Pub Date : 2017-01-01Epub Date: 2017-08-29DOI: 10.1186/s13633-017-0048-8
Huseyin Demirbilek, Sofia A Rahman, Gonul Gulal Buyukyilmaz, Khalid Hussain
Glucose homeostasis requires appropriate and synchronous coordination of metabolic events and hormonal activities to keep plasma glucose concentrations in a narrow range of 3.5-5.5 mmol/L. Insulin, the only glucose lowering hormone secreted from pancreatic β-cells, plays the key role in glucose homeostasis. Insulin release from pancreatic β-cells is mainly regulated by intracellular ATP-generating metabolic pathways. Hyperinsulinaemic hypoglycaemia (HH), the most common cause of severe and persistent hypoglycaemia in neonates and children, is the inappropriate secretion of insulin which occurs despite low plasma glucose levels leading to severe and persistent hypoketotic hypoglycaemia. Mutations in 12 different key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, PGM1 and PMM2) constitute the underlying molecular mechanisms of congenital HH. Since insulin supressess ketogenesis, the alternative energy source to the brain, a prompt diagnosis and immediate management of HH is essential to avoid irreversible hypoglycaemic brain damage in children. Advances in molecular genetics, imaging methods (18F-DOPA PET-CT), medical therapy and surgical approach (laparoscopic and open pancreatectomy) have changed the management and improved the outcome of patients with HH. This up to date review article provides a background to the diagnosis, molecular genetics, recent advances and therapeutic options in the field of HH in children.
{"title":"Diagnosis and treatment of hyperinsulinaemic hypoglycaemia and its implications for paediatric endocrinology.","authors":"Huseyin Demirbilek, Sofia A Rahman, Gonul Gulal Buyukyilmaz, Khalid Hussain","doi":"10.1186/s13633-017-0048-8","DOIUrl":"https://doi.org/10.1186/s13633-017-0048-8","url":null,"abstract":"<p><p>Glucose homeostasis requires appropriate and synchronous coordination of metabolic events and hormonal activities to keep plasma glucose concentrations in a narrow range of 3.5-5.5 mmol/L. Insulin, the only glucose lowering hormone secreted from pancreatic β-cells, plays the key role in glucose homeostasis. Insulin release from pancreatic β-cells is mainly regulated by intracellular ATP-generating metabolic pathways. Hyperinsulinaemic hypoglycaemia (HH), the most common cause of severe and persistent hypoglycaemia in neonates and children, is the inappropriate secretion of insulin which occurs despite low plasma glucose levels leading to severe and persistent hypoketotic hypoglycaemia. Mutations in 12 different key genes (<i>ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, PGM1 and PMM2</i>) constitute the underlying molecular mechanisms of congenital HH. Since insulin supressess ketogenesis, the alternative energy source to the brain, a prompt diagnosis and immediate management of HH is essential to avoid irreversible hypoglycaemic brain damage in children. Advances in molecular genetics, imaging methods (<sup>18</sup>F-DOPA PET-CT), medical therapy and surgical approach (laparoscopic and open pancreatectomy) have changed the management and improved the outcome of patients with HH. This up to date review article provides a background to the diagnosis, molecular genetics, recent advances and therapeutic options in the field of HH in children.</p>","PeriodicalId":14271,"journal":{"name":"International Journal of Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13633-017-0048-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35311597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01Epub Date: 2017-07-17DOI: 10.1186/s13633-017-0046-x
Juan F Sotos, Naomi J Tokar
Background: Testicular volumes obtained with orchidometers or external linear measurements in the scrotum (centimeter ruler or calipers) grossly over-estimate ultrasound volumes, have much variability and may not be accurate or reproducible. The reference of the values obtained by orchidometers or US, to age or Tanner stages is not useful to determine the normal values for stages of puberty, because overlapping of ages and values. Pubertal development is determined by two events, genital and pubic hair development, that should be analyzed independently because one could be out of step with the other. The ultrasound (US) measurement of testicular volumes is the gold standard but is somewhat inconvenient, because it requires another procedure and, mainly, is costly. The solution of the problems would be to determine testicular volumes matching US values, from the width of the testis obtained in the scrotum with a centimeter ruler, by formulas recently described, and to reference them to the stages of genital development.
