Optimal threshold of stimulated serum thyroglobulin level for 18F-FDG PET/CT imaging in patients with thyroid cancer.

This study was to explore the optimal threshold of thyroid-stimulating hormone (TSH)-stimulated serum thyroglobulin (s-Tg) for patients who were to receive 18F-fluorodeoxyglucose (18F-FDG) PET/CT scan owing to clinical suspicion of differentiated thyroid cancer (DTC) recurrence but negative post-therapeutic 131I whole-body scan (131I-WBS). A total of 60 qualified patients underwent PET/CT scanning from October 2010 to July 2014. The receiver operating characteristic (ROC) curve analyses showed that s-Tg levels over 49 µg/L led to the highest diagnostic accuracy of PET/CT to detect recurrence, with a sensitivity of 89.5% and a specificity of 90.9%. Besides, bivariate correlation analysis showed positive correlation between s-Tg levels and the maximum standardized uptake values (SUVmax) of 18F-FDG in patients with positive PET/CT scanning, suggesting a significant influence of TSH both on Tg release and uptake of 18F-FDG. So, positive PET/CT imaging is expected when patients have negative 131I-WBS but s-Tg levels over 49 µg/L.

Optimal Threshold of Stimulated Serum Thyroglobulin Level for 18F-FDG PET/CT imaging in Patients with Thyroid Cancer / 华中科技大学学报（医学）（英德文版）

This study was to explore the optimal threshold of thyroid-stimulating hormone (TSH)-stimulated serum thyroglobulin (s-Tg) for patients who were to receive 18F-fluorodeoxyglucose (18F-FDG) PET/CT scan owing to clinical suspicion of differentiated thyroid cancer (DTC) recurrence but negative post-therapeutic 131I whole-body scan (131I-WBS).A total of 60 qualified patients underwent PET/CT scanning from October 2010 to July 2014.The receiver operating characteristic (ROC) curve analyses showed that s-Tg levels over 49 μg/L led to the highest diagnostic accuracy of PET/CT to detect recurrence,with a sensitivity of 89.5％ and a specificity of 90.9％.Besides,bivariate correlation analysis showed positive correlation between s-Tg levels and the maximum standardized uptake values (SUVmax) of 18F-FDG in patients with positive PET/CT scanning,suggesting a significant influence of TSH both on Tg release and uptake of 18F-FDG.So,positive PET/CT imaging is expected when patients have negative 131I-WBS but s-Tg levels over 49 μg/L.

Clinical Evaluation of the Immune Colloidal Gold Method for Rapid Qualitative and Quantitative Measurement of Thyroid-Stimulating Hormone as an Assay for Hypothyroidism.

INTRODUCTION: The immune colloidal gold (ICG) method of measuring thyroid-stimulating hormone (TSH) is a rapid and easy-to-perform test, allowing off-site measurements. This study compared the clinical utility of the first ICG-based qualitative and quantitative TSH test methods in China with the third-generation serum TSH assay used worldwide. METHODS: Fingertip and venous blood was collected within 30 min from 283 patients initially suspected of hypothyroidism. TSH was measured in fingertip blood using ICG-based qualitative quantitative tests. Serum TSH in venous blood was tested using the third-generation serum TSH assay. Correlations between systems were tested by kappa or Spearman correlation coefficients. RESULTS: Compared with the third-generation serum TSH assay, the ICG-qualitative TSH test kit had a kappa coefficient of 0.86, a sensitivity of 85.00%, and a specificity of 99.38% in screening for hypothyroidism. The percentages of false negatives and false positives among all subjects were 6.38% and 0.35% respectively; the total consistency rate of the two methods was 93.26%. When compared with the third-generation serum TSH assay, the ICG-quantitative TSH analysis system had a Spearman correlation coefficient of 0.91, a sensitivity of 88.43%, and a specificity of 98.77%. The percentages of false negatives and false positives among all subjects were 4.95% and 0.71%, respectively; the total consistency rate of the two methods was 94.35%. CONCLUSION: Both ICG-based assays are easier and faster to perform than the third-generation, laboratory-based serum TSH assay method. The ICG-based methods showed acceptable performance in the simplified screening for hypothyroidism. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01921452. FUNDING: Merck Serono Co., Ltd.

TUBERCULOSIS INFECTION MIGHT INCREASE THE RISK OF INVASIVE CANDIDIASIS IN AN IMMUNOCOMPETENT PATIENT.

