ResearchPad - reports Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[A rapid and simple bead-bashing-based method for genomic DNA extraction from mammalian tissue]]> Extraction of genomic DNA is a critical and often rate-limiting step for many downstream genetic tests. However, existing methods can be time consuming, difficult to automate and require use of a fume hood. Here, we present a simple 12-min method for genomic DNA extraction from tissue without the need for a fume hood and which can be readily automated for high-throughput applications.

<![CDATA[Intratracheal aerosolization of viral vectors to newborn pig airways]]> Historically, achieving uniform distribution of a gene therapy reagent in the lungs has been challenging. Here, we describe an aerosolizing technique which can be used to achieve homogenous expression of a viral vector in newborn pig lungs. Briefly, pigs are sedated and intubated with an endotracheal tube, and a microsprayer is used to aerosolize a viral vector which results in its widespread distribution in the lungs.

<![CDATA[Atherosclerotic spontaneous coronary artery dissection (A-SCAD) in a patient with COVID-19: case report and possible mechanisms]]> Spontaneous coronary artery dissection (SCAD) may be atherosclerotic (A-SCAD) or non-atherosclerotic (NA-SCAD) in origin. Contemporary usage of the term ‘SCAD’ is typically synonymous with NA-SCAD. COVID-19 could induce a vascular inflammation localized in the coronary adventitia and periadventitial fat and contribute to the development of an A-SCAD of a vulnerable plaque in a susceptible patient.Case summaryIn this report we describe a case of a COVID-19 patient with past cardiac history of CAD who was admitted for acute coronary syndrome (ACS). Coronary angiography demonstrated the culprit lesion in the proximal LAD that presented with a very complex and unusual morphology, indicative of an A-SCAD. The diagnosis of A-SCAD was supported by the presence of a mild stenosis in the same coronary segment in the last angiogram performed 3 years previously. He was successfully treated by PCI, had a favourable course of the COVID-19 with no symptoms of pneumonia, and was discharged from the hospital after two negative tests for SARS-CoV-2.DiscussionA higher index of suspicion of A-SCAD is needed in patients with suspected or confirmed COVID-19 presenting with ACS. The proposed approach with ‘thrombolysis first’ for treating STEMI patients with suspected or confirmed COVID-19 infection could be unsafe in the case of underlying A-SCAD. ]]> <![CDATA[An Inflammatory Profile Correlates With Decreased Frequency of Cytotoxic Cells in Coronavirus Disease 2019]]> Increased production of inflammatory cytokines and myeloid-derived suppressor cells occurs in patients with coronavirus disease 2019. These inversely correlated with perforin-expressing natural killer (NK) and CD3+ T cells. We observed a lower number of perforin-expressing NK cells in intensive care unit (ICU) patients compared with non-ICU patients, suggesting an impairment of the immune cytotoxic arm as a pathogenic mechanism.

<![CDATA[Common Adverse Events Associated with the Use of Ribavirin for Severe Acute Respiratory Syndrome in Canada]]> Although information on efficacy and adverse drug reactions is lacking, ribavirin has been used empirically for the treatment of severe acute respiratory syndrome (SARS). We report common adverse events in 110 patients with suspected or probable SARS who were treated with ribavirin. Sixty-one percent of the patients had evidence of hemolytic anemia, and hypocalcemia and hypomagnesmia were reported in 58% and 46% of patients, respectively.

