Religious/spiritual coping, symptoms of depression, stress, and anxiety in caregivers of children and adolescents with type 1 diabetes.

BACKGROUND: It was verified the level of religiosity and spirituality, and symptoms of depression, stress, and anxiety of caregivers of children and adolescents with type 1 diabetes, and its interference in glycaemic control. METHODS: Socio-economic and demographic data were collected from caregivers of 59 children and adolescents with type 1 diabetes and obtained dosages of fasting glucose (FG); postprandial glycaemia (PPG); fructosamine (FRUTO); and HbA1c, as well as the glycaemic variability-∆HbA1c. Levels of religiosity were obtained by the DUREL scale; the use of religious/spiritual coping was verified by the SRCOPE-Brief scale. Symptoms of depression, anxiety, and stress were analysed by the DASS-21 scale. The correlations between the variables were analysed by the Pearson coefficient, with significance at 5% level. RESULTS: Inverse correlations were observed between caregivers' schooling with PPG (r = -0.30; P = 0.002) and FRUTO (r = -0.34; P = 0.008) and between family income and FRUTO (r = -0.37; P = 0.004). Direct, moderate correlations were observed between negative religious/spiritual coping (NSRCOPE) with symptoms of depression (r = 0.588; P < 0.0001), stress (r = 0.500; P < 0.0001), and anxiety (r = 0.551; P < 0.0001). CONCLUSION: The direct association between NSRCOPE with symptoms of depression, stress, and anxiety was the highlighted item in the present study emphasizing the need for greater attention to the emotional health of informal caregivers of children and adolescents with DM1. It is necessary to reflect on the religious/spiritual support especially for the main caregiver of children and adolescents with DM1.

Assessment of Gonadotropin Concentrations Stimulated by Gonadotropin-Releasing Hormone Analog by Electrochemiluminescence in Girls with Precocious Puberty and Premature Thelarche.

OBJECTIVE: The aim of this study is to determine the cutoff values of gonadotropin response to gonadotropin-releasing hormone analogs (GnRHas) corresponding to the activation of the hypothalamic-pituitary-gonadal axis that could differentiate central precocious puberty (CPP) from premature thelarche (PT) and using the electrochemiluminescence assay method. METHODS: A total of 49 girls underwent the stimulation test with an intramuscular injection of 3.75 mg leuprolide acetate. Based on the clinical and laboratory characteristics, they were divided into two groups: CPP (n = 22) and PT (n = 27). Baseline estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were collected before GnRHa administration and LH and FSH at 60 and 120 min, respectively, after GnRHa administration. RESULTS: The girls with CPP presented an increased height Z-score, advanced bone age, and higher baseline LH, FSH, estradiol, and LH/FSH ratio in relation to PT (p < 0.001). Stimulated LH differed significantly between the two groups, and the LH cutoff values were ≥4.29 IU/L (p < 0.001) and ≥3.95 IU/L at 60 and 120 min, respectively (p < 0.001). The LH peak was found at 60 min after stimulation. CONCLUSIONS: The GnRHa test is effective in distinguishing CPP from PT, and a single sampling, at 60 min, with LH concentrations above 4.29 may be the parameter of choice with the advantage of greater convenience and practicality.

Films from cashew byproducts: cashew gum and bacterial cellulose from cashew apple juice.

ABSTRACT: Cashew is a major crop in several tropical countries. Its cultivation is mostly aimed to the production of cashew nuts, whereas its byproducts (including cashew tree gum and cashew apples) are underutilized. In this study, cashew tree gum (CG) has been combined to nanofibrillated bacterial cellulose (NFBC) produced from cashew apple juice, at different ratios (from CG-only to NFBC-only), to produce edible films. While the CG-only dispersion (at 1 wt%) behaved as a quasi-Newtonian fluid, the addition of NFBC provided a shear-thinning behavior, making the dispersions easier to process, especially to cast. Moreover, the films containing increasing NFBC contents exhibited better physico-mechanical performance. When compared to the CG-only film, the films containing at least 25% NFBC presented remarkably higher strength and modulus (even similar to some conventional petroleum-derived polymers), lower water vapor permeability (WVP), and lower water solubility, although at the expense of lower elongation and higher opacity values. The combined use of both polysaccharides was demonstrated to be useful to overcome the limitations of both CG-only films (very low viscosity, poor tensile properties and very high WVP) and NFBC-only films (very high viscosity, making the dispersions difficult to mix and spread). Moreover, the use of different NFBC/CG ratios allow properties to be tuned to meet specific demands for different food packaging or coating purposes.

