Fractures of the proximal femur: correlation with vitamin D receptor gene polymorphism

Fractures are the feared consequences of osteoporosis and fractures of the proximal femur (FPF) are those that involve the highest morbidity and mortality. Thus far, evaluation of bone mineral density (BMD) is the best way to determine the risk of fracture. Genetic inheritance, in turn, is one of the major determinants of BMD. A correlation between different genotypes of the vitamin D receptor (VDR) and BMD has been recently reported. On this basis, we decided to determine the importance of the determination of VDR genotype in the presence of an osteoporotic FPF in a Brazilian population. We studied three groups: group I consisted of 73 elderly subjects older than 65 years (78.5 ± 7.2 years) hospitalized for nonpathological FPF; group II consisted of 50 individuals older than 65 years (72.9 ± 5.2 years) without FPF and group III consisted of 98 young normal Brazilian individuals aged 32.6 ± 6.6 years (mean ± SD). Analysis of VDR gene polymorphism by restriction fragment length polymorphism (RFLP) was performed by PCR amplification followed by BsmI digestion of DNA isolated from peripheral leukocytes. The genotype distribution in group I was 20.5% BB, 42.5% Bb and 37% bb and did not differ significantly from the values obtained for group II (16% BB, 36% Bb and 48% bb) or for group III (10.2% BB, 47.6% Bb and 41.8% bb). No differences in genotype distribution were observed between sexes or between the young and elderly groups. We conclude that determination of VDR polymorphism is of no practical use for the prediction of FPF. Other nongenetic factors probably start to affect bone mass, the risk to fall and consequently the occurrence of osteoporotic fractures with advancing age.A01Universidade Federal de São Paulo (UNIFESP)Hospital do Servidor Público Estadual de São PauloUNIFESPSciEL

Evidence for thyroid hormone as a positive regulator of serum thyrotropin bioactivity

Context: the regulation of TSH bioactivity in humans is not completely understood.Objective: the aim of the study was to investigate the role of serum thyroid hormones in regulating the bioactivity of TSH.Design: We determined in vitro TSH bioactivity and glycosylation in nine patients (six females and three males, age 41.3 yr) with primary hypothyroidism before and after L-T(4) replacement, in 11 age- and sex-comparable controls (seven females and four males, age 37.6 yr), and in two thyroidectomized patients with TSH-secreting adenomas during and after L-T4 withdrawal.Methods: in vitro TSH bioactivity was measured by a sensitive and specific bioassay based on cAMP generation by Chinese hamster ovary cells transfected with human TSH receptor. TSH glycosylation was assessed by concanavalin A lectin and ricin column affinity chromatography.Results: in vitro TSH bioactivity in hypothyroid patients was low as compared with controls (0.48 +/- 0.1 vs. 1.1 +/- 0.2; P = 0.004) and increased during L-T(4) (0.48 +/- 0.1 vs. 0.8 +/- 0.1; P = 0.01). A strong significant correlation (r = + 0.80; P = 0.004, Spearman) was observed between the absolute increments of serum TSH bioactivity and T(3) during L-T(4) replacement. the degree of sialylation was elevated in hypothyroid patients before treatment (47 +/- 2.4% vs. 29 +/- 4.3%; P = 0.002) and decreased significantly after L-T4 (47 +/- 2.4% vs. 33 +/- 4.3%; P = 0.02). the mannose content of serum TSH in hypothyroid patients was similar to controls and did not change during L- T(4). in vitro TSH bioactivity also decreased in patients with TSH-secreting adenomas during L-T(4) withdrawal.Conclusion: These data indicate that serum thyroid hormone level is a positive regulator of TSH bioactivity.Universidade Federal de São Paulo, Dept Med, Div Endocrinol, Neuroendocrine Unit, BR-04039002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Endocrinol, Neuroendocrine Unit, BR-04039002 São Paulo, BrazilWeb of Scienc

PARATHYROID-HORMONE SECRETORY RESERVE IN PATIENTS SUBMITTED TO 131-IODINE THERAPY FOR HYPERTHYROIDISM

Twelve euthyroid patients who had been treated with I-131 for hyperthyroidism due to Graves' disease and six normal controls were submitted to an EDTA infusion test. Ionized calcium and parathyroid hormone were measured in serum samples collected every 10 min during the 2-h test. Basal values for calcium (1.22 +/- 0.03 vs 1.23 +/- 0.03 pmol/l, mean +/- SD, controls vs patients) and parathyroid hormone (3.3 +/- 0.65 vs 5.1 +/- 2.32 pmol/l) as well as maximum response during infusion (1.01 +/- 0.04 vs 1.01 +/- 0.05 for calcium and 12.0 +/- 2.2 vs 13.1 +/- 3.7 for parathyroid hormone) were not significantly different. We conclude that I-131 treatment for hyperthyroidism due to Graves' disease had no effect on the parathyroid gland secretory reserve of the patients studied.ESCOLA PAULISTA MED SCH,DISCIPLINA ENDOCRINOL,CAIXA POSTAL 20266,BR-04619 SAO PAULO,SP,BRAZILESCOLA PAULISTA MED SCH,DISCIPLINA ENDOCRINOL,CAIXA POSTAL 20266,BR-04619 SAO PAULO,SP,BRAZILWeb of Scienc

