The effect of gonadoliberin analog treatment in precocious puberty on polycystic ovarian syndrome prevalence in adulthood.

Precocious puberty is diagnosed when pubertal characteristics appear before the age of 8 years in females. The most common form is gonadotropin-dependent, called axial. The primary method of treatment is administration of gonadotrophin-releasing hormone analogues (GnRHa). The aim of the study was to verify hypothesis that GnRHa therapy in the childhood may be of additive risk factor for polycystic ovary syndrome (PCOS) in adulthood. Material and Methods: The study group consists of 24 women (median age 22 88 years, median BMI 23.5) treated with GnRHa for central precocious puberty in childhood. The control group includes 40 women (median age 23 years, median BMI 25.6) diagnosed with isolated premature thelarche and not using GnRHa in the childhood. Anthropometric measurements, ultrasound examination of minor pelvis and hormonal profile were performed. PCOS diagnosis was based on Rotterdam criteria. Results: The study confirmed a higher prevalence of PCOS in the study group (50%) than in the control group (10%); p=0.0006. Significant, linear correlation between free testosterone levels and ovarian size was found in the study group (R=0.45 p= 0.03). Conclusions: GnRHa therapy during childhood may have a potential influence on incidence of PCOS in the adulthood. Therefore, in this group of patients long-term follow-up focused on screening for PCOS would seem beneficial.

Self-assessment and self-perception of the body in 18-year-old girls.

INTRODUCTION: Studies focusing on self-perception of one's body usually cover subjects with eating disorders. There is a lack of similar studies. AIM OF THE STUDY: Conducting survey research on self-assessment and self-perception of one's own body in girls. MATERIAL AND METHODS: A survey was conducted in 1047 female students (average age: 18 years ±0.25) focusing on self-assessment and self-perception of their body mass, body parts, and eating habits. The study subjects were divided into groups of normal weight, obese, and underweight according to their BMI and BMI-SDS. RESULTS: There were twice as many girls dissatisfied with their body weight in the underweight group and 10 times as many in the obese group. 8% of girls with normal body weight perceived their body as overweight. 70% of subjects with a normal body weight and ca. 25% of obese thought they were obese in the area of the abdomen, hips, buttocks, and thighs. Fear of gaining weight was characteristic most often for girls with abnormal body weight who confessed to eating disorders. CONCLUSIONS: 1. Most 18-year-old girls do not demonstrate any symptoms of distorted body self-perception; a vast majority of girls with normal body weight exaggerate the shapes of body parts, which causes them to undertake measures aiming to lose weight. Only a quarter of obese subjects perceive their individual body parts as obese, which might result in their lack of motivation to lose weight. 2. It is necessary to introduce healthy lifestyle educators in schools to prevent ED and obesity in adolescents.

Diagnostic difficulties in the diagnosis of high acute-phase proteins levels in a teenage drug addicted female patient.

BACKGROUND: Youth drug addiction is a significant social and health problem. Symptoms of the disease include a number of neurological, gastrointestinal and cardiovascular disorders. Possible hormonal disorders and dysregulation of the immune system could also occur. CASE PRESENTATION: We describe a case of a teenage patient with multiple diseases such as esophagitis, allergic disease, and numerous behavioral disorders leading to: self-injury of the body, suicide attempts by drugs overdosing, and experimentation with various psychoactive substances (morphine, amphetamine, methamphetamine, codeine). She was also diagnosed with bipolar disorder. A few hours before the admission to the ward, the patient had an intravenous injection of drugs. Toxicological tests confirmed the presence of amphetamine, ecstasy and opioids in the blood and urine. Laboratory tests revealed extremely increased inflammatory parameters, leucopenia, increased levels of IgG, IgA and IgE (total) immunoglobulins, low concentration of vitamin D. Bacteriological examinations were negative. General condition of the patient got better very quickly, antibiotic therapy was abandoned on the 4th day. It was concluded that the cause of the elevated concentration of acute-phase proteins was most likely caused by intoxication with psychoactive drugs. CONCLUSIONS: The discussed case shows the difficulties of differential diagnosis in a teenage patient struggling with many diseases, who has been abusing drugs for several years. Increased inflammatory parameters in the form of an raised PCT, CRP, NLR, PLR values may be caused by many factors. In adolescents who frequently experiment with psychoactive substances, such cause of these disturbances should also be taken into account.

