Elevated IL-6 levels in a patient with pheochromocytoma.

Pheochromocytoma is a chromaffin cell-derived adrenal medullary tumour and usually presents with paroxysms of hypertension, palpitations, sweating and headache due to excessive catecholamine release. These tumours can also secrete a variety of bioactive neuropeptides and hormones other than catecholamines, resulting in unusual clinical manifestations. We report a female in her mid-30s who presented with fever, anaemia, thrombocytosis and markedly elevated inflammatory markers. The fever profile, including cultures, was negative. Contrast-enhanced CT of abdomen showed a large solid-cystic right adrenal lesion with elevated plasma-free normetanephrine levels suggestive of pheochromocytoma. The fever persisted despite empirical antibiotics and antipyretics. Interleukin-6 (IL-6) levels were elevated (41.2 pg/mL (3-4 pg/mL)). She was initiated on naproxen (NPX) at a dose of 250 mg two times per day. The patient responded to NPX, and after stabilisation, she underwent an adrenalectomy. There was a complete resolution of fever with normalisation of IL-6 levels postoperatively.

Steroidogenic acute regulatory protein (STAR) deficiency: Our experience and systematic review for phenotype-genotype correlation.

OBJECTIVE: Lipoid congenital adrenal hyperplasia (LCAH) is caused by mutations in STAR. A systematic review of phenotype-genotype correlation and data on testicular histology in LCAH patients is unavailable. We aim to describe our experience and provide phenotype-genotype correlation. DESIGN, PATIENTS AND MEASUREMENTS: Retrospective review of three genetically proven LCAH patients from our centre and per-patient data analysis from a systematic review of 292 probands. The phenotypic subgroups of 46,XY were Group A (typical female genitalia), Group B (atypical genitalia) and Group C (typical male genitalia). RESULTS: We report three new LCAH probands from India, all diagnosed post-infancy with preserved gonadal function and one novel variant. The systematic review reports 46,XY to 46,XX LCAH ratio of 1.1 (155:140). Patients with 46,XY LCAH in Group A were diagnosed in infancy (116/117) and had higher mineralocorticoid involvement than Group C (96.4% vs. 75%, p = 0.035), whereas Group C had preserved gonadal function. Hyperplastic adrenals are noted in ~60% of LCAH diagnosed with primary adrenal insufficiency in infancy. There was no report of gonadal germ cell cancer and rare reports of germ cell neoplasia in situ in adolescents, especially with intraabdominal gonads. Two-thirds of LCAH probands were East-Asian and 11/16 regional recurrent variants were from East Asia. There was minimal overlap between variants in Groups A (n = 55), B (n = 9) and C (n = 8). All nonsense and frameshift and most of the splice-site variants and deletion/insertions were present in Group A. CONCLUSIONS: We report three new cases of LCAH from India. We propose a phenotype-derived genotypic classification of reported STAR variants in 46,XY LCAH.

Longitudinal brain structure changes in Parkinson's disease: A replication study.

CONTEXT: An existing major challenge in Parkinson's disease (PD) research is the identification of biomarkers of disease progression. While magnetic resonance imaging is a potential source of PD biomarkers, none of the magnetic resonance imaging measures of PD are robust enough to warrant their adoption in clinical research. This study is part of a project that aims to replicate 11 PD studies reviewed in a recent survey (JAMA neurology, 78(10) 2021) to investigate the robustness of PD neuroimaging findings to data and analytical variations. OBJECTIVE: This study attempts to replicate the results in Hanganu et al. (Brain, 137(4) 2014) using data from the Parkinson's Progression Markers Initiative (PPMI). METHODS: Using 25 PD subjects and 18 healthy controls, we analyzed the rate of change of cortical thickness and of the volume of subcortical structures, and we measured the relationship between structural changes and cognitive decline. We compared our findings to the results in the original study. RESULTS: (1) Similarly to the original study, PD patients with mild cognitive impairment (MCI) exhibited increased cortical thinning over time compared to patients without MCI in the right middle temporal gyrus, insula, and precuneus. (2) The rate of cortical thinning in the left inferior temporal and precentral gyri in PD patients correlated with the change in cognitive performance. (3) There were no group differences in the change of subcortical volumes. (4) We did not find a relationship between the change in subcortical volumes and the change in cognitive performance. CONCLUSION: Despite important differences in the dataset used in this replication study, and despite differences in sample size, we were able to partially replicate the original results. We produced a publicly available reproducible notebook allowing researchers to further investigate the reproducibility of the results in Hanganu et al. (2014) when more data is added to PPMI.

