RESUMO
El Síndrome de Turner es un desorden cromosómico causado por haploinsuficiencia completa o parcial de uno de los cromosomas sexuales. Incidencia 1: 2500 recién nacidas vivas. Clínicamente las pacientes presentan talla baja, un espectro amplio de anomalías somáticas y disgenesia gonadal. Desde el año 1968 hasta el presente se estudiaron clínica y citogenéticamente 630 niñas con fenotipo de Turner, sin ambigüedad genital y con cariotipos anormales, quienes consultaron en la División de Endocrinología del Hospital de Niños "Ricardo Gutiérrez". Se realizó cariotipo en sangre, al inicio con metodología estándar, luego con diferentes bandeos convencionales y de alta resolución. En casos especiales se aplicó la técnica FISH y el análisis molecular de los cromosomas X e Y. El número de metafases analizadas también varió con el tiempo, permitiendo evidenciar más de una línea celular. En casos de alta sospecha clínica, la lectura de 100 metafases permitió poner en evidencia mosaicismos bajos conteniendo la línea 45,X. En nuestra serie la monosomía de cromosoma sexual 45, X fue la más frecuente siguiendo los mosaicos numéricos y estructurales de uno de los cromosomas sexuales. Los diferentes hallazgos cromosómicos nos han permitido establecer una correlación fenotipo-cariotipo en regiones específicas de los cromosomas sexuales
Turner Syndrome is a common chromosomal disorder caused by total or partial haploinsufficiency of one of the sex chromosomes. Incidence: 1: 2500. Clinically is characterized by short stature, several typical somatic features, and gonadal dysgenesis. This is a retrospective study involving 630 girls with Turner phenotype and abnormal karyotype, evaluated at the Endocrinology Division of Children´s Hospital "Ricardo Gutiérrez" between 1968 and 2018. The karyotype was done in leucocytes from peripheral blood and the metaphases were analyzed at the beginning with standard methodology and then with different banding techniques, standard and high resolution. In special cases, the FISH technique and the molecular analysis of the X and Y chromosomes were applied. The number of metaphases analyzed also changed with time, allowing the finding of more than one cellular line. In cases where the clinical suspicion was strong, the analysis of 100 metaphases allowed us to put in evidence low mosaicisms containing the 45,X line. In our study the monosomy of sexual chromosome 45, X was the most frequent following the numerical and structural mosaics of one of the sex chromosomes. The different chromosomal constitutions have contributed to establish in our patients phenotype-karyotype correlation with specific regions of the sex chromosomes
Assuntos
Humanos , Cromossomos Sexuais , Síndrome de Turner , Fenótipo , Argentina , GenótipoRESUMO
BACKGROUND: In acid-labile subunit (ALS)-deficient families, heterozygous carriers of IGFALS gene mutations are frequently shorter than their wild-type relatives, suggesting that IGFALS haploinsufficiency could result in short stature. We have characterized IGFALS gene variants in idiopathic short stature (ISS) and in normal children, determining their impact on height and the IGF system. PATIENTS AND METHODS: In 188 normal and 79 ISS children levels of IGF-1, IGFBP-3, ALS, ternary complex formation (TCF) and IGFALS gene sequence were determined. RESULTS: In sum, 9 nonsynonymous or frameshift IGFALS variants (E35Gfs*17, G83S, L97F, R277H, P287L, A330D, R493H, A546V and R548W) were found in 10 ISS children and 6 variants (G170S, V239M, N276S, R277H, G506R and R548W) were found in 7 normal children. If ISS children were classified according to the ability for TCF enhanced by the addition of rhIGFBP-3 (TCF+), carriers of pathogenic IGFALS gene variants were shorter and presented lower levels of IGF-1, IGFBP-3 and ALS in comparison to carriers of benign variants. In ISS families, subjects carrying pathogenic variants were shorter and presented lower IGF-1, IGFBP-3 and ALS levels than noncarriers. CONCLUSIONS: These findings suggest that heterozygous IGFALS gene variants could be responsible for short stature in a subset of ISS children with diminished levels of IGF-1, IGFBP-3 and ALS.
