Mónica Reis, Ana Teixeira, Juliana Cardoso, Teresa Borges, Alberto Caldas Afonso, Liane Correia-Costa
Objectives Type 1 diabetes mellitus is considered a state of chronic low-grade inflammation and activation of the innate immune system, which is regulated by several proinflammatory cytokines and other acute-phase reactants. Arterial stiffness, a dynamic property of the vessels evaluated by the determination of pulse wave velocity (PWV), is increased in diabetic patients and is associated with microvascular and macrovascular complications of diabetes and higher cardiovascular risk. In the present study, we aimed to compare the proinflammatory state and arterial stiffness in diabetic and non-diabetic adolescents, and to characterize the association between these two parameters. Methods Twenty-three type 1 diabetic patients, aged 12–16 years, followed at a tertiary center, and 23 adolescents nonoverweighted healthy controls, from a Portuguese birth-cohort, were included in the present analysis. Anthropometry, blood pressure, glycemic control data, and lipid parameters were collected. Arterial stiffness was evaluated by carotid–femoral pulse wave velocity. Proinflammatory cytokines’ concentrations (TNF-α, IL-1β, IL-6, IL-10, IFN-γ, and GM-CSF) were quantified by multiplex immunoassays using a Luminex 200 analyzer. Results There were no statistically significant differences between the proinflammatory cytokines’ concentrations in the two groups. PWV [6.63 (6.23–7.07) vs. 6.07 (5.15–6.65) m/s, p=0.015] was significantly higher in the diabetic group. PWV was negatively correlated with GM-CSF (ρ=−0.437, p=0.037) in the diabetic group. A linear association was found between diabetes duration and PWV (with PWV increasing by 0.094 m/s (95 % confidence interval, 0.019 to 0.169) per month of disease duration). In the diabetic group, HbA1c was negatively correlated with IL-10 (ρ=−0.473, p=0.026). Negative correlations were also found between IL-10 and total, HDL, and LDL cholesterol only in the diabetic group. Conclusions Diabetic adolescent patients present higher PWV, when compared to their healthy counterparts, even though we could not find differences in the levels of several proinflammatory cytokines between the two groups. The negative correlation found between IL-10 and HbA1c might translate a protective counterbalance effect of this anti-inflammatory cytokine, which might also explain the negative correlations found with blood lipids. Further studies are needed to better clarify the association between arterial stiffness and the proinflammatory milieu of diabetes.
{"title":"Association between proinflammatory cytokines and arterial stiffness in type 1 diabetic adolescents","authors":"Mónica Reis, Ana Teixeira, Juliana Cardoso, Teresa Borges, Alberto Caldas Afonso, Liane Correia-Costa","doi":"10.1515/jpem-2023-0530","DOIUrl":"https://doi.org/10.1515/jpem-2023-0530","url":null,"abstract":"Objectives Type 1 diabetes mellitus is considered a state of chronic low-grade inflammation and activation of the innate immune system, which is regulated by several proinflammatory cytokines and other acute-phase reactants. Arterial stiffness, a dynamic property of the vessels evaluated by the determination of pulse wave velocity (PWV), is increased in diabetic patients and is associated with microvascular and macrovascular complications of diabetes and higher cardiovascular risk. In the present study, we aimed to compare the proinflammatory state and arterial stiffness in diabetic and non-diabetic adolescents, and to characterize the association between these two parameters. Methods Twenty-three type 1 diabetic patients, aged 12–16 years, followed at a tertiary center, and 23 adolescents nonoverweighted healthy controls, from a Portuguese birth-cohort, were included in the present analysis. Anthropometry, blood pressure, glycemic control data, and lipid parameters were collected. Arterial stiffness was evaluated by carotid–femoral pulse wave velocity. Proinflammatory cytokines’ concentrations (TNF-α, IL-1β, IL-6, IL-10, IFN-γ, and GM-CSF) were quantified by multiplex immunoassays using a Luminex 200 analyzer. Results There were no statistically significant differences between the proinflammatory cytokines’ concentrations in the two