RESUMO
In normal human beings the percentage of serum insulin excreted in the urine is constant over a wide range of values. The quantity of immunoreactive insulin found in the urine is believed to reflect the level of free insulin in the serum. Immunoreactive insulin was measured in the urine of nondiabetic children and diabetic children receiving exogenous insulin. Children with diabetes mellitus excreted greater amounts of immunoreactive insulin (18.5+/-8 muU./mg. creatinine) than did nondiabetic children (11.9+/-5 muU./mg. creatinine). This difference was statistically significant (p less than 0.0005). Children with "poor glycemic control" excreted a greater portion of their administered insulin dose than did those with "good control." The renal wastage of insulin correlated (r=0.94) with the duration of insulin treatment but not with the quantity administered. Antibody binding of serum insulin may explain in part these observations, but an acquired defect in the renal tubular reabsorption of insulin may also exist. Modifications in the management of diabetes that reduce the renal wastage of insulin may improve the metabolic stability of children with "poor diabetic control."
Assuntos
Diabetes Mellitus Tipo 1/urina , Insulina/urina , Adolescente , Proteínas Sanguíneas/metabolismo , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/fisiopatologia , Humanos , Insulina/uso terapêutico , Anticorpos Anti-Insulina , Túbulos Renais/fisiopatologia , Ligação ProteicaRESUMO
In patients with hypopituitarism, magnetic resonance (MR) imaging of the hypothalamus and pituitary has disclosed a high incidence of hypoplasia of the anterior pituitary lobe, attenuation or transection of the pituitary stalk, and formation of an "ectopic" posterior pituitary lobe at the base of the hypothalamus. These anatomic abnormalities may be associated with other congenital malformations of the central nervous system, or may be due to an in utero toxic or infectious insult, perinatal trauma, neonatal asphyxia and hypoxia, head injury, or hemorrhage into a pituitary adenoma. The progressive development of defects in pituitary hormone secretion in such patients is probably due to continued atrophy of an anterior pituitary remnant with a limited vascular supply unstimulated by hypothalamic neuropeptides. By contrast, in patients with isolated hypogonadotropic hypogonadism, hypothalamic pituitary anatomy is normal, although abnormalities of the olfactory sulcus are present in patients with anosmia and hypogonadotropism (Kallmann syndrome). In most patients with central diabetes insipidus, the neurohypophysis is absent on MR scan.
RESUMO
Five groups (n = 11) of 250-g female rats were oophorectomized and immediately thereafter received daily sc injections of estradiol benzoate (EB; 0.05, 0.5, 5.0, and 50.0 micrograms) or vehicle for 28 days. A sixth group underwent sham operation and received injections of vehicle. Somatomedin-C (SmC) concentrations were determined before EB administration. After 4 weeks of EB treatment, the GH response to human GH-releasing factor (1-44) (GRF; 5 micrograms/kg, iv) was determined under pentobarbital anesthesia in seven animals from each group. Serum PRL, LH, and estradiol and plasma SmC concentrations were also measured. The GH secretory response to GRF (delta GH) was greatest in castrated animals receiving vehicle (P less than 0.05) and was significantly blunted in animals receiving 5.0 and 50.0 micrograms EB (P less than 0.05) compared to that in sham-operated animals. A significant negative correlation was observed between delta GH and serum PRL concentrations (r = -0.53; P less than 0.0001). SmC concentrations after treatment were significantly lower in animals receiving 5.0 and 50.0 micrograms EB (P less than 0.01), than in sham-operated animals and were elevated compared to those in sham-operated controls in the group receiving the lowest dose of EB (0.05 microgram; P less than 0.01). Posttreatment SmC levels correlated positively with delta GH (r = 0.58; P less than 0.001) and negatively with serum estradiol concentrations (r = -0.47; P less than 0.01). Pituitary glands from the remaining animals in each group (n = 4) were weighed and assayed for GH, PRL, and LH content. Pituitary PRL content increased with increasing doses of EB replacement and correlated strongly (r = 0.82; P less than 0.0001) with pituitary weight. In the castrated adult female rat, high doses of estrogen inhibited the GH secretory response to GRF in vivo and decreased SmC concentrations. Low dose estrogen increased SmC concentrations, although the GH secretary response to GRF in this group was similar to that in sham-operated rats. The latter observation suggests that the rise in SmC levels associated with low dose estrogen may not be mediated through a change in GH secretion.
