Frequency of glutamic acid decarboxylase autoantibodies in Mexican diabetic children.

OBJECTIVE: Use radio binding assay (RBA) to quantify the frequency of autoantibodies to glutamic acid decarboxylase in Mexican children with type 1 diabetes mellitus (DM 1). RESEARCH DESIGN AND METHODS: GAD antibodies were measured in 140 mestizo children with DM 1, 66 female (47.14%) and 74 male (52.8%); age 11.7 +/- 3.55 years, and range 1.10 to 18.5 years. Most patients were treated with intermediate acting insulin, and some with the former combined with regular insulin. Mean disease duration was 3.11 +/- 2.94 years, and range 1 month to 14.5 years. Once the signed written consent was obtained, a 5.0-mL blood sample was drawn, immediately centrifuged, and the serum was kept frozen to -20 degrees C until RBA evaluation was performed with a commercial kit. RESULTS: The anti-GAD was positive in 76 DM 1 patients (54.28%) with values from 1.11 to 156.73 U/mL, and negative in 64 (45.71%). In 19 positive anti-GAD patients, the test was repeated and levels were found between 1.38 and 156.62 U/mL. An initial control group consisting of 25 healthy non-related volunteers matched by sex and age, showed negative anti-GAD for all. CONCLUSIONS: The frequency of anti-GAD in these patients was lower than that of the DM 1 European patients, but similar to that of Asians. This supports the heterogeneity of the etiopathogenic factors of DM 1 in different ethnic groups.

[Final results of the administration of biosynthetic growth hormone. Preliminary report]. / Resultado final de la administración de hormona de crecimiento biosintética. Informe preliminar.

From March, 1987 to November, 1995, we have included 89 growth hormone-deficient children for treatment for their low height with the biosynthetic growth hormone; 23 of them have concluded treatment. Without taking into account the etiological factor of their deficiency, 6 girls and 17 boys during different lapses had modified their initial height and the scores of the standard deviation as groups, range from 113.11 +/- 14.83 cm and -5.12 +/- 1.21 to 139.11 +/- 8.96 cm. and -2.68 +/- 1.17 in the girls, and from 128.46 +/- 12.49 cm and -4.13 +/- 1.35 to 158.61 +/- 6.47 cm and -1.76 +/- 0.9 in the boys, respectively. These results between the initial height and the score of the standard deviation compared with the final height and the standard deviation score, showed a statistically significant difference of p < 0.001 both in girls and boys. Two girls and 3 boys developed hypothyroidism during the treatment, without any other side effect. We concluded that early and prolonged biosynthetic growth hormone administration in growth hormone-deficient children might produce a final adult height similar to the normal population standards.

Molecular genetic analysis of patients carrying steroid 21-hydroxylase deficiency in the Mexican population: identification of possible new mutations and high prevalence of apparent germ-line mutations.

Steroid 21-hydroxylase deficiency is the underlying cause in over 90% of patients with congenital adrenal hyperplasia, an inherited metabolic disorder of adrenal steroidogenesis. We have characterized 94 mutant alleles from 47 unrelated Mexican patients and the corresponding mutant alleles in their parents by amplification of the functional CYP21 gene by PCR, followed by direct sequence analysis. The study included patients diagnosed with the three clinical forms of the disease. Our results revealed: (1) the presence of relatively few mutations or combinations of mutations associated with particular phenotypes; (2) the presence of putative new mutations; (3) the finding of identical genotypes in patients displaying discordant phenotypes; (4) the identification of patients lacking all previous reported mutations; and (5) an apparent high frequency of germ-line mutations. The absence of previously reported mutations in about 22% of the disease alleles, the finding of putative new mutations in some of the patients lacking previously known mutations, and the apparent high prevalence of germ-line mutations make evident the differences in the genetic background leading to this disorder between the Caucasian and the Mexican populations.

