Objective: Maturity onset diabetes of the young (MODY) occurs due to mutations in genes involved in pancreatic beta cell function and insulin secretion, has heterogeneous clinical and laboratory features, and account for 1-5% of all diabetes cases. The prevalence and distribution of MODY subtypes vary between countries. The aim of this study was to evaluate the clinical and laboratory characteristics, mutation distribution, and phenotype-genotype relationship in a large case series of pediatric Turkish patients genetically diagnosed with MODY.
Methods: MODY cases from 14 different pediatric endocrinology departments were included. Diagnosis, treatment, follow-up data, and results of genetic analysis were evaluated.
Results: A total of 224 patients were included, of whom 101 (45%) were female, and the mean age at diagnosis was 9.4±4.1 years. Gene variant distribution was: 146 (65%) GCK; 43 (19%) HNF1A; 8 (3.6%) HNF4A, 8 (3.6%) KLF11 and 7 (3.1%) HNF1B. The remaining 12 variants were: PDX (n=1), NEUROD1 (n=3), CEL (n=1), INS (n=3), ABCC8 (n= 3) and KJNC11 (n=1). Of the cases, 197 (87.9%) were diagnosed with incidental hyperglycemia, 16 with ketosis (7%) and 7 (3%) with diabetic ketoacidosis (DKA), while 30% presented with classical symptoms of diabetes. Two-hundred (89%) had a family history of diabetes. Anti-GAD antibody was detected in 13 cases, anti-islet antibody in eight and anti-insulin antibody in four. Obesity was present in 16. Distribution of therapy was: 158 (71%) diet only; 23 (11%) intensive insulin treatment; 17 (7.6%) sulfonylureas; 10 (4.5%) metformin; and 6 (2.7%) insulin and oral anti-diabetic treatment.
Conclusion: This was the largest genetically diagnosed series from Turkey. The most common gene variants were GCK and HNF1A with much lower proportions for other MODY types. Hyperglycemia was the most common presenting symptom while 11% of patients had diabetes-associated autoantibodies and 7% were obese. The majority of patients received dietary management only.
{"title":"Clinical and Laboratory Characteristics of MODY Cases, Genetic Mutation Spectrum and Phenotype-genotype Relationship","authors":"Elif Özsu, Semra Çetinkaya, Semih Bolu, Nihal Hatipoğlu, Şenay Savaş Erdeve, Olcay Evliyaoğlu, Firdevs Baş, Atilla Çayır, İsmail Dündar, Emine Demet Akbaş, Seyid Ahmet Uçaktürk, Merih Berberoğlu, Zeynep Şıklar, Şervan Özalkak, Nursel Muratoğlu Şahin, Melikşah Keskin, Ülkü Gül Şiraz, Hande Turan, Ayşe Pınar Öztürk, Eda Mengen, Elif Sağsak, Fatma Dursun, Nesibe Akyürek, Sevinç Odabaşı Güneş, Zehra Aycan","doi":"10.4274/jcrpe.galenos.2024.2023-10-16","DOIUrl":"10.4274/jcrpe.galenos.2024.2023-10-16","url":null,"abstract":"<p><strong>Objective: </strong>Maturity onset diabetes of the young (MODY) occurs due to mutations in genes involved in pancreatic beta cell function and insulin secretion, has heterogeneous clinical and laboratory features, and account for 1-5% of all diabetes cases. The prevalence and distribution of MODY subtypes vary between countries. The aim of this study was to evaluate the clinical and laboratory characteristics, mutation distribution, and phenotype-genotype relationship in a large case series of pediatric Turkish patients genetically diagnosed with MODY.</p><p><strong>Methods: </strong>MODY cases from 14 different pediatric endocrinology departments were included. Diagnosis, treatment, follow-up data, and results of genetic analysis were evaluated.</p><p><strong>Results: </strong>A total of 224 patients were included, of whom 101 (45%) were female, and the mean age at diagnosis was 9.4±4.1 years. Gene variant distribution was: 146 (65%) GCK; 43 (19%) <i>HNF1A</i>; 8 (3.6%) <i>HNF4A</i>, 8 (3.6%) <i>KLF11</i> and 7 (3.1%) <i>HNF1B</i>. The remaining 12 variants were: <i>PDX</i> (n=1), <i>NEUROD1</i> (n=3), <i>CEL</i> (n=1), <i>INS</i> (n=3), <i>ABCC8</i> (n= 3) and <i>KJNC11</i> (n=1). Of the cases, 197 (87.9%) were diagnosed with incidental hyperglycemia, 16 with ketosis (7%) and 7 (3%) with diabetic ketoacidosis (DKA), while 30% presented with classical symptoms of diabetes. Two-hundred (89%) had a family history of diabetes. Anti-GAD antibody was detected in 13 cases, anti-islet antibody in eight and anti-insulin antibody in four. Obesity was present in 16. Distribution of therapy was: 158 (71%) diet only; 23 (11%) intensive insulin treatment; 17 (7.6%) sulfonylureas; 10 (4.5%) metformin; and 6 (2.7%) insulin and oral anti-diabetic treatment.</p><p><strong>Conclusion: </strong>This was the largest genetically diagnosed series from Turkey. The most common gene variants were GCK and HNF1A with much lower proportions for other MODY types. Hyperglycemia was the most common presenting symptom while 11% of patients had diabetes-associated autoantibodies and 7% were obese. The majority of patients received dietary management only.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140866960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05Epub Date: 2024-03-15DOI: 10.4274/jcrpe.galenos.2024.2023-10-8
Erdal Eren, Semra Çetinkaya, Yasemin Denkboy Öngen, Ummahan Tercan, Şükran Darcan, Hande Turan, Murat Aydın, Fatma Yavuzyılmaz, Fatih Kilci, Beray Selver Eklioğlu, Nihal Hatipoğlu, Kübra Yüksek Acinikli, Zerrin Orbak, Emine Çamtosun, Şenay Savaş Erdeve, Emrullah Arslan, Oya Ercan, Feyza Darendeliler
Objective: Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported non-adherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the Coronavirus disease-2019 (COVID-19) pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated.