Assuntos
Estatura , Proteínas de Transporte/genética , Glicoproteínas/genética , Transtornos do Crescimento/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Proteínas de Transporte/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Mutação da Fase de Leitura/genética , Glicoproteínas/sangue , Heterozigoto , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Transdução de SinaisRESUMO
CONTEXT: Signal transducer and activator of transcription 5b (STAT5b) deficiency, first reported in a patient who carried a p.Ala630Pro missense mutation in the Src homology 2 (SH2) domain, results in a rare clinical condition of GH insensitivity (GHI), IGF-I deficiency (IGFD), and severe immune dysregulation manifesting as progressive worsening of pulmonary function. PATIENT: The new patient presented with severe cutaneous eczema, episodic infections in the first years of life, and autoimmune thyroiditis. Immunological evaluation revealed T lymphopenia, but severe pulmonary symptoms were notably absent. She concomitantly exhibited pronounced growth failure, reaching an adult height of 124.7 cm [-5.90 SD score (SDS)]. Endocrine evaluations (normal provocative GH tests; low serum IGF-I, -3.7 SDS, and IGF-binding protein-3, -4.5 SDS) were consistent with GHI and IGFD. RESULTS: Analysis of the STAT5B gene revealed a novel homozygous missense mutation, p.Phe646Ser, located within the ßD' strand of the SH2 domain. Reconstitution studies demonstrated expression of the p.Phe646Ser variant was less robust than wild type but, in contrast to the previously described STAT5B p.Ala630Pro SH2 mutation, could be phosphorylated in response to GH and interferon-γ. The phosphorylated p.Phe646Ser, however, could not drive transcription. CONCLUSION: A novel STAT5B p.Phe646Ser mutation has been identified in a patient with clinical characteristics of STAT5b deficiency. Only the second STAT5B missense mutation identified, its lack of transcriptional activities despite GH-induced phosphorylation, confirms the crucial role of STAT5b for regulating the expression of IGF1 and provides insights into the importance of the SH2 ßD' strand for full STAT5b transcriptional activities. Whether the phosphorylated p.Phe646Ser variant retained functions that prevented pulmonary distress remains unresolved.
Assuntos
Nanismo Hipofisário/genética , Doenças do Sistema Imunitário/genética , Fator de Crescimento Insulin-Like I/deficiência , Mutação de Sentido Incorreto , Fator de Transcrição STAT5/genética , Tireoidite Autoimune/genética , Análise Mutacional de DNA , Feminino , Humanos , Fator de Crescimento Insulin-Like I/genética , Pneumopatias/genética , Adulto Jovem , Domínios de Homologia de src/genéticaRESUMO
BACKGROUND: The karyotypes of 2 patients with abnormal stature and different phenotypes revealed one similar structural abnormality in the X chromosome by conventional cytogenetic studies and fluorescence in situ hybridization analysis (FISH). FISH strongly suggested the presence of two copies of the SHOX gene in the der(X) chromosome. PATIENTS AND RESULTS: Patient 1 is a teenager girl with tall stature, behavioral disturbances and normal pubertal development. The abnormal X chromosome was present in all cells studied. Parent's karyotypes were normal. Patient 2 is a girl with gonadal dysgenesis, mild Turner syndrome phenotype and short stature. The karyotype was a mosaic 45,X/46,X,r(X) and der(X) chromosome presented in most metaphases of the cell lines. Parent's karyotypes were normal. Nearly all duplication of Xp and partial deletion of the long arm (Xq) from Xq27 or Xq21 to Xqter, in cases 1 and 2, respectively, were observed. In both patients, duplication of Xp translocated to deleted Xq occurred leading to a triplication of the pseudoautosomal region 1 (PAR1) where the SHOX gene is located (Xp22.3). CONCLUSIONS: We propose that in some cases of trisomy for the SHOX gene, the effect of overdosage per se may affect the stature, even in patients with preserved ovarian function (case 1), and that estrogen deprivation may not always be a contributor for tall stature (case 2).
