Neuropsychological Aspects of Children's Somatic Disorders in Chronic Diseases: Diabetes and Short Stature in the Developmental Period.

Intellectual functioning studies carried out amongst children indicate that chronic diseases like type 1 diabetes and growth hormone deficiency (GHD), may, but do not necessarily, result in intellectual loss. Cognitive functions may decline as a child becomes older, as a disease persists over time and/or due to non-compliance with treatment recommendations or high stress levels. This study aimed to assess the cognitive functioning of children and youths with T1D and GHD-related short stature compared to healthy children. METHODS: The study was carried out on 88 children with type 1 diabetes, 38 children suffering from short stature caused by (GHD), as well as a control group comprising 40 healthy children. Weschler's tests were applied to measure intellectual and cognitive functions. RESULTS: The results suggest that for children suffering from type 1 diabetes and short stature, their chronic childhood diseases per se do not impair cognitive development. It was observed that the higher the age of chronically ill children and the longer the disease persists, the lower their scores in individual cognitive subtests. For healthy children, age is correlated with the acquisition of particular skills and higher scores in specific subtests. CONCLUSIONS: On the basis of qualitative analysis of the cognitive functions subject to the study and close clinical observation of chronically ill children, we have been able to conclude that chronic diseases may alter cognitive functioning.

Dietary treatment of type 1 diabetes - once upon a time versus today.

Type 1 diabetes is a disease in which nutrition is an integral part of treatment. The type of recommended diets for therapeutic purposes has changed over the years. Proper metabolic equalization of the disease is an enormous challenge and problem for patients at the same time. This review paper discusses the history of dietary treatment of type 1 diabetes and refers to current dietary recommendations and their impact on the patient's health. The important roles of glycaemic index and glycaemic load are pointed out for proper treatment and slowing of the development of complications. Attention is also paid to the role of dietary education as an integral part of therapeutic management. Continuous progress in the development of technology is of great help to the patient.

Non-invasive detection of early microvascular changes in juveniles with type 1 diabetes.

AIMS/HYPOTHESIS: The study aimed to assess the usefulness of capillaroscopy and photoplethysmography in the search for early vascular anomalies in children with type 1 diabetes. METHODS: One hundred sixty children and adolescents aged 6-18, 125 patients with type 1 diabetes, and 35 healthy volunteers were enrolled in the study. We performed a detailed clinical evaluation, anthropometric measurements, nailfold capillaroscopy, and photoplethysmography. RESULTS: Patients with diabetes had more often abnormal morphology in capillaroscopy (68.60%, p = 0.019), enlarged capillaries (32.6%, p = 0.006), and more often more over five meandering capillaries (20.90%, p = 0.026) compared to healthy controls. Meandering capillaries correlated with higher parameters of nutritional status. In a photoplethysmography, patients with diagnosed neuropathy had a higher percentage of flow disturbance curves (p < 0.001) with a reduced frequency of normal curves (p = 0.050). CONCLUSIONS: Capillaroscopic and photoplethysmographic examinations are non-invasive, painless, fast, and inexpensive. They are devoid of side effects, and there are no limitations in the frequency of their use and repetition. The usefulness of capillaroscopy and photoplethysmography in the study of microcirculation in diabetic patients indicates the vast application possibilities of these methods in clinical practice.

Developmental enamel defects and dental anomalies of number and size in children with growth hormone deficiency.

Growth hormone is meaningfully involved in the processes of tooth cells differentiation and tissue formation. The aim of the study was to evaluate the occurrence of dental anomalies: microdontia, macrodontia, hypodontia and developmental defects of enamel (DDE) amongst a group of isolated growth hormone deficient (GHD) patients and healthy children. This cross-sectional study was based on a group of 101 Caucasian children: 33 with GHD (mean age 10.94, SD 2.51) and 68 being healthy, normal height subjects (mean age 10.4, SD 2.38). The dental examination in primary and permanent teeth was carried out by one trained and calibrated dentist, in accordance with the WHO guidelines. It was observed that 33% of GHD patients suffer from dental anomalies (hypodontia, microdontia or macrodontia), the difference between the study group and the control group was statistically significant (33% vs 4%, p < 0.001). Hypodontia and microdontia/macrodontia were the most common problems affecting 18% and 21% of the GHD individuals, respectively. The prevalence of DDE did not differ significantly between GHD group and the control group (58% vs 48%, p > 0.05). As children with GHD present more dental anomalies than their healthy coevals, clinicians should be aware of the possible oral health problems associated with GHD and consider dental screening and management as part of the patient's overall health care plan.