Methods: This was a multicenter survey study that was sent to pediatric endocrinologists during the pandemic period (June-December 2021). Patient data, diagnosis, history of pituitary surgery, current GH doses, duration of GH therapy, the person administering therapy (either parent/patient), duration of missed doses, reasons for missed doses, as well as problems associated with GH therapy, missed dose data and the causes in the recent year (after the onset of the pandemic) were questioned. Treatment adherence was categorized based on missed dose rates over the past month (0 to 5%, full adherence; 5.1 to 10% moderate adherence; >10% non-adherence).
Results: The study cohort consisted of 427 cases (56.2% male) from thirteen centers. Median age of diagnosis was 8.13 (0.13-16) years. Treatment indications were isolated GH deficiency (61.4%), multiple pituitary hormone deficiency (14%), Turner syndrome (7.5%), idiopathic GH deficiency (7.5%), small for gestational age (2.8%), and “others“ (6.8%). GH therapy was administered by parents in 70% and by patients in 30%. Mean daily dose was 32.3 μg/kg, the annual growth rate was 1.15 standard deviation score (minimum -2.74, maximum 9.3). Overall GH adherence rate was good in 70.3%, moderate in 14.7%, and poor in 15% of the patients. The reasons for non-adherence were mainly due to forgetfulness, being tired, inability to access medication, and/or pen problems. It was noteworthy that there was a negative effect on adherence during the COVID-19 pandemic reported by 22% of patients and the main reasons given were problems obtaining an appointment, taking the medication, and anxiety about going to hospital. There was no difference between genders in the adherence rate. Non-adherence to GH treatment decreased significantly when the patient: administered the treatment; was older; had longer duration of treatment; and during the pandemic. There was a non-significant decrease in annual growth rate as non-adherence rate increased.
Conclusion: During the COVID-19 pandemic, the poor adherence rate was 15%, and duration of GH therapy and older age were important factors. There was a negative effect on adherence during the pandemic period.
{"title":"Adherence to Growth Hormone Treatment in Children During the COVID-19 Pandemic","authors":"Erdal Eren, Semra Çetinkaya, Yasemin Denkboy Öngen, Ummahan Tercan, Şükran Darcan, Hande Turan, Murat Aydın, Fatma Yavuzyılmaz, Fatih Kilci, Beray Selver Eklioğlu, Nihal Hatipoğlu, Kübra Yüksek Acinikli, Zerrin Orbak, Emine Çamtosun, Şenay Savaş Erdeve, Emrullah Arslan, Oya Ercan, Feyza Darendeliler","doi":"10.4274/jcrpe.galenos.2024.2023-10-8","DOIUrl":"10.4274/jcrpe.galenos.2024.2023-10-8","url":null,"abstract":"<p><strong>Objective: </strong>Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported non-adherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the Coronavirus disease-2019 (COVID-19) pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated.</p><p><strong>Methods: </strong>This was a multicenter survey study that was sent to pediatric endocrinologists during the pandemic period (June-December 2021). Patient data, diagnosis, history of pituitary surgery, current GH doses, duration of GH therapy, the person administering therapy (either parent/patient), duration of missed doses, reasons for missed doses, as well as problems associated with GH therapy, missed dose data and the causes in the recent year (after the onset of the pandemic) were questioned. Treatment adherence was categorized based on missed dose rates over the past month (0 to 5%, full adherence; 5.1 to 10% moderate adherence; >10% non-adherence).</p><p><strong>Results: </strong>The study cohort consisted of 427 cases (56.2% male) from thirteen centers. Median age of diagnosis was 8.13 (0.13-16) years. Treatment indications were isolated GH deficiency (61.4%), multiple pituitary hormone deficiency (14%), Turner syndrome (7.5%), idiopathic GH deficiency (7.5%), small for gestational age (2.8%), and “others“ (6.8%). GH therapy was administered by parents in 70% and by patients in 30%. Mean daily dose was 32.3 μg/kg, the annual growth rate was 1.15 standard deviation score (minimum -2.74, maximum 9.3). Overall GH adherence rate was good in 70.3%, moderate in 14.7%, and poor in 15% of the patients. The reasons for non-adherence were mainly due to forgetfulness, being tired, inability to access medication, and/or pen problems. It was noteworthy that there was a negative effect on adherence during the COVID-19 pandemic reported by 22% of patients and the main reasons given were problems obtaining an appointment, taking the medication, and anxiety about going to hospital. There was no difference between genders in the adherence rate. Non-adherence to GH treatment decreased significantly when the patient: administered the treatment; was older; had longer duration of treatment; and during the pandemic. There was a non-significant decrease in annual growth rate as non-adherence rate increased.</p><p><strong>Conclusion: </strong>During the COVID-19 pandemic, the poor adherence rate was 15%, and duration of GH therapy and older age were important factors. There was a negative effect on adherence during the pandemic period.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05Epub Date: 2024-04-29DOI: 10.4274/jcrpe.galenos.2024.2024-1-25
Francisca Marques Puga, Laura Correia, Inês Vieira, Joana Serra Caetano, Rita Cardoso, Isabel Dinis, Alice Mirante
Objective: Differentiated thyroid cancer (DTC) is the most common pediatric endocrine cancer but studies are scarce. Latest recommendations advocate for an individualized risk-based approach to select patients for additional therapy. Lymphovascular invasion is not considered, despite being a well-known risk factor in the adult population. The aim of this study was to describe the outcomes of a cohort of DTC patients diagnosed at pediatric age and to evaluate the impact of lymphovascular invasion on the risk of persistence/recurrence.