Assuntos
Estradiol/farmacologia , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Hormônio do Crescimento/metabolismo , Animais , Feminino , Hormônio do Crescimento/sangue , Hormônio Luteinizante/metabolismo , Ovariectomia , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Prolactina/metabolismo , Ratos , Ratos EndogâmicosRESUMO
Pregnant rats were maintained on diets either adequate or deficient in vitamin D. On the 20th day of gestation, animals were either nephrectomized bilaterally or sham operated. Immediately therafter, four groups of nephrectomized or sham-operated pregnant rats received iv [26,27-3H]25-hydroxyvitamin D3 ([26,27-3H]25OHD3), while two groups received [1,2-3H,4-14C]D3. The animals were sacrificed 10-24 h later. The distribution of the radiolabeled metabolites of vitamin D3 was determined in extracts of maternal plasma, maternal intestinal tract, placentae, and fetuses after Sephadex LH-20 column chromatography. Both vitamin D3 and 25OHD3 crossed the placenta and entered the fetus. In anephric animals receiving [26,27-3H]-25OHD3, 24,25-dihydroxyvitamin D and a polar peak eluting in the position of 1,25-dihydroxyvitamin D [1,25(OH)2D] and 25,26-dihydroxyvitamin D were identified in extracts of maternal plasma and intestinal tracts and of placentae and fetuses. The identities of 24,25-dihydroxyvitamin D and 1,25 (OH)2D were confirmed by high pressure liquid chromatography. In rats receiving [1,2-3H,4-14C]D3, approximately 50% of the polar metabolite consisted of 1,25(OH)2D. We conclude that the anephric pregnant rat is able to synthesize 1,25(OH)2D, that the fetal portion of the feto-placental unit is the most likely site of production of this hormone, and that this metabolite of vitamin D is able to cross the placenta from the fetus to the mother.
Assuntos
Di-Hidroxicolecalciferóis/biossíntese , Hidroxicolecalciferóis/biossíntese , Nefrectomia , Prenhez , Animais , Di-Hidroxicolecalciferóis/sangue , Feminino , Feto/metabolismo , Mucosa Intestinal/metabolismo , Placenta/metabolismo , Gravidez , RatosRESUMO
The effect of the 44-amino-acid peptide human pancreatic GH releasing factor (hpGRF-44) upon the secretion of GH was studied in control and hypothyroid adult male rats. In animals rendered hypothyroid by ingestion of propylthiouracil (PTU), basal and hpGRF-44-stimulated secretion of GH was depressed in vivo. Administration of T4 together with PTU prevented the decline in basal and hpGRF-provoked GH secretion in vivo. HpGRF-44-stimulated release of rat GH was also impaired in vitro, an effect partially reversed by administration of low doses of T4 in vivo. The depressed in vitro secretion of GH could not be restored in hypothyroidism pituitaries by incubation of the glands with T3. Thus, hypothyroidism blunts hpGRF-44-stimulated secretion of GH in vivo and in vitro in the hypothyroid adult male rat.
Assuntos
Hormônio Liberador de Hormônio do Crescimento/farmacologia , Hormônio do Crescimento/metabolismo , Hipotireoidismo/metabolismo , Animais , Técnicas In Vitro , Masculino , Ratos , Tiroxina/sangue , Tiroxina/farmacologiaRESUMO
The dopamine agonist, pyridoxine, was administered to 10 children being evaluated for short stature. Serum GH and PRL responses were contrasted to those after insulin-induced hypoglycemia (ITT) and L-dopa administration. Levels of GH did not change after pyridoxine, but PRL fell (P less than 0.05) to 42% of the zero time concentration. Significant increments of GH occurred during ITT and after L-dopa, while PRL was suppressed to a greater extent by L-dopa. We conclude that pyridoxine is not useful in assessment of hypothalamic-pituitary function.