<![CDATA[Human Bocavirus Infection in Young Children in the United States: Molecular Epidemiological Profile and Clinical Characteristics of a Newly Emerging Respiratory Virus<a href="#fn1"/>]]> BackgroundHuman bocavirus (HBoV) is a newly identified human parvovirus that was originally identified in the respiratory secretions of children with respiratory tract disease. To further investigate the epidemiological profile and clinical characteristics of HBoV infection, we screened infants and children <2 years of age (hereafter referred to as “children”) for HBoV

MethodsChildren for whom respiratory specimens submitted to a diagnostic laboratory tested negative for respiratory syncytial virus, parainfluenza viruses (types 1–3), influenza A and B viruses, and adenovirus, as well as asymptomatic children, underwent screening for HBoV by use of polymerase chain reaction (PCR). Respiratory specimens were obtained from the children from 1 January 2004 through 31 December 2004

ResultsTwenty-two (5.2%) of the 425 children who had a respiratory specimen submitted to the diagnostic laboratory and 0 of the 96 asymptomatic children were found to be positive for HBoV by PCR (P=.02). Fever, rhinorrhea, cough, and wheezing were observed in ⩾50% of the HBoV-positive children. Of the 17 children who had chest radiography performed, 12 (70.6%) had abnormal findings. HBoV appeared to have a seasonal distribution. Nucleotide polymorphisms were detected in the viral capsid protein (VP) 1/VP2 genes. Two distinct HBoV genotypes circulated during the study period

ConclusionsHBoV is circulating in the United States and is associated with both upper and lower respiratory tract disease in infants and young children

<![CDATA[Open Reading Frame 8a of the Human Severe Acute Respiratory Syndrome Coronavirus Not Only Promotes Viral Replication but Also Induces Apoptosis]]> Background. A unique genomic difference between human and civet severe acute respiratory syndrome coronaviruses (SARS-CoVs) is that the former has a deletion of 29 nucleotides from open reading frame (orf) 8d that results in the generation of orf8a and orf8b. The objectives of the present study were to analyze antibody reactivity to ORF8a in patients with SARS and to elucidate the function of ORF8a.

Methods. Western-blot and immunofluorescent antibody assays were used to detect anti-ORF8a antibody. SARS-CoV HKU39849 was used to infect stable clones expressing ORF8a and cells transfected with small interfering RNA (siRNA). The virus loads (VLs) and cytopathic effects (CPEs) were recorded. Confocal microscopy and several mitochondria-related tests were used to study the function of ORF8a.

Results. Two (5.4%) of 37 patients with SARS had anti-ORF8a antibodies. The VLs in the stable clones expressing ORF8a were significantly higher than those in control subjects 5 days after infection. siRNA against orf8a significantly reduced VLs and interrupted the CPE. ORF8a was found to be localized in mitochondria, and overexpression resulted in increases in mitochondrial transmembrane potential, reactive oxygen species production, caspase 3 activity, and cellular apoptosis.

Conclusions. ORF8a not only enhances viral replication but also induces apoptosis through a mitochondria-dependent pathway.

<![CDATA[Fixed Dosing of Liposomal Amphotericin B in Morbidly Obese Individuals]]> In this prospective study, we examined the pharmacokinetics of 1 and 2 mg/kg liposomal amphotericin B in 16 morbidly obese individuals (104–177 kg). Body size had no effect on clearance. We recommend a fixed dose in patients ≥100 kg (ie, 300 or 500 mg rather than the current dose of 3 and 5 mg/kg, respectively).

Clinical Trials Registration NCT02320604.

<![CDATA[Food insecurity in females with phenylketonuria]]> Phenylketonuria (PKU) is a genetic disorder characterized by insufficient metabolism of phenylalanine. Depending on severity, patients follow a low‐phenylalanine diet and may consume medical food (MF) and low‐protein modified foods; dietary and medical treatment can be expensive. This study assessed prevalence of food insecurity (FI), the lack of resources to access enough nutritious food to have an active, healthy life, in females with PKU and examined associations with diet and metabolic control. Participants were recruited from a research‐based camp in 2018. Adult and adolescent modules of the USDA Household Food Security survey were utilized to categorize participants as food secure [high food security (FS) or marginal FS] or food insecure (low FS or very low FS); results were compared to the general U.S. population. Dietary intake via three‐day food records and plasma amino acids were also assessed. Thirty females 11‐58 years of age (mean = 21.4 years) participated. Twelve (40%), including seven adolescents (44%) and five adults (36%), were FI compared to the U.S. prevalence of 11.1%. MF protein intake was significantly lower in those with very low FS compared to high FS and low FS (P = .04). Age and intact protein intake were significantly higher in those with very low FS compared to high FS (P < .05). Our study suggests adolescent and adult females with PKU have a higher prevalence of FI than the general U.S. population. Those with very low FS were older, consumed more dietary phenylalanine and intact protein, and less MF protein. Clinicians should consider screening for FI in patients with PKU.

