ABSTRACT Objectives Individuals with congenital isolated growth hormone deficiency (IGHD) in Northeastern Brazil have a normal lifespan with a prolonged healthspan. We hypothesize that their increased healthspan is accompanied by a reduced cognitive decline during aging. We have recently shown that these individuals have a similar total cognitive function and better attention and executive function than controls. These data were obtained using a Portuguese version of the Literacy Independent Cognitive Assessment (LICA) instrument, whose translation to facilitate cognitive research in Portuguese-speaking countries is described here. Subjects and methods In the first stage, a psychologist and a psychiatrist translated the LICA instrument from English into Portuguese, and an English teacher proofread the translation. The second stage included its synthesis and cultural adaptation, carried out by Brazilian authors, and changes in some words and images. The third stage involved an evaluation round with two referees (independent psychologists). The fourth stage involved a back translation of the instrument, which demonstrated > 95% agreement with the original version. The fifth stage included a study to verify the understanding of the questionnaire by responders. In the sixth stage, an endocrinologist and a psychiatrist approved the final Portuguese version of the instrument, which was then administered to 15 individuals with IGHD and 15 controls older than 50 years. Results The LICA instrument was applied 59 times (5 times in the pilot study, 24 in the variability studies, and 30 in the experimental step). The interobserver and intraobserver variabilities were 99% and 96%, respectively. Cronbach’s alpha was 0.76, indicating good reliability. The mean (± standard deviation) duration of the application was 39 ± 8.6 and 48.5 ± 5.8 minutes in literate and illiterate individuals, respectively. Conclusion The Portuguese version of the LICA instrument was valuable for the cognitive assessment of individuals with Itabaianinha syndrome. (IGHD aging (LICA Portuguesespeaking speaking here adaptation authors images independent psychologists. psychologists . psychologists) 95 responders 1 5 years ( 2 studies 3 step. step step) 99 96 96% respectively Cronbachs Cronbach s 076 0 76 0.76 reliability deviation 86 8 6 8. 485 48 48. 58 5. syndrome 9 07 7 0.7 4 0.

ABSTRACT Objectives: Congenital hypothyroidism (CH) can be permanent (PCH) or transient (TCH). While the importance of thyroxine in myelination of the brain is undisputed, the benefits to neurodevelopmental outcomes of TCH treatment are controversial. Our objectives were to determine predictive factors for PCH and verify its prevalence changes over time. Subjects and methods: A total of 165 children were evaluated at 3 years of age to verify the diagnosis of PCH. 130 were submitted to a two-step cluster analysis, with the aim of grouping them into homogeneous clusters. The mean incidence of PCH and TCH was calculated from 2004 to 2010 and 2011 to 2015. Results: Sixty-six children were diagnosed with PCH, and 99 were diagnosed with TCH. Eighty-one percent of PCH children and all TCH children with thyroid imaging had glands in situ. Eighty children (61.5%) were in Cluster 1, 8 children (6.2%) were in Cluster 2 and 42 children (32.3%) were in Cluster 3. No children had PCH in Cluster 1, while 87.5% of children in Cluster 2 and all children in Cluster 3 had PCH. The most important predictor for PCH was the initial serum TSH, which was marginally higher in importance than the blood spot TSH, followed by the initial serum free T4. The mean incidence of PCH (odds ratio: 1.95, 95% CI 1.36 to 2.95, p < 0.0001) and TCH (odds ratio 1.33, 95%, CI 1.02 to 1.77, p = 0,038) increased over time. Conclusions: The most important PCH predictors are the initial serum TSH and the blood spot TSH. The mean incidence of both PCH and TCH in our series increased. Objectives CH (CH (PCH . (TCH) undisputed controversial time methods 16 13 twostep two step analysis clusters 200 201 2015 Results Sixtysix Sixty six 9 Eightyone one situ 61.5% 615 61 5 (61.5% 1 6.2% 62 6 (6.2% 4 32.3% 323 32 (32.3% 875 87 87.5 T4 T odds 195 95 1.95 136 36 1.3 295 2.95 0.0001 00001 0 0001 133 33 1.33 102 02 1.0 177 77 1.77 0,038 0038 038 Conclusions (TCH 20 61.5 (61.5 6.2 (6.2 32.3 (32.3 87. 19 1.9 1. 29 2.9 0.000 0000 000 10 17 7 1.7 0,03 003 03 61. (61. 6. (6. 32. (32. 2. 0.00 00 0,0 (61 (6 (32 0.0 0, ( (3 0.