Ultrasound measurement of thyroid volume in euthyroid children under 3 years of age.

OBJECTIVE: To establish ultrasound reference values for thyroid volumes in children up to 3 years of age, given that ultrasound of the thyroid is an essential examination in the diagnosis of childhood thyroid disease. MATERIALS AND METHODS: This was a prospective study conducted in an iodine-sufficient city in southeastern Brazil. A total of 100 healthy children underwent clinical evaluation, anthropometric examination, and cervical ultrasound in accordance with conventional protocols. We evaluated characteristics such as echotexture, thyroid lobe volume, and total thyroid volume. The children were divided into five groups, by age: < 2 months; 2-12 months; 12-18 months; 18-24 months; and 24-36 months. RESULTS: The mean thyroid volume was lower in the < 2 month age group than in the other groups (0.4 mL vs. 0.18-0.70 mL; p < 0.001). For the subjects between 2 and 36 months of age, the mean volume was 1.0 mL (range, 0.30-2.0 mL). No other significant differences were observed between groups, thyroid lobes, or gender. However, body mass index correlated significantly with total thyroid volume (r = 0.347; p = 0.001). CONCLUSION: The mean thyroid dimensions were smallest in the < 2 month age group (0.35 ± 0.16 mL). For the subjects between 2 and 36 months of age, a reference value of 0.85 ± 0.42 mL can be used. Our data could guide the diagnostic investigation of thyroid disease, especially congenital hypothyroidism, in childhood.

OBJETIVO: Estabelecer valores de referência ultrassonográficos de volumes tireoidianos em crianças de até três anos de idade, por ser exame essencial no diagnóstico de doença tireoidiana infantil. MATERIAIS E MÉTODOS: Trata-se de estudo prospectivo conduzido em cidade do sudeste brasileiro suficiente em iodo. Participaram 100 crianças saudáveis, submetidas a exame clinicoantropométrico e ultrassonografia cervical seguindo protocolos convencionais. Características como ecotextura e volumes dos lobos e da tireoide total foram obtidos. Segundo a idade, as crianças foram distribuídas em cinco grupos: < 2 meses; 2-12 meses; 12-18 meses; 18-24 meses; e 24-36 meses. RESULTADOS: No grupo < 2 meses os volumes tireoidianos foram menores (p < 0,001) do que nos demais (0,4 mL; 0,18-0,70 mL). Além dessa idade, o volume total médio foi 1,0 mL (0,30-2,0 mL) e não diferiu entre os grupos. Não foram observadas diferenças entre lobos ou relacionadas a gênero. Houve correlação (r = 0,347; p = 0,001) entre índice de massa corporal e volume total. CONCLUSÃO: As dimensões tireoidianas foram menores até dois meses (0,35 ± 0,16 mL), e a partir dessa idade os mesmos valores de referência podem ser usados até 36 meses (0,85 ± 0,42 mL). Tais dados podem orientar a investigação diagnóstica, especialmente no hipotireoidismo congênito.

Ultrasound measurement of thyroid volume in euthyroid children under 3 years of age / Mensuração ultrassonográfica do volume tireoidiano em crianças eutireóideas menores de três anos

Abstract Objective: To establish ultrasound reference values for thyroid volumes in children up to 3 years of age, given that ultrasound of the thyroid is an essential examination in the diagnosis of childhood thyroid disease. Materials and Methods: This was a prospective study conducted in an iodine-sufficient city in southeastern Brazil. A total of 100 healthy children underwent clinical evaluation, anthropometric examination, and cervical ultrasound in accordance with conventional protocols. We evaluated characteristics such as echotexture, thyroid lobe volume, and total thyroid volume. The children were divided into five groups, by age: < 2 months; 2-12 months; 12-18 months; 18-24 months; and 24-36 months. Results: The mean thyroid volume was lower in the < 2 month age group than in the other groups (0.4 mL vs. 0.18-0.70 mL; p < 0.001). For the subjects between 2 and 36 months of age, the mean volume was 1.0 mL (range, 0.30-2.0 mL). No other significant differences were observed between groups, thyroid lobes, or gender. However, body mass index correlated significantly with total thyroid volume (r = 0.347; p = 0.001). Conclusion: The mean thyroid dimensions were smallest in the < 2 month age group (0.35 ± 0.16 mL). For the subjects between 2 and 36 months of age, a reference value of 0.85 ± 0.42 mL can be used. Our data could guide the diagnostic investigation of thyroid disease, especially congenital hypothyroidism, in childhood.

