Direct Hyperbilirubinemia Research Articles

АКТУАЛЬНЫЕ ПРОБЛЕМЫ НЕОНАТАЛЬНОГО ХОЛЕСТАЗА

Jaundice, caused by a primary violation of the excretion of conjugated bilirubin, occupy a separate place in the structure of jaundice of the newborn. Obstructive jaundice is accompanied by the development of mechanical obstruction of the bile-ducts, which is clinically manifested by yellowish pigmentation of the skin and sclera. Neonatal hepatitis is the main cause of neonatal jaundice with a predominance of direct hyperbilirubinemia. It is resulted in atresia of the extrahepatic or intrahepatic biliary tract. However, the hereditary nature of the disease cannot be ruled out. Neonatal jaundice workup is a very difficult task and requires non-routine laboratory and instrumental studies, such as abdominal ultrasound with duplex scanning and spectral Doppler ultrasonography, magnetic resonance imaging, liver elastography, percutaneous puncture liver biopsy. Consultation of a geneticist, hepatologist and surgeon is required. The treatment strategy of such severe neonatal pathology need complex, multidisciplinary approach and should be carried out only in highly specialized medical centers. The authors have analyzed the 3 clinical cases of neonatal cholestasis of various nature. Conflict of interests. The authors declare no conflicts of interest.

Weil syndrome coincident with upper gastrointestinal bleeding.

A 48 year old male was referred to our center due to a gastrointestinal bleeding with melena secondary to a Forrest IIb gastric ulcer treated endoscopically. Physical examination revealed bilateral conjunctival suffusion, bradypsychia, and asterixis. Epidemiological history included a trip to Dominican Republic two weeks before, presenting later a flu-like syndrome. He had no history of NSAID use. Laboratory tests showed a normocytic anemia, leukocytosis with neutrophilia, acute renal failure, severe hyponatremia, a predominant direct hyperbilirubinemia, hyperamylasemia, and mild coagulopathy (Table 1). An abdominal ultrasound was performed, with no pathological findings, and a chest-abdominal computed tomography (CT), bilateral diffuse ground glass pulmonary opacities and pleural effusion, mild hepatomegaly, and peritoneal and gastrohepatic ligament lymphadenopathy, with no signs of acute pancreatitis. A second look upper endoscopy revealed a Forrest III gastric ulcer. Gastric biopsies results ruled out malignancy and Helicobacter pylori infection. Due to his recent travel history combined with his characteristic signs and symptoms a clinical diagnosis of leptospirosis was made and empirical antibiotic therapy with meropenem was started. The serology for Leptospira was positive (IgG 1/1600) and antibiotic therapy was de-escalated to ceftriaxone with clinical and analytical remission on day five of his hospital stay with complete radiological resolution at 6 months.

Difficulty in the Diagnosis of Biliary Atresia Splenic Malformation Syndrome In Utero.

The fetus of a 30-year-old pregnant Japanese woman was diagnosed with absence of inferior vena cava (IVC) and azygos continuation of interrupted IVC without cardiac anomalies at 34 weeks of gestation, and a healthy male neonate weighing 2,910 g was delivered at 37 weeks of gestation. On day 42 after birth, direct bilirubin predominant hyperbilirubinemia and high serum gamma-GTP levels were detected. Computed tomography revealed the presence of a lobulated and accessory spleen, and laparotomy demonstrated type III biliary atresia (BA), confirming the final diagnosis of BA splenic malformation (BASM) syndrome. In retrospect, non-visualization of the gallbladder was missed in utero. The combination of the absence of IVC and BA without cardiac anomalies is far less likely to occur in left isomerism. Although BA remains difficult to detect in utero, special attention should be paid to cases of BA associated with findings of left isomerism, including the absence of IVC, to enable early diagnosis and treatment of BASM.

Lemmel's syndrome: Presentation of an uncommon cholangitis cause and a risk factor for failed endoscopic retrograde cholangiopancreatography. Case report.

