Art and science: impact of semioccluded vocal tract exercises and choral singing on quality of life in subjects with congenital GH deficiency.

Objective: Currently, not much is known about the interactions between voice and growth hormone (GH). We have described large kindred with isolated GH deficiency (IGHD) due to a GHRH receptor mutation, resulting in severe short stature and high-pitched voice. These IGHD individuals have little interest in GH treatment, as they consider themselves "short long-lived people", rather than patients. Interestingly, they report normal general quality of life, but they rate their Voice-Related Quality of Life (V-RQOL) as low. Here, we assessed the social and auditory-perceptual impacts of artistic-intervention voice therapy with semioccluded vocal tract exercises (SOVTE) and choral singing, on their voices. Methods: Seventeen GH-naïve adult IGHD individuals were enrolled in a single-arm interventional pre-post study with 13 weekly sessions of choir singing over 90 days. Outcome measures were V-RQOL scores, self-assessment of voice, and auditory-perceptual analysis (GRBAS scale, G: grade of the severity of dysphonia; R: roughness; B: breathiness; A: asthenia; and S: strain). Results: Marked improvements in total (p = 0.0001), physical (p = 0.0002), and socioemotional (p = 0.0001) V-RQOL scores and in self-assessment of voice (p = 0.004) were found. The general grades of vocal deviation (p = 0.0001), roughness (p = 0.0001), breathiness (p = 0.0001) and strain (p = 0.0001) exhibited accentuated reductions. Conclusion: Voice therapy with semioccluded vocal tract exercises and choral training improved social impact and perceptual voice assessments in IGHD subjects and markedly improved their voice-related quality of life. This is particularly important in a setting where GH replacement therapy is not widely accepted.

Effects of Therapy With Semi-occluded Vocal Tract and Choir Training on Voice in Adult Individuals With Congenital, Isolated, Untreated Growth Hormone Deficiency.

OBJECTIVES: Voice is produced by the vibration of the vocal folds expressed by its fundamental frequency (Hz), whereas the formants (F) are fundamental frequency multiples, indicating amplification zones of the vowels in the vocal tract. We have shown that lifetime isolated growth hormone deficiency (IGHD) causes high pitch voice, with higher values of most formant frequencies, maintaining a prepuberal acoustic prediction. The objectives of this work were to verify the effects of the therapy with a semi-occluded vocal tract (SOVTT) and choir training on voice in these subjects with IGHD. We speculated that acoustic vocal parameters can be improved by SOVTT or choir training. STUDY DESIGN: This is a prospective longitudinal study without control group. METHODS: Acoustic analysis of isolated vowels was performed in 17 adults with IGHD before and after SOVTT (pre-SOVTT and post-SOVTT) and after choir training (post training), in a 30-day period. RESULTS: The first formant was higher in post training compared with the pre-SOVTT (P = 0.009). The second formant was higher in post-SOVTT than in pre-SOVTT (P = 0.045). There was a trend of reduction in shimmer in post-choir training in comparison with pre-SOVTT (P = 0.051), and a reduction in post-choir training in comparison with post-SOVTT (P = 0.047). CONCLUSIONS: SOVTT was relevant to the second formant, whereas choir training improved first formant and shimmer. Therefore, this speech therapy approach was able to improve acoustic parameters of the voice of individuals with congenital, untreated IGHD. This seems particularly important in a scenario in which few patients are submitted to growth hormone replacement therapy.

Art and science: impact of semioccluded vocal tract exercises and choral singing on quality of life in subjects with congenital GH deficiency

ABSTRACT Objectives: Currently, not much is known about the interactions between voice and growth hormone (GH). We have described large kindred with isolated GH deficiency (IGHD) due to a GHRH receptor mutation, resulting in severe short stature and high-pitched voice. These IGHD individuals have little interest in GH treatment, as they consider themselves "short long-lived people", rather than patients. Interestingly, they report normal general quality of life, but they rate their Voice-Related Quality of Life (V-RQOL) as low. Here, we assessed the social and auditory-perceptual impacts of artistic-intervention voice therapy with semioccluded vocal tract exercises (SOVTE) and choral singing, on their voices. Material and methods: Seventeen GH-naïve adult IGHD individuals were enrolled in a single-arm interventional pre-post study with 13 weekly sessions of choir singing over 90 days. Outcome measures were V-RQOL scores, self-assessment of voice, and auditory-perceptual analysis (GRBAS scale, G: grade of the severity of dysphonia; R: roughness; B: breathiness; A: asthenia; and S: strain). Results: Marked improvements in total (p = 0.0001), physical (p = 0.0002), and socioemotional (p = 0.0001) V-RQOL scores and in self-assessment of voice (p = 0.004) were found. The general grades of vocal deviation (p = 0.0001), roughness (p = 0.0001), breathiness (p = 0.0001) and strain (p = 0.0001) exhibited accentuated reductions. Conclusions: Voice therapy with semioccluded vocal tract exercises and choral training improved social impact and perceptual voice assessments in IGHD subjects and markedly improved their voice-related quality of life. This is particularly important in a setting where GH replacement therapy is not widely accepted.

