[Show abstract][Hide abstract] ABSTRACT: Neonatal hyperkalemia and hyponatremia are medical conditions that require an emergent diagnosis and treatment to avoid morbidity and mortality. Here, we describe the case of a 10-day-old female baby presenting with life-threatening hyperkalemia, hyponatremia, and metabolic acidosis diagnosed as autosomal dominant pseudohypoaldosteronism type 1 (PHA1). This report aims to recognize that PHA1 may present with a life-threatening arrhythmia due to severe hyperkalemia and describes the management of such cases in neonates.
PHA1 may present with a life-threatening arrhythmia.Presentation of PHA can be confused with congenital adrenal hyperplasia.Timing and appropriate medical management in the critical care unit prevented fatality from severe neonatal PHA.
[Show abstract][Hide abstract] ABSTRACT: Objective
To examine whether peri-adolescent children demonstrate the significant racial/ethnic differences in body fatness relative to BMI and in the prevalence and relationship of body composition to risk factors for type 2 diabetes (T2DM) as in adults.
Design and Methods
We examined family history of obesity and T2DM, anthropometry, insulin sensitivity and secretory capacity, lipids, and cytokines (IL-6, CRP, TNF-α, and adiponectin) in a cohort of 994 middle school students (47% male, 53%, female; 12% African American, 14% East Asian, 13% South Asian, 9% Caucasian, 44% Hispanic, and 8% other).
Fractional body fat content was significantly greater at any BMI among South Asians. There were racial/ethnic specific differences in lipid profiles, insulin secretory capacity, insulin sensitivity, and inflammatory markers corrected for body fatness that are similar to those seen in adults. Family history of T2DM was associated with lower insulin secretory capacity while family history of obesity was more associated with insulin resistance.
Children show some of the same racial/ethnic differences in risk factors for adiposity-related co-morbidities as adults. BMI and waist circumference cutoffs to identify children at-risk for adiposity-related co-morbidities should be adjusted by racial/ethnic group as well as other variables such as birthweight and family history.
[Show abstract][Hide abstract] ABSTRACT: Human Immunodeficiency virus (HIV) infection and Acquired Immunodeficiency Syndrome (AIDS) are associated with dysfunction of many endocrine organs and their axis. HIV infectivity leads to altered metabolism, poor oral intake and increased prevalence of weight loss and wasting which may have a role in thyroid dysfunction. Overt thyroid dysfunction occurs at similar rates as the general population while subclinical disease such as nonthyroidal illness (sick euthyroid syndrome), subclinical hypothyroidism and isolated low T4 levels are more frequent. Moreover, HAART therapy can complicate thyroid function further through drug interactions and the immune reconstitution inflammatory syndrome (IRIS). In this review we report the common thyroid dysfunctions associated with HIV before and after HAART therapy. We discuss presentation, diagnostic work up, treatment and follow up in each condition.
Reviews in Endocrine and Metabolic Disorders 06/2013; 14(2). DOI:10.1007/s11154-013-9248-6 · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The hypothalamic pituitary adrenal (HPA) axis is the most common of the endocrine lines/axis' to be affected by HIV infection. There are multiple factors that contribute to this HPA axis dysregulation. Direct invasion of the various organs in the axis can be either by opportunistic infections or infiltrative diseases. The soluble factors or cytokines released during viral infection and the chronic inflammatory state that follows, also contribute to these alterations. The actions of these cytokines released by the immune response can both activate the HPA axis and cause a glucocorticoid resistant state. Further, many of the anti-retroviral and other medications used to treat HIV infection can contribute to HPA axis dysfunction. While the diagnosis and treatment of endocrine dysfunction is the same as in any other patient, management pathways may be quite different. While some may be adaptive responses, life threatening adrenal insufficiency can also be present. It is important the latter be picked up expeditiously and treated promptly to avoid mortality.
Reviews in Endocrine and Metabolic Disorders 06/2013; 14(2). DOI:10.1007/s11154-013-9244-x · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: HIV associated insulin resistance, lipodistrophy and cardiometabolic syndrome have been extensively studied and continue to be the scope of much research. There is compelling evidence that both the HIV itself and the therapeutical regimes are major contributors to all of these associated comorbidities. HIV has increasingly been recognized as a disease of accelerated aging, manifested by increased progression of vascular disease and cellular markers of aging. The antiretroviral medication can increase insulin resistance and cause lipotoxocity and HIV-associated lipodystrophy leading to cardiovascular pathology. In this article we review the pathogenesis, management, and prevention of the long-term complications of HIV and its therapies, including cardiovascular disease, lipodystrophy, and insulin resistance along with the growing focus on biomarkers to predict development of end-organ disease. Through a focused literature search we review the established evidence, the developing research about the treatment strategies in treated HIV infection as well as identify potential areas for future research.