Resumo Objetivo: Estabelecer valores de referência ultrassonográficos de volumes tireoidianos em crianças de até três anos de idade, por ser exame essencial no diagnóstico de doença tireoidiana infantil. Materiais e Métodos: Trata-se de estudo prospectivo conduzido em cidade do sudeste brasileiro suficiente em iodo. Participaram 100 crianças saudáveis, submetidas a exame clinicoantropométrico e ultrassonografia cervical seguindo protocolos convencionais. Características como ecotextura e volumes dos lobos e da tireoide total foram obtidos. Segundo a idade, as crianças foram distribuídas em cinco grupos: < 2 meses; 2-12 meses; 12-18 meses; 18-24 meses; e 24-36 meses. Resultados: No grupo < 2 meses os volumes tireoidianos foram menores (p < 0,001) do que nos demais (0,4 mL; 0,18-0,70 mL). Além dessa idade, o volume total médio foi 1,0 mL (0,30-2,0 mL) e não diferiu entre os grupos. Não foram observadas diferenças entre lobos ou relacionadas a gênero. Houve correlação (r = 0,347; p = 0,001) entre índice de massa corporal e volume total. Conclusão: As dimensões tireoidianas foram menores até dois meses (0,35 ± 0,16 mL), e a partir dessa idade os mesmos valores de referência podem ser usados até 36 meses (0,85 ± 0,42 mL). Tais dados podem orientar a investigação diagnóstica, especialmente no hipotireoidismo congênito.

PUBERTY IN A SAMPLE OF BRAZILIAN SCHOOLBOYS: ONSET AND ANTHROPOMETRIC CHARACTERISTICS.

OBJECTIVE: To determine the age of puberty onset in boys and collect anthropometric data of participants at different puberty stages. METHODS: This is a cross-sectional study that assessed 430 boys in a random sample representing 48,390 students from public and private schools from the city of Uberaba, Southeast Brazil. The inclusion criteria were males, aged between 5 and 18 years, and absence of previous diseases. Participants and their guardians filled a semistructured questionnaire with questions relevant to their and their parents' puberty. We set the significance at p<0.05 and calculated the 95% confidence intervals. RESULTS: The mean age found in the puberty stage G2 was 11.2±1.8 (95% of participants in stage G2 were 9.2-13.4 years old). Pubarche data showed a mean of age of 11.0±1.6 years (95% of the participants experienced pubarche when they were 8.0-14.0 years old). When compared to the confidence intervals of two classical studies on the subject, our results showed a trend toward earlier pubarche. In addition, the mean age of this event in the children's parents was of 12.1±1.4 years, which was significantly higher than the age of the children's pubarche (p<0.001). CONCLUSIONS: These results indicate a secular decreasing trend in pubarche age and an earlier puberty onset. Considering these parameters, is important to design public policies aimed at preventing these early events.

Puberty in a sample of brazilian schoolboys: onset and anthropometric characteristics / Puberdade em uma amostra de meninos escolares brasileiros: início e características antropométricas

ABSTRACT Objective: To determine the age of puberty onset in boys and collect anthropometric data of participants at different puberty stages. Methods: This is a cross-sectional study that assessed 430 boys in a random sample representing 48,390 students from public and private schools from the city of Uberaba, Southeast Brazil. The inclusion criteria were males, aged between 5 and 18 years, and absence of previous diseases. Participants and their guardians filled a semistructured questionnaire with questions relevant to their and their parents' puberty. We set the significance at p<0.05 and calculated the 95% confidence intervals. Results: The mean age found in the puberty stage G2 was 11.2±1.8 (95% of participants in stage G2 were 9.2-13.4 years old). Pubarche data showed a mean of age of 11.0±1.6 years (95% of the participants experienced pubarche when they were 8.0-14.0 years old). When compared to the confidence intervals of two classical studies on the subject, our results showed a trend toward earlier pubarche. In addition, the mean age of this event in the children's parents was of 12.1±1.4 years, which was significantly higher than the age of the children's pubarche (p<0.001). Conclusions: These results indicate a secular decreasing trend in pubarche age and an earlier puberty onset. Considering these parameters, is important to design public policies aimed at preventing these early events.