Assuntos
Hormônio do Crescimento/metabolismo , Adeno-Hipófise/metabolismo , Prolactina/metabolismo , Piridoxina , Adolescente , Criança , Feminino , Humanos , Cinética , Masculino , Adeno-Hipófise/efeitos dos fármacosRESUMO
The integrity of dopaminergic and alpha-adrenergic neurotransmitter regulation of GH secretion was examined in children with decreased GH secretion. Children with GH neurosecretory dysfunction (GHND; n = 16) those with classical GH deficiency (n = 9), and short but otherwise normal children (n = 12) underwent 24 h GH studies (blood sampling every 20 min for 24 h) and provocative tests using arginine, insulin hypoglycemia, L-dopa (dopaminergic) and clonidine (alpha-adrenergic), and GH-releasing hormone (GHRH). GHND was defined as children with height in the first percentile or below, growth velocity of 4 cm/yr or less, low plasma somatomedin-C for age, delayed skeletal age by 2 or more yr, peak serum GH responses to any one (or more) provocative test of 10 ng/ml or more, and mean 24-h GH concentration below 3 ng/ml. GHND and GH-deficient children had reduced endogenous GH secretion, expressed as mean serum 24-h GH concentration [1.6 +/- 0.1 (+/- SEM) and 2.1 +/- 0.1 vs. 6.1 +/- 0.5 ng/ml (GH-deficient and GHND vs. normal, respectively); P less than 0.01]. the mean peak serum GH levels after arginine [8.2 +/- 2.0 vs. 20.8 +/- 6.6 ng/ml (GHND vs. normal); P less than 0.05] and insulin [9.3 +/- 1.0 vs. 16.2 +/- 1.7 ng/ml (GHND vs. normal); P less than 0.01) were lower in GHND children. The mean peak responses after L-dopa [13.4 +/- 3.4 vs. 14.6 +/- 4.7 ng/ml (GHND vs. normal); P = NS] and clonidine [19.0 +/- 2.2 vs. 23.3 +/- 3.8 ng/ml (GHND vs. normal); P = NS] were preserved in GHND children. In GH-deficient children, mean peak serum GH concentrations after all four provocative tests were low (arginine, 2.7 +/- 0.8; insulin, 2.6 +/- 0.8; L-dopa, 3.0 +/- 0.9; clonidine, 3.4 +/- 1.0 ng/ml; all P less than 0.01 vs. normal). The mean peak serum GH concentration after GHRH was blunted in GH-deficient children (9.1 +/- 1.7 ng/ml) compared to those in GHND (32.9 +/- 8.5 ng/ml) and normal (43.2 +/- 6.4 ng/ml) children (P less than 0.01). The area under the GH curve after GHRH stimulation was greater for normal than GHND children (P less than 0.05). These data demonstrate preservation of dopaminergic and alpha-adrenergic neurotransmitter pathways in GHND children. They further suggest a defect in the release of pituitary GH secondary to an abnormality in alternative neurotransmitter pathways resulting in decreased GHRH and/or increased somatostatin secretion.