groups. PWV [6.63 (6.23–7.07) vs. 6.07 (5.15–6.65) m/s, p=0.015] was significantly higher in the diabetic group. PWV was negatively correlated with GM-CSF (ρ=−0.437, p=0.037) in the diabetic group. A linear association was found between diabetes duration and PWV (with PWV increasing by 0.094 m/s (95 % confidence interval, 0.019 to 0.169) per month of disease duration). In the diabetic group, HbA<jats:sub>1c</jats:sub> was negatively correlated with IL-10 (ρ=−0.473, p=0.026). Negative correlations were also found between IL-10 and total, HDL, and LDL cholesterol only in the diabetic group. Conclusions Diabetic adolescent patients present higher PWV, when compared to their healthy counterparts, even though we could not find differences in the levels of several proinflammatory cytokines between the two groups. The negative correlation found between IL-10 and HbA<jats:sub>1c</jats:sub> might translate a protective counterbalance effect of this anti-inflammatory cytokine, which might also explain the negative correlations found with blood lipids. Further studies are needed to better clarify the association between arterial stiffness and the proinflammatory milieu of diabetes.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140588311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gülhan Atakul, Huseyin Anıl Korkmaz, Ahmet Gönüllü, Özlem Saraç Sandal, Özge Köprülü, Nilüfer Uyar, Utku Karaaslan, Hurşit Apa, Hasan Ağın, Behzat Özkan
Objectives The aim of our study was to investigate the changes in thyroid hormone levels during and after acute metabolic disorder in patients with diabetic ketoacidosis (DKA). Methods Eighty five patients diagnosed with DKA were included in the study. Patients with control thyroid function test (TFT) values at admission (the first blood sample) and 1 month later were included in the study. Thyroid function tests obtained during diabetic ketoacidosis and at the first month follow-up were compared. Euthyroidism and euthyroid sick syndrome were defined and grouped according to current guidelines. The mild and moderate groups, according to DKA classification, were combined and compared with the severe group. Results A significant increase was observed between the first admission and the control TFT values 1 month later. However, there was no significant difference found in TFT between mild/moderate and severe groups taken at the time of DKA. Difference between two groups, euthyroid sick syndrome and euthyroid, was examined and the result that was different from the literature was the difference between TSH levels. We found that low FT4 levels were associated with higher HgbA1c, although the correlation was weak. Conclusions Thyroid hormone levels may not reflect a thyroid disease during severe DKA attack. Therefore, it is unnecessary to check thyroid function tests.
{"title":"Does an episode of diabetic ketoacidosis affect thyroid function tests in pediatric patients?","authors":"Gülhan Atakul, Huseyin Anıl Korkmaz, Ahmet Gönüllü, Özlem Saraç Sandal, Özge Köprülü, Nilüfer Uyar, Utku Karaaslan, Hurşit Apa, Hasan Ağın, Behzat Özkan","doi":"10.1515/jpem-2024-0022","DOIUrl":"https://doi.org/10.1515/jpem-2024-0022","url":null,"abstract":"Objectives The aim of our study was to investigate the changes in thyroid hormone levels during and after acute metabolic disorder in patients with diabetic ketoacidosis (DKA). Methods Eighty five patients diagnosed with DKA were included in the study. Patients with control thyroid function test (TFT) values at admission (the first blood sample) and 1 month later were included in the study. Thyroid function tests obtained during diabetic ketoacidosis and at the first month follow-up were compared. Euthyroidism and euthyroid sick syndrome were defined and grouped according to current guidelines. The mild and moderate groups, according to DKA classification, were combined and compared with the severe group. Results A significant increase was observed between the first admission and the control TFT values 1 month later. However, there was no significant difference found in TFT between mild/moderate and severe groups taken at the time of DKA. Difference between two groups, euthyroid sick syndrome and euthyroid, was examined and the result that was different from the literature was the difference between TSH levels. We found that low FT4 levels were associated with higher HgbA1c, although the correlation was weak. Conclusions Thyroid hormone levels may not reflect a thyroid disease during severe DKA attack. Therefore, it is unnecessary to check thyroid function tests.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140588495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carly Baxter, Claudia Martinez-Rios, Alexandra Ahmet
