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AbstractBackgroundIn patients with persistent (P‐PHPT) or recurrent (R‐PHPT) primary hyperparathyroidism, preoperative localization is important. Selective parathyroid hormone venous sampling (sPVS) is an invasive technique that can be used to regionalize and/or lateralize the source of PHPT when noninvasive imaging studies are nonlocalizing. The aim of the present study was to assess the role of sPVS in the preoperative evaluation of patients with P‐PHPT or R‐PHPT and negative, equivocal, or discordant noninvasive imaging localization.MethodsAfter IRB‐approval a retrospective review of all patients with P‐PHPT or R‐PHPT and nonlocalizing noninvasive imaging that underwent sPVS from 2000 to 2014 was performed. The location of the source of PHPT at sPVS was predicted by a parathyroid hormone (PTH) gradient and compared to the surgical, pathology, and biochemical follow‐up data as the gold standard. Sensitivity and positive predictive value (PPV) were calculated.ResultsOf 30 patients who underwent sPVS, 12 patients did not undergo surgical exploration due to negative or non‐localizing PTH gradient (n = 8) or opted for medical management (n = 4). Of the 18 patients who underwent surgical exploration, 17 (94 %) had a positive PTH gradient and pathologic parathyroid tissue identified at surgery. Sensitivity and PPV of sPVS were 93 and 77 %, respectively, for all surgical cases, 86 and 60.0 % for cervical cases (n = 11), and 100 and 100 % for mediastinal cases (n = 7). Sixteen patients (89 %) were surgically cured.ConclusionsIn patients with P‐PHPT or R‐PHPT and nonlocalizing imaging studies, sPVS is a sensitive test for localizing the source of PHPT when a positive PTH gradient is present.

AbstractBackgroundParathyroidectomy is a definitive treatment for primary hyperparathyroidism. Patients contemplating this intervention will benefit from knowledge regarding the expected outcomes and potential risks of the currently available surgical options.PurposeTo appraise and summarize the available evidence regarding benefits and harms of minimally invasive parathyroidectomy (MIP) and bilateral neck exploration (BNE).Data sourcesA comprehensive search of multiple databases (MEDLINE, EMBASE, and Scopus) from each database’s inception to September 2014 was performed.Study selectionEligible studies evaluated patients with primary hyperparathyroidism undergoing MIP or BNE.Data extractionReviewers working independently and in duplicate extracted data and assessed the risk of bias.Data synthesisWe identified 82 observational studies and 6 randomized trials at moderate risk of bias. Most of them reported outcomes after MIP (n = 71). Using random‐effects models to pool results across studies, the cure rate was 98 % (95 % CI 97–98 %, I2 = 10 %) with BNE and 97 % (95 % CI 96–98 %, I2 = 86 %) with MIP. Hypocalcemia occurred in 14 % (95 % CI 10–17 % I2 = 93 %) of the BNE cases and in 2.3 % (95 % CI 1.6–3.1 %, I2 = 87 %) with MIP (P < 0.001). There was a statistically significant lower risk of laryngeal nerve injury with MIP (0.3 %) than with BNE (0.9 %), but similar risk of infection (0.5 vs. 0.5 %) and mortality (0.1 vs. 0.5 %).LimitationsThe available evidence, mostly observational, is at moderate risk of bias, and limited by indirect comparisons and inconsistency for some outcomes (cure rate, hypocalcemia).ConclusionMIP and BNE are both effective surgical techniques for the treatment of primary hyperparathyroidism. The safety profile of MIP appears superior to BNE (lower rate of hypocalcemia and recurrent laryngeal nerve injury).

AbstractBlood and urine acylcarnitine profiles are commonly used to diagnose long‐chain fatty acid oxidation disorders (FAOD: i.e., long‐chain hydroxy‐acyl‐CoA dehydrogenase [LCHAD] and carnitine palmitoyltransferase 2 [CPT2] deficiency), but the global metabolic impact of long‐chain FAOD has not been reported. We utilized untargeted metabolomics to characterize plasma metabolites in 12 overnight‐fasted individuals with FAOD (10 LCHAD, two CPT2) and 11 healthy age‐, sex‐, and body mass index (BMI)‐matched controls, with the caveat that individuals with FAOD consume a low‐fat diet supplemented with medium‐chain triglycerides (MCT) while matched controls consume a typical American diet. In plasma 832 metabolites were identified, and partial least squared‐discriminant analysis (PLS‐DA) identified 114 non‐acylcarnitine variables that discriminated FAOD subjects and controls. FAOD individuals had significantly higher triglycerides and lower specific phosphatidylethanolamines, ceramides, and sphingomyelins. Differences in phosphatidylcholines were also found but the directionality differed by metabolite species. Further, there were few differences in non‐lipid metabolites, indicating the metabolic impact of FAOD specifically on lipid pathways. This analysis provides evidence that LCHAD/CPT2 deficiency significantly alters complex lipid pathway flux. This metabolic signature may provide new clinical tools capable of confirming or diagnosing FAOD, even in subjects with a mild phenotype, and may provide clues regarding the biochemical and metabolic impact of FAOD that is relevant to the etiology of FAOD symptoms.