RESUMO Objetivo: Determinar a idade em que a puberdade começa em meninos e coletar dados antropométricos de participantes em diferentes fases da puberdade. Métodos: Trata-se de um estudo transversal no qual foram avaliados 430 meninos, uma amostra aleatória representativa da população total de 48.390 estudantes de escolas públicas e particulares de Uberaba, Minas Gerais. Os critérios de inclusão foram: ser do sexo masculino, ter idade de 5 a 18 anos e ausência de doenças prévias. Os participantes e seus responsáveis preencheram um questionário semiestruturado com perguntas pertinentes à sua puberdade e à de seus pais. Os dados foram considerados significantes para p<0,05, e os intervalos de confiança calculados foram de 95%. Resultados: A média de idade encontrada no estágio G2 foi de 11,2±1,8 anos, sendo que 95% dos participantes em G2 tinham entre 9,2 a 13,4 anos. Quanto à pubarca, a média de idade foi de 11,0±1,6 anos, e 95% dos participantes apresentaram pubarca entre 8,0 e 14,0 anos. Quando tais resultados foram comparados aos intervalos de confiança de dois estudos clássicos sobre o tema, houve tendência à pubarca mais precoce. Além disso, a média de idade da pubarca nos pais das crianças foi de 12,1±1,4 anos, significantemente maior em relação à dos filhos (p<0,001). Conclusões: Os resultados indicam uma tendência secular em direção à diminuição da idade da pubarca e um possível início mais precoce da puberdade. É muito importante considerar esses parâmetros para estabelecer políticas públicas destinadas a prevenir esses eventos iniciais.

Papain immobilization on heterofunctional membrane bacterial cellulose as a potential strategy for the debridement of skin wounds.

We combined the chemical and physical methods of papain immobilization through the aldehyde groups available on oxidized bacterial cellulose (OxBC) to provide high proteolytic activity for future applications as bioactive dressing. Bacterial cellulose (BC) was obtained by the fermentation of Komagataeibacter hansenii in Hestrin-Schramm medium for 5 days, followed by purification and oxidation using NaIO4. Surface response methodology was used to optimize papain immobilization (2%, w/v) for 24 h. The independent variables: pH (3-7) and temperature (5 to 45 °C) were investigated. The mathematically validated optimal conditions of 45 °C and pH 7 had a statistical effect on the immobilization yield (IY) of papain in OxBC (52.9%). These ideal conditions were also used for papain immobilization in BC (unoxidized). The IY of 9.1% was lower than that of OxBC. OxBC-Papain and BC-Papain were investigated using thermal analysis, confocal microscopy, and diffusion testing. The OxBC support exhibited a more interactive chemical structure than the BC support, and was capable of immobilizing papain by covalent bonds (-C-NHR) and adsorption (ion exchange), with 93.3% recovered activity, 49.4% immobilization efficiency, and better thermal stability. Papain immobilized to OxBC by adsorption displayed 53% widespread papain activity. The results indicate the potential of prolonged bioactivity in debrided chronic wounds.

Effects of the laying on of hands on anxiety, stress and autonomic response of employees in a hospital: A double-blind randomized controlled trial.

Mental and behavioral disorders result in increased absenteeism and abandonment of work. The objective of this study was to evaluate the anxiety, stress, depression, negative and positive affects, and hematological and autonomic responses of employees in a public hospital exposed to laying on of hands with (LHS) or without Spiritual connection (control-LHW). METHODOLOGY: Eighty-four employees with anxiety/stress were enrolled and randomly allocated into two groups of intervention LHS by Spiritist "passe" and control-LHW by volunteers with healing intent. Anxiety, stress and depression were evaluated by Depression Anxiety and Stress Scale (DASS21). Negative and positive affects by Subjective Well-being Scale (SWS), cardiac autonomic modulation by heart rate variability and cytokines and blood count were assessed by blood sample. RESULTS: Our study showed a significant improvement in the neutrophils (p = 0.041; d = 0.70) and cardiac parasympathetic activity, and reduction in VLF (p < 0.005) in the LHS. There was reduction in erythrocyte parameters and interleukin 10 (p < 0.005) in the control-LHW. In both groups there was a significant reduction in anxiety, stress, depression and negative affects after one session (p < 0.005). CONCLUSION: Laying on of hands with Spiritual connection by Spiritist "passe" appears to be effective in increasing cardiac vagal activity and regulation of immune responses of employees in a public hospital with stress/anxiety.

In vitro degradability and bioactivity of oxidized bacterial cellulose-hydroxyapatite composites.