Background Resistance to thyroid hormone (RTH) is a genetic condition, caused by mutations in the thyroid hormone receptor gene and characterized by impaired end organ responsiveness to thyroid hormone. Here we describe a novel case of THR associated with large goiter mimicking infiltrative c. Case presentation A 13-year-old male with a hyperthyroid phenotype of RTH diagnosed as a toddler, on methimazole and nadolol therapies presented with an increase in goiter size and possible nodule. Thyroid ultrasound was concerning for a diffuse infiltrative process or malignancy. Methimazole was discontinued and he underwent further imaging, fine needle aspiration and core biopsies. Biopsy results were reassuring and imaging findings were subsequently attributed to RTH rather than malignancy. He started every other day liothyronine therapy, which led to a decrease in goiter size, thyroglobulin level, and improvement of hyperthyroid symptoms. Conclusions This is the first case to our knowledge describing the above thyroid imaging findings in association with RTH. It also adds important information to the pediatric literature regarding management of the hyperthyroid phenotype of RTH, including the role of liothyronine therapy.
{"title":"Thyroid hormone resistance and large goiter mimicking infiltrative carcinoma in a pediatric patient","authors":"Carly Baxter, Claudia Martinez-Rios, Alexandra Ahmet","doi":"10.1515/jpem-2023-0466","DOIUrl":"https://doi.org/10.1515/jpem-2023-0466","url":null,"abstract":"Background Resistance to thyroid hormone (RTH) is a genetic condition, caused by mutations in the thyroid hormone receptor gene and characterized by impaired end organ responsiveness to thyroid hormone. Here we describe a novel case of THR associated with large goiter mimicking infiltrative c. Case presentation A 13-year-old male with a hyperthyroid phenotype of RTH diagnosed as a toddler, on methimazole and nadolol therapies presented with an increase in goiter size and possible nodule. Thyroid ultrasound was concerning for a diffuse infiltrative process or malignancy. Methimazole was discontinued and he underwent further imaging, fine needle aspiration and core biopsies. Biopsy results were reassuring and imaging findings were subsequently attributed to RTH rather than malignancy. He started every other day liothyronine therapy, which led to a decrease in goiter size, thyroglobulin level, and improvement of hyperthyroid symptoms. Conclusions This is the first case to our knowledge describing the above thyroid imaging findings in association with RTH. It also adds important information to the pediatric literature regarding management of the hyperthyroid phenotype of RTH, including the role of liothyronine therapy.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139561837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives Abdominal pain is a common presentation in patients of diabetic ketoacidosis (DKA). However, this pain generally resolves with resolution of dehydration and acidosis. Persistence of abdominal pain even after resolution of ketosis and acidosis should warrant careful reassessment to find evidence of sepsis and concomitant abdominal pathology. Case presentation We report a rare case of type 1 diabetes mellitus in a 15 year old girl diagnosed 6 months ago who presented with mild DKA (pH 7.24, HCO3− 13.5 mmol/L). Her hospital course was extremely stormy and despite best of our efforts she succumbed due to colonic ischemia and perforation peritonitis. Conclusions A high index of suspicion for gut ischemia or perforation should be kept if DKA is associated with septic shock and there is suboptimal response to standard treatment. Mesenteric ischemia can occur in pediatric patients even with mild DKA having very poor diabetes control.