<![CDATA[A patient survey on the impact of alkaptonuria symptoms as perceived by the patients and their experiences of receiving diagnosis and care]]> Alkaptonuria (AKU) is an ultrarare and multifaceted disease characterized by the absence of functional homogentisate 1,2‐dioxygenase activity, the enzyme responsible for breakdown of homogentisic acid—a tyrosine‐degradation product. The presymptomatic phase of the disease makes diagnosis difficult, with many patients unidentified or diagnosed late in life.ObjectiveTo date, no study has analyzed the perceived impact of different symptoms or the experiences of individuals through the patient journey in the context of AKU. This study aimed to examine patients' perceptions of AKU symptoms and their impact on quality of life as well as patients' experiences of being diagnosed and living with the disease.MethodsData for this study were collected using a quantitative self‐report questionnaire administered online to people with AKU.ResultsData from 45 participants indicate that symptoms with the highest impact for patients are those related to pain and ruptures, disability and inability to perform normal routines, emotional/mental health issues, and heart complications. Findings also revealed significant delays in contact with healthcare services and time to diagnosis. Furthermore, patients reported difficulty in receiving information about AKU, treatment and care, and long‐term disease management support.ConclusionsTime to diagnosis and care of AKU is significantly delayed. Symptoms of AKU with the highest impact on quality of life for patients are those related to pain and disability and the inability to perform normal routines. Bridging any gaps between patients with AKU and healthcare professionals through education could help improve patients' experiences with AKU through the patient journey. ]]> <![CDATA[Developmental brain abnormalities and acute encephalopathy in a patient with myopathy with extrapyramidal signs secondary to pathogenic variants in MICU1]]> Mitochondria play a variety of roles in the cell, far beyond their widely recognized role in ATP generation. One such role is the regulation and sequestration of calcium, which is done with the help of the mitochondrial calcium uniporter (MCU) and its regulators, MICU1 and MICU2. Genetic variations in MICU1 and MICU2 have been reported to cause myopathy, developmental disability and neurological symptoms typical of mitochondrial disorders. The symptoms of MICU1/2 deficiency have generally been attributed to calcium regulation in the metabolic and biochemical roles of mitochondria. Here, we report a female child with heterozygous MICU1 variants and multiple congenital brain malformations on MRI. Specifically, she shows anterior perisylvian polymicrogyria, dysmorphic basal ganglia, and cerebellar dysplasia in addition to white matter abnormalities. These novel findings suggest that MICU1 is necessary for proper neurodevelopment through a variety of potential mechanisms, including calcium‐mediated regulation of the neuronal cytoskeleton, Miro1‐MCU complex‐mediated mitochondrial movement, or enhancing ATP production. This case provides new insight into the molecular pathogenesis of MCU dysfunction and may represent a novel diagnostic feature of calcium‐based mitochondrial disease.

<![CDATA[Breast reconstruction in a patient with an implanted deep brain stimulator]]> Deep brain stimulators (DBSs) are sometimes used to treat refractory movement disorders such as Parkinson's disease. When DBSs are implanted in a subcutaneous pocket in the chest region, breast reconstruction becomes a challenge because monopolar electrocautery can lead to DBS dysfunction or brain tissue damage caused by heat. We report a patient with a DBS who underwent one-stage implant-based breast reconstruction. We switched off the DBS before surgery and used monopolar electromagnetic cautery with minimum power settings to undermine the subcutaneous pocket for the breast implant. The DBS was switched back on immediately after completion of the surgery. The patient's postoperative recovery was uneventful with the DBS fully functional.