Analysis of the glucokinase gene in Mexican families displaying early-onset non-insulin-dependent diabetes mellitus including MODY families.

Non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes, affecting 5% of the general population. Genetic factors play an important role in the development of the disease. While in other populations NIDDM is usually diagnosed after the fifth decade of life, in Mexico a large proportion of patients develop the disease at an early age (between the third and the fourth decade). In Caucasian population, mutations in the glucokinase gene, the TCF1, and TCF14 genes, have been identified in a subgroup of early-onset NIDDM patients denominated MODY (maturity-onset diabetes of the young), which show an autosomal dominant pattern of inheritance. As a first step in the molecular characterization of Mexican families displaying early-onset NIDDM we searched for mutations in the glucokinase gene through SSCP analysis and/or direct sequencing in 26 individuals from 22 independent families, where at least four can be classified as MODY. No mutations were detected in the exons or the intron-exon boundaries of the gene in any of the screened individuals. The phenotype and clinical profile of some of the studied patients is compatible with that of patients carrying mutations in the TCF1 or TCF14 genes, while others may carry mutations in different loci. Through computer simulation analysis we identified at least four informative families which will be used for further linkage studies.

Lipoprotein(a) levels in children and adolescents with diabetes.

OBJECTIVE: To determine lipoprotein(a) in children and adolescents with IDDM and assess its relation with Lp(a) levels in their first degree relatives. RESEARCH DESIGN AND METHODS: In a cross-sectional study we included 141 IDDM patients, (58 male and 83 female) with mean ages 12.2 +/- 2.8 and 12.6 +/- 3.1 years, respectively. Patients with microalbuminuria, hepatopathy, thyroid dysfunction, infectious disease, acute decompensation or surgery three months prior to the study, were excluded. Clinical history, physical examination, blood chemistry, glycosilated hemoglobin, microalbuminuria and lipid profile including total cholesterol triglycerides, HDL-C, Apo A-I, Apo B and Lp(a) were determined. Parents and non-diabetic siblings were also studied when feasible. RESULTS: Mean plasma concentration of total cholesterol, HDL-C and Apo A-I were significantly higher in diabetic boys compared to their non-diabetic sibs. Mean Lp(a) plasma values and the prevalence of Lp(a) > 30 mg/dL were similar in the IDDM patients, their healthy sibs and parents. Hypercholesterolemia and hypertriglyceridemia were more frequent among the IDDM patients. No correlation was found between HbA1, and Lp(a) concentrations. However, a correlation was observed between Lp(a) plasma concentrations of parents and their diabetic and healthy offspring. CONCLUSION: Diabetes mellitus does not seem to affect Lp(a) levels. These data are consistent with a genetic regulation of Lp(a) plasma levels.

Low frequency of deletion alleles in patients with steroid 21-hydroxylase deficiency in a Mexican population.

Steroid 21-hydroxylase deficiency is caused by mutations in the CYP21 gene. Approximately 95% of mutant alleles are generated by recombination events between the active gene CYP21 and its highly homologous pseudogene, CYP21P. Deletion alleles are generated by unequal crossing over, while point mutations are the result of gene conversion events. Deletions account for 20-25% of the 21-hydroxylase deficiency alleles in most populations studied. We have looked for deletions among 53 unrelated Mexican patients with steroid 21-hydroxylase deficiency and found that deletions represent less than 1% of the disease alleles. These findings suggest that nearly all mutant alleles in our patient population contain point mutations and that the low representation of deletion alleles among clinically diagnosed patients may be due to missing detection of salt wasters, mainly males, who may die during the neonatal period.

[Microalbuminuria and macrovascular risk factors in insulin-dependent diabetic children]. / Microalbuminuria y factores de riesgo macrovascular en niños diabéticos insulino-dependientes.