Obesity-induced ocular changes in children and adolescents: A review.

Childhood obesity has reached epidemic levels worldwide. Overweight and obesity is associated with an increase in several inflammatory markers, leading to chronic low-grade inflammation responsible for macro- and microvascular dysfunction. While the impact of obesity on overall health is well-described, less is known about its ocular manifestations. Still, there are few studies in children and adolescents in this regard and they are inconsistent. However, some evidence suggests a significant role of overnutrition in the development of changes in retinal microvasculature parameters (wider venules, narrower arterioles, lower arteriovenous ratio). Higher values of intraocular pressure were found to be positively correlated with high body mass index (BMI) as well as obesity. In addition, the retinal nerve fiber layer (RNFL) values seem to be lower in obese children, and there is a significant negative correlation between RNFL values and anthropometric and/or metabolic parameters. Changes also could be present in macular retinal thickness and choroidal thickness as well as in the retinal vessel density in children with obesity. However, these associations were not consistently documented. The purpose of this review is to present the most current issues on child obesity and the related potential ocular effects through an overview of international publications from the years 1992-2022.

Skeletal and dental age discrepancy and occlusal traits in children with growth hormone deficiency and idiopathic short stature.

OBJECTIVES: The aim of the study was to evaluate the dental and bone age delay and occlusal traits of children with growth hormone deficiency (GHD) and idiopathic short stature (ISS). MATERIAL AND METHODS: The study group included 46 patients aged 5 to 14 years: 15 with ISS, 17 with GHD before growth hormone treatment, and 14 with GHD during substitution therapy. The control group consisted of 46 age and sex-matched subjects of normal height. A calibrated dentist assessed all subjects in terms of dental age and occlusal characteristics. Bone age was evaluated only in GHD and ISS children as a part of a hospital's diagnostic protocol. RESULTS: The subgroup of GHD before treatment differed significantly concerning dental age delay from their healthy peers (- 0.34 and 0.83 year, respectively, p = 0.039). Dental age delay in short stature children was less marked than bone age delay (- 0.12 and - 1.76, respectively, p < 0.00001). Dental crowding was recorded in 57% of ISS patients and 53% of GHD children before treatment compared to only 22% of the control subjects (p = 0.027 and p = 0.021, respectively). CONCLUSIONS: Dental age was retarded in GHD children before growth hormone (GH) therapy, but the delay does not seem clinically significant. ISS children and GHD children before therapy showed marked bone age delay and tendency to crowding. CLINICAL RELEVANCE: The different pace of teeth eruption and skeletal growth in short stature children should be considered when planning their dental treatment.

Clinical Implications of Growth Hormone Deficiency for Oral Health in Children: A Systematic Review.

Growth hormone (GH) is involved in the regulation of the postnatal dental and skeletal growth, but its effects on oral health have not been clearly defined. This paper aims to provide a review of current clinical knowledge of dental caries, tooth wear, developmental enamel defects, craniofacial growth and morphology, dental maturation, and tooth eruption in growth hormone deficient (GHD) children. A systematic review was carried out using Scopus, MEDLINE-EbscoHost and Web of Science from 2000 to May 2021. PRISMA guidelines for reporting systematic reviews were followed. All the selected studies involved groups under eighteen years of age, covering a total of 465 GHD patients. The studies that were selected provide reliable evidence for delayed dental maturity and orthodontic disturbances in GHD patients. Data on dental hard tissues pathology are scarce and are limited to occurrences of dental caries. GHD children showed abnormal craniofacial morphology with reduced mandibular dimensions, with a resulting tendency towards Angle's Class II occlusion, which affected up to 31% of patients. Dental age has been shown to be delayed in GHD patients by about 1 to 2 years. Moreover, the risk of dental caries in children with GHD decreases with increasing levels of vitamin D. Hence, further studies would be valuable for evaluating the risk of various oral health problems and to organize targeted dental care for this vulnerable group.