<![CDATA[MitraClip<sup>®</sup> as bridging strategy for heart transplantation in Chagas cardiomyopathy: a case report]]> Patients with end-stage heart failure, suffering from severe pulmonary hypertension (PH) and elevated pulmonary vascular resistance, are not eligible for heart transplant due to high mortality risk and primary graft dysfunction. Severe PH may be favoured by functional severe mitral regurgitation, which is present in many cardiopathies like end-stage Chagasic cardiomyopathy.Case summaryWe present a case of a young man with end-stage heart failure secondary to Chagas cardiomyopathy with severe functional mitral regurgitation (FMR) and severe PH. The patient received percutaneous correction with MitraClip® system reducing PH and making him a suitable candidate for heart transplant.DiscussionIn patients with advanced heart failure, FMR, and severe PH, optimal treatment according to current guide lines is recommended. MitraClip® therapy appears to be safe and effective for control of severe PH as a bridge measure for cardiac transplantation. ]]> <![CDATA[MON-372 Treatment-Resistant Vitamin D Deficiency: Is It a Vitamin D Binding Protein Issue?]]> Introduction

Vitamin D is present in free and bound forms; the bound form is complexed mainly to vitamin D binding protein (DBP). Vitamin D levels are affected by age, pregnancy, liver disease, obesity, and DBP mutations. We report a patient with treatment-resistant vitamin D deficiency suggestive of a DBP with abnormal vitamin D binding.

Clinical Case

A 58-year-old Pakistani male with a history of hypertension, sleep apnea and hypogonadism presented to endocrine clinic with symptoms including fatigue, generalized muscle cramps, and joint pain. Evaluation of common causes of fatigue, such as anemia, thyroid dysfunction and adrenal insufficiency were ruled out with CBC, thyroid hormone levels and ACTH stimulation test results all within normal ranges. A 25-OH vitamin D level was profoundly low (4.2 ng/ml; normal 30-100), and a 1,25-OH vitamin D level was undetectable (<8 pg/ml; normal 18-72), leading to a presumptive diagnosis of severe vitamin D deficiency. However, his calcium, phosphorus, alkaline phosphatase and kidney function were in the normal range. Furthermore, the absence of osteoporosis, fracture history, or kidney stones suggested adequate vitamin D action at target tissues; PTH levels were high-normal to minimally elevated, ranging 70-94 pg/ml (12-88pg/mL). Aggressive supplementation with vitamin D3 at 50,000 IU 3 times a week and 5,000 IU daily failed to normalize 25-OH vitamin D (ranged 4.6-10ng/ml; normal 30-100) and 1,25-OH vitamin D levels remained undetectable. Addition of calcitriol resulted in mild hypercalcemia and was discontinued. Malabsorption did not appear to be a contributing factor, as a negative tTG antibody (with normal IgA) excluded celiac disease. Vitamin D metabolites levels measured with mass spectrometry showed undetectable 25-OH vitamin D levels (D2 <4 ng/ml, D3 <2 ng/ml; total <6ng/ml; normal 20-50) and 1,25-OH vitamin D levels (<8 pg/ml). Urine N-telopeptide, 24-hour urine calcium (177mg; 100-240) and bone-specific alkaline phosphatase were all normal. Repeat testing over more than five years showed similar results. DBP levels of 269 ug/ml [104-477] excluded DBP deficiency.

Clinical Lesson

Vitamin D deficiency is increasingly part of routine testing in internal medicine and endocrinology clinics, as is repletion with high-dose vitamin D. However, in rare cases such as this, relying on 25-OH vitamin D levels can be misleading, and supplementation unnecessary or potentially harmful. Thus, treatment decisions should consider the full clinical context and further evaluation performed when warranted. This patient’s labs are suggestive of an abnormality in the DBP, supporting future examination using molecular testing.