OBJECTIVE: To investigate the prevalence of microalbuminuria in children and teenagers with IDDM and its relationship with other variables. METHODS: We studied 160 IDDM children and teenagers with a mean age of 13 +/- 4 years from our endocrine department outpatient clinic. A complete medical history was obtained as well as a fasting blood sample for glycemia, glycosilated hemoglobin and lipid profile and a urine sample for microalbuminuria using laser immunonephelometry. RESULTS: 13 patients (8%) had microalbuminuria (20-200 micrograms/min) and 5 (3%) clinical proteinuria (> 200 micrograms/min). The abnormal excretion was more prevalent in females with the poorest metabolic control, the longest duration of diabetes, and the highest age (13-18 years). The presence of microalbuminuria or clinical proteinuria associated with a more atherogenic risk profile compared to patients with a normal urinary albumin excretion. CONCLUSIONS: There was a poor metabolic control in our IDDM population. In addition, our current findings in a population with a relatively short duration of their diabetes point out the need to improve an integral management strategy to prevent or delay the late complications associated with IDDM.

[Biosynthetic growth hormone in the treatment of low stature in Turner syndrome]. / Hormona de crecimiento biosintética en el tratamiento de la talla baja del síndrome de Turner.

Fifteen patients with Turner's syndrome with ages between 6.8 to 13.2 years were treated with biosynthetic growth hormone due to their low height. Twelve of them had a 45XO karyotype and three were mosaics; none had a Y line. They started with 0.7 IU/kg/week which were increased to 1.0 IU/kg/week if no height gain was observed during three months. The 15 patients have completed one year of treatment, 8 of them for two years. The height velocity increased significantly (p < 0.001) from 0.24 +/- 0.10 cm/month before treatment (mean +/- SD) to 0.48 +/- 0.09 in the first 12 months of treatment (height increased from 119.1 +/- 8.79 to 124.9 +/- 8.70). In the eight cases who have reached 24 months of treatment, the height velocity increased from 0.27 +/- 0.07 cm/month to 0.47 +/- 0.09 and 0.54 +/- 0.10 at 12 and 24 months respectively (p < 0.001 and p < 0.01 versus the pretreatment gain); height increased from 116.8 +/- 7.0 cm to 122.0 +/- 7.45 and 129.0 +/- 7.18. We found no adverse effects in the patients. It is concluded that the biosynthetic growth hormone treatment in Turner's syndrome can improve low height.

[Metabolic control and the prevalence of dyslipidemia in children and adolescents with insulin-dependent diabetes mellitus]. / El control metabólico y la prevalencia de dislipidemia en niños y adolescentes con diabetes mellitus insulino-dependiente.

Cholesterol, triglycerides and lipoprotein levels were assayed in serum of 152 children and teenagers with IDDM and in 228 non-diabetic siblings. A poor control of diabetes, reflected by high levels of glycosylated hemoglobin and/or high fasting blood glucose, was associated with statistically significant increases in total cholesterol, LDL-cholesterol and triglycerides, and a reduction in HDL-cholesterol. Mean total cholesterol levels in diabetic patients (171 +/- 33 mg/dL for males and 199 +/- 53 mg/dL for females) were statistically higher than those in their siblings (158 +/- 30 mg/dL and 164 +/- 33 mg/dL respectively). The prevalence of hypercholesterolemia (HC) and hypertriglyceridemia (HTG) were higher in the diabetic patients but statistically significant exclusively in females (prevalences of 40% vs 12% for HC and 30% vs 9% for HTG with a p value < 0.005). The diabetic patients in good metabolic control had similar lipid levels to those of their non-diabetic siblings. These data support the hypothesis that poor control of blood glucose is associated with atherogenic lipid profiles. The prevalence of hypercholesterolemia is impressively high in our diabetic population and indicates that all IDDM patients should have a serum lipid and lipoprotein analysis done annually; blood glucose control and dietary guidelines should be improved in these cases.

