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Undescended parathyroid adenomas are rare, representing 0.08% of all parathyroid adenomas; however, they make up 7% of the underlying cause of failed cervical exploration in patients with persistent primary hyperparathyroidism. A 43-year-old woman with no significant medical or family history presented with fatigue and was diagnosed with primary hyperparathyroidism; however, preoperative imaging including sestamibi scan and ultrasound was unable to identify the hyperfunctioning gland. She underwent a neck exploration and hemithyroidectomy and partial parathyroidectomy with failure of resolution of her disease. Subsequent work up including a CT of the neck demonstrated a 1.9 cm mass adjacent to the left submandibular gland. This was removed with postoperative normalisation of the patient's serum calcium and parathyroid hormone levels.

BackgroundAge at diagnosis is incorporated into all relevant staging systems for differentiated thyroid carcinoma (DTC). There is growing evidence that a specific age cutoff may not be ideal for accurate risk stratification. We sought to evaluate the interplay between age and oncologic variables in patients with DTC using the largest cohort to date.MethodsThe Surveillance, Epidemiology, and End RESULTS (SEER) database was queried to identify patients with DTC as their only malignancy for the period 1973 to 2009. Multivariate analyses using a range of age cutoffs and age subgroupings were utilized in order to search for an optimal age that would provide the most significant risk stratification between young and old patients. The primary outcome was disease-specific survival (DSS) and covariates included: age, race, sex, tumor/nodal/metastasis (TNM) stage, decade of diagnosis, and radioactive iodine therapy.ResultsA total of 85,740 patients were identified. Seventy-six percent of patients were American Joint Committee on Cancer (AJCC) stage I, 8% were stage II, 7% were stage III, and 8% were stage IV. Age over 45 years (hazard ratio [HR] 19.2, p

The subcutaneous (S) and visceral (V) adipose tissue (AT) depots are increasingly recognized as distinct. To test the hypothesis that depot differences exist for adiponectin, fresh and cultured human VAT and SAT from obese type 2 diabetic (T2D) and obese nondiabetic (ND) subjects was examined to determine whether differences in adiponectin content and secretion occurred as a function of depot studied, diabetic status, and response to thiazolidinedione treatment. VAT and SAT were obtained by biopsy and AT explants cultured in defined media for 7 days. Protein expression was assessed by Western blot. Adiponectin content of conditioned medium was determined by radioimmunoassay. Diabetic status had no effect on adiponectin secretion over days 0-2 of culture. In ND SAT, secretion fell over days 2-4 but was sustained at greater levels vs. T2D SAT. In both ND and T2D VAT, adiponectin secretion was low, similar to T2D SAT. Over the 7-day culture period, cellular adiponectin increased in ND SAT and VAT; it remained unchanged in T2D SAT and VAT. Pioglitazone increased adiponectin secretion and content in all SAT. Pioglitazone failed to increase adiponectin secretion from either ND or T2D VAT and increased cellular content only in ND VAT. AT depot differences exist in the secretion of adiponectin and responsiveness to thiazolidinedione treatment. These data suggest that SAT, not VAT, appears to be the major contributor to increased circulating adipopnectin levels in response to pioglitazone treatment. adipose tissue physiology; type 2 diabetes mellitus; body tat distribution; thiazolidinediones; leptin