Comparative Study of Insulin Sensitivity and Resistance and Their Correlation with Androgens in Lean and Obese Women with Polycystic Ovary Syndrome.

There is a lack of consensus on the optimal screening strategy for insulin resistance (IR), particularly in lean women with polycystic ovary syndrome (PCOS). Therefore, we conducted a cross-sectional study in 80 women with PCOS (28 lean/52 obese) and 80 age- and body mass index (BMI)-matched controls. Using a 5-point 75-g oral glucose tolerance test (OGTT) (0, 30, 60, 90, 120 min), we examined glucose and insulin excursions, IR, insulin sensitivity, beta-cell function (ßF), and the effect of androgens on IR. Lean and obese women with PCOS had similar glucose but higher insulin (except fasting in lean women) and insulin AUC as compared to their respective controls (p < 0.05). Lean women with PCOS were equally insulin-resistant but more hyperinsulinemic than the obese controls (p < 0.05). Although ßF ([1st phase: 481.71 ± 263.53 vs. 430.56 ± 232.37], [2nd phase: 815.16 ± 447.12 vs. 752.66 ± 428.95]) was comparable in lean and obese women with PCOS, lean women had better insulin sensitivity (112.78 ± 66.26 vs. 75.49 ± 55.6) (p < 0.05). Dehydroepiandrosterone sulfate (DHEAS) and androstenedione decreased with increasing BMI in lean women, and this correlated with deteriorating insulin sensitivity and exaggerated hyperinsulinemia. In obese women with PCOS, sex hormone-binding globulin (SHBG) correlated negatively with BMI and hyperinsulinemia, and positively with insulin sensitivity. This data suggests that estimating only fasting insulin may miss IR in lean women with PCOS; hence, additional time points in OGTT will add value to screening for IR. DHEAS and androstenedione may have a beneficial effect on insulin sensitivity and may be used to screen IR in lean women, while SHBG can be used as a predictive marker for IR in obese women with PCOS.

Correlation between Serum Vitamin D3 Levels and Severity of COVID-19, Experience from a COVID-19-Dedicated Tertiary Care Hospital from Western India.

Context: It is postulated that 25(OH)D deficiency is associated with a worse prognosis of COVID-19. Aims: We aimed to find out whether baseline serum 25-hydroxy vitamin D levels were correlated with COVID-19 disease severity or not in Indian population. Settings and Design: It is a prospective observational study. Methods and Material: We prospectively recruited 200 COVID-19-positive adult patients and measured their baseline vitamin D levels on admission and prospectively followed their clinical course for their outcome and correlated the association. Statistical Analysis Used: The continuous data were represented as mean (±SD) or median (IQR), while the categorical data were represented as proportions. Parametric data were analysed using unpaired T-test and ANOVA for two and more than two groups, and for categorical, nonparametric data, Chi-square test were applied. A two-sided P value of <0.05 was considered as statistically significant with 95% confidence interval. Results: Eighty-six per cent (172/200) of patients had hypovitaminosis D (<30 ng/mL). The prevalence of 25(OH) severe deficiency, deficiency and vitamin D insufficiency was 23%, 41% and 22%, respectively. Clinical severity was graded as asymptomatic (11%), mild (14%), moderate (14.5%), severe (37.5%) and critical (22%). Sixty per cent of patients had clinically severe or critical disease requiring oxygen support with eleven per cent (n = 22) mortality overall. Age (P: 0.001), HTN (P: 0.049) and DM (P: 0.018) were negatively associated with clinical severity. No linear association was found between vitamin D levels and clinical severity. Low vitamin D levels had a significant inverse association with inflammatory markers like neutrophil-lymphocyte ratio (NLR, P: 0.012) and IL-6 (P: 0.002). Conclusions: Vitamin D deficiency was not associated with worse outcomes of COVID-19 infection in Indian population.

Endogenous pathology in tauopathy mice progresses via brain networks.

