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[PMID]: 29360619
[Au] Autor:Whyte MP; Coburn SP; Ryan LM; Ericson KL; Zhang F
[Ad] Address:Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, St. Louis, MO 63110, USA; Division of Bone and Mineral Diseases, Department of Internal Medicine, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO 63110, USA. Electronic address
[Ti] Title:Hypophosphatasia: Biochemical hallmarks validate the expanded pediatric clinical nosology.
[So] Source:Bone;110:96-106, 2018 Jan 31.
[Is] ISSN:1873-2763
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Hypophosphatasia (HPP) is the inborn-error-of-metabolism due to loss-of-function mutation(s) of the ALPL (TNSALP) gene that encodes the tissue non-specific isoenzyme of alkaline phosphatase (TNSALP). TNSALP represents a family of cell-surface phosphohydrolases differing by post-translational modification that is expressed especially in the skeleton, liver, kidney, and developing teeth. Thus, the natural substrates of TNSALP accumulate extracellularly in HPP including inorganic pyrophosphate (PPi), a potent inhibitor of mineralization, and pyridoxal 5'-phosphate (PLP), the principal circulating form of vitamin B . The superabundance of extracellular PPi regularly causes tooth loss, and when sufficiently great can lead to rickets or osteomalacia. Sometimes diminished hydrolysis of PLP engenders vitamin B -dependent seizures in profoundly affected babies. Autosomal dominant and autosomal recessive inheritance from among >340 ALPL mutations identified to date, typically missense and located throughout the gene, largely explains the remarkably wide-ranging severity of HPP, greatest of all skeletal diseases. In 2015, our demographic, clinical, and DXA findings acquired over 25 years from 173 children and adolescents with HPP validated and expanded the clinical nosology for pediatric patients to include according to increasing severity "odonto" HPP, "mild childhood" HPP, "severe childhood" HPP, "infantile" HPP, and "perinatal" HPP. Herein, we assessed this expanded nosology using biochemical hallmarks of HPP. We evaluated exclusively data from the 165 preteenage HPP patients in this cohort to exclude potential effects from physiological changes in TNSALP levels across puberty. All patients had subnormal serum total and bone-specific ALP and elevated plasma PLP, and nearly all had excessive urinary PPi excretion. Only the PLP levels were unchanged across puberty. Mean levels of all four biomarkers correlated with HPP severity ranked according to the HPP nosology, but the data overlapped among all four patient groups. Hence, these four biochemical hallmarks represent both a sensitive and reliable tool for diagnosing children with HPP. Furthermore, the hallmarks validate our expanded clinical nosology for pediatric HPP that, with limitations, is an improved framework for conceptualizing and working with this disorder's remarkably broad-ranging severity.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  2 / 32704 MEDLINE  
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[PMID]: 29346554
[Au] Autor:Hao P; Waxman DJ
[Ad] Address:Department of Biology and Bioinformatics Program, Boston University, Boston, Massachusetts.
[Ti] Title:Functional Roles of Sex-Biased, Growth Hormone-Regulated MicroRNAs miR-1948 and miR-802 in Young Adult Mouse Liver.
[So] Source:Endocrinology;159(3):1377-1392, 2018 Mar 01.
[Is] ISSN:1945-7170
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Sex-specific temporal patterns of pituitary growth hormone (GH) secretion determine the sex-biased transcription of hundreds of genes in the liver and impart important sex differences in liver physiology, metabolism, and disease. Sex differences in hepatic gene expression vary widely, ranging from less than twofold to >1000-fold in the mouse. Here, we use small RNA sequencing to discover 24 sex-biased mouse liver microRNAs (miRNAs), and then investigate the roles of two of these miRNAs in GH-regulated liver sex differences. Studies in prepubertal and young adult mice, and in mice in which pituitary hormones are ablated or where sex-specific hepatic GH signaling is dysregulated, demonstrated that the male-biased miR-1948 and the female-biased miR-802 are both regulated by sex-specific pituitary GH secretory patterns, acquire sex specificity at puberty, and are dependent on the GH-activated transcription factor STAT5 for their sex-specific expression. Both miRNAs are within genomic regions characterized by sex-biased chromatin accessibility. miR-1948, an uncharacterized miRNA, has essential features for correct Drosha/Dicer processing, generates a bona fide mature miRNA with strong strand bias for the 5p arm, and is bound by Argonaute in liver tissue, as is miR-802. In vivo studies using inhibitory locked nucleic acid sequences revealed that miR-1948-5p preferentially represses female-biased messenger RNAs (mRNAs) and induces male-biased mRNAs in male liver; conversely, miR-802-5p preferentially represses male-biased mRNAs and increases levels of female-biased mRNAs in female liver. Cytochrome P450 mRNAs were strongly enriched as targets of both miRNAs. Thus, miR-1948-5p and miR-802-5p are functional components of the GH regulatory network that shapes sex-differential gene expression in mouse liver.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:In-Data-Review
[do] DOI:10.1210/en.2017-03109