Methods: The width and length of the testes in the scrotum with a centimeter ruler were obtained in 159 study subjects, in different stages of genital development and adults, for a total of 318 testicular determinations, from the age of 3 to 34 years. The width obtained in the scrotum was corrected by subtracting the values of the double scrotal skin (ss). The formulas were then applied and the testicular volumes matching US values were calculated. The volumes and the range of ages for different stages of genital development were determined. Penile measurements were obtained in 145 subjects and pubic and other hair recorded. Paired and unpaired 2 tail student t-test was used to compare the means of the different groups expressed as means and SD and, in addition the Wilcoxon rank sum test and Bootstrap methods for the testicular volume groups. A p value of 0.05 or less was considered significant. The Institutional Review Board (IRB) of Nationwide Children's Hospital determined that this study did not require IRB approval.
Results: With a simple measurement of the width of the testis in the scrotum, with a centimeter ruler, testicular volumes matching US values were calculated and normative values for each stage of genital development were determined.
Conclusion: This information should solve present problems.
{"title":"Appraisal of testicular volumes: volumes matching ultrasound values referenced to stages of genital development.","authors":"Juan F Sotos, Naomi J Tokar","doi":"10.1186/s13633-017-0046-x","DOIUrl":"https://doi.org/10.1186/s13633-017-0046-x","url":null,"abstract":"<p><strong>Background: </strong>Testicular volumes obtained with orchidometers or external linear measurements in the scrotum (centimeter ruler or calipers) grossly over-estimate ultrasound volumes, have much variability and may not be accurate or reproducible. The reference of the values obtained by orchidometers or US, to age or Tanner stages is not useful to determine the normal values for stages of puberty, because overlapping of ages and values. Pubertal development is determined by two events, genital and pubic hair development, that should be analyzed independently because one could be out of step with the other. The ultrasound (US) measurement of testicular volumes is the gold standard but is somewhat inconvenient, because it requires another procedure and, mainly, is costly. The solution of the problems would be to determine testicular volumes matching US values, from the width of the testis obtained in the scrotum with a centimeter ruler, by formulas recently described, and to reference them to the stages of genital development.</p><p><strong>Methods: </strong>The width and length of the testes in the scrotum with a centimeter ruler were obtained in 159 study subjects, in different stages of genital development and adults, for a total of 318 testicular determinations, from the age of 3 to 34 years. The width obtained in the scrotum was corrected by subtracting the values of the double scrotal skin (ss). The formulas were then applied and the testicular volumes matching US values were calculated. The volumes and the range of ages for different stages of genital development were determined. Penile measurements were obtained in 145 subjects and pubic and other hair recorded. Paired and unpaired 2 tail student t-test was used to compare the means of the different groups expressed as means and SD and, in addition the Wilcoxon rank sum test and Bootstrap methods for the testicular volume groups. A <i>p</i> value of 0.05 or less was considered significant. The Institutional Review Board (IRB) of Nationwide Children's Hospital determined that this study did not require IRB approval.</p><p><strong>Results: </strong>With a simple measurement of the width of the testis in the scrotum, with a centimeter ruler, testicular volumes matching US values were calculated and normative values for each stage of genital development were determined.</p><p><strong>Conclusion: </strong>This information should solve present problems.</p>","PeriodicalId":14271,"journal":{"name":"International Journal of Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13633-017-0046-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35182638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01Epub Date: 2017-08-04DOI: 10.1186/s13633-017-0047-9
Dinesh Giri, Daniel Rigden, Mohammed Didi, Matthew Peak, Paul McNamara, Senthil Senniappan
Background: De novo truncating and splicing mutations in the additional sex combs-like 3 (ASXL3) gene have been implicated in the development of Bainbridge-Ropers syndrome (BRPS) characterised by severe developmental delay, feeding problems, short stature and characteristic facial features.
Case presentation: We describe, for the first time, a patient with severe short stature, learning difficulties, feeding difficulties and dysmorphic features with a novel compound heterozygous mutation in ASXL3.Additionally the patient also has primary insulin like growth factor-1 (IGF1) deficiency. The mutations occur in exon 11 and proximal part of exon 12 and are strongly conserved at the protein level across various species. In-silico analyses using PolyPhen-2 and SIFT predict the amino acid substitutions to be potentially deleterious to the protein function. Detailed bioinformatics analysis show that the molecular defects caused by the two compound heterozygous mutations synergistically impact on two points of the molecular interaction network of ASXL3.
Conclusion: We hypothesise that ASXL3 potentially has a role in transcriptional activation of IGF1 involved in signalling pathways that regulate cell proliferation and growth, which could be contributing to short stature encountered in these patients.