Neurodegenerative tauopathies are hypothesized to propagate via brain networks. This is uncertain because we have lacked precise network resolution of pathology. We therefore developed whole-brain staining methods with anti-p-tau nanobodies and imaged in 3D PS19 tauopathy mice, which have pan-neuronal expression of full-length human tau containing the P301S mutation. We analyzed patterns of p-tau deposition across established brain networks at multiple ages, testing the relationship between structural connectivity and patterns of progressive pathology. We identified core regions with early tau deposition, and used network propagation modeling to determine the link between tau pathology and connectivity strength. We discovered a bias towards retrograde network-based propagation of tau. This novel approach establishes a fundamental role for brain networks in tau propagation, with implications for human disease.

Reproducibility of cerebellar involvement as quantified by consensus structural MRI biomarkers in advanced essential tremor.

Essential tremor (ET) is the most prevalent movement disorder with poorly understood etiology. Some neuroimaging studies report cerebellar involvement whereas others do not. This discrepancy may stem from underpowered studies, differences in statistical modeling or variation in magnetic resonance imaging (MRI) acquisition and processing. To resolve this, we investigated the cerebellar structural differences using a local advanced ET dataset augmented by matched controls from PPMI and ADNI. We tested the hypothesis of cerebellar involvement using three neuroimaging biomarkers: VBM, gray/white matter volumetry and lobular volumetry. Furthermore, we assessed the impacts of statistical models and segmentation pipelines on results. Results indicate that the detected cerebellar structural changes vary with methodology. Significant reduction of right cerebellar gray matter and increase of the left cerebellar white matter were the only two biomarkers consistently identified by multiple methods. Results also show substantial volumetric overestimation from SUIT-based segmentation-partially explaining previous literature discrepancies. This study suggests that current estimation of cerebellar involvement in ET may be overemphasized in MRI studies and highlights the importance of methods sensitivity analysis on results interpretation. ET datasets with large sample size and replication studies are required to improve our understanding of regional specificity of cerebellum involvement in ET. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 21 March 2022. The protocol, as accepted by the journal, can be found at: https://doi.org/10.6084/m9.figshare.19697776 .

Yeast ORC sumoylation status fine-tunes origin licensing.

Sumoylation is emerging as a posttranslation modification important for regulating chromosome duplication and stability. The origin recognition complex (ORC) that directs DNA replication initiation by loading the MCM replicative helicase onto origins is sumoylated in both yeast and human cells. However, the biological consequences of ORC sumoylation are unclear. Here we report the effects of hypersumoylation and hyposumoylation of yeast ORC on ORC activity and origin function using multiple approaches. ORC hypersumoylation preferentially reduced the function of a subset of early origins, while Orc2 hyposumoylation had an opposing effect. Mechanistically, ORC hypersumoylation reduced MCM loading in vitro and diminished MCM chromatin association in vivo. Either hypersumoylation or hyposumoylation of ORC resulted in genome instability and the dependence of yeast on other genome maintenance factors, providing evidence that appropriate ORC sumoylation levels are important for cell fitness. Thus, yeast ORC sumoylation status must be properly controlled to achieve optimal origin function across the genome and genome stability.

"The Bitter Truth of Sugar"-Euglycemic Diabetic Ketoacidosis due to Sodium-glucose Cotransporter-2 Inhibitors: A Case Series.

Diabetic ketoacidosis (DKA) is an acute and major complication of diabetes mellitus (DM), both type I and type II. Biochemically, DKA consists of a triad of blood sugar levels greater than 250 mg/dL, ketonemia of greater than 3 mmol/L and/or significant ketonuria, and a blood pH less than 7.3 with an increased anion gap. Currently, the sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are widely used in management of type II diabetes. There have been several reports of an association between euglycemic diabetic ketoacidosis (EuDKA) and SGLT-2i agents. We present three different patients who were on SGLT-2i therapy who developed recurrent EuDKA postprocedure or sepsis. We believe that prolonged treatment (5-6 days) with intravenous (IV) insulin with glucose until resolution of glycosuria can be considered as an inexpensive marker of resolution of EuDKA. Moreover, the recommended duration for discontinuation of these drugs prior to elective procedures should be longer than 3 days. How to cite this article: Shah M, Pathrose E, Bhagwat NM, Chandy D. "The Bitter Truth of Sugar"-Euglycemic Diabetic Ketoacidosis due to Sodium-glucose Cotransporter-2 Inhibitors: A Case Series. Indian J Crit Care Med 2022;26(1):123-126.

Ventral clitoroplasty preserves dorsal nerves in case of partial androgen insensitivity syndrome: 4 years follow-up.

