Hormona de crecimiento en sangre de papel filtro para el diagnóstico de deficiencia de hormona de crecimiento / Growth hormone of dried blood spot for the diagnosis of growth hormone deficiency

INTRODUCCIÓN: El diagnóstico de deficiencia de hormona de crecimiento (DHC) es difícil de establecer, y se puede asociar a serias complicaciones, especialmente en el período neonatal. La prueba de estímulo de secreción de hormona de crecimiento (HC) se considera de elección para el diagnóstico, pero presenta complicaciones metodológicas y se asocia a efectos adversos. Los neonatos presentan aumento de la secreción de HC de forma fisiológica, siendo una ventana diagnóstica. OBJETIVO: Evaluar si la muestra de sangre en papel filtro tomada en el período neonatal, en contexto del tamizaje neonatal de hipotiroidismo congénito y fenilcetonuria, permite diferenciar pacientes con DHC, de los que no la presentan. PACIENTES Y MÉTODO: Estudio de casos y controles mediante determinación de concentración de HC en sangre de papel filtro extraída en período neonatal, comparando controles con DHC con casos con deficiencia descartada. Se realizó extracción de la muestra del papel filtro, obteniendo dos discos de 0,125 pulgada por cada uno de los pacientes desde el centro de la mancha de sangre del papel, para un ELISA de HC humana altamente sensible basado en el uso de anticuerpos policlonales dirigidos contra la HC humana recombinante de 22kDa de peso molecular. RESULTADOS: Se obtuvo un total de 7 casos de DHC y 10 controles. La mediana de concentración de HC de papel filtro en los casos es 2,0 ng/ml (Rango intercuartil 3,6 ng/ml) y controles 2,05 ng/mL (RIC 2,0 ng/ml), U de Mann-Withney 30,5 (p = 0,68). Los dos casos con deficiencia de hormonas hipofisarias múltiples (DHHM) presentan concentraciones menores a 1 ng/ml. CONCLUSIÓN: La muestra de papel filtro no permitió diferenciar a los pacientes con DHC de los casos controles, aunque los casos con DHHM presentaron concentraciones mucho menores, en comparación a la deficiencia de hormona de crecimiento aislada (DHCA).

INTRODUCTION: The diagnosis of growth hormone deficiency (GHD) is difficult to determine, and could be associated with severe complications, especially in the neonatal period. The stimulation test of growth hormone (GH) secretion is considered the gold standard for diagnosis, but it has methodological complications and is associated with adverse effects. Neonates present physiological increased secretion of GH, representing a diagnostic window. OBJECTIVE: To evaluate if the dried blood spot on filter paper obtained in the neonatal period, as part of a neonatal screening for con genital hypothyroidism and phenylketonuria, allows differentiating patients with GHD from those who do not have it. PATIENTS AND METHOD: Study of cases and controls by measuring the GH concen tration in dried blood spot on filter paper obtained in the neonatal period, comparing controls with GHD with cases with discarded deficiency. The sample was extracted from the filter paper, obtaining two 0.125 inch discs per each patient from the center of the blood spot on the paper, for a highly sen sitive ELISA assay for human GH based on the use of polyclonal antibodies against 22 kDa recom binant human GH. RESULTS: Seven cases of GHD and ten controls were obtained. The median GH concentration of the dried blood spot in the cases is 2.0 ng/ml (Interquartile range 3.6 ng/ml) and 2.05 ng/ml (Interquartile range 2.0 ng/ml) in the controls, Mann-Whitney U test 30.5 (p = 0.68). The two cases with multiple pituitary-hormone deficiency (MPHD) present concentrations lower than 1 ng/ml. CONCLUSION: The dried blood spot sample did not differentiate GHD patients from control cases, although MPHD cases present much lower concentrations compared to isolated growth hor mone deficiency (IGHD).

