Diagnosis and management of precocious sexual maturation: an updated review.

The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in boys. It is classified as central precocious puberty when premature maturation of the hypothalamic-pituitary-gonadal axis occurs, and as peripheral precocious puberty when there is excessive secretion of sex hormones, independent of gonadotropin secretion. Precocious sexual maturation is more common in girls, generally central precocious puberty of idiopathic origin. In boys, it tends to be linked to central nervous system abnormalities. Clinical evaluation should include a detailed history and physical examination, including anthropometric measurements, calculation of growth velocity, and evaluation of secondary sexual characteristics. The main sign to suspect the onset of puberty is breast tissue development (thelarche) in girls and testicular enlargement (≥4 mL) in boys. Hormonal assessment and imaging are required for diagnosis and identification of the etiology. Genetic testing should be considered if there is a family history of precocious puberty or other clinical features suggestive of a genetic syndrome. Long-acting gonadotropin-releasing hormone analogs are the standard of care for central precocious puberty management, while peripheral precocious puberty management depends on the etiology.Conclusion: The aim of this review is to address the epidemiology, etiology, clinical assessment, and management of precocious sexual maturation. What is Known: • The main sign to suspect the onset of puberty is breast tissue development (thelarche) in girls and testicular enlargement (≥4 mL) in boys. The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in boys. • Long-acting gonadotropin-releasing hormone agonist (GnRHa) is the standard of care for CPP management, and adequate hormone suppression results in the stabilization of pubertal progression, a decline in growth velocity, and a decrease in bone age advancement. What is New: • Most cases of precocious sexual maturation are gonadotropin-dependent and currently assumed to be idiopathic, but mutations in genes involved in pubertal development have been identified, such as MKRN3 and DLK1. • A different preparation of long-acting GnRHa is now available: 6-month subcutaneous injection.

Accuracy of doppler assessment of the uterine arteries for the diagnosis of pubertal onset in girls: a scoping review.

The uterine artery pulsatility index (PI) assessed by Doppler ultrasound reflects the impedance to the blood flow in the vessel distal to the sampling point. We aimed to assess the accuracy of the uterine artery PI for the diagnosis of puberty in girls. A PRISMA-ScR-compliant scoping review was performed in the MEDLINE and Embase databases with the search terms "puberty" and "Doppler ultrasonography". Studies that included girls aged 0-18 years who underwent pelvic Doppler ultrasound with calculation of uterine artery PI were eligible. Ten studies comprising 1385 girls aged 1.2-18 years were included. The selected studies included participants from Italy, Brazil, Iran, Belgium and Denmark, and were published between 1996 and 2021. Six studies selected girls who were referred for evaluation of pubertal disorders, while four studies included only healthy girls. Nine studies found a significant difference in Doppler signal pattern and PI according to pubertal stage, with PI cutoff points ranging from 2.5 to 4.6 for the diagnosis of puberty, with a sensitivity of 77%-94%, specificity of 85%-100%, and accuracy of 79%-98%. Doppler assessment of the uterine arteries with PI calculation is a useful noninvasive tool in the diagnosis of pubertal onset in girls.

Association between socioeconomic and nutritional factors and height of Brazilian adolescents: results from the Study of Cardiovascular Risk in Adolescents.