Hydroxyapatite-associated bacterial cellulose (BC/HA) is a promising composite for biomedical applications. However, this hybrid composite has some limitations due to its low in vivo degradability. The objective of this work was to oxidize BC and BC/HA composites for different time periods to produce 2,3 dialdehyde cellulose (DAC). The BC and oxidized BC (OxBC) membranes were mineralized to obtain the hybrid materials (BC/HA and OxBC/HA) and their physico-chemical, degradability, and bioactivity properties were studied. The results showed that OxBC/HA was more bioactive and degradable than BC/HA, which isa function of the degree of BC oxidation. High glucose levels in the BC degradation were observed as a function of oxidation degree, and other products, such as butyric acid and acetic acid resulted from DAC degradation. Therefore, this chemical modification reaction favors BC degradation, making it a good biodegradable and bioactive material with a potential for bone regeneration applications.

Analysis of serum inflammatory mediators in type 2 diabetic patients and their influence on renal function.

AIM: To evaluate the serum concentrations of inflammatory mediators in patients with type 2 diabetes mellitus (T2DM) with or without renal alteration (RA) function. METHODS: Serum samples from 76 patients with T2DM and 24 healthy individuals were selected. Patients with T2DM were divided into two groups according to eGFR (> or < 60mL/min/1.73m2). Cytokines, chemokines and adipokines levels were evaluated using the Multiplex immunoassay and ELISA. RESULTS: TNFR1 and leptin were higher in the T2DM group with RA than in the T2DM group without RA and control group. All patients with T2DM showed increased resistin, IL-8, and MIP-1α compared to the control group. Adiponectin were higher and IL-4 decreased in the T2DM group with RA compared to the control group. eGFR positively correlated with IL-4 and negatively with TNFR1, TNFR2, and leptin in patients with T2DM. In the T2DM group with RA, eGFR was negatively correlated with TNFR1 and resistin. TNFR1 was positively correlated with resistin and leptin, as well as resistin with IL-8 and leptin. CONCLUSION: Increased levels of TNFR1, adipokines, chemokines and decrease of IL-4 play important role in the inflammatory process developed in T2DM and decreased renal function. We also suggest that TNFR1 is a strong predictor of renal dysfunction in patients with T2DM.

Effect of Spiritist "Passe" on Preoperative Anxiety of Surgical Patients: A Randomized Controlled Trial, Double-Blind.

The objective of this study was to evaluate the preoperative anxiety of hospitalized patients exposed to Spiritist "passe," laying on of hand with the intention of healing (Sham) and without laying on of hand. Other variables as depression, pain, physiological parameters, muscle tension, and well-being were assessed. Patients in the Spiritist "passe" intervention group showed greater reductions in anxiety (p < 0.05) and muscle tension (p < 0.01) and increases in well-being (p < 0.01). More marked reductions in preoperative anxiety and muscle tension and improvement in well-being were observed in patients exposed to Spiritist "passe" compared to Sham or standard medical care.Trial registration: ClinicalTrials.gov Identifier NCT03356691.

Religiosidade/espiritualidade, indicadores de saúde mental e parâmetros hematológicos de profissio-nais de enfermagem / Religiosity/spirituality, mental health indicators and hematologic parameters of nursing professionals / Religiosidad/espiritualidad, indicadores de salud mental y parámetros hematológicos de profesionales de enfermeiras

Objetivo:analisara relação entre Religiosidade e Espiritualidade,indicadores de saúde mental, parâmetros hematológicos e percepção dasaúde de profissionais deenfermagem.Método:estudo transversal com 53 funcionários. Utilizou-se Medida Multidimensional Breve de Religiosidade e Espiritualidade, Inventário Stress Lipp,Ansiedade e Depressão de Beck, Bem-Estar Subjetivo,hemograma e imunoglobulina A. Resultados:Dimensões Experiências Espirituais Diárias eAutoavaliação Global são os fatores commaior forçade relação com os índices de estresse, depressão e Bem-Estar em profissionais.Participação religiosa e comprometimento foramosfatores que influenciarammaiores valores de leucócitos,neutrófilose imunoglobulina A. Conclusão:os resultados identificaram relação entre Religiosidade e Espiritualidade, indicadores de saúde mental e parâmetros hematológicos. Profissionais de enfermagemmais religiosos e espiritualistas apresentam melhor saúde mental e maior imunidade, além de melhor percepção de saúde (AU).