Methods: A retrospective study of patients diagnosed with DTC at pediatric age from 2010 to 2022 at a single center was performed. All patients had total thyroidectomy. Radioactive iodine therapy (RAI) was used in selected patients. The response to therapy and occurrence of persistent/recurrent disease were evaluated.
Results: A total of 21 DTC were diagnosed, mostly papillary thyroid carcinoma (PTC) (81.0%, n=17). Six patients (28.6%) had nodal involvement and one (4.8%) had lung metastasis at the time of the diagnosis. Lymphovascular invasion was present in 11 patients (52.4%). After surgery, 13 patients (61.9%) underwent RAI. The mean follow-up time was 5.7±3.1 years. In total, 6 patients (31.6%) experienced persistent/recurrent disease during the follow-up time. Among PTC patients, persistent/recurrent disease was more frequent in the presence of lymphovascular invasion [55.6% (5/9) vs. 0.0% (0/6), p=0.031].
Conclusion: An individualized risk-based approach is recommended. Our study suggests that lymphovascular invasion may be associated with a higher risk of persistence/recurrence and should therefore be considered for decision making in children and adolescents with PTC.
{"title":"Differentiated Thyroid Cancer in Children and Adolescents: 12-year Experience in a Single Center","authors":"Francisca Marques Puga, Laura Correia, Inês Vieira, Joana Serra Caetano, Rita Cardoso, Isabel Dinis, Alice Mirante","doi":"10.4274/jcrpe.galenos.2024.2024-1-25","DOIUrl":"10.4274/jcrpe.galenos.2024.2024-1-25","url":null,"abstract":"<p><strong>Objective: </strong>Differentiated thyroid cancer (DTC) is the most common pediatric endocrine cancer but studies are scarce. Latest recommendations advocate for an individualized risk-based approach to select patients for additional therapy. Lymphovascular invasion is not considered, despite being a well-known risk factor in the adult population. The aim of this study was to describe the outcomes of a cohort of DTC patients diagnosed at pediatric age and to evaluate the impact of lymphovascular invasion on the risk of persistence/recurrence.</p><p><strong>Methods: </strong>A retrospective study of patients diagnosed with DTC at pediatric age from 2010 to 2022 at a single center was performed. All patients had total thyroidectomy. Radioactive iodine therapy (RAI) was used in selected patients. The response to therapy and occurrence of persistent/recurrent disease were evaluated.</p><p><strong>Results: </strong>A total of 21 DTC were diagnosed, mostly papillary thyroid carcinoma (PTC) (81.0%, n=17). Six patients (28.6%) had nodal involvement and one (4.8%) had lung metastasis at the time of the diagnosis. Lymphovascular invasion was present in 11 patients (52.4%). After surgery, 13 patients (61.9%) underwent RAI. The mean follow-up time was 5.7±3.1 years. In total, 6 patients (31.6%) experienced persistent/recurrent disease during the follow-up time. Among PTC patients, persistent/recurrent disease was more frequent in the presence of lymphovascular invasion [55.6% (5/9) vs. 0.0% (0/6), p=0.031].</p><p><strong>Conclusion: </strong>An individualized risk-based approach is recommended. Our study suggests that lymphovascular invasion may be associated with a higher risk of persistence/recurrence and should therefore be considered for decision making in children and adolescents with PTC.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Microcephaly, epilepsy and diabetes syndrome 1 (MEDS1) is a rare autosomal recessive disorder caused by defects in the immediate early response 3 interacting protein 1 (IER3IP1) gene. Only nine cases have been described in the literature. MEDS1 manifests as microcephaly with simplified gyral pattern in combination with severe infantile epileptic encephalopathy and early-onset permanent diabetes. A simplified gyral pattern has been described in all cases reported to date. Diagnosis is made by demonstration of specific mutations in the IER3IP1 gene. In this study, we present an additional case of a patient with MEDS1 who was homozygous for the c.53C>T p.(Ala18Val) variant. This case, the first to be reported from Turkey, differs from other cases due to the absence of a typical simplified gyral pattern on early brain magnetic resonance imaging, the late onset of diabetes, and the presence of a new genetic variant. The triad of microcephaly, generalized seizures and permanent neonatal diabetes should prompt screening for mutations in IER3IP1.