{"title":"Novel compound heterozygous <i>ASXL3</i> mutation causing Bainbridge-ropers like syndrome and primary IGF1 deficiency.","authors":"Dinesh Giri, Daniel Rigden, Mohammed Didi, Matthew Peak, Paul McNamara, Senthil Senniappan","doi":"10.1186/s13633-017-0047-9","DOIUrl":"https://doi.org/10.1186/s13633-017-0047-9","url":null,"abstract":"<p><strong>Background: </strong>De novo truncating and splicing mutations in the additional sex combs-like 3 (<i>ASXL3</i>) gene have been implicated in the development of Bainbridge-Ropers syndrome (BRPS) characterised by severe developmental delay, feeding problems, short stature and characteristic facial features.</p><p><strong>Case presentation: </strong>We describe, for the first time, a patient with severe short stature, learning difficulties, feeding difficulties and dysmorphic features with a novel compound heterozygous mutation in <i>ASXL3</i>.Additionally the patient also has primary insulin like growth factor-1 (IGF1) deficiency. The mutations occur in exon 11 and proximal part of exon 12 and are strongly conserved at the protein level across various species. <i>In-silico</i> analyses using PolyPhen-2 and SIFT predict the amino acid substitutions to be potentially deleterious to the protein function. Detailed bioinformatics analysis show that the molecular defects caused by the two compound heterozygous mutations synergistically impact on two points of the molecular interaction network of <i>ASXL3.</i></p><p><strong>Conclusion: </strong>We hypothesise that <i>ASXL3</i> potentially has a role in transcriptional activation of <i>IGF1</i> involved in signalling pathways that regulate cell proliferation and growth, which could be contributing to short stature encountered in these patients.</p>","PeriodicalId":14271,"journal":{"name":"International Journal of Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13633-017-0047-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35299371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01Epub Date: 2017-06-02DOI: 10.1186/s13633-017-0044-z
Melinda Chen, Matthew Lash, Todd Nebesio, Erica Eugster
Background: We aimed to determine the extent of post-treatment weight gain that occurs in pediatric patients in the first year following radioactive iodine (RAI) therapy for Graves disease (GD) and its relationship to clinical characteristics.
Methods: A retrospective chart review of patients receiving RAI therapy for GD between 1998-2015 was performed. Change in BMI SDS (∆BMI SDS) from baseline to one year after treatment was determined. We also investigated whether individual clinical and/or biochemical factors were associated with the weight trajectory in these patients.
Results: One hundred fifty seven patients aged 12.7 ± 3 years (80% girls) were included in the analysis. Average ∆BMI SDS was 0.70 ± 0.71 (p < 0.001) at 1 year. Patients with weight loss at presentation had a greater ∆BMI SDS than those without (0.92 vs 0.56, p = 0.005), whereas no association was seen with gender, pubertal status, use of antithyroid drugs, history of ADHD, or Down syndrome. Baseline BMI SDS was negatively correlated with ∆BMI SDS, with a stronger correlation in males. From baseline to 1 year, the proportion of overweight and obese patients increased from 9.6% to 18.5% and from 6.4% to 21%, respectively. In a subset of 81 patients, a positive correlation was noted between time to euthyroidism and ∆BMI SDS, particularly in boys.
Conclusions: The number of our patients in the overweight category doubled and the number in the obese category more than tripled in the first year following RAI treatment for GD. Anticipatory guidance regarding this important issue is badly needed.
背景:我们旨在确定放射性碘(RAI)治疗Graves病(GD)后第一年儿科患者治疗后体重增加的程度及其与临床特征的关系。方法:回顾性分析1998-2015年间接受RAI治疗的GD患者。测定BMI SDS(∆BMI SDS)从基线到治疗后一年的变化。我们还调查了个体临床和/或生化因素是否与这些患者的体重轨迹有关。结果:157例患者(12.7±3岁)纳入分析,其中80%为女孩。1年平均∆BMI SDS为0.70±0.71 (p 0.001)。出现体重减轻的患者比没有出现体重减轻的患者有更大的∆BMI SDS (0.92 vs 0.56, p = 0.005),而与性别、青春期状态、使用抗甲状腺药物、ADHD史或唐氏综合症没有关联。基线BMI SDS与∆BMI SDS呈负相关,其中男性相关性更强。从基线到1年,超重和肥胖患者的比例分别从9.6%增加到18.5%和从6.4%增加到21%。在81例患者的亚组中,注意到甲状腺功能减退的时间与BMI SDS之间呈正相关,特别是在男孩中。结论:在RAI治疗GD后的第一年,超重类别的患者数量增加了一倍,肥胖类别的数量增加了两倍多。迫切需要对这一重要问题提供前瞻性指导。
