Multiple Gland Research Articles

Gene expression profiling reveals candidate genes for defining spider silk gland types

Molecular studies of the secretory glands involved in spider silk production have revealed candidate genes for silk synthesis and a complicated history of spider silk gene evolution. However, differential gene expression profiles of the multiple silk gland types within an individual orb-web weaving spider are lacking. Each of these gland types produces a functionally distinct silk type. Comparison of gene expression among spider silk gland types would provide insight into the genes that define silk glands generally from non-silk gland tissues, and the genes that define silk glands from each other. Here, we perform 3’ tag digital gene expression profiling of the seven silk gland types of the silver garden orb weaver Argiope argentata. Five of these gland types produce silks that are non-adhesive fibers, one silk includes both fibers and glue-like adhesives, and one silk is exclusively glue-like. We identify 1275 highly expressed, significantly upregulated, and tissue specific silk gland specific transcripts (SSTs). These SSTs include seven types of spider silk protein encoding genes known as spidroin genes. We find that the fiber-producing major ampullate and minor ampullate silk glands have more similar expression profiles than any other pair of glands. We also find that a subset of the SSTs is enriched for transmembrane transport and oxidoreductases, and that these transcripts highlight differences and similarities among the major ampullate, minor ampullate, and aggregate silk glands. Furthermore, we show that the wet glue-producing aggregate glands have the most unique SSTs, but still share some SSTs with fiber producing glands. Aciniform glands were the only gland type to share a majority of SSTs with other silk gland types, supporting previous hypotheses that duplication of aciniform glands and subsequent divergence of the duplicates gave rise to the multiple silk gland types within an individual spider.

Sporadic multiple parathyroid gland disease in young woman with primary hyperparathyroidism

Sporadic multiple parathyroid gland disease in young woman with primary hyperparathyroidism

Non-MAS Non-APS Rare Case: Co-Occurrence of Graves’ Disease (GD), Latent Autoimmune Diabetes in Adult (LADA), Systemic Lupus Erythematosus (SLE), and Ulcerative Colitis (UC)

Background: Advancement in medical technology has allowed us to diagnose complicated autoimmune diseases. There is a growing report of multiple autoimmunity co-occurence. Multiple Autoimmune Syndrome (MAS) is a combination of at least three autoimmune diseases, whereas Autoimmune Polyendocrine Syndromes (APS) comprise autoimmunity that involves multiple endocrine gland. Case Illustration: A 47-year old female came with chief complaint of palpitation. She had a history of systemic lupus erythematosus in the last three years, after suffering from malar rash, alopecia, and polyarthritis. Her 24-hour urine protein was 1575 mg. She routinely consumes methylprednisolone, hydroxychloroquine, and mycophenolic acid. She also experienced hematochezia and the biopsy from colonoscopy revealed chronic colitis with crypt destruction. She was diagnosed with ulcerative colitis and was treated with mesalazine. Since last year, her blood glucose was consistently high, accompanied with polydipsia and polyuria. She was treated with metformin, despite persistent increase in her A1C, as well as fasting and random blood glucose. We performed GAD65 test which came back positive, hence we diagnosed her with latent autoimmune diabetes in adult. In the past three months, she experienced palpitations, tremor, diarrhea, diaphoresis, and unexplainable weight loss. No exophthalmos was found, but she complained of an enlargement around her neck. We run thyroid hormone test, her TSHs was <0.003 (0.35-4.94 μIU/mL) and FT4 was 4.17 (0.70-1.48 ng/mL). Her ultrasound revealed diffuse enlargement of both thyroid with increased vascularization. We diagnosed her with Graves’ disease and treated her with methimazole and propranolol. Discussion: This case highlighted the rare co-occurrence of four autoimmune diseases. The underlying genetic predisposition of individual with autoimmune disease, will make them prone to develop multiple defect in their self-tolerance mechanism. However, the strict criteria of APS or MAS constrained us from putting all her autoimmunities into one big umbrella. Based on epidemiological data, hyperthyroidism in female productive age, with diffuse thyroid enlargement, is commonly due to Graves’ disease. However, this diagnosis needs to be further evaluated with thyroid scintigraphy and confirmed with TSH-receptor antibody test. Conclusion: Improvement in medical diagnostic tools as well as better understanding of the underlying pathophysiology will make it inevitable to find more autoimmunity co-occurrence in the future. In order to keep up with this progress, the traditional classification of APS or MAS should be reviewed to allow clinician to see the case in one big entity. Keywords: GD, LADA, SLE, UC

CD8+ T Lymphocytes: Crucial Players in Sjögren's Syndrome.

Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease associated with damage to multiple organs and glands. The most common clinical manifestations are dry eyes, dry mouth, and enlarged salivary glands. Currently, CD4+ T lymphocytes are considered to be key factors in the immunopathogenesis of pSS, but various studies have shown that CD8+ T lymphocytes contribute to acinar injury in the exocrine glands. Therefore, in this review, we discussed the classification and features of CD8+ T lymphocytes, specifically describing the role of CD8+ T lymphocytes in disease pathophysiology. Furthermore, we presented treatment strategies targeting CD8+ T cells to capitalize on the pathogenic and regulatory potential of CD8+ T lymphocytes in SS to provide promising new strategies for this inflammatory disease.

Atypical parathyroid adenoma: clinical and anatomical pathologic features.

BackgroundPrimary hyperparathyroidism is an endocrine pathology that affects calcium metabolism. Patients with primary hyperparathyroidism have high concentrations of serum calcium or high concentrations of parathyroid hormone, or incorrect parathyroid hormone levels for serum calcium values. Primary hyperparathyroidism is due to the presence of an adenoma/single-gland disease in 80–85%. Multiple gland disease or hyperplasia accounts for 10–15% of cases of primary hyperparathyroidism. Atypical parathyroid adenoma and parathyroid carcinoma are both responsible for about 1.2–1.3% and 1% or less of primary hyperparathyroidism, respectively.MethodsWe performed a retrospective cohort study and enrolled 117 patients with primary hyperparathyroidism undergoing minimally invasive parathyroidectomy. Histological and immunohistochemical examination showed that 107 patients (91.5%) were diagnosed with typical adenoma (group A), while 10 patients (8.5%) were diagnosed with atypical parathyroid adenoma (group B). None of the patients were affected by parathyroid carcinoma.ResultsSignificant statistical differences were found in histological and immunohistochemical parameters as pseudocapsular invasion (p < 0.001), bands of fibrosis (p < 0.001), pronounced trabecular growth (p < 0.001), mitotic rates of > 1/10 high-power fields (HPFs) (p < 0.001), nuclear pleomorphism (p = 0.036), thick capsule (p < 0.001), Ki-67+ > 4% (p < 0.001), galectin-3 + (p = 0.002), and protein gene product (PGP) 9.5 + (p = 0.038).ConclusionsAtypical parathyroid adenoma is a tumor that has characteristics both of typical adenoma and parathyroid carcinoma. The diagnosis is reached by excluding with strict methods the presence of malignancy criteria. Atypical parathyroid adenoma compared to typical adenoma showed significant clinical, hematochemical, histological, and immunohistochemical differences. We did not find any disease relapse in the 10 patients with atypical parathyroid adenoma during 60 months of follow-up time.

Identification of key non-coding RNAs and transcription factors regulators and their potential drugs for steroid-induced femoral head necrosis

Steroid-induced necrosis of femoral head (SINFH) is a femoral head necrotic disease caused by prolonged use of hormones. The detailed pathogenesis has not been fully demonstrated. In this study, we employed the bioinformatics approach to probe the roles of SINFH inhibitors. Core dysfunction modules related to SINFH was obtained. Meanwhile, GO and KEGG analysis of genes in dysfunction modules are carried out. Furthermore, the pivot prediction analysis of dysfunction modules related to ncRNA and transcription factor (TF) has been performed. The functions of the enriched modules were focused on multiple perspectives, including circulation, gland development, bone development and reconstruction, calcium production, and fatty acid metabolism regulation. The ncRNAs and TFs analysis showed that miR-322-5p, miR-124-3p, miR-125a-3p, and Ctnnb1 were important members of SINFH dysfunction. Drug targets suggested that Zinc and adenosine monophosphate may have an impact on SINFH dysfunction. SINFH was closely related to bone development and reconstruction.

Requirement of FAT and DCHS protocadherins during hypothalamic-pituitary development.