Objective:to analyze the relationship between Religiosity and Spirituality, mental health indicators and haematological parameters of nurses. Method:cross-sectional study with 53 employees. It was used Brief Multidimensional Measure of Religiosity and Spirituality (BMMRS), Lipp Stress Inventory, Beck Anxiety and Depression and Subjective Wellbeing, hemogram and immunoglobulin A. Results:dimensions Daily Spiritual Experiences and Global Religiosity and Spirituality Self-evaluation are the factors that present greater strength of relation with the indices of stress, depression and Subjective Wellbeing in professionals. Religious participation and impairment were the factors that influenced higher leukocyte, neutrophil and immunoglobulin A values.Conclusion:the results identified a relation between Religiosity and Spirituality, mental health indicators and haematological parameters, demonstrating that more religious and spiritualist nurses have better mental health and immunity,as well as a better perception of health (AU).

Objetivo:analizar la relación entre Religiosidad y Espiritualidad, indicadores de salud mental y parámetros hematológicos de enfermeras. Método:estudio transversal con 53 empleados. Se utilizó Medida Multidimensional Breve de Religiosidad y Espiritualidad (BMMRS), Inventario Stress Lipp, Escalas de Ansiedad y Depresión Beck y Bienestar Subjetivo, cuestionario de clasificación de la salud,hemograma yinmunoglobulina A. Resultados:las dimensiones Experiencias Espirituales Diarias y Autoevaluación Global de Religiosidad y Espiritualidad son los factores que presentan mayor fuerza de relación con los índices de estrés, depresión y Bienestar Subjetivo en profesionales. La participación religiosa y compromiso fueron los principales factores que influyen en los valores de leucocitos, neutrófilos, y la inmunoglobulina A. Conclusión:los resultados identificaron relación entre R/E, indicadores de salud mental y parámetros hematológicos, demostrandoque enfermeras más religiosos y espiritualistas presentan mejor salud mental y mayor inmunidad, además de una mejor percepción de la salud (AU).

A recurrent mutation in tshb gene underlying central congenital hypothyroidism undetectable in neonatal screening / Uma mutação recorrente no gene tshb resultando em hipotireoidismo congênito central não detectável na triagem neonatal

ABSTRACT Objective: To describe the case of a patient with central congenital hypothyroidism (CCH) due to a recurrent mutation in the TSHB gene, as well as to conduct a genetic study of his family. Case description: It is presented a case report of a 5-month-old boy with a delayed diagnosis of isolated CCH in whom the molecular analysis was performed 12 years later and detected a recurrent mutation (c.373delT) in TSHB gene. The parents and sister were carriers of the mutant allele. Comments: The c.373delT mutation has previously been reported in patients from Brazil, Germany, Belgium, United States, Switzerland, Argentina, France, Portugal, United Kingdom and Ireland. In summary, our case and other ones reported in the literature support the theory that this mutation may be a common cause of isolated TSH deficiency. Isolated TSH deficiency is not detected by routine TSH-based neonatal screening, representing a clinical challenge. Therefore, when possible, molecular genetic study is indicated. Identification of affected and carriers allows the diagnosis, treatment and adequate genetic counseling.

RESUMO Objetivo: Descrever o caso de um paciente com hipotireoidismo congênito central (HCC) por conta de uma mutação recorrente no gene TSHB, bem como realizar um estudo genético de sua família. Descrição do caso: Relato de caso de um menino de 5 meses de idade com diagnóstico tardio de HCC isolado, em quem a análise molecular foi realizada 12 anos depois e detectou uma mutação recorrente (c.373delT) no gene TSHB. Os pais e a irmã eram portadores do alelo mutante. Comentários: A mutação c.373delT já foi relatada em pacientes do Brasil, da Alemanha, da Bélgica, dos Estados Uinidos, da Suíça, da Argentina, da França, de Portugal, do Reino Unido e da Irlanda. Em resumo, nosso caso e outros relatados na literatura reforçam a teoria de que essa mutação pode ser uma causa comum de deficiência isolada de TSH. A deficiência isolada de TSH não é detectada na triagem neonatal com base na dosagem de TSH, representando um desafio clínico. Portanto, quando possível, o estudo genético molecular é indicado. A identificação dos afetados e dos portadores permite o diagnóstico, o tratamento e o aconselhamento genético adequado.

Clinical and Laboratory Parameters of Gonadotropin-Releasing Hormone Analog Treatment Effectiveness in Children with Precocious Puberty.