Evaluation of effectiveness and outcome of PKU screening and management in the State of Sergipe, Brazil.

OBJECTIVES: Phenylketonuria (PKU) was the first inherited metabolic disease known to cause mental retardation for which a newborn screening program (NBS) was developed. The objective of this study was to evaluate the effectiveness of PKU NBS and the management of cases in the northeastern Brazilian state of Sergipe (SE). MATERIALS AND METHODS: We reviewed the phenylalanine concentrations in filter-paper collected from the heel (PKUneo) of 43,449 newborns; blood concentrations obtained by venipuncture in the subjects with abnormal PKUneo; the children's age at several phases of the program, the incidence of the disease from January 2007 to June 2008; and metabolic control of the patients. RESULTS: The coverage of NBS/SE was 78.93%. The children's age was 10 ± 7 days at PKUneo collection. Twelve children were recalled based on the PKUneo cutoff value at 28 ± 13 days. From these, the concentrations of phenylalanine collected by venipuncture were normal in five children. The incidence of hyperphenylalaninemia was 1/43,449, and of PKU was 1/8,690 (5 cases). One suspected subject died. Another death occurred in the cohort, in a confirmed PKU case. PKU treatment began within 51 ± 12 days of life. In the four patients under dietary phenylalanine restriction, metabolic control was often difficult. CONCLUSIONS: PKU NBS/SE has satisfactory coverage and adequate cutoff for recalling patients and diagnosis, but the onset of treatment is delayed, and follow-up metabolic control is frequently inadequate.

Comparison between the growth response to growth hormone (GH) therapy in children with partial GH insensitivity or mild GH deficiency.

OBJECTIVES: GH therapy is still controversial, except in severe GH deficiency (SGHD). The objective of this study was to compare the response to growth hormone (GH) therapy in children with partial GH insensitivity (PGHIS) and mild GH deficiency (MGHD) with those with SGHD. SUBJECTS AND METHODS: Fifteen PGHIS, 11 MGHD, and 19 SGHD subjects, followed up for more than one year in the Brazilian public care service, were evaluated regarding anthropometric and laboratory data at the beginning of treatment, after one year (1st year) on treatment, and at the last assessment (up to ten years in SGHD, up to four years in MGHD, and up to eight years in PGHIS). RESULTS: Initial height standard deviation score (SDS) in SGHD was lower than in MGHD and PGHIS. Although the increase in 1 st year height SDS in comparison to initial height SDS was not different among the groups, height-SDS after the first year of treatment remained lower in SGHD than in MGHD. There was no difference in height-SDS at the last assessment of the children among the three groups. GH therapy, in the entire period of observation, caused a trend towards lower increase in height SDS in PGHIS than SGHD but similar increases were observed in MGHD and SGHD. CONCLUSION: GH therapy increases height in PGHIS and produces similar height effects in MGHD and SGHD.

Lifetime congenital isolated GH deficiency does not protect from the development of diabetes.

OBJECTIVES: Adult subjects with untreated, lifetime, isolated GH deficiency (IGHD) due to a homozygous GHRH receptor gene mutation (MUT/MUT) residing in Itabaianinha, Brazil, present with lower BMI, higher prevalence of impaired glucose tolerance (IGT), increased insulin sensitivity (IS), and reduced ß-cell function (ßCF) when compared with non-BMI-matched homozygous normal controls. However, the prevalence of diabetes mellitus (DM) in this cohort is unknown. Comparing their IS and ßCF with BMI-matched individuals heterozygous for the same mutation (MUT/N) may be useful to elucidate the role of the GH-IGF1 axis in IS and ßCF. The purposes of this work were to verify the prevalence of IGT and DM in adult MUT/MUT subjects from this kindred and to compare IS and ßCF in MUT/MUT and MUT/N. DESIGN: Cross-sectional study. METHODS: We studied most (51) of the living IGHD adults of this kindred who are GH naive. The oral glucose tolerance test (OGTT) could be performed in 34 subjects, fasting glucose was measured in 15, while two had a previous diagnosis of DM. The OGTT results of 24 MUT/MUT subjects were compared with those of 25 BMI-matched MUT/N subjects. IS was assessed by homeostatic model assessment of insulin resistance (HOMA-IR), quantitative IS check index, and oral glucose IS index for 2 and 3 h. ßCF was assayed by HOMA-ß, insulinogenic index, and the area under the curve of insulin:glucose ratio. RESULTS: The prevalence of DM and IGT in IGHD was 15.68 and 38.23% respectively. IS was increased and ßCF was reduced in MUT/MUT in comparison with MUT/N. CONCLUSIONS: Lifetime, untreated IGHD increases IS, impairs ßCF, and does not provide protection from diabetes.