Pituitary developmental defects lead to partial or complete hormone deficiency and significant health problems. The majority of cases are sporadic and of unknown cause. We screened 28 patients with pituitary stalk interruption syndrome for mutations in the FAT/DCHS family of protocadherins that have high functional redundancy. We identified 7 variants, 4 of which are putatively damaging, in FAT2 and DCHS2 in 6 patients with pituitary developmental defects recruited through a cohort of patients with mostly ectopic posterior pituitary gland and/or pituitary stalk interruption. All patients had growth hormone deficiency, and 2 presented with multiple hormone deficiencies and small glands. FAT2 and DCHS2 were strongly expressed in the mesenchyme surrounding the normal developing human pituitary. We analyzed Dchs2–/– mouse mutants and identified anterior pituitary hypoplasia and partially penetrant infundibular defects. Overlapping infundibular abnormalities and distinct anterior pituitary morphogenesis defects were observed in Fat4–/– and Dchs1–/– mouse mutants, but all animal models displayed normal commitment to anterior pituitary cell types. Together our data implicate FAT/DCHS protocadherins in normal hypothalamic-pituitary development and identify FAT2 and DCHS2 as candidates underlying pituitary gland developmental defects such as ectopic pituitary gland and/or pituitary stalk interruption.

Superficial peritoneal endometriotic lesions are histologically diverse and rarely demonstrate menstrual cycle synchronicity with matched eutopic endometrium.

Do menstrual cycle-dependent changes occur in the histological appearance of superficial peritoneal endometriotic lesions, and are they equivalent to those observed in the eutopic endometrium? Only a small subset of superficial peritoneal endometriotic lesions exhibits some histological features in phase with menstrual cycle-related changes observed in eutopic endometrium. Endometriotic lesions are frequently described as implants that follow menstrual cycle-related changes in morphology, as per the eutopic endometrium. This concept has been widely accepted despite the lack of conclusive published evidence. This was a retrospective cohort study of 42 patients, from across the menstrual cycle, with surgically and histologically confirmed endometriosis. Patients were a subset selected from a larger endometriosis study being conducted at the Royal Women's Hospital, Melbourne since 2012. Histological features of epithelium, stroma and gland morphology were examined in haematoxylin and eosin stained sections of superficial peritoneal endometriotic lesions and matched eutopic endometrium (menstrual: n = 4, proliferative: n = 11, secretory: n = 17, hormone-treated: n = 10). At least two biopsies (average = 4, range = 2-8 biopsies) and a matched endometrial sample were analysed for each patient and results were presented per endometriotic gland profile (n = 1051). Data were analysed using mixed effects logistic regression to account for multiple patients and multiple endometriotic biopsies, each with multiple endometriotic gland profiles. This model also enabled analysis of endometriotic lesions versus eutopic endometrium. There was considerable inter- and intra-patient variability in the morphology of superficial peritoneal endometriotic lesions. Menstrual cycle-associated changes were only observed for some features in a subset of endometriotic gland profiles. The proportion of endometriotic gland profiles with epithelial mitoses significantly increased in the proliferative phase (18% of gland profiles) relative to the menstrual phase (0% of endometriotic gland profiles) (odds ratios (OR) 9.30; 95% confidence intervals (CI) = 3.71-23.32; P < 0.001). Fewer blood-filled gland lumens were observed in the secretory phase (45% of endometriotic gland profiles) compared to the menstrual phase (67% of endometriotic gland profiles) (OR, 0.30; 95% CI = 0.11-0.79; P = 0.015). The features of the eutopic endometrium analysed in this study did not reflect the results in matched endometriotic lesions (P > 0.05). Not applicable. This study focused on features observed in sections of superficial peritoneal lesions and these may differ from features of deep infiltrating endometriosis or ovarian endometriomas. Cycle phases were limited to menstrual, proliferative and secretory phases to allow appropriate statistical modelling. This study highlights heterogeneity in the histological characteristics of superficial peritoneal lesions. It challenges the assumption that lesion morphology consistently reflects menstrual cycle-associated changes. Research reported in this publication was supported in part by National Health and Medical Research Council (NHMRC) project grants GNT1012245, GNT1105321 and GNT1026033 (P.A.W.R., J.E.G. and S.J.H.-C.). There are no competing interests.

S2933 Vanishing Polyps: Can Switching From a PPI to an H2 Blocker Cause Regression of Fundic Gland Polyps?

