Blood Pressure over Height Ratios: Simple and Accurate Method of Detecting Elevated Blood Pressure in Children

Background. Blood pressure (BP) percentiles in childhood are assessed according to age, gender, and height. Objective. To create a simple BP/height ratio for both systolic BP (SBP) and diastolic BP (DBP). To study the relationship between BP/height ratios and corresponding BP percentiles in children. Methods. We analyzed data on height and BP from 2006-2007 NHANES data. BP percentiles were calculated for 3775 children. Receiver-operating characteristic (ROC) curve analyses were performed to calculate sensitivity and specificity of BP/height ratios as diagnostic tests for elevated BP (>90%). Correlation analysis was performed between BP percentiles and BP/height ratios. Results. The average age was 12.54 ± 2.67 years. SBP/height and DBP/height ratios strongly correlated with SBP & DBP percentiles in both boys (P < 0.001, R2 = 0.85, R2 = 0.86) and girls (P < 0.001, R2 = 0.85, R2 = 0.90). The cutoffs of SBP/height and DBP/height ratios in boys were ≥0.75 and ≥0.46, respectively; in girls the ratios were ≥0.75 and ≥0.48, respectively with sensitivity and specificity in range of 83–100%. Conclusion. BP/height ratios are simple with high sensitivity and specificity to detect elevated BP in children. These ratios can be easily used in routine medical care of children

Genetic Conditions of Short Stature: A Review of Three Classic Examples

Noonan, Turner, and Prader-Willi syndromes are classical genetic disorders that are marked by short stature. Each disorder has been recognized for several decades and is backed by extensive published literature describing its features, genetic origins, and optimal treatment strategies. These disorders are accompanied by a multitude of comorbidities, including cardiovascular issues, endocrinopathies, and infertility. Diagnostic delays, syndrome-associated comorbidities, and inefficient communication among the members of a patient\u27s health care team can affect a patient\u27s well-being from birth through adulthood. Insufficient information is available to help patients and their multidisciplinary team of providers transition from pediatric to adult health care systems. The aim of this review is to summarize the clinical features and genetics associated with each syndrome, describe best practices for diagnosis and treatment, and emphasize the importance of multidisciplinary teams and appropriate care plans for the pediatric to adult health care transition

LHX3 deficiency presenting in the United States with severe developmental delay in a child of Syrian refugee parents

In this case report, we present a novel mutation in Lim-homeodomain (LIM-HD) transcription factor, LHX3, manifesting as combined pituitary hormone deficiency (CPHD). This female patient was originally diagnosed in Egypt during infancy with Diamond Blackfan Anemia (DBA) requiring several blood transfusions. Around 10 months of age, she was diagnosed and treated for central hypothyroidism. It was not until she came to the United States around two-and-a-half years of age that she was diagnosed and treated for growth hormone deficiency. Her response to growth hormone replacement on linear growth and muscle tone were impressive. She still suffers from severe global development delay likely due to delay in treatment of congenital central hypothyroidism followed by poor access to reliable thyroid medications. Her diagnosis of DBA was not confirmed after genetic testing in the United States and her hemoglobin normalized with hormone replacement therapies. We will review the patient’s clinical course as well as a review of LHX3 mutations and the associated phenotype

Isolated micropenis reveals partial androgen insensitivity syndrome confirmed by molecular analysis

Abstract Partial androgen insensitivity syndrome (PAIS) is the milder variant of androgen receptor (AR) defects. The subtle effects of AR mutations present in a patient with micropenis, peno-scrotal hypospadias, infertility, clitoromegaly and posterior labial fusion. We studied the association of isolated micropenis with the genetic defects resulting in androgen resistance, that is, AR gene defects and 5-α reductase type 2 (SRD5A2) deficiency. We describe two cases of isolated micropenis: one in a 14-year-old boy and the other in a 3-year-old boy who was followed until he was 10 years old. There were no findings of hypospadias, cryptorchidism or gynecomastia in either of these patients. Serum gonadotrophin and androgen levels were obtained and karyotyping was done. Human chorionic gonadotropin (hCG) stimulation testing assessed the functional capacity of the testes. DNA was extracted from peripheral leukocytes, and all exons of the SRD5A2 and AR genes were amplified by polymerase chain reaction and sequenced. In both patients, baseline testosterone (T) level was low and the values were elevated after hCG testing. The sequence of the SRD5A2 gene was normal in patient 1, and a heterozygous polymorphism, V89L, was found in patient 2. Two known mutations, P390S and A870V, were identified in patients 1 and 2, respectively. Mutations in the AR gene can be associated with isolated micropenis without other features of PAIS, such as hypospadias or gynecomastia. This underlines the importance of including AR gene analysis in the evaluation of isolated micropenis with normal plasma T to ensure proper management of the patient and appropriate genetic counseling for the family

