bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Spatial Epidemiology of Patients Who Were Screened for and Diagnosed With Primary Aldosteronism in Southern Thailand
Authors: Suntornlohanakul Onnicha , Kietsiriroje Noppadol , Sakarin Suporn , Sriplung Hutcha 
Published: May 2021

Abstract
Background: In Thailand where biochemical testing for detection of primary aldosteronism (PA) is only available in a few tertiary centers, which may contribute to a delay in case detection. This study aimed to identify the geographic distribution of PA screening and diagnosis and its contributing epidemiologic and geographic factors in Southern Thailand. Method: Data of 688 patients who underwent PA screening between 2011–2017 were reviewed from the electronic database. The patients’ residences were extracted from the identification cards or the address recorded in the hospital system. The presence of an endocrinologist and the dominant religion in each province were recorded. The province, district and subdistrict of each patient were transformed to a 6-digit administrative area code corresponding with the global one (GADM©). A generalized log-linear model was used to identify predictors for individuals being screened. Results: Overall, the prevalence and crude incidence rates of PA in Southern Thailand were 15.6% and 1.66/1,000,000 person-years, respectively. The provinces located adjacent to the Andaman Sea had the highest incidences of PA (3.62–5.17 patients/1,000,000 person-years). Areas with the highest screening rates were located at and near Songkhla where the major tertiary medical center is located. A multivariate log-linear model demonstrated that the distance from the major tertiary center was the only predictive factor for screening while the availability of an endocrinologist and cultural differences were not. The chances of patients who lived in Songkhla, lived less than or more than 200 km from Songkhla to receive PA screening were 100% (reference), 82% (95% CI:0.69–0.97, p-value 0.03), and 66% (95% CI:0.55–0.78, p-value &lt; 0.001), respectively. Conclusion: Geographic location was the main factor contributing to a delay in case detection for PA. A public health policy should be developed to mitigate the geographic barrier thus improving the ability of patients to access healthcare services. Further research relating to the underlying risk of the disease such as genetic transmission in populations with a high incidence of PA should be performed.
Time-Varying Risk of Atrial Fibrillation in Patient With Medically and Surgically Treated Primary Aldosteronism: A Nationwide Cohort Study
Authors: Kim Kyoung Jin , Hong Namki , Lee Seunghyun , Rhee Yumie , Lim Jung Soo 
Published: May 2021

Abstract
Evidence of increased cardiovascular risk, especially atrial fibrillation, has been accumulating among patients with primary aldosteronism (PA), but there is still limited information about long-term prognosis related to different treatment strategy. The aim of this study was not only to investigate the incidence of atrial fibrillation, but also to evaluate their time-dependent changes after adrenalectomy (surgery group) or mineralocorticoid receptor antagonists (drug group) for patients with PA compared to those with essential hypertension (EH). From a nationwide cohort in Korea (2003–2017), PA were individually matched for sex, age (±10 years), and index year in a 1:5 ratio with EH. The primary end point was the time-varying risk of new-onset atrial fibrillation (NOAF) among PA according to treatment mode compared to EH. The secondary end points were the risks of major adverse cardiovascular events (composite of non-fatal myocardial infarction, non-fatal stroke, and death from cardiovascular causes), hospitalization for heart failure, and all-cause mortality. Cox proportional-hazards analysis or time-dependent Cox analysis based on the Schoenfeld residuals testing were performed. We enrolled 1,418 PA patients (755 in PA surgery group and 663 in PA drug group), and matched theses with 7,090 EH controls with a median of 5 years. The risk of incident NOAF was statistically higher in patients with PA (both surgery and drug groups) within the three years after diagnosis (adjusted hazard ratio, 3.02; p&lt;0.001), whereas there was no statistically significance after the three years compared to EH (adjusted hazard ratio, 0.50; p=0.053). Patients in the PA drug group had higher risk of non-fatal stroke during the total followed up period (adjusted hazard ratio, 1.53, p=0.031), although the PA surgery group didn’t. In contrast, patients with PA had no statistically significant difference in risks for other secondary cardiovascular outcomes. In conclusion, this propensity cohort study of adults with PA demonstrated the changeable risk of NOAF over time possibly due to the residual effect of inappropriate aldosterone levels. These findings can provide clinically relevant guidance in the
monitoring the cardiovascular complications, especially NOAF and non-fatal stroke, even after treatment among patients with PA.
Acknowledgements: This study was supported by Collaborative Research Project of Korean Endocrine Society and National Health Insurance Sharing Service (NHIS-2019-4-005). We also thank Minheui Yu and Doori Cho, the members of the SENTINEL (Severance ENdocrinology daTa scIeNcE pLatform) team for technical assistance in searching and summarizing the relevant literature (4-2018-1215).
Utility of Plasma Metanephrines in Adrenal Venous Sampling in Primary Aldosteronism
Authors: Sharma Aditi , Mohsin Zaineb Amin , Moore-Gillon Claudia , Derry Joseph , Thomas Kate , Whitlock Matthew , Williams Emma Louise , Barnes Sophie , Palazzo Fausto , Alsafi Ali , Wernig Florian 
Published: May 2021