Sweet, Salty, and Umami Taste Sensitivity and the Hedonic Perception of Taste Sensations in Adolescent Females with Anorexia Nervosa.

OBJECTIVE: The aim of this study was to perform analysis of sensitivity to sweet, salty, and umami tastes based on three measurement methods and of the hedonic perception of taste sensations in adolescent females with anorexia nervosa (AN). The aim of the research was to confirm the results of other authors in terms of the perception of sweet and salty taste in patients with AN, and then develop knowledge about the perception of umami taste, which is still insufficiently studied. METHOD: A total of 110 females with an age ranging from 13 to 19 years, including 50 newly diagnosed patients with a restrictive subtype of AN and 60 healthy controls participated in gustatory research involving analyses of taste perception (recognition thresholds, ability to identify the taste correctly, taste intensity, and hedonic response) applying the sip and spit method. RESULTS: Females with AN showed reduced sensitivity to salty taste and increased sensitivity to umami taste and, more often than healthy controls, wrongly classified the taste of solutions with a low sucrose concentration. Patients with AN assessed the sodium chloride and monosodium glutamate tastes less negatively than did control participants, and they did not show differences in their hedonic assessment of sucrose. CONCLUSIONS: The taste sensitivity alterations in females with AN demonstrated in this paper do not entail decreased hedonic assessment of taste experiences. Based on our results, we cannot consider the observed variation in taste sensitivity in patients with AN to be a factor that increases their negative attitude toward food consumption.

Assessment of Long-Term Treatment Results in Women Suffering from Anorexia Nervosa in Adolescence.

INTRODUCTION: Reports assessing long-term treatment outcomes for anorexia nervosa (AN) are divergent and refer to different populations. They lack long-term observations in AN patients in Poland. AIM OF THE STUDY: Analysis of the recovery, relapse rate, and predictive factors in patients treated due to AN in adolescence. MATERIAL AND METHODS: A total of 201 subjects were given a survey. Ninety-seven women were recruited: 56 reported to the clinic and 41 filled in the survey. RESULTS: The average period from hospitalization to the survey was 7.76 ±4.39 years. Remission was found in 78.4%, 21.6% still pre-sented AN, and 84.2% required a one-off hospitalisation, 10.5% twice. The average BMI was: 20.08 ±3.24 kg/m 2 . The rate of attempted suicides was 6.2%. Predictive factors for poor outcome were as follows: older age of the patient when falling ill, lower SDS-BMI score at the onset of AN, transition from the restrictive type of AN into a binge-eating/purging type, and fail-ure to maintain contact with the mother. CONCLUSIONS: 1. Most girls suffering from the restricting type of AN in adolescence are cured permanently. 2. The severity of symptoms in these girls does not eliminate the chance of recovery and achieving important life goals, com-pleting education, finding a life partner, and having children. 3. Girls with a smaller degree of cachexia at onset of AN, with no binge-eating/purging symptoms, maintaining regular con-tact with their mothers, have a better prognosis for recovery. 4. Six per cent of women treated in their youth for AN face the risk of attempted suicide, which points to the need to monitor their mental state for many years.

Assessment of the frequency of hormonal disorders of the gonads and bone mineral density among women treated for anorexia nervosa in adolescence.

INTRODUCTION: There are very few studies evaluating the activity of gonads in women treated for anorexia nervosa (AN) in adolescence, and reports on the bone mineral density in such patients are divergent. Objective Assessment of the incidence of gonadal hormonal function disorders and reduction of bone mineral density in women treated for AN in adolescence. MATERIAL AND METHODS: Out of 97 women who had participated in a survey study, 56 reported personally to the clinic. Their somatic condition, body weight, and BMI were evaluated, as well as levels of oestradiol, LH, FSH in blood serum were determined and DEXA scans were performed. RESULTS: The average period of hospitalisation until the time of the study was 7.08 ±4.47 years. BMI was as follows: 20.01 ±3.6 kg/m2. 25% women were still sick, 75% were considered cured. In 17.9% of the study subjects hypogonadotropic hy-pogonadism was diagnosed. Abnormal results of the densitometric scan were confirmed in 85.7% of the study subjects. In the group of women with normal body weight only 19% had normal levels of bone mineral density. CONCLUSIONS: 1. In almost 18% of women treated for AN in adolescence, disorders of the hormonal function of gonads persist, despite normal body weight in 50% of them. 2. Bone mineral density is reduced in most women treated for AN, which indicates the need to monitor the condition of the bones, an early introduction of prevention of osteopenia and osteoporosis since the onset of AN in order to prevent bone fractures in adulthood.