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[PMID]: 29522416
[Au] Autor:Torre YS; Wadeea R; Rosas V; Herbst KL
[Ad] Address:TREAT Program, College of Medicine, University of Arizona, Tucson, AZ, USA.
[Ti] Title:Lipedema: friend and foe.
[So] Source:Horm Mol Biol Clin Investig;, 2018 Mar 09.
[Is] ISSN:1868-1891
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:Background Lipedema is a chronic disorder presenting in women during puberty or other times of hormonal change such as childbirth or menopause, characterized by symmetric enlargement of nodular, painful subcutaneous adipose tissue (fat) in the limbs, sparing the hands, feet and trunk. Healthcare providers underdiagnose or misdiagnose lipedema as obesity or lymphedema. Materials and methods The benefits (friend) and negative aspects (foe) of lipedema were collected from published literature, discussions with women with lipedema, and institutional review board approved evaluation of medical charts of 46 women with lipedema. Results Lipedema is a foe because lifestyle change does not reduce lipedema fat, the fat is painful, can become obese, causes gait and joint abnormalities, fatigue, lymphedema and psychosocial distress. Hypermobility associated with lipedema can exacerbate joint disease and aortic disease. In contrast, lipedema fat can be a friend as it is associated with relative reductions in obesity-related metabolic dysfunction. In new data collected, lipedema was associated with a low risk of diabetes (2%), dyslipidemia (11.7%) and hypertension (13%) despite an obese average body mass index (BMI) of 35.3 ± 1.7 kg/m2. Conclusion Lipedema is a painful psychologically distressing fat disorder, more foe than friend especially due to associated obesity and lymphedema. More controlled studies are needed to study the mechanisms and treatments for lipedema.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher

  4 / 32704 MEDLINE  
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[PMID]: 29466239
[Au] Autor:Ding Y; Li J; Yu Y; Yang P; Li H; Shen Y; Huang X; Liu S
[Ad] Address:Department of Endocrinology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
[Ti] Title:Evaluation of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal axis.
[So] Source:J Pediatr Endocrinol Metab;31(3):323-329, 2018 Mar 28.
[Is] ISSN:2191-0251
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:BACKGROUND: This study aimed to identify the predictive value of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal (HPG) axis in girls. METHODS: Gonadotropin-releasing hormone (GnRH) stimulation tests were performed and evaluated in a total of 1750 girls with development of secondary sex characteristics. Correlation analyses were conducted between basal sex hormones and peak luteinizing hormone (LH) levels ≥5 IU/L during the GnRH stimulation test. Receiver operating characteristic (ROC) curves for basal levels of LH, follicle-stimulating hormone (FSH), LH/FSH, and estradiol (E2) before the GnRH stimulation test were plotted. The area under the curve (AUC) and 95% confidence intervals (CIs) were measured for each curve. RESULTS: The maximum AUC value was observed for basal LH levels (0.77, 95% CI: 0.74-0.79), followed by basal FSH levels (0.73, 95% CI: 0.70-0.75), the basal LH/FSH ratio (0.68, 95% CI: 0.65-0.71), and basal E2 levels (0.61, 95% CI: 0.59-0.64). The appropriate cutoff value of basal LH levels associated with a positive response of the GnRH stimulation test was 0.35 IU/L, with a sensitivity of 63.96% and specificity of 76.3% from the ROC curves when Youden's index showed the maximum value. When 100% of patients had peak LH levels ≥5 IU/L, basal LH values were >2.72 IU/L, but the specificity was only 5.45%. CONCLUSIONS: Increased basal LH levels are a significant predictor of a positive response during the GnRH stimulation test for assessing activation of the HPG axis in most girls with early pubertal signs.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Process