Do the intervals in growth hormone therapy positively affect the growth velocity?

INTRODUCTION: A significant increase in growth velocity is observed during recombinant human growth hormone (rhGH) therapy in patients with growth hormone deficiency (GHD), especially just after the beginning of treatment. This phenomenon is referred to as catch-up growth". After some time, the growth velocity decreases to the physiological value, i.e. the value that is observed in healthy children. The treatment is continued until the time of the growth process is completed. The continuity of the therapy makes it impossible to assess whether the catch-up phenomenon occurs only at the beginning of the treatment or may be observed after treatment cessation and its re-introduction. MATERIAL AND METHODS: Growth velocity was evaluated in a group of 35 patients with GHD after repeated therapy application, in which, due to non-medical reasons, the rhGH treatment was abandoned for a short time. RESULTS: Patients with GHD after treatment re-introduction presented the catch-up growth phenomenon and obtained growth velocity results that were significantly higher than those observed during primary treatment. CONCLUSIONS: Re-introduction of rhGH treatment after short-term therapy cessation leads to the re-occurrence of catch- up growth in patients with GHD.

Maternal anxiety in relation to growth failure and growth hormone treatment in children.

Health disorders in mothers and their children are subject to mutual influences arising from the nature of mother-child relationship. The aim of the study was to analyze the issue of anxiety amongst mothers of short children in aspect of growth hormone (GH) therapy in Poland.The study was based on a group of 101 mothers of originally short-stature children: 70 with GH deficiency treated with recombinant human GH and 31 undergoing the diagnostic process, without any treatment. Collected medical data included the child's gender, height and weight, chronological age, bone age delay, and GH therapy duration. For all children the height SDS (standard deviation score of height) and BMI SDS (standard deviation score of body mass index) were calculated. The Spielberger State-Trait Anxiety Inventory (STAI) was used to evaluate anxiety levels among the recruited mothers. Obtained results revealed low trait anxiety levels in all mothers, with no statistically significant differences between the groups. State anxiety levels were significantly higher in mothers of children without diagnosis and treatment than in mothers of children receiving appropriate therapy. Significantly lower levels of maternal state anxiety were observed during the first stage of the GH therapy, and they were further reduced in mothers of children treated for more than 4 years.Growth failure in Polish children is not associated with high maternal anxiety as a personality trait, but lack of diagnosis and lack of appropriate treatment seem to generate high levels of anxiety as a transient state in mothers. The initiation of GH therapy induces a substantial reduction of maternal state anxiety, and the duration of this treatment causes its further decrease. Mothers of short children undergoing diagnostic process could benefit from psychological support, but it seems to be unnecessary when their children are treated with GH.

Changes in cognitive functions in a girl with severe acquired hypothyroidism in comparison to the healthy twin sister.

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Polymorphism of the growth hormone gene GH1 in Polish children and adolescents with short stature.

PURPOSE: Short stature in children is a significant medical problem which, without proper diagnosis and treatment, can lead to long-term consequences for physical and psychological health in adult life. Since human height is a polygenic and highly heritable trait, numerous variants in the genes involved in growth-including the growth hormone (GH1) gene-have been identified as causes of short stature. METHODS: In this study, we performed for the first time molecular analysis of the GH1 gene in a cohort (n = 186) of Polish children and adolescents with short stature, suffering from growth hormone deficiency (GHD) or idiopathic short stature (ISS), and a control cohort (n = 178). RESULTS: Thirteen SNP variants were identified, including four missense variants, six in 5'UTR, and three in introns. The frequency of minor missense variants was low (<0.02) and similar in the compared cohorts. However, two of these variants, Ala39Val (rs151263636) and Arg42Leu (rs371953554), were found (heterozygote status) in only two GHD patients. These substitutions, according to databases, can potentially be deleterious. CONCLUSIONS: Mutations of GH1 causing short stature are very rare in the Polish population, but two potentially causative variants need further studies in a larger cohort of GHD patients.