Assuntos
Estatura/genética , Deleção Cromossômica , Duplicação Cromossômica , Cromossomos Humanos X/genética , Proteínas de Homeodomínio/genética , Trissomia/genética , Adolescente , Criança , Feminino , Dosagem de Genes , Humanos , Proteína de Homoeobox de Baixa EstaturaRESUMO
To determine the influence of age, gestational age, gender and methodological protocol on serum 17OHP and cortisol concentrations. 17OHP in non-extracted (NE) and extracted (E) sera was measured by RIA in 319 full-term (FT) (1 d-5 yr) infants, 38 pre-term (PT) and in 19 neonates with classical CAH at diagnosis. 17OHP (NE- and E-) decreased with age in normal children. The extraction procedure significantly reduced 17OHP by eliminating interfering steroids in children < 1 year. Sexual dimorphism was only observed in NE-17OHP. 17OHP in PT was always higher than in FT up to 2 months of age (p < 0.001). Neither NE- nor E-17OHP in CAH overlapped with those of FT or PT (p < 0.001) allowing to omit the extraction procedure to confirm CAH diagnosis. Cortisol levels were within normal range in neonates with CAH, thus not adding useful information about adrenal function. Chronological and gestational age, gender, and extraction for 17OHP measurement are important factors to know when assessing adrenal function during the first year of life.
Assuntos
Glândulas Suprarrenais/crescimento & desenvolvimento , Química Clínica/métodos , Química Clínica/normas , Hidrocortisona/sangue , Progesterona/análogos & derivados , Glândulas Suprarrenais/fisiologia , Fatores Etários , Pré-Escolar , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Progesterona/análise , Progesterona/sangue , Valores de ReferênciaRESUMO
Adrenal insufficiency is defined by impaired secretion of adrenocortical hormones. It is classified upon the etiology in primary and secondary. Rapid recognition and therapy of adrenocortical crisis are critical to survival. Patients often have nonspecific symptoms: anorexia, vomiting, weakness, fatigue and lethargy. They are followed by hypotension, shock, hypoglicemia, hyponatremia and hyperkalemia. All patients with adrenal insufficiency require urgent fluid reposition, correction of hypoglycemia and glucocorticoid replacement, in order to avoid serious consequences of adrenal crisis. After initial crisis treatment, maintenance dose of corticoids should be indicated. Mineralocorticoids replacement, if necessary, should also be initiated.
Assuntos
Insuficiência Adrenal , Insuficiência Adrenal/terapia , Criança , Emergências , Humanos , Índice de Gravidade de DoençaRESUMO
La insuficiencia suprarrenal aguda es un cuadro originado por deficiencia mineralocorticoidea o glucocorticoidea, cuyo no diagnóstico y adecuado tratamiento lleva a una emergenciagrave con riesgo para la vida del paciente. Se clasifica en insuficiencia suprarrenal primaria, que presenta en general compromiso glucocorticoideo y mineralocorticoideo, y secundaria,sin deficiencia mineralocorticoidea. Los pacientes pueden no presentar síntomas que alerten precozmente, comoanorexia, náuseas, astenia, vómitos y dolor abdominal. De no corregirse, aparecen hipotensión, hipoglucemia, hiponatremia con hipercaliemia, deshidratación y shock. Es indispensable,aun en caso de duda, corregir la hipovolemia, el desequilibrioelectrolítico y la hipoglucemia, y administrar glucocorticoidesa dosis de estrés. Superada la fase aguda, administrar la dosis de corticoides de mantenimiento y, en caso necesario, añadir mineralocorticoides.