ABSTRACT In the late 19th century, José Dantas de Souza Leite, a physician born in Sergipe, published the first detailed clinical description of acromegaly under the guidance of the French neurologist Pierre Marie. In 2014, the Brazilian Society of Endocrinology and Metabolism created the “José Dantas de Souza Leite Award”, which is granted every two years to a Brazilian researcher who has contributed to the development of endocrinology. In 2022, the award was given to another physician from Sergipe, Manuel Hermínio de Aguiar Oliveira, from the Federal University of Sergipe for the description of “Itabaianinha syndrome” in a cohort of individuals with isolated GH deficiency due to a homozygous inactivating mutation in the GH-releasing hormone receptor gene. This research, which was carried out over almost 30 years, was performed in partnership with Roberto Salvatori from Johns Hopkins University and in collaboration with other researchers around the world. This review article tells the story of Souza Leite, some milestones in the history of GH, and summarizes the description of Itabaianinha syndrome.

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.

ABSTRACT Objectives To assess the evolution to permanent or transient conditions in children with positive neonatal TSH tests in Sergipe, Brazil, from 2004 to 2010. Subjects and methods Out of 193,794 screened newborns, 713 presented a neonatal TSH level higher than the local cutoff (5.2 µU/mL). From the confirmatory serum TSH values, the children were diagnosed with initial congenital hypothyroidism (CH) or suspect CH. From the evolution, they were classified as permanent CH, hyperthyrotropinemia, or transient TSH elevation. The mean incidence of each final condition was calculated for the total period of time. Results The initial diagnosis included 37 CH (18.1%) and 167 suspect CH (81.9%) cases. The final diagnosis included 46 cases of permanent CH (22.5%), 56 of hyperthyrotropinemia (27.5%), and 102 of transient TSH elevation (50.0%). Out of the 37 cases of initial CH, 23 (62.2%) had permanent CH, nine (24.3%) had hyperthyrotropinemia, and five (13.5%) had transient TSH elevation. Out of the 167 suspect CH cases, 23 (13.8%) had permanent CH, 47 (28.1%) had hyperthyrotropinemia and 97 (58.1%) had transient TSH elevation. The mean incidence after the follow up was 1:4,166 for permanent CH, 1:3,448 for hyperthyrotropinemia, and 1:1,887 for transient TSH elevation. Eighty-six percent of the children with an initial diagnosis of CH and 41.9% with suspect CH had a permanent condition (CH or hyperthyrotropinemia). Conclusions The follow-up of children with an initial diagnosis of CH or suspect CH is necessary to determine whether the disorder is permanent because predicting the evolution of the condition is difficult.

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.

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: 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.

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.

O hormônio de crescimento (GH), principal regulador do crescimento pós-natal, tem importantes ações metabólicas em diferentes tecidos, sinérgicas ou até antagônicas às do fator de crescimento semelhante à insulina tipo I (IGF-I), produzido sobretudo no fígado após ligação do GH ao seu receptor. Experimentos em modelos animais indicam um papel importante do GH na resistência a insulina, enquanto o papel do IGF-I nessa condição ainda não está completamente elucidado. Em humanos, o GH promove aumento da lipólise e da oxidação lipídica, enquanto o IGF-I desencadeia o aumento da oxidação lipídica apenas cronicamente. Enquanto as ações sobre o crescimento são tempo limitado, as ações metabólicas e cardiovasculares do eixo GH/IGF-I perduram durante toda a vida. Os potenciais efeitos anabólicos do GH têm sido utilizados em condições crônicas e hipercatabólicas, embora as investigações sobre os desfechos clínicos ainda sejam escassas. Neste artigo, pretendemos revisar as ações metabólicas do GH oriundas de modelos animais, os estudos em humanos normais e indivíduos com deficiência de GH, diabete melito tipo 1, síndrome metabólica, estados hipercatabólicos e a relação do eixo GH/IGF-I com as adipocinas, disfunção endotelial e aterogênese