{"title":"Change in BMI after radioactive iodine ablation for graves disease.","authors":"Melinda Chen, Matthew Lash, Todd Nebesio, Erica Eugster","doi":"10.1186/s13633-017-0044-z","DOIUrl":"https://doi.org/10.1186/s13633-017-0044-z","url":null,"abstract":"<p><strong>Background: </strong>We aimed to determine the extent of post-treatment weight gain that occurs in pediatric patients in the first year following radioactive iodine (RAI) therapy for Graves disease (GD) and its relationship to clinical characteristics.</p><p><strong>Methods: </strong>A retrospective chart review of patients receiving RAI therapy for GD between 1998-2015 was performed. Change in BMI SDS (∆BMI SDS) from baseline to one year after treatment was determined. We also investigated whether individual clinical and/or biochemical factors were associated with the weight trajectory in these patients.</p><p><strong>Results: </strong>One hundred fifty seven patients aged 12.7 ± 3 years (80% girls) were included in the analysis. Average ∆BMI SDS was 0.70 ± 0.71 (<i>p <</i> 0.001) at 1 year. Patients with weight loss at presentation had a greater ∆BMI SDS than those without (0.92 vs 0.56, <i>p =</i> 0.005), whereas no association was seen with gender, pubertal status, use of antithyroid drugs, history of ADHD, or Down syndrome. Baseline BMI SDS was negatively correlated with ∆BMI SDS, with a stronger correlation in males. From baseline to 1 year, the proportion of overweight and obese patients increased from 9.6% to 18.5% and from 6.4% to 21%, respectively. In a subset of 81 patients, a positive correlation was noted between time to euthyroidism and ∆BMI SDS, particularly in boys.</p><p><strong>Conclusions: </strong>The number of our patients in the overweight category doubled and the number in the obese category more than tripled in the first year following RAI treatment for GD. Anticipatory guidance regarding this important issue is badly needed.</p>","PeriodicalId":14271,"journal":{"name":"International Journal of Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13633-017-0044-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35065740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01Epub Date: 2017-09-29DOI: 10.1186/s13633-017-0050-1
Juan F Sotos, Naomi J Tokar
[This corrects the article DOI: 10.1186/s13633-017-0046-x.].
[这更正了文章DOI: 10.1186/s13633-017-0046-x]。
{"title":"Erratum to: Appraisal of testicular volumes: volumes matching ultrasound values referenced to stages of genital development.","authors":"Juan F Sotos, Naomi J Tokar","doi":"10.1186/s13633-017-0050-1","DOIUrl":"https://doi.org/10.1186/s13633-017-0050-1","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1186/s13633-017-0046-x.].</p>","PeriodicalId":14271,"journal":{"name":"International Journal of Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13633-017-0050-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35503308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01Epub Date: 2017-10-13DOI: 10.1186/s13633-017-0052-z
Juan Sotos, Katherine Miller, Donald Corsmeier, Naomi Tokar, Benjamin Kelly, Vijay Nadella, Huachun Zhong, Amy Wetzel, Brent Adler, Chack-Yung Yu, Peter White
Background: We report a female patient with endocrine abnormalities, hypogonadotropic hypogonadism and amazia (breasts aplasia/hypoplasia but normal nipples and areolas) in a rare syndrome: Van Maldergem syndrome (VMS).
Case presentation: Our patient was first evaluated at age 4 for intellectual disability, craniofacial features, and auditory malformations. At age 15, she presented with no breast development and other findings consistent with hypogonadotropic hypogonadism. At age 37, she underwent whole exome sequencing (WES) to identify pathogenic variants. WES revealed compound heterozygous variants in DCHS1 (rs145099391:G > A, p.P197L & rs753548138:G > A, p.T2334 M) [RefSeq NM_003737.3], diagnostic of Van Maldergem syndrome (VMS-1). VMS is a rare autosomal disorder reported in only 13 patients, characterized by intellectual disability, typical craniofacial features, auditory malformations, hearing loss, skeletal and limb malformations, brain abnormalities with periventricular neuronal heterotopia and other variable anomalies. Our patient had similar phenotypic abnormalities. She also had hypogonadotropic hypogonadism and amazia. Based on the clinical findings reported, two previously published patients with VMS may also have been affected by hypogonadotropic hypogonadism, but endocrine abnormalities were not evaluated or mentioned.
Conclusion: This case highlights an individual with VMS, characterized by compound heterozygous variants in DCHS1. Our observations may provide additional information on the phenotypic spectrum of VMS, including hypogonadotropic hypogonadism and amazia. However, the molecular genetic basis for endocrine anomalies observed in some VMS patients, including ours, remains unexplained.