{"title":"A New Variant of the <i>IER3IP1</i> Gene: The First Case of Microcephaly, Epilepsy, and Diabetes Syndrome 1 from Turkey","authors":"Elif Söbü, Gül Demet Kaya Özçora, Elif Yılmaz Güleç, Bahtiyar Şahinoğlu, Feride Tahmiscioğlu Bucak","doi":"10.4274/jcrpe.galenos.2022.2022-8-12","DOIUrl":"10.4274/jcrpe.galenos.2022.2022-8-12","url":null,"abstract":"<p><p>Microcephaly, epilepsy and diabetes syndrome 1 (MEDS1) is a rare autosomal recessive disorder caused by defects in the immediate early response 3 interacting protein 1 (<i>IER3IP1</i>) gene. Only nine cases have been described in the literature. MEDS1 manifests as microcephaly with simplified gyral pattern in combination with severe infantile epileptic encephalopathy and early-onset permanent diabetes. A simplified gyral pattern has been described in all cases reported to date. Diagnosis is made by demonstration of specific mutations in the <i>IER3IP1</i> gene. In this study, we present an additional case of a patient with MEDS1 who was homozygous for the c.53C>T p.(Ala18Val) variant. This case, the first to be reported from Turkey, differs from other cases due to the absence of a typical simplified gyral pattern on early brain magnetic resonance imaging, the late onset of diabetes, and the presence of a new genetic variant. The triad of microcephaly, generalized seizures and permanent neonatal diabetes should prompt screening for mutations in <i>IER3IP1</i>.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40480348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dyshormonogenesis (DG) is the failure of thyroid hormone production due to a defect in thyroid hormonogenesis. Loss-of-function mutations in the thyroglobulin (TG) gene are a cause of DG, leading to gland stimulation by thyroid-stimulating hormone (TSH), resulting in goiter. We report a mitotically active follicular nodule in an 11-year-old female with a novel mutation in the TG gene. The patient had been under follow-up for congenital hypothyroidism (CH) since the neonatal period, and she had normal TSH levels on replacement therapy. Genetic test revealed a novel compound heterogeneous mutation [c.2149C>T (p.R717*) (P.Arg717Ter) / c.5361_5362delCCinsG (p.H1787Qfs*3) (p.His1787GlnfsTer3)] in the TG gene. She underwent total thyroidectomy for a thyroid nodule that was reported as Bethesda IV on fine needle aspiration biopsy (FNAB) and noted as suspicious for noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Pathological examination revealed a 16 mm, well-demarcated follicular nodule with a solid/insular pattern. Mitotic activity and Ki67 proliferation index were unusually high (10 mitoses/mm2 and 10%, respectively). Marked cellular pleomorphism and nuclear atypia are well-known diagnostic pitfalls in patients with dyshormonogenetic goiter. However, high mitotic activity is a feature that is less commonly reported in dyshormonogenetic goiter and may raise suspicion of poorly differentiated carcinoma when observed together with a solid pattern. The absence of signs of invasion, history of CH, and awareness of the presence of mutations compatible with dyshormonogenetic goiter can prevent the overinterpretation of such lesions. The risk of cancer development in the dyshormonogenetic thyroid gland is possible in childhood. The close follow-up is life-saving and prevents morbidities and possible mortality.