INTRODUCTION: Fundic gland polyps (FGPs) are identified as a sequalae of prolonged acid suppression. Though some studies show that acid suppression with a proton pump inhibitor (PPI) or Histamine 2 receptor blockers (H2RB) may cause FGPs, stronger evidence supports PPIs as a culprit. Studies have shown improvement of FGPs with cessation of acid suppression, but few studies investigated the effect of changing therapy to an H2RB. This case demonstrates a reduction of polyp size and number upon transition to an H2RB in a patient who developed FGPs as a result of long-term PPI use. CASE DESCRIPTION/METHODS: An 85-year-old female with rheumatoid arthritis on methotrexate and prednisone and on chronic PPI for 15 years for acid reflux presented to the gastroenterology clinic for possible gastritis. Upper endoscopy was performed and showed multiple 5–50 mm pedunculated and sessile polyps throughout the entire stomach. A majority of the polyps were about 3–5 cm. A hot snare and a Roth net were used to remove polyps to confirm histopathology (Figure 1). Gastric biopsies revealed FGPs without evidence of H. pylori, intestinal metaplasia, dysplasia or malignancy. Despite concern for FAP, malignancy, or high-grade dysplasia, the patient elected for continued endoscopic surveillance. She transitioned from a PPI to an H2RB. Serial endoscopies showed marked improvement in the size and number of gastric polyps at 6-months (Figure 2) and at 1-year (Figure 3). DISCUSSION: Some studies have shown a 4 fold increased risk of FGP formation in patients on chronic PPI. These polyps likely form as a response to low acid production causing increased parietal cell growth due to increased gastrin and chromogranin-A circulation causing gland proliferation. Few case reports demonstrate improvement of polyp size and number with transitioning therapy from PPI to H2RB and no large trials support changing therapy to H2RB. Still, H2RBs may be an ideal alternative since studies have shown an improvement in polyp size with cessation of PPI. Though FGPs are benign, PPI may increase the risk of adenomatous polyps and biopsy is necessary to differentiate these, particularly in patients with FAP. Our case demonstrates that discontinuing PPI for H2RB may lead to a sheer reduction in both number of polyps and polyp size, making lesions more amenable to continued resection and sampling and, therefore decreasing and minimizing risk of malignancy.Figure 1.: Initial endoscopy showing multiple large Fundic Gland Polyps in patient on chronic PPI for 15 years.Figure 2.: Repeat Endoscopy 6 months after transitioning from PPI to H2RB and showing smaller and fewer number of Fundic Gland Polyps.Figure 3.: Repeat Endoscopy 1 year after transitioning to H2RB and demonstrating continued, marked improvement in the size and number of Fundic Gland Polyps.

Factors increasing surgery success in primary hyperparathyroidism

Aim: Standart procedure for Primary hyperparathyroidism patients’ is two sides neck exploration, during the last years minimal incision started to be used for primary hyperparathyroidisim patients at primary hyperparathyrodism patients. Some researchers had been done to which patients should perform minimal incision surgery that a set of indexes proposed to use. So we can try to show which parameters should be use for get better surgery results.Material and Methods: Files of the patients, that undergo surgery for primary parathyroidism between January 2009-2016, will be studied retrospectively.Results: There 166 patients operated for primary hyperparathyroidism. 14 of these patients have multi gland disease. There is no difference for single gland disease and multigland disease patients between age and gender statistically. Multiglands disease patients’ pathology specimens lenght and weight is lower than single gland disease group statistically. Preoperative and post operative parathormone(Pth) and calcium levels have no statistical difference. Comparing minimal invasive parathyroidectomy(MIP) and bilateral neck exploration parathyroidectomy shows there is no statistically difference between them. Avaible parameters applied advised parameters.Conclusion: There is scoring systems, that made from combination of biochemical parameters and screening methods, seperate single gland disease and multiple glands disease. We evaluated these scoring system among our patients. CaPTHUS scoring system seems useful at our patient group. Wisconsin index is statisticaly meaningless with slight difference. So there is need to more crowded and prospective studies to be done for seperating multi gland disease and solitary adenoma. Comparing Minimal invasive parathyroidectomy and bilateral neck exploration parathyroidectomy shows that MIP is a safe procedure in selected patients.