Clonidine-stimulated growth hormone concentrations (cut-off values) measured by immunochemiluminescent assay (ICMA) in children and adolescents with short stature

OBJECTIVES: To establish cut-off values for growth hormone concentrations using clonidine as a secretagogue and an immunochemiluminescent assay as the method of measurement and to analyze the response time as well as the influence of gender, nutritional status and pubertal stage. METHODS: A total of 225 tests were performed in 3 patient groups, categorized as group 1 (normal), group 2 (idiopathic short stature) and group 3 (growth hormone deficiency). Among the 199 disease-free individuals, 138 were prepubertal, and 61 were pubertal. Clonidine (0.1 mg/m2) was orally administered, and the growth hormone level was measured by immunochemiluminescent assay. The growth hormone peak and the difference between the growth hormone peak and the baseline level were then analyzed. Statistical analyses were performed using Student’s t-test or the Mann-Whitney test and Kruskal-Wallis test followed by Dunn’s post hoc test. Cut-off values were determined using a receiver operating characteristic curve. RESULTS: Group 1 and group 2 had no difference in growth hormone peak, gender, body mass index standard deviation score, or pubertal stage. Group 3 exhibited a significantly lower growth hormone peak than the other groups did. The receiver operating characteristic curve demonstrated that growth hormone concentrations ≥ 3.0 ng/mL defined responsiveness to clonidine. In total, 3.02% of individuals in group 1 and group 2 were considered false positive, i.e., these children lacked growth hormone deficiency and had a peak below 3.0 ng/mL. CONCLUSION: Clonidine-stimulated growth hormone concentrations ≥3 ng/mL, as measured by immunochemiluminescent assay, suggest responsiveness to the stimulus regardless of gender, body mass index standard deviation score or pubertal stage.

Lower waist circumference in mildly-stunted adolescents is associated with elevated insulin concentration / A menor circunferência da cintura em adolescentes de baixa estatura leve está relacionada à concentração elevada de insulina

Objective: Augmented waist circumference (WC) is associated with non-communicable diseases and could represent a valuable marker in screening for metabolic dysfunctions in subjects with insufficient linear growth. The objective of the present study was to determine whether bio-chemical and hemodynamic parameters and waist circumference vary between mildly-stunted and non-stunted adolescents from impoverished communities of São Paulo, Brazil. Methods: The cross-sectional study involved 206 subjects, aged between 9 and 19 years and living in impoverished areas of São Paulo, Brazil. The sample population was divided according to height-for-age Z-score (HAZ) into stunted (−1 > HAZ ≥ −2) and non-stunted (HAZ ≥ −1) groups, and was sub-divided according to gender. Logistic regression analysis was employed to compare individuals with elevated (> 75th percentile) insulin concentrations. The receiver operating characteristic curves were constructed to determine WC cut-off points that could be used to identify stunted and non-stunted individuals with elevated insulin concentrations. Results: WC cut-off points of 58.25 cm and 67.2 cm allowed for correct classification of 90.7% of stunted and 88.7% of non-stunted individuals in the studied population. While the sensitivity of the model was high for stunted and non-stunted subjects (98.8% and 97.2%, respectively), the specificity was modest (57.1% and 41.2%, respectively). Conclusion: The results presented herein suggest that an increase in plasma insulin is one of the primary metabolic modifications in stunted individuals, and that this alteration could be identified at a lower WC cut-off point than in non-stunted counterparts. .

