Pediatric Endocrinology Clinic

Pea Ridge, WV, United States

Pediatric Endocrinology Clinic

Pea Ridge, WV, United States
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Guran T.,Marmara University | Guran T.,University of Birmingham | Buonocore F.,University College London | Buonocore F.,Istanbul University | And 36 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2016

Context: Primary adrenal insufficiency (PAI) is a life-threatening condition that is often due to monogenic causes in children. Although congenital adrenal hyperplasia occurs commonly, several other important molecular causes have been reported, often with overlapping clinical and biochemical features. The relative prevalence of these conditions is not known, but making a specific diagnosis can have important implications for management. Objective: The objective of the study was to investigate the clinical and molecular genetic characteristics of a nationwide cohort of children with PAI of unknown etiology. Design: A structured questionnaire was used to evaluate clinical, biochemical, and imaging data. Genetic analysis was performed using Haloplex capture and next-generation sequencing. Patients with congenital adrenal hyperplasia, adrenoleukodystrophy, autoimmune adrenal insufficiency, or obvious syndromic PAI were excluded. Setting: The study was conducted in 19 tertiary pediatric endocrinology clinics. Patients: Ninety-five children (48 females, aged 0i18 y, eight familial) with PAI of unknown etiology participated in the study. Results: A genetic diagnosis was obtained in 77 patients (81%). The range of etiologies was as follows: MC2R (n = 25), NR0B1 (n = 12), STAR (n = 11), CYP11A1 (n = 9), MRAP (n = 9), NNT (n = 7), ABCD1 (n=2), NR5A1 (n=1), and AAAS (n=1). Recurrent mutations occurred in several genes, such as c.560delT in MC2R, p.R451W in CYP11A1, and c.IVS3ds 1delG in MRAP. Several important clinical and molecular insights emerged. Conclusion: This is the largest nationwide study of the molecular genetics of childhood PAI undertaken. Achieving a molecular diagnosis in more than 80% of children has important translational impact for counseling families, presymptomatic diagnosis, personalized treatment (eg, mineralocorticoid replacement), predicting comorbidities (eg, neurological, puberty/fertility), and targeting clinical genetic testing in the future.


Tosson H.,Pediatric Endocrinology Clinic | Rose S.R.,Cincinnati Childrens Hospital Medical Center | Gartner L.A.,Children's Hospital of Buffalo
European Journal of Pediatrics | Year: 2012

We hypothesized that because 45,X/46,XY (X/ XY) children share a cell line with Turner syndrome (TS), they also share co-morbidities described in TS. In addition, the presence of the Y chromosome in brain and in other body tissues would influence their function. On the basis of our findings, we aimed to establish optimal procedures for clinical evaluation, management, and follow-up of these children. Sixteen X/XY children were evaluated and managed at a single institution as part of standard clinical care as established at the time between 1969 and 2009. In January of 2005, we started retrospective record review of all X/XY children in combination with cohort follow-up (of those who had not reached adult height) until August of 2009. The study included review of clinical presentation, clinical characteristics, diagnostic measures, radiologic studies, karyotype studies, psycho-endocrinology evaluation, and growth-promoting treatments. There was no specific intervention. Phenotype reflected cell line distribution. The presence of 45,X cell line explains how X/XY children have abnormalities similar to girls with TS, while presence of Y chromosome explains why they have tomboyish behavior. In conclusion, these children require clinical evaluation similar to that performed in female children with TS, including cardiovascular, renal, endocrine, growth and development, autoimmune, psychological, and educational evaluation. Specific management needs to be tailored to the presence of Y chromosomal material. © Springer-Verlag 2011.


Tosson H.,Pediatric Endocrinology Clinic | Rose S.R.,University of Cincinnati | Gartner L.A.,State University of New York at Buffalo
Hormone Research in Paediatrics | Year: 2010

Background: Growth pattern of children with 45,X/46,XY karyotype (X/XY children) has not been characterized. Objective: Our objective is to describe growth pattern and long-term outcome of X/XY children and to develop guidelines for management of their short stature. Our hypothesis was that abnormal karyotype and deficiency of gonadal function might play a role in growth deceleration in X/XY children. Methods: Retrospective record review and cohort follow-up of X/XY children were conducted between January 2005 and August of 2009. Sixteen X/XY children were evaluated and managed at a single institution as part of standard clinical care as established at the time between 1969 and 2009. The main outcome measures were clinical presentation, clinical characteristics, growth pattern, radiologic studies, pathological studies, and endocrine function of X/XY children. Results: Only X/XY female children underwent bilateral gonadectomy. As a group, X/XY female children were shorter at all age groups and at adult height relative to X/XY male children. Both groups manifested growth deceleration rather than growth spurt at the time of puberty. In both groups, adult height was compromised relative to mid-parental height. Conclusions: X/XY children, similar to girls with Turner syndrome, benefit from growth hormone treatment. Deficiencies of both hypothalamic gonadal axis and primary gonadal function appear to play a role in their growth deceleration. Sex steroid replacement at the time of puberty has an important role in management. Copyright © 2010 S. Karger AG, Basel.