{"title":"Mitotically Active Follicular Nodule in Early Childhood: A Case Report with a Novel Mutation in the Thyroglobulin Gene","authors":"Sirmen Kızılcan Çetin, Zehra Aycan, Zeynep Şıklar, Serpil Dizbay Sak, Serdar Ceylaner, Elif Özsu, Merih Berberoğlu","doi":"10.4274/jcrpe.galenos.2022.2022-8-20","DOIUrl":"10.4274/jcrpe.galenos.2022.2022-8-20","url":null,"abstract":"<p><p>Dyshormonogenesis (DG) is the failure of thyroid hormone production due to a defect in thyroid hormonogenesis. Loss-of-function mutations in the thyroglobulin (<i>TG</i>) gene are a cause of DG, leading to gland stimulation by thyroid-stimulating hormone (TSH), resulting in goiter. We report a mitotically active follicular nodule in an 11-year-old female with a novel mutation in the <i>TG</i> gene. The patient had been under follow-up for congenital hypothyroidism (CH) since the neonatal period, and she had normal TSH levels on replacement therapy. Genetic test revealed a novel compound heterogeneous mutation [c.2149C>T (p.R717*) (P.Arg717Ter) / c.5361_5362delCCinsG (p.H1787Qfs*3) (p.His1787GlnfsTer3)] in the <i>TG</i> gene. She underwent total thyroidectomy for a thyroid nodule that was reported as Bethesda IV on fine needle aspiration biopsy (FNAB) and noted as suspicious for noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Pathological examination revealed a 16 mm, well-demarcated follicular nodule with a solid/insular pattern. Mitotic activity and Ki67 proliferation index were unusually high (10 mitoses/mm2 and 10%, respectively). Marked cellular pleomorphism and nuclear atypia are well-known diagnostic pitfalls in patients with dyshormonogenetic goiter. However, high mitotic activity is a feature that is less commonly reported in dyshormonogenetic goiter and may raise suspicion of poorly differentiated carcinoma when observed together with a solid pattern. The absence of signs of invasion, history of CH, and awareness of the presence of mutations compatible with dyshormonogenetic goiter can prevent the overinterpretation of such lesions. The risk of cancer development in the dyshormonogenetic thyroid gland is possible in childhood. The close follow-up is life-saving and prevents morbidities and possible mortality.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40714116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05Epub Date: 2024-03-25DOI: 10.4274/jcrpe.galenos.2024.2023-11-16
Maria Grazia Clemente, Dario Argiolas, Stefania Bassu, Angela Bitti, Cristian Locci, Mauro Argiolas, Lino Argiolas, Laura Saderi, Mariangela V Puci, Giovanni Sotgiu, Mary E Blue, Roberto Antonucci
Objective: Vitamin D deficiency is a common public health issue worldwide. The purpose of this study was to investigate the vitamin D status and its potential determinants in children residing in Sardinia (40°N), Italy.
Methods: Children were enrolled over a 12-month period. Serum 25(OH)D was measured by an immunochemiluminescence assay. A questionnaire was used to gather information on other variables, including passive smoke exposure.
Results: A total of 182 children (males: 51.7%; median age: 9 years) were included. Mean±standard deviation serum 25(OH)D was 25.2±8.3 ng/mL for the whole group. The majority (n=123, 67.6%) had vitamin D sufficient values >20 ng/mL, while 32.4% (n=59) had vitamin D insufficient/deficient values (≤20 ng/mL). Among the variables investigated, passive smoke exposure was significantly associated with insufficient 25(OH)D levels (p<0.0001).
Conclusion: Our results confirm that hypovitaminosis D is common in Italian children. Furthermore, passive smoke exposure was identified as a significant risk factor for hypovitaminosis D.
引言维生素 D 缺乏症是全球常见的公共卫生问题。本研究旨在调查意大利撒丁岛(北纬 40°)儿童的维生素 D 状况及其潜在决定因素:共招募了 182 名儿童(男性:51.7%;年龄中位数:9 岁),为期 12 个月。血清 25(OH)D 通过免疫-化学发光测定法进行测量。调查问卷用于收集包括被动吸烟在内的其他变量信息:全组平均(标清)血清 25(OH)D 为 25.2(8.3)纳克/毫升。大多数儿童(人数=123,占67.6%)的维生素D充足值大于20纳克/毫升,而约1/3的儿童维生素D不足/缺乏值(小于20纳克/毫升,人数=59,占32.4%)。在所调查的变量中,被动吸烟与 25(OH)D 水平不足显著相关(p 结论:我们的研究结果进一步证明,维生素 D 不足在意大利儿童中很常见,并证明被动吸烟是导致维生素 D 不足的一个重要风险因素。
{"title":"Vitamin D Status in an Italian Pediatric Cohort: Is There a Role for Tobacco Smoking Exposure?","authors":"Maria Grazia Clemente, Dario Argiolas, Stefania Bassu, Angela Bitti, Cristian Locci, Mauro Argiolas, Lino Argiolas, Laura Saderi, Mariangela V Puci, Giovanni Sotgiu, Mary E Blue, Roberto Antonucci","doi":"10.4274/jcrpe.galenos.2024.2023-11-16","DOIUrl":"10.4274/jcrpe.galenos.2024.2023-11-16","url":null,"abstract":"<p><strong>Objective: </strong>Vitamin D deficiency is a common public health issue worldwide. The purpose of this study was to investigate the vitamin D status and its potential determinants in children residing in Sardinia (40°N), Italy.</p><p><strong>Methods: </strong>Children were enrolled over a 12-month period. Serum 25(OH)D was measured by an immunochemiluminescence assay. A questionnaire was used to gather information on other variables, including passive smoke exposure.</p><p><strong>Results: </strong>A total of 182 children (males: 51.7%; median age: 9 years) were included. Mean±standard deviation serum 25(OH)D was 25.2±8.3 ng/mL for the whole group. The majority (n=123, 67.6%) had vitamin D sufficient values >20 ng/mL, while 32.4% (n=59) had vitamin D insufficient/deficient values (≤20 ng/mL). Among the variables investigated, passive smoke exposure was significantly associated with insufficient 25(OH)D levels (p<0.0001).</p><p><strong>Conclusion: </strong>Our results confirm that hypovitaminosis D is common in Italian children. Furthermore, passive smoke exposure was identified as a significant risk factor for hypovitaminosis D.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05Epub Date: 2023-04-19DOI: 10.4274/jcrpe.galenos.2023.2022-10-3
Qing Zhou, Li-Yong Zhang, Qing-Xian Fu, Chao-Chun Zou, Hui Liu
Thyroid storm is a rare but life-threatening condition mainly triggered by infection and abrupt discontinuation of antithyroid drug therapy for Graves’ disease. Pancytopenia is a rare adverse reaction to antithyroid drugs. We present a 13-year-old girl with thyroid storm and pancytopenia with symptoms similar to those of methimazole-induced pancytopenia. Although in this context the use of methimazole is still under debate, due to multiple normal complete blood counts (CBC) monitored during fever, sepsis-induced pancytopenia with thyroid storm was considered, and methimazole treatment combined with methylprednisolone and meropenem was able to resolve both pancytopenia and thyroid storm. During the period of infection and antithyroid drug therapy, close monitoring of CBC may help differentiate the aetiology of pancytopenia. This is the first paediatric case report that outlines the use of methimazole in the management of thyroid storm with pancytopenia.