Abstract
Introduction: Adrenal Venous Sampling (AVS) is the most reliable means of identifying surgically curable subtypes of primary aldosteronism (PA). Cortisol levels are used to determine cannulation success and lateralization. However, cortisol has a variable secretion pattern and long-half life, and can be co-secreted by adrenal adenomas, leading to misinterpretation of results. Plasma metanephrines (MN) are a possible alternative analyte. MN levels are unaffected by stress, have a short half-life of 3–6 minutes and are released continuously by the adrenals, resulting in very high concentration gradients between the adrenal veins (AV) and peripheral veins (PV), thus providing a sensitive means to determine cannulation success. Premise:The objective of this study was to see if MN can be used in lieu of cortisol in AVS. A secondary end-point was to see if the data was particularly useful in patients who are known co-secretors of cortisol. Methods: Data from AVS carried out without cosyntropin stimulation, from October 2018 to March 2020, were analysed retrospectively. Of these, 51 had additional samples drawn for MN at the time of the procedure and were recruited. Six patients were identified as having autonomous cortisol secretion as they failed an overnight dexamethasone suppression test (ONDST). The data was analysed using cortisol and MN separately and then compared with regards to their selectivity and lateralization index. Data was also analysed to see if known co-secretors had an elevated cortisol/MN ratio of more than 2 on the affected side as described in previous papers. Results: When compared to cannulation and lateralization outcomes using cortisol, similar results were obtained using, a MN AV/PV ratio of more than 12 to indicate successful cannulation and an aldosterone/MN ratios of greater than 5 to confirm lateralization. Contralateral suppression to less than 0.5 for aldosterone/MN below the PV was seen in unilateral disease. With regards to the six co-secretors, all had elevated cortisol/MN ratios of more than 2 on the affected side. Three had concordant results but the other three had discrepant results, with MN analysis suggesting unilateral disease and cortisol measurements suggesting bilateral disease. Two had undergone surgery with biopsy confirming unilateral disease that correlated with MN analysis. The third is under medical management. Conclusion: This is the first study evaluating the use of MN to determine lateralisation of aldosterone production in PA. Further studies are needed, but using MN may be a more reliable alternative to cortisol in the analysis of AVS before definitive surgery in particular in patients with cortisol co-secretion.
A Case of Hypolipidemia and Hypocholesterolemia; Cause and Consequences
Authors: West William A , Romo Karina , Zaidi Raza , Hoard Brandon , Uwaifo Gabriel Ikponmosa 
Published: May 2021

