Severe Hypertriglyceridemia Without Pancreatitis Causing Total Pseudohypocalcemia With True Ionized Symptomatic Hypocalcemia: A Diagnostic Pitfall.

Hypertriglyceridemia induced pancreatitis (HTGP) is the third most common causes of acute pancreatitis (AP) after alcohol and gallstones. The commonly used treatment for HTGP is either intravenous (IV) insulin or heparin along with fenofibrates. A 34 year old obese Hispanic female with past medical history of hyperlipidemia (HPL) presented to the emergency room with a chief complaint of 3 days history of progressively worsening severe epigastric pain radiating to her lower back, associated with nausea and vomiting. She had no prior similar episodes. Her personal, family, medication and social history was unremarkable except occasional alcohol drinking of the standard one to two drinks every month, but prior to this ER visit she reported drinking more than 3 standard drinks per day for the past 2 days. Relevant laboratory tests revealed mild hyponatremia of 130 mEq/L, lipase of 1039 U/L, with a normal calcium, blood glucose (BG) and liver function tests, but the serum was abnormally milky white in appearance. The lipid panel revealed triglycerides (TG) > 3000 mg/dl. An abdominal ultrasound showed non-obstructive cholelithiasis with a common bile duct size of 7 mm. She was managed conservatively with AP treatment guidelines, but due to severe hypertriglyceridemia (SHTG) and symptoms she underwent one session of plasmapheresis with albumin replacement. The TG subsequently trended down to 349 mg/dl and she was advanced on a low fat diet and Fenofibrate. Follow-up TG after 1 month was 80 mg/dl. HTGP is clinically evident when levels are > 1000mg/dl and is classified as SHTG and very severe HTG for levels > 2000 mg/dl. The goal of the treatment is lowering the TG levels to < 250 mg/dl and identifying the underlying cause. Patients with HTGP have higher chances of recurrent AP than pancreatitis from other causes. There is evidence of improvement in symptoms as well as lowering TG levels with IV insulin in patients with HTGP and marked hyperglycemia, but in patients with normal BG levels treatment of HTGP is not very well defined. Our patient was treated with plasmapheresis leading to a significant improvement in her TG levels, clinical and laboratory parameters in a relatively short time leading to a shorter hospital stay. Currently there are no guidelines for the use of plasmapheresis in treatment of HTGP. Plasmapheresis seems to be an effective method for the treatment of HTGP and an important area of future research, especially in patients with severe AP and normal BG levels.

Background Hypertriglyceridemia (HTG) is one of the major modifiable risk factors for the development of several metabolic diseases. Determining the factors associated with HTG is an important step for increasing awareness of the problem and proper planning of health programs for HTG prevention. This study aimed to determine the conditions associated with HTG in adult patients in Basrah, Iraq. Methodology This retrospective study was conducted at Faiha Specialized Diabetes Endocrine and Metabolism Center (FDEMC) in Basra, southern Iraq, in January 2024. The data were retrieved from the center database of 37,133 subjects registered from 2008 to 2023 (16,284, 43.8% males and 20,849, 56.2% females) who attended the FDEMC in Basra due to different reasons. Results The most common causes of HTG were type 2 diabetes mellitus (T2DM) (29,799, 80%), obesity (19,914, 53.63%), and smoking (7,309, 12.68%). The age group of 18-45 years displayed higher triglyceride (TG) levels (281.1 ± 210.1 mg/dL) than other age groups. Furthermore, male patients had higher TG levels than females (288.0 ± 196.3 mg/dL vs. 268.9 ± 165.9 mg/dL). Regarding body mass index, overweight and obese patients had higher mean TG levels (284.4 ± 182.1 mg/dL and 281.7 ± 184.6 mg/dL, respectively). Current and ex-smokers had higher TG levels (305.1 ± 212.2 mg/dL and 283.4 ± 161.3 mg/dL, respectively) than non-smokers (272.5 ± 175.4 mg/dL). Moderate HTG was the most common category encountered in 24,137 patients (65%), followed by mild HTG (12,705, 34.2%). Very few patients had severe (264, 7%) or very severe HTG (27, 0.07%). Male patients had more frequent severe and very severe HTG than females. Conclusions The most common conditions associated with HTG were T2DM, obesity, and smoking. Smoker males were prone to severe and very severe HTG.

