| 1. |
- Rodanaki, Maria, 1987-, et al.
(författare)
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The Incidence of Childhood Thyrotoxicosis Is Increasing in Both Girls and Boys in Sweden
- 2019
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 91:3, s. 195-202
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We found an increase in the incidence rate (IR) of childhood thyrotoxicosis (CT) during the 1990s in central Sweden. The optimal treatment method for CT is a subject that is still debated upon.OBJECTIVES: To investigate whether the increase in IR of CT in Sweden persists and to study the treatment outcome.METHOD: Children <16 years of age diagnosed with CT during 2000-2009 and living in 1 of 5 counties in central Sweden were identified retrospectively using hospital registers. Data on clinical and biochemical characteristics and outcomes of treatment were collected from medical records. The corresponding data from 1990 to 1999 were pooled with the new data.RESULTS: In total, 113 children were diagnosed with CT during 1990-2009 in the study area. The overall IR was 2.2/100,000 person-years (95% CI 1.2-2.5/100,000 person-years). The IR was significantly higher during 2000-2009 than during 1990-1999 (2.8/100,000 [2.2-3.6] vs. 1.6/100,000 person-years [1.2-2.2], p = 0.006). The increase was significant for both sexes. Seventy percent of the patients who completed the planned initial treatment with antithyroid drugs (ATDs) and were not lost to follow-up relapsed within 3 years. Boys tended to relapse earlier than girls (6.0 months after drug withdrawal [95% CI 1.9-10.0] vs. 12.0 months [95% CI 6.8-17.3], p = 0.074).CONCLUSIONS: The IR of CT is increasing in both girls and boys. Relapse rate after withdrawal of ATD treatment is 70%. Boys tend to relapse earlier than girls, and this needs to be further investigated.
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| 2. |
- Rodanaki, Maria, 1987-, et al.
(författare)
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A Randomized Trial of the Effect of a GnRH Analogue Injection on Ghrelin Levels in Girls
- 2022
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 95:5, s. 442-451
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Ghrelin concentrations decline during puberty by an unclear mechanism. Acylated ghrelin (AG) is unstable in sampling tubes, but no standardized sampling protocol exists. We hypothesized that ghrelin levels decrease as a consequence of increased gonadotropin-releasing hormone (GnRH) signalling and that the addition of a protease inhibitor to sampling tubes preserves the AG levels.Methods: In this randomized, placebo-controlled, cross-over study, 13 girls with suspected central precocious puberty were included. They performed an adjusted GnRH stimulation test twice and were given Relefact LHRH (R)(100 mu g/m(2)) or saline in a randomized order. Blood was sampled repeatedly for 150 min for the analysis of hormone concentrations. Oestradiol levels were only measured at baseline. The protease inhibitor 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) was added to the sampling tubes. Specific ELISA kits were used for the analysis of AG and desacylated ghrelin (DAG) levels.Results: Neither AG nor DAG levels changed after GnRH analogue injection in comparison to saline. The addition of AEBSF preserved AG levels (650.1 +/- 257.1 vs. 247.6 +/- 123.4 pg/mL, p < 0.001) and decreased DAG levels (51.9 [12.5-115.7] vs. 143.5 [71.4-285.7] pg/mL, p < 0.001). Both AG and DAG levels were inversely associated with insulin levels (r = -0.73, p = 0.005, and r = -0.78, p = 0.002, respectively). AG levels were inversely associated with oestradiol levels (rho = -0.57, p = 0.041).Conclusion: Ghrelin levels do not decrease following a pharmacological dose of a GnRH analogue in the short term in girls. Addition of a protease inhibitor to the sampling tubes decreases AG degradation, resulting in preserved AG and decreased DAG levels. (C) 2022 The Author(s). Published by S. Karger AG, Basel
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| 3. |
- Rodanaki, Maria, 1987-, et al.