<![CDATA[SAT-081 Hidden in Plain Sight: Rethinking Our Approach to Allan-Herndon-Dudley Syndrome]]> Background: Allan-Herndon-Dudley (AHD) is a rare X-linked disorder with neurological manifestations secondary to a mutation in monocarboxylate transporter 8, a protein that transports T3 into nerve cells in the brain. AHD is characterized by increased serum free T3, decreased serum free T4 and normal serum TSH levels as well as the severe neurological manifestations including global developmental delay, hypotonia, and joint contractures (1). A phase 2 trial using triodyothyroacetic acid has shown promise in treating this disorder (2). We report on three children who were diagnosed by whole exome sequencing after presenting with neurological manifestations.

Clinical Cases: Patient 1 presented at 4 months to the neurology clinic for seizures. He had a normal newborn screen. Worsening developmental delays and central hypotonia prompted a brain MRI that revealed delayed myelination for age. At 6 months a chromosomal microarray and metabolic work-up were performed and were nondiagnostic. Whole exome sequencing was obtained at the age of 4.5 years revealing a mutation in the SLC16A2 gene (p.Ser210Tyr). Thyroid studies were consistent with the diagnosis.

Patient 2 presented to neurology at 9 months for developmental delay. A brain MRI was obtained which was within normal limits. At 14 months an acylcarnitine profile was obtained which indicated a possible CPT1 deficiency, which did not fit his clinical picture. Chromosomal microarray as well as work-up for inborn errors of metabolism were performed and were nondiagnostic. Thyroid studies were obtained which showed low free T4 with normal TSH. Whole exome sequencing was obtained at the age of 2.5 years, which revealed a mutation in SLC16A2 (p.R371C).

Patient 3 presented as sibling of patient 2 with known AHD syndrome. Testing for SLC16A2 was performed at the age of 5 months and returned positive for same mutation as sibling (p.R371C).

Conclusion: Allan-Herndon-Dudley syndrome is a rare neurological disease secondary to a mutation in the T3 transporter protein to nervous tissue. A high index of suspicion as well as thyroid studies should be obtained in patients presenting with central hypotonia and global developmental delay with normal newborn screens, particularly in states that use TSH as a screening test. This is especially important as treatments are becoming available that may help prevent neurological devastation seen in these patients.


1. Dumitrescu AM, Fu J, Dempsey MA, Refetoff S. MCT8-Specific Thyroid Hormone Cell-Membrane Transporter Deficiency. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993

2. Groeneweg S, Peeters RP, Moran C, et al. Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: an international, single-arm, open-label, phase 2 trial. Lancet Diabetes Endocrinol. 2019;7(9):695-706.

<![CDATA[MON-365 Novel Use of Abaloparatide to Augment Spinal Fusion in Patient Undergoing Cervicothoracic Revision Surgery]]> Objective To present a case of using Abaloparatide (PTHrP 1–34 analogue) to promote spinal fusion in a patient with history of cervical instability s/p multiple cervical operations with non-union. Case Presentation 66 year-old female with a history of multiple sclerosis, obesity and hypothyroidism underwent neurosurgical evaluation of neck pain. She was found to have cervical spinal stenosis causing neck pain, radiculopathy, motor deficits and ataxia. Initially underwent anterior cervical discectomy and fusion which temporarily alleviated symptoms before suffering nonunion. Subsequently underwent two additional surgeries which also eventually failed. She presented to our facility for revision corpectomy and spinal fusion. Given her history of nonunion, endocrinology was consulted for evaluation of metabolic bone disease. No known personal or family history of metabolic bones disease. No history of chronic steroid use. Initial endocrine evaluation excluded common pathologies. A decision was made to pursue anabolic osteoporosis therapy to attempt to augment the spinal fusion process. Patient started on Abaloparatide 80mcg daily 2 weeks post procedure with planned 12-week therapy course. Cervical CT at 3 and 6 months showed post-surgical cervicothoracic fusion with no signs of non-union. Discussion Abaloparatide is a 34 amino acid synthetic analogue of parathyroid hormone related peptide (PTHrP) which works by selectively activating PTH1 receptor found on osteoblasts. Currently anabolic therapies are only FDA approved for treatment of osteoporosis but there is reported off label use in cases of spinal fusions, arthroplasty and fracture healing. Studies have shown that presence of PTH and PTHrP are necessary for fracture healing. Animal studies have also shown that intermittent PTH promotes spinal fusion. This case represents a novel use for Abaloparatide to augment spinal fusion in a human clinical model. Conclusion Further studies are warranted to better understand mechanism of action, drug timing and duration for optimal treatment of anabolic therapies in bone fractures and healing. The use of anabolic therapies like Abaloparatide can be considered in patients undergoing spinal fusion surgery at high risk for non-union or undergoing revision for failed fusion.ReferencesO’Loughlin PF, Cunningham ME, Bukata SV et al. Parathyroid Hormone Augments spinal fusion, fusion mass, and fusion mass quality in a rabbit spinal fusion model. Spine 2009 January; 34: 121–130

