RESUMO
UNLABELLED: In order to delineate the spectrum of thyroid abnormalities in children with Down's syndrome (DS), first visit height data (SDS) and serum TSH, T4 and antiperoxidase antibodies concentrations were retrospectively evaluated in 137 children (71 girls) with DS (0.04-16 years). RESULTS: Congenital hypothyroidism was detected in 2.9% of patients. Thyroid disease occurred in 9%: four hyperthyroidism and eight hypothyroidism. Overt thyroid disease was always related to thyroid autoimmunity. The remaining 121 patients had normal T4 levels but increased mean TSH compared with controls (4.7 +/- 2.8 vs 2.3 +/- 1.3 mU/l). According to TSH levels, they were divided into two groups: G1 (n = 68) with normal TSH (<5 mU/l), and G2 (n = 53) with high TSH (> 5 mU/l). T4 levels were significantly lower in G2 (p < 0.01 vs G1 and controls). Height SDS was not different. CONCLUSIONS: Thyroid disorders are frequent in children with DS. Subtle thyroid abnormalities found in patients with DS with no evidence of clinical dysfunction need further investigation to demonstrate whether there is a need for therapeutic intervention.
Assuntos
Síndrome de Down/complicações , Doenças da Glândula Tireoide/etiologia , Tireotropina/sangue , Adolescente , Criança , Pré-Escolar , Hipotireoidismo Congênito , Síndrome de Down/sangue , Feminino , Humanos , Hipertireoidismo/etiologia , Hipotireoidismo/etiologia , Masculino , Estudos RetrospectivosRESUMO
UNLABELLED: Aldosterone producing adenoma (APA) is a rare but potentially curable form of paediatric hypertension. We report a case of APA in a 9-year-old boy, suspected due to persistent hypokalaemia. Neither BP nor initial laboratory investigations disclosed the diagnosis and the presence of an APA was suggested by functional tests and radiological findings. Histologically, a cortical tumour was found associated with a marked medullary hyperplasia of both chromaffin and ganglion cells. CONCLUSION: This case reinforces the need for further investigations in patients with misleading clinical and laboratory data.
Assuntos
Adenoma/complicações , Neoplasias das Glândulas Suprarrenais/complicações , Hiperaldosteronismo/etiologia , Adenoma/patologia , Neoplasias das Glândulas Suprarrenais/patologia , Medula Suprarrenal/patologia , Criança , Humanos , Hiperplasia , Hipertensão Renal/etiologia , Hipopotassemia/etiologia , MasculinoRESUMO
We have studied the effect of estradiol (E2) on the GH-insulin-like growth factor (GH-IGF) axis in 15 prepubertal GH deficiency (GHD) children and 44 prepubertal or early pubertal children with idiopathic short stature (SS). All of them received a daily dose of micronized E2 (1 or 2 mg) or placebo, for 3 days, before a sequential arginine-clonidine test. In SS children, GH maximal responses were 17.8+/-10.9 on placebo and 27.9+/-14.5 microg/L on estrogen (P < 0.0001). The lower 95% confidence limits for GH maximal response changed from 3.7 microg/L (without E2) to 8.3 microg/L (on E2). In GHD children, no significant stimulatory effect of estrogen on GH levels was observed. After placebo, a cut-off limit of 3.7 microg/L (the lower 95% confidence interval limit) resulted in 73% sensitivity, 95% specificity, and an overall 90% diagnostic efficiency. After E2, a cut-off limit of 8.3 microg/L resulted in a sensitivity of 87%, a specificity of 98%, and a diagnostic efficiency of 95%. After placebo, 68% of SS showed normal IGF-I levels, and the mean did not change on E2 (13.7+/-6.3 vs. 14.3+/-6.8 nmol/L, not significant). In 93% of SS, IGF binding protein (IGFBP)-3 levels were normal during placebo. On E2, mean IGFBP-3 did not change (2.63+/-0.70 vs. 2.70+/-0.70 mg/L, not significant). In 14 of 15 GHD patients, IGF-I values were below normal on placebo, and the mean of the group did not change after E2. During placebo, 13 of 15 GHD children presented low IGFBP-3 values. During E2, there was a small significant increase in IGFBP-3 values (1.06+/-0.58 vs. 1.20+/-0.69 mg/L, P < 0.02). The highest diagnostic efficiencies for IGF-I and IGFBP-3 were observed during placebo (75% and 91%, respectively). We conclude that GH stimulation tests after E2 priming had the highest diagnostic efficiency. Our findings suggest that the effect of estrogen priming on GH stimulated levels, by reducing the number of false nonresponders, might be useful to better discriminate between normal and abnormal GH status in SS children.