Glycogen synthase kinase-3 (GSK-3) is a ubiquitous kinase implicated in both insulin action and adipogenesis. To determine how these multiple roles may relate to insulin resistance, we studied the regulation of GSK-3 protein expression and phosphorylation in skeletal muscle and isolated adipocytes from nonobese healthy control (HC), obese control (OC), and obese type 2 diabetic (OT2D) subjects. At baseline there were no differences in the GSK-3 protein expression in adipocytes. OC subjects underwent a 6-mo caloric restriction resulting in a 7% decrease in body mass index (BMI) and a 21% improvement in insulin-stimulated whole body glucose disposal rate (GDR). GSK-3[alpha] and GSK-3[beta] expression decreased in adipocytes (P < 0.05), whereas GSK-3[alpha] protein expression increased in skeletal muscle (P < 0.05). OT2D subjects were treated with troglitazone or metformin for 3-4 mo. After troglitazone treatment GDR improved (P < 0.05) despite an increase in BMI (P < 0.05), whereas metformin had no significant effect on GDR. There was no significant change in GSK-3 expression in adipocytes following troglitazone, whereas both GSK-3[alpha] and -[beta] were decreased in skeletal muscle (P < 0.05). Metformin treatment had no significant impact on GSK-3 protein expression in either adipocytes or skeletal muscle. Neither treatment influenced GSK-3 serine phosphorylation in skeletal muscle or adipocytes. These results suggest that there is tissue specificity for the regulation of GSK-3 in humans. In skeletal muscle GSK-3 plays a role in control of metabolism and insulin action, whereas the function in adipose tissue is less clear. glycogen synthase kinase-3; weight loss; thiazolidinedione; type 2 diabetes mellitus; metabolism; insulin action

We have developed a fiber optic fluorometer to measure fluorescent signal intensities across an epithelium barrier. As a medically relevant example, we have measured the pH of the effusion formed during Hemophilus influenzae induced otitis media infection in the chinchilla, the classical animal model for human middle ear disease. Because the choice of antibiotic used in clinical therapy is dependent on the pH of the effusion, a noninvasive method of measuring pH is highly desirable. Using the fluorescent pH probe carboxy-seminapthorhodafluor, we were able to detect pH changes of 0.15 units in the pH range around 7.0. The development and resolution of the otitis media was followed with magnetic resonance imaging to confirm the presence of the effusion formed during the infection.

Molecular testing in thyroid cancer proposes many novel approaches to this disease. Traditional histologic diagnosis and classification of thyroid cancer may one day soon be refined by genomic profiling, a common theme in the era of precision medicine. An increasing understanding of the molecular pathogenesis of this disease has led to the discovery of driving somatic genetic alterations, largely explained by, although not limited to, the MAPK and PI3K pathways. Identification of these molecular markers suggests better methods to risk-stratify patients prior to surgery, reducing the number of thyroidectomies performed for benign nodules, and also identifying patients at risk for recurrence, or even dedifferentiation, into a more aggressive thyroid cancer, thus mandating more aggressive therapy approaches beyond traditional surgery and radioactive iodine therapy. Molecular profiling also offers tremendous benefit in the metastatic setting, as these patients typically do not respond to cytotoxic chemotherapy, and identification of targetable pathogenic lesions may select for more precise therapeutic options, such as the small molecular kinase inhibitors. [ABSTRACT FROM AUTHOR]

Bariatric surgery results in improvement of insulin action in the majority of patients. The mechanisms behind this phenomenon are still unclear. This study was designed to investigate potential molecular mechanisms behind the improvement of insulin resistance seen after bariatric surgery-induced weight loss by comparing the gene and protein expression in subcutaneous adipose tissue (SAT) of molecules involved in insulin action before and after Rouxen-Y gastric bypass surgery and resultant weight loss (GBP/WL). SAT was obtained from 10 obese subjects (average BMI = 42.93, 4 diabetic, 6 nondiabetic) before ('pre-') and after ('post-') GBP. Pre-GBP SAT was obtained intra-operatively at the beginning of the procedure. Post-GBP SAT was obtained by needle biopsy after approximately 20% weight loss was attained (time range I to 16 months post-op). SAT was extracted for RNA (n=10) and total tissue protein (n=6). Protein expression was measured by western blotting, while mRNA was quantified by qPCR. The subjects had lost 22 ± 2% of their initial weight by the time of the follow up biopsy. After GBP/WL, there were significant increases in the gene expression of GLUT4 (3.55 ± 0.89 fold of baseline, p=0.018) and p85 (3.81 ± 1.21 fold of baseline, p=0.045). Unlike the result for GLUT4 mRNA, there was no significant change in total tissue protein expression of GLUT4 (p=0.67) with GBP/WL. While there was a tendency (p=0.15) for IR-β protein expression to increase with GBP/WL, Akt protein expression was unchanged. SAT content of mRNA for CD68, a marker of activated macrophage infiltration of the tissue, was unaltered by GBP/WL. In summary, after a surgically-induced weight loss of>20%, there were: 1) improvements in the mRNA expression of molecules involved in insulin action (GLUT4, p85) in SAT, 2) no significant change in GLUT4 protein expression in SAT, and 3) no change in an inflammatory marker in SAT. We conclude that the impact of GBP/WL to improve insulin action involves multiple levels of regulation in subcutaneous adipose tissue, transcriptional as well as post-translational. [ABSTRACT FROM AUTHOR]