Growth hormone (GH), the main regulator for post-natal growth, has important metabolic actions on different tissues, similar or opposite to insulin like growth factor I (IGF-I), mainly produced by the liver after the binding of GH to its receptor. Experiments with animal models indicate an important role of GH on insulin resistance although the IGF-I role is not yet completely established. In humans, GH promotes an increase on lypolisis and lipid oxidation, while IGF-I leads to an increase on lipid oxidation only in a chronic way. While growth actions are time-limited, metabolic and cardiovascular actions of the GH/IGF-I axis are throughout life. GH anabolic effects have been used on chronic and hypercatabolic conditions, although investigations on the clinical outcomes are still scarce. In this paper, we intend to review GH metabolic actions experienced by animal models, studies with normal humans and GH deficient individuals, individuals with diabetes mellitus type 1 and metabolic syndrome individuals, hypercatabolic states and the relationship between GH and adipokines, endothelial disfunction and atherogenesis

la hormona de crecimiento (GH), principal regulador del crecimiento postnatal, tiene importantes acciones metabólicas en diversos tejidos, sinérgicas o incluso antagónicas a las del factor de crecimiento, a semejanza de la insulina tipo I (IGF-I) producido, principalmente, en el hígado y después del vínculo del GH con su receptor. Experimentos en modelos animales indican un papel importante del GH en la resistencia a la insulina, mientras que el papel del IGF-I en esa condición, todavía no está completamente elucidado. En los humanos, el GH genera el aumento de la lipólisis y de la oxidación lipídica, mientras que el IGF-I desencadena el aumento de la oxidación lipídica solamente desde el punto de vista crónico. Mientras las acciones sobre el crecimiento son de tiempo limitado, las acciones metabólicas y cardiovasculares del eje GH/IGF-I duran toda la vida. Los efectos potenciales anabólicos del GH han sido utilizados en condiciones crónicas e hipercatabólicas, aunque las investigaciones sobre los desenlaces clínicos todavía sean escasas. En este artículo, pretendemos revisar las acciones metabólicas del GH provenientes de modelos animales, los estudios en humanos normales y en individuos con deficiencia de GH, diabetes mellitus tipo 1, síndrome metabólico, estados hipercatabólicos y la relación del eje GH/IGF-I con las adipocinas, disfunción endotelial y aterogénesis

OBJETIVOS: Deficiência de 21-hidroxilase é a forma mais comum de hiperplasia adrenal congênita (CAH-21OH). O objetivo deste estudo foi determinar, por PCR alelo-específica, a freqüência de microconversões no CYP21A2, em 16 pacientes com a forma clássica e em cinco pacientes com a forma não-clássica (NC) de CAH-21OH e correlacionar o genótipo com o fenótipo. MÉTODOS: Genótipo foi classificado em três grupos de mutações (A, B e C), baseado no grau de atividade enzimática. A técnica de PCR alelo-específico diagnosticou 74,3% (n = 26) dos 35 alelos não relacionados. RESULTADOS: As mutações mais freqüentes foram Q318X (25,7%), V281L (17,1%), I2 Splice (14,3%), I172N (14,3%) e R356W (14,3%). O genótipo foi identificado em 57,1% dos pacientes. Houve correlação genótipo-fenótipo em 91,7% dos casos. CONCLUSÃO: A mais alta freqüência da mutação Q318X (25,7%) comparada a outros estudos pode refletir variações individuais desta população do nordeste.

OBJETIVES: Deficiency of 21-hydroxylase is the most common form of congenital adrenal hyperplasia (CAH-21OH). The aim of this study was to determine, by allele-specific PCR, the frequency of microconversions of the CYP21A2, in sixteen patients with the classical forms and in 5 patients with the nonclassical (NC) form of CAH-21OH and correlate genotype with phenotype. METHODS: Genotypes were classified into 3 mutation groups (A, B and C), based on the degree of enzymatic activity. Screening for 7 microconversions by allele-specific PCR diagnosed 74.3% (n=26) of the 35 unrelated alleles. RESULTS: The most frequent mutations were Q318X (25.7%), V281L (17.1%), I2 Splice (14.3%), I172N (14.3%), and R356W (14.3%). Genotype was identified in 57.1% of the patients. We observed correlation between genotype and phenotype in 91.7% of the cases. CONCLUSION: The highest frequency for Q318X (25.7%) when compared to other studies may reflect individual sample variations in this Northeastern population.