Identificación de variantes en el gen LMF1 asociadas con hipertrigliceridemia primaria

Background and aimsSevere hypertriglyceridemia (HTG), defined as plasma triglyceride (TG) concentration > 10 mmol/L, is relatively uncommon, and its implications for atherosclerotic cardiovascular disease (ASCVD) risk remain somewhat unclear. We evaluated the association between severe HTG and carotid intima-media thickness (IMT), a marker for ASCVD. MethodsWe studied three clinical cohorts: 88 patients with severe HTG (mean TG level 20.6 mmol/L), 271 patients with familial hypercholesterolemia (FH) as a contrast group, and 70 normolipidemic controls. Carotid IMT was measured using standardized ultrasound imaging. Statistical analysis was conducted using one-way analysis of variance (ANOVA) to compare mean IMT values, analysis of covariance (ANCOVA) to adjust for confounding variables, specifically age and sex, as well as Spearman pairwise correlation analysis between variables. ResultsUnadjusted mean carotid IMT was greater in severe HTG and FH groups compared to controls, however, this was no longer significant for severe HTG after adjustment for age and sex. In contrast, adjusted carotid IMT remained significantly different between the FH and control groups. ConclusionsOur findings suggest that extreme TG elevations in severe HTG patients are not significantly associated with carotid IMT, in contrast to the increased IMT seen in FH patients. These findings add perspective to the complex relationship between severe HTG and ASCVD risk.

Asparaginase (ASP) is an effective chemotherapy agent extensively used in children with acute lymphocytic leukemia (ALL). There has been a recent interest in using ASP in adults with ALL, particularly the less toxic pegylated (PEG) formulation. Hypertriglyceridemia (HTG) is a rare complication of PEG-ASP therapy. We report two cases of obese patients who developed severe HTG after receiving PEG for ALL. Both patients were incidentally found to have severe HTG (TG of 4,330 and 4,420 mg/dL). In both patients, there was no personal or family history of dyslipidemia or hypothyroidism. There was no evidence of pancreatitis or skin manifestations of HTG. Both patients were treated with PEG cessation, low-fat diet and pharmacotherapy. Both patients were re-challenged with PEG, with subsequent increase in TG but no associated complications. TG returned to baseline after discontinuing PEG and while on therapy for HTG. A literature review of PEG-induced HTG in adults demonstrated similar results: asymptomatic presentation despite very severe HTG. HTG is a rare but clinically important adverse effect of PEG. Underlying obesity and/or diabetes may represent risk factors. Clinicians should monitor TG levels during PEG therapy to avoid TG-induced pancreatitis.

Hypertriglyceridemia (HTG) represents a major health problem with prevalence exceeding 30% in the U.S. The present study aims to assess the effect of elevated serum triglyceride (TG) levels on the severity of acute pancreatitis (AP). Prospectively enrolled AP patients were categorized into normal, mild, moderate, and severe/very severe categories based on their TG levels and compared in respect to demographics, comorbidities, and clinical outcomes. Multivariate analysis determined whether elevated TG levels were independently associated with persistent organ failure. Two hundred and one out of 400 AP patients had serum TGs measured within 72 h of presentation, of which 115 had normal TG levels and 86 HTG (20 mild, 41 moderate, and 25 severe/very severe). Patients with HTG were of younger age (44 vs. 52 years), predominantly male (65% vs. 45%), obese (57% vs. 34%), diabetic (38% vs. 17%), and developed more frequently persistent organ failure (40% vs. 17%) compared with those with normal TGs (P<0.02). The rate of persistent organ failure increased proportionally with HTG severity grades (17% when normal TGs, 30% in mild, 39% in moderate, and 48% in severe/very severe HTG, Ptrend<0.001). On multivariate analysis controlling for age, gender, body mass index, diabetes, and alcohol etiology, moderate HTG (odds ratio (OR), 2.6; P=0.04) and severe/very severe HTG (OR, 4.9; P=0.009) were independently associated with persistent organ failure. Elevated serum TGs in AP patients are independently and proportionally correlated with persistent organ failure regardless of etiology. TG-mediated lipotoxicity may be an attractive target to design novel interventions for severe AP.