[The relationship between chemerin, bone metabolism, the RANKL/RANK/OPG system, and bone mineral density in girls with anorexia nervosa].

INTRODUCTION: Based on recent studies in humans, chemerin has been classified as an adipokine that might be associated with osteoporosis and BMD. Bone loss is common in adolescents with anorexia nervosa (AN). Moreover, dysfunction in the production of chemerin has also been shown. Therefore, we carried out a comparative analysis between chemerin, bone metabolism, the RANKL/RANK/OPG system, and BMD in girls with AN. MATERIAL AND METHODS: Plasma chemerin, OC, CTx, OPG, and sRANKL were determined by ELISA in 75 girls with AN aged 12.6-17.8 years. BMD was assessed by DXA and expressed as Z-score according to the lumbar spine (s) and total body (TB) sites. According to the s-BMD- and TB-BMD Z-score, girls with AN were divided into two subgroups with parallel analyses used: normal (Z-score > -2.0) and low (Z-score ≤ -2.0) s-BMD, and normal (Z-score > -2.0) and low (Z-score ≤ -2.0) TB-BMD. RESULTS: Mean OC and the OPG/sRANKL ratio were markedly lower in the low s-BMD subgroup compared to the normal s-BMD subgroup. The s-Z-score values (both low and normal) correlated significantly and positively with the OPG/sRANKL ratio. Only in the low s-BMD subgroup did chemerin correlate significantly and positively with all nutritional indices and the OPG/sRANKL ratio. In the low TB-BMD subgroup the mean OC and the OPG/sRANKL ratio were lower than in the normal TB-BMD subgroup. The TB-Z-score values (both normal and low) correlated significantly and positively with all nutritional indices and the OPG/sRANKL ratio. The low TB-Z-score values correlated significantly and positively also with chemerin. In the low TB-BMD subgroup chemerin correlated significantly and positively with weight and BMI (expressed as absolute values), Cole index, the duration of the disease, and OPG/sRANKL ratio while its correlation with age was negative. CONCLUSIONS: Undernutrition and associated deficit of adipose tissue may result in inadequate chemerin production and skeletal disorders in girls with AN. Chemerin acts as a coordinator of the dynamic balance between bone metabolism and the OPG/RANK/RANKL system and, in turn, may contribute to the loss of bone mass in girls with AN. The cortical bone site seems to be more severely responsive to chemerin actions than the trabecular bone site.

Exocrine Pancreatic Function in Girls with Anorexia Nervosa.

OBJECTIVES: To assess pancreatic exocrine function in patients with anorexia nervosa using a breath test with 13C-labeled mixed triglycerides (MTG-BT) and to determine the relationship between the test results and selected biochemical and hormonal parameters. MATERIAL AND METHODS: Anthropometric measurements, biochemical and hormonal parameters (serum leptin, soluble leptin receptor (sLR), acylated and desacylated ghrelin, free leptin index (FLI)), and MTG-BT were performed in a group of 31 girls with the restrictive type of AN, as well as 38 healthy girls (C). RESULTS: The average cumulative dose of 13C-triglycerides recovered with exhaled air (%CD) was similar in both study groups, while the average time from 13C-triglycerides administration to peak 13CO2 excretion in expired air (time to peak (TTP)) was significantly longer in patients with AN compared to C. In both groups, %CD correlated negatively with FLI. TTP correlated negatively with sLR and FLI in the AN and with serum insulin and HOMA-IR values in the C. CONCLUSIONS: In girls with AN, the pancreatic efficiency of lipase secretion was found to be normal, while the kinetics of this enzyme secretion were disturbed. These changes may result from disorders in the functioning of the adipose-insular and islet-acinar axes.