Assuntos
Humanos , Masculino , Criança , Corticosteroides/uso terapêutico , Emergências , Insuficiência Adrenal/classificação , Insuficiência Adrenal/complicações , Insuficiência Adrenal/prevenção & controle , Insuficiência Adrenal/terapiaRESUMO
La insuficiencia suprarrenal aguda es un cuadro originado por deficiencia mineralocorticoidea o glucocorticoidea, cuyo no diagnóstico y adecuado tratamiento lleva a una emergenciagrave con riesgo para la vida del paciente. Se clasifica en insuficiencia suprarrenal primaria, que presenta en general compromiso glucocorticoideo y mineralocorticoideo, y secundaria,sin deficiencia mineralocorticoidea. Los pacientes pueden no presentar síntomas que alerten precozmente, comoanorexia, náuseas, astenia, vómitos y dolor abdominal. De no corregirse, aparecen hipotensión, hipoglucemia, hiponatremia con hipercaliemia, deshidratación y shock. Es indispensable,aun en caso de duda, corregir la hipovolemia, el desequilibrioelectrolítico y la hipoglucemia, y administrar glucocorticoidesa dosis de estrés. Superada la fase aguda, administrar la dosis de corticoides de mantenimiento y, en caso necesario, añadir mineralocorticoides.(AU)
Assuntos
Humanos , Masculino , Criança , Emergências , Insuficiência Adrenal/classificação , Insuficiência Adrenal/complicações , Insuficiência Adrenal/prevenção & controle , Insuficiência Adrenal/terapia , Corticosteroides/uso terapêuticoRESUMO
La talla baja idiopática (TBI) incluye a un grupo heterogéneo de pacientes con fallas en su crecimiento. Una causa probable de TBI puede ser la insensibilidad a la GH (IGH). La proteína de unión de GH de alta afinidad (GHBP) se genera por el clivaje proteolítico de la porción extracelular del receptor de GH (GHR) y su determinación se propone como un marcador periférico del nivel de GHR en los tejidos. El objetivo de este trabajo fue evaluar los niveles de GHBP circulantes y su asociación con factores de crecimiento y el polimorfismo del exón 3 del gen GHR en niños con TBI. Los niños con TBI presentaron talla, IMC, IGF-I, IGFBP-3, ALS y niveles de GHBP significativamente más bajos que un grupo de niños de edad comparable (p<0.001). El genotipo del exón 3 del GHR no fue un factor determinante de las diferencias observadas. La máxima respuesta de GH de los tests de estímulo de secreción correlacionó negativa y significativamente con los niveles de GHBP (r= -0.28, p= 0.012). Los perfiles de distribución de la concentración de GHBP, IGF-I, ALS y BP3 expresadas en score de desvío estándar (SDE) en la TBI, mostraron un sesgo hacia niveles bajos. En conclusión, los marcadores de acción de GH y los niveles de GHBP fueron bajos en la TBI, independientemente del genotipo del exón 3 del gen GHR. En un subgrupo de niños con TBI, niveles disminuidos de GHBP y de componentes del sistema de los IGFs, colaborarían en la evaluación de la IGH sugiriendo la búsqueda de defectos en el GHR.