Objetivo: A circunferência da cintura (CC) aumentada está relacionada a doenças não transmissíveis e pode representar um indicador valioso no exame de verificação de disfunções metabólicas em indivíduos com crescimento linear insuficiente. O objetivo deste estudo foi determinar se os parâmetros bioquímicos e hemodinâmicos e a circunferência da cintura variam entre adolescentes de baixa estatura leve e de estatura normal de comunidades pobres de São Paulo, Brasil. Métodos: O estudo transversal envolveu 206 indivíduos com idades entre 9 e 19 anos que moram em áreas pobres de São Paulo, Brasil. A população da amostra foi dividida, de acordo com o escore z de estatura por idade (HAZ), em um grupo de baixa estatura (−1 > HAZ ≥ −2) e um de estatura normal (HAZ ≥ −1), e subdividida de acordo com o gênero. A análise de regressão logística foi empregada para comparar indivíduos com concentrações elevadas de insulina (> 75° percentil). As curvas de característica de operação do receptor foram construídas para determinar os pontos de corte de CC que poderiam ser usados para identificar os indivíduos de baixa estatura e de estatura normal com concentrações elevadas de insulina. Resultados: Os pontos de corte de CC de 58,25 e 67,2 cm permitiram a classificação correta de 90,7% de indivíduos de baixa estatura e 88,7% de indivíduos de estatura normal na população estudada. Embora a sensibilidade do modelo fosse alta para indivíduos de baixa estatura e de estatura normal (98,8% e 97,2%, respectivamente), a especificidade foi pequena (57,1% e 41,2%, respectivamente). Conclusâo: Os resultados apresentados neste instrumento sugerem que um aumento na insulina plasmática é uma das principais ...

Efficacy of Short-Term Growth Hormone Treatment in Prepubertal Children with Idiopathic Short Stature

PURPOSE: It has been reported that daily recombinant human growth hormone (GH) treatment showed beneficial effects on growth in prepubertal children with idiopathic short stature (ISS). The present study aimed to validate the GH (Eutropin(R)) effect on growth promotion and safety after short-term GH treatment. MATERIALS AND METHODS: This study was an open-label, multicenter, interventional study conducted at nine university hospitals in Korea between 2008 and 2009. Thirty six prepubertal children with ISS were enrolled in this study to receive 6-month GH treatment. Yearly growth rate, height standard deviation score (SDS), and adverse events were investigated during treatment. RESULTS: After 26 weeks of GH treatment, the height velocity significantly increased by 6.36+/-3.36 cm/year (p<0.001). The lower end of one-sided 95% confidence interval was 5.22 cm/year, far greater than the predefined effect size. The gain in height SDS at week 26 was 0.57+/-0.27 (p<0.0001). Bone age significantly increased after GH treatment, however, bone maturation rate (bone age for chronological age) showed limited advancement. This 26-week GH treatment was effective in increasing serum levels of insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 from baseline (p<0.0001). Eutropin was well tolerated and there were no withdrawals due to adverse events. No clinically significant changes in laboratory values were observed. CONCLUSION: This 6-month daily GH treatment in children with ISS demonstrated increased height velocity, improved height SDS, and increased IGF-I and IGFBP-3 levels with a favorable safety profile.

Eixo hormônio de crescimento/fator de crescimento semelhante à insulina-1: um possível fator não nutricional para o retardo de crescimento em crianças com paralisia cerebral / Growth hormone/insulin-like growth factor-1 axis: a possible non-nutritional factor for growth retardation in children with cerebral palsy

OBJETIVO: Avaliar o eixo hormônio de crescimento (GH)/fator de crescimento semelhante à insulina 1 (IGF-1) como possível fator não nutricional para o retardo de crescimento em crianças com paralisia cerebral (PC). MÉTODOS: Um estudo caso-controle foi realizado em um hospital universitário terciário. Trinta crianças com PC [sete crianças com crescimento normal (PC-N) e 23 com retardo de crescimento (PC-R)], 30 crianças com desnutrição proteico-energética (DPE), e 30 crianças sadias (grupo REF) tiveram avaliados seus parâmetros de crescimento, IGF-1 sérico, GH basal, e pico de GH após estímulo com insulina. RESULTADOS: Os pacientes com DPE apresentaram níveis basais mais elevados de GH do que os grupos PC-N, PC-R e REF (p = 0,026, p < 0,001 e p = 0,001, respectivamente). Após estímulo com insulina, os grupos PC-N, PC-R e DPE apresentaram níveis menores de GH se comparados ao grupo REF (p = 0,04, p = 0,007, p = 0,036, respectivamente). O nível de IGF-1 foi menor no grupo PC-R se comparado aos grupos PC-N e REF (p = 0,037 e p < 0,001, respectivamente), e no grupo DPE se comparado aos grupos PC-N e REF (p < 0,001 e p < 0,001, respectivamente). CONCLUSÕES: Os pacientes com PC-R não demonstraram a mesma resposta basal elevada do GH apresentada pelos pacientes com DPE, e responderam de forma inadequada ao estímulo com insulina, mas apresentaram níveis de IGF-1 comparáveis aos dos pacientes com DPE. Por outro lado, os pacientes com PC-N tiveram comportamento semelhante ao dos controles com relação aos níveis basais de GH e IGF-1, mas não responderam adequadamente ao estímulo com insulina. O grupo DPE apresentou GH basal elevado e IGF-1 baixo. Esses achados sugerem que fatores não nutricionais contribuem para o retardo de crescimento em crianças com PC.