(författare)
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Adding a protease inhibitor to sampling tubes increases the acylated ghrelin and decreases the desacylated ghrelin levels in girls
- 2021
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 94:Suppl. 1, s. 111-112
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Ghrelin is a growth hormone-releasing acylated peptide stimulating the appetite, mainly produced in the stomach, and with an important role in pubertal development (1). Two ghrelin forms have been described, acylated (AG) and desacylated (DAG), but it is debated whether DAG is an active hormone or a degradation product of AG (2). Our aim was to evaluate the effects of adding the protease inhibitor 4-(2-aminoethyl) benzenesufonyl fluoride hydrochloride (AEBSF) to sampling tubes and acidification of plasma on levels of AG and DAG in girls with suspected central precocious puberty (CPP).Methods: 13 girls aged 6.6 to 10.1 years with suspected CPP undergoing a gonadotropin-releasing hormone stimulation test during 2015-2017 at the Departments of Paediatrics, at Örebro or Uppsala University Hospital were included. Blood samples were collected at 0 min in precooled EDTA tubes with or without AEBSF at a final concentration of 2mg/ml. After cold centrifugation, HCl at a final concentration of 50 μmol/l, was added to 50% of the plasma tubes containing AEBSF. The AG and DAG concentrations were measured by ELISA kits. Comparison was performed using one-way ANOVA for repeated measurements.Results: The mean plasma AG levels were significantly higher after the addition of AEBSF only (650.9 +/- 257.1 pg/ml) or AEBSF+HCl (681.2 +/- 299 pg/ml) compared to the concentrations without additives (247.6 +/- 123.4 pg/ml, p<0.01 for both comparisons). There was no significant difference between the AG levels after AEBSF and AEBSF+HCl addition. The plasma levels of DAG were significantly lower after the addition of AEBSF+HCl (69.3 +/- 30.6 pg/ml) and even further lowered after the addition of AEBSF only (56.3+/- 30.9 pg/ml) compared to the concentrations of DAG in tubes without any additives (149.9 +/- 73.7 pg/ml, p < 0.01 for both comparisons).Discussion: Due to the unstable nature of AG, special procedures are required for accurate measurement of its plasma levels in children, including the use of a protease inhibitor like AEBSF. However, DAG was still measurable indicating that it may not only be a degradation product of AG. 1. Kojima M, Kangawa K. Ghrelin: structure and function. Physiol Rev. 2005;85(2):495-522.2. Blatnik M, Soderstrom CI, Dysinger M, Fraser SA. Prandial ghrelin attenuation provides evidence that des-acyl ghrelin may be an artifact of sample handling in human plasma. Bio-analysis. 2012;4(20):2447-55.
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| 4. |
- Rodanaki, Maria, 1987-, et al.
(författare)
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Delayed puberty in boys in central Sweden : an observational study on diagnosing and management in clinical practice
- 2022
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To compare the usefulness of the classical definition of delayed puberty (DP) in boys with puberty nomograms and to describe the management of DP in boys in a hospital-based setting.STUDY DESIGN: Observational retrospective multicentre study with a short-term follow-up.SETTING AND PARTICIPANTS: Boys diagnosed with DP during 2013-2015 at paediatric departments in four counties in central Sweden. The medical records of 165 boys were reviewed.PRIMARY AND SECONDARY OUTCOME MEASURES: Number of boys with DP after re-evaluation of the diagnosis according to the classical definition in comparison with puberty nomograms. Description of investigations performed and treatment provided to boys with DP.RESULTS: In total, 45 and 58 boys were found to have DP according to the classical definition and the nomograms, respectively. Biochemical and/or radiological testing was performed in 91% of the 58 boys, but an underlying disease was only found in 9% of them. Approximately 79% of the boys received testosterone treatment, either as injections of testosterone enanthate or as testosterone undecanoate.CONCLUSIONS: Puberty nomograms may be helpful instruments when diagnosing pubertal disorders in boys as they are not limited to an age close to 14 years and also identify boys with pubertal arrest. The majority of boys with DP undergo biochemical or radiological examinations, but underlying diseases are unusual emphasising the need for structural clinical practice guidelines for this patient group.
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| 5. |
- Rodanaki, Maria, 1987-, et al.
(författare)
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Incidence and Treatment Outcome of Childhood Thyrotoxicosis
- 2018
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 90:Suppl.1, s. 90-91
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To study the incidence of childhood thyrotoxicosis in five counties in central Sweden during 1990–2009 and to study the treatment outcome.Methods: Children below the age of 16 years diagnosed with thyrotoxicosis during the 20-years period and living in the study area were identified retrospectively. Data on the total number of children below 16 years of age living in the area during the study period was collected from the National Board of Statistics, Sweden. Data regarding clinical and biochemical characteristics and the outcome of the treatment were collected from medical records.Results: 113 patients were identified. The annual incidence was 2.2/100,000 children during the whole study period. The incidence was higher during the last ten studied years as compared to the first ten studied years (2.8 vs. 1.6/100,000, p = 0.006). The increase in incidence was seen in both girls and boys (p = 0.041 and p = 0.038, respectively). Treatment with antithyroid drugs (ATD) was the first hand choice, but 69% of the patients relapsed within three years after the planned discontinuation of the ATD treatment. Boys relapsed more often than girls (p = 0.013), but we could not identify any other significant predictor for relapse.Conclusion: Thyrotoxicosis is uncommon in pediatric patients but the incidence seems to be increasing. The outcome of the initial treatment with ATD is poor with high relapse rates. Boys seems to have an increased risk for relapse compared to girls. More studies are needed to identify an optimal treatment protocol for each individual.