Deep Candida infections commonly occur in immunosuppressed patients. A rare case of a multiple deep organ infection with Candida albicans and spinal tuberculosis was reported in a healthy young man. The 19-year-old man complained of month-long fever and lower back pain. He also had a history of scalded mouth syndrome. Coinfection with Mycobacterium tuberculosis and Candida albicans was diagnosed using the culture of aspirates from different regions. Symptoms improved considerably after antifungal and antituberculous therapy. This case illustrates that infection with tuberculosis might impair the host's immune system and increase the risk of invasive candidiasis in an immunocompetent patient.

Tuberculosis ineection might increase the risk f invasive candidiasis in an immmunocompetent patient / Tuberculose pode aumentar o risco de candidíase invasiva em paciente imunocompetente

Deep Candida infections commonly occur in immunosuppressed patients. A rare case of a multiple deep organ infection with Candida albicans and spinal tuberculosis was reported in a healthy young man. The 19-year-old man complained of month-long fever and lower back pain. He also had a history of scalded mouth syndrome. Coinfection with Mycobacterium tuberculosis and Candida albicans was diagnosed using the culture of aspirates from different regions. Symptoms improved considerably after antifungal and antituberculous therapy. This case illustrates that infection with tuberculosis might impair the host's immune system and increase the risk of invasive candidiasis in an immunocompetent patient.

As infecções profundas por Candida ocorrem geralmente em pacientes imunossuprimidos. Relatamos caso raro de infecções profundas em múltiplos órgãos por Candida albicans e neuro tuberculose em homem jovem saudável. Um jovem de 19 anos de idade queixou-se de febre e lombalgia há um mês. Relatava ainda histórico de síndrome da boca escaldada. Foi diagnosticada co-infecção por Mycobacterium tuberculosis e Candida albicans em cultura do aspirado de diferentes regiões do organismo. Os sintomas melhoraram significativamente após a terapia antifúngica e antituberculosa. Este caso é apresentado para mostrar que a tuberculose pode prejudicar o sistema imune do hospedeiro e aumentar o risco de candidíase invasiva em paciente imunocompetente.

FDG-anorectic parathyroid carcinoma with FDG-avid bone metastasis on PET/CT images.

A 53-year-old man complained of aggravated left hip pain of more than 2 months. Whole-body (18)F-FDG PET/CT revealed only 1 hypermetabolic lesion in the left ilium. Histopathologic examination of the lesion suggested metastatic disease. Blood tests documented mildly elevated blood calcium and parathyroid hormone. Subsequent neck ultrasonography, contrast-enhanced CT, and dual-phase scintigraphy with (99m)Tc-MIBI showed a right parathyroid tumor, which was confirmed to be a parathyroid carcinoma postoperatively. We report a case of parathyroid carcinoma rarely encountered with a FDG-negative primary but a FDG-positive metastasis on PET/CT images.

FDG PET/CT showing erythema nodosum associated with tuberculous lymphadenitis.

Erythema nodosum (EN) is histopathologically an acute septal panniculitis of subcutaneous adipose lobule. It can be either idiopathic or secondary to various underlying conditions. A female patient with EN underwent FDG PET/CT to search underlying cause. The images showed enlarged lymph nodes in the mediastinum with moderately elevated FDG uptake and multifocal increased FDG uptake over her lower extremities. The patient's condition was subsequently diagnosed with EN associated with mediastinal tuberculous lymphadenitis based on skin biopsy, tuberculin skin test, and treatment response.

Imaging proliferation in human leukemia-tumor bearing mice with (18)F-FLT: Comparison with (18)F-FDG PET.

Leukemia threatens human life due to its uncontrolled proliferative malignancy. 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) has been suggested as a new positron emission tomography (PET) tracer for imaging tumor proliferation. The aim of the study was to investigate the usefulness of (18)F-FLT PET for imaging human leukemia-tumor bearing mice, compared with fluorine-18-fluorodesoxyglucose ((18)F-FDG PET). In vitro the experiments of (18)F-FLT and (18)F-FDG uptake were performed in K562 cell lines at various time points and radioactive tracer uptake was measured in a gamma counter. (18)F-FLT and (18)F-FDG PET imaging were performed both in the same mouse when eight tumor-bearing mice models of human chronic myeloid leukemia were established successfully by injecting K562 cells. Regions of interest were drawn over the tumor, the crossed normal tissue was regarded as background and the ratio of tumor to non-tumor counts (T/NT) in tissues was calculated. A higher uptake of (18)F-FLT (15min, 5.73±0.05%; 30min, 5.90±0.06%; 60min, 6.16±0.19%; 120min, 6.32±0.08%) than that of (18)F-FDG (15min, 1.05±0.10%; 30min, 1.11±0.14%; 60min, 1.14±0.37%; 120 min, 1.36±0.25%) was observed in K562 cells in the tracer uptake experiment. Ratios of T/NT of (18)F-FLT PET (0.5h, 5.39±0.42; 1h, 4.88±0.43; 2h, 3.81±0.38) were higher than those of (18)F-FDG PET/CT (0.5h, 0.34±0.12; 1h, 0.21±0.06; 2h, 0.13±0.05) after injection. Both uptake and T/NT differences of (18)F-FLT versus (18)F-FDG were significant (P>0.05). In conclusion, (18)F-FLT and (18)F-FDG quantitative and semi-quantitative uptake measurements resulting from cell lines and PET imaging respectively suggested a promising potential of (18)F-FLT for metabolic imaging of human chronic myeloid leukemia.