Abstract
Background: Hypolipidemia and hypocholesterolemia are uncommon and because of the established risk of hypercholesterolemia for cardiovascular disease, reduced lipids and total cholesterol levels are often clinically desired and/or deemed clinically inconsequential. A finding of persistently low lipid levels and total cholesterol may however not be innocuous nor desirable. We describe the case of a 46 yr old man with persistently low total cholesterol levels &lt;70mg/dl and the associated complications and comorbidities identified. Clinical Case: A 46 yr old Hispanic man with non-alcoholic fatty liver disease (NAFLD) was referred for evaluation of hyperhidrosis in the setting of persistent hypolipidemia and hypocholesterolemia. Review of the patient’s clinical and biochemical history showed persistently low total cholesterol (mean 58mg/dl), hypotriglyceridemia, and low LDL-C (mean 13.4mg/dl) over the prior 7 yrs in addition to undetectable serum lipoprotein A. Evaluation for secondary causes of hypolipidemia, such as multiple myeloma, was unremarkable. He was found to have low carotene, borderline vitamin A and low vitamin E levels while the rest of his serum fat-soluble vitamins were normal. His mother who had presumed Alzheimer’s dementia also had a history of very low cholesterol levels. The degree and persistence of his hypolipidemia and hypocholesterolemia raised the possibility of a genetic etiology of his hypolipidemia. Genetic testing confirmed that the patient was heterozygous for a pathogenic variant in the APOB gene, consistent with familial hypobetalipoproteinemia (FHBL) which is autosomal recessive linked. Subsequent close review of his clinical history revealed other potential complications and comorbidities of FHBL including NAFLD with prediabetes, hypogonadism, progressive cognitive and memory decline, peripheral neuropathy and multiple neuropsychiatric syndromes including adult ADHD, borderline personality disorder, bipolar disorder and chronic anxiety. He is presently on vitamin E and A supplementation and being followed by neurology and psychiatry in addition to ongoing endocrine and metabolic clinical surveillance. In addition, in view of his maternal history and several biologic children he has undergone formal genetic and family counselling. Conclusions: While lipid panels are ubiquitous in clinical care, clinicians need to be vigilant in settings of severe persistent hypolipidemia and/or hypocholesterolemia to evaluate for possible genetic basis for this and to also screen for possible associated complications and comorbidities.
Diet-Responsive Hypercholesterolemia With Cardiofaciocutaneous Syndrome Type 3
Authors: Patni Nivedita , Garg Abhimanyu , Xing Chao 
Published: May 2021

Abstract
Background: Molecular basis of diet responsive hypercholesterolemia remains unclear. We report diet-responsive severe hypercholesterolemia in a young female with cardiofaciocutaneous syndrome type 3 (CFC3) due to a heterozygous pathogenic MAP2K1 variant, suggesting a role of common MAPK variants in LDL-cholesterol (LDL-C) response to diet. Clinical case: A 3-year-old Caucasian female with CFC3 (macrocephaly, frontal bossing, wide nasal root with depressed bridge, anteverted nares, low set fleshy ears, congenital pulmonic valve stenosis, postnatal growth deficiency, hypotonia, and neurocognitive impairment) due to a de novo heterozygous c.389A&gt;G, p.Tyr130Cys pathogenic variant in MAP2K1, presented with extremely elevated serum total cholesterol of 446 mg/dL, triglycerides of 239 mg/dL, HDL-cholesterol of 53 mg/dL, LDL-C of 335 mg/dL (normal range &lt; 110 mg/dL) and serum apolipoprotein B level 219 mg/dL (normal range &lt; 90 mg/dL). Her LDL-C was 252 mg/dL a year ago and 215 mg/dL one month prior to presentation. Reducing total dietary fat to 20–25% of total energy and saturated fat to &lt;6% of total energy over the next 4 months lowered LDL-C to 104 mg/dL. However, her weight decreased by 0.5 kg and liberalization of fat intake again increased LDL-C to 222 mg/dL. Her father has mildly elevated LDL-C of 160 mg/dL and her mother had normal LDL-C of 80 mg/dL. Her plasma phytosterol levels were normal and she had ApoE3/E3 genotype. Targeted genetic testing of the patient and parents showed a benign heterozygous LDL receptor (LDLR) variant c.2242G&gt;A; p.Asp748Asn, (Minor allele frequency 0.00008) in the patient and her father. Whole exome sequencing of the patient and both parents showed no known disease-causing variants in LDLR, APOB, PCSK9, LDLRAP1, APOE, STAP1, LIPA, ABCG5, ABCG8 and other known hyperlipidemia-related genes. There are no previous reports of hypercholesterolemia in patients with CFC3. MAP2K1 stimulates various MAP kinases upon wide variety of extra- and intracellular signal and is involved in cell proliferation, differentiation, transcription regulation and development. Previous studies of the relationship between p42/44MAPK activation and LDLR expression in human hepatoma HepG2-derived cell line showed that that activation of the Raf-1/MEK/p42/44MAPK cascade induces LDLR expression and modulation of the Raf-1 kinase signal strength can determine LDLR expression levels. Thus, extent of MAPK activation can alter signaling of LDLR, resulting in hypercholesterolemia. Conclusion: Our case report suggests that MAP2K1 may play a significant role in LDLR signaling, and some MAP2K1 variants may be associated with diet-responsive hypercholesterolemia. Larger studies are required to assess dietary response to LDL-C in subjects with MAP2K1 variants.
Fluphenazine-Induced Severe Hypertriglyceridemia
Authors: Taneja Charit , Beuttler Marc , Thavaraputta Subhanudh 
Published: May 2021