Assuntos
Dopamina/fisiologia , Hormônio do Crescimento/metabolismo , Receptores Adrenérgicos alfa/fisiologia , Adolescente , Arginina , Criança , Clonidina , Feminino , Transtornos do Crescimento/sangue , Hormônio Liberador de Hormônio do Crescimento , Humanos , Insulina , Levodopa , MasculinoRESUMO
GH secretion was studied in 73 children with classical GH deficiency or GH neurosecretory dysfunction (GHND), intrinsic short stature, or normal stature. The GH-deficient group was defined by a peak GH secretory response below 10 ng/ml to all provocative tests (arginine, L-dopa, insulin hypoglycemia, and clonidine). GHND was defined by a mean serum 24-h GH concentration below 3 ng/ml, with a normal response (greater than or equal to 10 ng/ml) to provocative testing. Twenty-one GH-deficient children, 21 children with GHND, and 18 short control children underwent provocative GH testing and a 24-h study with GH sampling every 20 min. A group of 13 normal stature control children also underwent 24-h GH sampling. The mean stimulated peak serum GH level [4.7 +/- 0.6 (+/- SEM) ng/ml] in the GH-deficient group was significantly below that in the GHND (19.5 +/- 1.7 ng/ml) and short control groups (24.0 +/- 3.5 ng/ml; P less than 0.01). The mean 24-h serum GH concentration was reduced in GH-deficient (1.5 +/- 0.2 ng/ml) and GHND (2.0 +/- 0.1 ng/ml) children compared to those in short (5.6 +/- 0.5 ng/ml) and normal stature (5.8 +/- 0.8 ng/ml) control children (P less than 0.01). Peak GH concentrations after provocative testing correlated poorly with 24-h mean concentrations in GH-deficient, GHND, and short control children (r = 0.38, 0.23, and 0.41, respectively; P = NS for all groups). Mean serum GH concentrations from blood sampling intervals of 12 h (day/night; 0800-2000/2000-0800 h, respectively) or even 6 h (day; 0900-1500 h) were statistically different in GHND or GH-deficient groups compared to those in control children; however, there was significantly more overlap for individual children using the 6- and 12-h daytime intervals than for the 24-h data. Plasma somatomedin-C/insulin-like growth factor I correlated with mean 24-h GH concentration endogenous secretion (r = 0.7; P less than 0.001). These data suggest that provocative GH testing frequently does not correlate with endogenous GH secretion.
Assuntos
Transtornos do Crescimento/sangue , Hormônio do Crescimento/metabolismo , Adolescente , Adulto , Arginina , Criança , Pré-Escolar , Ritmo Circadiano , Clonidina , Feminino , Hormônio do Crescimento/sangue , Humanos , Insulina , Fator de Crescimento Insulin-Like I/sangue , Levodopa , MasculinoRESUMO
A urinary product with immunological similarity to Gn-RH has been quantified by radioimmunoassay. The i-Gn-RH-like material apparently has a (partial) structure consistent with the 5 leads to 9 amino acid sequence of hypothalamic Gn-RH. It inhibits the binding of 125I-Gn-RH to anti Gn-RH serum in a manner parallel to synthetic standard, is absorbed by incubation with anti Gn-RH serum, and comigrates with synthetic Gn-RH on Sephadex column chromatography. The concentration of i-Gn-RH-like material is maximal in pubertal males. The total urinary excretion of this substance is two-fold greater in pubertal subjects of both sexes than in prepubertal children. There is no diurnal variation in the excretion of this material. There are significant positive correlations between the urinary content of iGN-RH-like material and LH and FSH. The site of origin, structure and physiological significance of this immunological product remain to be elucidated.
Assuntos
Hormônio Liberador de Gonadotropina/urina , Puberdade , Adolescente , Adulto , Fatores Etários , Animais , Criança , Pré-Escolar , Reações Cruzadas , Feminino , Hormônio Liberador de Gonadotropina/imunologia , Humanos , Masculino , Coelhos/imunologia , Radioimunoensaio , Fatores Sexuais , Relação Estrutura-AtividadeRESUMO
LH-RH was administered to 17 normal prepubertal and 14 pubertal children as well as to 6 GH deficient prepubertal patients. Urinary immunoreactive LH and FSH were measured in acetone extracts of 3 h collections prior to, during, and immediately after a 3 h infusion of 100 mug LH-RH. Peak LH excretion in response to LH-RH was higher in pubertal than prepubertal children. Girls excreted larger quantities of FSH after LH-RH than did boys. Serum LH and FSH increments evoked by LH-RH correlated significantly (P less than 0.01) with peak urinary gonadotropin excretion. These data suggest that measurement of urinary immunoreactive LH and FSH prior to and after LH-RH administration is clinically useful in evaluation of the reproductive endocrine system of young children and of individuals with low basal levels of gonadotropin.