Isolated GH deficiency due to a GHRH receptor mutation causes hip joint problems and genu valgum, and reduces size but not density of trabecular and mixed bone.

CONTEXT: The GH/IGF-I axis is important for bone growth, but its effects on joint function are not completely understood. Adult-onset GH-deficient individuals have often reduced bone mineral density (BMD). However, there are limited data on BMD in adult patients with untreated congenital isolated GH-deficient (IGHD). We have shown that adult IGHD individuals from the Itabaianinha, homozygous for the c.57+1G>A GHRHR mutation, have reduced bone stiffness, but BMD and joint status in this cohort are unknown. OBJECTIVE: The goal is to study BMD, joint function, and osteoarthritis score in previously untreated IGHD adults harboring the c.57+1G>A GHRHR mutation. DESIGN: This is a cross-sectional study. METHODS: Areal BMD by dual-energy X-ray absorptiometry was measured in 25 IGHD and 23 controls (CO). Volumetric BMD (vBMD) was calculated at the lumbar spine and total hip. Joint function was assessed by goniometry of elbow, hips, and knees. X-rays were used to measure the anatomic axis of knee and the severity of osteoarthritis, using a classification for osteophytes (OP) and joint space narrowing (JSN). RESULTS: Genu valgum was more prevalent in IGHD than CO. The osteoarthritis knees OP score was similar in both groups, and knees JSN score showed a trend to be higher in IGHD. The hips OP score and JSN score were higher in IGHD. Areal BMD was lower in IGHD than CO, but vBMD was similar in the two groups. Range of motion was similar in elbow, knee, and hip in IGHD and CO. CONCLUSIONS: Untreated congenital IGHD due to a GHRHR mutation causes hip joint problems and genu valgum, without apparent clinical significance, reduces bone size, but does not reduce vBMD of the lumbar spine and hip.

Evaluation of effectiveness and outcome of PKU screening and management in the State of Sergipe, Brazil / Avaliação da eficiência e desfecho da triagem e manejo da PKU no Estado de Sergipe, Brasil

Objectives: Phenylketonuria (PKU) was the first inherited metabolic disease known to cause mental retardation for which a newborn screening program (NBS) was developed. The objective of this study was to evaluate the effectiveness of PKU NBS and the management of cases in the northeastern Brazilian state of Sergipe (SE).Materials and methods: We reviewed the phenylalanine concentrations in filter-paper collected from the heel (PKUneo) of 43,449 newborns; blood concentrations obtained by venipuncture in the subjects with abnormal PKUneo; the children’s age at several phases of the program, the incidence of the disease from January 2007 to June 2008; and metabolic control of the patients.Results: The coverage of NBS/SE was 78.93%. The children’s age was 10 ± 7 days at PKUneo collection. Twelve children were recalled based on the PKUneo cutoff value at 28 ± 13 days. From these, the concentrations of phenylalanine collected by venipuncture were normal in five children. The incidence of hyperphenylalaninemia was 1/43,449, and of PKU was 1/8,690 (5 cases). One suspected subject died. Another death occurred in the cohort, in a confirmed PKU case. PKU treatment began within 51 ± 12 days of life. In the four patients under dietary phenylalanine restriction, metabolic control was often difficult.Conclusions: PKU NBS/SE has satisfactory coverage and adequate cutoff for recalling patients and diagnosis, but the onset of treatment is delayed, and follow-up metabolic control is frequently inadequate.

