervous system, and 6 (11.1%) had musculoskeletal abnormalities. CONCLUSIONS: The analysis of our data and current literature suggests that genetic factors play the most important role in the development of extrathy-roidal abnormalities in newborns with CH. Identifying the mutation causing CH, the potential defects that can accompany newborns with CH, screening could be offered for these patients in order to obtain an earlier diagnosis and implement early and appropriate treat-ment.

Amiodarone-induced thyroid dysfunction in the developmental period: prenatally, in childhood, and adolescence - case reports and a review of the literature.

INTRODUCTION: Amiodarone is an important antiarrhythmic drug used in paediatric practice, mainly in children with complex congenital cardiac diseases and/or severe arrhythmias. One of the side effects of amiodarone therapy is thyroid dysfunction, which is observed in about 20% of patients. The thyroid dysfunction may present with various forms: from subclinical changes in hormone levels to amiodaroneinduced thyrotoxicosis (AIT) and amiodarone-induced hypothyroidism (AIH). MATERIAL AND METHODS: We reported six patients in the age range from two weeks to 14 years, with complex congenital cardiac diseases and severe arrhythmias, who developed amiodarone-induced thyroid dysfunctions: thyrotoxicosis or hypothyroidism or both together. The clinical signs and symptoms of all thyroid dysfunctions were atypical, most patients presented with an aggravation of heart insufficiency. Our patients with thyrotoxicosis were treated with combined therapy including thionamides and corticosteroids due to the presentation of mixed-identified type of AIT. RESULTS: Currently, five patients (one patient's status is unknown) are in biochemical and clinical euthyreosis; however, in one of them it was impossible to discharge amiodarone treatment. Three of them are still treated with levothyroxine, and two do not need thyroid treatment. CONCLUSIONS: Amiodarone-induced thyroid dysfunction is usually atypical; therefore, monitoring of thyroid status before, during, and after amiodarone is demanded. AIH could significantly influence the development of the child, while AIT could significantly deteriorate the clinical status of children with complex cardiac diseases. Early and proper diagnose of AIT and AIH allows the introduction of immediate and appropriate treatment considering the cardiac condition of the young patient.