{"title":"Sepsis-induced Pancytopenia in an Adolescent Girl with Thyroid Storm: A Case Report","authors":"Qing Zhou, Li-Yong Zhang, Qing-Xian Fu, Chao-Chun Zou, Hui Liu","doi":"10.4274/jcrpe.galenos.2023.2022-10-3","DOIUrl":"10.4274/jcrpe.galenos.2023.2022-10-3","url":null,"abstract":"<p><p>Thyroid storm is a rare but life-threatening condition mainly triggered by infection and abrupt discontinuation of antithyroid drug therapy for Graves’ disease. Pancytopenia is a rare adverse reaction to antithyroid drugs. We present a 13-year-old girl with thyroid storm and pancytopenia with symptoms similar to those of methimazole-induced pancytopenia. Although in this context the use of methimazole is still under debate, due to multiple normal complete blood counts (CBC) monitored during fever, sepsis-induced pancytopenia with thyroid storm was considered, and methimazole treatment combined with methylprednisolone and meropenem was able to resolve both pancytopenia and thyroid storm. During the period of infection and antithyroid drug therapy, close monitoring of CBC may help differentiate the aetiology of pancytopenia. This is the first paediatric case report that outlines the use of methimazole in the management of thyroid storm with pancytopenia.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9380036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05Epub Date: 2024-03-25DOI: 10.4274/jcrpe.galenos.2024.2023-8-17
Ahmet Anık, Mustafa Gök, Göksel Tuzcu
<p><strong>Objective: </strong>Point-of-Care Ultrasound (POCUS) refers to the use of portable ultrasound machines to perform quick and focused ultrasound examinations at a patient’s bedside or point-of-care. POCUS can be performed by all health workers with specific training to use POCUS. The aim of this study was to investigate the radiological performance and feasibility of POCUS using a handheld ultrasound device (HHUSD) in children for examining the thyroid gland.</p><p><strong>Methods: </strong>A pediatric endocrinologist performed thyroid imaging in children referred to our hospital with suspected thyroid disease using an HHUSD. The same children underwent ultrasonography (US) imaging using the same device by the first radiologist, and a second radiologist performed thyroid US using an advanced high-range ultrasound device (AHUSD) (defined as the gold-standard method) within two hours. The data obtained by the three researchers were compared with each other.</p><p><strong>Results: </strong>This study included 105 patients [68.6% girls (n=72)] with a mean age 12.8±3.6 years. When the thyroid volume was evaluated, a strong correlation was found between the measurements of the three researchers (AA vs. MG: r=0.963, AA vs. GT: r=0.969, MG vs. GT: r=0.963, p<0.001). According to the Bland-Altman analysis for total thyroid volume, AA measured 0.43 cc [95% confidence interval (CI): -0.89-0.03] smaller than MG, and 0.11 cc (95% CI: -0.30-0.52) larger than GT, whereas MG measured 0.52 cc (95% CI: 0.09-0.94) larger than GT. When evaluated for the presence of goiter and nodules, a near-perfect agreement was found between the results of the three researchers (AA vs. GT; κ=0.863, MG vs. GT; κ=0.887, p<0.001, and AA vs. GT; κ=1.000, MG vs. GT; κ=0.972, p<0.001, respectively). When evaluated in terms of the longest axis of nodules, a high correlation was found between the measurements of the three researchers (AA vs. MG; r=0.993, AA vs. GT; r=0.996, MG vs. GT; r=0.996, p<0.001). When evaluated in terms of the final diagnosis, the evaluations of the three researchers showed excellent agreement with each other (AA vs. GT; κ=0.893, MG vs. GT; κ=0.863, p<0.001, accuracy rate AA vs. GT: 93.3%; MG vs. GT: 91.4%).</p><p><strong>Conclusion: </strong>A pediatric endocrinologist, equipped with sufficient training in thyroid US evaluation, incorporated HHUSD examination as a routine clinical tool in an outpatient setting. It was shown that, they could effectively assess normal thyroid tissue in pediatric patients. Moreover, the HHUSD proved to be useful in detecting thyroid pathologies. However, it is important to note that for a more comprehensive evaluation of thyroid nodules, including detailed assessment and Thyroid Imaging Reporting and Data System (TIRADS) classification, patients should be referred to radiology departments equipped with AHUSD systems. These specialized devices, along with the expertise of radiologists, are essential for in-depth evaluations a
背景:护理点超声检查(POCUS)是指使用便携式超声波机在病人床边或护理点进行快速、集中的超声波检查。所有接受过 POCUS 使用专门培训的医务工作者均可进行 POCUS 检查。本研究旨在从甲状腺的角度研究使用手持式超声系统(HHUSD)对儿童进行POCUS检查的放射学性能和可行性:一名儿科内分泌专家使用HHUSD系统对转诊到我院的疑似甲状腺疾病患儿进行了甲状腺成像检查。第一位放射科医生使用相同的设备对同样的患儿进行了甲状腺 US 成像检查,第二位放射科医生在两小时内使用先进的高频超声设备(AHUSD)(被定义为黄金标准方法)对患儿进行了甲状腺 US 成像检查。三位研究人员获得的数据进行了比较:本研究共纳入 105 名患者(68.6% 为女孩[n=72];平均年龄(12.8±3.6)岁)。在评估甲状腺容积时,发现三位研究者的测量结果之间存在很强的相关性(AA vs. MG:r=0.963,AA vs. GT:r=0.969,MG vs. GT:r=0.963,pConclusion):受过甲状腺 US 评估充分培训的儿科内分泌医生将 HHUSD 作为门诊临床检查的常规工具,可以有效评估儿科患者的正常甲状腺组织。此外,HHUSD系统还可用于检测甲状腺病变。不过,必须指出的是,要对甲状腺结节进行更全面的评估,包括详细评估和甲状腺成像报告和数据系统(TIRADS)分类,患者应转诊到配备有AHUSD系统的放射科。这些专业设备和放射科医生的专业知识对于甲状腺结节的深入评估和准确分类至关重要。