Assessment of anterior-posterior spinal curvatures in children suffering from hypopituitarism.

BACKGROUND: Body posture may be disordered by vestibular dysfunction, neurological disorders, problems with the distribution of muscle tone, brain injuries, and other dysfunctions. Growth hormone deficiency (GHD) can lead to many disorders, particularly of the musculoskeletal system. During treatment with recombinant human growth hormone (rhGH), an increase in muscle mass and an improvement in bone structure can be observed in children suffering from hypopituitarism from GHD. METHODS: The study involved 33 children suffering from hypopituitarism with GHD (9 girls and 24 boys), aged 10-14 years old. Measurements of the magnitude of their anterior-posterior spinal curvatures were made using an inclinometer. The children were examined at the medianus of the sacrum bone, the Th12-L1 intervertebral area, and the C7-Th1 intervertebral area. In order to characterize the anterior-posterior curvature of the spine, the results were compared with the general norms reported by Saunders. Statistical calculations were carried out using the statistical package Statistica 10 PL. RESULTS: Lumbar lordosis angles were higher in the patients currently receiving growth hormone (GH) treatment than in those who had yet to receive it. There is a statistically significant positive correlation between the length of growth hormone treatment and the alpha angle. There are also statistically significant correlations between age at the beginning of growth hormone therapy and the angle of lordosis. Statistically significant correlations were also seen between age at the beginning of growth hormone therapy and the alpha angle. CONCLUSIONS: Although there may be changes in posture at the beginning of rhGH treatment, the sooner growth hormone therapy begins, the better the body posture. The longer the growth hormone treatment, the better the posture, as expressed by the alpha angle in the sagittal plane.

Acquired autoimmune hypothyroidism as a cause of severe growth deficiency in one of the twin sisters.

Acquired autoimmune hypothyroidism is rare in early childhood, however, it must be considered in a 4 year old child with medical his-tory of delayed growth, increased somnolence, difficulty concentrating, and reduced activity. We report on the case of full clinical picture of severe hypothyroidism in one of the twins. Thyroid function deteriorated in one of the sisters, resulting in mental, motor and growth slowdown, remaining undiagnosed for about 2 years, while the other sister developed normally. In the reported case, severe hypothy-roidism and growth deficiency were accompanied by celiac disease. Initiation of L-thyroxine therapy resulted in an immediate response that increased the growth velocity by more than 2.2 times. This confirms the dominant role of thyroid hormones over celiac disease in the growth process, as the catch up effect started before gluten free diet was introduced.

Treatment of severe primary IGF-1 deficiency using rhIGF-1 preparation - first three years of Polish experience.

INTRODUCTION: The objective of this study was to analyse the effects of the first three years of treatment with recombinant human insulinlike growth factor 1 (rhIGF-1) in patients from the Polish population. MATERIAL AND METHODS: Twenty-seven children (22 boys and five girls) aged 2.8 to 16.0 years old were qualified for treatment with rhIGF-1 (mecasermin) in different treatment centres, according to Polish criteria: body height below -3.0 SD and IGF-1 concentration below percentile 2.5 with normal growth hormone (GH) levels. Mecasermin initial dose was 40 µg/kg bw twice a day and was subsequently increased to an average of 100 µg/kg bw twice a day. Body height, height velocity, weight, body mass index (BMI), and adverse events were measured. RESULTS: Mecasermin treatment resulted in a statistically significant increase in body height (1.45 ± 1.06 SD; p < 0.01) and height velocity in comparison with pre-treatment values. The biggest change in height velocity happened during the first year and diminished during subsequent years. Body weight and BMI also increased significantly after treatment (1.16 ± 0.76 SD and 0.86 ± 0.75 SD, respectively; p < 0.01). Eight patients reported adverse events. These were mild and temporary and did not require treatment modification except in two patients. CONCLUSIONS: Treatment with rhIGF-1 was effective and safe in Polish patients with primary IGF-1 deficiency. It had a clear beneficial effect on the height of the patients and significantly accelerated the height velocity, particularly in the first year of treatment.