Multiglandular Parathyroid Disease: the Results of Surgical Treatment

Background. Sporadic multiple gland disease in primary hyperparathyroidism occurs in 7 to 33 % of cases. The absence of specific risk factors, low sensitivity of imaging methods, and low efficiency of bilateral neck exploration and intraoperative monitoring of parathyroid hormone indicate the complexity of the diagnosis and treatment of this disease’s form. Aim of the research. To analyze the results of surgical treatment of multiple lesions of the parathyroid gland in primary and secondary hyperparathyroidism. Methods. There was retrospective study, which included 100 observations of surgical treatment for primary and secondary hyperparathyroidism in the thoracic department of Irkutsk Regional Clinical Hospital from May 2018 to September 2019. The main point was to identify the frequency of surgical treatment outcomes in patients with multiple parathyroid lesions. As part of the study, potential predictors of multiple gland disease in primary hyperparathyroidism were analyzed. Results. Multiple gland disease in primary hyperparathyroidism occurs in 29 % of cases and causes persistence of the disease (p ≤ 0.01). Signs of multiple gland disease in primary hyperparathyroidism include the level of ionized calcium, parathyroid hormone (p ≤ 0.05), creatinine level and glomerular filtration rate (p ≤ 0.01). A negative result of intraoperative monitoring correlates with persistence of primary hyperparathyroidism in multiple lesions (χ2, p ≤ 0.05). Selective parathyroidectomy is associated with persistence of hyperparathyroidism in multiple lesions (χ2, p ≤ 0.05), while total parathyroidectomy is associated with remission of the disease (χ2, p ≤ 0.05). We did not find a statistically significant relationship between the results of surgical treatment for morphology of the parathyroid glands (χ2, p &gt; 0.1). Conclusion. Multiple gland disease is the main cause of persistence of primary hyperparathyroidism. This form of the disease corresponds to lower levels of calcium, parathyroid hormone, and kidney function. Persistence factors have been established: removal of less than four parathyroid glands and a negative result of intraoperative monitoring of parathyroid hormone. Bilateral neck exploration does not reduce the incidence of disease persistence.

4D-CT facilitates focused parathyroidectomy in patients with primary hyperparathyroidism by maintaining a high negative-predictive value for uninvolved quadrants.

Improved preoperative localization facilitates minimally invasive parathyroidectomy for removal of parathyroid lesions therefore preventing an invasive bilateral neck exploration. As 4D-CT has emerged, its high specificity has helped with preoperative parathyroid lesion localization. A high negative predictive value (NPV) would serve to further confirm parathyroid lesion localization and limit unnecessary surgical exploration. This study's objective was to determine the NPV of preoperative 4D-CT and its facilitation of minimally invasive parathyroidectomy. A retrospective review was compiled for patients undergoing parathyroidectomy for primary hyperparathyroidism with a preoperative 4D-CT. Included patients were sorted into various groups for comparison: those with 4D-CT localizing to a single lesion, localizing to multiple lesions, and those with nonlocalizing findings; multiple hypercellular parathyroid gland versus single gland findings; extent of surgical exploration; lesion location; and patients with concomitant thyroid nodules. Negative predictive value was calculated and used to quantify the ability for 4D-CT to rule out biochemically significant parathyroid lesions. In our review of 68 patients: sensitivity was 81.3%, specificity was 95.5%, positive predictive value was 87.1%, and negative predictive value was 93.3%. 86% had a single localizing 4D-CT, 7% had a non-localizing 4D-CT, and 7% had a multiple quadrant localizing 4D-CT. NPV for single and multi-localizing 4D-CT were 96.8% and 88.9%, respectively. Preoperative 4D-CT has a high negative predictive value (93.3%), suggesting in the majority of cases, a quadrant with no 4D-CT radiographic findings suspicious for parathyroid is unlikely to harbor biochemically significant parathyroid lesions.

Multiple Morphological Constraints-Based Complex Gland Segmentation in Colorectal Cancer Pathology Image Analysis

Histological assessment of glands is one of the major concerns in colon cancer grading. Considering that poorly differentiated colorectal glands cannot be accurately segmented, we propose an approach for segmentation of glands in colon cancer images, based on the characteristics of lumens and rough gland boundaries. First, we use a U-net for stain separation to obtain H-stain, E-stain, and background stain intensity maps. Subsequently, epithelial nucleus is identified on the histopathology images, and the lumen segmentation is performed on the background intensity map. Then, we use the axis of least inertia-based similar triangles as the spatial characteristics of lumens and epithelial nucleus, and a triangle membership is used to select glandular contour candidates from epithelial nucleus. By connecting lumens and epithelial nucleus, more accurate gland segmentation is performed based on the rough gland boundary. The proposed stain separation approach is unsupervised, and the stain separation makes the category information contained in the H&amp;E image easy to identify and deal with the uneven stain intensity and the inconspicuous stain difference. In this project, we use deep learning to achieve stain separation by predicting the stain coefficient. Under the deep learning framework, we design a stain coefficient interval model to improve the stain generalization performance. Another innovation is that we propose the combination of the internal lumen contour of adenoma and the outer contour of epithelial cells to obtain a precise gland contour. We compare the performance of the proposed algorithm against that of several state-of-the-art technologies on publicly available datasets. The results show that the segmentation approach combining the characteristics of lumens and rough gland boundary has better segmentation accuracy.

