Clinical usefulness of single photon emission tomography/computed tomography with stress analysis in early diagnoses of stem instability of noncemented hip arthroplasty.

OBJECTIVE: Hip pain arising from implant instability is generally caused by repetitive stress injury, which subsequently leads to induction or exacerbation of abnormal metabolism of bone around the implant. single photon emission tomography/computed tomography (SPECT-CT) has advantages in localizing areas of increased tracer uptake that reflects such abnormal bone metabolism. Therefore, we investigated whether the application of SPECT/CT with stress analysis can be an effective practice in evaluating the instability of stem in noncemented hip arthroplasty or not. METHOD: In total 16 patients were collected for unexplained painful hip arthroplasties. When physical examination and blood tests were unremarkable, radiographs were inconclusive and bone scan indicated increased scintigraphic uptake at the proximal part and at the tip of the stem; SPECT/CT was performed. Stem stability was assessed by measuring whether there was consistency between the increased scintigraphic uptake and the direction of the stress around the implant along with the location of the prosthesis. RESULT: Among the 16 symptomatic hips, 9 hips showed the stability of the stem, 3 hips showed the stem instability and 4 hips showed the acetabular loosening with the stem stability. With the application of SPECT/CT with stress analysis, 15 out of 16 (93.7%) cases were found to have the change in the diagnoses, and managements were implemented in 11 out of 16 (68.7%) cases. When comparing before and after SPECT/CT, there was no significant association in clinical diagnosis and management (Pearson chi- square test = 4.61 and 1.33, P = 0.33 and 0.25). CONCLUSION: SPECT/CT combined with stress analysis can be a useful tool in early diagnosis of stem instability and can assist surgeons in subsequent management and decision implementation when other radiographic imagings are inconclusive.

FAM172A protein promotes the proliferation of human papillary thyroid carcinoma cells via the p38 mitogen-activated protein kinase pathway.

Family with sequence similarity 172, member A (FAM172A), was cloned from human aortic tissues and confirmed in our previous study in 2009, however, its functions remain to be fully elucidated. In our previous studies, the protein expression of FAM172A in human aortic smooth muscle cells was found to be upregulated by high glucose in a concentration­ and time­dependent manner. Several reports have shown that insulin resistance is associated with papillary thyroid carcinoma (PTC). Thus, in the present study, the protein expression levels of FAM172A in human papillary thyroid carcinoma were investigated, and the effect of the FAM172A protein on the proliferation of IHH­4 human papillary thyroid carcinoma cells, and its potential molecular underlying mechanisms were examined. Immunohistochemistry and western blotting demonstrated that the protein expression of FAM172A in papillary thyroid carcinoma tissues was not only significantly higher than that in noncancerous tissues adjacent to the carcinoma tissues, but it was also markedly higher than that in normal thyroid and thyroid adenoma tissues. Overexpression of the FAM172A protein activated the p38 MAPK pathway, but not the PI3K and AMPK pathways, in the IHH­4 cells. In addition, overexpression of the FAM172A protein accelerated IHH­4 cell proliferation, compared with the control group, and the pro­proliferative effect of FAM172A protein on IHH4 cells was markedly attenuated by SB202190, an inhibitor of p38 MAPK. Taken together, these results suggest that the FAM172A protein is expressed at high levels in human PTC, which may promote cell proliferation via activation of the p38 MAPK signaling pathway, and be involved in the pathogenesis of PTC.

Localized subacute thyroiditis presenting as a painful hot nodule.

BACKGROUND: A diagnosis of subacute thyroiditis is readily considered when patients present with a particular set of typical clinical characteristics. Subacute thyroiditis sometimes presents as a solitary cold nodule; however, the presence of a hot nodule in patients with subacute thyroiditis is exceedingly rare. CASE PRESENTATION: Here, the case of a 57-year-old woman complaining of pain in the left neck and fatigue for two weeks is presented. Physical examination revealed a painful and tender nodule with a diameter of approximately 1.5 cm in the left neck, although all laboratory tests, including white blood cell count, neutrophil percentage, erythrocyte sedimentation rate (ESR), thyroid function, and thyroglobin levels, were normal. A neck ultrasound revealed a hypoechoic mass (1.5 × 0.8 cm) in the left thyroid, and thyroid scintigraphy of the left thyroid with Technetium-99 m (99 m-Tc) demonstrated a focal accumulation of radiotracer. Furthermore, fine-needle aspiration biopsy from the nodule revealed the presence of multinuclear giant cells. The patient was well; there was no cervical mass detected upon palpation following two months of prednisone treatment, and follow-up ultrasound screening and scintigraphy demonstrated the disappearance of the nodule. CONCLUSION: This case, presenting with a localized painful hot nodule, normal thyroid function, normal ESR, and normal serum thyroglobulin levels, is a rare case of subacute thyroiditis, which should be considered during differential diagnosis.