Tosson H.,Pediatric Endocrinology Clinic | Rose S.R.,University of Cincinnati
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: This is a case report of a proband and his family presenting with apparent autosomal dominant 25-hydroxylase enzyme deficiency and bone disease. Objective: The aim of the study was to present an alternative pattern of transmission of 25-hydroxylase enzyme deficiency other than autosomal recessive. Design: We diagnosed our patient with 25-hydroxylase enzyme deficiency, treated him, and examined his DNA for mutations. Evaluations at other institutions, clinical history of all family members, and laboratory testing for the mother, aunt, and maternal grandmother were reviewed. Family consent was obtained for all testing and record review. Setting: The patient was evaluated serially in an outpatient clinic. Routine laboratory studies for proband, mother, and maternal grandmother were obtained. Genetic testing was performed in another institution after obtaining family consent. Interventions: No research intervention was performed. Main Outcome Measures: Routine clinical care included an evaluation of growth pattern. Laboratory evaluation included 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D [1,25(OH)2D], alkaline phosphatase, intact PTH, phosphate, calcium, ionized calcium, and magnesium levels. Results: Results showed consistently low 25-hydroxylase enzyme function. They also showed elevated alkaline phosphatase and PTH, as well as decreased phosphate and calcium. These abnormalities were corrected with 1,25(OH)2D therapy. Conclusion: We conclude that 25-hydroxylase enzyme deficiency can be inherited in an autosomal dominant pattern. This case raises a question about different tributary pathways affecting the function of the 25-hydroxylase enzyme. Physiological dosing of 1,25(OH)2D was sufficient for treatment. There were no detectable mutations in any of the coding regions of the gene or its intronic junctions. Copyright © 2012 by The Endocrine Society.


PubMed | Pediatric Endocrinology Clinic
Type: Case Reports | Journal: The Journal of clinical endocrinology and metabolism | Year: 2012

This is a case report of a proband and his family presenting with apparent autosomal dominant 25-hydroxylase enzyme deficiency and bone disease.The aim of the study was to present an alternative pattern of transmission of 25-hydroxylase enzyme deficiency other than autosomal recessive.We diagnosed our patient with 25-hydroxylase enzyme deficiency, treated him, and examined his DNA for mutations. Evaluations at other institutions, clinical history of all family members, and laboratory testing for the mother, aunt, and maternal grandmother were reviewed. Family consent was obtained for all testing and record review.The patient was evaluated serially in an outpatient clinic. Routine laboratory studies for proband, mother, and maternal grandmother were obtained. Genetic testing was performed in another institution after obtaining family consent.No research intervention was performed.Routine clinical care included an evaluation of growth pattern. Laboratory evaluation included 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D [1,25(OH)(2)D], alkaline phosphatase, intact PTH, phosphate, calcium, ionized calcium, and magnesium levels.Results showed consistently low 25-hydroxylase enzyme function. They also showed elevated alkaline phosphatase and PTH, as well as decreased phosphate and calcium. These abnormalities were corrected with 1,25(OH)(2)D therapy.We conclude that 25-hydroxylase enzyme deficiency can be inherited in an autosomal dominant pattern. This case raises a question about different tributary pathways affecting the function of the 25-hydroxylase enzyme. Physiological dosing of 1,25(OH)(2)D was sufficient for treatment. There were no detectable mutations in any of the coding regions of the gene or its intronic junctions.


PubMed | Pediatric Endocrinology Clinic
Type: Journal Article | Journal: European journal of pediatrics | Year: 2012

We hypothesized that because 45,X/46,XY (X/XY) children share a cell line with Turner syndrome (TS), they also share co-morbidities described in TS. In addition, the presence of the Y chromosome in brain and in other body tissues would influence their function. On the basis of our findings, we aimed to establish optimal procedures for clinical evaluation, management, and follow-up of these children. Sixteen X/XY children were evaluated and managed at a single institution as part of standard clinical care as established at the time between 1969 and 2009. In January of 2005, we started retrospective record review of all X/XY children in combination with cohort follow-up (of those who had not reached adult height) until August of 2009. The study included review of clinical presentation, clinical characteristics, diagnostic measures, radiologic studies, karyotype studies, psycho-endocrinology evaluation, and growth-promoting treatments. There was no specific intervention. Phenotype reflected cell line distribution. The presence of 45,X cell line explains how X/XY children have abnormalities similar to girls with TS, while presence of Y chromosome explains why they have tomboyish behavior. In conclusion, these children require clinical evaluation similar to that performed in female children with TS, including cardiovascular, renal, endocrine, growth and development, autoimmune, psychological, and educational evaluation. Specific management needs to be tailored to the presence of Y chromosomal material.

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