MONOCLONAL-ANTIBODIES SPECIFIC FOR THE FREE ALPHA-SUBUNIT OF GLYCOPROTEIN HORMONES AND THEIR USE IN THE DEVELOPMENT OF A SENSITIVE IMMUNOFLUOROMETRIC ASSAY

Glycoprotein hormone free alpha subunit has been used as a marker for some pituitary tumors and to study the reactivity of glycoprotein hormone-producing cells under different circumstances. We describe a highly sensitive and specific immunofluorometric assay for the measurement of serum free alpha subunit levels. The assay is based on a monoclonal antibody, specific for free alpha subunit, bound to microtiter plates. As tracer antibody we employed an europium-labelled free/complexed alpha subunit specific monoclonal antibody. Using overnight incubation and 50-mu l samples, the least detectable dose was of the order of 4 ng/l. Cross-reactivity with LH, TSH, FSH and hCG was 6.5, 1.2, 4.3 and 1.1%, respectively. Normal adult males showed values ranging from 120 to 790 ng/l, not different from normal adult premenopausal females (88 to 604 ng/l). In post-menopausal females, serum concentrations were significantly higher, ranging from 341 to 4071 ng/l. In 56 patients with untreated pituitary tumors (18 ''non-secreting'', 25 GH-producing and 13 prolactin-producing tumors), 10 showed high values, 3 of them from the first group, 3 from the second and 4- from the third. We conclude that this highly sensitive assay can be a valuable tool for the diagnosis and followup of selected patients with pituitary tumors and in other circumstances in which the glycoprotein hormone-producing cells of the pituitary require evaluation.UNIV FED SAO PAULO,ESCOLA PAULISTA MED,DEPT MED,DISCIPLINA ENDOCRINOL,CAIXA POSTAL 20266,BR-04034970 SAO PAULO,BRAZILUNIV FED SAO PAULO,ESCOLA PAULISTA MED,DEPT MED,DISCIPLINA ENDOCRINOL,CAIXA POSTAL 20266,BR-04034970 SAO PAULO,BRAZILWeb of Scienc

Lipoatrofia generalizada atípica e resistência insulínica grave devido à mutação p.T10I em heterozigose no gene LMNA

Lipodystrophies are a group of heterogeneous disorders characterized by the loss of adipose tissue and metabolic complications. The main familial forms of lipodystrophy are Congenital Generalized Lipodystrophy and Familial Partial Lipodystrophy (FPLD). FPLD may result from mutations in the LMNA gene. Besides FPLD, mutations in LMNA have been shown to be responsible for other inherited diseases called laminopathies. Here we describe the case of a 15-year-old girl who was referred to our service due to diabetes mellitus and severe hypertriglyceridemia. Physical examination revealed generalized loss of subcutaneous fat, confirmed by DEXA (total body fat 8.6%). As the patient presented with pubertal-onset of generalized lipodystrophy and insulin resistance, molecular analysis of the LMNA gene was performed. We identified a heterozygous substitution in exon 1 (c.29C > T) predicting a p.T101 mutation. In summary, we describe an atypical phenotype of lipodistrophy associated with a de novo appearance of the p.T101 mutation in LMNA gene. (Arq Bras Endocrinol Metab 2008; 52/8:1252-1256)Univ Fed Sao Paulo, Escola Paulista Med, Disciplina Endocrinol, BR-04034970 Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Disciplina Endocrinol, BR-04034970 Sao Paulo, BrazilWeb of Scienc

Persistent hyperactivity of the parathyroid glands in treated hypothyroid patients

Twelve untreated hypothyroid patients were submitted to EDTA infusion and the parathyroid hormone response to the induced hypocalcemia was studied with an amino-terminal specific assay. Eight of these patients were retested 6 months after achieving clinical and laboratory euthyroidism. The PTH response in the pretreatment condition was significantly higher than that obtained in a group of 10 normal individuals; this increased response had not normalized after 6 months of euthyroidism. This persisting hyperresponsiveness can be a contributory factor to the bone hypersensitivity to thyroid hormone replacement seen in hypothyroid patients.ESCOLA PAULISTA MED SCH,DIV ENDOCRINOL,CP 20266,BR-04034 SAO PAULO,BRAZILESCOLA PAULISTA MED SCH,DIV ENDOCRINOL,CP 20266,BR-04034 SAO PAULO,BRAZILWeb of Scienc

Influence of the polymorphisms Tpr64Arg in the beta 3-adrenergic receptor gene and Pro12Ala in the PPAR gamma 2 gene on metabolic syndrome-related phenotypes in an indigenous population of the Brazilian Amazon

Universidade Federal de São Paulo, Escola Paulista Med, Dept Med, Div Endocrinol,Disciplina Endocrinol, BR-04034970 São Paulo, BrazilUniv São Paulo, Fac Med Ribeirao Preto, Dept Social Med, São Paulo, BrazilUniv São Paulo, Dept Biol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Med, Div Endocrinol,Disciplina Endocrinol, BR-04034970 São Paulo, BrazilWeb of Scienc

Effect of long-term corticosteroid (cs) treatment on the biochemical markers of bone formation

FLWINinfo:eu-repo/semantics/publishedSupplement: Journal of Bone and Mineral Research. ASBMR 19th annual meetin