<![CDATA[SAT-183 Right Adrenal Mass: An Unusual Presentation]]> Background: Adrenal masses may be incidentally found on imaging done for other reasons. The prevalence is 4.4% and up to 10% in older patients. Malignancy is an uncommon cause in patients without a known diagnosis of cancer. The frequency of primary adrenal carcinoma in patients with adrenal incidentalomas is approximately 2.0 to 5.0%; another 0.7 to 2.5% have non-adrenal metastases to the adrenal gland.

Clinical Case: 54-year-old man with Hepatitis C, prior alcohol abuse, and cirrhosis was found to have an increase in the alpha-fetoprotein (AFP) level from normal to 244 ng/ml (nl<15.1) over a 6-month period. Liver MRI was consistent with a cirrhotic liver without focal enhancing lesions and showed a new indeterminate 7.6 cm right retroperitoneal lesion arising from the adrenal gland compared to a prior CT of the abdomen a year early. Further imaging confirmed a 9.6 x 9 x 7.6 cm heterogeneously enhancing right adrenal lesion with a necrotic center, concerning for a primary malignancy; up to 11.1cm a month later. Patient referred to Endocrine for further evaluation. There were no symptoms suggestive of Cushing’s, pheochromocytoma or primary hyperaldosteronism. On exam there were no hypertension, dorsal fat pad, supraclavicular fullness, skin thinning or purplish striae. Biochemical workup was consistent with a non-functioning adrenal mass. DHEA-S was 11 (38-313 mcg/dl). CT-guided core needle biopsy of right adrenal gland was consistent with metastatic hepatocellular carcinoma. CT pelvis with contrast re-demonstrated the right adrenal mass now measuring 11.4 x 10 x 10 cm with new enlarged retrocaval lymph node and no focal arterially enhancing lesions. During embolization of adrenal lesion/ hepatic angiogram, multiple liver lesions not previously identified were reported with the largest of 2.9cm size and enhancing lesions in the sacrum and bilateral iliac bones; decrease in size of the necrotic right adrenal mass measuring 8.2 x 9.1 x 9.1 cm 1-month post-embolization. Patient following with Oncology.

Conclusion:Unilateral isolated adrenal metastasis from occult hepatocellular carcinoma (HCC) is extremely rare. Adrenal gland is the second most common site of hematogenous spread from HCC after the lung and has been found in up to 8.4% of cases at autopsy. In our case, the adrenal metastasis was the first clinical presentation of HCC with no evident hepatic lesion until 9 months of adrenal finding; few cases have been reported. Fine needle aspiration/needle biopsy of suspected malignancy is useful to detect primary tumor in case of metastatic disease that is silent at this stage. Adrenal metastasis in HCC are seldom treated by surgery as by the time of diagnosis the tumor is usually far advanced and/or patients are poor surgical candidates. This case highlights the importance of suspecting underlying HCC in isolated adrenal mass in a patient with high risk factors.