OBJECTIVE: To assess growth hormone (GH)/insulin like growth factor-1 (IGF-1) axis as a possible non-nutritional factor for growth retardation in children with cerebral palsy (CP). METHODS: A case-control study was conducted at a tertiary university hospital. Thirty children with CP (seven children with normal growth [CP-N] and 23 with retarded growth [CP-R]), 30 children with protein energy malnutrition (PEM), and 30 healthy children (REF group) underwent an assessment of growth parameters, serum IGF-1, basal GH, and peak GH after stimulation with insulin. RESULTS: PEM patients had higher basal GH levels than CP-N, CP-R and REF groups (p = 0.026, p < 0.001, and p < 0.001 respectively). After insulin stimulation, CP-N, CP-R, and PEM patients had lower GH levels compared to the REF group (p = 0.04, p = 0.007, and p = 0.036 respectively). IGF-1 levels were lower in CP-R group compared to CP-N and REF groups (p = 0.037 and p < 0.001 respectively), and in PEM group compared to CP-N and REF groups (p < 0.001 and p < 0.001 respectively). CONCLUSIONS: CP-R patients failed to demonstrate the same high basal GH response as PEM patients, and responded inadequately to the insulin stimulation test, but they had IGF-1 levels comparable to those of PEM patients. On the other hand, CP-N patients behaved as controls regarding their basal GH and IGF-1 levels, but failed to respond adequately to the insulin stimulation test. The PEM group presented high basal GH and low IGF-1 levels. These findings suggest that non-nutritional factors contribute to growth retardation in CP children.

Association between anthropometric hormonal measurements and bone mineral density in puberty and constitutional delay of growth and puberty / Asociación entre las mediciones hormonales antropométricas y la densidad mineral ósea en la pubertad y el retraso constitucional del crecimiento y la pubertad

The aim of this study is to evaluate the acquisition of bone mineral in healthy children throughout puberty and in children with constitutional delay of growth and puberty (CDGP), and to relate changes in bone mass to age, weight, height, sitting height, body mass index and sex hormones in healthy boys. A total of 90 boys: 15 boys with CDGP and 75 healthy boys in different pubertal stages were examined. The number of children assigned to each Tanner stages was 15. Although bone age, weight and Body Mass Index (BMI) were significantly higher in stages II, III, IV, V compared to stage I and CDGP, mean height and sitting height values were higher in stages III, IV, V compared to stage I and CDGP. Also, serum FSH, LH, oestradiol, total and free testosterone levels progressively increased, although serum sex hormone binding globulin (SHBG) levels decreased, in healthy children with progression of sexual development. Significant increase was observed for serum oestradiol levels at stage II and above (p < 0.001), for serum total and free testosterone levels at stage III and above (p < 0.001), for serum FSH and LH levels at stage IV and above (p < 0.01 and p < 0.001) respectively. Also, it was shown that bone mineral content (BMC) and bone mineral density (BMD) measurements were significantly higher for pubertal stage lll and above groups according to both the CDGP group and stage I group. When BMD and BMC measurements of children with CDGP (0.62 ± 0.05 gr/cm² and 23.4 ± 2.8 gr) were compared with bone age, age, BMI and height-matched controls, there was no significant difference between children with CDGP and controls, except for age. Bone mineral density and BMC measurements in children with CDGP were significantly lower than those of age-matched controls (for pubertal stage lll: p < 0.05, for pubertal stage IV: p < 0.01). The strongest correlation coefficients were found between BMD and height among auxological parameters (r = 0.63, p < 0.001) and serum oestradiol levels among hormones (r = 0.55, p < 0.001). The most important findings of this investigation was the determination of body composition and hormonal measurement changes during puberty in boys; oestradiol was the most potent determinant of BMD among pubertal boys. We suggested that there is a critical age period for accumulation of bone mass according to the results. Longitudinal studies will elucidate why sufficient mineralization does take place after puberty starts in CDGP.