A first described chest wall metastasis from colon cancer demonstrated with (18)F-FDG PET/CT.

It is well known that, haematogenous colon cancer metastases are most commonly found in the liver, less likely in the lungs through the paravertebral venous system and rarely in other organs. Sporadic clinical cases of colon cancer metastases to the abdominal wall, the thyroid or the adrenal glands have been reported. Here, we present an uncommon case of chest wall metastasis from colon cancer demonstrated with 2-fluoro [fluorine-18]-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT). A 52 years old female patient was examined after she felt a swelling mass above her left breast. Tumor makers, such as serum cancer embryonic antigen (CEA) 146.22kU/L (normal range:0.00~37.0kU/L) and CA19-9 (258.16µg/L (normal range:0.00~10.0µg/L) and neuron-specific enolase (NSE) 78.2 (normal range: 0.00~17.00) were abnormally high. Chest CT revealed the soft tissue density mass on the left anterior chest wall with invasion of left 4th rib, and CT-guided biopsy showed a poorly differentiated adenocarcinoma of unkown origin. The patient was then referred for the (18)F-FDG-PET scan which was performed one hour after the intravenous injection of 370MBq of (18)F-FDG (Discovery Camera, VCT, GE, USA) and showed in addition to the chest mass, abnormal (18)F-FDG accumulation in both lungs, left supraclavicular and peritoneal lymph nodes. Furthermore, high (18)F-FDG uptake was detected in the sigmoid. Pathology findings from colonoscopy confirmed that this was a sigmoid colon adenocarcinoma. So far, chest wall metastasis from colon cancer as an initial finding has not been reported. Usually, an initial chest wall mass is hardly suspected to be a colon cancer metastasis. Abnormal serum tumor markers such as CEA and CA19-9 supported the diagnosis of a gastrointestinal adenocarcinoma. In our case, we found high serum NSE and normal findings of bowel wall on the CT scan, thus without the positive (18)F-FDG findings, one would probably consider as first diagnosis: chest wall metastasis from lung cancer, or a neuroendocrine tumor. The unusual finding in this case was that on the CT images there was no obvious local density of the intestine, no bowel wall thickening, or suspicious nodular lesions. Segmental (18)F-FDG accumulation seen in the sigmoid colon had early maximum standardized uptake value (SUV(max)) 7.3 and in 1h delayed estimation, 8.1. Colonoscopy showed that the (18)F-FDG-avid area at the colon was circular and thickened. "Hot" lesions found in both lungs, the supraclavicular and retroperitoneal lymph nodes by (18)F-FDG PET/CT scan were considered to be most probably metastases from colon adenocarcinoma. In conclusion, PET as a rather simple procedure and less dependent on bowel preparation diagnosed the primary colon cancer, its metastases and specifically a first described chest wall metastasis, while CT alone did not show the primary tumor.

Relationship between serum osteocalcin and glycaemic variability in Type 2 diabetes.