IntroductionLemmel's syndrome is a rare pathology that presents jaundice or dilation of common biliary tract, secondary to duodenal diverticula. Due to infrequency, a high suspicion has to be considered to avoid omitting this diagnosis, mainly in patients who present direct hyperbilirubinemia without choledocholithiasis.Presentation of caseA 76-year-old female admitted to the emergency department with cholangitis, secondary to an ampullary diverticulum (papilla was located inside the diverticulum). As a consequence, the endoscopic retrograde cholangiopancreatography failed and a biliodigestive derivation (choledochal duodenum anastomosis) was performed.Discussion and conclusionsThis case is an example of an unusual clinical and anatomical presentation of duodenal diverticulum. This unusual presentation is an example of the importance of not overlooking a diagnosis, which can lead to more severe complications such as cholangitis. It is also important to consider that cases like this are risk factors for failed endoscopic management and surgical possibilities procedures should also be considered in the management.

Clinical Implications for Children Developing Direct Hyperbilirubinemia on Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO)-associated direct hyperbilirubinemia (DHB) is likely multifactorial. The objective of this study is to assess the frequency and risk factors for developing direct hyperbilirubinemia while on ECMO, and its implication on the mortality of children. We performed a retrospective study between January 2010 and January 2020. Using Mayo Clinic electronic health record, we identified children (<18 years) who required veno-arterial (VA) ECMO support. Demographics, ECMO indication, laboratory findings, and outcomes were abstracted. Illness acuity scores, including vasoactive-ionotropic score (VIS), were used to assess disease severity at time of admission. Study cohort was divided into two groups: children who developed direct hyperbilirubinemia (DHB) on ECMO and children who did not (control). DHB was defined as direct bilirubin (DB) of >1.0 mg/dL. Disease acuity and mortality rates were compared between the two groups. Logistic regression was used to analyze the risk of mortality independent of potential confounding variables. We identified 106 children who required ECMO support during the study period. Of those, 36 (34%) children developed DHB on ECMO. Illness acuity scores were significantly higher in the DHB group on ECMO day 2 (P = 0.046) and day 7 (P = 0.01). Mortality rate was higher in the DHB group 72%, versus 29% in the control group (P < 0.001). DHB was associated with a higher mortality rate than the control group.

Direct hyperbilirubinemia and cholestasis in trisomy 13 and 18.

Trisomy 13 and 18 are common chromosomal abnormalities that affect multiple organ systems. There is a paucity of published data, however, on the hepatic complications seen in these patient populations. One of the most common pathologic hepatobiliary issues seen in the newborn period is direct hyperbilirubinemia (DH). Thus, this study sought to estimate the incidence and evaluate possible etiologies of DH in neonates with trisomy 13 or 18. This retrospective cohort study included all infants admitted to our two neonatal intensive care units between 2012 and 2020 with the diagnosis of trisomy 13 or 18. DH is most commonly diagnosed as a direct bilirubin >1mg/dl but a cutoff of >2mg/dl is more specific for cholestasis, so both cutoffs were evaluated. Continuous data were compared using Fisher's exact test and categorical variables by the Mann-Whitney U test. Thirty-five patients met inclusion: 13 with trisomy 13 and 22 with trisomy 18. DH of >2mg/dl was seen in seven (53.8%) patients with trisomy 13 and five (22.7%) with trisomy 18. Using a cutoff of >1mg/dl, the rate of trisomy 13 was unchanged, but the rate in trisomy 18 increased to 9/22 (40.9%). There was a trend toward more DH in trisomy 13 patients (p=0.079) versus trisomy 18 and higher rates in infants who received total parenteral nutrition (TPN) (50.0 vs. 13.3%, p=0.026). The presence of cardiac or ultrasound-defined hepatobiliary abnormalities was not correlated with DH. Due to the high rates of DH in hospitalized neonates with trisomy 13 and 18, we recommend screening newborns with trisomy 13 or 18 for DH starting in the first week of life and continuing at least weekly until 4 weeks of life or until completion of TPN, whichever comes later. Future studies should further evaluate possible etiologies of DH in this population.

