Diagnostic value of ultrasonography to distinguish between benign and malignant lesions in the management of thyroid nodules.

OBJECTIVE: We analyzed the sonographic characteristics of thyroid nodules and assessed the diagnostic value of ultrasonography in order to distinguish between benign and malignant lesions in terms of the management of thyroid nodules. DESIGN: We retrospectively analyzed the sonographic features of thyroid nodules in 580 patients who had been examined with fine-needle aspiration cytology or who underwent surgery for a thyroid nodule. The sonographic features that suggested malignancy include microcalcifications, an irregular or microlobulated margin, marked hypoechogenicity, and a shape that was taller than it was wide. The presence of one or more of these features indicated classification as category 3 (malignant). The absence of all of these features indicated classification as category 2 (benign). Presence of an anechogenic cystic nodule was classified as category 1 (benign). MAIN OUTCOME: Of 124 lesions classified as category 3, 60 of the lesions were malignant. Of 418 lesions classified as category 1 or 2, 409 were benign. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy based on the sonographic classification method were 87.0%, 86.5%, 48.4%, 97.8%, and 86.5%, respectively. CONCLUSIONS: Our results identified this sonographic classification as a useful tool in the differentiation of malignant nodules from benign nodules. In view of the high negative predictive value of sonographic classification, a more aggressive approach is recommended only for category 3 nodules.

Changes in the serum sex steroids, IL-7 and RANKL-OPG system after bone marrow transplantation: influences on bone and mineral metabolism.

This study prospectively investigated the changes of the serum levels of the sex steroids, IL-7, soluble receptor activator of nuclear factor kappaB ligand (sRANKL) and osteoprotegerin (OPG) in bone marrow transplantation (BMT) recipients. This study also examined whether the changes of these cytokine levels and sex steroids actually influence bone turnover and post-BMT bone loss by correlation analysis. Data were analyzed from 39 patients (33.6+/-6.4 years, 19 men and 20 women) who had DXA performed before BMT and at 1 year after BMT. The bone turnover markers, sex steroids and the cytokine levels were measured before BMT and serially after BMT. The mean bone loss in the lumbar spine and the total proximal femur was 5.9% (P < 0.01) and 11.3% (P < 0.01), respectively. During the immediate post-BMT period, bone formation decreased, whereas the bone resorption increased. For the female recipients, the estradiol levels declined at 1 week after BMT, and they did not recover to the basal levels. For the male recipients, the testosterone levels decreased at 1 week and then it increased to its baseline level. The IL-7 levels reached their maximum at 1 week and then declined to baseline level by 3 months. The serum sRANKL, OPG levels and the sRANKL/OPG ratio showed their peak at post-BMT 3 weeks. The mean daily dose of steroid was associated with suppressed bone formation, enhanced bone resorption and increased sRANKL levels. The IL-7 levels were also noted to be either positively correlated with the levels of ICTP or they were negatively correlated with the levels of osteocalcin at 1 and 3 weeks after BMT. Bone loss at the lumbar spine and the proximal femur was influenced by the decreased sex steroids and increased IL-7 levels. During the observation period, the IL-7 levels showed positive correlations with the sRANKL levels and the sRANKL/OPG ratio. For the female patients, the serum IL-7 levels were negatively associated with the estradiol levels at 1 and 3 weeks after BMT. All these findings suggest that IL-7 plays an important role for post-BMT bone loss, and this possibly happens via the RANKL pathway. These data also suggest that the up-regulation of IL-7 during the early post-BMT period may result from a deficiency of estrogen.

Relationship between subclinical thyroid dysfunction and femoral neck bone mineral density in women.