Evaluation of the frequency of ADIPOQ c.45 T>G and ADIPOQ c.276 G>T polymorphisms in adiponectin coding gene in girls with anorexia nervosa.

INTRODUCTION: Anorexia nervosa (AN) is a serious chronic psychosomatic disorder, the essence of which are attempts by the sufferer to obtain a slim silhouette by deliberate weight loss (restrictive diet, strenuous physical exercise, provoking vomiting). The aetiology of this disorder is multifactorial. Genetic factors that influence the predisposition to AN have been sought. A broad meta-analysis points to a strong genetic correlation between AN and insulin resistance. Adiponectin (ADIPO) increases insulin sensitivity. In our pilot study we demonstrated that the TT genotype in locus ADIPOQ c.276 G>T of the ADIPO gene and a higher concentration of ADIPO in blood serum occurred significantly more frequently in 68 girls suffering from AN than in 38 healthy girls. The objective of this study was to evaluate the frequency of the occurrence of ADIPOQ c.45 T>G and ADIPOQ c.276 G>T in the ADIPO gene in a larger cohort of girls with AN and healthy girls, as well as an analysis of correlations between variants of the aforementioned polymorphisms and the levels of ADIPO in blood serum. MATERIAL AND METHODS: The study covered 472 girls (age: 11-19 years): 308 with the restrictive form of AN (AN) and 164 healthy girls (C). The level of ADIPO in blood serum was determined by means of the ELISA method on a Bio-Vendor, LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out in a ThermoCycle T100 thermocycler. 80-150 ng of the studied DNA and relevant F and R starters were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP). RESULTS: The distribution of genotypes in the polymorphic site ADP c.45 of the ADIPO gene and ADP c.276 was similar in both groups. In both groups the T allele was most frequent in locus ADIPOQ c.45 and the G allele in locus ADIPOQ c.276. In all the study subjects collectively (AN and C) a statistically significant negative correlation between the levels of ADIPO in blood serum on one hand and body weight (r = -0.46; p < 0.0001) and BMI (r = -0.67; p < 0.0001) on the other was demonstrated. Exclusively in the AN group a significant correlation between the level of ADIPO in blood and the distribution of TG, TT, and GG alleles in loci ADIPOQ c.45 and ADIPOQ c.276 was demonstrated (p = 0.0052 and p < 0.0001, respectively). CONCLUSIONS: The genotype in loci ADIPOQ c.45 and ADIPOQ c.276 of the ADIPO gene seems to have no effect on the predisposition to AN. Girls suffering from AN with the TT genotype in loci ADIPOQ c.45 and ADIPOQ c. 276 may demonstrate higher insulin sensitivity because they have significantly higher levels of ADIPO than girls suffering from AN with other genotypes. This may be suggestive of their better adaptation to the state of malnutrition, and it has a potential effect on treatment results.

Evaluation of the frequency of RETN c.62G>A and RETN c.-180C>G polymorphisms in the resistin coding gene in girls with anorexia nervosa.