This study aims to describe the mean height of adolescents from the five regions of Brazil and to evaluate socioeconomic and nutritional factors associated with normal growth. This is a cross-sectional study conducted in the Brazilian urban and rural areas with students aged 12 to 17 years (n = 71,553). Anthropometry, socioeconomic variables, physical activity, and diet were evaluated. Height-for-age z-scores were calculated and multiple linear regression models were used to investigate the association of exposure variables with height (outcome) by sex and age (12-13, 14-15, and 16-17 years). We observed a lower mean height in adolescents from the North Region and in individuals with low socioeconomic status. At 17 years of age, the closest to the final height in this sample, mean heights for girls and boys were 160.9 ± 0.1cm and 173.7 ± 0.3cm, respectively. In multiple linear regression analysis, physical activity (girls ß = 0.119, 95%CI: 0.035; 0.202; boys ß = 0.092, 95%CI: 0.012; 0.172) and high level of maternal education (girls ß = 0.103, 95%CI: 0.001; 0.204; boys ß = 0.39, 95%CI: 0.245; 0.534) were positively associated with height-for-age z-score in 16- to 17-year-old boys and girls. Other factors positively associated with height-for-age z-score in older students include higher protein consumption (ß = 0.022, 95%CI: 0.010; 0.035) and obesity (ß = 0.217, 95%CI: 0.084; 0.350) for boys, and low weight (ß = 0.205, 95%CI: 0.028, 0.382) for girls. We observed differences in the mean height among adolescents from the five Brazilian regions. Normal growth, especially among older adolescents, was associated with high maternal education, practice of physical activity, protein consumption, and body mass index (BMI) categories.

Accuracy of Doppler assessment of the uterine arteries in healthy girls for the diagnosis of pubertal onset.

PURPOSE: To evaluate the accuracy of the uterine artery pulsatility index (PI) for the diagnosis of pubertal onset in girls. METHODS: Cross-sectional study of girls with normal pubertal development. Puberty was diagnosed by the presence of Tanner breast development score ≥2. All girls underwent pelvic ultrasound and Doppler imaging of the uterine arteries. We evaluated the uterine artery PI and uterine, endometrial, and ovarian measurements. We used ROC curves with cutoffs determined by Youden index for data analysis. RESULTS: We included 169 girls aged 5-16 years who underwent 202 pelvic ultrasound examinations. Prepubertal girls had a significantly higher mean PI (6.70 ± 2.15) than girls in initial puberty (4.14 ± 1.55) and in late puberty (2.81 ± 1.05) (P < 0.001 for all comparisons), which reflects a progressive increase in blood flow to the uterus with the progression of puberty. ROC curve analysis showed that the PI was able to identify the onset of puberty with a mean area under the curve of 0.838 ± 0.04 (P < 0.001), and the PI cutoff point of 5.05 had a sensitivity of 77%, specificity of 85%, positive predictive value (PPV) of 92%, and accuracy of 79%. The combination of PI < 5.05 plus uterine volume >3.75 cm³ had a sensitivity of 73%, specificity of 95%, PPV of 97%, and accuracy of 79% to detect initial puberty. CONCLUSIONS: We found a significant reduction in the PI during pubertal development, which can possibly be a valuable noninvasive tool in the evaluation of pubertal disorders, alone or in combination with uterine and ovarian volumes.

Performance of Cystatin C-Based Equations for Estimation of Glomerular Filtration Rate in Diabetes Patients: A Prisma-Compliant Systematic Review and Meta-Analysis.

The accuracy of estimated glomerular filtration rate (eGFR) equations in diabetes mellitus (DM) patients has been extensively questioned. We evaluated the performance of cystatin C-based equations alone or in combination with creatinine to estimate GFR in DM patients. A PRISMA-compliant systematic review was performed in the MEDLINE and Embase databases, with "diabetes mellitus" and "cystatin C" as search terms. Studies comparing cystatin C-based eGFR equations with measured GFR (mGFR) in DM patients were eligible. Accuracies P10, P15, P20, and P30 indicated the proportion of eGFR results within 10, 15, 20, and 30% of mGFR. Single-arm meta-analyses were conducted, and the Quality of Diagnostic Accuracy Studies-II tool (QUADAS-2) was applied. Twenty-three studies comprising 7065 participants were included, and 24 equations were analyzed in a broad range of GFRs. Meta-analyses were completed for 10 equations. The mean P30 accuracies of the equations ranged from 41% to 87%, with the highest values found with both CKD-EPI equations. Mean P10-P15 achieved 35% in the best scenario. A sensitivity analysis to evaluate different mGFR methods did not change results. In conclusion, cystatin C-based eGFR equations represent measured GFR fairly at best in DM patients, with high variability among the several proposed equations.