El objetivo de este estudio es evaluar la adquisición de mineral óseo del hueso en niños saludables a través de la pubertad y en niños varones con retraso constitucional del crecimiento y la pubertad (RCCP), y relacionar los cambios de masa ósea a la edad, el peso, la altura, la altura sentado, el índice de masa corporal, y las hormonas del sexo en niños varones saludables. Examinamos un total de 90 niños, 15 niños con RCCP y 75 niños saludables en diferentes etapas de la pubertad. El número de niños asignados a cada etapa de Tanner fue 15. Aunque la edad ósea, el peso y el IMC fueron significativamente más altos en las etapas II, III, IV, V, comparados con la etapa I y el RCCP; la altura promedio y los valores de la altura sentado fueron más altos en las etapas III, IV, V, comparados con la etapa I y el RCCP. Por otra parte, los niveles séricos de HEF, HL, estradiol y testosterona total y libre, aumentaron progresivamente, aunque los niveles séricos de SHBG disminuyeron en los niños saludables con el avance del desarrollo sexual. Se observó un aumento significativo en los niveles de estradiol sérico en la etapa II y por encima (p <0.001), en los niveles séricos de testosterona libre y total en la etapa II y por encima (p < 0.001), y en los niveles séricos de HEF, HL en la etapa IV y por encima (p < 0.01 y p < 0.001). Además se observó que las mediciones del contenido mineral óseo (CMO) y la densidad mineral ósea (DMO) fueron significativamente mayores en la etapa III de la pubertad y grupos por encima, de acuerdo tanto con el grupo de RCCP cómo el grupo de la etapa I. Cuando las mediciones de DMO y CMO de niños con RCCP (0.62 ± 0.05 gr/cm² y 23.4 ± 2.8 gr) fueron comparadas con la edad ósea, la edad, IMC y los controles pareados por altura, no se halló ninguna diferencia significativa entre los niños con RCCP y los controles, excepto la edad. Las mediciones de DMO y CMO en niños con RCCP fueron significativamente más bajas que las de los controles pareados por edad (para la etapa III de la pubertad: p < 0.05; para la etapa IV de la pubertad: p < 0.01). Los coeficientes de correlación más fuertes se encontraron entre la DMO y la altura entre los parámetros auxológicos (r = 0.63, p < 0.001), los niveles séricos de estradiol entre las hormonas (r = 0.55, p < 0.001). Los hallazgos más importantes de esta investigación fueron la determinación de la composición corporal y los cambios en la medición hormonal durante la pubertad en los muchachos; el estradiol fue el determinante más potente de la DMO entre los niños en la pubertad. Sugerimos que hay un periodo de edad crítico para la acumulación de masa ósea de acuerdo con nuestros resultados. Los estudios longitudinales esclarecerán por qué se produce suficiente mineralización después de que la pubertad empieza en RCCP.

Growth and bone mineralization in patients with juvenile idiopathic arthritis.