背景:我们报告了一位女性内分泌异常,促性腺功能低下和amazia(乳房发育不全/发育不全但乳头和乳晕正常)的罕见综合征:Van Maldergem综合征(VMS)。病例介绍:我们的患者在4岁时首次被评估为智力残疾,颅面特征和听觉畸形。15岁时,她没有乳房发育,其他表现符合促性腺功能减退症。37岁时,她接受了全外显子组测序(WES)来鉴定致病变异。WES检测发现DCHS1 (rs145099391:G > A, p.P197L和rs753548138:G > A, p.T2334 M) [RefSeq NM_003737.3]复合杂合变异体,诊断Van Maldergem综合征(VMS-1)。VMS是一种罕见的常染色体疾病,仅报道了13例患者,其特征为智力残疾,典型颅面特征,听觉畸形,听力丧失,骨骼和肢体畸形,脑异常伴脑室周围神经元异位和其他可变异常。我们的病人也有类似的表型异常。她还患有促性腺激素减退症和amazia。根据所报道的临床结果,先前发表的两例VMS患者也可能受到促性腺功能低下的影响,但内分泌异常未被评估或提及。结论:该病例突出了一个VMS个体,其特征是DCHS1的复合杂合变异体。我们的观察结果可能为VMS的表型谱提供额外的信息,包括促性腺功能低下和amazia。然而,在包括我们在内的一些VMS患者中观察到的内分泌异常的分子遗传学基础仍未得到解释。
{"title":"A patient with van Maldergem syndrome with endocrine abnormalities, hypogonadotropic hypogonadism, and breast aplasia/hypoplasia.","authors":"Juan Sotos, Katherine Miller, Donald Corsmeier, Naomi Tokar, Benjamin Kelly, Vijay Nadella, Huachun Zhong, Amy Wetzel, Brent Adler, Chack-Yung Yu, Peter White","doi":"10.1186/s13633-017-0052-z","DOIUrl":"https://doi.org/10.1186/s13633-017-0052-z","url":null,"abstract":"<p><strong>Background: </strong>We report a female patient with endocrine abnormalities, hypogonadotropic hypogonadism and amazia (breasts aplasia/hypoplasia but normal nipples and areolas) in a rare syndrome: Van Maldergem syndrome (VMS).</p><p><strong>Case presentation: </strong>Our patient was first evaluated at age 4 for intellectual disability, craniofacial features, and auditory malformations. At age 15, she presented with no breast development and other findings consistent with hypogonadotropic hypogonadism. At age 37, she underwent whole exome sequencing (WES) to identify pathogenic variants. WES revealed compound heterozygous variants in <i>DCHS1</i> (rs145099391:G > A, p.P197L & rs753548138:G > A, <i>p</i>.T2334 M) [RefSeq NM_003737.3], diagnostic of Van Maldergem syndrome (VMS-1). VMS is a rare autosomal disorder reported in only 13 patients, characterized by intellectual disability, typical craniofacial features, auditory malformations, hearing loss, skeletal and limb malformations, brain abnormalities with periventricular neuronal heterotopia and other variable anomalies. Our patient had similar phenotypic abnormalities. She also had hypogonadotropic hypogonadism and amazia. Based on the clinical findings reported, two previously published patients with VMS may also have been affected by hypogonadotropic hypogonadism, but endocrine abnormalities were not evaluated or mentioned.</p><p><strong>Conclusion: </strong>This case highlights an individual with VMS, characterized by compound heterozygous variants in <i>DCHS1</i>. Our observations may provide additional information on the phenotypic spectrum of VMS, including hypogonadotropic hypogonadism and amazia. However, the molecular genetic basis for endocrine anomalies observed in some VMS patients, including ours, remains unexplained.</p>","PeriodicalId":14271,"journal":{"name":"International Journal of Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13633-017-0052-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35522946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Hypoglycemia due to a pancreatic beta cell neoplasm - insulinoma, is uncommon with only a few cases described. We report on a previously healthy 15-year-old Hispanic female with insulinoma who presented with a loss of consciousness due to hypoglycemia unawareness.
Case presentation: EM was first brought to the emergency department (ED) after she was found unresponsive at home with point of care (POC) glucose of 29 mg/dL(1.6 mmol/L) documented by emergency medical services (EMS) upon arrival. After treatment with dextrose and normal laboratory evaluation, including complete blood count, basal metabolic profile and urine drug screen, she was sent home with recommendations to follow-up the next day with an endocrinologist. Due to insurance issues, the family did not keep the appointment. Two days later, she returned to the ED with POC of 19 mg/dL (1.05 mmol/L). Detailed history review identified vague fatigue, excessive sleepiness, poor oral intake and weight gain for a 2-3 month period and no suspicion for drug, alcohol or prescription medication abuse. Family history of multiple endocrine neoplasia was negative. Physical examination revealed mild acanthosis nigricans and a body mass index of 32.8 kg/m2 (98th percentile). Laboratory evaluation showed elevated insulin with low cortisol and growth hormone levels at the time of hypoglycemia. Abdominal magnetic resonance imaging revealed a pancreatic mass, also supported by ultrasound, computed tomography and positron emission tomography scans. The patient underwent a partial pancreatectomy with removal of a well-circumscribed insulinoma from the anterior-superior aspect of the pancreatic neck confirmed by histology. Hypoglycemia resolved post-operatively and she remained euglycemic during a 48-h cure fast. At her 3-month follow-up visit, she had no symptoms of hypoglycemia.