Este artigo descreve as conseqüências puras, em longo prazo, da deficiência isolada e vitalícia do hormônio de crescimento (GH) porque usa um modelo único de resistência ao hormônio liberador do GH (GHRH), em virtude da mutação homozigótica no gene do receptor do GHRH, em uma centena de indivíduos acometidos. Elas incluem baixa estatura grave com estatura final entre -9,6 a -5,2 desvios-padrão abaixo da média, com redução proporcional das dimensões ósseas, redução do volume da adenohipófise corrigido para o volume craniano e da tireóide, do útero, do baço e da massa ventricular esquerda, todos corrigidos para a superfície corporal, em contraste com o tamanho de pâncreas e fígado, maior que o de controles, quando igualmente corrigidos. As alterações características da composição corporal incluem redução acentuada da quantidade de massa magra (kg) e aumento do percentual de gordura com depósito predominante no abdome. Nos aspectos metabólicos são encontrados aumento de colesterol total e LDL, redução de insulina e do índice de resistência à insulina homeostasis model assessment, acompanhados de aumento da proteína C reativa de alta sensibilidade e da elevação da pressão arterial sistólica nos adultos, embora sem evidências de aterosclerose precoce. Outros achados incluem resistência óssea menor, embora acima do limiar de fraturas, puberdade atrasada, fertilidade normal, paridade diminuída, climatério antecipado e qualidade de vida normal.

This article describes the long time consequences of the isolated and lifetime growth hormone (GH) deficiency using a single model of GH releasing hormone resistance (GHRH) due to a homozygous mutation in the GHRH receptor gene, in a hundred of subjects. These consequences include severe short stature with final height between -9.6 and -5.2 standard deviations below of the mean, with proportional reductions of the bone dimensions; reduction of the anterior pituitary corrected to cranial volume and the thyroid, the uterus, the spleen and left ventricular mass volume, all corrected to body surface, in contrast of pancreas and liver size, bigger than in controls, when equally corrected. Body composition features included marked reduction in the amount of fat free mass (kg) and increase of fat mass percentage, with predominant abdominal deposit. In the metabolic aspects, we find increase in the total cholesterol and LDL cholesterol; reduction of the insulin and the insulin resistance assessed by Homeostasis model assessment; increase of ultra sensitive C reactive protein and systolic body pressure in adults, although without evidences of premature atherosclerosis. Other findings include smaller bone resistance, although above of the threshold of fractures, delayed puberty, normal fertility, small parity, anticipated climacteric and normal quality of life.

Nos últimos 20 anos, o hormônio de crescimento recombinante humano (GHhr) vem sendo utilizado para tratar a deficiência do hormônio de crescimento (GH) em crianças e, mais recentemente, em adultos. Porém, a necessidade de injeções diárias compromete a aderência ao tratamento. Esforços de melhorar esta aderência incluem o uso de canetas e dispositivos desprovidos de agulha, haja vista que as bombas de infusão, nem sempre são fisiológicas e são de uso restrito. Quando a finalidade do tratamento for o crescimento, a terapêutica diária com GHhr continua a mais recomendada. Contudo, a expansão da terapêutica com GH, especialmente nos usos mais recentes e em adultos, necessitará de outras preparações. No momento atual, os secretagogos orais não têm eficácia comprovada para a utilização clínica, e as formulações de depósito de GHRH e de GH, que melhorariam a aderência dos pacientes, ainda requerem mais estudos de eficácia em longo prazo e segurança.

In the last twenty years, recombinant human Growth hormone (hrGH) has been available for the treatment of Growth Hormone Deficiency (GHD) in children and more recently in adults. However, the necessity of daily injections compromises the patient's compliance. Attempts to improve this compliance includes the use of pens and needle free devices, once the infusion pumps, not always physiologic, are of restricted use. When growth is the purpose of treatment, daily subcutaneous hrGH is still the most indicated. Nevertheless the expansion of GH replacement to new uses and especially in adults will need new preparations. Nowadays, the oral secretagogues have not proved efficacy to be used in clinical practice and the slow- release preparations of GH and GH releasing hormone that could improve the patient's compliance will need to be studied considering long term efficacy and safety.

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% e 73%, respectivamente. Verificamos que em 99,484% 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% 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 5,20µU/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.