Objetivos: A fenilcetonúria (PKU) foi a primeira causa metabólica hereditária de retardamento mental para a qual foi desenvolvido um programa de triagem em recém-nascidos (NBS). O objetivo deste estudo foi avaliar a eficácia do NBS para a PKU e o manejo dos casos em Sergipe (SE), Brasil.Materiais e métodos: Revisamos as concentrações de fenilalanina no filtro de papel coletado do calcanhar (PKUneo) de 43.449 recém-nascidos, suas concentrações de sangue obtidas por punção venosa em indivíduos com PKUneo anormal, a idade das crianças em diversas fases do programa, a incidência da doença no período de janeiro de 2007 a junho de 2008 e o controle metabólico dos pacientes.Resultados: A cobertura da NBS/SE foi de 78,93%. A idade das crianças era de 10 ± 7 dias na coleta de PKUneo. Doze crianças foram reconvocadas com base no ponto de corte de PKUneo aos 28 ± 13 dias de idade. Destas, as concentrações de fenilalanina por venipunctura foram normais em cinco. A incidência da hiperfenilalaninemia foi 1/43.449 e de PKU foi 1/8.690 (5 casos), e um indivíduo suspeito foi a óbito. Outro óbito ocorreu na coorte em um caso de PKU confirmado. O tratamento para a PKU começou com 51 ± 12 dias. Nos quatro pacientes sob restrição de fenilalanina alimentar, o controle metabólico foi frequentemente difícil.Conclusões: PKU NBS/SE apresenta uma cobertura satisfatória e ponto de corte adequado para reconvocação e diagnóstico, mas o início do tratamento é atrasado e o controle no seguimento é frequentemente inadequado.

Comparison between the growth response to growth hormone (GH) therapy in children with partial GH insensitivity or mild GH deficiency / Comparação entre a resposta de crescimento ao tratamento com hormônio de crescimento (GH) em crianças com insensibilidade parcial ao GH ou deficiência de GH leve

Objectives: GH therapy is still controversial, except in severe GH deficiency (SGHD). The objective of this study was to compare the response to growth hormone (GH) therapy in children with partial GH insensitivity (PGHIS) and mild GH deficiency (MGHD) with those with SGHD.Subjects and methods: Fifteen PGHIS, 11 MGHD, and 19 SGHD subjects, followed up for more than one year in the Brazilian public care service, were evaluated regarding anthropometric and laboratory data at the beginning of treatment, after one year (1 st year) on treatment, and at the last assessment (up to ten years in SGHD, up to four years in MGHD, and up to eight years in PGHIS).Results: Initial height standard deviation score (SDS) in SGHD was lower than in MGHD and PGHIS. Although the increase in 1 st year height SDS in comparison to initial height SDS was not different among the groups, height-SDS after the first year of treatment remained lower in SGHD than in MGHD. There was no difference in height-SDS at the last assessment of the children among the three groups. GH therapy, in the entire period of observation, caused a trend towards lower increase in height SDS in PGHIS than SGHD but similar increases were observed in MGHD and SGHD.Conclusion: GH therapy increases height in PGHIS and produces similar height effects in MGHD and SGHD.

Objetivos: O tratamento com GH é ainda controverso, salvo na deficiência grave de GH (SGHD). O objetivo deste estudo foi comparar a resposta ao tratamento com GH em indivíduos com insensibilidade parcial ao GH (PGHIS) e na deficiência moderada do GH (MGHD) com SGHD.Sujeitos e métodos: Quinze pacientes com PGHIS, 11 com MGHD e 19 com SGHD, seguidos por mais de um ano no Sistema Único de Saúde, foram avaliados antropométrica e laboratorialmente, no início, com um ano de tratamento e na última avaliação (tempo máximo de dez anos na SGHD, quatro anos na MGHD e oito anos na PGHIS).Resultados: O escore de desvio-padrão (EDP) da estatura inicial foi menor nos indivíduos com SGHD do que naqueles com MGHD e PGHIS. Embora o aumento no EDP da estatura no primeiro ano em comparação com o inicial não fosse diferente entre os grupos, o EDP da altura no primeiro ano de tratamento permaneceu menor na SGHD que na MGHD. Não houve diferença no EDP da estatura na última avaliação entre os três grupos. O tratamento com GH, no período completo da observação, provocou uma tendência a menor aumento no EDP da estatura nos pacientes com PGHIS que naqueles com SGHD, entretanto aumentos semelhantes foram encontrados nos grupos MGHD e SGHD.Conclusão: O tratamento com GH aumentou a estatura nos indivíduos com PGHIS e produziu efeitos similares na estatura em MGHD e SGHD.

[Neonatal screening program for congenital hypothyroidism in northeast of Brazil: criteria, diagnosis and results]. / Programa de triagem neonatal para hipotireoidismo congênito no nordeste do Brasil: critérios diagnósticos e resultados.