Conclusion: Documented hypoglycemia in an otherwise healthy adolescent should be fully investigated before discharging a patient. Even a short duration of symptoms should prompt, in-depth diagnostic evaluations to rule out a potentially life threatening diagnosis of insulinoma.
{"title":"Insulinoma masquerading as a loss of consciousness in a teenage girl: case report and literature review.","authors":"Meghana Gudala, Mahmuda Ahmed, Rushika Conroy, Ksenia Tonyushkina","doi":"10.1186/s13633-017-0049-7","DOIUrl":"https://doi.org/10.1186/s13633-017-0049-7","url":null,"abstract":"<p><strong>Background: </strong>Hypoglycemia due to a pancreatic beta cell neoplasm - insulinoma, is uncommon with only a few cases described. We report on a previously healthy 15-year-old Hispanic female with insulinoma who presented with a loss of consciousness due to hypoglycemia unawareness.</p><p><strong>Case presentation: </strong>EM was first brought to the emergency department (ED) after she was found unresponsive at home with point of care (POC) glucose of 29 mg/dL(1.6 mmol/L) documented by emergency medical services (EMS) upon arrival. After treatment with dextrose and normal laboratory evaluation, including complete blood count, basal metabolic profile and urine drug screen, she was sent home with recommendations to follow-up the next day with an endocrinologist. Due to insurance issues, the family did not keep the appointment. Two days later, she returned to the ED with POC of 19 mg/dL (1.05 mmol/L). Detailed history review identified vague fatigue, excessive sleepiness, poor oral intake and weight gain for a 2-3 month period and no suspicion for drug, alcohol or prescription medication abuse. Family history of multiple endocrine neoplasia was negative. Physical examination revealed mild acanthosis nigricans and a body mass index of 32.8 kg/m<sup>2</sup> (98th percentile). Laboratory evaluation showed elevated insulin with low cortisol and growth hormone levels at the time of hypoglycemia. Abdominal magnetic resonance imaging revealed a pancreatic mass, also supported by ultrasound, computed tomography and positron emission tomography scans. The patient underwent a partial pancreatectomy with removal of a well-circumscribed insulinoma from the anterior-superior aspect of the pancreatic neck confirmed by histology. Hypoglycemia resolved post-operatively and she remained euglycemic during a 48-h cure fast. At her 3-month follow-up visit, she had no symptoms of hypoglycemia.</p><p><strong>Conclusion: </strong>Documented hypoglycemia in an otherwise healthy adolescent should be fully investigated before discharging a patient. Even a short duration of symptoms should prompt, in-depth diagnostic evaluations to rule out a potentially life threatening diagnosis of insulinoma.</p>","PeriodicalId":14271,"journal":{"name":"International Journal of Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13633-017-0049-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35552130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01Epub Date: 2017-11-21DOI: 10.1186/s13633-017-0053-y
Juan F Sotos, Naomi J Tokar
The determination of the testicular volume is of considerable importance to assess the onset, progression and disorders of puberty, abnormal testicular development, and a number of other conditions; and in adults, assessment of fertility. A number of clinical methods have been used for the measurement of testicular volumes in the scrotum: a centimeter ruler, sliding calipers, and orchidometers. All the clinical methods calculate the volumes by the ellipsoid equation, grossly overestimate ultrasound (US) volumes by 70 to 80% for adults, to 150 to 250% for prepubertal subjects, mainly because the inclusion of the scrotal skin and epididymis and may not be accurate of reproducible. Ultrasound measurements have a high degree of accuracy and reproducibility and are the standard for quantitation of testicular volume. Formulas, equivalent to the ellipsoid equations used, were developed to match ultrasound volumes, with corrections of the width and length of the testis obtained in the scrotum, to avoid the inclusion of the scrotal skin (ss) and epididymis. A calculator was developed, requiring only the identification of ① the width of the testis in cm obtained in the scrotum with a ruler (without corrections) (i.e. 0.9, 1.5, 2.0, 2.4 cm etc.) and ② the stage of genital development. The calculator will subtract the scrotal skin for the stage of genital development, from the measurement of the width provided, apply the formula and identify the testicular volume of the subject that matches the US volume. The calculator will also provide, in a Table form, the values for the different stages of genital development. Benefit: The information provided by the calculator will solve the problem of overestimation by the orchidometers and the external measurements, problems with the reference of values to age, and Tanner stages, would permit assessment of the beginning and progression of puberty, of micro and macroorchidism, and other conditions mentioned.