Androgen insensitivity syndrome (AIS) causes feminization of the external genitalia, in 46XY individuals. We report a notable case of partial AIS (PAIS), which was treated with ventral clitoroplasty and vaginal dilatation. The patient is a 17-year-old phenotypically female, presented with primary amenorrhea, infantile vagina, clitoromegaly, and presence of testes. Feminizing genitoplasty was done in form of ventral clitoroplasty with gonadectomy and was put on hormone replacement therapy and advised regular use of vaginal dilators to improve vaginal length. In ventral approach, the erectile tissues are excised without disturbing the neurovascular structure. Vibratory threshold perception of clitoris assessed by biothesiometer was normal 4 years after the surgery. Vaginal corrective surgery is not required when presentation is at later stage and has some vaginal depth to work out with vaginal dilators. Regular psychiatric consultations and support are needed in patients with PAIS to develop their confidence in gender identity and sexual orientation.

Targeting Predialysis Glucose up to 180 mg/dl Reduces Glycemic Variability in End Stage Diabetic Nephropathy.

Context: Glycemic variability plays a major role in the development as well as the progression of cardiovascular disease in diabetes. Aims: We compared the mean plasma glucose and glycemic variability (GV) parameters on and off hemodialysis (HD) in patients with End-Stage Diabetic Nephropathy (ESDN) and End-Stage Renal Disease (ESRD). Settings and Design: Cross-sectional study. Methods and Material: We included 23 ESDN and 6 ESRD patients who underwent continuous glucose monitoring (CGM) (iPro2) for 6 days and a glucose-free dialysate for 4 hours thrice weekly. EasyGV software was used to calculate the variability parameters {mean glucose, Time in range (TIR), Time above and below range (TAR/TBR), CV (Coefficient of Variation) and MAGE}. Statistical Analysis Used: The quantitative data variables were expressed by using mean and SD. Unpaired t-test was used to compare the two groups. P value <0.05 was considered significant. Results: In the ESDN group, TIR was significantly lower whereas TAR and TBR were significantly higher on HD day. MAGE (101.88 ± 40.5 v/s 89.46 ± 30.0, P < 0.007) and CV (29.41% v/s 21.67%) were higher on HD day. Subjects with pre-HD glucose values ≥180 mg/dl (Group B, n = 24) had a rapid drop with a delayed higher rise in glucose values than those with pre-HD glucose values <180 mg/dl (Group A, n = 27). Ten patients had 13 episodes of hypoglycemia. The CGM parameters were not different in the ESRD group. Conclusions: Targeting a pre- HD glucose value <180 mg/dl could be a good strategy to prevent larger fluctuation during and post HD.

SUMO fosters assembly and functionality of the MutSγ complex to facilitate meiotic crossing over.

Crossing over is essential for chromosome segregation during meiosis. Protein modification by SUMO is implicated in crossover control, but pertinent targets have remained elusive. Here we identify Msh4 as a target of SUMO-mediated crossover regulation. Msh4 and Msh5 constitute the MutSγ complex, which stabilizes joint-molecule (JM) recombination intermediates and facilitates their resolution into crossovers. Msh4 SUMOylation enhances these processes to ensure that each chromosome pair acquires at least one crossover. Msh4 is directly targeted by E2 conjugase Ubc9, initially becoming mono-SUMOylated in response to DNA double-strand breaks, then multi/poly-SUMOylated forms arise as homologs fully engage. Mechanistically, SUMOylation fosters interaction between Msh4 and Msh5. We infer that initial SUMOylation of Msh4 enhances assembly of MutSγ in anticipation of JM formation, while secondary SUMOylation may promote downstream functions. Regulation of Msh4 by SUMO is distinct and independent of its previously described stabilization by phosphorylation, defining MutSγ as a hub for crossover control.

Prevalence and predictors of abnormal glucose tolerance and its resolution in acromegaly: Single Centre retrospective study of 90 cases.