Severe hypertriglyceridemia is a well-known cause of pancreatitis. Usually, there is a moderate increase in plasma triglyceride level during pregnancy. Additionally, certain pre-existing genetic traits may render a pregnant woman susceptible to development of severe hypertriglyceridemia and pancreatitis, especially in the third trimester. To elucidate the underlying mechanism of gestational hypertriglyceridemic pancreatitis, we undertook DNA mutation analysis of the lipoprotein lipase (LPL), apolipoprotein C2 (APOC2), apolipoprotein A5 (APOA5), lipase maturation factor 1 (LMF1), and glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) genes in five unrelated pregnant Chinese women with severe hypertriglyceridemia and pancreatitis. DNA sequencing showed that three out of five patients had the same homozygous variation, p.G185C, in APOA5 gene. One patient had a compound heterozygous mutation, p.A98T and p.L279V, in LPL gene. Another patient had a compound heterozygous mutation, p.A98T & p.C14F in LPL and GPIHBP1 gene, respectively. No mutations were seen in APOC2 or LMF1 genes. All patients were diagnosed with partial LPL deficiency in non-pregnant state. As revealed in our study, genetic variants appear to play an important role in the development of severe gestational hypertriglyceridemia, and, p.G185C mutation in APOA5 gene appears to be the most common variant implicated in the Chinese population. Antenatal screening for mutations in susceptible women, combined with subsequent interventions may be invaluable in the prevention of potentially life threatening gestational hypertriglyceridemia-induced pancreatitis.

Disclosure: A. Iqbal: None. U. Alwahab: None. Introduction The use of incretin-mimetic therapy (IMT), which includes human glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) agonists, in patients with a history of pancreatitis is controversial. While clinical trials have demonstrated a slightly increased incidence of acute pancreatitis (AP) in patients on IMT, it is unclear if patients with hypertriglyceridemia (HTG)-induced pancreatitis areat similar risk. In patients with type 2 diabetes (T2D) and HTG, control of diabetes and improvement of metabolic profile using IMT could decrease the risk of HTG-induced pancreatitis. Case Description We report a case of a patient with diabetes and a history of HTG-induced pancreatitis where IMT was successfully used without precipitation of AP. Patient A is a 44-year-old male with obesity (BMI 38.25 kg/m2 ), T2D, and severe HTG associated with recurrent episodes of AP. His triglyceride (TG) level has ranged from 983 to &amp;gt;4,000 mg/dL. He is on fenofibrate, icosapent ethyl, and rosuvastatin. His last hospitalization for acute pancreatitis was 3months prior. His most recent hemoglobin A1c is 7.4%, TG is 302mg/dL, and he is being treated with glipizide, metformin, empagliflozin, and multiple daily injections of insulin. For management of his obesity and T2D, he is then started on tirzepatide, in conjunction with diet and lifestyle modification, which is slowly up-titrated to 7.5 mg weekly. After 12 months of tirzepatide treatment, he has lost 10 lbs, his A1C is now 5.9%, triglycerides have improved to 172 mg/dL, and he has had no precipitation of AP. Discussion While a history of pancreatitis is a relative contraindication to the use of IMT, attention should be paid to the cause of pancreatitis. Obesity and uncontrolled diabetes are frequent triggers of AP. IMT helps improve metabolic profile in patients with obesity, uncontrolled diabetes, and hypertriglyceridemia, thus decreasing triglyceride levels and preventing further episodes of AP as seen in our patient. The use of IMT in patients with a history of AP should be done on an individualized basis. Controlling the trigger for the AP (such as hypertriglyceridemia) should be prioritized and shared medical decision-making with the patient should be done regarding the benefits and risks of IMT. Presentation: 6/3/2024