Association between socioeconomic and nutritional factors and height of Brazilian adolescents: results from the Study of Cardiovascular Risk in Adolescents / Associação entre fatores socioeconômicos e nutricionais e altura de adolescentes brasileiros: resultados do Estudo de Riscos Cardiovasculares em Adolescentes / Asociación entre los factores socioeconómicos y nutricionales y la estatura de los adolescentes brasileños: resultados del Estudio de Riesgo Cardiovascular en Adolescentes

This study aims to describe the mean height of adolescents from the five regions of Brazil and to evaluate socioeconomic and nutritional factors associated with normal growth. This is a cross-sectional study conducted in the Brazilian urban and rural areas with students aged 12 to 17 years (n = 71,553). Anthropometry, socioeconomic variables, physical activity, and diet were evaluated. Height-for-age z-scores were calculated and multiple linear regression models were used to investigate the association of exposure variables with height (outcome) by sex and age (12-13, 14-15, and 16-17 years). We observed a lower mean height in adolescents from the North Region and in individuals with low socioeconomic status. At 17 years of age, the closest to the final height in this sample, mean heights for girls and boys were 160.9 ± 0.1cm and 173.7 ± 0.3cm, respectively. In multiple linear regression analysis, physical activity (girls β = 0.119, 95%CI: 0.035; 0.202; boys β = 0.092, 95%CI: 0.012; 0.172) and high level of maternal education (girls β = 0.103, 95%CI: 0.001; 0.204; boys β = 0.39, 95%CI: 0.245; 0.534) were positively associated with height-for-age z-score in 16- to 17-year-old boys and girls. Other factors positively associated with height-for-age z-score in older students include higher protein consumption (β = 0.022, 95%CI: 0.010; 0.035) and obesity (β = 0.217, 95%CI: 0.084; 0.350) for boys, and low weight (β = 0.205, 95%CI: 0.028, 0.382) for girls. We observed differences in the mean height among adolescents from the five Brazilian regions. Normal growth, especially among older adolescents, was associated with high maternal education, practice of physical activity, protein consumption, and body mass index (BMI) categories.

Buscou-se descrever a altura média dos adolescentes das cinco regiões do Brasil e avaliar os fatores socioeconômicos e nutricionais que estejam associados ao seu crescimento normal. Este é um estudo transversal realizado em ambientes urbanos e rurais no Brasil com estudantes de 12 a 17 anos (n = 71.553). Avaliamos antropometria, variáveis socioeconômicas, atividade física e dieta. Calculou-se os escores-z por idade e investigou-se a associação das variáveis de exposição com altura (desfecho) por sexo e idade (12-13, 14-15 e 16-17 anos) através de múltiplos modelos de regressão linear. Observou-se menor altura média em adolescentes da região Norte e em baixos níveis socioeconômicos. Aos 17 anos, o mais próximo da altura final nesta amostra, as alturas médias para meninas e meninos foram de 160,9 ± 0,1cm e 173,7 ± 0,3cm, respectivamente. Na análise de regressão linear múltipla, atividade física (meninas β = 0,119, IC95%: 0,035; 0,202; meninos β = 0,092, IC95%: 0,012; 0,172) e Ensino Médio materno (meninas β = 0,103, IC95%: 0,201; 0,204; meninos β = 0,39, IC95%: 0,245; 0,534) estiveram positivamente associados ao escore-z de altura por idade em meninos e meninas de 16-17 anos. Maior consumo de proteína (β = 0,022, IC95%: 0,010; 0,035) e obesidade (β = 0,217, IC95%: 0,084; 0,350) estiveram positivamente associados ao escore-z de altura para a idade meninos mais velhos, enquanto a variável associada às meninas foi baixo peso (β = 0,205, IC95%: 0,028; 0,382). Observou-se diferenças na altura média de adolescentes das cinco regiões brasileiras. O crescimento normal, especialmente entre adolescentes mais velhos, esteve associado à escolaridade materna, à prática de atividade física, ao consumo de proteínas e às categorias de índice de massa corporal (IMC).