Abstract
Introduction: Antipsychotics are known to result in lipid dysregulation, possibly through their effects on weight, appetite and increased glucose intolerance. These effects are seen in varying degrees with both typical and atypical antipsychotics. This results in a cohort of patients with drug-induced hyperlipidemia, who benefit from lipid-lowering therapy. We describe an extreme scenario where the use of fluphenazine resulted in very severe hypertriglyceridemia, in addition to new onset diabetes requiring inpatient management.
Case: A 42-year-old man with schizophrenia and a history of mild hypertriglyceridemia presented to the emergency department with one month of polyuria and polydipsia, and a home glucose measurement of &gt;500 mg/dL. Six months earlier, he had been started on fluphenazine for schizophrenia. Laboratory testing at that time showed Hemoglobin A1c of 6.0% and a mild elevation in triglycerides to 188 mg/dL. He endorsed a family history of hypertriglyceridemia and type two diabetes. On physical exam, he appeared healthy with no abnormal focal findings. Labs revealed Hemoglobin A1c of 14% and a triglyceride level of 15,213 mg/dL. His blood samples became rapidly lipemic within a few minutes of the blood draw, corrupting the majority of the lab values. He was admitted to the ICU for continuous IV insulin, which improved his severe hypertriglyceridemia over the course of one week. Fluphenazine was switched to ziprasidone for schizophrenia. Pancreatic autoimmune workup was negative. Once the patient’s triglyceride level was &lt;1000 mg/dL, insulin drip was discontinued and gemfibrozil was started. His triglyceride level at discharge was 449 mg/dL, and decreased to within the normal range over the course of a few months at outpatient follow up.
Discussion: The highest on the differential for this case is fluphenazine-associated worsening of pre-existing hypertriglyceridemia in a patient with risk factors for metabolic syndrome. Antipsychotics can result in new-onset or worsening of metabolic syndrome. These patients can usually be managed in the outpatient setting with lipid-lowering therapies and glycemic control. This case represents a rare scenario of a dramatic hypertryglyceridemia and worsening of diabetes secondary to the use of the typical antipsychotic fluphenazine.
Hypertriglyceridemia-Induced Pancreatitis
Authors: Mung Sai Man , Jude Edward 
Published: May 2021

Abstract
A 31-year-old woman was admitted with abdominal pain. Her blood sample was noted to be lipemic. She was not known to have diabetes, hypothyroidism or family history of hyperlipidaemia and denied alcohol intake. She had no eruptive xanthoma or corneal arcus. On admission, triglycerides were 118mmol/L (normal range &lt; 1.8). Computed tomographic scan demonstrated swollen pancreas, extensive peripancreatic inflammation and fatty liver. A diagnosis of hypertriglyceridemia-induced pancreatitis was made.
She was kept nil by mouth and commenced on insulin infusion, fenofibrate and a low-fat diet. Her admission was complicated by acute respiratory distress syndrome and difficult pain control requiring morphine patient-controlled analgesia. Her triglycerides gradually reduced and on day 12 it was 6.6mmol/L.
This case illustrates the importance of multidisciplinary input with endocrinologist, intensivist, gastroenterologist and dietician. Other treatments that could have been initiated was plasma apheresis but as she improved this was not required.
Importance of Diet Modification in Preventing Recurrent Episodes of Hypertriglyceridemic Pancreatitis (HTGP)
Authors: Janakiram Nikhila 
Published: May 2021