A severe case of testotoxicosis in an infant due to a c.1732G>C (p.ASP578His) LHCGR gene mutation associated with nodular Leydig cell hyperplasia

Introduction: Testotoxicosis is a rare gonadotropin-independent form of precocious puberty. Herein we discuss a uniquely severe case of severe testotoxicosis in infant male with a c.1732G>C (p.ASP578His) LHCGR gene mutation requiring surgical intervention. Case Description: This 9-month-old male initially presented with extremely elevated levels of testosterone (1383 ng/dl) and undetectable ultrasensitive LH and FSH titers. On physical exam he was Tanner stage 3. Scrotal ultrasound showed multiple bilateral nodular hypoechoic lesions. A genomic DNA 1732G->C mutation within the LHCGR gene leading to a p.Asp578His amino acid change was confirmed on genetic testing. Combination medical therapy with an androgen receptor blocker and aromatase inhibitor was initiated for testotoxicosis; however, his condition worsened on medical therapy with a further rise in testosterone levels (2177 ng/dl). He subsequently underwent 2 sequential orchiectomies for his condition with both pathologies demonstrating diffuse nodular Leydig cell hyperplasia. Conclusions Herein we report the youngest case of medically refractory testotoxicosis associated with progressive bilateral diffuse nodular Leydig cell hyperplasia requiring aggressive surgical intervention. The germline c.1732G>C (p.ASP578His) mutation found in this case was previously described as somatic mutations in 3 boys with benign nodular adenoma of the testes

A severe case of testotoxicosis in an infant due to a c.1732G>C (p.ASP578His) LHCGR gene mutation associated with nodular Leydig cell hyperplasia

Introduction: Testotoxicosis is a rare gonadotropin-independent form of precocious puberty. Herein we discuss a uniquely severe case of severe testotoxicosis in infant male with a c.1732G>C (p.ASP578His) LHCGR gene mutation requiring surgical intervention. Case Description: This 9-month-old male initially presented with extremely elevated levels of testosterone (1383 ng/dl) and undetectable ultrasensitive LH and FSH titers. On physical exam he was Tanner stage 3. Scrotal ultrasound showed multiple bilateral nodular hypoechoic lesions. A genomic DNA 1732G->C mutation within the LHCGR gene leading to a p.Asp578His amino acid change was confirmed on genetic testing. Combination medical therapy with an androgen receptor blocker and aromatase inhibitor was initiated for testotoxicosis; however, his condition worsened on medical therapy with a further rise in testosterone levels (2177 ng/dl). He subsequently underwent 2 sequential orchiectomies for his condition with both pathologies demonstrating diffuse nodular Leydig cell hyperplasia. Conclusions Herein we report the youngest case of medically refractory testotoxicosis associated with progressive bilateral diffuse nodular Leydig cell hyperplasia requiring aggressive surgical intervention. The germline c.1732G>C (p.ASP578His) mutation found in this case was previously described as somatic mutations in 3 boys with benign nodular adenoma of the testes

Hyperandrogenism Does Not Influence Metabolic Parameters in Adolescent Girls with PCOS

Background. Underlying insulin resistance and/or obesity has clearly been implicated in the development of metabolic syndrome in adolescents and young adults with polycystic ovarian syndrome (PCOS). It is not clear however what role hyperandrogenism has on the development of metabolic syndrome or its role on those metabolic parameters associated with metabolic syndrome. Methods. We studied 107 adolescent girls; 54 had PCOS according to NIH criteria. Data was obtained for systolic and diastolic blood pressure (SBP and DBP), body mass index (BMI), total testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, fasting lipid profile, and glucose. The PCOS group was divided initially into subgroups according to BMI (kg/m2), then based on T (ng/dL) levels as follows: High Testosterone PCOS (HT), Intermediate Testosterone PCOS (IT), Obese and Normal Testosterone (ONT), and lean and normal T (Control, C). t-test analysis was performed in between all the groups. Results. There was no statistical difference between HT and IT, HT and ONT, or IT and ONT in SBP, DBP, fasting blood glucose, lipid panel, LH, FSH, and prolactin levels. The control group had lower SBP and BMI comparing with ONT, IT, and HT groups. There were no statistical differences found in DBP, fasting blood glucose, lipid panel, LH, FSH, or Prolactin. Conclusion. Metabolic profile in adolescent girls with PCOS is not affected by either the presence of hyperandrogenism or the degree of hyperandrogenism