Background: Primary hyperparathyroidism is a relatively common disorder caused by the inappropriate autonomous secretion of parathyroid hormone which subsequently leads to hypercalcemia. There is increased prevalence of vitamin D deficiency in patients with primary hyperparathyroidism. As these patients are already hypercalcemic, there is reluctance within the medical community to provide vitamin D supplementation due to fear of exacerbating hypercalcemia. Clinical Case: A 17 year old African American male was referred to the pediatric endocrinology clinic for hypercalcemia (total serum calcium level 11.2 mg/dL, 8.6-10.6). His past medical history was significant for a diagnosis of membranoproliferative glomerulonephritis type 2 which was in remission. His most recent blood tests showed normal renal function. A review of his hospital chart showed that his calcium levels had been on the upper end of the reference range or above it for at least a year prior to his presentation to the clinic. He had no signs or symptoms concerning for hypercalcemia. He was not taking any calcium supplements or other medications which are known to be associated with elevated calcium levels. There was no known family history of hypercalcemia. He denied any history of renal stones, adrenal disease, weight loss, or osteoporosis but did report a wrist and knee fracture both of which occurred during competitive wrestling matches. His vital signs and physical exam were unremarkable. On laboratory analysis his serum calcium was 11.0 mg/dL, intact PTH 112 pg/mL (ref range 12-88), 25 hydroxyvitamin D was 10 ng/mL (ref range 20-80), Alk Phos 145 U/L (ref range 100-300), Albumin 4.8 g/dL (3.4-5.0), TSH 1.97 mcIU/mL (0.35-4.0), Free T4 0.8 ng/dL (0.6-1.7), Cr 0.94 mg/dL (0.5-1.3), 24 hour urine calcium excretion was 228 mg and calculated calcium to creatinine ratio was 0.07. Ultrasound of the neck and nuclear parathyroid scan and did not definitively show a parathyroid adenoma but could also not rule out the presence of an adenoma. Given patient’s low 25 OH vitamin D level he was given a 4 week course of supplemental vitamin D (1,000 units daily) with resultant 25 OH vitamin D level of 21 ng/mL. His serum calcium and intact PTH level remained elevated at 10.9 mg/dL and 108 pg/mL respectively. The patient was sent to otolaryngology for evaluation should the need arise in the future for surgical intervention and genetic testing to definitively rule out familial hypocalciuric hypercalcemia was sent. As he is asymptomatic with mild hypercalcemia currently, we will continue to monitor yearly per guideline recommendations. Conclusion: Supplementation with modest doses of vitamin D did not significantly raise our patient’s calcium level and led to an improvement in the 25 hydroxyvitamin D level. Vitamin D repletion should be considered in cases of asymptomatic primary hyperparathyroidism associated with mild hypercalcemia.

BACKGROUND:Pregnancy is described as a normal physiologic state associated with various biochemical changes. Magnesium and calcium are essential macronutrients required for foetal growth. Complications associated with their deficiency during normal pregnancy include; low neonatal birth weight, pre-eclampsia, eclampsia and preterm labour. Changes in serum levels of magnesium and calcium in normal pregnancy have not been extensively studied among Ghanaian women.AIM:To determine the variation in serum magnesium and calcium levels with gestational age in normal pregnancy in Ghanaian women.METHODS:A hospital-based comparative cross-sectional study was conducted among 32 normal non-pregnant women (Group A) and 100 normal pregnant women (Group B) attending the clinic at the Korle-Bu Teaching hospital. The group B pregnant women were further divided into Group B1 (n = 33), Group B2 (n = 37) and Group B3 (n = 30) based on their pregnancy gestation as first, second and third trimester respectively. Blood samples were obtained from the antecubital vein of subjects and total serum calcium, magnesium, protein and albumin were estimated. Data obtained were analysed using SPSS for windows version 20. Analysis of variance (ANOVA) was employed to determine the statistical differences between the groups. A p-value of ≤ 0.05 was considered significant.RESULTS:Mean serum total calcium and magnesium in first, second and third trimester normal pregnant women were 2.14 ± 0.16, 2.13 ± 0.44, 2.13 ± 0.35 mmol/L and 0.77 ± 0.11, 0.77 ± 0.16 and 0.76 ± 0.14 mmol/L respectively. Mean serum total calcium and magnesium levels in non-pregnant women were 2.20 ± 0.16 and 0.80 ± 0.10 mmol/L respectively. There was a statistically non-significant difference in serum total calcium and magnesium between non-pregnant and normal pregnant women, with p-values of 0.779 and 0.566 respectively. Mean total serum protein and albumin in first, second and third-trimester normal pregnant women were 68.42 ± 10.37, 70.46 ± 6.84, 66.70 ± 7.83 g/L and 39.92 ± 3.22, 40.75 ± 8.06, 38.26 ± 3.02 g/L respectively. Mean total serum protein and albumin in non-pregnant women were 73.13 ± 7.02 and 42.94 ± 3.03 g/L respectively. Mean total serum protein and albumin levels were lower in pregnant women as compared to non-pregnant women with the difference being significant in the third trimester (p-values of 0.012 and 0.002).CONCLUSION:Total serum calcium and magnesium levels in normal pregnancy were non-significantly lower compared to non-pregnant women in Ghana. There was a reduction in total serum protein, and albumin levels during pregnancy with a significant reduction noticed during the third trimester compared to the non-pregnant state.