Hybrid Stem Cell States: Insights Into the Relationship Between Mammary Development and Breast Cancer Using Single-Cell Transcriptomics.

Similarities between stem cells and cancer cells have implicated mammary stem cells in breast carcinogenesis. Recent evidence suggests that normal breast stem cells exist in multiple phenotypic states: epithelial, mesenchymal, and hybrid epithelial/mesenchymal (E/M). Hybrid E/M cells in particular have been implicated in breast cancer metastasis and poor prognosis. Mounting evidence also suggests that stem cell phenotypes change throughout the life course, for example, through embryonic development and pregnancy. The goal of this study was to use single cell RNA-sequencing to quantify cell state distributions of the normal mammary (NM) gland throughout developmental stages and when perturbed into a stem-like state in vitro using conditional reprogramming (CR). Using machine learning based dataset alignment, we integrate multiple mammary gland single cell RNA-seq datasets from human and mouse, along with bulk RNA-seq data from breast tumors in the Cancer Genome Atlas (TCGA), to interrogate hybrid stem cell states in the normal mammary gland and cancer. CR of human mammary cells induces an expanded stem cell state, characterized by increased expression of embryonic stem cell associated genes. Alignment to a mouse single-cell transcriptome atlas spanning mammary gland development from in utero to adulthood revealed that NM cells align to adult mouse cells and CR cells align across the pseudotime trajectory with a stem-like population aligning to the embryonic mouse cells. Three hybrid populations emerge after CR that are rare in NM: KRT18+/KRT14+ (hybrid luminal/basal), EPCAM+/VIM+ (hybrid E/M), and a quadruple positive population, expressing all four markers. Pseudotime analysis and alignment to the mouse developmental trajectory revealed that E/M hybrids are the most developmentally immature. Analyses of single cell mouse mammary RNA-seq throughout pregnancy show that during gestation, there is an enrichment of hybrid E/M cells, suggesting that these cells play an important role in mammary morphogenesis during lactation. Finally, pseudotime analysis and alignment of TCGA breast cancer expression data revealed that breast cancer subtypes express distinct developmental signatures, with basal tumors representing the most “developmentally immature” phenotype. These results highlight phenotypic plasticity of normal mammary stem cells and provide insight into the relationship between hybrid cell populations, stemness, and cancer.

MON-376 Head to Toe Hyperparathyroidism - Impending Hyperparathyroid Crisis and Subsequent Crystal Arthropathies

The myriad of presentations associated with PHP are well established, however gout is not commonly associated with this disease. Additionally, it is unusual to see multiple threatening and potentially debilitating complications occur concurrently in one patient.An asymptomatic elderly male with hypertension presented to the PCP for the first time and was found on routine blood work to have a serum creatinine of 4.03 mg/dl, a serum calcium of 12.1mg/dl, and a PTH of 831.7ng/L. Subsequent Tc-99 Sestamibi scanning suggested that the source was both a single right inferior parathyroid adenoma and an ectopic mediastinal adenoma. At the initial encounter the patient’s hypercalcemia was treated with IV fluid resuscitation and calcitonin then subsequently cinacalcet. Renal ultrasound at that time showed normal sized kidneys with several cysts, and phosphate levels ranged from 2.0-3.9 mg/dl (range 2.5-4.5mg/dl. The patient’s serum calcium was controlled at 10.44mg/dl, and his renal function improved to a serum creatinine of 3.08mg/dl. Prior to discharge patient developed acute left knee pain, and was found to have an inflammatory arthritis, with urate crystals seen. The patient was diagnosed with an acute gout flare, which responded well to colchicine and was discharged. The patient eventually underwent parathyroidectomy, which showed a large 4cm left superior parathyroid as well as a large right superior parathyroid gland extending into the mediastinum. Pathology was consistent with parathyroid hyperplasia. After surgery, the patient developed hungry bone syndrome, with an admitting serum level calcium of 6.05mg/dl, serum magnesium of 2.00mg/dl, serum phosphorus of 2.8mg/dl, and serum potassium of 5.1mg/dl, with clinical features of tetany and weakness that resolved after two days with calcium and calcitriol administration. He again had an acute monoarticular arthritis prior to discharge that had both urate and calcium pyrophosphate crystals in the joint fluid and again responded well to colchicine and glucocorticoids. He was eventually discharged on vitamin D and calcium supplementation, with cinacalcet and colchicine.This case illustrates the multiple clinical teaching points that exist in primary hyperparathyroidism, including both types of presentation and potential complications. It also expresses the need to be vigilant of some rarer clinical features, such as potential hyperparathyroid crisis and multiple enlarged parathyroid glands. Physicians should also be wary of both gout and CPPD, as well as complications that occur post parathyroidectomy such as hungry bone syndrome.