{"title":"From neglect to peril: diabetic ketoacidosis unleashing colonic necrosis and perforation in an adolescent girl with type 1 diabetes mellitus","authors":"Mritunjay Kumar, Rini Dixit, Rohit Kapoor, Sunita Singh","doi":"10.1515/jpem-2023-0412","DOIUrl":"https://doi.org/10.1515/jpem-2023-0412","url":null,"abstract":"Objectives Abdominal pain is a common presentation in patients of diabetic ketoacidosis (DKA). However, this pain generally resolves with resolution of dehydration and acidosis. Persistence of abdominal pain even after resolution of ketosis and acidosis should warrant careful reassessment to find evidence of sepsis and concomitant abdominal pathology. Case presentation We report a rare case of type 1 diabetes mellitus in a 15 year old girl diagnosed 6 months ago who presented with mild DKA (pH 7.24, HCO<jats:sub>3</jats:sub> <jats:sup>−</jats:sup> 13.5 mmol/L). Her hospital course was extremely stormy and despite best of our efforts she succumbed due to colonic ischemia and perforation peritonitis. Conclusions A high index of suspicion for gut ischemia or perforation should be kept if DKA is associated with septic shock and there is suboptimal response to standard treatment. Mesenteric ischemia can occur in pediatric patients even with mild DKA having very poor diabetes control.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139084579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives Newborn screening (NBS) for primary carnitine deficiency (PCD) exhibits suboptimal performance. This study proposes a strategy to enhance the efficacy of second-tier genetic screening by adjusting the cutoff value for free carnitine (C0). Methods Between January 2021 and December 2022, we screened 119,898 neonates for inborn metabolic disorders. Neonates with C0 levels below 12 μmol/L were randomly selected for second-tier genetic screening, employing a novel matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) assay. Results In total, 2,515 neonates with C0 <12 μmol/L underwent further screening, including 206 neonates with C0 <8.5 μmol/L and 320 neonates with 8.5<C0<12 μmol/L. Genetic screening identified positive results in 12.36 % (65) of neonates, with one being homozygous, 10 compound heterozygotes, and 54 heterozygotes. Sanger sequencing revealed a second SLC22A5 variant in three of the 54 neonates. Ultimately, 14 patients were diagnosed with PCD; all 14 patients exhibited low C0 levels, though two had normal C0 levels during the recall review. The MALDI-TOF MS assay demonstrated detection and diagnostic rates of 89.29 % and 78.57 %, respectively. Eleven distinct SLC22A5 variants were identified, with the most common variant being c.51C>G, accounting for 25 % (7/28) of allelic frequencies. Conclusions A novel MALDI-TOF MS assay targeting 21 SLC22A5 variants in a Chinese population was successfully established. This assay exhibits a high detection and diagnostic rate, making it suitable for population-based genetic screening. Combined genetic screening is recommended to enhance the efficiency of PCD–NBS.
{"title":"Newborn screening for primary carnitine deficiency using a second-tier genetic test","authors":"Yiming Lin, Chunmei Lin, Zhenzhu Zheng, Chenggang Huang, Weilin Peng","doi":"10.1515/jpem-2023-0513","DOIUrl":"https://doi.org/10.1515/jpem-2023-0513","url":null,"abstract":"Objectives Newborn screening (NBS) for primary carnitine deficiency (PCD) exhibits suboptimal performance. This study proposes a strategy to enhance the efficacy of second-tier genetic screening by adjusting the cutoff value for free carnitine (C0). Methods Between January 2021 and December 2022, we screened 119,898 neonates for inborn metabolic disorders. Neonates with C0 levels below 12 μmol/L were randomly selected for second-tier genetic screening, employing a novel matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) assay. Results In total, 2,515 neonates with C0 <12 μmol/L underwent further screening, including 206 neonates with C0 <8.5 μmol/L and 320 neonates with 8.5<C0<12 μmol/L. Genetic screening identified positive results in 12.36 % (65) of neonates, with one being homozygous, 10 compound heterozygotes, and 54 heterozygotes. Sanger sequencing revealed a second SLC22A5 variant in three of the 54 neonates. Ultimately, 14 patients were diagnosed with PCD; all 14 patients exhibited low C0 levels, though two had normal C0 levels during the recall review. The MALDI-TOF MS assay demonstrated detection and diagnostic rates of 89.29 % and 78.57 %, respectively. Eleven distinct <jats:italic>SLC22A5</jats:italic> variants were identified, with the most common variant being c.51C>G, accounting for 25 % (7/28) of allelic frequencies. Conclusions A novel MALDI-TOF MS assay targeting 21 <jats:italic>SLC22A5</jats:italic> variants in a Chinese population was successfully established. This assay exhibits a high detection and diagnostic rate, making it suitable for population-based genetic screening. Combined genetic screening is recommended to enhance the efficiency of PCD–NBS.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139064875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bibi Zeyah Fatemah Sairally, Rima K. Dhillon-Smith, Geetu Jethwani, Pallavi Latthe