Editorial

Background: The pathophysiology of preeclampsia remains poorly understood despite having many studies. The association of decreased calcium level Preeclampsia (PE) has been proposed for decades. This study aimed to compare serum total calcium levels between women with preeclampsia and normotensive pregnant women at a tertiary care teaching hospital in Bangladesh. Materials and methods: One hundred pregnant women with a gestational age of more than 28 weeks and singleton pregnancy [50 preeclamptic (Cases) women and 50 normotensive pregnant women (Control)] were included in the selected case-control study from the Obstetrics &amp; Gynecology Department of Chittagong Medical College Hospital. On admission, venous blood samples were collected before the commencement of treatment. Serum total calcium levels were estimated and compared between the two groups. Results: Out of 50 cases, 23 (46%) had preeclampsia without severe features and 27 (54%) had preeclampsia with severe features. The mean (± standard deviation) serum level of calcium in the control group, PE patients without severe features and PE patients with severe features were 9.14±0.48 mg/dl, 8.31±0.59and 8.29±0.61mg/dl, respectively. The meanserum total calcium level was significantly lower in preeclamptic patients with severe features and preeclamptic patients without severe features than the normotensive women (p&lt;0.001 for both). Hypocalcemia was found to have an incidence rate of 12% in controls and 58% among cases. The adjusted odds of having preeclampsia was almost eleven times higher among those participants with low total serum calcium level (Odds ratio 10.81, 95% confidence interval 2.98-39.16). Conclusion: In conclusion, reducing serum calcium levels during pregnancy might contribute to the aetiology of preeclampsia, and supplementing these elements to the diet may be useful in preventing preeclampsia. JCMCTA 2024 ; 35 (1) : 114-119

The causes of temporary hypocalcemia after thyroidectomy are not well understood. In 18 patients undergoing unilateral (UL) and bilateral thyroid lobectomy (BL), an attempt was made to preserve all parathyroid glands with an intact blood supply. Total calcium (bound and free), free calcium (physiologically active form), albumin, parathyroid hormone, and calcitonin levels were serially measured. After UL, free calcium, parathyroid hormone, and calcitonin levels were unchanged, but total calcium level decreased because albumin level decreased. After BL, total calcium level decreased due to a decrease in albumin-bound calcium level. Free calcium level also decreased due to a decrease in parathyroid hormone level. Calcitonin level did not change. Despite careful preservation of the parathyroids and their blood supply, BL is frequently associated with temporary hypoparathyroidism. Techniques for preservation of parathyroid glands with their vascular integrity, correlation of surgical manipulation of parathyroids and calcium level, and calcium binding are discussed.