SUN-137 Clonal Status of Multigland Disease Primary Hyperparathyroidism

Primary hyperparathyroidism (PHPT) is a common endocrine disorder that arises due to single or multiple parathyroid gland disease (MGD). The molecular mechanism(s) of parathyroid neoplasia are incompletely understood and both monoclonal (mono-X) and polyclonal (poly-X) parathyroid tumors have been described using methylation-sensitive PCR of X-linked Human Androgen Receptor (HUMARA) alleles. Our previous investigations of parathyroid tumor clonal status has shown that poly-X tumors are common and are associated with MGD in patients with non-familial PHPT (Shi et al. 2014 & 2018). This work examined the clonal status of the dominant gland and the clonal relationship of multiple tumors from the same patient has not been examined. The goal of the current study was to determine the clonal relationship of parathyroid tumors from PHPT patients with MGD. Banked parathyroid tissues from twenty-nine PHPT patients with MGD were examined in this study. Clonal status (mono-X vs poly-X) of multiple abnormal parathyroid glands from each patient was determined using a modification of the HUMARA assay used in our prior work. Briefly, methylation-sensitive PCR of HUMARA alleles was performed followed by fragment analysis using Capillary-Electrophoresis performed. Raw fragment sizing data analyzed using Peak Scanner software. Classification of samples as either mon-X or poly-X was made as described in (Shattuck et al.) Of 29 PHPT patients with MGD, 13 (45%) had pure mono-X, 5 (17%) had pure poly-X, and 11 (38%) had a mixture of mono-X and poly-X tumors. Five of 29 patients had three or more abnormal glands evaluated: 3 had mixture of poly-X and mono-X, 2 had pure mono-X tumors, and none were pure polyclonal-X. Eighteen (62%) out of 29 patients had paired upper or lower double adenomas. Of these, 9 (50%) were pure mono-X, 4 were pure poly-X, and 5 were mixed mono-X/poly-X. In 2 patients with multiple mono-X tumors, allele distribution was not the same in different abnormal glands. Our previous work has demonstrated that among patients with non-familial PHPT, poly-X parathyroid tumors are common and are associated with MGD. Our new data extend these findings to show that the clonal relationship between multiple parathyroid tumors from the same patient is complex and may reflect the emergence of single or multiple tumors from a background of parathyroid hyperplasia, or other mechanism(s). Future studies to explore the mechanisms behind these apparent clonal relationships are warranted and ongoing. Reference: (1) Shi et al., PNAS 2014, 201319742. (2) Shi et al., Surgery 2018, 9-14. (3) Shattuck. N Engl J Med 2005, 2406-12.

Surgical management and prognostic factors of spinal metastatic tumors

ObjectiveThis study aims to evaluate different prognostic factors after surgical management of metastatic spinal tumors regarding clinical condition, preoperative investigations, histopathological results, and surgical data.MethodsSeventy patients diagnosed as metastatic spinal tumors with neurological deficits and/or unstable spine operated for spinal decompression with or without instrumental fixation according to Spinal Instability Neoplastic Score (SINS) at our institute during the period from May 2014 to October 2018 with follow-up at least 9 months.ResultsLymphoma metastases were the commonest spinal metastases of 23% with significant p value = 0.001, males and ages above 50 years old were significantly affected. High vascularity and bone invasion were significant operative findings. Significant good prognostic factors for both survival and Klekampe score improvement were paretic patients, > 15 preoperative Klekampe score, early surgery, ≤ 3 vertebral affection, extradural tumor location, gross total resection, and metastatic tumors from multiple myeloma, thyroid gland, lymphoma, and prostatic gland.ConclusionEarly surgeries aiming neural decompression and keeping spinal stability according to Spinal Instability Neoplastic Score for patients with spinal metastases are the main hope for better survival and neurological improvement.