Prevalence and Outcome of Cholelithiasis in Children with Sickle Cell Disease at King Saud Medical City, Saudi Arabia

BACKGROUND: Sickle cell disease (SCD) is one of the common hereditary blood diseases in Saudi Arabia. The hepatobiliary system is one of the common organs to be affected either directly from the sickling process or indirectly as a result of chronic hemolysis and multiple blood transfusions. Cholelithiasis is one of the common complications of sickle cell anemia. OBJECTIVES: To assess the prevalence of cholelithiasis in children with SCD treated at King Saud Medical City (KSMC); Pediatric Hospital in Saudi Arabia and describe the outcome, management, and clinical profile of children with SCD and cholelithiasis. MATERIALS AND METHODS: This is a retrospective descriptive study conducted at a single tertiary health care center, KSMC, Pediatric Hospital, Riyadh from 2012 to 2019 on 277 patients aged &lt;14 years. Medical records of all pediatric patients with SCD included in the study were identified and reviewed. RESULTS: From total of 277 patients, 87 (31.4%) had cholelithiasis. Forty three (49.4%) of them were female and 44 (50.6%) were male. From 87 patients who developed cholelithiasis, 15 patients aged &lt;5 years old, 50 aged (5–10 years), and 22 aged &gt;10 years. According to the genotype of sickle cell (SS), the occurrence of cholelithiasis were (75.9% in SS, 23% in S/BETA 0 and 1.1% in S/BETA+). The majority were symptomatic (59.8%) compared to asymptomatic (40.2%) and 26 patients (29.9%) were complicated. In our study, we found that complications for the gallstones were acute calcular cholecystitis, chronic cholecystitis, direct hyperbilirubinemia, transaminitis, and acute pancreatitis. CONCLUSION: The prevalence of cholelithiasis in our study was significant. The large majority of patients were symptomatic. Cholecystectomy must be strongly recommended in symptomatic patients.

S2614 An Unconventional Presentation of Hemophagocytic Lymphohistiocytosis

Introduction: Hemophagocytic Lymphohistiocytosis (HLH) characterized as a cytokine storm secondary to a dysregulated immune state predominantly affects the pediatric population but, reports of adult cases are increasing. The cytokine storm mediated by natural killer cells, macrophages and cytotoxic lymphocytes can be triggered by a genetic variation, infection, malignancy, or rheumatologic disease. This case discusses an unconventional presentation of HLH. Case Description/Methods: A 61 year-old male with a past medical history of coronary artery disease, aortic stenosis, type 2 diabetes mellitus and chronic hepatitis with cirrhosis (of unknown etiology from prior workup) presented with lethargy and fevers. Physical exam was significant for jaundice and tender hepatosplenomegaly. Bloodwork showed: lymphopenia, neutropenia, direct hyperbilirubinemia, and transaminitis. Right upper quadrant ultrasound showed a diffusely echogenic nodular liver with gallbladder dilation in the absence of biliary ductal dilation. Patient was empirically treated for ascending cholangitis with broad spectrum antibiotics and was later found to have E.coli bacteremia. Given patients septic state he underwent percutaneous cholecystostomy tube placement without complication. A complete infectious, hematologic, and hepatologic workup found negative/normal: CMV, EBV, TB, HIV, COVID-19, parvovirus B19, viral hepatitis, DAT, ANA, RF, ANCA, AMA, ASMA, ceruloplasmin, alpha-1 antitrypsin, and C282Y/S/6/5/C. Fibrinogen, ferritin, D-dimer, triglycerides, CXCL-9, and CD-25 were found to be abnormal. Patient's former records were reviewed and showed: cirrhosis with lymphocytic infiltrate on liver biopsy, a normal endoscopy, and an inconclusive bone marrow biopsy only showing clusters of histiocytes. The patient met criteria for HLH and was started on dexamethasone and etoposide. The patients condition continued to worsen and he was transferred to a tertiary care center where he was diagnosed with T-cell histiocyterich diffuse large B-cell lymphoma on repeated biopsy with HLH. Discussion: In patients with high-grade fevers of unknown etiology and multi-organ failure, HLH should be on the differential despite the rarity of adult cases. This case represents an unconventional presentation of HLH in the setting of a confounding bacteremia from ascending cholangitis and underlying B-cell Lymphoma.