  5 / 32704 MEDLINE  
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[PMID]: 29447956
[Au] Autor:Hou X; Huang D; Meng Q; Zhang Q; Jia L; Wang S; Cheng Z; Wu S; Shang L; Jiang J; Hao W
[Ad] Address:Department of Toxicology, School of Public Health, Peking University Health Science Center, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China.
[Ti] Title:Pubertal chlorocholine chloride exposure inhibits testicular testosterone synthesis by down-regulating steroidogenic enzymes in adult rats.
[So] Source:Toxicol Lett;288:17-24, 2018 Feb 12.
[Is] ISSN:1879-3169
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Chlorocholine chloride (CCC) is widely used to regulate plant growth. Considerable attention has been focused on its reproductive and developmental toxicities. In order to investigate the effects of pubertal CCC exposure on testicular testosterone (T) synthesis, male SD rats were exposed to CCC by oral gavage at doses of 0, 75, 150 and 300 mg/kg bw/day from postnatal day 23 to 70. We observed that pubertal CCC exposure lowered the body weight and the mean Johnsen's score. The percentage of seminiferous tubules with deciduous spermatogenic cells was increased in the 75 and 150 mg/kg bw/day groups. In addition, pubertal CCC exposure reduced the testicular absolute weights in the 75 and 300 mg/kg bw/day groups as well as the sperm motility in epididymides in the 150 mg/kg bw/day group. A significant decrease of testicular T was observed while levels of hypothalamic gonadotropin-releasing-hormone (GnRH) and serum luteinizing hormone (LH) were increased. Protein levels of steroidogenic acute regulatory (StAR), cholesterol side-chain cleavage enzyme (P450scc) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) were decreased. Taken together, these results indicate that pubertal CCC exposure in rats might decrease testicular T synthesis by suppressing the expression of steroidogenic enzymes, which partially lead to an impairment on spermatogenesis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher

  6 / 32704 MEDLINE  
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[PMID]: 29425110
[Au] Autor:Yamaguchi T; Hothubo T; Morikawa S; Nakamura A; Mori T; Tajima T
[Ad] Address:Department of Pediatrics, Hokkaido University School of Medicine, Kita-ku, Sapporo, Japan.
[Ti] Title:A Japanese patient with congenital central hypothyroidism caused by a novel IGSF1 mutation.
[So] Source:J Pediatr Endocrinol Metab;31(3):355-359, 2018 Mar 28.
[Is] ISSN:2191-0251
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:BACKGROUND: IGSF1 abnormality causes diverse symptoms, including congenital central hypothyroidism (CCH), prolactin hyposecretion, testicular enlargement and delayed puberty. CASE PRESENTATION: Here, we report a case of a male patient who visited our hospital with a chief complaint of abdominal pain and short stature, in whom we identified a novel IGSF1 mutation. He was closely examined because of chronic constipation since infancy, persistent abdominal pain at 14 years of age and marked short stature (-4.7 standard deviation [SD] for normal Japanese boys). He was diagnosed with CCH. Decreased prolactin (PRL) secretion was also observed. IGSF1 analysis revealed a novel mutation at the splicing donor site (c.2065+1G>A) in intron 11. In silico analysis predicted this mutation to be a non-functional splice donor site. After thyroid hormone replacement, his thyroid function, constipation and growth rate improved. CONCLUSIONS: This is the first report of a patient in whom constipation and short stature led to a diagnosis of CCH with a novel IGSF1 mutation.
[Pt] Publication type:CASE REPORTS
[Em] Entry month:1802
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Process