OBJECTIVE: To investigate growth, development and bone mineralization of children with juvenile idiopathic arthritis (JIA). METHODS: Thirty patients between 4-17 years of age (mean 11.34 +/- 3.88) resistant to therapy were studied. Enrollment began in November 1999 and continued through November 2004 and children with chronic disease were excluded. Data like height, weight, medications and acute phase reactants were obtained from medical records. On study-visit, puberty was assessed by physical examination and bone mineral density (BMD) was measured. Serum Ca, P, ALP, insulin-like growth factor-1 (IGF-1) and urinary Ca/Cr and hydroxyproline /Cr levels were measured. Results were compared with the control group that consisted of 30 cases of similar age and gender. RESULTS: Patients with JIA had decreased height standard deviation score (SDS) and growth retardation. BMD of the cases in the study group was lower than the control group (p< 0.05). Patients who were at younger age at the onset of the disease had lower BMD. Among the drugs, only steroids had a negative effect on growth. Serum IGF-1 levels of the study group were significantly lower than the control group (p< 0.0001). CONCLUSION: Early diagnosis and suppression of disease activity is important in prevention of osteoporosis and growth retardation in children with JIA. BMD has to be measured yearly in patients for accurate diagnosis of osteoporosis. Vitamin D and Ca-rich nutrition with promotion of physical activity and controlled use of steroids may protect the children against bone loss.

The usefulness of serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) for evaluation of children with short stature.

The diagnostic value of serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) was studied in 24 growth hormone deficient (GHD) and 36 normal variant short stature (NVSS) children. The serum IGF-1 and IGFBP-3 concentrations were markedly below the 5th centile for chronological age in all 24 GHD children, but were in the low normal range for age in most of the NVSS children. The concentrations of IGF-1 and IGFBP-3 significantly correlated with peak GH concentration, height age, and bone age. To account for the age- and sex-dependency, IGF-1 and IGFBP-3 levels were transformed to standard deviation score (SDS). Using the -2 SDS as a cut-off level to differentiate between GHD and NVSS, the diagnostic value of IGF, as well as IGFBP-3, showed sensitivity 100 per cent, specificity 66.7 per cent, and accuracy 80 per cent. The combined use of IGF-1 and IGFBP-3 < -2 SDS improved the diagnostic value with sensitivity 100 per cent, specificity 77.8 per cent, and accuracy 86.7 per cent. We concluded that the serum concentrations of IGF-1 and IGFBP-3 could reflect endogenous GH secretion and could be used as a screening evaluation of GH status in short children.

Measurement of serum free IGF-I in diagnosis of growth hormone deficiency.

Serum levels of total insulin-like growth factor-I (IGF-I) are growth hormone (GH) dependent and can be used as the screening tool for GH deficient status. However, most of them are bound to IGF-binding proteins, leaving less than 1 per cent in the free or unbound forms which represent the active biological fractions. Serum free IGF-I levels were measured by radioimmunoassay (IRMA) in 48 short children with various conditions. We found that the means +/- SEM of free IGF-I in children with panhypopituitarism (PAN) and complete growth hormone deficiencies (cGHD) were significantly lower than those in sex and age matched normal children (0.02 +/- 0.01 vs 2.01 +/- 0.7 ng/ml, p = 0.0006 and 0.42 +/- 0.18 vs 1.72 +/- 0.27 ng/ml, p = 0.0007 respectively) but not in children with partial growth hormone deficiencies (pGHD) (0.91 +/- 0.3 vs 1.97 +/- 0.4 ng/ml, p = 0.27) and idiopathic short stature (ISS) (0.94 +/- 0.3 vs 1.95 +/- 0.6 ng/ml, p = 0.13). However, when we classified the pGHD children into 2 groups according to IGFBP-3 SDS for normal Thai children, we found that the mean of free IGF-I levels in pGHD children with IGFBP-3 SDS < or = -1.3 was significantly lower than that of the controls. (0.68 +/- 0.55 vs 2.66 +/- 0.71 ng/ml, p = 0.04) In conclusion, the measurement of free IGF-I level can be used to evaluate the GH status of short children and might be used as a guide when starting treatment.

Thyroid function in thalassaemia major.