Avaliamos o tempo gasto nas diferentes etapas do Programa de Triagem para o Hipotireoidismo Congênito (HC) e Fenilcetonúria (PKU), sua cobertura e a freqüência em Sergipe, de 1998 a 2003, e comparamos com 1995. A idade da criança na coleta foi 12 ± 11 dias (Média ± Desvio Padrão) em 2003, inferior aos 30 ± 19 dias no 2º semestre de 1995. No 2º semestre/2003, o resultado foi analisado pelo médico com 28 ± 15 dias para o HC e 25 ± 15 dias para o PKU, menor que o tempo utilizado pelo médico no 2º semestre de 1995, 80 ± 40 dias. O tempo, no 2º semestre de 2003, entre o recebimento da amostra da coleta no laboratório e a realização do ensaio foi de 6 ± 4 dias para o TSH e de 3 ± 2 dias para a fenilalanina. A cobertura, em 2003, para o Interior foi de 67% e 85% para a Capital contra 5% e 42% no 2º semestre de 1995, respectivamente. A incidência de 1998 a 2003, no Serviço Público de Saúde de Sergipe para o HC, foi de 1/4850 e para o PKU, de 1/23036. De 1998 a 2003, a terapia foi iniciada com 49 ± 17 e 51 ± 12 dias para o HC e PKU, respectivamente. A redução do tempo nas etapas do programa e o aumento da cobertura indicam uma evolução favorável do referido programa.

An evaluation was made of the timing delays in the various phases of the Screening Program for Congenital Hypothyroidism (HC) and Phenylketonuria (PKU), the coverage and incidence in the State of Sergipe from 1998 to 2003. The results were compared to the data from 1995. The age of the children in the sampling was 12 ± 11 days (mean ± standard deviation) lower than the 30 ± 19 days in the second semester of 1995. In the second half of 2003, the results were analyzed by the physician after 28 ± 15 days for HC and 25 ± 15 days for PKU, lower than 80 ± 40 days for the second semester of 1995. The period between the receipt of the samples at the laboratory and the assay in the second half of 2003 was 6 ± 4 days for TSH and 3 ± 2 days for phenylalanine. The coverage in 2003 for the interior of the State and the Capital was 67% and 85%, compared with 5% and 42% in the second semester of 1995, respectively. The incidence from 1998 to 2003 in the Public Health Service of Sergipe for HC was 1/4928 and 1/23406 for PKU. From 1998 to 2003 the therapy was initiated after 49 ± 17 days and 51 ± 12 days for HC and PKU, respectively. The reduction in the program timing delays and the increase in the coverage indicate development in the referred program.

O diagnóstico da deficiência de IGF-1 por anormalidade do eixo GH-IGF deve utilizar os parâmetros diagnósticos mais adequados para cada faixa etária e estágio puberal. Propomos o diagnóstico da deficiência de GH (DGH) baseado em uma hierarquia de dados clínicos e laboratoriais. A avaliação clínica e os exames laboratoriais gerais, incluindo função tireoideana, permitem excluir etiologias de deficiência de IGF que não as intrínsecas ao eixo GH-IGF. Nestas, a dosagem do IGF-1 sérico deve ser o primeiro hormônio a ser dosado nos grupos pré-púberes, púberes e idosos. No grupo de adultos jovens, a dosagem do ALS livre é a mais adequada. As concentrações de IGF-1 podem caracterizar 4 situações: muito reduzido, reduzido, normal e elevado. IGF-1 menor que 35µg/L ou -2 DP da média para a idade cronológica (EDP-IC) permite o diagnóstico de deficiência de IGF-1. Nesta situação, a realização de apenas um teste de secreção de GH é necessária para diferenciar deficiência e resistência ao GH. O teste de geração de IGF-1 ajuda a confirmar o diagnóstico de resistência ao GH. IGF-1 menor que 70µg/L em pré-púberes ou adultos e menor que 170µg/L em indivíduos púberes, ou entre -2 e -1 EDP-IC indicam provável deficiência de IGF-1. A realização de 2 testes de secreção de GH é recomendada; resposta sub-normal em ambos indica DGH. Exame de imagem da região hipotálamo-hipofisária deve ser realizado nos casos de DGH. Resposta normal ao teste de secreção do GH frente à forte suspeita clínica e laboratorial de deficiência de IGF-1 indica a realização de perfil noturno de GH para afastar o diagnóstico de disfunção neurossecretora de GH. IGF-1 maior que -1 DP, mas menor que a média para idade cronológica sugere ausência de deficiência de IGF-1. Concentrações altas de IGF-1 impõem a dosagem das IGFBPs e consideração da resistência ao IGF-1. Apesar das dificuldades, todo o esforço deve ser feito no sentido de diagnosticar adequadamente as alterações do eixo GH-IGF para instituir a terapia apropriada.