Reviews in Endocrine and Metabolic Disorders 05/2013; 14(2). DOI:10.1007/s11154-013-9247-7 · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human immunodeficiency virus (HIV) infection has progressed to a chronic disease and HIV positive individuals are living longer lives. This has lead to an increase in morbidity and mortality due to secondary issues, one being HIV bone disease. HIV infected pediatric and adult populations have a greater incidence in reduction of BMD as compared to the controls. Osteoporosis has been reported to be present in up to 15 % of HIV positive patients. We are starting to understand the mechanism behind the changes in HIV bone disease. Viral proteins interfere with osteoblastic activity either by direct interaction or by the inflammatory process that they induce. Anti-viral management, including highly active antiretroviral therapy (HAART), protease inhibitors, and nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) also are involved in disrupting proper bone metabolism. Vitamin D levels have strong correlation with bone disease in HIV patients, and are dependent not only to chronic disease state, but interaction of pharmacologic management and inflammatory process as well. Work up of the secondary causes of osteopenia and osteoporosis should be undertaken in all patients. DEXA scan is recommended in all post-menopausal women with HIV, all HIV infected men 50 years of age or older and in those with a history of fragility fractures regardless of age or gender. Preventive measures include adequate nutrition, calcium and Vitamin D intake daily, muscle strengthening and balance exercises to increase BMD and reduce fractures. Bisphosphonates are considered to be the first line for the treatment of HIV associated bone disease. This review will describe how the balanced mechanism of bone metabolism is interrupted by the HIV infection itself, the complications that arise from HIV/AIDS, and its treatment options.
Reviews in Endocrine and Metabolic Disorders 05/2013; 14(2). DOI:10.1007/s11154-013-9246-8 · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aberrations in GHRH-GH -IGF-I axis are common in the complex of HIV, HAART and AIDS. There are 2 distinct mechanisms at play in HIV and AIDS. One is primarly associated with development of lipodystrophy and results in complications such as chronic inflammation, insulin resistance, lipid and metabolic abnormalities. HIV lipodystrophy is found especially in those on highly active anti-retroviral therapy (HAART). The various processes involved in lipodystrophy result in the suppression of pituitary GH production. The mechanism of low GH levels relates to increased somatostatin tone, decreased Ghrelin, increased free fatty acids (FFA) and insulin resistance. On the other hand in AIDS wasting syndrome; elevated GH and low IGF-1 levels are seen suggesting GH resistance. The GHRH analog-Tesamorelin is the only treatment option, which is FDA approved for use in reduction of excess abdominal fat in patients with HIV-associated lipodystrophy. Although long-term clinical trials and experience is needed to further study the benefits and risks of Tesamorelin.
Reviews in Endocrine and Metabolic Disorders 05/2013; 14(2). DOI:10.1007/s11154-013-9245-9 · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: The mineralocorticoid receptor is protected from excess of glucocorticoids by conversion of active cortisol to inactive cortisone by enzyme 11β-hydroxysteroid dehydrogenase type 2 present in the kidney. The metabolites of cortisol and cortisone are excreted in the urine as tetrahydrocortisol (5αTHF+5βTHF) and tetrahydrocortisone (THE), respectively. Hypothesis: Patients with chronic kidney disease (CKD) and essential hypertension have a functional defect in their ability to convert cortisol to cortisone, thus leading to the activation of mineralocorticoid receptor. Objective: The objective of the investigation was to study the ratio of urinary steroids (5αTHF+5βTHF) to THE in patients with CKD, postrenal transplant, and essential hypertension and to compare the ratio with controls. Design/Methods: We enrolled 44 patients (17 with CKD, eight postrenal transplant, 19 with essential hypertension) and 12 controls. We measured spot urinary 5α-THF, 5β-THF, THE, free active cortisol and inactive cortisone by gas chromatography/mass spectrometry. We collected data on age, sex, cause of kidney disease, height, weight, body mass index, blood pressure, serum electrolytes, aldosterone, and plasma renin activity. Blood pressure percentiles and z-scores were calculated. The glomerular filtration rate was calculated using the modified Schwartz formula. Results: The ratios of 5αTHF+5βTHF to THE were significantly higher in patients with CKD [mean ± sd score (SDS) = 1.31 ± 1.07] as compared with essential hypertension (mean ± SDS = 0.59 ± 0.23; P = 0.02) and controls (mean ± SDS = 0.52 ± 0.25; P = 0.01). In the postrenal transplant group, the ratio was not significantly different (mean ± SDS = 0.71 ± 0.55). The urinary free cortisol to free cortisone ratios were significantly higher in the hypertension and CKD groups as compared with the controls. The 5αTHF+5βTHF to THE ratio negatively correlated with the glomerular filtration rate and positively correlated with systolic and diastolic blood pressure z-scores. The correlation of the blood pressure z-scores with ratios was stronger in the CKD group than the essential hypertension and posttransplant groups. Conclusions: We have elucidated a functional deficiency of 11β-hydroxysteroid dehydrogenase type 2 in children with CKD and a subset of essential hypertension. Urinary 5α-THF, 5β-THF, and THE analysis by gas chromatography/mass spectrometry should be a part of routine work-up of CKD and hypertensive patients.