INTRODUCTION: Short stature is common in thalassaemia major. Hypothyroidism resulting from haemosiderosis has been implicated, but this complication has not been investigated in Sri Lanka. OBJECTIVES: To estimate the thyroid hormone level of patients with thalassaemia major and correlate height with age, iron status and thyroid hormone level. SETTING: University Unit, Lady Ridgeway Hospital, Colombo. DESIGN: A cross-sectional comparative study. METHODS: 33 patients with thalassemia major (19 males) aged 2 years 6 months to 23 years were studied. 21 healthy age and sex matched subjects from the same neighbourhood as the patients served as controls. Anthropometric measurements, skeletal maturity, serum ferritin and thyroid hormone levels were estimated. RESULTS: The height centiles and height standard deviation scores (SDS) were significantly lower in the patient group. Skeletal maturation was delayed by more than 1 year in 69% of patients. Undernutrition was not seen. The height SDS showed significant reduction with age (r = -0.5, 95% confidence limit -0.72 to -0.18) and with elevated serum ferritin levels (r = -0.8, 95% confidence limit = -0.9 to 0.62). Serum ferritin levels were elevated in the entire patient group with 70% being heavily iron overloaded (serum ferritin > 7000 ng/ml). The thyroxine (T4) levels were within the normal range in all 33 patients. The TSH levels were normal in 32 patients. The patient too had a normal T4 level. The control group had TSH levels comparable with the patients. CONCLUSION: Hypothyroidism was not present in our iron overloaded thalassaemic patients. The thyroid hormone levels were similar in patients with mild and heavy iron overload. We conclude that routine surveillance for hypothyroidism is unnecessary in thalassaemia major. Other causes for delayed skeletal maturation and short stature need investigation.

Profile of growth hormone deficiency in Bombay.

Of the 430 children referred for the evaluation of short stature 100 (23%) were confirmed to have growth hormone deficiency. The male to female ratio was 1.94:1. Less than 10% belonged to the lower socio-economic group. Most of the cases (73%) presented between the ages of 6-15 years though growth failure was usually recognised earlier. Minimum of two stimulation tests were performed in each case. Seventy five GH deficient children had idiopathic GHD (IGHD) and 31% of these were familial. Fourteen had organic causes and 11 had GH resistance. Of 75 with IGHD, 18 had abnormal deliveries, breech or birth asphyxia. Multitropic pituitary hormone deficiency (MPHD) was found in 9/75 cases of idiopathic GHD and in three of the organic group. The height age was much more retarded than chronologic age in the GH resistant group (p less than 0.05) and the HA/BA ratio was also lowest in this group (p less than 0.001). Growth velocity was less than 4 cm/year in all the GHD children but was lowest in those with MPHD. The interesting feature of this study is the marked predominance of the familial cases 31% and a high incidence of growth hormone resistant cases (11%).

Growth hormone deficiency in Sri Lanka: a preliminary study.

Growth hormone deficiency is a recognised cause of severe short stature. A community of 16,001 Sri Lankan children aged between 5 and 6 years was screened for short stature using a simple growth chart, and a sample of 172 identified as short was investigated for the aetiology. Growth hormone deficiency was confirmed in 12 out of the 172 children using the insulin-induced hypoglycaemia test. Another group of 27 out of the 172 children who could potentially benefit from growth hormone therapy were identified using an exercise screening test. Growth hormone deficiency has not been previously documented in Sri Lanka.

Etiología del retraso estatural en hijos de adolescentes / Etiology of growth retardation in children from adolescent mothers

Se estudió la influencia de la edad materna, factores nutricionales y hormonales que pudieran explicar la mayor prevalencia de retraso de talla detectado en hijos de madres adolescentes de nivel socioeconómico medio bajo. Se encontró que sólo los lactantes con retraso de talla, hijos de adolescentes, tenían significativo retraso de la maduración ósea con respecto a la edad cronológica (14,8 +-4,1 vs 18,2+-2,2 meses respectivamente). El conjunto de lactantes con retraso de talla tenía concentraciones de Zn (85,7+-13,3 vs 94,6+-17,9 ug/dl), Cu (106,2+-32,5 vs 122,0+-31,8 ug/dl) y Hb (11,7+-2,1 vs 12,8+-2,1 ug/dl) significativamente menores que el grupo con talla adecuada. Sin embargo, no se enciontraron diferencias en estos parámetros de acuerdo a la edad materna. No hubio disparidad en las concentraciones plasmáticas de hormonas tiroideas, tirotropina y en la respuesta de hormona de crecimniento al estímulo con L-Dopa. Pensamos que la etiología del retraso de talla de los hijos de adolescentes y adultas es similar. Es posible que la mayor prevalencia del retraso de talla en hijos de adolescentes se deba a una mayor frecuencia o a un impacto mas intenso de los factores ambientales analizados. De todo lo anterior se desprende la importancia de una especial preocupación por estas últimas madres que constituyen un grupo con riesgo de alteraciones del crecimiento y desarrollo en sus hijos