S3650 Isolated Direct Hyperbilirubinemia After Cytarabine for the Treatment of Acute Myelogenous Leukemia

S3650 Isolated Direct Hyperbilirubinemia After Cytarabine for the Treatment of Acute Myelogenous Leukemia

Neonatal Hyperbilirubinemia and Cholestasis.

Neonatal Hyperbilirubinemia and Cholestasis.

Pancreatic Origin Hepatoid Adenocarcinoma with Liver Metastasis

Hepatoid Adenocarcinoma (HAC) is a rare form of aggressive extrahepatic neoplasm with similar morphologic features to Hepatocellular Carcinoma (HCC). HAC with pancreatic origin is rare and the exact incidence is unknown. Given shared morphological and Immunohistochemical (IHC) characteristics, it may be difficult to distinguish metastatic HAC with liver involvement from primary HCC. We present a rare case of ductal type pancreatic hepatoid adenocarcinoma involving the pancreatic head, ampulla of Vater, and liver, and illustrate strategies for diagnosis and treatment. A 65-year-old woman presented with epigastric pain, vomiting, melena, and weight loss. There was direct hyperbilirubinemia with elevated hepatic markers. Imaging displayed a pancreatic head mass with moderate biliary obstruction and a hepatic lobe lesion. Fine needle biopsy of the liver mass initially was consistent with HCC, and biopsies of the pancreatic mass and ampulla walls showed pancreatic adenocarcinoma. Due to the unusual finding of co-existing HCC and pancreatic adenocarcinoma, the hepatic mass biopsy was sent for external evaluation, which revealed poorly differentiated adenocarcinoma, consistent with HAC of pancreatic origin. The tumor was positive for mucicarmine stain, HepPar1, CEA, and CK7. It was negative for MOC-31, Arginase, ALBISH, MGB, ER, TTF-1, GCDFP15, CK-20 and CDX2, thus confirming HAC. The patient was referred to outpatient chemotherapy with gemcitabine and paclitaxel however demonstrated progression and expired following recurrent bilateral pulmonary emboli. HAC may present with non-specific symptoms, is highly aggressive, and may be difficult to distinguish from primary HCC from histopathologic characteristics alone. Accurate diagnosis requires clinicohistopathologic and IHC analysis.

Case Report of A Rare Idiosyncratic Hepatotoxicity Induced by Valproic Acid

Valproate induced hepatotoxicity is a well-known side effect, which frequently required periodic monitoring of serum drug level. Hepatotoxicity caused by valproate typically occurs at supratherapeutic drug levels. Once in a while, an idiosyncratic reaction is elicited, liver injury might occur despite normal serum valproate level mainly in chronic users. We hereby identify an unusual case of acute idiosyncratic valproate induced hepatotoxicity. We report a case of a 65 years old male with dyslipidemia and history of seizure, on valproic acid therapy, presented with altered mental status and drowsiness. The patient’s home medications include only zenil 10 mg daily and valproate which was started one month ago. At presentation, He was awake, oriented, but lethargic. Laboratory testing reveals hepatocellular injury with elevated transaminase levels, direct hyperbilirubinemia and coagulopathy. The ammonia level was normal and valproate level was within the therapeutic range. Abdomen computed tomography with IV contrast and MRCP results were irrelevant. Idiosyncratic valproate toxicity was diagnosed after exclusion of all other possible etiologies and after a rapid clinical and laboratory improvement once the drug was discontinued. Based on the patient’s clinical context the diagnosis of valproate induced hepatotoxicity was confirmed. This case emphasizes the importance of identifying, diagnosing, and managing valproate toxicity when no alternative clarification for their symptoms. We need further attempts and more researches to improve the detection of adverse hepatic reactions and to obtain reliable information about the discovery of new biomarkers or tools for early prediction of DILI, as well as to obtain accurate information on epidemiology, drug safety, and pathogenesis in order to improve management for better survival.