  7 / 32704 MEDLINE  
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[PMID]: 29394157
[Au] Autor:Irewole-Ojo FO; Senbanjo IO; Oduwole AO; Njokanma OF
[Ad] Address:Endocrinology and Metabolic Unit, Massey Street Children's Hospital, Lagos, Nigeria.
[Ti] Title:Age of pubertal events among school girls in Lagos, Nigeria.
[So] Source:J Pediatr Endocrinol Metab;31(3):313-321, 2018 Mar 28.
[Is] ISSN:2191-0251
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:BACKGROUND: Globally, there is a secular trend towards the reduced age for sexual maturity and menarche. This study aimed to determine the current age and factors associated with attainment of various stages of puberty in Nigerian girls. METHODS: This study was a cross-sectional study involving 800 girls aged 6-15 years. The subjects were selected by stratified random sampling method from schools in Oshodi Local Government Area, Lagos State. They were interviewed and a physical examination was carried out to classify them into the various Tanner stages of breast and pubic hair maturational stages. RESULTS: The median age of girls at first stage of breast maturation (B2), first stage of pubic hair development (PH2) and at menarche were 9.0, 9.0 and 12.0 years, respectively. Breast development was significantly related to normal nutritional status (adjusted odds ratio [AOR] 4.5, p<0.001), overweight (AOR 40.2, p<0.001), obesity (AOR 154.2, p<0.001) and upper social class (AOR 15.7, p<0.031). Pubic hair development was significantly related only to overweight (AOR 4.7, p<0.007) and obesity (AOR 15.7, p<0.001) while achievement of menarche was significantly related to overweight (AOR 0.1, p=0.005), obesity (AOR 0.1, p=0.0009), high social class (AOR 4.7, p<0.001) and being a member of the Hausa tribe (AOR 35.8, p<0.029). CONCLUSIONS: There is decline in age of pubertal maturation of girls in Nigeria and the major contributory factors appear to be overweight and obesity. These findings are consistent with the pattern in developed countries.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Process

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[PMID]: 29373318
[Au] Autor:Çiçek D; Savas-Erdeve S; Cetinkaya S; Aycan Z
[Ad] Address:Dr. Sami Ulus Obstetrics and Gynecology, Children's Health and Disease Training and Research Hospital, Pediatric Endocrinology Department, Ankara, Turkey.
[Ti] Title:Clinical follow-up data and the rate of development of precocious and rapidly progressive puberty in patients with premature thelarche.
[So] Source:J Pediatr Endocrinol Metab;31(3):305-312, 2018 Mar 28.
[Is] ISSN:2191-0251
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:BACKGROUND: We aimed to evaluate the clinical follow-up data of patients with premature thelarche and determine the rate of development of precocious and early puberty in these patients. METHODS: The charts of 158 girls with premature thelarche who were followed-up in our pediatric endocrinology polyclinic were reviewed. The patients were divided into three groups according to the age at onset: group 1 (0-1 month) (n=12), group 2 (1-24 months) (n=40) and group 3 (2-8 years) (n=106). RESULTS: At admission, the mean height standard deviation score (SDS), body weight (BW)-SDS, body mass index (BMI) and BMI-SDS were significantly higher in group 3 than in group 1 and group 2. At admission, 8.8% of the patients were obese and 24% of the patients were overweight. The majority of patients who were obese and overweight were in group 3. At the end of the follow-up, thelarche regressed in 24.7%, persisted in 32.9%, progressed in 25.9% and had a cyclic pattern in 16.5% of the patients. Precocious or rapidly progressive puberty developed in 47 of the 158 patients (29.7%). The mean age at progression to early or rapidly progressive puberty was 98.1±17.6 months. A total of 89.3% of the patients who progressed to early or rapidly progressive puberty were in group 3. CONCLUSIONS: Precocious or rapidly progressive puberty developed in 29.7% of subjects with premature thelarche. As patients who developed rapidly progressive puberty had a higher BW-SDS and BMI-SDS than those who did not, it is suggested that the increase in weight could stimulate rapidly progressive puberty in cases with premature thelarche.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Process