Idiopathic Short Stature (ISS) includes a heterogeneous group of children with growth failure. One possible explanation for the growth failure is a reduced responsiveness to growth hormone (GH). Human circulating GH is partially bound to a highaffinity binding protein (GHBP) which is derived from proteolytical cleavage of the extracellular domain of the GH receptor. Many reports have demonstrated a close relationship between GHBP and liver GH receptor status in physiological conditions and diseases. Moreover, serum GHBP measurement has been proposed as an useful peripheral index of GH receptor abundance. Our objective was the evaluation of serum GHBP levels and its probable association with serum growth factors (IGF-I, IGFBP-3 and ALS) and the exon 3 polymorphism of the extracellular domain of the GHR gene in ISS children. Children with ISS presented significantly lower height SDS, BMI SDS, serum components of the IGFs system and GHBP concentration as compared to an age-matched control group of normal children (p<0.001). Interestingly, exon 3 genotype did not influence the differences observed in these parameters. The maximal GH response obtained after two GH provocative tests inversely and significantly correlated to GHBP serum levels (r= -0.28, p= 0.012). A frequency study showed a deviation to low SDS values of serum GHBP, IGF-I, IGFBP-3 and ALS. Conclusion: 1- in children with ISS the exon 3 genotype of the GHR gene is not a factor that could explain the lower levels observed in circulating GHBP concentration and components of the IGFs system; 2- low serum GHBP together with low IGF-I, IGFBP-3 or ALS levels would help pointing to GH insensitivity due to GH receptor gene abnormalities in ISS.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Hormônio do Crescimento Humano/biossíntese , Insuficiência de Crescimento/etiologia , Biomarcadores/metabolismo , Hormônio do Crescimento Humano/genética , Peptídeos e Proteínas de Sinalização Intercelular/genéticaRESUMO
BACKGROUND: Fifteen percent of small for gestational age (SGA) children remain short and undergo thyroid axis evaluations. METHODS: We analyzed data on thyroid assessment of 58 SGA children. Five had primary autoimmune hypothyroidism. In the remaining 53 patients, TSH, free T4 (FT4), antithyroid antibodies and 90-min TRH test results were analyzed. Patients were grouped into G1 (n = 27; normal) and G2 (n = 26; abnormal) according to their response to the TRH test compared with 30 normal children. RESULTS: No differences were found in chronological age, gestational age, or birth weight standard deviation score (SDS) between groups. G2 showed higher SDS BMI at consultation (p < 0.05). FT4 (ng/dl) levels were similar in all groups, while basal TSH levels were statistically different in G2 compared with G1 and controls. In 21 G2 patients treated with thyroxine, FT4 levels did not change, TSH normalized, BMI SDS and height remained unchanged. CONCLUSION: These data suggest that in SGA short children thyroid abnormalities may occur. Some of them may be due to a different setting of the hypothalamic-hypophyseal-thyroid axis during intrauterine life. Intrauterine growth retardation may permanently influence endocrine systems by affecting their programming during development. Further follow-up is needed to confirm these findings and to assess their natural history and potential clinical impact.
Assuntos
Transtornos do Crescimento/tratamento farmacológico , Sistema Hipotálamo-Hipofisário/fisiologia , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Tireotropina/sangue , Adolescente , Autoimunidade , Estatura , Criança , Pré-Escolar , Feminino , Humanos , Recém-Nascido , Masculino , Glândula Tireoide/imunologia , Tireotropina/uso terapêuticoRESUMO
INTRODUCTION: Around 50% of Noonan syndrome (NS) patients present heterozygous mutations in the PTPN11 gene. AIM: To evaluate the frequency of mutations in the PTPN11 in patients with NS, and perform phenotype-genotype correlation. PATIENTS: 33 NS patients (23 males). METHODS: DNA was extracted from peripheral blood leukocytes, and all 15 PTPN11 exons were directly sequenced. RESULTS: Nine different missense mutations, including the novel P491H, were found in 16 of 33 NS patients. The most frequently observed features in NS patients were posteriorly rotated ears with thick helix (85%), short stature (79%), webbed neck (77%) and cryptorchidism (60%) in boys. The mean height SDS was -2.7 +/- 1.2 and BMI SDS was -1 +/- 1.4. Patients with PTPN11 mutations presented a higher incidence of pulmonary stenosis than patients without mutations (38% vs. 6%, p< 0.05). Patients with and without mutations did not present differences regarding height SDS, BMI SDS, frequency of thorax deformity, facial characteristics, cryptorchidism, mental retardation, learning disabilities, GH peak at stimulation test and IGF-1 or IGFBP-3 SDS. CONCLUSION: We identified missense mutations in 48.5% of the NS patients. There was a positive correlation between the presence of PTPN11 mutations and pulmonary stenosis frequency in NS patients.