Abstract
Background: Hypertriglyceridemic pancreatitis (HTGP) typically occurs in patients with an underlying dyslipidemia. While the incidence is low (2–4%), HTGP has a higher likelihood of recurrence than other forms of pancreatitis. A multifaceted approach is necessary to prevent recurrences of HTGP. Diet modification is an integral part of management, but is usually not well emphasized in this patient population.
Clinical Case: A 22 year old male with hx of recurrent pancreatitis due to familial hypertriglyceridemia presented to the emergency department with epigastric pain beginning on morning of admission. The patient’s 1st pancreatitis episode was 1 year ago and he had 8 incidences of pancreatitis due to elevated triglyceride levels. One episode required ICU stay due to pressor requirement. Patient noted medication compliance to gemfibrozil since this admission, however stated that he had not made any changes in his diet since diagnosis 1 year ago. Patient had been abstinent from alcohol and drugs 6 months prior to admission. Patient’s triglyceride level on admission was 1,203 and was started on insulin drip. However, due to persistent hypoglycemia was also placed on D5 mIVFs. Despite the fluids, patient continued to be hypoglycemic and insulin drip was stopped for a short period of time with the triglyceride level in the 700s. The following night, patient was placed back on insulin drip at higher rate and became hypoglycemic again. Consequently, insulin drip was turned off the following morning. Triglyceride level continued to downtrend to 510. Insulin drip was restarted at a lower rate later that day. A recheck of triglyceride level that day showed that triglyceride decreased to 470. Patient was placed back on gemfibrozil with niacin added to the regimen and discharged home after a detailed discussion about diet changes.
Discussion: This case study illustrates a patient with multiple episodes of pancreatitis due to elevated triglyceride levels despite compliance to gemfibrozil, resulting in refractory hypoglycemic episodes during his most recent admission from chronic damage to the pancreas’s alpha cell activity. While medication compliance is important, diet modification is as well. The above case sheds light on the importance of long-term diet modification in patients including restriction of dietary fat, simple carbohydrates and alcohol.
The Importance of Ophthalmic Examination in Initial Diagnostic Process of Xanthoma: Two Case Reports and Literature Review of Cerebrotendinous Xanthomatosis
Authors: Goak Insun , Jang Seol A , Park Ji Hyun 
Published: May 2021

Abstract
Background: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disease where deficiency of sterol 27-hydroxylase leads to reduced production of CDCA. In such cases, life expectancy is only 4–6 decades, with progressive neurologic dysfunction such as dementia and spinal cord paresis, unless the condition is diagnosed early and treated appropriately. Herein, we aim to raise awareness regarding the importance of ophthalmic examination in evaluating of xanthoma. Clinical Cases: Case 1: In a 58-year-old man with no neurological symptoms; bilateral cataracts were detected during the initial diagnostic process. This patient had two siblings with xanthoma; one died from cerebral infarction and the other from biliary tract cancer. Another sibling had premature acute cardiovascular disease without xanthomas. Baseline lipid profiles were nearly within the normal range, while lipoprotein A was approximately 2.5 times higher than the normal. CTX was confirmed by the detection of a homozygous mutation in the CYP27A1 gene and high plasma cholestanol level (8.5 mg/L; reference range 0.0–5.0 mg/L). He has been taking oral CDCA (250 mg, three times daily). Case 2: In a 24-year-old man with no neurological symptoms or intellectual disability, premature bilateral cataracts were detected 1 year prior to diagnosis of CTX. None of his family members had xanthoma or premature cardiovascular disease. Lipid profile showed a similar pattern to that of Case 1; CTX was confirmed by the detection of a homozygous mutation in the CYP27A1 gene and high plasma cholestanol level (21.33 mg/L). One year after starting CDCA (250 mg, three times daily), cholestanol levels dropped to 7.34 mg/L. They were measured annually and identified as 5.08 mg/L, 4.2 mg/L, 4.7 mg/L, and 3.8 mg/L at 24, 38, 61, and 72 months, respectively. It took approximately 2 years for the normalization of his cholestanol level. There were no recurrences of xanthoma or progression of complications in target organs after 6 years of treatment. Conclusion: Early diagnosis improves the outcomes of CTX, allowing proper treatment. Bilateral cataracts caused by cholestanol buildup on the crystalline lens due to CTX usually occur within the first three decades of life. This manifestation does not occur in patients with xanthoma, familial hypercholesterolemia, or sitosterolemia. Taken together, this report suggests that premature bilateral cataracts are a specific marker that can accelerate early diagnosis of CTX. References: (1) Duell PB et al. Diagnosis, Treatment and Clinical Outcomes in 43 Cases with CTX. Journal of Clinical Lipidology. 2018;12:1169 (2) Salen G, Steiner RD. Epidemiology, diagnosis, and treatment of CTX. J Inherit Metab Dis 2017: 40:771