1. Recent reports have described the role of osteocalcin in glucose metabolism and glycaemic variability has been proven to be associated with an increased risk of diabetes complications. However, the relationship between osteocalcin and glycaemic variability remains unclear. The aim of the present study was to examine the relationship between serum osteocalcin and glycaemic variability, as determined by a continuous glucose monitoring (CGM) system in patients with Type 2 diabetes mellitus (T2DM). 2. Fifty-nine T2DM patients with glycosylated haemoglobin (HbA1c) levels between 7.0% and 10.9% were recruited to the present study. Biochemical information and CGM parameters were collected at baseline and after 8 weeks of antihyperglycaemic therapy (either sulphonylurea, sulphonylurea + an α-glucosidase inhibitor or insulin + metformin combination therapy). 3. Compared with baseline, serum osteocalcin increased significantly (P = 0.014), whereas parameters related to glucose variability, including the mean amplitude of glycaemic excursions (MAGE) and the standard deviation of blood glucose values, decreased significantly (P < 0.001) after the 8 week treatment period. At baseline, there was a positive correlation between serum osteocalcin levels and fasting C-peptide levels (P = 0.004) and homeostatic model assessment of ß-cell function (P = 0.048), but a negative correlation between serum osteocalcin levels and fasting plasma glucose (P = 0.023), HbA1c (P = 0.020), glycated albumin (P = 0.019) and 24 h mean blood glucose (P < 0.001). Multiple stepwise regression analysis indicated that baseline osteocalcin was the single parameter that best predicted the change in MAGE (ß = -0.122; P = 0.039). 4. In conclusion, serum osteocalcin concentrations increased with improved glucose control. High initial osteocalcin levels were associated with subsequent improvements in glucose variability during glucose-lowering treatment.

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.

Predictive value of osteocalcin in bone metastatic differentiated thyroid carcinoma.

OBJECTIVES: To evaluate the diagnostic value of serum osteocalcin in the detection of bone metastases from differentiated thyroid carcinoma (DTC). DESIGN AND METHODS: Serum samples from DTC patients with (DTC BM+, n=19) or without bone metastases (DTC BM-, n=19), and matched healthy volunteers (n=30) were tested for serum osteocalcin with electrochemiluminescent immunoassay. RESULTS: Osteocalcin was higher in DTC BM+ than in DTC BM- patients (+35.8%, p=0.002), acting as an independent risk factor for bone metastases (R(2)=0.142, p=0.039). The sensitivity was 78.9% and the specificity was 63.2% at a cut-off value of 11.2 microg/L. CONCLUSIONS: Serial measurements of osteocalcin could be useful in the detection of bone metastases from DTC.

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.

Serum osteocalcin concentrations in relation to glucose and lipid metabolism in Chinese individuals.

OBJECTIVES: Osteocalcin, a bone-derived protein, has recently been reported to affect energy metabolism. We investigated the relationship between serum osteocalcin and parameters of adiposity, glucose tolerance, and lipid profile in Chinese subjects. METHODS: Serum osteocalcin was measured by electrochemiluminescence immunoassay in 254 men (128 with newly diagnosed type 2 diabetes mellitus (T2DM) and 126 with normal glucose tolerance (NGT)), 66 premenopausal women (33 with T2DM and 33 with NGT) as well as 180 postmenopausal women (92 with T2DM and 88 with NGT). Their associations with parameters of adiposity, glucose tolerance, and lipid profile were examined. RESULTS: Serum osteocalcin concentrations in diabetic patients were significantly lower than those in NGT subjects after adjusted for age, gender, and body mass index (P=0.003). Postmenopausal women had higher osteocalcin concentrations than premenopausal women and men (both P<0.001). Multiple stepwise regression analysis showed that age, %fat, high-density lipoprotein cholesterol, fasting plasma glucose, and fasting serum insulin were independently associated with osteocalcin in men (P<0.05). Age and HbA1c were independently correlated with osteocalcin in postmenopausal women. Besides age and HbA1c, serum triglyceride was also an independent factor influencing osteocalcin in premenopausal women. In addition, osteocalcin was also positively associated with homeostasis model assessment of beta-cell function. Furthermore, multiple logistic regression analysis demonstrated that osteocalcin was independently associated with T2DM. CONCLUSIONS: Serum osteocalcin was closely associated with not only fat and glucose metabolism but also with lipid metabolism.

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.

Mutual interference between serum thyroglobulin and antithyroglobulin antibody in an automated chemiluminescent immunoassay.

OBJECTIVES: To investigate the analytical interference between serum Tg and TgAb. DESIGN AND METHODS: Tg and TgAb were measured on an automated chemiluminescent immunoassay system in mixed sera from DTC patients and individual samples spiked with exogenous Tg. RESULTS: Tg and TgAb recoveries in mixed patient samples were inversely correlated with expected TgAb or Tg concentrations, respectively. Impaired TgAb recoveries were also found in 50% (10/20) samples with high Tg in the exogenous recovery tests. CONCLUSIONS: Mutual but not equal analytical interference between Tg and TgAb is present and concentration-dependent with interpatient variability.