Diagnostic value of insulin-like growth factor-I in short stature

For the present, to determine growth hormone(GH) deficiency in patients with short stature, many provocative tests using various pharmacological agents such as glucagon, insulin, clonidine, arginine, growth hormone releasing factor, etc. should be done. These are not only complicated but are also misleading in some patients. In search of a simple and accurate method of detecting GH deficiency that may replace the more complicated provocative tests, we measured basal plasma insulin-like growth factor-I (IGF-I) to see the correlation with the peak GH values in the GH stimulation test. But, in each group of patients with different types of short stature, IGF-I values were poorly correlated. In addition, IGF-I values of the patients with short stature compared to the age- and sex-matched normal ranges showed a significant overlap, and the difference between the proportion of patients with subnormal values in GH deficient patients and non-GH deficient patients was not prominent. Nevertheless, in response to human growth hormone (hGH) administration, both the yearly growth rate and IGF-I levels increased conspicuously. Therefore, even though it may not be feasible to use IGF-I as a single diagnostic measure of patients with short stature, the change in IGF-I values in the follow up of hGH therapy may well represent the response to hGH.

Diagnostic value of insulin-like growth factor-I in short stature

For the present, to determine growth hormone(GH) deficiency in patients with short stature, many provocative tests using various pharmacological agents such as glucagon, insulin, clonidine, arginine, growth hormone releasing factor, etc. should be done. These are not only complicated but are also misleading in some patients. In search of a simple and accurate method of detecting GH deficiency that may replace the more complicated provocative tests, we measured basal plasma insulin-like growth factor-I (IGF-I) to see the correlation with the peak GH values in the GH stimulation test. But, in each group of patients with different types of short stature, IGF-I values were poorly correlated. In addition, IGF-I values of the patients with short stature compared to the age- and sex-matched normal ranges showed a significant overlap, and the difference between the proportion of patients with subnormal values in GH deficient patients and non-GH deficient patients was not prominent. Nevertheless, in response to human growth hormone (hGH) administration, both the yearly growth rate and IGF-I levels increased conspicuously. Therefore, even though it may not be feasible to use IGF-I as a single diagnostic measure of patients with short stature, the change in IGF-I values in the follow up of hGH therapy may well represent the response to hGH.

El uso del factor liberador de hormona de crecimiento (GRF) como prueba de reserva hipofisiaria para hormona de crecimiento (hGH) / Growth hormone releasing factor (GRF) as a test of pituitary reserve of growth hormone (hGH)

Diferentes pruebas inespecíficas de estimulación se emplean para estudiar la capacidad de la hipófisis para secretar hormona del crecimiento, pero ninguno es totalmente confiable. Los autores emplearon factor liberador de hormona del crecimiento (1microng x kg de peso corporal endovenoso) en 6 niños de talla baja pero sin afecciones endocrinas y en 4 pacientes con deficiencia comprobada de hormona del crecimiento. La concentración plasmática máxima de la hormona en los niños normales, durante la prueba, fue de 47,4 + ou - 15,4 ng x ml. Tres de los cuatro pacientes no mostraron respuesta a la provocación y en el cuatro la concentración plasmática máxima alcanzada fue de 5,3 ng x ml sugiriendo un origen hipotalámico para su deficiencia hormonal. El empleo de factor liberador sería de utilidad en el futuro para el diagnóstico y tratamiento de la deficiencia de hormona del crecimiento