A Stiffness Controllable Multimodal Whisker Sensor Follicle for Texture Comparison

Mammals like rats, who live in dark burrows, heavily depend on tactile perception obtained through the vibrissal system to move through gaps and to discriminate textures. The organization of a mammalian whisker follicle contains multiple sensory receptors and glands strategically organized to capture tactile sensory stimuli of different frequencies. In this paper, we used a controllable stiffness soft robotic follicle to test the hypothesis that the multimodal sensory receptors together with the controllable stiffness tissues in the whisker follicle form a physical structure to maximize tactile information. In our design, the ring sinus and ringwulst of a biological follicle are represented by a linear actuator connected to a stiffness controllable mechanism in-between two different frequency-dependent data capturing modules. In this paper, we show for the first time the effect of the interplay between the stiffness and the speed of whisking on maximizing a difference metric for texture classification.

Epigenetic Conservation Is a Beacon of Function: An Analysis Using Methcon5 Software for Studying Gene Methylation.

PURPOSEDifferent epigenetic configurations allow one genome to develop into multiple cell types. Although the rules governing what epigenetic features confer gene expression are increasingly being understood, much remains uncertain. Here, we used a novel software package, Methcon5, to explore whether the principle of biologic conservation can be used to identify expressed genes. The hypothesis is that epigenetic configurations of important expressed genes will be conserved within a tissue.MATERIALS AND METHODSWe compared the DNA methylation of approximately 850,000 CpG sites between multiple clonal crypts or glands of human colon, small intestine, and endometrium. We performed this analysis using the new software package, Methcon5, which enables detection of regions of high (or low) conservation.RESULTSWe showed that DNA methylation is preferentially conserved at gene-associated CpG sites, particularly in gene promoters (eg, near the transcription start site) or the first exon. Furthermore, higher conservation correlated well with gene expression levels and performed better than promoter DNA methylation levels. Most conserved genes are in canonical housekeeping pathways.CONCLUSIONThis study introduces the new software package, Methcon5. In this example application, we showed that epigenetic conservation provides an alternative method for identifying functional genomic regions in human tissues.

Risk Factors of Severe Hypocalcemia After US-Guided Percutaneous Microwave Ablation of the Parathyroid Gland in Patients with Secondary Hyperparathyroidism.

Our aim was to identify potential risk factors associated with severe hypocalcemia (SH) after microwave ablation (MWA) in patients with secondary hyperparathyroidism (SHPT). This retrospective cross-sectional study enrolled 204 consecutive patients (with 387 parathyroid glands) who underwent MWA between July 2015 and May 2018. Clinical parameters, laboratory indices, and parathyroid gland characteristics were analyzed to assess risk factors associated with SH after MWA. SH was defined as serum calcium level lower than 1.875 mmol/L (7.5 mg/dL) after MWA. Two models (I and II) for pre-MWA and post-MWA prediction were established, respectively. In accordance with the KDIGO guidelines, the target value for intact parathyroid hormone (iPTH) less than 300 pg/mL within 7 days after MWA was considered as a successful procedure. The success rate of MWA was 71.6% (146/204). The incidence of hypocalcemia and SH after MWA was 35.8% and 22.06%, respectively. The pre-MWA prediction models I and II showed that high pre-MWA iPTH, a dramatic reduction in iPTH, low pre-MWA serum calcium, multiple ablated gland, and lack of pruritus symptoms were risk factors for developing SH. The accuracy (82.23% versus 83.25% in models I and II, respectively), sensitivity (34.88% versus 44.19%), specificity (95.45% versus 94.59%), positive predictive value (PPV) (68.18% versus 70.37%), and negative predictive value (NPV) (84% versus 85.37%) of both models were promising. The logistic regression fitting of the nomograms showed high prediction efficiency (0.845 and 0.863). High pre-MWA iPTH, dramatic reductions in iPTH, low pre-MWA serum calcium, multiple gland ablation, and no pruritus symptoms were predictors of SH. © 2019 American Society for Bone and Mineral Research.