Assuntos
Hormônio Foliculoestimulante/metabolismo , Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Luteinizante/metabolismo , Adolescente , Criança , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/urina , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio do Crescimento/deficiência , Humanos , Infusões Parenterais , Hormônio Luteinizante/sangue , Hormônio Luteinizante/urina , Masculino , Puberdade , Fatores SexuaisRESUMO
The pattern of LHRH-evoked release of LH and FSH by pituitary gonadotrophs and the concomitant gonadal steroid secretion were studied in 28 pubertal and 16 prepubertal children. LHRH was administered at doses of 100 mug and 10 mug by a constant-infusion pump over 3 hours following a 2-hour control period. Gonadotropin concentrations were measured at 15-minutes intervals. Mean LH concentrations rose from 2.0 +/- 0.4 (SE) mIU/ml (IRP-2-hMG) to 6.2 +/- 0.9 (P less than .001) in normal prepubertal and from 5.8 +/- 0.9 to 28.0 +/- 3.6 (P less than .001) in normal pubertal children. The peak rise of LH, the mean level attained during the LHRH infusion, and the area under the time-response curve were greater (P less than .001) in pubertal than prepubertal children. The serum LH rise had two components in pubertal children in contrast to a single-phased increase in prepubertal children. Pulsatile release of LH was demonstrated during the basal period in pubertal children and during the LHRH infusion in both groups. FSH release was greater in girls than boys at both stages of pubertal development. A 10 mug LHRH infusion released less LH than did 100 mug in the pubertal children, but more than in prepubertal children. In pubertal boys, plasma testosterone rose (P less than .001) from 222 +/- 45 ng/dl in the control period to 301 +/- 59 following 100 mug LHRH. There was no change in plasma testosterone in the prepubertal boys after 100 mug LHRH or in the pubertal boys following 10 mug LHRH. Plasma estradiol did not rise in girls of either maturity group. In children with hypogonadotropic hypogonadism and structural abnormalities of the hypothalamic-pituitary region, there was no LHRH-evoked gonadotropin release. In 2 agonadal girls, the secretion of LH and FSH was greatly exaggerated. The 3-hour LHRH infusion evoked a maturity-related pituitary LH release and a sex-specific FSH release; a 2-phased pattern of LH secretion was present in pubertal but not in prepubertal children; pulsatile LH release was evoked by the LHRH infusion in prepubertal children.
Assuntos
Hormônio Liberador de Gonadotropina , Gonadotropinas Hipofisárias/metabolismo , Hipogonadismo/fisiopatologia , Puberdade , Adolescente , Criança , Pré-Escolar , Estradiol/metabolismo , Feminino , Hormônio Foliculoestimulante/metabolismo , Humanos , Hipogonadismo/diagnóstico , Hipotálamo/metabolismo , Lactente , Hormônio Luteinizante/metabolismo , Masculino , Ovário/metabolismo , Hipófise/metabolismo , Testículo/metabolismo , Testosterona/metabolismoRESUMO
PRL secretion was determined in 63 children undergoing evaluation of GH status. Children were assigned to 1 of 3 groups based on GH studies: group 1, those with abnormal GH responses to provocative testing (n = 23); group 2, children with normal GH responses to provocative testing and mean 24-h GH concentrations below 2.5 micrograms/L (n = 14); or group 3, those with normal stimulated GH secretion and mean 24-h GH concentrations of 2.5 micrograms/L or more (n = 26). Serum PRL concentrations were measured in daytime (0800-1600 h), nighttime (2200-0600 h), and 24-h pools of serum specimens obtained every 20 min over a 24-h period. Mean (+/- SD) daytime (17.5 +/- 14.3 micrograms/L) and 24-h (19.2 +/- 13.0 micrograms/L) pool PRL concentrations were significantly higher in group 1 than in group 3 (daytime, 6.7 +/- 2.3; 24 h, 10.2 +/- 2.5 micrograms/L; P less than 0.01). Mean nighttime pool PRL concentrations did not differ among groups. Mean nighttime pool PRL values were significantly higher (P less than 0.01) than daytime pool values in group 3 (nighttime pool, 13.6 +/- 3.6 micrograms/L; night to day ratio, 2.2 +/- 1.0) and group 2 (16.8 +/- 9.0 micrograms/L; night to day ratio, 2.5 +/- 1.5), but not within group 1 (21.4 +/- 13.5 micrograms/L; night to day ratio, 1.4 +/- 0.5). The mean peak