OBJECTIVE: There are no doubts about the clinical benefits of treatment with GnRH analogs for patients diagnosed with central precocious puberty (CPP). However, laboratory monitoring of CPP is still a matter of considerable controversy in the literature. Therefore, the main objective of this study was to evaluate the cut-off values of stimulated LH that determine gonadotrophic suppression. METHODS: Twenty-four girls, on treatment with leuprorelin acetate (LA) at 3.75 mg IM every 28 days, were studied. The clinical parameters used to indicate clinical effectiveness were regression or maintenance of sexual characteristics according to the Tanner stage, growth velocity reduction, reduction or maintenance of the difference between bone age and chronological age and maintenance or improvement of the final height prediction. For the laboratory effectiveness test, basal estradiol, LH, and FSH levels were collected before and 1 and 2 h after the administration of 3.75 mg LA. RESULTS: Eleven girls showed improvement in all clinical parameters, and their effectiveness tests were compared to those of the other patients to calculate the cut-off values, which were ≤3.64 IU/L (p=0.004*) for LH after 1 h and ≤6.10 IU/L (p<0.001*) for LH after 2 h. CONCLUSION: The LH response after the LA stimulation test, associated with clinical data and within a context of CPP, constitutes a reliable and feasible resource and can assist in monitoring the effectiveness of treatment.

Metabolic and hormonal assessment of adolescent and young adult women with prior premature adrenarche.

OBJECTIVE: Follow-up studies of girls with premature adrenarche have reported the development of polycystic ovary syndrome, insulin resistance, and dyslipidemia and a propensity to cardiovascular disease. The aim of this study was to analyze the presence of these conditions in patients previously treated at the Universidade Federal do Triângulo Mineiro. METHODS: A total of 130 medical records reported premature adrenarche. One hundred and twenty-two patients were invited to participate, of whom 54 accepted; 34 patients were selected, as they had reached their final height. Anthropometric, blood glucose, insulin, and lipid and hormonal profile (LH, FSH, estradiol, 17α-OH-progesterone, androstenedione, dehydroepiandrosterone sulfate, testosterone) data were obtained, the HOMA-IR index was calculated, and pelvic ultrasonography was performed. To characterize polycystic ovary syndrome and metabolic syndrome, the Rotterdam and International Diabetes Federation criteria, respectively, were used. Data were analyzed according to measures of dispersion, frequency and correlations of interest. RESULTS: The age of the participants ranged from 15.2 to 28.2 years/months; 23.5% of the patients were overweight, 11.8% were obese, 29.4% had a large waist circumference, and 8.8% were hypertensive. None of the patients had altered glucose levels, and insulin levels and HOMA-IR were elevated in 29.4% and 38.2% of the participants, respectively; 14.7% of the patients exhibited acanthosis nigricans. The lipid profiles of the participants were variable, and one patient (2.9%) had metabolic syndrome. Polycystic ovary syndrome was found in 41.2% of patients. CONCLUSION: The percentage of patients with polycystic ovary syndrome who also had overweight, obesity and insulin resistance corroborates the literature data about the need for follow-up aiming at interventions, especially for conditions associated with cardiometabolic risk.

A RECURRENT MUTATION IN TSHB GENE UNDERLYING CENTRAL CONGENITAL HYPOTHYROIDISM UNDETECTABLE IN NEONATAL SCREENING.

OBJECTIVE: To describe the case of a patient with central congenital hypothyroidism (CCH) due to a recurrent mutation in the TSHB gene, as well as to conduct a genetic study of his family. CASE DESCRIPTION: It is presented a case report of a 5-month-old boy with a delayed diagnosis of isolated CCH in whom the molecular analysis was performed 12 years later and detected a recurrent mutation (c.373delT) in TSHB gene. The parents and sister were carriers of the mutant allele. COMMENTS: The c.373delT mutation has previously been reported in patients from Brazil, Germany, Belgium, United States, Switzerland, Argentina, France, Portugal, United Kingdom and Ireland. In summary, our case and other ones reported in the literature support the theory that this mutation may be a common cause of isolated TSH deficiency. Isolated TSH deficiency is not detected by routine TSH-based neonatal screening, representing a clinical challenge. Therefore, when possible, molecular genetic study is indicated. Identification of affected and carriers allows the diagnosis, treatment and adequate genetic counseling.