Tumor primario de células germinales del sistema nervioso central en pediatría: presentación de 14 casos / Primary tumor of germinal cells in pediatric central nervous system: presentation of 14 cases

De 200 casos de tumores primarios del sistema nervioso central, 14 (7 por ciento) resultaron tumores de células germinales, histológicamente 11 de ellos fueron germinomas, dos teratomas inmaduros con áreas de coroacarcinoma y tumor de senos endodérmicos (TI-C-TSE) y un teratoma maduro. Las manifestaciones clínicas iniciales fueron de tipo neuronal y endocrinológicas: hidrocefalia (57 por ciento) de campo visual (50 por ciento), ataxia y signos piramidales (43 por ciento), convulsiones (43 por ciento), paresias de pares craneános (36 por ciento), signo de Parinaud (21 por ciento), atrofia óptica 14 por ciento; hiperprolactinemia (43 por ciento), talla baja (43 por ciento), diabetes insípida (43 por ciento), pubertad precoz, hipotiroidismo e insuficiencia adrenal (7 por ciento) respectivamente. Las tomografías computarizadas de cráneo (TCC) evidenciaron el proceso tumoral en el 100 por ciento de los casos, contrastando con las radiografías simples de cráneo que sólo lo mostraron en el 36 por ciento de los casos. El tratamiento en todos fue cirugía y radioterapia sólo uno recibió quimioterapia, el TI-C.TSE con metástasis pulmonar. Concluimos que los germinomas deberán recibir radioterapia como tratamiento inicial. Es imprescindible la TCC, la búsqueda de células exfoliativas en líquido cefalorraquídeo y marcadores tumorales para el diagnóstico, así como las determinaciones hormonales necesarias

[The null effect of Somatrem during typhoid fever]. / Efecto nulo de Somatrem durante fiebre tifoidea.

The simultaneous occurrence of typhoid fever in a child with an idiopathic growth hormone insufficiency treated with Somatrem, produced a lack of response to the recombinant hormone, evidenced by a lack of growth during the acute disease. It is concluded that the administration of Somatrem should be suspended during the simultaneous occurrence of any severe illness.

[The quantitative analysis of thyroid hormones and thyrotropin in children critically ill with septicemia]. / Cuantificación de hormonas tiroideas y tirotropina en niños críticamente enfermos con septicemia.

The function of the hypothalamus, hypophysis, and thyroid glands was studied in 23 critically-ill septicemic children and 15 other healthy children used as controls. A comparison in the quantification of 3,3'5-triiodothyronine (T3), 3,3',5'triiodothyronine (T3r), thyroxine (T4) and thyrotropin (TSH) from those in the control group with the initial values from the patients showed a notable decrease of T3 and T4 and a rise in T3r and TSH in the septicemic children, with a statistical significant difference (P less than 0.001). These biochemical changes which translate into a homeostatic command to avoid catabolism through the conservation of energy, spontaneously returned to normal in 18 of the surviving septicemic children once they recuperated.

[Clinical and biochemical evaluation of the administration of growth hormone]. / Evaluación clínica y bioquímica de la administración de hormona de crecimiento.

Ten children with isolated growth hormone deficiency were treated for 1 year with 0.5 UI/kg week with Somatrem (recombinant human growth hormone), given as intramuscular injections three times weekly. Before treatment the children had a chronological age of 7-12.4 years (mean 10.4 years), with a bone age at least 25% below the chronological age. There was no radiological evidence of an intra or suprasellar mass in any child, and no response to provocative growth hormone tests (with exercise or arginine-insulin injection). Informed written consent for treatment was obtained from the parents of each child. Clinical signs were registered every month; triiodothyronine, thyroxine, thyrotropine, glucose, urea, creatinine, blood cells count, and hemoglobine, glycosylated hemoglobine, glutamic-piruvic and glutamic-oxalacetic transaminases, alkaline phosphatase, anti-human growth hormone and, E. coli antibodies, insulin like growth factor 1, and bone age were assessed every 3 months. The mean height velocity was 0.27 +/- 0.1 cm/month before treatment, and increased throughout treatment to a value of 0.62 +/- 0.16 cm/month after 12 months. Within the first year eight of the 10 children had a height increase of 8.4 +/- 0.98 cm. The other two children showed no significant difference; one of them with a very low socioeconomic status, and the other developed typhoid fever. All of the children showed an advance in bone age, but none reached a bone age appropriate for their chronological age; without modifications in the laboratory parameters. Insulin like growth factor 1 increased in 9 children. Pain at the injection site was the only side effect reported.