Background and Aims Hypertriglyceridemia (HTG) is defined as the plasmatic concentration of triglycerides above 150 mg/dl. With a current prevalence ranging from 15% to 20% in clinical practice, it's a prevalent condition that´s increasing alongside other cardiovascular risk factors such as diabetes mellitus, obesity and hypertension. In most patients HTG is asymptomatic, except in certain circumstances such as hereditary HTG, which can present with skin lesions such as eruptive xanthomas and xanthelasmas. Another exception is severe HTG, which can manifest with pancreatitis. Pharmacological treatment for HTG is typically initiated when serum triglyceride levels exceed 885 mg/dl or when patients with a previous episode of pancreatitis. However, in cases of severe HTG (triglycerides &amp;gt; 1000 mg/dl), conventional pharmacological therapies become less effective. Therefore, alternative therapeutic interventions, such as apheresis, become increasingly relevant for the management of severe HTG. Current guidelines from the American Society of Apheresis (ASFA) consider the use of therapeutic plasmapheresis in patients with acute pancreatitis secondary to severe hypertriglyceridemia as a category III/grade 1C recommendation and that in most cases it is an adjunct to medical treatment. Case series Below, we describe a series of cases in which we used this technique to control metabolic in our center during the last year. Case 1 A 30-year-old man with familial primary hypertriglyceridemia, schizophrenia, and sporadic drinking, was admitted from the Emergency Department with a 24h long severe abdominal pain with difficult management and vomiting. After complementary analysis, acute edematous pancreatitis without necrosis was diagnosed. Given the analytical values (Table 1), therapeutic plasmapheresis was decided, with a plasma volume of 3.5 liters calculated with the patient's weight and hematocrit and using albumin as the replacement fluid. As a complication, and despite administration of heparin, the filter required replacement halfway through the session due to problems with transmembrane pressure. Two sessions were completed on consecutive days until clinical and analytical control of triglycerides was achieved. Case 2 A 55-year-old man with a history of mild dyslipidemia controlled with diet and hypertension, was admitted from the Emergency Department with abdominal pain of 12 hours duration. After completing the study and diagnosis of acute pancreatitis of probable HTG origin, a plasmapheresis session was completed with a volume of 3 liters, albumin replacement fluid and heparinization during the technique, without complications, along with triglyceride control after the procedure maintaining medical treatment. Case 3 A 62-year-old man with a history of familial HTG, bronchial hyperreactivity, and occasional drinking, was admitted with abdominal pain of 72 hours duration accompanied by nausea and vomiting. Complementary studies confirmed acute severe pancreatitis with hemodynamic and respiratory failure. Given the analytical findings, a plasmapheresis session was performed with a volume of 2.5 liters per weight and hematocrit, with albumin replacement and heparin as per protocol. Subsequent HTG control with medical treatment was achieved without the need for further apheresis sessions. Conclusion Cardiovascular disease is responsible for the death of more than 4 million people in Europe each year, 2.2 million women (55%) and 1.8 million men (45%). Lipoprotein apheresis has preventive effects on the progression of atherosclerosis in addition to being an effective technique for reducing LDL, so its indication in groups of patients with severe and primarily familial hypercholesterolemia is well established. In our center, the recent start of the control of apheresis techniques from Nephrology in metabolic diseases, although still with limited experience and a limited number of patients, may constitute a new field of work in the specialty itself and collaboration with the different hospital specialties to improve the prevention, control, and treatment of patients with a high cardiovascular risk.

The severe forms of hypertriglyceridaemia (HTG) are caused by mutations in genes that lead to the loss of function of lipoprotein lipase (LPL). In most patients with severe HTG (TG > 10 mmol L(-1) ), it is a challenge to define the underlying cause. We investigated the molecular basis of severe HTG in patients referred to the Lipid Clinic at the Academic Medical Center Amsterdam. The coding regions of LPL, APOC2, APOA5 and two novel genes, lipase maturation factor 1 (LMF1) and GPI-anchored high-density lipoprotein (HDL)-binding protein 1 (GPIHBP1), were sequenced in 86 patients with type 1 and type 5 HTG and 327 controls. In 46 patients (54%), rare DNA sequence variants were identified, comprising variants in LPL (n = 19), APOC2 (n = 1), APOA5 (n = 2), GPIHBP1 (n = 3) and LMF1 (n = 8). In 22 patients (26%), only common variants in LPL (p.Asp36Asn, p.Asn318Ser and p.Ser474Ter) and APOA5 (p.Ser19Trp) could be identified, whereas no mutations were found in 18 patients (21%). In vitro validation revealed that the mutations in LMF1 were not associated with compromised LPL function. Consistent with this, five of the eight LMF1 variants were also found in controls and therefore cannot account for the observed phenotype. The prevalence of mutations in LPL was 34% and mostly restricted to patients with type 1 HTG. Mutations in GPIHBP1 (n = 3), APOC2 (n = 1) and APOA5 (n = 2) were rare but the associated clinical phenotype was severe. Routine sequencing of candidate genes in severe HTG has improved our understanding of the molecular basis of this phenotype associated with acute pancreatitis and may help to guide future individualized therapeutic strategies.