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| 6. |
- Rodanaki, Maria, 1987-, et al.
(författare)
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Incidence of Delayed Puberty in Adolescents : A Population-Based Study in a County in Central Sweden
- 2018
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 90:Suppl.1, s. 510-510
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Delayed puberty is defined as the absence of physical signs of puberty by the age of 14 years in boys and 13 years in girls. According to this definition, the prevalence of delayed puberty would be 2%, if the ages of pubertal onset were normally distributed in the population. However, the prevalence or incidence of delayed puberty has not been described before, as far as we know. Our aim was to study the incidence of delayed puberty in central Sweden.Methods: In this population-based retrospective study all adolescents given the ICD-10 diagnosis “delayed puberty” in Örebro county during the period 2013-2015 were identified. Adolescents with other diagnoses potentially related to delayed puberty (e.g. short stature) were also identified to ensure that there were no additional cases. The medical records of these patients, except those not willing to participate, were systematically reviewed to ensure that the diagnosis was correct. The cases were then categorized into four groups depending on how accurate we found the diagnosis (certain, possible, wrong diagnosis, or unclear cases). Data on the total numbers of adolescents in Örebro county were obtained from the authority of statistics in Sweden.Results: One hundred and twenty-eight of 180 eligible medical records were reviewed (response rate: 71 %). Nine boys and one girl were diagnosed with delayed puberty during the study time period and fulfilled our strict criteria for a certain diagnosis and 4 boys were classified as possible new cases. The total population in Örebro county for boys aged 14-18 years was on average 6,546 each year during the time period. The minimal annual incidence for boys was 46 per 100,000 (95% confidence interval (CI) 15-142 per 100,000). When possible cases were included, the annual incidence for boys increased to 66 (CI 26-170) per 100,000. Due to the low number of girls with delayed puberty no incidence for girls was calculated.Discussion: This is, to our knowledge, the first study describing the incidence of delayed puberty in boys. We evaluated the accuracy of the diagnosis using strict criteria. The presented incidence should be regarded as the minimum incidence since some adolescents with delayed puberty may not seek medical advice or may be unrecognized by the health services in schools. Because of our small study population, larger studies are needed to confirm our findings and for calculation of the incidence in girls, where our data implies a much lower incidence.
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| 7. |
- Rodanaki, Maria, 1987-, et al.
(författare)
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The effect of a GnRH analogue injection on the circulating levels of kisspeptin-1 in girls with suspected central precocious puberty
- 2022
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 95:Suppl. 2, s. 341-341
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Kisspeptin stimulates the gonadotropin releasing hormone (GnRH) neurons in hypothalamus initiating puberty. However, it is not known whether GnRH inhibits kisspeptin secretion by negative feedback and whether there are any associations between circulating levels of kisspeptin and other hormones, like ghrelin, important for the onset of puberty.Methods: Thirteen girls with suspected central precocious puberty performed an adjusted GnRH stimulation test twice, placebo-controlled in a randomized order, at Örebro or Uppsala University Hospital, Sweden. Blood was sampled 0, 30, 60, 90, 120 and 150 min after the iv injection of either Relefact LHRH® or saline. The protease inhibitor 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) was added to the sampling tubes to a final concentration of 2 mg/ml. An ELISA kit from LifeSpan BioSciences, Inc. (No LS-F8231) was used for the analyses of Kisspeptin-1 levels. The levels of acylated ghrelin were analyzed with Millipore® Human Ghrelin (Active) ELISA kit (#EZGRA-88K). Serum ultrasensitive estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), insulin and glucose levels were analyzed using the usual clinical methods.Results: The median Kisspeptin-1 level at baseline was 39 pg/ml (min–max: 0.1–221.3 pg/ml). The area-under-the curve for Kisspeptin-1 levels was not significantly lower after the GnRH injection as compared to the placebo injection. We did not find any significant correlations between the levels of kisspeptin-1 and acylated ghrelin, estradiol, LH, FSH, or insulin. However, we could see a positive correlation between kisspeptin-1 and glucose levels at baseline (Spearman’s rank test, rho = 0.63, p=0.021).Discussion: We did not find evidence of a negative feedback mechanism between GnRH and kisspeptin in girls with suspected central precocious puberty since the circulating levels of kisspeptin-1 were unaffected by an intravenous injection of a GnRH analogue. However, paracrine actions in the hypothalamus cannot be ruled out by this study. The positive correlation found between kisspeptin-1 and glucose levels is in accordance with previous findings in both adults and children, suggesting a possible role for kisspeptin signaling in glucose metabolism.