AbstractIntroductionFocused parathyroidectomy in primary hyperparathyroidism (1°HPT) is possible with accurate preoperative localization and intraoperative PTH monitoring (IOPTH). The added benefit of multimodal imaging techniques for operative success is unknown.MethodPatients with 1°HPT, who underwent parathyroidectomy in 2012–2014 at a single institution, were retrospectively reviewed. Only the patients who underwent the standardized multimodal imaging workup consisting of 123I/99Tc‐sestamibi subtraction scintigraphy, SPECT, and SPECT/CT were assessed.ResultsOf 360 patients who were identified, a curative operation was performed in 96 %, using pre‐operative imaging and IOPTH. Imaging analysis showed that 123I/99Tc‐sestamibi had a sensitivity of 86 % (95 % CI 82–90 %), positive predictive value (PPV) 93 %, and accuracy 81 %, based on correct lateralization. SPECT had a sensitivity of 77 % (95 % CI 72–82 %), PPV 92 % and accuracy 72 %. SPECT/CT had a sensitivity of 75 % (95 % CI 70–80 %), PPV of 94 %, and accuracy 71 %. There were 3 of 45 (7 %) patients with negative sestamibi imaging that had an accurate SPECT and SPECT/CT. Of 312 patients (87 %) with positive uptake on sestamibi (93 % true positive, 7 % false positive), concordant findings were present in 86 % SPECT and 84 % SPECT/CT. In cases where imaging modalities were discordant, but at least one method was true‐positive, 123I/99Tc‐sestamibi was significantly better than both SPECT and SPECT/CT (p < 0.001). The inclusion of SPECT and SPECT/CT in 1°HPT imaging protocol increases patient cost up to 2.4‐fold.Conclusion123I/99Tc‐sestamibi subtraction imaging is highly sensitive for preoperative localization in 1°HPT. SPECT and SPECT/CT are commonly concordant with 123I/99Tc‐sestamibi and rarely increase the sensitivity. Routine inclusion of multimodality imaging technique adds minimal clinical benefit but increases cost to patient in high‐volume setting.

Objective The aim of this study was to determine if differences in coronary endothelial function are observed between asymptomatic women with type 2 diabetes mellitus (DM) and control subjects using coronary phase contrast flow velocity magnetic resonance imaging in response to cold pressor stress, an established endothelium-dependent vasodilatory stress. Methods Phase contrast flow velocity imaging of the right coronary artery was performed in 7 asymptomatic premenopausal women with DM and 8 healthy female participants in response to the cold pressor test at 3 T. Results There was no significant difference in percent increase in coronary flow velocity from rest to peak flow velocity between DM and control subjects (32% ± 22% vs 46% ± 17%; P = 0.11). However, percent increase in coronary flow velocity was lower in DM than in control subjects (−3% ± 14% vs 31% ± 30%; P = 0.01) during the second minute of cold pressor stress, when endothelial-mediated vasodilation should occur. Conclusions Asymptomatic women with DM demonstrate reduced coronary flow velocity during the second minute of cold pressor stress, indicating coronary endothelial dysfunction.

Objective Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout. Methods An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multicriterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set. Results The entry criterion for the new classification criteria requires the occurrence of at least 1 episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (i.e., synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU‐negative synovial fluid aspirate), and imaging (double‐contour sign on ultrasound or urate on dual‐energy computed tomography, radiographic gout‐related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively). Conclusion The new classification criteria, developed using a data‐driven and decision analytic approach, have excellent performance characteristics and incorporate current state‐of‐the‐art evidence regarding gout.

Abstract Estrogen receptor (ER) β is highly expressed in normal breast epithelium and a putative tumor suppressor. Atypical hyperplasia substantially increases breast cancer risk, but identification of biomarkers to further improve risk stratification is needed. We evaluated ERβ expression in breast tissues from women with atypical hyperplasia and association with subsequent breast cancer risk. ERβ expression was examined by immunohistochemistry in a well-characterized 171-women cohort with atypical hyperplasia diagnosed 1967–1991. Nuclear ERβ percent and intensity was scored in the atypia and adjacent normal lobules. An ERβ sum score (percent + intensity) was calculated and grouped as low, moderate, or high. Competing risks regression was used to assess associations of ERβ expression with breast cancer risk. After 15-year median follow-up, 36 women developed breast cancer. ERβ expression was lower in atypia lobules in than normal lobules, by percent staining and intensity (both P &lt; 0.001). Higher ERβ expression in the atypia or normal lobules, evaluated by percent staining, intensity or sum score, decreased the risk of subsequent breast cancer by 2-fold (P = 0.04) and 2.5-fold (P = 0.006). High normal lobule ERβ expression conferred the strongest protective effect in premenopausal women: the 20-year cumulative incidence of breast cancer was 0% for women younger than 45 years with high versus 31% for low–moderate ERβ expression (P = 0.0008). High ERβ expression was associated with a significantly decreased risk of breast cancer in women with atypical hyperplasia. These data suggest that ERβ may be a useful biomarker for risk stratification and a novel therapeutic target for breast cancer risk reduction. Cancer Prev Res; 8(11); 1084–92. ©2015 AACR.