Hipofisectomia transesfenoidal. / Transphenoidal hypophysectomy

La hipofisectomia transesfenoidal a traves de un acceso oronasal a traves de la linea media fue introducida por Cushing en 1907.Guiot y Hardy introdujeron innovaciones tales como el uso de la fluoroscopia transoperatoria y del microscopio quirurgico.Se hizo hipofisectomia transesfenoidal con reseccion total del tumor y la glandula a 18 pacientes tratados en el Servicio de Neurocirugia del Hospital General del CM La Raza IMSS desde febrero de 1975 hasta junio de 1977. Hubo desaparicion de los sintomas de "hiperfuncionamiento" en estos pacientes y mejoria de la hemianopsia en el caso que tenia este defecto campimetrico. Todos los casos recibieron tratamiento hormonal de substitucion. Una paciente murio 36 horas despues de la operacion. En casos de "microadenomas" no debe hacerse reseccion total de la glandula, sino unicamente del tumor

Treatment of ketoacidosis and diabetic coma by continuous intravenous administration of water, glucose, regular insulin and electrolytes.

The therapeutical scheme prescribed for the treatment of ketoacidosis and diabetic coma before the 1970s is quite stereotyped and inflexible in regard to the routes of administration and doses of insulin, as well as the management of dehydration and metabolic acidosis. This paper reports the experience of the Endocrinology Service of the General Hospital of the "La Raza" Medical Center for over 10 years. 35 patients with diabetic ketoacidosis were included in a treatment by continuous intravenous administration of glucose, water, insulin and potassium. These patients were programmed in a 12 hour study. The dose of insulin was estimated at a ratio of 1 IU per 1 gm of excess glucose over 2.0 gm/l. The amount of glucose administered was in ratio to the caloric requirements per kilo of bodyweight of the individual patient. The volume of water was administered on the basis of the degree of dehydration estimated. The potassium was prescribed at a ratio of 20 mEq/l of solution, or more if necessary. The patient's recovery was observed during a period of from 7 to 10 hours, with improvement of the hyperglycemia, dehydration and metabolic acidosis. The method has allowed us to observe the diabetic patient's rapid recovery when he has been in ketoacidosis or coma, without complications such as hypoglycemia. No mortality was observed.

Circulating gonadotropin pattern in anorchia syndrome. Response to treatment.

Two anorchidic brothers, 16 and 25 years of age were studied; three, 60 min interval samples were drawn on the day -1 followed by a daily sample for five days, and after every seven days. 25 mg of testosterone propionate were administered daily during 24 days and after, 100 mg of testosterone enanthate were administered every 14 days (prolonged action). Testosterone, F S H and L H were quantified by R I A. Testosterone concentrations were 0.75 and 0.52 ng/ml; F S H 22.0 and 24.0 ng/ml and L H, 18.0 and 25.0 ng/ml respectively in A. F. M. and A.F.J. With testosterone propinate, F S H basal levels were decreased in 53 and 55 per cent, and L H, 80 and 86 per cent in A.F.M. and A.F.J. respectively. With prolonged action testosterone, F S H and L H levels were within normal limits after a 7 day administration course. Due to the decrease in F S H and L H initial levels as a result of treatment we concluded that in the anorchia syndrome, receptors in the hypothalamus - pituitary axis maintain their normal ability of feedback mechanism response with testosterone administration and thus prolonged action testosterone is the best substitute.