Assuntos
Estatura , Estradiol , Transtornos do Crescimento/diagnóstico , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/deficiência , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Intervalos de Confiança , Diagnóstico Diferencial , Feminino , Transtornos do Crescimento/sangue , Transtornos do Crescimento/fisiopatologia , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Placebos , Sensibilidade e EspecificidadeRESUMO
AIM: The absence of the hyperintense signal of the posterior pituitary in magnetic resonance imaging (MRI) is considered by some authors to be evidence of neurohypophyseal dysfunction. To evaluate the utility of MRI as a complementary diagnostic aid in patients with central diabetes insipidus (CDI), we studied the MR images of pediatric patients at diagnosis and during follow-up. METHODS: MR images from 14 patients (4 females, 10 males; mean age 8.5 years) who were referred for polyuria and polydipsia and whose diagnosis was central diabetes insipidus (CDI) were analyzed. Mean time of evolution from onset of polyuria until the first MRI was 1.5 years. In 11 patients more than one MR image was obtained during follow-up. Mean time of follow-up was 2.8 years. RESULTS: In 10 patients CDI was idiopathic, in 3 it was secondary to a hypothalamic tumor and in 1 it was secondary to histiocytosis. In one patient with idiopathic CDI, the hyperintense signal was present at diagnosis but disappeared during the following 15 months. Four of the patients with idiopathic CDI developed thickening of the pituitary stalk, some at their diagnosis and others during follow-up. Of the three patients in whom CDI was secondary to a germinoma, the hyperintense signal was absent in two of them, while in one the signal was ectopic and associated with a thickened pituitary stalk. In the patient with histiocytosis, the hyperintense signal was absent at diagnosis. CONCLUSIONS: 1. In most of the patients with CDI the hyperintense signal of the posterior pituitary was absent at diagnosis; however in one patient this signal disappeared during follow-up and consequently its presence does not rule out a diagnosis of CDI. 2. Although a thickened pituitary stalk could reflect only a non-specific, transient inflammatory process, its presence makes ruling out tumoral or infiltrative disease obligatory.
Assuntos
Diabetes Insípido/etiologia , Imageamento por Ressonância Magnética , Doenças da Hipófise/complicações , Adolescente , Criança , Diabetes Insípido/diagnóstico , Feminino , Humanos , Masculino , Doenças da Hipófise/diagnósticoRESUMO
Social disabilities have been described in GHD patients. The aim of this study was to evaluate the social outcome of a group of adult hypopituitary patients diagnosed and treated during childhood. Seventy patients were interviewed at a mean age of 25.6 years (range 18-50 yr). They answered a semistructured questionnaire and the Beck Depression Inventory test. Patients were compared for academic achievement, marital status and employment with the nearest age sibling. We found high levels of school repeaters, school was often not completed, and around 50% were overprotected by teachers and teased by peers. 32% were unemployed, while 58% of those employed work with their families. 80% still live with their parents; only 16% are married and 9% have children. 44% had no dating experience and 52% had never had sexual intercourse. Depression was common, especially in hypogonadic subjects. Juvenilization was the most common complaint. We did not found differences in maximal educational achievements and levels of employment between patients and siblings, but significantly more married siblings were found. Depression, social isolation and dependent life style were found in GHD patients. Appropriate medical and psychological counseling should be included for patients and their families as part of treatment.