Case Report of A Rare Idiosyncratic Hepatotoxicity Induced by Valproic Acid

Valproate induced hepatotoxicity is a well-known side effect, which frequently required periodic monitoring of serum drug level. Hepatotoxicity caused by valproate typically occurs at supratherapeutic drug levels. Once in a while, an idiosyncratic reaction is elicited, liver injury might occur despite normal serum valproate level mainly in chronic users. We hereby identify an unusual case of acute idiosyncratic valproate induced hepatotoxicity. We report a case of a 65 years old male with dyslipidemia and history of seizure, on valproic acid therapy, presented with altered mental status and drowsiness. The patient’s home medications include only zenil 10 mg daily and valproate which was started one month ago. At presentation, He was awake, oriented, but lethargic. Laboratory testing reveals hepatocellular injury with elevated transaminase levels, direct hyperbilirubinemia and coagulopathy. The ammonia level was normal and valproate level was within the therapeutic range. Abdomen computed tomography with IV contrast and MRCP results were irrelevant. Idiosyncratic valproate toxicity was diagnosed after exclusion of all other possible etiologies and after a rapid clinical and laboratory improvement once the drug was discontinued. Based on the patient’s clinical context the diagnosis of valproate induced hepatotoxicity was confirmed. This case emphasizes the importance of identifying, diagnosing, and managing valproate toxicity when no alternative clarification for their symptoms. We need further attempts and more researches to improve the detection of adverse hepatic reactions and to obtain reliable information about the discovery of new biomarkers or tools for early prediction of DILI, as well as to obtain accurate information on epidemiology, drug safety, and pathogenesis in order to improve management for better survival.

Case 2: Early-Onset Neonatal Sepsis in a Term Neonate

Case 2: Early-Onset Neonatal Sepsis in a Term Neonate

Hepatic Langerhans cell histiocytosis: A review.

Hepatic Langerhans cell histiocytosis (LCH) is characterized by proliferation and accumulation of Langerhans cells in the liver, causing liver dysfunction or forming a mass lesion. The liver can be involved in isolation, or be affected along with other organs. A common clinical hepatic presentation is cholestasis with pruritis, fatigue and direct hyperbilirubinemia. In late stages, there may be hypoalbuminemia. Liver biopsy may be required for the diagnosis of hepatic LCH. Histologic finding may be diverse, including lobular Langerhans cell infiltrate with mixed inflammatory background, primary biliary cholangitis-like pattern, sclerosing cholangitis-like pattern, and even cirrhosis at later stages. Because of its non-specific injury patterns with broad differential diagnosis, establishing a diagnosis of hepatic LCH can be challenging. Hepatic LCH can easily be missed unless this diagnosis is considered at the time of biopsy interpretation. A definitive diagnosis relies on positive staining with CD1a and S100 antigen. Liver involvement is a high risk feature in LCH. The overall prognosis of hepatic LCH is poor. Treating at an early stage may improve the outcome. Systemic chemotherapy is the mainstay of treatment and liver transplantation may be offered. New molecular markers involved in pathogenesis of LCH are being explored with a potential for targeted therapy. However, further studies are needed to improve outcome.