The Journal of Clinical Endocrinology and Metabolism 08/2012; 97(10):3622-9. DOI:10.1210/jc.2012-1411 · 6.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: First-degree relatives (FDRs) of women with PCOS are at increased risk for impaired insulin sensitivity and diabetes mellitus. Glucose tolerant FDR have evidence of insulin resistance and hyperinsulinemia prior to emergence of frank PCOS.
To study insulin dynamics parameters in the early adolescent FDR of women with PCOS.
This is a cross-sectional study involving 18 adolescents whose mothers or sisters had been diagnosed with PCOS and 21 healthy, age-matched control adolescents without FDR. Subjects underwent anthropometric measurements, steroid profiling and frequently sampled Intravenous Glucose Tolerance Test (IVGTT), Homeostasis Model Assessment (HOMA) index, Glucose Disposal Index (GDI), Acute Insulin Response (AIR) and Quantitative insulin sensitivity check index (QUICKI) were derived from IVGTT results.
FDRs showed significantly higher mean HOMA and lower GDI. There were no differences in mean age or BMI Z-score between the cohorts. No differences in sex steroids or AIR were identified between groups.
Female adolescent FDR of women with PCOS have higher HOMA index and lower QUICKI, reflecting altered insulin sensitivity and lower GDI reflecting poorer beta-cell function. The presence of multiple risk factors for type 2 diabetes suggests that aggressive screening of the early adolescent FDR of women with PCOS is indicated.
International Journal of Pediatric Endocrinology 05/2012; 2012(1):14. DOI:10.1186/1687-9856-2012-14
[Show abstract][Hide abstract] ABSTRACT: 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, R(2) = 0.85, R(2) = 0.86) and girls (P < 0.001, R(2) = 0.85, R(2) = 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.
International Journal of Pediatrics 04/2012; 2012(14):253497. DOI:10.1155/2012/253497
[Show abstract][Hide abstract] ABSTRACT: 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/m(2)), 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.
International Journal of Endocrinology 03/2012; 2012(1687-8337):434830. DOI:10.1155/2012/434830 · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the context of present epidemic of childhood obesity, we aimed to find the prevalence of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) in a cohort of obese children.
Retrospective chart analysis of 700 obese children was done for their anthropometric and biochemical investigations.
Some 15.4% (9.8% girls, 22% boys) subjects had NAFLD (ALT > 40 IU/L) after excluding other identifiable causes of liver dysfunction. Age, weight, TG, fasting serum insulin and HOMA-IR levels were higher in children with NAFLD. Twenty-eight percent children had MS. Children with NAFLD had an odds ratio of 2.65 for having MS (boys 4.6, girls 1.7). The prevalence of MS increased with age 5-9 years (21%), 10-16 years (30%), 17-20 years (35%).
Given high prevalence of NAFLD and MS in obese children, childhood obesity should be seriously considered as a disease and not just a cosmetic issue.
[Show abstract][Hide abstract] ABSTRACT: 17-β-Hydroxysteroid dehydrogenase type 3 (17βHSD-3) is expressed exclusively in the testes where it converts Δ4 androstenedione (Δ4) to testosterone (T). Here, we report a patient with a rare mutation at a critical site in HSD17B3 gene leading to deficiency of 17β HSD-3 enzyme.
We describe a 3-year old healthy female of consanguineous Lebanese descent, who presented to the endocrine service with isolated mild clitoromegaly. Adrenocorticotropic hormone (ACTH) and human chorionic gonadotrophin (hCG) stimulation tests were performed. Genes for sex-determining region Y (SRY), steroidogenic factor-1 (SF-1) and 17βHSD-3 (HSD17B3) were sequenced.
The post-hCG stimulation T levels and T/Δ4 ratio was low. Patient had a 46,XY karyotype. Sequence analysis of the HSD17B3 gene revealed a homozygous R80W missense mutation on exon 3. No mutation was found in SRY and SF1 genes. Mullerian structures were not detected on pelvic imaging.