Aims The aim of the study was to evaluate the prevalence and predictors of abnormal glucose tolerance (Diabetes + Prediabetes) and its resolution in Acromegaly. SETTINGS AND DESIGN: Retrospective observational study. METHODS AND MATERIAL: Ninety patients with acromegaly and followed up post operatively for 1 year were included. The study cohort was divided into two groups: Group A: abnormal glucose tolerance [AGT: Diabetes + prediabetes (n = 40)] and Group B: normal glucose tolerance (NGT) (n = 50).The impact of the following parameters: age, sex, Waist Circumference(WC), Body Mass Index (BMI), duration of acromegaly, Growth Hormone (GH) levels, Insulin like Growth Factor 1 (IGF1) levels, pituitary tumour size, hypertension, and family history of diabetes as predictors for diabetes were studied pre surgery and post-surgery at 3 months and 1 year affecting glycaemia. Unpaired t-test, chi-square test and binary logistic regression analysis were used for statistical analysis. RESULTS: The prevalence of AGT in our cohort was 44.44% (Diabetes 37.77%, prediabetes 6.66%).Patients with AGT were older (44.2 ± 12.21 years vs. 34.92 ± 11.62 years; p = 0.00040) and had higher WC (in cm) (91.35 ± 7.87 vs.87.12 ± 6.07; p = 0.005) than NGT. Hypertension and family history of diabetes were significantly more frequent in patients with AGT. GH and IGF1 levels were not significantly different between the groups. On binary logistic regression, Sex (p = 0.0105) (OR = 6.0985), waist circumference (p = 0.0023) (OR = 1.2276) and hypertension (p = 0.0236) (OR = 1.632) were found to be significant predictors of AGT in acromegaly. After surgery 42.5% and 62.5% patients became normoglycemic at 3 months and 1 year respectively. On binary logistic regression there were no predictors for achieving normoglycemia at 3 months or 1 year, however the delta change in GH, BMI and tumour size were significant. CONCLUSIONS: The prevalence of AGT was 44.44%. Female sex, WC and hypertension were found to be significant predictors of AGT in acromegaly. Post-surgery normoglycemia was achieved in 42.5% at 3 months and 62.5% at 1 year with no predictors for normalisation of AGT.

Unrecognized Primary Hypothyroidism As a Possible Cause of Hyperreactio Luteinalis.

Hyperreactio luteinalis (HRL) is characterised by benign enlargement of ovaries in pregnancy associated with hyperandrogenism. A 19-year-old primigravida presented with breathlessness, abdominal distension and vomiting in the thirteenth week of gestation. Abdominal examination revealed distension of abdomen disproportionate to the gestational age. Ultrasound was suggestive of bilaterally enlarged multicystic ovaries with a characteristic "spoke-wheel" pattern and a diagnosis of HRL was made. Laboratory investigations revealed primary hypothyroidism and elevated testosterone. She was initiated on levothyroxine therapy. Her respiratory distress worsened on the third day of admission for which she underwent emergency laparotomy with cyst aspiration. Thyroid function tests normalized within six weeks after the initiation of therapy and remained normal for the remainder of pregnancy. Serum testosterone levels returned to normal six weeks postpartum. The elevated thyroid-stimulating hormone levels could have contributed to development of HRL by cross-reacting with human chorionic gonadotropin and follicle-stimulating hormone receptors. Hyperandrogenism and ovarian enlargement regresses with levothyroxine therapy.

SUMO is a pervasive regulator of meiosis.

Protein modification by SUMO helps orchestrate the elaborate events of meiosis to faithfully produce haploid gametes. To date, only a handful of meiotic SUMO targets have been identified. Here, we delineate a multidimensional SUMO-modified meiotic proteome in budding yeast, identifying 2747 conjugation sites in 775 targets, and defining their relative levels and dynamics. Modified sites cluster in disordered regions and only a minority match consensus motifs. Target identities and modification dynamics imply that SUMOylation regulates all levels of chromosome organization and each step of meiotic prophase I. Execution-point analysis confirms these inferences, revealing functions for SUMO in S-phase, the initiation of recombination, chromosome synapsis and crossing over. K15-linked SUMO chains become prominent as chromosomes synapse and recombine, consistent with roles in these processes. SUMO also modifies ubiquitin, forming hybrid oligomers with potential to modulate ubiquitin signaling. We conclude that SUMO plays diverse and unanticipated roles in regulating meiotic chromosome metabolism.