<![CDATA[SAT-278 Vaginal Cabergoline: A Simple Solution to a Challenging Problem]]> Introduction: Prolactinomas is a common endocrine disorder that can be associated with significant morbidity. Generally, prolactinomas are more responsive to pharmacologic treatment than any other types of pituitary adenoma. Dopamine agonists (DA), including cabergoline and bromocriptine, are the first line of treatment in all sizes of prolactinomas and they decrease both the secretion and size of these adenomas. However, treatment remains challenging for patients who are intolerance to those medications. Case: We report a 32-year-old Hispanic woman who presented with secondary amenorrhea, she was found to have hyperprolactinemia of 1496 mcg/L. MRI of the brain showed a pituitary adenoma measuring 2.7 cm with sella turcica invasion and mass effect on the optic chiasma. She failed the lowest doses of oral cabergoline and bromocriptine and underwent TSS and gamma knife radiosurgery. Given her persistent symptoms (marked depression, insomnia, fatigue, short-term memory loss, and lack of concentration along with constipation) and elevation of prolactin, she was started on low dose vaginal cabergoline leading to a marked improvement of her symptoms and a steady decrease in serum prolactin. Discussion: Despite the availability of DA as a first-line treatment of Prolactinoma, treatment remains challenging, given the commonly reported side effects for all DA. Cabergoline is oftentimes the treatment of choice due to efficacy and favorable side-effect profile. However, intolerance to those medications can lead to discontinuation of therapy and increase morbidity. Other strategies, including transsphenoidal surgery (TSS) or radiation therapy, have been considered for the minority of patients whose adenomas are resistant to DA or who cannot tolerate these drugs. Interestingly, tolerance to DA can be improved by administering the drug intravaginally, which can have similar efficacy to the oral route and a more favorable side-effect profile. However, only a few studies assessed the effectiveness and tolerance of vaginal DAs in hyperprolactinemic patients intolerant to oral medications, little evidence supports the use of intravaginal DA to improve drug tolerance, and further studies are necessary to determine the safety and efficacy of vaginal cabergoline.

<![CDATA[SUN-903 Insulinoma - a Tricker Diagnosis When Some Pieces Are Missing]]> Insulinoma is a rare pancreatic neuroendocrine tumour that secretes insulin, causing hypoglycemia. Because of the nonspecific symptoms, the diagnosis could constitute a challenge. Early detection is important to prevent serious consequences.

A 31-year old woman was admitted for prolonged fasting test. She had no relevant past medical or surgical history till eight months before, when she had an episode of generalized tonic-clonic seizure with loss of consciousness. At this time, she was taken to emergency, with identification of a hypoglycaemia of 33 mg/dL. Unfortunately this was undervalued and she was discharged with an appointment on a neurologist. After evaluation, she did an EEG, which was normal, and blood tests that identified a fasting glycemia of 50 mg/dL. By recommendation of her general practitioner, she began to monitor her glycemia during the day, identifying multiple glycemia <50mg/dL – in fasting and post-prandial period. After the first generalized seizure, she had multiple seizures, always associated with hypoglycaemia. During the night she had to wake up every two hours to eat, in order to prevent hypoglycaemia. Moreover, in the last 6 months, she augmented 12 Kg. She also described two episodes of behavioural changes with confusion and speech alteration.