and increment in PRL concentrations after an iv bolus of insulin-TSH-LHRH were not different among groups. The mean decrement in serum PRL level after L-dopa ingestion was greater in group 1 than in group 3 (P less than 0.05). Two children in group 2 and 10 in group 1 had significantly elevated daytime pool PRL concentrations (greater than 11.3 micrograms/L; 2 SD above the mean value for group 3). Two additional children in group 2 and 2 in group 1 had elevated 24-h (greater than 15.2 micrograms/L) pool PRL concentrations. One child in group 2 and 3 in group 1 had low 24-h PRL concentrations (less than 5.2 micrograms/L; less than 2 SD below the mean of group 3). Fourteen of 20 children with elevated daytime and/or 24-h pool PRL levels or low 24-h pool PRL values had structural or radiation-associated insults to the hypothalamic-pituitary axis evident in the history or with brain-imaging techniques; 1 had microphallus with panhypopituitarism and 5 children had no structural abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Transtornos do Crescimento/fisiopatologia , Hormônio do Crescimento/metabolismo , Prolactina/metabolismo , Adolescente , Estatura , Criança , Ritmo Circadiano , Feminino , Hormônio Liberador de Gonadotropina , Transtornos do Crescimento/sangue , Hormônio do Crescimento/sangue , Hormônio do Crescimento/deficiência , Humanos , Insulina , Fator de Crescimento Insulin-Like I/deficiência , Levodopa , Masculino , Prolactina/sangue , Hormônio Liberador de TireotropinaRESUMO
Immunoreactive LRH (iLRH)-like material has been measured in extracts of urine from normal children and adolescents, adult men and women, and postmenopausal women. The urinary excretion of iLRH-like material was significantly greater in pubertal than in prepubertal subjects and in boys than girls at both stages of sexual maturation [prepubertal males, 3.26 +/- 0.49 ng/24 h (SE; n = 24); pubertal males, 5.94 +/- 1.36 (n = 12); prepubertal females, 1.14 +/- 0.21 (n = 19); pubertal females, 2.85 +/- 0.56 (n = 13)]. In adult males (n = 5) the urinary excretion of iLRH-like material was 7.8 +/- 1.3 ng/24 h, and in adult women in the follicular phase of the menstrual cycle (n = 8) it was 2.9 +/- 0.3. In five postmenopausal women the urinary iLRH-like content was 7.32 +/- 0.92 ng/24 h (P less than 0.01 relative to normal pubertal and adult women). In children the 24-h urinary excretion of iLRH-like material was positively correlated with chronological and bone ages, Tanner stage of genital (male) and breast (female) development, and the urinary excretion of LH and FSH in males. It did not correlate with the urinary excretion of either LH or FSH in females. Carboxymethylcellulose chromatography of extracts of urine from pubertal boys and girls, adult men and women, and postmenopausal women suggested that the iLRH-like material may be the 2-10 fragment of LRH rather than the intact decapeptide.
Assuntos
Hormônio Liberador de Gonadotropina/urina , Puberdade , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Fase Folicular , Humanos , Lactente , Masculino , Menopausa , Pessoa de Meia-Idade , Fatores Sexuais , Maturidade SexualRESUMO
Generalized resistance to thyroid hormones (GRTH) commonly results from mutations in the T3-binding domain of the c-erbA beta thyroid hormone receptor gene. We have reported on a novel deletion mutation in c-erbA beta in a kindred, S, with GRTH. One patient from this kindred was the product of a consanguineous union from two affected members and was homozygous for the beta-receptor defect. This patient at 3.5 weeks of age had unprecedented elevations of TSH, free T4, and free T3 (TSH, 389 mU/L; free T4, 330.8 pmol/L; free T3, 82,719 fmol/L). He displayed a complex mixture of tissue-specific hyperthyroidism and hypothyroidism. He had delayed growth (height age, 1 3/12 yr at chronological age 2 9/12 yr) and skeletal maturation (bone age, 4 months), and developmental delay (developmental age, 8 months), but he was quite tachycardic. The homozygous patient of kindred S is markedly different from a recently reported patient with no c-erbA beta-receptor. This difference indicates that a dominant negative form of c-erbA beta in man can inhibit at least some thyroid hormone action mediated by the c-erbA alpha-receptors.