High prevalence of vitamin D insufficiency in China: relationship with the levels of parathyroid hormone and markers of bone turnover.

There is a lack of large-scale studies on vitamin D status and its relationship to parathyroid hormone (PTH) and bone turnover markers in adults living in Shanghai. The objectives were to determine the prevalence of vitamin D insufficiency in Shanghai and to investigate the relationship of 25(OH)D with parathyroid function and bone turnover markers. This cross-sectional study involved 649 men and 1939 women aged 20-89 years who were randomly sampled in Shanghai. Serum concentrations of 25(OH)D, PTH, albumin, and bone turnover markers were measured. During the winter season, the prevalence of vitamin D insufficiency (<30 ng/mL) was 84% in males and 89% in females. The prevalence of vitamin D deficiency (<20 ng/mL) was 30% in males and 46% in females. With increasing serum 25(OH)D concentrations categorized as <10, 10-20, 20-30, and ≥30 ng/mL, the mean PTH and bone turnover markers levels gradually decreasd in both sexes (p<0.001). There was an inverse relationship between the serum 25(OH)D and PTH concentrations in both genders, but no threshold of 25(OH)D at which PTH levels plateaued was observed. There were modest but significantly inverse relationships between the levels of 25(OH)D and bone turnover markers, but no plateau was observed for serum 25(OH)D levels up to 40 ng/mL.

Bone turnover markers in patients with differentiated thyroid carcinoma after levothyroxine withdrawal.

BACKGROUND: Patients receiving postoperative radioiodine therapy for advanced differentiated thyroid carcinoma (DTC) are repeatedly in short-term thyroid hormone deficiency, whose bone turnover state is not fully understood. METHODS: Serum bone turnover markers (BTMs), bone specific alkaline phosphatase (BALP), type 1 procollagen N-terminal propeptide (P1NP), osteocalcin (OC), and the beta-isomerized C-terminal telopeptide of type 1 collagen (beta-CTx) were measured in 50 adult male DTC patients after 4-week suspension of levothyroxine replacement therapy and 40 matched euthyroid controls. Relationships between parameters of thyroid function (free triiodothyronine, FT3; free thyroxine, FT4; thyroid stimulating hormone, TSH) and the BTMs were studied. RESULTS: The patients had significantly decreased OC (-37.6%, P<0.001) and beta-CTx (-35.5%, P<0.001) compared with the controls, showing FT3 as the independent risk factor for OC (R2=0.425, P<0.001) and beta-CTx (R2=0.124, P<0.001). Partial correlation analysis showed that only FT3 was significantly correlated with OC after controlling FT4 and TSH (r=0.362, P=0.001). CONCLUSIONS: DTC patients have moderately decreased bone turnover after short-term suspension of thyroxine suppressive therapy, with serum FT3 concentration as the predominant and independent risk factor.

Outcome after high-dose radioiodine therapy for advanced differentiated thyroid carcinoma in childhood.

OBJECTIVE: To evaluate the clinical outcome in childhood patients receiving postoperative high-dose radioiodine therapy for advanced differentiated thyroid carcinoma. METHOD: Patients under 18 years old with neck diseases (n = 4) or distant metastases (n = 10) received postoperative radioiodine ablation and repeated treatments for a median of 2 (0.8 10) years with an averaged activity of 25.0 (7.0 72.2) GBq. RESULTS: Partial remission was achieved in 6, stable disease in 6 and progressive disease in 2 patients, without severe side effects except for two Grade 1 and one Grade 2 WHO haematological toxicity. The median survival time from diagnosis to the last treatment sessions was 5.3 (range, 0.7 14.5) years. CONCLUSION: High-dose radioiodine treatment was well tolerated with satisfactory outcome in childhood patients with advanced differentiated thyroid carcinoma.