Los objetivos fueron describir la estatura media de los adolescentes de las cinco regiones de Brasil y evaluar los factores socioeconómicos y nutricionales asociados al crecimiento normal. Estudio transversal realizado en entornos urbanos y rurales de Brasil con estudiantes de 12 a 17 años (n = 71.553). Se evaluaron la antropometría, las variables socioeconómicas, la actividad física y la dieta. Se calculó la puntuación Z de la altura para la edad y se utilizaron modelos de regresión lineal múltiple para investigar la asociación de las variables de exposición con la altura (resultado) por sexo y edad (12-13, 14-15 y 16-17 años). Se observó una estatura media más baja en los adolescentes de la región norte y en los de nivel socioeconómico bajo. A los 17 años, la edad más cercana a la estatura final en esta muestra, las estaturas medias de las chicas y los chicos eran de 160,9 ± 0,1cm y 173,7 ± 0,3cm, respectivamente. En el análisis de regresión lineal múltiple, la actividad física (chicas β = 0,119, IC95%: 0,035; 0,202; chicos β = 0,092, IC95%: 0,012; 0,172) y la madre con educación secundaria (chicas β = 0,103, IC95%: 0,001; 0,204; chicos β = 0,39, IC95%: 0,245; 0,534) se asociaron positivamente con la puntuación z de la altura para la edad en chicos y chicas de 16-17 años. En el caso de los chicos, el mayor consumo de proteínas (β = 0,022, IC95%: 0,010; 0,035) y la obesidad (β = 0,217, IC95%: 0,084; 0,350), mientras que, en el caso de las chicas, el bajo peso (β = 0,205, IC95%: 0,028; 0,382) también se asociaron positivamente con la puntuación z de la altura para la edad en los estudiantes mayores. Se observaron diferencias en la estatura media entre los adolescentes de las cinco regiones brasileñas. El crecimiento normal, especialmente entre los adolescentes de mayor edad, se asoció con la alta escolaridad de la madre, la práctica de actividad física, el consumo de proteínas y las categorías de índice de masa corporal (IMC).

Circulating microRNAs in obese and lean heart failure patients: A case-control study with computational target prediction analysis.

AIMS: MicroRNAs (miRs) regulate processes involved in both cardiac remodeling and obesity. We investigated if the expression of selected miRs in patients with heart failure (HF) is influenced by the presence of obesity. METHODS: In this case-control study, we compared plasma levels of miR-21, -130b, -221, -423-5p, and the -221/-130b ratio in 57 age- and gender-matched subjects: 40 HF patients (20 obese HF and 20 lean HF) and 17 lean healthy controls. Body composition was estimated by bioelectrical impedance analysis. MiRs were measured by quantitative reverse transcription-PCR. Bioinformatics analysis was performed based on miRs findings to predict their putative targets and investigate their biological function. RESULTS: HF was associated with increased miR-423-5p levels in both lean and obese patients (P<0.05 vs. controls) without differences between HF groups. MiR-130b levels were reduced in obese HF patients compared with HF lean (P=0.036) and controls (P=0.025). MiR-221 levels were non-significantly increased in obese HF patients. MiR-21 levels were not different among the groups. MiR-221/-130b ratio was increased in obese HF patients, and was positively associated with body fat percentage (r=0.43; P=0.002), body mass index (r=0.44; P=0.002), and waist circumference (r=0.40; P=0.020). Computational prediction of target genes followed by functional enrichment analysis indicated a relevant role of miR-130b and miR-221 in modulating the expression of genes associated to cardiovascular and endocrine diseases, and suggested their influence in important signaling mechanisms and in numerous processes related to the circulatory and endocrine systems. CONCLUSIONS: In HF patients, the presence of obesity is associated with a differential expression of selected miRs and the miR-221/-130b ratio had significant correlations with adiposity parameters. Computational target prediction analysis identified several interrelated pathways targeted by miR-130b and miR-221 with a known relationship with endocrine and cardiovascular diseases, representing potential mechanisms to be further validated.