Assuntos
Homozigoto , Mutação , Proteínas Proto-Oncogênicas/genética , Proto-Oncogenes , Receptores dos Hormônios Tireóideos/genética , Doenças da Glândula Tireoide/genética , Adolescente , Adulto , Células Cultivadas , Pré-Escolar , Deleção Cromossômica , DNA/genética , DNA/isolamento & purificação , Enzimas de Restrição do DNA , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Linhagem , Polimorfismo de Fragmento de Restrição , Cintilografia , Pele/metabolismo , Doenças da Glândula Tireoide/diagnóstico , Doenças da Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/diagnóstico por imagem , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
Klinefelter syndrome of testicular dysgenesis is the most common form of male hypogonadism. It may be suspected and identified by specific physical signs in infants, children, and adolescents as well as in adults. This review discusses the genetics, clinical manifestations, complications, and treatment of Klinefelter syndrome and its variants.
Assuntos
Síndrome de Klinefelter , Testículo/anormalidades , Humanos , Cariotipagem , Síndrome de Klinefelter/complicações , Síndrome de Klinefelter/tratamento farmacológico , Síndrome de Klinefelter/genética , Síndrome de Klinefelter/patologia , Síndrome de Klinefelter/fisiopatologia , Síndrome de Klinefelter/psicologia , Masculino , Testosterona/uso terapêuticoRESUMO
During adolescence, there are marked changes in the metabolism of calcium and phosphorus and a dramatic increase in the rate of bone mineralization under the influence of the sex hormones, growth hormone, and insulin-like growth factor-1. More than 50% of adult bone mass is accumulated during puberty; failure to achieve maximum bone mineralization at this time may lead to osteopenia and its complications in later adulthood. This article discusses the causes, evaluation, and management of adolescents with hypocalcemia, hypercalcemia, and disorders of bone mineralization.
Assuntos
Distúrbios do Metabolismo do Cálcio/metabolismo , Distúrbios do Metabolismo do Fósforo/metabolismo , Adolescente , Cálcio/metabolismo , Feminino , Humanos , Masculino , Fósforo/metabolismoRESUMO
The role of hypercalciuria and hyperphosphaturia in the growth retardation of children with diabetes mellitus was investigated in 157 children with diabetes whose mean height was less than that of 37 nondiabetic siblings of similar age (P less than .025). Hyperglycemia, hypercalciuria, and hyperphosphaturia were assessed coincident with the height measurement of each child in a cross-sectional survey. The distribution of height percentiles of the children with diabetes was skewed to the left with 61% at or below the 50th percentile. Eleven percent of the insulin-dependent children with diabetes mellitus were shorter than would be anticipated by a normal distribution of the 157 children. The duration of diabetes (hyperglycemia) had the greatest influence upon the children's height. Children with diabetes were shorter than the nondiabetic subjects by the fourth year of hyperglycemia, and this difference in height became statistically significant after 7 years or more of diabetes. The degree of hypercalciuria and hyperphosphaturia was more closely associated with reduced height in children with diabetes than was the degree of hyperglycemia, although the renal wastage of calcium and phosphorus seemed to be the result of glucosuria. Because hypercalciuria and hyperphosphaturia impair growth in nondiabetic children, they may also play an important role in the poor growth of children with diabetes mellitus.