{"title":"Assessment of Thyroid Gland in Children with Point-of-Care Ultrasound (POCUS): Radiological Performance and Feasibility of Handheld Ultrasound in Clinical Practice","authors":"Ahmet Anık, Mustafa Gök, Göksel Tuzcu","doi":"10.4274/jcrpe.galenos.2024.2023-8-17","DOIUrl":"10.4274/jcrpe.galenos.2024.2023-8-17","url":null,"abstract":"<p><strong>Objective: </strong>Point-of-Care Ultrasound (POCUS) refers to the use of portable ultrasound machines to perform quick and focused ultrasound examinations at a patient’s bedside or point-of-care. POCUS can be performed by all health workers with specific training to use POCUS. The aim of this study was to investigate the radiological performance and feasibility of POCUS using a handheld ultrasound device (HHUSD) in children for examining the thyroid gland.</p><p><strong>Methods: </strong>A pediatric endocrinologist performed thyroid imaging in children referred to our hospital with suspected thyroid disease using an HHUSD. The same children underwent ultrasonography (US) imaging using the same device by the first radiologist, and a second radiologist performed thyroid US using an advanced high-range ultrasound device (AHUSD) (defined as the gold-standard method) within two hours. The data obtained by the three researchers were compared with each other.</p><p><strong>Results: </strong>This study included 105 patients [68.6% girls (n=72)] with a mean age 12.8±3.6 years. When the thyroid volume was evaluated, a strong correlation was found between the measurements of the three researchers (AA vs. MG: r=0.963, AA vs. GT: r=0.969, MG vs. GT: r=0.963, p<0.001). According to the Bland-Altman analysis for total thyroid volume, AA measured 0.43 cc [95% confidence interval (CI): -0.89-0.03] smaller than MG, and 0.11 cc (95% CI: -0.30-0.52) larger than GT, whereas MG measured 0.52 cc (95% CI: 0.09-0.94) larger than GT. When evaluated for the presence of goiter and nodules, a near-perfect agreement was found between the results of the three researchers (AA vs. GT; κ=0.863, MG vs. GT; κ=0.887, p<0.001, and AA vs. GT; κ=1.000, MG vs. GT; κ=0.972, p<0.001, respectively). When evaluated in terms of the longest axis of nodules, a high correlation was found between the measurements of the three researchers (AA vs. MG; r=0.993, AA vs. GT; r=0.996, MG vs. GT; r=0.996, p<0.001). When evaluated in terms of the final diagnosis, the evaluations of the three researchers showed excellent agreement with each other (AA vs. GT; κ=0.893, MG vs. GT; κ=0.863, p<0.001, accuracy rate AA vs. GT: 93.3%; MG vs. GT: 91.4%).</p><p><strong>Conclusion: </strong>A pediatric endocrinologist, equipped with sufficient training in thyroid US evaluation, incorporated HHUSD examination as a routine clinical tool in an outpatient setting. It was shown that, they could effectively assess normal thyroid tissue in pediatric patients. Moreover, the HHUSD proved to be useful in detecting thyroid pathologies. However, it is important to note that for a more comprehensive evaluation of thyroid nodules, including detailed assessment and Thyroid Imaging Reporting and Data System (TIRADS) classification, patients should be referred to radiology departments equipped with AHUSD systems. These specialized devices, along with the expertise of radiologists, are essential for in-depth evaluations a","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Phosphate has a fundamental role in bone mineralization, and its chronic deficiency has multiple negative consequences in the body, including defects in bone mineralization that will manifest in children as rickets and osteomalacia. Here we present a young boy known to have Wiedemann-Steiner syndrome with multiple co-morbidities that necessitated gastric tube feeding. The child at 22 months was found to have hypophosphatemia and a high alkaline phosphatase level associated with rachitic skeletal manifestations that were attributed to low phosphate intake and/or gastrointestinal absorption, as there was no evidence of excessive phosphate wasting based on appropriate tubular renal re-absorption of phosphate. The primary nutritional source was an elemental amino acid-based milk formula (Neocate®) from 12 months of age. After switching from Neocate® to another elemental amino-acid based milk formula, all biochemical and radiological abnormalities returned to normal, indicating that the Neocate® formula was the possible cause of the patient’s low phosphate intake. However, in the literature, this formula-associated effect was only described in a limited number of patients. Whether or not some patient-related factors, such as the very rare syndrome described in our patient, could influence this effect warrants further exploration.