She wasn’t under any medication that could be associated with hypoglycemias. Previous records showed she had a fasting glycemia of 50 mg/dL two years ago. When she was admitted to our department, besides she had eat one hour before, she had glycemia <55 mg/dL. Blood tests showed glucose level=22 mg/dL, insulin=39 μU/mL (normal range 2.6-24.9 μU/mL), C-Pep=0.90 ng/mL (normal range 1.1-4-4 ng/mL). Plasma B-hydroxybutyrate was negative. After Glucagon EV, glucose level increase to 53 mg/dL (>25 mg/dL). We also evaluated cortisol and growth hormone that were normal. Abdominal computed tomography scan with contrast demonstrated a well-defined hypervascular lesion involving pancreas tail. Abdominal MRI was also performed showing a hypervascular lesion involving pancreas tail with 11x21mm. Laparoscopic surgery to enucleate the lesion was made. Pathological evaluation revealed a well-differentiated neuroendocrine tumour (positive staining for synaptophysin, cromogranin and insulin) measuring 0.3 cm. The diagnosis of pancreatic insulinoma was confirmed. After surgery, the glucose level increased to the normal range. The patient is currently in 6 months follow-up with a good evolution.

The diagnosis of insulinoma requires high suspicion. In this case, the patient didn’t have the typical insidious neurogenic symptoms. There is a need to value neuroglycopenic symptoms associated with hypoglycemia, otherwise serious consequences can occur.

<![CDATA[MON-917 Carney Complex Due to a Contiguous Gene Deletion Syndrome (17q24.2-17q24.3)]]> Background

While genomic rearrangements of chromosome 17 are not uncommon, deletions of chromosome band 17q24.2-q24.3 are rare, and associated features include cardiac abnormalities, characteristic facial appearance, short stature, obesity, syndactyly, intellectual disability, seizures, delayed dentition, and features of Carney Complex. It has been suggested that the involvement of KCNJ2, PRKCA, CACNG gene cluster (CACNG1, CACNG4, CACNG5), and PRKAR1A genes contribute to this phenotype. A case of a child with a 3.7 Mb deletion at chromosome band 17q24.2-q24.3, as well as a 2.1 Mb gain at chromosome 17q22, is described.

Clinical Case

A now 6 year old female was born at 34 weeks gestational age with prenatal course complicated by oligohydramnios and intrauterine growth restriction. Birth weight was at the 9th percentile, and birth length was at the 92nd percentile. She was noted to have a patent ductus arteriosus (PDA), poor suck and swallow, and dysmorphic features. Chromosome microarray revealed a 3.7 Mb deletion at Chromosome 17q24.2-q24.3, involving KCNJ2, PRKCA, CACNG gene cluster (CACNG1, CACNG4, CACNG5), and PRKAR1A, as well as a 2.1 Mb gain at Chromosome 17q22, involving C17orf112 and KIP2B.

At 6 years old, she continues to be small for weight (-4.5 SDs), BMI (-4.22 SDs), and height (-2.5 SDs), though with appropriate pre-pubertal linear growth velocity. She is minimally verbal and continues to receive physical, occupational and speech therapies. Examination showed dysmorphic facial features, including triangular face with pointed chin, prominent forehead with low-set ears, retro-micrognathia, almond-shaped eyes with up-slanting palpebral fissures, bulbous nose, thin lips, and irregularly-shaped teeth. She had bilateral 5th digit clinodactyly, tapering of the distal aspects of bilateral first digits of the hands, and syndactyly of bilateral 2nd/3rd digits of the feet. She had scant freckling over the nasal bridge and cheeks, as well as freckles of the left arm, left groin, and back. She had no clinical stigmata of hypercortisolism. Echocardiogram continues to show a PDA with no cardiac myxomas. Thyroid ultrasound was normal. However, she does have mild hypercalcemia, most recently 2.61 mmol/L (2.15-2.55), and mildly elevated alkaline phosphatase of 341 U/L (96-297).


This case highlights a child with many of the previously reported findings associated with 17q24.2-q24.3 deletions. However, she also was noted to have a 2.1 Mb gain at chromosome 17q22 involving C17orf112 and KIP2B genes, which have not yet been associated with a clinical phenotype. It is therefore unclear if her phenotype is partially explained by the chromosomal gain. Clinicians should suspect a contiguous gene deletion syndrome in a patient with Carney Complex and atypical features. Patients with this condition have also been described as “Carney Complex-plus”, a term that we do not recommend be used.