Assuntos
Hormônio do Crescimento Humano/deficiência , Hipopituitarismo/psicologia , Adulto , Depressão/etiologia , Escolaridade , Emprego , Feminino , Humanos , Hipogonadismo/psicologia , Relações Interpessoais , Masculino , Estado Civil , Isolamento SocialRESUMO
In the kidney, the 11beta-hydroxysteroid dehydrogenase type 2 enzyme (11betaHSD2) inactivates glucocorticoids to their inactive ketoforms and thus prevents endogenous glucocorticoids from occupying the nonselective mineralocorticoid receptor in epithelial tissues. Several mutations have been described in the 11betaHSD2 gene in the congenital syndrome of apparent mineralocorticoid excess. These mutations generate partially or completely inactive 11betaHSD2 enzymes. In the present work, we describe an already known mutation in a new patient affected by apparent mineralocorticoid excess, which results in an arginine-to-cysteine mutation (R213C) in the 11betaHSD2 enzyme. This mutation has been found in two other independent families. In vitro expression studies of this mutant provide evidence that the mutant protein is normally expressed, but its activity is abolished. The CGC-to-TGC (C-toT) transition at codon 213 can be considered a typical CpG-consequence mutation. The present finding suggests that the codon R213 of 11betaHSD2 is a hot spot for mutations in this gene, as shown by the occurrence of an R213C point-mutation in several families unrelated to each other.
Assuntos
Códon/genética , Hidroxiesteroide Desidrogenases/genética , Isoenzimas/genética , Mineralocorticoides/metabolismo , Mutação/genética , 11-beta-Hidroxiesteroide Desidrogenases , Sequência de Aminoácidos/genética , Sequência de Bases/genética , Criança , Humanos , Hidroxiesteroide Desidrogenases/metabolismo , Hipertensão/etiologia , Hipertensão/fisiopatologia , Isoenzimas/metabolismo , Masculino , SíndromeRESUMO
OBJECTIVE: We studied retrospectively the statural growth and bone maturation of 32 children with primary hypothyroidism in order to relate their final heights to their chronological ages, height deficits and bone ages at the beginning of treatment. Patients were grouped according to age when treatment was started: Group 1 (G1) (n = 17): (15 girls, 1 boy) 3.09 +/- 0.8 yr; Group 2 (G2) (n = 9): (7 girls, 2 boys) 9.1 +/- 1.2 yr, and Group 3 (G3) (n = 6): (5 girls, 1 boy) 13.58 +/- 1.13 yr. At diagnosis G1 and G2 were prepubertal and G3 children were in puberty. In 10 patients of G1, 7 of G2 and 6 (all) of G3 final height was compared with target height. RESULTS: (SDS) Initial height: G1: -3.74 +/- 1.2; G2: -3.94 +/- 1.32; G3 -3.65 +/- 1. Height at onset of puberty: G1: -1.06 +/- 1.1; G2: -2.5 +/- 1.4. Height menarche stage 5: G1: -0.63 +/- 1.1; G2: -1.76 +/- 1.2; G3: -2.6 +/- 1.7. Final height: (whole group) G1: -0.85 +/- 0.91; G2: -1.6 +/- 1.3; G3: -2 +/- 1.5. Final height G1 (n = 10): -1.05 +/- 0.89; G2 (n = 7) 1.2 +/- 1. Target height G1 (n = 10): -1.22 +/- 0.78; G2 (n = 7): -0.8 +/- 1.2; G3 (n = 6): -1.07 +/- 1.5. Initial bone age: G1: -4.9 +/- 0.85; G2: -7.2 +/- 2.6; G3: -4.5 +/- 1.9. Bone age (onset of puberty) G1: -0.26 +/- 1.74; G2: -2 +/- 1.7; Bone age (menarche) G1: 0.09 +/- 0.6; G2: -0.5 +/- 0.6; G3: -0.76 +/- 0.82. CONCLUSION: G1 and G2, prepubertal at diagnosis, reached a normal adult height with respect to target height; G3 did not, the difference being statistically significant (p < 0.04). Puberty plays a decisive role in the incomplete catch-up growth of longstanding hypothyroid patients.