{"title":"Elemental Milk Formula as a Possible Cause of Hypophosphatemic Rickets in Wiedemann-Steiner Syndrome","authors":"Fahad Al-Juraibah, Maali Melha, Azam Alromaih, Areej Al-Sunaid, Hamad Abdullah Alkhalaf","doi":"10.4274/jcrpe.galenos.2022.2022-8-23","DOIUrl":"10.4274/jcrpe.galenos.2022.2022-8-23","url":null,"abstract":"<p><p>Phosphate has a fundamental role in bone mineralization, and its chronic deficiency has multiple negative consequences in the body, including defects in bone mineralization that will manifest in children as rickets and osteomalacia. Here we present a young boy known to have Wiedemann-Steiner syndrome with multiple co-morbidities that necessitated gastric tube feeding. The child at 22 months was found to have hypophosphatemia and a high alkaline phosphatase level associated with rachitic skeletal manifestations that were attributed to low phosphate intake and/or gastrointestinal absorption, as there was no evidence of excessive phosphate wasting based on appropriate tubular renal re-absorption of phosphate. The primary nutritional source was an elemental amino acid-based milk formula (Neocate<sup>®</sup>) from 12 months of age. After switching from Neocate<sup>®</sup> to another elemental amino-acid based milk formula, all biochemical and radiological abnormalities returned to normal, indicating that the Neocate<sup>®</sup> formula was the possible cause of the patient’s low phosphate intake. However, in the literature, this formula-associated effect was only described in a limited number of patients. Whether or not some patient-related factors, such as the very rare syndrome described in our patient, could influence this effect warrants further exploration.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10731938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In terms of prevalence, 11β-hydroxylase deficiency (11β-OHD), a common form of congenital adrenal hyperplasia, closely follows 21-hydroxylase deficiency. 11β-OHD has been attributed to diminished enzymatic activity owing to CYP11B1 gene variants, mainly encompassing single nucleotide variations and insertions-deletions. The involvement of chimeric CYP11B2/CYP11B1 genes in 11β-OHD has rarely been reported. We conducted a genetic investigation on a male infant with generalized pigmentation and abnormal steroid hormone levels. Whole-exome sequencing revealed a heterozygous variant in CYP11B1 inherited from the mother (NM_000497.4: c.1391_1393dup [p.Leu464dup]). Long-range polymerase chain reaction revealed an additional allele, a chimeric CYP11B2/CYP11B1 gene, inherited from the father. The current case report highlights the need to consider the occurrence of gene fusion variants in the diagnosis of neonatal or early infantile 11β-OHD.
{"title":"Clinical Presentation and Genetic Analysis of Neonatal 11β-Hydroxylase Deficiency Induced by a Chimeric <i>CYP11B2/CYP11B1</i> Gene","authors":"Wenjuan Cai, Dan Yu, Jian Gao, Qian Deng, Huihui Lin, Yuqing Chen","doi":"10.4274/jcrpe.galenos.2023.2023-9-13","DOIUrl":"10.4274/jcrpe.galenos.2023.2023-9-13","url":null,"abstract":"<p><p>In terms of prevalence, 11β-hydroxylase deficiency (11β-OHD), a common form of congenital adrenal hyperplasia, closely follows 21-hydroxylase deficiency. 11β-OHD has been attributed to diminished enzymatic activity owing to <i>CYP11B1</i> gene variants, mainly encompassing single nucleotide variations and insertions-deletions. The involvement of chimeric <i>CYP11B2/CYP11B1</i> genes in 11β-OHD has rarely been reported. We conducted a genetic investigation on a male infant with generalized pigmentation and abnormal steroid hormone levels. Whole-exome sequencing revealed a heterozygous variant in <i>CYP11B1</i> inherited from the mother (NM_000497.4: c.1391_1393dup [p.Leu464dup]). Long-range polymerase chain reaction revealed an additional allele, a chimeric <i>CYP11B2/CYP11B1</i> gene, inherited from the father. The current case report highlights the need to consider the occurrence of gene fusion variants in the diagnosis of neonatal or early infantile 11β-OHD.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}