A low T/Δ4 ratio is indicative of 17βHSD-3 deficiency and associated with isolated clitoromegaly. The R80 site is critical for NADPH binding, thus the mutation at this site leads to 17βHSD-3 deficiency presenting as 46,XY disorder of sex development.
[Show abstract][Hide abstract] ABSTRACT: Sex steroids, such as estrogens, are known to influence endothelial function by their vasodilator action. The aim of this study was to study the relation of puberty and sex steroids with endothelial function using peripheral arterial tonometry (PAT).
In 89 healthy school boys and girls, we determined height, weight, waist circumference, percent body fat, BMI, BMI z-score, blood pressure (BP), BP percentiles, lipid profile, insulin, and glucose levels after overnight fast. Estrone (E(1)), estradiol (E(2)), DHEAS and E(1)-sulfate were measured using ultrasensitive assays. Participants were divided into 3 pubertal groups on the basis of their estrogen levels: group 1 (Tanner stage I), group 2 (Tanner stages II-III), and group 3 (Tanner stages IV-V). Endothelial function was measured by Endo-PAT 2000® and expressed as PAT index. A higher PAT index represents a higher reactive hyperemia response.
The PAT index was lowest at 1.42 ± 0.44 (mean ± SD) in group 1 and significantly increased in group 2 at 1.71 ± 0.35 (p = 0.02) and group 3 at 1.92 ± 0.38 (p < 0.001). The PAT index correlated positively with E(2), DHEAS and age.
Enhancement of the PAT index was associated with an increment in Tanner stages. The changes in E(2) and DHEAS levels may contribute to increasing endothelial response to shear stress or arterial blood flow.
Hormone Research in Paediatrics 07/2011; 76(4):226-33. DOI:10.1159/000328455 · 1.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Micropenis is defined as a stretched penile length of less than 2-2.5SD for age. Aetiologies include hypogonadotropic hypogonadism, testicular dysgenesis, defects in testosterone synthesis, androgen resistance [5α-reductase (5αR) deficiency or partial androgen insensitivity] and other rare causes like growth hormone GH deficiency. Often, the cause remains unknown. The aim of this study was to determine whether isolated micropenis with normal plasma testosterone could hide a molecular defect in the androgen pathway. Twenty-six boys with isolated micropenis were included in this study. All of them had 46,XY karyotype, normal luteinizing hormone and follicle-stimulating hormone and a normal plasma testosterone response to human chorionic gonadotropin testing. Androgen receptor (AR), 5αR and steroidogenic factor 1 (SF1) genes were sequenced. A mutation in the AR gene was found in two patients, and a new mutation in the SF1 gene was found in one patient who was the only one to have a low level of inhibin B (InhB). This is the first report of isolated micropenis as a revealing symptom of AR and SF1 mutations. Anti-Mullerian hormone and InhB should thus be evaluated in patients with isolated micropenis, even when plasma testosterone is in the normal range. Detection of gene mutations is helpful for diagnosis, treatment and genetic counselling for probands.
International Journal of Andrology 04/2011; 34(6 Pt 2):e518-25. DOI:10.1111/j.1365-2605.2010.01135.x · 3.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Leydig cell hypoplasia (LCH) due to inactivating mutations of luteinizing hormone receptor gene (LHCGR) is a relatively rare form of 46,XY disorder of sex development (DSD). LCH is inherited in an autosomal recessive manner, which leads to aberration of Leydig cell differentiation and ultimately subnormal androgen production both pre- and postnatally. In males, two distinct phenotypes have been described in the literature depending on the degree of remaining activity of LHCGR. Leydig cell hypoplasia type 1 (LCH type 1) represents more severe form with 46,XY DSD while Leydig cell hypoplasia type 2 (LCH type 2) is more diverse with micropenis to several degrees of undervirilization. We identified one kindred with 27-bp insertion in exon 1 causing 46,XY DSD.
Advances in Experimental Medicine and Biology 01/2011; 707:147-8. DOI:10.1007/978-1-4419-8002-1_32 · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The steroidogenic acute regulatory (StAR) protein is essential for all hormone-stimulated steroid biosynthesis. Accordingly, its absence gives rise to the most severe form of congenital adrenal hyperplasia (CAH), lipoid CAH. This life-threatening condition typically manifests itself in the perinatal period. Partial loss-of-function StAR mutations incompletely manifest the condition later in life and are a cause of familial glucocorticoid deficiency type 3. Here, we discuss StAR, its expression pattern and the clinical consequences of the loss of its activity.
Endocrine development 01/2011; 20:47-53. DOI:10.1159/000321214