Clinical and laboratory parameters of gonadotropin-releasing hormone analog treatment effectiveness in children with precocious puberty

OBJECTIVE: There are no doubts about the clinical benefits of treatment with GnRH analogs for patients diagnosed with central precocious puberty (CPP). However, laboratory monitoring of CPP is still a matter of considerable controversy in the literature. Therefore, the main objective of this study was to evaluate the cut-off values of stimulated LH that determine gonadotrophic suppression. METHODS: Twenty-four girls, on treatment with leuprorelin acetate (LA) at 3.75 mg IM every 28 days, were studied. The clinical parameters used to indicate clinical effectiveness were regression or maintenance of sexual characteristics according to the Tanner stage, growth velocity reduction, reduction or maintenance of the difference between bone age and chronological age and maintenance or improvement of the final height prediction. For the laboratory effectiveness test, basal estradiol, LH, and FSH levels were collected before and 1 and 2 h after the administration of 3.75 mg LA. RESULTS: Eleven girls showed improvement in all clinical parameters, and their effectiveness tests were compared to those of the other patients to calculate the cut-off values, which were ≤3.64 IU/L (p=0.004*) for LH after 1 h and ≤6.10 IU/L (p<0.001*) for LH after 2 h. CONCLUSION: The LH response after the LA stimulation test, associated with clinical data and within a context of CPP, constitutes a reliable and feasible resource and can assist in monitoring the effectiveness of treatment.

Metabolic and hormonal assessment of adolescent and young adult women with prior premature adrenarche

OBJECTIVE: Follow-up studies of girls with premature adrenarche have reported the development of polycystic ovary syndrome, insulin resistance, and dyslipidemia and a propensity to cardiovascular disease. The aim of this study was to analyze the presence of these conditions in patients previously treated at the Universidade Federal do Triângulo Mineiro. METHODS: A total of 130 medical records reported premature adrenarche. One hundred and twenty-two patients were invited to participate, of whom 54 accepted; 34 patients were selected, as they had reached their final height. Anthropometric, blood glucose, insulin, and lipid and hormonal profile (LH, FSH, estradiol, 17α-OH-progesterone, androstenedione, dehydroepiandrosterone sulfate, testosterone) data were obtained, the HOMA-IR index was calculated, and pelvic ultrasonography was performed. To characterize polycystic ovary syndrome and metabolic syndrome, the Rotterdam and International Diabetes Federation criteria, respectively, were used. Data were analyzed according to measures of dispersion, frequency and correlations of interest. RESULTS: The age of the participants ranged from 15.2 to 28.2 years/months; 23.5% of the patients were overweight, 11.8% were obese, 29.4% had a large waist circumference, and 8.8% were hypertensive. None of the patients had altered glucose levels, and insulin levels and HOMA-IR were elevated in 29.4% and 38.2% of the participants, respectively; 14.7% of the patients exhibited acanthosis nigricans. The lipid profiles of the participants were variable, and one patient (2.9%) had metabolic syndrome. Polycystic ovary syndrome was found in 41.2% of patients. CONCLUSION: The percentage of patients with polycystic ovary syndrome who also had overweight, obesity and insulin resistance corroborates the literature data about the need for follow-up aiming at interventions, especially for conditions associated with cardiometabolic risk.

Methylome profiling of healthy and central precocious puberty girls.

BACKGROUND: Recent studies demonstrated that changes in DNA methylation (DNAm) and inactivation of two imprinted genes (MKRN3 and DLK1) alter the onset of female puberty. We aimed to investigate the association of DNAm profiling with the timing of human puberty analyzing the genome-wide DNAm patterns of peripheral blood leukocytes from ten female patients with central precocious puberty (CPP) and 33 healthy girls (15 pre- and 18 post-pubertal). For this purpose, we performed comparisons between the groups: pre- versus post-pubertal, CPP versus pre-pubertal, and CPP versus post-pubertal. RESULTS: Analyzing the methylome changes associated with normal puberty, we identified 120 differentially methylated regions (DMRs) when comparing pre- and post-pubertal healthy girls. Most of these DMRs were hypermethylated in the pubertal group (99%) and located on the X chromosome (74%). Only one genomic region, containing the promoter of ZFP57, was hypomethylated in the pubertal group. ZFP57 is a transcriptional repressor required for both methylation and imprinting of multiple genomic loci. ZFP57 expression in the hypothalamus of female rhesus monkeys increased during peripubertal development, suggesting enhanced repression of downstream ZFP57 target genes. Fourteen other zinc finger (ZNF) genes were related to the hypermethylated DMRs at normal puberty. Analyzing the methylome changes associated with CPP, we demonstrated that the patients with CPP exhibited more hypermethylated CpG sites compared to both pre-pubertal (81%) and pubertal (89%) controls. Forty-eight ZNF genes were identified as having hypermethylated CpG sites in CPP. CONCLUSION: Methylome profiling of girls at normal and precocious puberty revealed a widespread pattern of DNA hypermethylation, indicating that the pubertal process in humans is associated with specific changes in epigenetically driven regulatory control. Moreover, changes in methylation of several ZNF genes appear to be a distinct epigenetic modification underlying the initiation of human puberty.