Most mammalian, yeast and other eukaryote cells have two sets of chromosomes, one from each parent, which contain all the cell's DNA. Sex cells ­ like the sperm and egg ­ however, have half the number of chromosomes and are formed by a specialized type of cell division known as meiosis. At the start of meiosis, each cell replicates its chromosomes so that it has twice the amount of DNA. The cell then undergoes two rounds of division to form sex cells which each contain only one set of chromosomes. Before the cell divides, the two duplicated sets of chromosomes pair up and swap sections of their DNA. This exchange allows each new sex cell to have a unique combination of DNA, resulting in offspring that are genetically distinct from their parents. This complex series of events is tightly regulated, in part, by a protein called the 'small ubiquitin-like modifier' (or SUMO for short), which attaches itself to other proteins and modifies their behavior. This process, known as SUMOylation, can affect a protein's stability, where it is located in the cell and how it interacts with other proteins. However, despite SUMO being known as a key regulator of meiosis, only a handful of its protein targets have been identified. To gain a better understanding of what SUMO does during meiosis, Bhagwat et al. set out to find which proteins are targeted by SUMO in budding yeast and to map the specific sites of modification. The experiments identified 2,747 different sites on 775 different proteins, suggesting that SUMO regulates all aspects of meiosis. Consistently, inactivating SUMOylation at different times revealed SUMO plays a role at every stage of meiosis, including the replication of DNA and the exchanges between chromosomes. In depth analysis of the targeted proteins also revealed that SUMOylation targets different groups of proteins at different stages of meiosis and interacts with other protein modifications, including the ubiquitin system which tags proteins for destruction. The data gathered by Bhagwat et al. provide a starting point for future research into precisely how SUMO proteins control meiosis in yeast and other organisms. In humans, errors in meiosis are the leading cause of pregnancy loss and congenital diseases. Most of the proteins identified as SUMO targets in budding yeast are also present in humans. So, this research could provide a platform for medical advances in the future. The next step is to study mammalian models, such as mice, to confirm that the regulation of meiosis by SUMO is the same in mammals as in yeast.

Understanding the impact of preprocessing pipelines on neuroimaging cortical surface analyses.

BACKGROUND: The choice of preprocessing pipeline introduces variability in neuroimaging analyses that affects the reproducibility of scientific findings. Features derived from structural and functional MRI data are sensitive to the algorithmic or parametric differences of preprocessing tasks, such as image normalization, registration, and segmentation to name a few. Therefore it is critical to understand and potentially mitigate the cumulative biases of pipelines in order to distinguish biological effects from methodological variance. METHODS: Here we use an open structural MRI dataset (ABIDE), supplemented with the Human Connectome Project, to highlight the impact of pipeline selection on cortical thickness measures. Specifically, we investigate the effect of (i) software tool (e.g., ANTS, CIVET, FreeSurfer), (ii) cortical parcellation (Desikan-Killiany-Tourville, Destrieux, Glasser), and (iii) quality control procedure (manual, automatic). We divide our statistical analyses by (i) method type, i.e., task-free (unsupervised) versus task-driven (supervised); and (ii) inference objective, i.e., neurobiological group differences versus individual prediction. RESULTS: Results show that software, parcellation, and quality control significantly affect task-driven neurobiological inference. Additionally, software selection strongly affects neurobiological (i.e. group) and individual task-free analyses, and quality control alters the performance for the individual-centric prediction tasks. CONCLUSIONS: This comparative performance evaluation partially explains the source of inconsistencies in neuroimaging findings. Furthermore, it underscores the need for more rigorous scientific workflows and accessible informatics resources to replicate and compare preprocessing pipelines to address the compounding problem of reproducibility in the age of large-scale, data-driven computational neuroscience.

A Lean Lady With Acanthosis Nigricans and Uncontrolled Diabetes Mellitus.

A 47-year-old Asian Indian woman presented with uncontrolled hyperglycaemia and osmotic symptoms despite multiple oral antidiabetic medications and insulin. She had a history of recurrent oral ulcers, profound weight loss, and intermittent fever for one and a half years before the presentation. She had severe acanthosis nigricans, although her body mass index (BMI) was 14.6 kg/m2. Her blood glucose remained uncontrolled despite very large dosages of intravenous insulin (more than 12,000 units daily). Evaluation for possible underlying collagen vascular diseases and malignancies were negative. Her serum insulin levels were high. She tested negative for anti-insulin antibodies but positive for anti-insulin-receptor antibodies. She improved with a pulse dose of intravenous methylprednisolone but relapsed within one month. A second pulse dose was given following which a complete remission of diabetes and regression of acanthosis was observed. Type B insulin resistance, a rare cause of severe insulin resistance, may respond favourably to immunosuppressive therapy with high-dose methylprednisolone.