Assuntos
Estatura , Transtornos do Crescimento/etiologia , Mutação de Sentido Incorreto/genética , Síndrome de Noonan/genética , Fenótipo , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Adolescente , Estatura/efeitos dos fármacos , Criança , Feminino , Genótipo , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Síndrome de Noonan/complicações , Síndrome de Noonan/tratamento farmacológicoRESUMO
INTRODUÇÃO: Aproximadamente 50 por cento dos pacientes com síndrome de Noonan (SN) apresentam mutações em heterozigose no gene PTPN11. OBJETIVO: Avaliar a freqüência de mutações no PTPN11 em pacientes com SN e analisar a correlação fenótipo-genótipo. PACIENTES: 33 pacientes com SN. MÉTODO: Extração de DNA de leucócitos periféricos e seqüenciamento dos 15 exons do PTPN11. RESULTADOS: Nove diferentes mutações missense no PTPN11, incluindo a mutação P491H, ainda não descrita, foram encontradas em 16 dos 33 pacientes. As características clínicas mais freqüentes dos pacientes com SN foram: pavilhão auricular com rotação incompleta e espessamento da helix (85 por cento), baixa estatura (79 por cento), prega cervical (77 por cento) e criptorquidismo nos meninos (60 por cento). O Z da altura foi de -2,7 ± 1,2 e o do IMC foi de -1 ± 1,4. Os pacientes com mutação no PTPN11 apresentaram maior freqüência de estenose pulmonar do que os pacientes sem mutação (38 por cento vs. 6 por cento, p< 0,05). Pacientes com ou sem mutação no PTPN11 não diferiram em relação à média do Z da altura, Z do IMC, freqüência de alterações torácicas, características faciais, criptorquidia, retardo mental, dificuldade de aprendizado, pico de GH ao teste de estímulo e Z de IGF-1 ou IGFBP-3. CONCLUSÃO: Identificamos mutações no PTPN11 em 48,5 por cento dos pacientes com SN, os quais apresentaram maior freqüência de estenose pulmonar.
INTRODUCTION: Around 50 percent of Noonan syndrome (NS) patients present heterozygous mutations in the PTPN11 gene. AIM: To evaluate the frequency of mutations in the PTPN11 in patients with NS, and perform phenotype-genotype correlation. PATIENTS: 33 NS patients (23 males). METHODS: DNA was extracted from peripheral blood leukocytes, and all 15 PTPN11 exons were directly sequenced. RESULTS: Nine different missense mutations, including the novel P491H, were found in 16 of 33 NS patients. The most frequently observed features in NS patients were posteriorly rotated ears with thick helix (85 percent), short stature (79 percent), webbed neck (77 percent) and cryptorchidism (60 percent) in boys. The mean height SDS was -2.7 ± 1.2 and BMI SDS was -1 ± 1.4. Patients with PTPN11 mutations presented a higher incidence of pulmonary stenosis than patients without mutations (38 percent vs. 6 percent, p< 0.05). Patients with and without mutations did not present differences regarding height SDS, BMI SDS, frequency of thorax deformity, facial characteristics, cryptorchidism, mental retardation, learning disabilities, GH peak at stimulation test and IGF-1 or IGFBP-3 SDS. CONCLUSION: We identified missense mutations in 48.5 percent of the NS patients. There was a positive correlation between the presence of PTPN11 mutations and pulmonary stenosis frequency in NS patients.