Assuntos
Peso Corporal/efeitos dos fármacos , Hipotireoidismo/tratamento farmacológico , Tireotropina/uso terapêutico , Adolescente , Determinação da Idade pelo Esqueleto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de TempoRESUMO
To assess the efficacy of treatment with oral desmopressin (DDAVP), 20 patients, aged 5-20 y, with central diabetes insipidus were studied during 3 d of hospitalization and for 3 months at the outpatient clinic. At baseline the median rate of diuresis was 12.7 ml kg-1 h-1. Urinary output decreased significantly under treatment with an increase in urinary osmolality, normalization of plasma osmolality and absence of nocturia. Patients were discharged from hospital with a median dose of 500 micrograms d-1 (100-1200 micrograms d-1). An adjustment in dosage was necessary in seven patients during follow-up, resulting in a final dose of 600 micrograms d-1. Body weight and DDAVP doses (r = 0.75, p = 0.001) and body surface and DDAVP doses (r = 0.72, p < 0.001) were significantly correlated. The average dosage was 474 +/- 222 micrograms m-2 d-1 (mean +/- SD). The oral DDAVP treatment remained effective during the 3 months of follow-up. This therapy offers an alternative for the treatment of central diabetes insipidus in children.
Assuntos
Desamino Arginina Vasopressina/uso terapêutico , Diabetes Insípido/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Administração Oral , Adolescente , Adulto , Criança , Pré-Escolar , Diurese/efeitos dos fármacos , Hospitalização , HumanosRESUMO
To assess the degree of reproducibility of spontaneous GH secretion and pharmacological tests we studied 15 prepubertal children with short stature and abnormal growth rate. In all children, spontaneous overnight GH secretion was measured followed by a clonidine test in 8 children and an arginine test in the remaining 7. The same protocol was repeated a week later. Intra-individual variability of GH secretion in both physiological and pharmacological tests was expressed as the coefficient of variation (CV%). No significant difference was found between the first and second value of parameters of spontaneous GH secretion. Maximum spontaneous GH peak (MS) and mean 12-h GH concentration (MGH) correlated significantly (r = 0.78, p < 0.001). Mean CV% of all parameters of repeated GH profiles (around 30%) were lower than those of provocative tests (around 70%) (p < 0.05). No significant difference was found between CV% of clonidine and arginine tests. There was no correlation between MGH or MS and GH response to provocative test in the same child. We found a significant correlation between the log transformed maximum provocative GH response to the arginine test and the length of the time interval (in min) from the end of the last GH peak in the previous profile to the time zero of the provocative test (r = 0.60, p < 0.05). This relationship was not found for the clonidine test. We conclude that spontaneous GH secretion in children with short stature is more reproducible than stimulated GH response with a week's difference. Perhaps the higher variability of provocative GH secretion may be related to the state of the endogenous hypothalamic rhythm of both GHRH and somatostatin release at the time of the test.
Assuntos
Transtornos do Crescimento/fisiopatologia , Hormônio do Crescimento Humano/metabolismo , Reprodutibilidade dos Testes , Arginina , Estatura , Criança , Clonidina , Feminino , Humanos , Masculino , PeriodicidadeRESUMO
Growth data on 254 patients with Turner syndrome from Argentina-120 with XO karyotype and 134 with other chromosomal abnormalities-were analysed. Birth weight and height were significantly reduced. Ninety patients had received oestrogen treatment from a mean age of 14-0 years (SD 1.2) and 17 patients had spontaneous menarche. Patients who underwent spontaneous menarche had a small growth spurt. Final height was slightly higher (139.8 cm SD 5.6), though not significantly different from the mean adult height of the whole sample (137.9 cm SD 5.7). Mean adult height was 3.73 SD below mean of the normal local population. Mean height velocities from birth to maturity are very similar to those found in other samples. Distance standards were prepared by fitting a fifth-degree polynomial to the interpolated mean heights at each 0.5 year of age, and to the raw SD. Selected centiles were then calculated from the smoothed values. Differences between adult height in local Turner syndrome girls and local normal population are very similar to the same Turner-normal differences described in other communities. Standards presented here are useful for evaluating Turner syndrome patients from Argentina, and may also be used by those with similar growth pattern in their normal population.