[Papillary thyroid carcinoma in a patient with Turner syndrome treated with human growth hormone].

Thyroid cancer is a rare pathology in childhood and adolescence, being responsible for 1.5-3% of all carcinomas in this age group. Differentiated thyroid carcinoma is the most commonly found variant, especially papillary carcinoma of the thyroid (PCT). Currently available data support the hypothesis that growth hormone (GH) as well as insulin-like growth factor 1 (IGF-1) can facilitate carcinogenesis. There is a confirmed role of the GH/IGF-1 axis in cancer progression as an initiator of tumorigenesis and neoplastic transformation, metastasis, and resistance to chemotherapy and radiotherapy. Presently, application of recombinant GH is an acceptable method to treat female patients with growth failure during the course of Turner syndrome (TS). This article reports the case of a fourteen-year-old female patient with Turner syndrome, Hashimoto thyroiditis, and papillary thyroid carcinoma diagnosed during GH treatment. The immunochemical analysis of tumour tissue in our patient revealed intensive brown reaction that labelled expression of the IGF-1R vs. traced reaction or its lack in normal thyroid tissue. A significant role is played by IGF-1 in the pathogenesis of invasion of thyroid cancer; however, this effect is complex, and how it works is not well established.

EVALUATION OF THE TEA TREE OIL ACTIVITY TO ANAEROBIC BACTERIA--IN VITRO STUDY.

The study of the sensitivity to tea tree oil (Australian Company TTD International Pty. Ltd. Sydney) was carried out on 193 strains of anaerobic bacteria isolated from patients with various infections within the oral cavity and respiratory tracts. The susceptibility (MIC) of anaerobes was determined by means of plate dilution technique in Brucella agar supplemented with 5% defibrinated sheep blood, menadione and hemin. Inoculum contained 10(5) CFU per spot was cultured with Steers replicator upon the surface of agar with various tea tree oil concentrations or without oil (anaerobes growth control). Incubation the plates was performed in anaerobic jars under anaerobic conditions at 37 degrees C for 48 h. MIC was defined as the lowest concentrations of the essential oil completely inhibiting growth of anaerobic bacteria. Test results indicate, that among Gram-negative bacteria the most sensitive to essential oil were strains of Veillonella and Porphyromonas species. Essential oil in low concentrations (MIC in the range of = 0.12 - 0.5 mg/mL) inhibited growth of accordingly 80% and 68% strains. The least sensitive were strains of the genus Tannerella, Parabacteroides and Dialister (MIC 1.0 - 2.0 mg/mL). In the case of Gram-positive anaerobic bacteria the tea tree oil was the most active to strains of cocci of the genus Anaerococcus and Ruminococcus (MIC in range = 0.12 - 0.5 mg/mL) or strains of rods of the genus Eubacterium and Eggerthella (MIC = 0.25 mg/mL). Among Gram-positive rods the least sensitive were the strains of the genus Bifidobacterium ( MIC = 2.0 mg/mL). The tea tree oil was more active to Gram-positive than to Gram-negative anaerobic bacteria.

Polymorphisms in the P1 promoter of the IGF-1 gene in children with growth disorders.

BACKGROUND/AIMS: The aim of this study was to associate children's growth disorders with polymorphisms detected in the P1 promoter region of IGF1 (including SNP and (CA) n microsatellite repeat polymorphism) and IGF1 and IGFPB3 levels. METHODS: IGF-1 gene P1 promoter polymorphism was analyzed in DNA obtained from the blood of 51 children with growth disorders and 50 healthy children without growth disorders by means of PCR-SSCP and sequencing. RESULTS: Among children with growth disorders and the control group we found previously described polymorphisms in the P1 promoter of the IGF-1 gene (rs35767, rs5742612) and different genotypes. The frequency of both detected polymorphisms was no significantly different in the study and the control groups. The CA repeat sequence within the group of children in the study ranged from 11 to 21. The most common were homozygote 19/19 (49.02%) and heterozygote 19/20 (27.45%). Our results did not show any association between polymorphisms in the P1 promoter and IGF-1 levels in the serum of children with growth disorders. CONCLUSIONS: This study demonstrated that SNP and (CA) n microsatellite repeat polymorphisms by themselves are not the primary regulatory elements of IGF-1 expression. However, our bioinformatics analysis has shown that the (CA) n microsatellite region in the P1 promoter of IGF-1 is able to form DNA loop structures which can modulate transcription.