Comparison of free plasma metanephrines enzyme immunoassay with (131)I-MIBG scan in diagnosis of pheochromocytoma.

Measurement of free plasma metanephrines (metanephrine and normetanephrine), usually performed by high-performance liquid chromatography with electrochemical detection (HPLC-ECD), has been recommended as the single biochemical test of choice for the diagnosis of pheochromocytoma. Alternatively, a widely available, simple means to measure these biomarkers with enzyme immunoassay (EIA) needs to be studied. The aim of this study was to investigate the diagnostic efficacy of such a method in comparison with (131)I-metaiodobenzylguanidine (MIBG) whole body scan (WBS) in patients with pheochromocytoma. We enrolled patients undergoing (131)I-MIBG WBS due to clinical findings suggestive of pheochromocytoma (n = 45), and patients with primary hypertension (n = 36). All subjects had blood tests for free plasma metanephrine (MN) and normetanephrine (NM) with a commercially available EIA kit. WBS was positive in 30 pheochromocytoma patients and negative in 15 refuted ones, with 100% accuracy. The sensitivity, specificity and accuracy of MN and NM in combination (either or both positive) were 96.7%, 86.3% and 90.1%, showing comparable diagnostic performance both to (131)I-MIBG WBS (all p > 0.1), and also to the same markers measured with HPLC-ECD reported in the literature. These results showed that the EIA method may be eligible as an alternative to HPLC-ECD for plasma metanephrine determination in the identification of pheochromocytoma.

Preparation and bioevaluation of (99m)Tc-HYNIC-annexin B1 as a novel radioligand for apoptosis imaging.

Annexin B1, a novel Ca2+-dependent PS-binding protein, has been shown to have a high affinity for PS exposed on the surface of apoptotic cells. To develop and bioevaluate an annexin B1 based PS-targeting radiotracer, annexin B1 was radiolabeled with (99m)Tc using HYNIC as a bifunctional chelator. Binding assays with activated platelets and apoptotic SP2/0 cells were carried out to evaluate the in vitro biological activity of (99m)Tc-HYNIC-annexin B1. Biodistribution of this radioligand was studied in normal mice. Dexamethasone-induced murine thymus apoptosis and fas-mediated murine liver apoptosis models were used to investigate the ability of radiolabeled annexin B1 to detect apoptosis in vivo. The labeling procedure yielded a compound with up to 98% radiochemical purity and good in vitro stability. The in vitro binding assays indicated that (99m)Tc-HYNIC-annexin B1 retain its PS-binding activity. Biodistribution of the compound in mice showed that (99m)Tc-HYNIC-annexin B1 is rapidly cleared from the blood and predominantly accumulates in the kidney. The marked increase in dexamethasone-treated murine thymus uptake and fas-mediated murine liver uptake correlated with histologic evidence of apoptosis. These data suggested that (99m)Tc-HYNIC-annexin B1 retain its in vitro and in vivo biological activities. This radiotracer may therefore be useful as a novel radioligand for the noninvasive detecting of PS externalization associated with apoptosis.

Preparation, in vitro and in vivo evaluation of (99m)Tc-Annexin B1: a novel radioligand for apoptosis imaging.

To develop a radiopharmaceutical for apoptosis imaging, Annexin B1, a new Ca2+-dependent phosphatidylserine (PS)-binding protein, was directly radiolabeled with (99m)Tc. This procedure yields up to 96% of radiochemical purity and higher radiolabeling efficiency. The preparation has been found to be sufficiently stable in vitro. Binding assay with human activated platelets indicated that (99m)Tc-Annexin B1 retained its PS binding activity. Biodistribution in mice revealed that (99m)Tc-Annexin B1 rapidly cleared from the blood and predominantly accumulated in the kidney. The increase in hepatic uptake in anti-Fas antibody treated mice correlated to histologic evidence of fulminant hepatic apoptosis. These data suggest that (99m)Tc-Annexin B1 can be used as a novel radiotracer to detect apoptosis in vivo.