  9 / 32704 MEDLINE  
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[PMID]: 29353265
[Au] Autor:Vandewalle S; Van Caenegem E; Craen M; Taes Y; Kaufman JM; T'Sjoen G
[Ad] Address:Department of Endocrinology, Ghent University Hospital, De Pintelaan 185 6K12IE, 9000 Ghent, Belgium, Phone: +32 9 332 34 13, Fax: +32 9 332 38 17.
[Ti] Title:Growth, sexual and bone development in a boy with bilateral anorchia under testosterone treatment guided by the development of his monozygotic twin.
[So] Source:J Pediatr Endocrinol Metab;31(3):361-367, 2018 Mar 28.
[Is] ISSN:2191-0251
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:BACKGROUND: Sex steroids are essential for sexual maturation, linear growth and bone development. However, there is no consensus on the optimal timing, dosage and dosage interval of testosterone therapy to induce pubertal development and achieve a normal adult height and bone mass in children with hypogonadism. CASE PRESENTATION: A monozygotic monochorial male twin pair, of which one boy was diagnosed with anorchia at birth due to testicular regression syndrome was followed from the age of 3 until the age of 18 years. Low dose testosterone substitution (testosterone esters 25 mg/2 weeks) was initiated in the affected twin based on the start of pubertal development in the healthy twin and then gradually increased accordingly. Both boys were followed until age 18 and were compared as regards to linear growth, sexual maturation, bone maturation and bone development. Before puberty induction both boys had a similar weight and height. During puberty, a slightly faster weight and height gain was observed in the affected twin. Both boys ended up however, with a similar and normal (near) adult height and weight and experienced a normal development of secondary sex characteristics. At the age of 17 and 18 years, bone mineral density, body composition and volumetric bone parameters at the forearm and calf were evaluated in both boys. The affected boy had a higher lean mass and muscle cross-sectional area. The bone mineral density at the lumbar spine and whole body was similar. Trabecular and cortical volumetric bone parameters were comparable. At one cortical site (proximal radius), however, the affected twin had a smaller periosteal and endosteal circumference with a thicker cortex. CONCLUSIONS: In conclusion, a low dose testosterone substitution in bilateral anorchia led to a normal onset of pubertal development and (near) adult height. Furthermore, there was no difference in bone mineral density at the age of 17 and 18 years.
[Pt] Publication type:CASE REPORTS
[Em] Entry month:1801
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Process

  10 / 32704 MEDLINE  
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[PMID]: 29521487
[Au] Autor:Vila G; Luger A
[Ad] Address:Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria - greisa.vila@meduniwien.ac.at.
[Ti] Title:Growth hormone deficiency and pregnancy: any role for substitution?
[So] Source:Minerva Endocrinol;, 2018 Mar 08.
[Is] ISSN:1827-1634
[Cp] Country of publication:Italy
[La] Language:eng
[Ab] Abstract:Growth hormone (GH) is not approved for use during conception and pregnancy. Nevertheless, data from the clinical care practice reveal that most women concieve on GH replacement therapy (GHRT), and more than half continue on GHRT also during pregnancy. GH stimulates the hypothalamic-pituitary-gonadal axis at all levels, and there is evidence that GH deficiency impacts the morphology of reproductive organs, onset of puberty, ovarian function and fertility. Patients with hypopituitarism often conceive using assisted reproductive techniques and several studies support the benefit of GH supplementation for achieving fertility in women with growth hormone deficiency. During gestation the growth hormone system is regulated by the placental growth hormone, which increases continuously with the growth of placenta and stimulates maternal IGF-1 levels, leading to a concomitant decline in pituitary GH secretion. GHRT regimens that aim to mimick the pathophysiology of GH/IGF-I concentrations during pregnancy continue GHRT during the first trimester, gradually reduce GH dose during the second trimester and stopp GHRT at the beginning of the third trimester. Pregnancy outcomes were not found to be related to GHRT treatment patterns during pregnancy, but female patients with childhood-onset hypopituitarism have lower fertility rates and less positive pregnancy outcomes. Although current guidelines recommend against GHRT during pregnancy, GHRT might be needed for achieving fertility and satisfactory pregnancy outcomes are reported following the decision of patients and physicians for adapting the GHRT dose during pregnancy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.23736/S0391-1977.18.02834-1


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