Cystic Lesions of Celiac Disease

Cystic Lesions of Celiac Disease

A Case Series of Four Preterm Intrauterine Growth Restricted Babies With Transient Hyper-Insulinemic Hypoglycemia and Cholestasis

Background: Premature infants with intrauterine growth restriction (IUGR) are predisposed to stress related hyper Insulinemic hypoglycemia (HIH). These babies are at risk for other prematurity related complications including direct hyperbilirubinemia. However, association of HIH with this has not been described, and transient cholestasis in HIH infants has not been reported. We present 4 such infants with perinatal stress related HIH who had cholestasis that resolved with time. Case series: In our retrospective review of these preemies with IUGR who had developed HIH, we found that 4 infants developed direct hyperbilirubinemia. Their gestational ages at birth ranged between 26 to 27 weeks, with birth weights between 527 to 642 grams. These infants had received total parenteral nutrition (TPN) for durations ranging between 12 to 19 days of life (DOL). HIH was established in them at variable ages between 55 to 75 DOL, based on an exaggerated glycemic response to glucagon. Of these, 1 baby was not started on Diazoxide due to underlying fluid overload. His HIH resolved by DOL 182. Two babies responded to therapy and while one remained on this till its resolution at 9 months age, another had the Diazoxide discontinued due to acute respiratory worsening leading to readmission. HIH in the latter resolved by 109 DOL. Fasting The last baby developed fluid overload early in therapy leading to its discontinuation without establishing response. Hypoglycemia in these infants resolved by ages between 4 to 9 months of life. Interestingly direct hyperbilirubinemia was noted by age 16 to 59 DOL. In all infants, the diagnosis of HIH was established after the onset of cholestasis. Extensive work up for hyperbilirubinemia ruled out any organic pathology. This transient cholestasis was noted to have resolved by ages 80 to 115 DOL. Conclusion: It appears from our experience in these premature infants, cholestasis may be associated with HIH. Its diagnosis preceded the establishment of HIH. We noted that HIH diagnosis was delayed by around 30 days after the onset of intermittent hypoglycemia. Both the cholestasis and HIH were transient. Whether the cholestasis may prognosticate the development of HIH or is indicative of transient HIH needs to be investigated. Any association between the two needs to be studied to address a common causality. IUGR babies with conjugated hyperbilirubinemia develop a mild and transient HI state which is self-resolving. Due to transient nature of this HIH in these IUGR babies with cholestasis, a genetic work up for HIH may be deferred.

Severe Hyperbilirubinemia Associated With Thyrotoxicosis: Importance of Early Recognition

Abstract Thyroid storm (TS) is a rare and life-threatening condition due to a profound hypermetabolic state, leading to decompensation of homeostasis. It is commonly associated with a precipitating factor such as surgery, trauma, or infection. Occasionally, the clinical presentation may be non-specific, thus causing a potential delay in diagnosis. This could be problematic due to the condition’s high mortality rate, especially if not recognized early. Thyrotoxic jaundice presenting with a pattern of cholestatic hyperbilirubinemia (HBR) has been reported in the literature, although uncommon. We present the case of a 71-year-old woman with unexplained jaundice and direct HBR who was diagnosed with impending TS in the setting of toxic multinodular goiter (TMNG). This is a case of a 71-year-old woman with a remote history of hypothyroidism who presented with acute onset right upper quadrant abdominal pain, jaundice, a non-tender asymmetric nodular large goiter, and bilateral non-pitting leg edema. Ancillaries were significant for total and direct HBR of 4.3 and 3.5 mg/dL, respectively. An abdominal sonogram, abdomen CT and ERCP, all ruled out an obstructive biliary etiology. Unfortunately, the patient developed post-ERCP pancreatitis, with subsequent worsening of direct HBR. TSH was found to be suppressed, free T4 was significantly elevated at 4.3 ng/dL. A Burch-Wartofsky score of &amp;gt;40 was highly suggestive of TS. In addition, elevated thyroglobulin levels ruled out exogenous thyrotoxicosis, the absence of orbitopathy, pretibial myxedema, and negative TRAb pointed towards TMNG as the most likely etiology of hyperthyroidism. This diagnosis was confirmed through neck ultrasound, showing multiple nodules and the absence of high vascularity of the thyroid gland. The patient was managed in the ICU with beta-blockers, methimazole, potassium iodide solution, glucocorticoids, and bile acid sequestrants, leading to satisfactory and significant clinical improvement of thyrotoxicosis and bilirubin levels. Hepatic dysfunction has been described in patients with hyperthyroidism since the nineteenth century. Although the underlying mechanism remains unclear, it may be multifactorial. Different hypotheses have been proposed suggesting that the hypermetabolic state secondary to decompensated hyperthyroidism causes a supply-demand mismatch between hepatic oxygen consumption and hepatic blood flow, decreasing the oxygen tension in the centrilobular region resulting in cholestasis. Furthermore, hepatic hypermetabolism in response to excess thyroid hormone leads to the saturation of the bile flow rate. A possible direct toxic effect of T4 in the hepatocytes has been described although further research is needed. This case highlights the importance of considering decompensated hyperthyroidism as a differential diagnosis of cholestatic HBR.