BACKGROUND: Osteoporosis associated with thyroid dysfunction has been traditionally viewed as a secondary consequence of altered thyroid function, but there was recently a report about the direct effects of thyroid-stimulating hormone (TSH) on bone remodeling, which was mediated via the TSH receptor found on osteoblast and osteoclast precursor cells. Endogenous subclinical thyroid dysfunction seems to be an appropriate model to examine the direct effect of TSH on bone metabolism while ruling out the direct effect of thyroid hormone on bone metabolism. Thus, we aimed to investigate the relationship between subclinical thyroid dysfunction and bone mineral metabolism in women. METHODS: We enrolled 413 women (mean age: 52.2 +/- 6.6 years) in our study. Serum levels of TSH, free T4 and the biochemical markers of bone turnover were measured by the standard methods. BMD at the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry. RESULTS: Femoral neck BMD was significantly reduced both in the subclinical hyperthyroid group and in the subclinical hypothyroid group as compared with the euthyroid group (one-way ANOVA, p <0.001; post-hoc analysis, p = 0.041, p = 0.033). In contrast to the femoral neck BMD, the lumbar spine BMD showed no difference between the two groups. Additionally, serum calcium and alkaline phosphatase levels, urine deoxypyridinoline levels, and urine calcium to creatinine ratio showed no differences between the two groups. CONCLUSIONS: Women having subclinical hyperthyroidism and women with subclinical hypothyroidsm have reduced femoral neck BMD. Additional studies are required to elucidate the mechanism for this finding.

A novel splice site mutation of the arginine vasopressin-neurophysin II gene identified in a kindred with autosomal dominant familial neurohypophyseal diabetes insipidus.

Autosomal dominant familial neurohypophyseal diabetes insipidus is an inherited deficiency of arginine vasopressin (AVP), and this is caused by mutations in the AVP-neurophysin II (AVP-NP II) gene. Most of these mutations have been located in the signal peptide or in the NP II moiety. In the present study, we have analyzed the AVP-NP II gene in a Korean family. Clinical and genetic studies were performed on three members of the family, and on a normal healthy unrelated individual. The diagnosis of neurohypophyseal diabetes insipidus was done by performing a fluid deprivation test and a vasopressin challenge. For genetic analysis, the genomic DNA was extracted and the AVP-NP II gene was amplified by polymerase chain reaction (PCR). Clinical assessment of the affected individuals confirmed the diagnosis of neurohypophyseal diabetes insipidus. Genetic analysis of the AVP-NP II gene revealed a novel deletion mutation of a single nucleotide (guanine) within the splice acceptor site of intron 2 (IVS2 +1 delG). The affected individuals were heterozygous for this mutation. We also demonstrated through RT-PCR analysis of the mutant gene that this mutation resulted in the retention of intron 2 during pre-mRNA splicing. We concluded that a novel splicing mutation in the AVP-NP II gene causes neurohypophyseal diabetes insipidus in this family.

The effect of simvastatin on the proliferation and differentiation of human bone marrow stromal cells.

Statins have been postulated to affect the bone metabolism. Recent experimental and epidemiologic studies have suggested that statins may also have bone protective effects. This study assessed the effects of simvastatin on the proliferation and differentiation of human bone marrow stromal cells (BMSCs) in an ex vivo culture. The bone marrow was obtained from healthy donors. Mononuclear cells were isolated and cultured to osteoblastic lineage. In the primary culture, 10(-6) M simvastatin diminished the mean size of the colony forming units-fibroblastic (CFU-Fs) and enhanced matrix calcification. At near confluence, the cells were sub-cultured. Thereafter, the alkaline phosphatase (ALP) activities of each group were measured by the time course of the secondary culture. Simvastatin increased the ALP activity in a dose dependent manner, and this stimulatory effect was more evident during the early period of culture. A 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay was performed during the secondary culture in order to estimate the effect of simvastatin on the proliferation of human BMSCs. When compared to the control group, simvastatin significantly decreased the proliferation of cells of each culture well. 10(-6) M of simvastatin also significantly enhanced the osteocalcin mRNA expression level. This study shows that simvastatin has a stimulatory effect on bone formation through osteoblastic differentiation, and has an inhibitory effect on the proliferative potential of human BMSCs.