Introduction Polycystic ovary syndrome (PCOS) treatment in adolescents currently focuses on lifestyle interventions, with pharmacological treatment options often limited to hormonal contraceptives. Several of these carry broad side-effect profiles and are not always accepted by young girls. There is growing interest in non-hormonal therapies for PCOS. We aimed to collate the evidence on the use of myoinositol or D-chiro-inositol in the improvement of PCOS symptoms in symptomatic adolescents. Content Design Narrative review. Methods A systematic literature review identifying key articles from inception to March 2023. Participants Female adolescents (aged 12–19 years) with PCOS or PCOS-like features. Intervention Myoinositol or D-chiro-inositol with or without additional interventions. Comparison Any other treatment, including lifestyle interventions, hormonal therapy, metformin or no treatment. Main outcome measures Improvement in symptoms, quality of life and adverse effects. Summary Eight studies were included: two randomised open-label trials, one quasi-randomised and three non-randomised interventional studies, one case-control study and one cohort study. All studies showed improvements in some biochemical markers, metabolic parameters or clinical symptoms, but these were not reproducible across all studies. Outlook The benefit of myoinositol in adolescents with PCOS remains unclear, with limited high-quality evidence. This review highlights the need for robustly conducted research to inform clinical practice.
{"title":"Myoinositol or D-chiro-inositol for PCOS symptoms in adolescents: a narrative review","authors":"Bibi Zeyah Fatemah Sairally, Rima K. Dhillon-Smith, Geetu Jethwani, Pallavi Latthe","doi":"10.1515/jpem-2023-0458","DOIUrl":"https://doi.org/10.1515/jpem-2023-0458","url":null,"abstract":"Introduction Polycystic ovary syndrome (PCOS) treatment in adolescents currently focuses on lifestyle interventions, with pharmacological treatment options often limited to hormonal contraceptives. Several of these carry broad side-effect profiles and are not always accepted by young girls. There is growing interest in non-hormonal therapies for PCOS. We aimed to collate the evidence on the use of myoinositol or D-chiro-inositol in the improvement of PCOS symptoms in symptomatic adolescents. Content Design Narrative review. Methods A systematic literature review identifying key articles from inception to March 2023. Participants Female adolescents (aged 12–19 years) with PCOS or PCOS-like features. Intervention Myoinositol or D-chiro-inositol with or without additional interventions. Comparison Any other treatment, including lifestyle interventions, hormonal therapy, metformin or no treatment. Main outcome measures Improvement in symptoms, quality of life and adverse effects. Summary Eight studies were included: two randomised open-label trials, one quasi-randomised and three non-randomised interventional studies, one case-control study and one cohort study. All studies showed improvements in some biochemical markers, metabolic parameters or clinical symptoms, but these were not reproducible across all studies. Outlook The benefit of myoinositol in adolescents with PCOS remains unclear, with limited high-quality evidence. This review highlights the need for robustly conducted research to inform clinical practice.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138824370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Central precocious puberty (CPP) is the premature activation of the hypothalamus–pituitary–gonadal axis, resulting in the early development of secondary sexual characteristics. CPP classically occurs before the age of 8 years in girls and 9 years in boys. The aetiology of this precocious onset of puberty is governed by complex mechanistic interactions between genetic and environmental factors. The rates of CPP have been documented to have been rising before the COVID-19 pandemic; despite this, the incidence of CPP has increased exponentially since the start of the pandemic. There are multiple theories potentially explaining this change in incidence of CPP over COVID-19. These include the direct effect of SARS-coV-2 infection, increasing body mass index of adolescents over sequential lockdowns, changes in sleep patterns, increased use of electronic devices and levels of stress, and additionally potential earlier detection of signs of CPP by parents and carers. Whilst there is evidence from observational cohorts, case studies and animal models for each of these factors, it is difficult to definitively prove which has had the greatest impact due to the mainly retrospective nature of the human research that has been conducted. Moreover, studies set in diverse settings with varying population make comparison complex. Additionally, each country responded differently to the COVID-19 pandemic and the lockdowns varied between locations, hence the effect of lockdown was not equal or universal. Despite this, similar trends have been identified, with various lifestyle changes that occurred over the pandemic being potentially influential factors on the development of CPP.