INTRODUCTION: Anorexia nervosa (AN) is a serious psychosomatic syndrome, classified as an eating disorder. AN patients strive to lose weight below the normal limits defined for a specific age and height, achieving their goal even at the expense of extreme emaciation. AN has a multifactorial aetiology. Genetic factors are believed to be significant in the predisposition to the development of AN. In girls suffering from AN significantly lower levels of resistin (RES) in blood serum are observed as compared to healthy girls. These differences may lead to a thesis that functional genetic polymorphisms in RES coding genes can be responsible for this phenomenon. In our pilot study we demonstrated significant differences in the distribution of genotypes in the locus RETN c.-180C>G of the RES gene in 67 girls with AN and 38 healthy girls. It seems reasonable to compare the frequency of polymorphisms of RETN c.62G>A and RETN c.-180C>G in the RES gene in girls with AN and in healthy subjects in a bigger cohort and to analyse correlations between individual variants of the polymorphisms referred to above and the RES levels in blood plasma. MATERIAL AND METHODS: The study covered 308 girls with the restrictive form of AN (AN) and 164 healthy girls (C) (aged 11-19 years). The RES levels in blood serum were determined by means of the ELISA method on a Bio-Vendor machine from LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out on a ThermoCycle T100 thermocycler. 80-150 ng of the studied DNA and relevant F and R starters were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP). RESULTS: The average RES level in blood serum in the AN group was significantly lower (p < 0.0001) than in the C group. The distribution of genotypes in the locus RETN c.62 of the RES gene was similar in both groups. A significant difference was demonstrated in the distribution of genotypes in the polymorphic site RETN c.-180 of the RES gene between AN and C (p = 0.0145) and in the distribution of the C and G alleles in the locus RETN c.-180 (p < 0.0001). The C allele occurred significantly more frequently than the G allele in the C group as compared to the AN group. In all the study subjects jointly (AN and C) a significant positive correlation between the blood RES levels on one hand and the body mass (r = 0.42; p < 0.0001) and BMI (r = 0.61; p< 0.0001) on the other was observed. There was no correlation between the concentration of RES in blood serum and the distribution of genotypes in the loci of the resistin gene referred to above. CONCLUSIONS: The CG genotype in the locus RETN c.-180 C>G of the RES gene may constitute one of the factors predisposing to the development of AN in girls. The genotype in the loci RETN c.62 G>A and RETN c.-180 C>G of the resistin gene has no influence on the levels of this hormone in blood in AN patients.

A rare case of primary amenorrhoea and breast development in a 46,XY 15-year-old girl.

A disorder of sex development (DSD) is defined as a congenital condition in which development of chromosomal, gonadal, or anatomical sex is atypical. Swyer syndrome is an example of 46,XY DSD with a female phenotype. It usually becomes apparent in adolescence with delayed puberty and amenorrhoea. Spontaneous breast development is very rare. A 15-year-old girl was presented due to primary amenorrhoea with breast development compatible with Tanner stage V. Hormonal tests revealed hypergonadotropic hypogonadism with low level of oestradiol. Pelvic ultrasound and magnetic resonance imaging revealed a small uterus, and no ovaries were found. In the right lower abdomen, a structure of unknown origin was visible. The chromosome analysis revealed a 46,XY karyotype. The patient was qualified for a laparoscopic bilateral gonadectomy. Postoperative histopathological examination revealed gonadoblastoma. We underline the need to consider DSD 46,XY in the presence of primary amenorrhoea, even when pubertal development is present. Germ cell tumors have a tendency to grow and metastasize rapidly. Delayed diagnosis may increase the risk of malignant transformation and cause a poor diagnosis.

Is adiponectin in children with immunoglobulin A vasculitis a suitable biomarker of nephritis in the course of the disease?

INTRODUCTION: Immunoglobulin A vasculitis (IgAV) is the most common form of vasculitis in children. Nephritis in the course of this disease (IgAVN) is observed in 30-50% of patients and might lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Finding a non-invasive biomarker to distinguish initially between patients with and without nephritis and to facilitate a therapeutic decision to reduce the risk of long-term renal impairment is currently the target of much research. The aim of this study was to evaluate the adiponectin concentration in children with IgAV and estimate whether it might be used as a marker of IgAVN. MATERIAL AND METHODS: The study involved 29 IgAV children and 34 healthy controls. Eleven (38%) patients had renal involvement (IgAV-N) and 18 (62%) did not exhibit nephritis (IgAV-noN). The serum adiponectin level was estimated in children in an acute phase of IgAV and after 2-6 months during a follow-up visit. The relationship between the concentration of adiponectin and anthropometric measurements, epidemiological data and laboratory parameters were evaluated. RESULTS: The concentration of adiponectin in serum was significantly higher in children with acute phase of IgAV as compared to the control group (p < 0.001), and in patients without renal involvement in comparison with IgAV-N children (p < 0.049). In analysis of correlation we found a negative relationship between adiponectin level and serum creatinine concentration (r = -0.437, p = 0.02). The logistic regression evaluation demonstrated that a low adiponectin level increased the risk of nephritis in the course of IgAV. CONCLUSIONS: Our study revealed that the serum adiponectin level increased markedly in patients with IgAV. We also documented that higher risk of nephritis in the course of the disease was associated with lower concentration of this hormone.