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| 8. |
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| 9. |
- Allbrand, Marianne, 1958-, et al.
(författare)
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Adipocytokines in placenta and cord blood in relation to maternal obesity, and foetal and postnatal growth of the child
- 2015
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Ingår i: Hormone Research in Paediatrics. - Basel, Switzerland : S. Karger. - 1663-2818 .- 1663-2826. ; 82:Suppl. 1, s. 47-48
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: The nutritional and hormonal state in utero may be a link between maternal obesity and obesity in the offspring. The gene expression in placentae in pregnancies complicated by diabetes is reduced for leptin, but increased for ghrelin. It is not known whether these genes’ expressions in placentae are altered in maternal obesity.Objectives and hypotheses: To compare obese and normal-weight women and their children concerning gene expressions of leptin and ghrelin in placentae; leptin, ghrelin, adiponectin, and C-peptide levels in cord blood, birth size and postnatal growth. Changes in the expression of these adipocytokines may lead to an altered hypothalamic sensitivity to leptin and ghrelin resulting in an increased risk of obesity in the offspring.Method: 32 women with pre-pregnancy obesity, but otherwise healthy, were compared to 32 matched, normal-weight controls. Full-term placenta biopsies were analysed with qPCR for leptin mRNA and ghrelin mRNA. Cord blood samples were examined with ELISA for leptin, ghrelin, adiponectin, and C-peptide concentrations. Birth size and postnatal growth of the children were collected from clinical registers at the Child Health Care Units.Results: The leptin and ghrelin gene expressions in placentae did not differ between obese and normal-weight women. The leptin concentration in cord blood was higher in children of obese mothers (P=0.021). It correlated with birth weight Z-score (r=0.467, P<0.001) and C-peptide level in cord blood (r=0.446, P<0.001). Children of obese women were slightly heavier at birth, but postnatal growth did not differ between groups. Children with birth weight ≤−0.67 Z-score had higher ghrelin levels in cord blood than heavier children (P=0.042). The leptin level in cord blood correlated negatively with weight gain at 6 months (r=−0.332, P=0.009). The ghrelin level in cord blood correlated with weight gain at 3 months in girls (r=0.611, P=0.001), but not in boys. The adiponectin level in cord blood correlated negatively with length gain at 3 years in the obese group (r=−0.571, P=0.033), but not in the normal-weight group.Conclusion: Leptin and ghrelin placental gene expressions are not altered in obese women, but foetal adipocytokine production may influence early postnatal growth, possibly by influencing hunger signalling or insulin levels
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| 10. |
- Allbrand, Marianne, 1958-, et al.
(författare)
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Expression of genes involved in inflammation and growth : does sampling site in human full-term placenta matter?
- 2019
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Ingår i: Journal of Perinatal Medicine. - : Walter de Gruyter. - 0300-5577 .- 1619-3997. ; 47:5, s. 539-546
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the placental gene expression of substances in the inflammatory cascade and growth factors at nine different well-defined sampling sites in full-term placentas from 12 normal weight healthy non-smoking women with an uncomplicated singleton pregnancy.Methods: All placentas (six girls and six boys) were delivered vaginally. Quantitative real-time polymerase chain reaction was used to analyze toll receptor-2 and -4, interleukin-6 and -8, tumor necrosis factor-α, leptin, ghrelin, insulin-like growth factor-1 and -2, hepatocyte growth factor, hepatocyte growth factor receptor and insulin receptor (IR).Results: The leptin gene and the IR gene showed higher expression in lateral regions near the chorionic plate compared to central regions near the basal plate (P = 0.028 and P = 0.041, respectively).Conclusion: Our results suggest that the sampling site may influence the gene expression for leptin and IR in placental tissue obtained from full-term normal pregnancies. We speculate that this may be due to differences in placental structure and perfusion and may be important when future studies are designed.
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