{"title":"A medical calculator to determine testicular volumes matching ultrasound values from the width of the testis obtained in the scrotum with a centimeter ruler.","authors":"Juan F Sotos, Naomi J Tokar","doi":"10.1186/s13633-017-0053-y","DOIUrl":"https://doi.org/10.1186/s13633-017-0053-y","url":null,"abstract":"<p><p>The determination of the testicular volume is of considerable importance to assess the onset, progression and disorders of puberty, abnormal testicular development, and a number of other conditions; and in adults, assessment of fertility. A number of clinical methods have been used for the measurement of testicular volumes in the scrotum: a centimeter ruler, sliding calipers, and orchidometers. All the clinical methods calculate the volumes by the ellipsoid equation, grossly overestimate ultrasound (US) volumes by 70 to 80% for adults, to 150 to 250% for prepubertal subjects, mainly because the inclusion of the scrotal skin and epididymis and may not be accurate of reproducible. Ultrasound measurements have a high degree of accuracy and reproducibility and are the standard for quantitation of testicular volume. Formulas, equivalent to the ellipsoid equations used, were developed to match ultrasound volumes, with corrections of the width and length of the testis obtained in the scrotum, to avoid the inclusion of the scrotal skin (ss) and epididymis. <b>A calculator</b> was developed, requiring only the identification of ① the width of the testis in cm obtained in the scrotum with a ruler (without corrections) (i.e. 0.9, 1.5, 2.0, 2.4 cm etc.) and ② the stage of genital development. The calculator will subtract the scrotal skin for the stage of genital development, from the measurement of the width provided, apply the formula and identify the testicular volume of the subject that matches the US volume. The calculator will also provide, in a Table form, the values for the different stages of genital development. <b>Benefit</b>: The information provided by the calculator will solve the problem of overestimation by the orchidometers and the external measurements, problems with the reference of values to age, and Tanner stages, would permit assessment of the beginning and progression of puberty, of micro and macroorchidism, and other conditions mentioned.</p>","PeriodicalId":14271,"journal":{"name":"International Journal of Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13633-017-0053-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35307381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01Epub Date: 2017-06-06DOI: 10.1186/s13633-017-0045-y
Serwah Bonsu Asafo-Agyei, Emmanuel Ameyaw, Jean-Pierre Chanoine, Margaret Zacharin, Samuel Blay Nguah
Background: Data on normative clitoral sizes in newborns is relatively sparse and racial/ethnic differences have also been reported. This study was performed to establish norms for clitoral size in term Ghanaian female newborns.
Methods: This was a cross-sectional study of all apparently well full-term newborns of postnatal age < 48 h and birth weight between 2.5 and 4.0 kg delivered at Komfo Anokye Teaching Hospital between May and September, 2014. Anthropometric and genital parameters were documented for study subjects as well as parental socio-demographic indices.
Results: In 612 newborn females studied, the mean (±SD) clitoral length (MCL) and the mean (±SD) clitoral width (MCW) were 4.13 ± 1.6 mm and 4.21 ± 1.1 mm, respectively. MCL was inversely related to birth weight (r = -0.62; p < 0.001 ) while MCW was inversely related to both gestational age (r = -0.1; p = 0.02 ) and birth weight (r = -0.54; p < 0.001 ). Babies with a clitoris that was completely covered by the labia majora had relatively lower clitoral sizes (p < 0.001) than those who had a partially covered or prominent clitoris. Neither MCL nor MCW differed significantly by birth length or maternal tribe.
Conclusions: Clitoral size varies with birth weight and gestational age. Babies with a completely covered clitoris are unlikely to warrant detailed clitoral measurements for clitoromegaly.