Current Status of Diagnosis and Management of Functioning Pituitary Tumors: Part II.

Functioning pituitary tumors contribute to significant morbidity and mortality. Proper diagnostic approach and management is essential for optimal outcomes. Prolactinomas, the commonest of these, are the only tumors which can be managed medically. Acromegaly, apart from acral enlargement, can have multiple comorbidities like diabetes, hypertension, and obstructive sleep apnea. The primary treatment is surgical and it can be supplemented by radiotherapy and medications such as somatostatin analogs, growth hormone receptor blockers, or cabergoline. Thyrotropin-secreting tumors are rare and present with hyperthyroidism. Optimal preoperative management followed by surgical resection often leads to cure.

A study of glycemic variability in patients with type 2 diabetes mellitus with obstructive sleep apnea syndrome using a continuous glucose monitoring system.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) in association with Type 2 Diabetes Mellitus (DM) may result in increased glycemic variability affecting the glycemic control and hence increasing the risk of complications associated with diabetes. We decided to assess the Glycemic Variability (GV) in patients with type 2 diabetes with OSAS and in controls. We also correlated the respiratory disturbance indices with glycemic variability indices. METHODS: After fulfilling the inclusion and exclusion criteria patients from the Endocrinology and Pulmonology clinics underwent modified Sleep Apnea Clinical Score (SACS) followed by polysomnography (PSG). Patients were then divided into 4 groups: Group A (DM with OSAS, n = 20), Group B (DM without OSAS, n = 20), Group C (Non DM with OSAS, n = 10) and Group D (Non DM without OSAS, n = 10). Patients in these groups were subjected to continuous glucose monitoring using the Medtronic iPro2 and repeat PSG. Parameters of GV: i.e. mean glucose, SD (standard Deviation), CV (Coefficient of Variation), Night SD, Night CV, MAGE and NMAGE were calculated using the Easy GV software. GV parameters and the respiratory indices were correlated statistically. Quantitative data was expressed as mean, standard deviation and median. The comparison of GV indices between different groups was performed by one-way analysis of variance (ANOVA) or Kruskal Wallis (for data that failed normality). Correlation analysis of AHI with GV parameters was done by Pearson correlation. RESULTS: All the four groups were adequately matched for age, sex, Body Mass Index (BMI), waist circumference (WC) and blood pressure (BP). We found that the GV parameters Night CV, MAGE and NMAGE were significantly higher in Group A as compared to Group B (p values < 0.05). Similarly Night CV, MAGE and NMAGE were also significantly higher in Group C as compared to Group D (p value < 0.05). Apnea-hypopnea index (AHI) correlated positively with Glucose SD, MAGE and NMAGE in both diabetes (Group A plus Group B) and non- diabetes groups (Group C plus Group D). CONCLUSIONS: OSAS has a significant impact on the glycemic variability irrespective of glycemic status. AHI has moderate positive correlation with the glycemic variability.

Identifying psychosis spectrum youth using support vector machines and cerebral blood perfusion as measured by arterial spin labeled fMRI.

Altered cerebral blood flow (CBF), as measured by arterial spin labelling (ASL), has been observed in several psychiatric conditions, but is a generally underutilized MRI technique, especially in the study of psychosis spectrum (PS) symptoms. We aimed to determine group differences in ASL resting state functional connectivity (rsFC) between PS and non-PS youth, and the reliability of a support vector machine (SVM) classifier trained on ASL rsFC features to differentiate PS and non-PS youth, especially compared to blood oxygen level dependent (BOLD) fMRI. 1146 youth aged 8-22 with ASL and BOLD data from the Philadelphia Neurodevelopmental Cohort were analyzed. Widespread ASL hyperconnectivity was found in the left cuneus, precuneus, and dorsolateral prefrontal cortex, and hypoconnectivity was found in the left cingulate cortex and orbitofrontal area (multiple linear regression, FDR corrected). An SVM trained on ASL and BOLD features outperformed either modality alone (AUCBOTH = 0.72 versus AUCASL = 0.68 and AUCBOLD = 0.67). Classification performance and precision improved when the non-PS group had no psychiatric comorbidities. The relative success of the classifier suggests ASL rsFC changes exist in PS individuals that differ from BOLD rsFC changes, and extends previous findings of CBF dysregulation in PS.