The diagnosis of IGF-1 deficiency due to GH-IGF abnormalities must use the most appropriate parameters for age and pubertal stage. We propose the diagnosis of growth hormone deficiency (GHD) based in an hierarchy of clinical and laboratory data. Clinical evaluation and general laboratory tests, e.g. thyroid tests, permit to exclude other causes of IGF deficiency that are not intrinsic to the GH-IGF axis. In these, the measurement of serum IGF-1 must be the first step in prepubertal, pubertal and elderly groups of patients whereas free ALS is better among young adults. IGF-1 analysis can revel 4 different situations: very low, low, normal and high levels. IGF-1 lower than 35µg/L or -2 SD of mean for chronological age (SDS-CA) allows diagnosis of IGF-1 deficiency. In this situation, only 1 test for GH secretion is necessary to differentiate GH deficiency and GH insensitivity. IGF-1 generation test can confirm GH insensitivity. IGF-1 lower than 70µg/L in prepubertal or adult patients and IGF-1 lower than 170µg/L in pubertal subjects, or between -2 and -1 SDS-CA, suggest IGF-1 deficiency. Two tests to assess GH secretion are recommended. Sub-normal GH peak in 2 tests confirm the diagnosis of GHD. These patients should undergo image test in order to search for hypothalamus-pituitary morphological abnormalities. Normal GH peak prompts to nocturnal GH physiological profile in order to run out the possibility of neurosecretory GH dysfunction when there are strong clinical evidences of IGF deficiency and low serum IGF-1 levels. IGF-1 higher than -1 SD but lower than the mean for chronological age suggests no IGF-1 deficiency. High IGF-1 level imposes the IGFBPs determination and consideration of IGF-1 resistance. Although the difficulties, all effort has to be made in order to diagnose properly the abnormalities of GH-IGF axis and install the adequate therapy.

Nesta pesquisa fizemos uma avaliação da oportunidade nas diversas etapas que compõem o mecanismo de detecção do Programa de Triagem para o Hipotireoidismo Congênito, sua cobertura e a freqüência de casos no serviço público de saúde em Sergipe. Levantamos a idade de todas as crianças (2994) submetidas à triagem para detecção neonatal do hipotireoidismo congênito e fenilcetonúria em suas diversas fases, no período de junho a dezembro de 1995. A idade da criança na coleta do exame, foi de 30±19 dias (média±DP). A idade, quando o resultado da triagem chegou ao centro de saúde, foi de 48±7 dias, quando entregue à família, de 66±18 dias e quando visto pelo pediatra da unidade, de 80±40 dias. Crianças com resultados alterados são referidas para serviços especializados sem nenhum pacto de prioridade. Com relação à cobertura, apenas 5% das crianças do interior do Estado e 42% da capital foram examinadas. A morosidade nas etapas do programa e a baixa cobertura de crianças submetidas ao teste de triagem comprovam a hipótese de que o referido programa de governo não está atingindo seus objetivos principais que são o tratamento oportuno e a cobertura a todas as crianças recém-nascidas, a fim de que sejam prevenidas suas seqüelas.

In this research we evaluated the time spent in several follow-up steps of the screening mechanism of the "Early Detection of Congenital Hypothyroidism Program", its coverage and its occurrence in the civil health service in Sergipe. To accomplish this purpose, we raised data for all the infants (2994) that had been submitted to screening for neonatal hypothyroidism and phenylketonuria in the period from June to December of 1995. We verified that the age at the time of the examination was 30±19 days (mean±SD). When the result arrived at the Healthy Center was 48±7 days, the families were informed 66±18 days, the infants were reviewed by the Health Center pediatrician at the age of 80±40 days. Children with altered results were still referred to specialized centers without priority. Regarding the coverage, only 5% of the infants from the interior of the state and 42% from the capital, on average, were covered by the test. This extended process and the inefficient coverage of infants submitted to screening, confirm the hypothesis that this government program is not achieving its main objectives: the timely treatment and the coverage of all newborn infants, in order to prevent their impact.