Obesity and T2DM are increasingly significant health care concerns. Excess adipose tissue (AT) is highly correlated with and may contribute to insulin resistance. Studies have suggested that greater insulin resistance and metabolic dysfunction results from accumulation of visceral (v) rather than subcutaneous (se) AT. One possible contributing factor is adiponectin (Ad), an adipocyte-specific insulin-sensitizing secretory protein. Circulating Ad levels are reduced in obesity and T2DM and elevated in response to thiazolidinedione (TZD) treatment. Ad release from adipose tissue was evaluated in human SAT and VAT maintained in organ culture over a seven-day period. Over 0-48 hrs in culture SAT and VAT from obese healthy (OH) and obese diabetic (OD) was similar. Over the seven-day culture period no differences were seen in the rate of Ad release from OH-AT versus OD-AT nor in the behavior of Ad release by either SAT or VAT depots. Likewise Ad content of isolated adipocytes, normalized to cell protein, was similar in OH-AT and OD-AT and no depot differences were observed. Pioglitazone (Pio, 2-10 uM) treatment of AT resulted in an approximate 2-fold increase in Ad secretion in SAT from both OH and OD AT. Greater than 48 hr was needed for this effect to appear. In contrast, Pin treatment of VAT from OH and OD subjects showed no significant TZD response. Analysis of cellular Ad content showed no depletion of SAT or VAT cell content over the culture period, although there was a tendency for accumulation of Ad in VAT. In summary AT from OH and OD subjects have similar Ad release and cell content. Reductions in Ad release in culture are not due to depletion of cellular Ad. TZD-induced increases in Ad secretion are not associated with increased cellular Ad content. Intrinsic AT depot differences exist in responsiveness to TZDs, but no differences were evident between D and non-diabetic AT. ADA-Funded Research [ABSTRACT FROM AUTHOR]

Purpose: To determine long-term survival and associated prognostic factors after intraperitoneal (IP) chemotherapy in patients with advanced ovarian cancer., Patients and Methods: Data from Gynecologic Oncology Group protocols 114 and 172 were retrospectively analyzed. Cox proportional hazards regression models were used for statistical analyses., Results: In 876 patients, median follow-up was 10.7 years. Median survival with IP therapy was 61.8 months (95% CI, 55.5 to 69.5), compared with 51.4 months (95% CI, 46.0 to 58.2) for intravenous therapy. IP therapy was associated with a 23% decreased risk of death (adjusted hazard ratio [AHR], 0.77; 95% CI, 0.65 to 0.90; P = .002). IP therapy improved survival of those with gross residual (≤ 1 cm) disease (AHR, 0.75; 95% CI, 0.62 to 0.92; P = .006). Risk of death decreased by 12% for each cycle of IP chemotherapy completed (AHR, 0.88; 95% CI, 0.83 to 0.94; P < .001). Factors associated with poorer survival included: clear/mucinous versus serous histology (AHR, 2.79; 95% CI, 1.83 to 4.24; P < .001), gross residual versus no visible disease (AHR, 1.89; 95% CI, 1.48 to 2.43; P < .001), and fewer versus more cycles of IP chemotherapy (AHR, 0.88; 95% CI, 0.83 to 0.94; P < .001). Younger patients were more likely to complete the IP regimen, with a 5% decrease in probability of completion with each year of age (odds ratio, 0.95; 95% CI, 0.93 to 0.96; P < .001)., Conclusion: The advantage of IP over intravenous chemotherapy extends beyond 10 years. IP therapy enhanced survival of those with gross residual disease. Survival improved with increasing number of IP cycles., (© 2015 by American Society of Clinical Oncology.)