Assuntos
Adolescente , Criança , Feminino , Humanos , Masculino , Estatura , Transtornos do Crescimento/etiologia , Mutação de Sentido Incorreto/genética , Síndrome de Noonan/genética , Fenótipo , /genética , Estatura/efeitos dos fármacos , Genótipo , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Síndrome de Noonan/complicações , Síndrome de Noonan/tratamento farmacológicoRESUMO
BACKGROUND: In a recently described patient with acid-labile subunit (ALS) deficiency, the inability to form ternary complexes resulted in a marked reduction in circulating total insulin-like growth factor (IGF)-I, whereas skeletal growth was only marginally affected. To further study the role of circulating versus locally produced IGF-I in skeletal growth in this patient, we now describe in detail growth changes and their relationship with several components of the circulating IGF system. DESIGN AND METHODS: We followed growth and development up to the final height in a patient with complete ALS deficiency and determined both spontaneous and growth hormone (GH)-stimulated changes in the IGF system, including measurements of total, free and bioactive IGF-I, total IGF-II and insulin-like growth factor binding protein (IGFBP)-1, IGFBP-2 and IGFBP-3. RESULTS: The patient had a delayed growth and pubertal onset. Six months of GH treatment had no effect on growth. At the age of 19.3 years, he spontaneously completed puberty and had a normal growth spurt for a late adolescent (peak height velocity of 8.4 cm/year). A normal final height was attained at 21.3 years (167.5 cm; -0.78 SDS). During as well as after puberty, basal levels of total, free and bioactive IGF-I were low, as were total IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3. GH treatment for 6 months normalized free IGF-I and increased bioactive IGF-I, but had no effect on growth velocity. CONCLUSIONS: This case story shows that in the presence of complete ALS deficiency, a height within normal limits can be obtained despite low levels of all forms of circulating IGF-I. Furthermore, the patient presented a delayed but normal growth spurt without any marked increment of circulating IGF-I.
Assuntos
Estatura , Glicoproteínas/deficiência , Transtornos do Crescimento/fisiopatologia , Crescimento/fisiologia , Fator de Crescimento Insulin-Like I/análise , Adulto , Envelhecimento/sangue , Envelhecimento/fisiologia , Proteínas de Transporte , Seguimentos , Transtornos do Crescimento/sangue , Humanos , MasculinoRESUMO
Simple childhood obesity is characterized by normal or even accelerated growth in spite of reduced growth hormone (GH) secretion. There are conflicting reports on the effects of obesity upon components of the GH-insulin-like growth factor-I (IGF-I)-IGF binding proteins (IGFBPs) system. In the present study we aimed to determine GH, IGF-I, IGFBP-3 and IGFBP-2 as well as some of the less explored components of this axis (IGFBP-3 proteolytic activity, IGFBP-3 plasma fragments, and total acid labile subunit [ALS]) in 22 obese and 17 age-matched control children. We also evaluated not only total GH binding protein (GHBP) serum levels but also GHBP bound to GH (complexed) in both groups. Obese and control groups strongly differed in BMI (obese: 4.7 +/- 0.36 vs control: 0.37 +/- 0.25 SDS, p <0.0001). In the obese group, we found lower GH serum levels, but normal serum levels of GH-GHBP complex, IGF-I, IGFBP-3, IGF-I/IGFBP-3 molar ratio, IGFBP-3 proteolytic activity, IGFBP-3 plasma fragments and total ALS. Obese children presented higher total circulating GHBP (6.0 +/- 0.44 vs 2.9 +/- 0.29 nmol/l, p <0.001) and insulin levels (10.5 +/- 1.5 vs 5.1 +/- 0.8 mU/l, p <0.001), while IGFBP-2 (4.6 +/- 0.5 vs 6.6 +/- 0.7%, p <0.05) and the ratio IGFBP-2/IGF-I (0.032 +/- 0.019 vs 0.095 +/- 0.01, p = 0.013) were lower than in controls. BMI and insulin were directly, and IGFBP-2 serum levels inversely, correlated to total GHBP serum levels when multiple regression analysis was performed (r = 0.74, p <0.001). By stepwise regression analysis, insulin (r = -0.37, p <0.05) and BMI (r = -0.52, p <0.01) inversely determined IGFBP-2. In summary, obese children present normal growth in spite of reduced GH secretion, probably because the combination of increased total GHBP and normal GH-GHBP complex serum levels (suggesting increased GH receptor [GHR] number and a normal serum GH reservoir, respectively) allow for the achievement of normal levels of IGF-I, IGFBP-3, IGFBP-3 proteolytic activity, IGFBP-3 plasma fragments and total ALS. Reduced IGFBP-2 serum levels and a lower ratio of IGFBP-2/IGF-I in obese children may suggest an increase of tissue IGF-I bioavailability, thus promoting its action. Normal IGF-I and GH availability may be contributing to maintain normal growth in obese children.