Comparison between IDMS-traceable Jaffe and enzymatic creatinine assays for estimation of glomerular filtration rate by the CKD-EPI equation in healthy and diabetic subjects.

OBJECTIVES: The aim of this paper was to compare the agreement between creatinine measured by Jaffe and enzymatic methods and their putative influence on eGFR as calculated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation in healthy and diabetic individuals. DESIGN AND METHODS: Cross-sectional study conducted in 123 adult southern Brazilians with GFR>60 mL/min/1.73 m² (53 patients with type 2 diabetes, 70 healthy volunteers). Mean age was 49±16 years (range of 19-86). Most were female (55%) and white (83%). Creatinine was measured by a traceable Jaffe method (Modular P, Roche Diagnostic) and by an enzymatic method (CREA plus, Roche/Hitachi 917). GFR was measured by the 5¹Cr-EDTA single-injection method. RESULTS: Serum creatinine measured by the Jaffe and enzymatic methods was similar in healthy subjects (0.79±0.16 vs. 0.79±0.15 mg/dL, respectively, P=0.76), and diabetic patients (0.96±0.22 vs. 0.92±0.29 mg/dL, respectively, P=0.17). However, the correlation between the two methods was higher in the healthy group (r=0.90 vs. 0.76, P<0.001). The difference between Jaffe creatinine and enzymatic creatinine was <10% in 63% of cases in the healthy group and 40% of cases in the diabetes group (P=0.018). In the subset of patients with diabetes, eGFR based on enzymatic assay results showed better agreement with measured GFR than did eGFR based on Jaffe results. CONCLUSION: Jaffe and enzymatic creatinine methods show adequate agreement in healthy subjects, but in the presence of diabetes, the enzymatic method performed slightly better.

Low rates of automatic reporting of estimated glomerular filtration rate in Southern Brazilian laboratories.

OBJECTIVES: The aim of this study was to evaluate the rate of eGFR reporting in Southern Brazilian laboratories. DESIGN AND METHODS: The eGFR automatic reporting, as assessed by Modification of Diet in Renal Disease (MDRD) and/or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based equations, was evaluated in a representative cross-sectional sample. A standardized questionnaire to obtain this information was given out by mail or email. RESULTS: Five-hundred fifty laboratories, evenly distributed in the different state regions, completed the questionnaire. The eGFR was automatically reported by 54 (9.8%) laboratories, and the MDRD was the most commonly used equation (94.5%). The Jaffe methods were the most employed technique (94%) to measure serum creatinine. CONCLUSION: The automatic eGFR reporting rate was unacceptably low, emphasizing the crucial role of educating medical teams and laboratories on the importance of having these tools available to optimize detection of renal disease and proper treatment.

Availability of urinary albumin measurement in Southern Brazilian Laboratories

Diabetic kidney disease (DKD) is the leading worldwide cause of endstage renal disease. The current recommendation is to screen for DKD by evaluating estimated glomerular filtration rate (eGFR) and measuring urinary albumin (UA) levels in a spot sample. The aim of this study was to evaluate the availability of UA measurement in Southern Brazilian laboratories. Methods: A cross-sectional study was conducted to assess the routine use of UA in all laboratories registered in the State Pharmacy Council of Rio Grande do Sul, the southernmost state of Brazil. Data was collected by mail, e-mail, telephone, or personal interview. A sample size of at least 384 laboratories was necessary to achieve 5% precision at a 95% confidence level based on a fixed proportion of 0.5. Results: Eight hundred and eighty laboratories currently registered in the state were invited to participate in the study; 548 (62%) answered the technical specification questionnaire. Only 306 (55%) of the 548 surveyed laboratories performed UA measurements. The laboratories were also required to provide the number of UA measurements performed per day, which ranged from less than one per week to 65 per day. Conclusion: The availability of UA measurements is undesirably low in Southern Brazil. This demonstrates the urgent need to increase the availability of this important test. It also reveals the gap between the current guidelines and the awareness about them among health care professionals...