Hypertrophic scars in a patient with Turner's syndrome treated with recombinant growth hormone.

Turner's syndrome is a common genetic disorder of girls and women, for which characteristic clinical symptoms encompass short stature, gonadal dysgenesis, systemic defects, multiple dysmorphic features and skin changes, including an increased number of melanocytic nevi, hypertrophic scars and keloids. The affected girls are treated with recombinant human growth hormone to improve the height. We present a case of a 15-year-old girl with Turner's syndrome, hypertrophic scars and a keloid. At the age of 12 years and 8 months, the girl started recombinant human growth hormone treatment. During the therapy, a surgical excision of 4 out of 42 benign melanocytic nevi was performed. After 2 months the hypertrophic scars as well as a keloid were noted at sites of excision. Parents of girls with Turner's syndrome undertake various attempts to improve not only the height and maturity of their daughters, but also their appearance by commonly performed surgical corrections of the webbed neck and pigmented nevi. The presented case suggests an increased risk of scars hypertrophy and keloid formations after surgical intervention in Turner's syndrome patients who are treated with recombinant human growth hormone at the same time. Due to that it should be advised to postpone all planned surgical procedures until the therapy has been completed.

Evaluation of final height prediction and selected parameters in Polish patients with severe and partial growth hormone deficiency.

OBJECTIVES: The main goal of growth hormone therapy is to reach the height in the population ranges. The aim of the study was the comparison of selected methods for predicting final height in Polish patients with severe (sGHD) and partial (pGHD) growth hormone deficiency. METHODS: 149 children with growth hormone deficiency treated with rhGH in the Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology Developmental Age, PUM, in Szczecin, in 2000-2010 have been evaluated. Patient were divided into two groups: sGHD and pGHD. Two methods of final height prediction have been used: Roche-Weiner-Thissen (RWT) and target height (TH), results were compared to the final height (FH). 117 children finished therapy in the analysed period and reached final height. RESULTS: The mean FH was similar in both groups. There was no significant difference between the accuracy of prediction methods of TH and RWT between groups of pGHD v. sGHD. Further analysis revealed, that in the group of boys with sGHD the prediction error of RWT was significantly lower than of the TH method (p < 0.05). CONCLUSIONS: It seems that in the group of boys with sGHD RWT is a more accurate method than TH.

Placental growth hormone (PGH), pituitary growth hormone (GH1), insulin-like growth factor (IGF-I) and ghrelin in pregnant women's blood serum.

OBJECTIVES: The aim of this work is to evaluate levels of placental growth hormone (PGH), pituitary growth hormone (GH1), insulin-like growth factor (IGF-I) and ghrelin in pregnant women's blood serum before, during and after delivery. Furthermore, the aim is to search for links and interdependence of GH1, PGH and IGF-I concentrations. MATERIAL AND METHODS: Seventy nine blood samples were taken one to two hours before, during and half an hour after expulsion of placenta. All proteins studied were determined by ELISA method, using ELISA Kit. RESULTS: The highest PGH concentration and IGF-I concentration in pregnant women's blood serum was observed before delivery while GH1 concentration was lowest. During and after delivery PGH and IGF-I concentration decreased proportionately and pituitary growth hormone concentration increased accordingly. About half an hour after delivery of the placenta, GH1 concentration was highest. CONCLUSIONS: In pregnant women's blood there is a metabolic interdependence between PGH and IGF-I. Their concentration increases proportionately during pregnancy and decreases after delivery. It appears that labor and delivery releases GH1 blockade, which level rises three-fold during delivery. After parturition its role and concentration returns to levels before pregnancy.