Serum interleukin 15 in anorexia nervosa: Comparison to normal weight and obese girls.

Background: Interleukin 15 (IL-15) plays a key role in the muscle-fat interaction, reducing adipose tissue mass without changes in the lean body mass and reduction of food intake. Here we assess serum IL-15 levels in girls with anorexia nervosa (AN) relative to obese and normal weight female adolescents.Methods: Serum IL-15 concentrations were evaluated using a commercially available ELISA kit in 32 Polish girls with restrictive AN, 29 girls with obesity (O), and 21 healthy controls (C). Anthropometric measurements (weight, height, BMI) and laboratory assays (serum fasting glucose, insulin, HOMA-IR, total cholesterol, HDL, LDL, triglycerides, and C-reactive protein (CRP)) were performed.Results: Mean serum IL-15 in the AN group was significantly higher than in C, but lower than in O. In all examined girls, significant positive correlations between IL-15 and body weight, BMI, insulin, HOMA, LDL, triglycerides and CRP were noted. We also observed an inverse relationship between IL-15 and HDL.Conclusions: Our study demonstrated that serum IL-15 concentrations in adolescent girls with AN and obesity are significantly elevated in comparison to normal weight controls. However, the role of IL-15 in the pathogenesis of AN and obesity remains still unclear.

[The new adipokine zinc-α2-glycoprotein (ZAG) as a link between adipose tissue and kidney? [Czy nowa adipocytokina cynkowa α2-glikoproteina (ZAG) stanowi ogniwo miedzy tkanka tluszczowa a nerkami?]].

Adipose tissue is currently considered not only as an energy store but also as an organ of internal secretion. Numerous adipocytokines regulating a number of human body processes are important in many disease processes, including chronic kidney disease (CKD). Nowadays, the role of zinc α2-glycoprotein (ZAG) is being sought as a potential link between these two organs. ZAG, through its lipolytic effect, contributes to progressive malnutrition in patients undergoing dialysis, and this significantly increases their mortality. It seems that ZAG may be a new potential biomarker of kidney damage, and the specific pharmacotherapy will significantly reduce the progressive process of cachexia.

The role of adipokines in the pathogenesis and course of selected respiratory diseases.

Adipose tissue is also a secretory organ producing active substances called adipokines. Some of them (apelin, resistin, adiponectin, leptin, chemerin, or visfatin) may play a role in the pathogenesis and course of respiratory diseases, e.g. COPD, asthma, pulmonary hypertension, or lung cancer. There are limited and conflicting data on the role of adipokines in asthma. It has been confirmed, however, that visfatin and leptin can be markers of inflammation in COPD. Elevated concentrations of leptin and resistin play a pro-inflammatory role in the development of cancer cachexia. The role of adipokines has also been demonstrated in pulmonary hypertension, and the apelinadiponectin axis disruption may exacerbate pulmonary hypertension.

Evidence of a significant vitamin D deficiency among 9-13-year-old Polish children: results of a multicentre study.

PURPOSE: To evaluate the extent to which the population of Polish preadolescents is vitamin D deficient and to assess seasonal variations in vitamin D status. PARTICIPANTS AND METHODS: A total of 720 healthy children aged 9-13 years (409 girls, 311 boys) residing in 6 representative geographical locations in Poland were studied. A parental-assisted questionnaire provided data on nutritional habits, vitamin D supplements and sun exposure. Serum concentration of 25-hydroxyvitamin was determined twice, after the winter in March and after the summer in October. RESULTS: In March, vitamin D deficiency (25-50 nmol/L) was found in 64%, and severe deficiency (< 25 nmol/L) in 20.2% of children. In October, the deficiency and severe deficiency were still noticed in 25.9 and 0.1% of children, respectively. The mean serum concentration of 25-OHD was 52% higher in October (55.4 ± 14.0 nmol/L) than in March (36.4 ± 13.5 nmol/L), (p < 0.01). In children with 25-OHD < 50 nmol/L in March, their 25-OHD concentration increased by 64% through March to October (32.5 ± 8.2 vs. 53.2 ± 7.9 nmol/L, p < 0.01). An association was found between 25-OHD concentration and regular consumption of vitamin D supplements, cod-liver oil and fish. CONCLUSIONS: The majority of preadolescent Polish boys and girls show vitamin D deficiency after the winter period, although a distinct amelioration over summertime is found in this age group. There is a need to implement effective prevention and intervention strategies in the management of vitamin D deficiency among schoolchildren in Poland, with the supplementation throughout the entire year.