{"title":"Effects of the COVID-19 pandemic on the incidence of central precocious puberty; a narrative review","authors":"Rebecca B. Hoskyns, Sasha R. Howard","doi":"10.1515/jpem-2023-0507","DOIUrl":"https://doi.org/10.1515/jpem-2023-0507","url":null,"abstract":"Central precocious puberty (CPP) is the premature activation of the hypothalamus–pituitary–gonadal axis, resulting in the early development of secondary sexual characteristics. CPP classically occurs before the age of 8 years in girls and 9 years in boys. The aetiology of this precocious onset of puberty is governed by complex mechanistic interactions between genetic and environmental factors. The rates of CPP have been documented to have been rising before the COVID-19 pandemic; despite this, the incidence of CPP has increased exponentially since the start of the pandemic. There are multiple theories potentially explaining this change in incidence of CPP over COVID-19. These include the direct effect of SARS-coV-2 infection, increasing body mass index of adolescents over sequential lockdowns, changes in sleep patterns, increased use of electronic devices and levels of stress, and additionally potential earlier detection of signs of CPP by parents and carers. Whilst there is evidence from observational cohorts, case studies and animal models for each of these factors, it is difficult to definitively prove which has had the greatest impact due to the mainly retrospective nature of the human research that has been conducted. Moreover, studies set in diverse settings with varying population make comparison complex. Additionally, each country responded differently to the COVID-19 pandemic and the lockdowns varied between locations, hence the effect of lockdown was not equal or universal. Despite this, similar trends have been identified, with various lifestyle changes that occurred over the pandemic being potentially influential factors on the development of CPP.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138690027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John Odom, Carlos A. Bacino, Lefkothea P. Karaviti, Weimin Bi, Alfonso Hoyos-Martinez
Objectives Pseudohypoparathyroidism (PHP1B) is most commonly caused by epigenetic defects resulting in loss of methylation at the GNAS locus, although deletions of STX16 leading to GNAS methylation abnormalities have been previously reported. The phenotype of this disorder is variable and can include hormonal resistances and severe infantile obesity with hyperphagia. A possible time relationship between the onset of obesity and endocrinopathies has been previously reported but remains unclear. Understanding of the condition’s natural history is limited, partly due to a scarcity of literature, especially in children. Case presentation We report three siblings with autosomal dominant PHP1B caused by a deletion in STX16 who presented with early childhood onset PTH-resistance with normocalcemia with a progressive nature, accompanied by TSH-resistance and severe infantile obesity with hyperphagia in some, not all of the affected individuals. Conclusions PHP1B from a STX16 deletion displays intrafamilial phenotypic variation. It is a novel cause of severe infantile obesity, which is not typically included in commercially available gene panels but must be considered in the genetic work-up. Finally, it does not seem to have a clear time relationship between the onset of obesity and hormonal resistance.