Assuntos
Cálcio/urina , Diabetes Mellitus Tipo 1/metabolismo , Transtornos do Crescimento/metabolismo , Fosfatos/urina , Adolescente , Estatura , Criança , Doença Crônica , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Transtornos do Crescimento/etiologia , Humanos , Hiperglicemia/complicações , Hiperglicemia/metabolismo , MasculinoRESUMO
Estrogen has a biphasic effect on growth, stimulatory at low doses but inhibitory at higher doses. Therefore, designing optimal sex hormone replacement treatment in girls with Turner syndrome (TS) who are being treated with growth hormone (GH) involves considering the dose and form of the estrogen as well as the route and timing of its administration. We report here a preliminary analysis of a study to test the concept that an optimal estrogen replacement regimen should consist of estradiol administered in a low dose by a systemic route. The study population consisted of 9 girls with TS who had been treated with GH for 6 or more months. When the girls were 12 to 15 years old, we added depot estradiol at a monthly intramuscular dose of 0.2 mg and increased the dose at 6-month intervals to 0.4, 0.6, and, in 7 of the girls, 0.8 mg. We compared the results in these subjects with those in a matched group of 37 patients with TS in whom routine estrogen treatment had been started at similar ages and who were treated with a similar course of GH therapy. The gain in height at 2 years was 2.6 cm greater in those who were treated with depot estradiol than in those who were treated with routine estrogen. The bone age in the patients who were treated with depot estradiol increased in proportion to their chronologic age, suggesting that this difference indicates an increase in their predicted adult height. We conclude that using very low doses of systemic estradiol to induce puberty before the age of 15 years in girls with TS who are treated with GH, instead of using routine estrogen therapy, can result in increased final heights.
Assuntos
Terapia de Reposição de Estrogênios , Transtornos do Crescimento/terapia , Síndrome de Turner/terapia , Adolescente , Estatura , Criança , Preparações de Ação Retardada , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios/métodos , Feminino , Transtornos do Crescimento/complicações , Hormônio do Crescimento/uso terapêutico , Humanos , Síndrome de Turner/complicações , Síndrome de Turner/fisiopatologiaRESUMO
We analyzed 12-hour serial sampling of growth hormone (GH) levels in two cohorts of short children: 96 children referred to a university endocrine clinic or studied on a research protocol and 825 children in the National Cooperative Growth Study of children treated with exogenous GH. The mean 12-hour GH levels correlated with growth velocity in 60 children with normal height and growth velocity in the university study, and this correlation was stronger in the boys. The testosterone levels also correlated with growth velocity and mean 12-hour GH levels in the boys. The mean 12-hour GH levels were lower in a group of 36 children with idiopathic short stature than in the control subjects, as were the peak GH levels within 1 hour after the onset of sleep and the insulin-like growth factor I levels. In the National Cooperative Growth Study cohort, pooled 12-hour GH levels were lower in the group with idiopathic GH deficiency (n = 300) than in the group with idiopathic short stature (n = 525), but the difference was not significant. The duration of GH treatment was the most significant predictor of change in the height SD score in both groups. Indices of spontaneous secretion of GH were not predictive of the response to GH treatment, nor were the results of provocative GH testing, the responses to GH treatment being similar in both groups over time. We conclude that the results of GH testing must be interpreted for each patient and that several testing modalities may be helpful in finding GH insufficiency that originates at various levels of the somatotropic axis.
Assuntos
Hormônio do Crescimento/sangue , Hormônio do Crescimento/deficiência , Coleta de Amostras Sanguíneas , Estatura , Criança , Feminino , Crescimento , Transtornos do Crescimento/diagnóstico , Humanos , MasculinoRESUMO
Pituitary content or concentration of follicle-stimulating hormone (FSH), prolactin and growth hormone in the genetically androgen insensitive male rat pseudohermaphrodite is intermediate between normal male and female rats, while pituitary luteinizing hormone (LH) concentration and serum FSH levels are the same as in the normal male. The concentration of serum LH, prolactin and growth hormone indicated no sexual dimorphism. Although the pseudohermaphrodite is genetically male with a female phenotype, our results suggest some degree of masculinization of the hypothalamic-pituitary system.