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.

Endothelin-1 (ET-1), N-terminal fragment of pro-atrial natriuretic peptide (NTpro-ANP), and tumour necrosis factor alpha (TNF-α) in children with primary hypertension and hypertension of renal origin.

INTRODUCTION: Hypertension is regarded as a condition of mild inflammation and endothelial imbalance. The aim of the study was to evaluate serum concentrations of biomarkers of inflammation and endothelial function: tumour necrosis factor alpha (TNF-α), endothelin-1 (ET-1), and N-terminal fragment of pro-atrial natriuretic peptide (NTpro-ANP) in hypertensive and normotensive children. MATERIAL AND METHODS: We studied 63 children aged 13.56 ± 3.73 years, divided into two groups: a group with primary hypertension (n = 50) and a group with renal hypertension (n = 13). The control group consisted of 34 normotensive children aged 12.76 ± 3.96 years. Biomarkers were measured with ELISA tests. RESULTS: ET-1 levels were significantly higher in primary hypertension (9.93 ± 1.73 pg/ml) and renal hypertension (10.77 ± 1.50 pg/ml) in comparison to controls (4.03 ± 0.97 pg/ml), (p < 0.001, p < 0.001, respectively). NT-pro ANP concentrations in primary hypertension (71.03 ± 10.02 pg/ml), and renal hypertension (84.78 ± 6.44 pg/ml) were significantly higher than in the control group (29.62 ± 5.56 pg/ml) (p < 0.001, p < 0.001, respectively). TNF-α concentrations in primary hypertension (8.36 ± 1.60 pg/ml) and renal hypertension (7.35 ± 0.93 pg/ml) significantly exceeded concentrations in controls (4.49 ± 0.93 pg/ml), (p < 0.001, p < 0.001, respectively). ET-1 and NT-pro ANP concentrations in renal hypertension significantly exceeded those in primary hypertension (p = 0.049, p < 0.001, respectively) while TNF-α levels in renal hypertension were significantly lower than in primary hypertension (p = 0.046). CONCLUSIONS: The results of our study show that ET-1, NT-pro ANP, and TNF-a concentrations are increased in hypertension in children. Our investigation indicates significant importance of inflammation and endothelial involvement in hypertension in youth.

A Patient with Berardinelli-Seip Syndrome, Novel AGPAT2 Splicesite Mutation and Concomitant Development of Non-diabetic Polyneuropathy

Primary polyneuropathy in the context of Seip-Berardinelli type 1 seipinopathy, or congenital generalized lipodystrophy type 1 (CGL1) has not been previously reported. We report the case history of a 27 year old female CGL1 patient presenting with an unusual additional development of non-diabetic peripheral neuropathy and learning disabilities in early adolescence. Whole exome sequencing (WES) of the patient genome identified a novel variant, homozygous for a 52 bp intronic deletion in the AGPAT2 locus, coding for 1-acylglycerol-3-phosphate O-acyltransferase 2, which is uniquely associated with CGL1 seipinopathies, with no molecular evidence for dual diagnosis. Functional studies using RNA isolated from patient peripheral blood leucocytes showed abnormal RNA splicing resulting in the loss of 25 amino acids from the patient AGPAT2 protein coding sequence. Stability and transcription levels for the misspliced AGPAT2 mRNA in our patient nonetheless remained normal. Any AGPAT2 protein produced in our patient is therefore likely to be dysfunctional. However, formal linkage of this deletion to the neuropathy observed remains to be shown. The classical clinical presentation of a patient with AGPAT2-associated lipodystrophy shows normal cognition and no development of polyneuropathy. Cognitive disabilities and polyneuropathy are features associated exclusively with clinical CGL type 2 arising from seipin (BSCL2) gene mutations. This case study suggests that in some genetic contexts, AGPAT2 mutations can also produce phenotypes with primary polyneuropathy.