High Insulin Resistance in Pancreatic Adenocarcinoma

Abstract Introduction: Diabetes mellitus and obesity is associated with increased risk of pancreatic cancer which has been postulated to be due to pancreatic beta cell dysfunction and increased insulin resistance. Pancreatic cancer also exerts its effect on pancreatic beta cells, reducing insulin secretion, affecting glucose uptake and increasing insulin resistance. We present a case of pancreatic adenocarcinoma with severe insulin resistance and uncontrolled diabetes which reversed after tumor removal. Clinical Description: 79 year old male patient with no prior diagnosis of diabetes, history of hypertension, atrial fibrillation, cerebrovascular accident got admitted to the hospital with painless jaundice, dark colored urine and pruritus for a month. He also endorsed polyuria, polydipsia and weight loss for 2 months. He underwent Magnetic Resonance Cholangiopancreatography and was diagnosed with a 2.8 cm pancreatic head mass, consistent with adenocarcinoma along with intraductal papillary mucinous neoplasm. He was diagnosed with new onset of diabetes, A1c 12.6% during that hospitalization. He weighed about 75 kg and height 170cm (BMI 26.6). Labs showed normal renal function, deranged liver enzymes with direct hyperbilirubinemia, elevated transaminases and alkaline phosphatase. C-peptide level was 1.2 ng/ml for a blood glucose of 197 mg/dl. He was discharged on once daily insulin Glargine 25 units and mealtime insulin Lispro 10 units three times a day (TID) requiring 0.7 units/kg. During follow-up, his insulin requirement started to increase despite proper insulin injection technique and medication compliance. He required glargine 150 units/day and U500 insulin 50 units TID requiring about 4 units/kg. He underwent Whipple’s procedure, partial pancreas resection after a month of his diagnosis. Patient was started on clear liquid diet and his blood glucose started to get better on post-op day 1 with just correctional insulin. He was discharged on Repaglinide 0.5mg TID with each meal and all his insulin was discontinued. His blood glucose was in range of 80 to 160 mg/dl with Repaglinide during clinical follow-up with regular diabetic diet. His severe insulin resistance got reversed after the resection of pancreatic neoplasm. Conclusion: The pathogenesis of pancreatic cancer associated diabetes has not been studied well. Basic science research found that adrenomedullin, an amionopeptide, is up-regulated in patients with pancreatic cancer and causes insulin resistance in β Cells. Cancer theories also found about metabolic reprogramming and metabolic cross talk happens between pancreatic cancer and peripheral tissue, inhibiting cellular glucose intake and inducing insulin resistance. More research is required to understand these paraneoplastic phenomenon caused by diabetogenic tumor-secreted product in pancreatic cancer associated diabetes.

The impact of Parvovirus B19 on hereditary haemolytic anaemias.

The impact of Parvovirus B19 on hereditary haemolytic anaemias.