{"title":"Clitoral size in term newborns in Kumasi, Ghana.","authors":"Serwah Bonsu Asafo-Agyei, Emmanuel Ameyaw, Jean-Pierre Chanoine, Margaret Zacharin, Samuel Blay Nguah","doi":"10.1186/s13633-017-0045-y","DOIUrl":"https://doi.org/10.1186/s13633-017-0045-y","url":null,"abstract":"<p><strong>Background: </strong>Data on normative clitoral sizes in newborns is relatively sparse and racial/ethnic differences have also been reported. This study was performed to establish norms for clitoral size in term Ghanaian female newborns.</p><p><strong>Methods: </strong>This was a cross-sectional study of all apparently well full-term newborns of postnatal age < 48 h and birth weight between 2.5 and 4.0 kg delivered at Komfo Anokye Teaching Hospital between May and September, 2014. Anthropometric and genital parameters were documented for study subjects as well as parental socio-demographic indices.</p><p><strong>Results: </strong>In 612 newborn females studied, the mean (±SD) clitoral length (MCL) and the mean (±SD) clitoral width (MCW) were 4.13 ± 1.6 mm and 4.21 ± 1.1 mm, respectively. MCL was inversely related to birth weight (<i>r</i> = -0.62; <b><i>p < 0.001</i></b> ) while MCW was inversely related to both gestational age (<i>r</i> = -0.1; <b><i>p = 0.02</i></b> ) and birth weight (<i>r</i> = -0.54; <b><i>p < 0.001</i></b> ). Babies with a clitoris that was completely covered by the labia majora had relatively lower clitoral sizes (<i>p</i> < 0.001) than those who had a partially covered or prominent clitoris. Neither MCL nor MCW differed significantly by birth length or maternal tribe.</p><p><strong>Conclusions: </strong>Clitoral size varies with birth weight and gestational age. Babies with a completely covered clitoris are unlikely to warrant detailed clitoral measurements for clitoromegaly.</p>","PeriodicalId":14271,"journal":{"name":"International Journal of Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13633-017-0045-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35069986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01Epub Date: 2017-10-02DOI: 10.1186/s13633-017-0051-0
Christine E Cherella, Ari J Wassner
Congenital hypothyroidism occurs in approximately 1 in 2000 newborns and can have devastating neurodevelopmental consequences if not detected and treated promptly. While newborn screening has virtually eradicated intellectual disability due to severe congenital hypothyroidism in the developed world, more stringent screening strategies have resulted in increased detection of mild congenital hypothyroidism. Recent studies provide conflicting evidence about the potential neurodevelopmental risks posed by mild congenital hypothyroidism, highlighting the need for additional research to further define what risks these patients face and whether they are likely to benefit from treatment. Moreover, while the apparent incidence of congenital hypothyroidism has increased in recent decades, the underlying cause remains obscure in most cases. However, ongoing research into genetic causes of congenital hypothyroidism continues to shed new light on the development and physiology of the hypothalamic-pituitary-thyroid axis. The identification of IGSF1 as a cause of central congenital hypothyroidism has uncovered potential new regulatory pathways in both pituitary thyrotropes and gonadotropes, while mounting evidence suggests that a significant proportion of primary congenital hypothyroidism may be caused by combinations of rare genetic variants in multiple genes involved in thyroid development and function. Much remains to be learned about the origins of this common disorder and about the optimal management of less severely-affected infants.
{"title":"Congenital hypothyroidism: insights into pathogenesis and treatment.","authors":"Christine E Cherella, Ari J Wassner","doi":"10.1186/s13633-017-0051-0","DOIUrl":"https://doi.org/10.1186/s13633-017-0051-0","url":null,"abstract":"<p><p>Congenital hypothyroidism occurs in approximately 1 in 2000 newborns and can have devastating neurodevelopmental consequences if not detected and treated promptly. While newborn screening has virtually eradicated intellectual disability due to severe congenital hypothyroidism in the developed world, more stringent screening strategies have resulted in increased detection of mild congenital hypothyroidism. Recent studies provide conflicting evidence about the potential neurodevelopmental risks posed by mild congenital hypothyroidism, highlighting the need for additional research to further define what risks these patients face and whether they are likely to benefit from treatment. Moreover, while the apparent incidence of congenital hypothyroidism has increased in recent decades, the underlying cause remains obscure in most cases. However, ongoing research into genetic causes of congenital hypothyroidism continues to shed new light on the development and physiology of the hypothalamic-pituitary-thyroid axis. The identification of <i>IGSF1</i> as a cause of central congenital hypothyroidism has uncovered potential new regulatory pathways in both pituitary thyrotropes and gonadotropes, while mounting evidence suggests that a significant proportion of primary congenital hypothyroidism may be caused by combinations of rare genetic variants in multiple genes involved in thyroid development and function. Much remains to be learned about the origins of this common disorder and about the optimal management of less severely-affected infants.</p>","PeriodicalId":14271,"journal":{"name":"International Journal of Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13633-017-0051-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35504344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}