{"title":"Intrafamilial phenotypic heterogeneity in siblings with pseudohypoparathyroidism 1B due to maternal STX16 deletion","authors":"John Odom, Carlos A. Bacino, Lefkothea P. Karaviti, Weimin Bi, Alfonso Hoyos-Martinez","doi":"10.1515/jpem-2023-0249","DOIUrl":"https://doi.org/10.1515/jpem-2023-0249","url":null,"abstract":"Objectives Pseudohypoparathyroidism (PHP1B) is most commonly caused by epigenetic defects resulting in loss of methylation at the GNAS locus, although deletions of <jats:italic>STX16</jats:italic> leading to GNAS methylation abnormalities have been previously reported. The phenotype of this disorder is variable and can include hormonal resistances and severe infantile obesity with hyperphagia. A possible time relationship between the onset of obesity and endocrinopathies has been previously reported but remains unclear. Understanding of the condition’s natural history is limited, partly due to a scarcity of literature, especially in children. Case presentation We report three siblings with autosomal dominant PHP1B caused by a deletion in <jats:italic>STX16</jats:italic> who presented with early childhood onset PTH-resistance with normocalcemia with a progressive nature, accompanied by TSH-resistance and severe infantile obesity with hyperphagia in some, not all of the affected individuals. Conclusions PHP1B from a <jats:italic>STX16</jats:italic> deletion displays intrafamilial phenotypic variation. It is a novel cause of severe infantile obesity, which is not typically included in commercially available gene panels but must be considered in the genetic work-up. Finally, it does not seem to have a clear time relationship between the onset of obesity and hormonal resistance.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138632535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives Hereditary hypomagnesemia with secondary hypocalcemia (HSH), which results from variations in the transient receptor potential melastatin 6 (TRPM6) genes, is a rare hereditary cause of extremely low serum magnesium levels. We describe an infant with triggered seizures due to hypomagnesemia and a novel mutation in TRPM6 gene was identified. Case presentation A 10-month-old boy presented with multidrug resistant seizures, and axial hypotonia due to severe hypomagnesemia. Electroencephalography and neuroimaging of the patient was normal. He had a favorable outcome with magnesium supplement. In this study, the patient underwent clinical exome sequencing (CES) which detected a novel homozygous variant in the TRPM6 gene: NM_017662.5: c.5571-3C>G. After replacing his magnesium orally, he was free from seizures and had an encouraging outcome at the twelfth-month follow-up. Conclusions HSH often presents with developmental issues, treatment-resistant seizures, and increased neuromuscular excitability. Untreated hypomagnesemia can potentially be fatal and severely impair cognitive function. Clinical suspicion is essential for early diagnosis and treatment.
{"title":"Hereditary hypomagnesemia with secondary hypocalcemia caused by a novel mutation in TRPM6 gene","authors":"İpek Dokurel Çetin, Hamide Betül Gerik-Çelebi, Meliha Demiral, Orkun Çetin","doi":"10.1515/jpem-2023-0378","DOIUrl":"https://doi.org/10.1515/jpem-2023-0378","url":null,"abstract":"Objectives Hereditary hypomagnesemia with secondary hypocalcemia (HSH), which results from variations in the transient receptor potential melastatin 6 (<jats:italic>TRPM6</jats:italic>) genes, is a rare hereditary cause of extremely low serum magnesium levels. We describe an infant with triggered seizures due to hypomagnesemia and a novel mutation in <jats:italic>TRPM6</jats:italic> gene was identified. Case presentation A 10-month-old boy presented with multidrug resistant seizures, and axial hypotonia due to severe hypomagnesemia. Electroencephalography and neuroimaging of the patient was normal. He had a favorable outcome with magnesium supplement. In this study, the patient underwent clinical exome sequencing (CES) which detected a novel homozygous variant in the <jats:italic>TRPM6</jats:italic> gene: NM_017662.5: c.5571-3C>G. After replacing his magnesium orally, he was free from seizures and had an encouraging outcome at the twelfth-month follow-up. Conclusions HSH often presents with developmental issues, treatment-resistant seizures, and increased neuromuscular excitability. Untreated hypomagnesemia can potentially be fatal and severely impair cognitive function. Clinical suspicion is essential for early diagnosis and treatment.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138579597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-01DOI: 10.1515/jpem-2023-frontmatter11
{"title":"Frontmatter","authors":"","doi":"10.1515/jpem-2023-frontmatter11","DOIUrl":"https://doi.org/10.1515/jpem-2023-frontmatter11","url":null,"abstract":"","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135714566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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