It was evaluated the concentration of TSH in blood spot (TSHneo) of 48,039 children included in the Neonatal Screening Program (NSP) for Congenital Hypothyroidism (CH) of Sergipe (SE), a state in the northeast of Brazil. It was also evaluated the concentration of serum TSH, total T4 and free T4 in the recalled children suspicious of having CH, their age in several phases of the program, the covering and frequency of the NSP in the cases from January 2005 to August 2006, comparing them with literature data. The following parameters were used or the analysis: mean, standard deviation, median, coefficient of variation and frequency distribution. The children's age at the collection in filter-paper specimen was 10 +/- 9 days (mean+/-SD) and the TSHneo execution assay was done in the period of 31 +/- 13 days. In 2005 the covering by the NSP was about 77% in the countryside and 73% in Aracaju, the capital of Sergipe. It was verified that in 99.484% of the children included in the screening, the TSHneo varied from 0,01 to 5.20 microU/ml, decreasing according to the age and stabilizing when they were between 11 and 15 days. 248 children were recalled from the TSHneo (1/194).The concentrations of TSH, T4 and free T4 collected by venous puncture were normal in 119 children (1/404). The frequency of suspected CH was 1/485 (99 cases), of CH was 1/6005 (8 cases) and of hypothyroxinemia was 1/16013 (3 cases). Therapy for CH began within 51 +/- 12 days.

Programa de triagem neonatal para hipotireoidismo congênito no nordeste do Brasil: critérios diagnósticos e resultados / Neonatal screening program for congenital hypothyroidism in northeast of Brazil: criteria, diagnosis and results

Avaliamos as concentrações do TSH em papel-filtro colhido no calcanhar (TSHneo) de 48.039 crianças triadas do programa de triagem neonatal (PTN) para o hipotireoidismo congênito (HC) de Sergipe, as concentrações de TSH, T4 total e T4 livre colhidas em sangue periférico nas crianças convocadas suspeitas de HC, a idade nas diversas fases do programa, a cobertura e a freqüência do PTN de janeiro de 2005 a agosto de 2006, comparando-as com dados da literatura. Utilizamos para análise os seguintes parâmetros: média, mediana, coeficiente de variação e distribuição de freqüência. A idade da criança por ocasião da coleta em papel filtro no calcanhar foi 10 ± 9 dias (média ± desvio-padrão) e a idade na reali-zação do ensaio do TSHneo foi de 31 ± 13 dias. Em 2005, a cobertura do PTN, para o interior e para a capital de Sergipe, foi de 77 por cento e 73 por cento, respectivamente. Verificamos que em 99,484 por cento das crianças triadas as concentrações do TSH coletado em papel-filtro encontravam-se entre 0,01 e 5,20 µU/mL. As concentrações do TSH decrescem com o aumento da idade até estabilizar entre 11 e 15 dias de vida. Foram convocadas 248 crianças a partir do TSH coletado em papel-filtro (1/194). Na convocação, as concentrações do TSH, T4 e T4 livre coletado por punção venosa estavam normais em 119 crianças (1/404). A freqüência de HC suspeito foi de 1/485 (99 casos), de HC foi de 1/6.005 (8 casos) e de hipotiroxinemia foi de 1/16.013 (3 casos). A terapia para o HC foi iniciada com 51 ± 12 dias.

It was evaluated the concentration of TSH in blood spot (TSHneo) of 48.039 children included in the Neonatal Screening Program (NSP) for Congenital Hypothyroidism (CH) of Sergipe (SE), a state in the northeast of Brazil. It was also evaluated the concentration of serum TSH, total T4 and free T4 in the recalled children suspicious of having CH, their age in several phases of the program, the covering and frequency of the NSP in the cases from January 2005 to August 2006, comparing them with literature data. The following parameters were used or the analysis: mean, standard deviation, median, coefficient of variation and frequency distribution. The children's age at the collection in filter-paper specimen was 10 ± 9 days (Mean±SD) and the TSHneo execution assay was done in the period of 31 ± 13 days. In 2005 the covering by the NSP was about 77 percent in the countryside and 73 percent in Aracaju, the capital of Sergipe. It was verified that in 99,484 percent of the children included in the screening, the TSHneo varied from 0,01 to 5,20µU/ml, decreasing according to the age and stabilizing when they were between 11 and 15 days. 248 children were recalled from the TSHneo (1/194).The concentrations of TSH, T4 and free T4 collected by venous puncture were normal in 119 children (1/404). The frequency of suspected CH was 1/485 (99 cases), of CH was 1/6005 (8 cases) and of hypothyroxinemia was 1/16013 (3 cases). Therapy for CH began within 51 ± 12 days.