No abstract

Participants carrying PCSK9-LOF variants had attenuated levels of fasting and postprandial TG, apoB48, and total apoB. This may confer protection from CVD and further validate the use of PCSK9 inhibitors to lower CVD risk.

Background Although hemodialysis is a highly effective treatment for diffusive clearance of low molecular weight uremic toxins, its effect on circulating extracellular vesicles and submicron particles is less clear. The purpose of this study was to examine the impact of hemodialysis on circulating levels of submicron particles. Methods Plasma samples from patients were collected immediately before and after the mid-week hemodialysis session. Total submicron particles were assessed by nanoparticle tracking analysis and levels of endothelial (CD144 + ), platelet (CD41 + ), leukocyte (CD45 + ), and total (Annexin V + ) membrane microparticles (MPs) were assessed by flow cytometry. Results Total submicron particle number was significantly lower post-dialysis with reductions in particles < 40 nm, 40–100 nm, and 100–1000 nm in size. Circulating annexin V + MPs, platelet MPs, leukocyte MPs, and endothelial MPs were all reduced following dialysis. Assessment of protein markers suggested that extracellular vesicles were not present in the dialysate, but rather adsorbed to the dialysis membrane. Conclusions In summary, hemodialysis is associated with reductions in circulating submicron particles including membrane MPs. Accordingly, there may be significant interdialytic variation in circulating submicron particles. Investigators interested in measuring extracellular vesicles in patients undergoing hemodialysis should therefore carefully consider the timing of biosampling.

Serum sLDLR levels correlate with several lipoprotein parameters, especially TG, and the presence of PCSK9 loss-of-function variants alters sLDLR levels and correlations, except for TG. Ectodomain LDLR shedding has a role in LDL metabolism, distinct from PCSK9, with interplay between these two pathways that regulate cell-surface LDLRs. Findings suggest alteration of LDLR shedding could emerge as a target to treat dyslipidemia.

Background. Serum lipids including total cholesterol (TC), triglycerides (TG), and low density lipoprotein cholesterol (LDL-C) are increased in pregnancy. Serum proprotein convertase subtilisin kexin 9 (PCSK9) is a significant player in lipoprotein metabolism. Circulating PCSK9 downregulates the LDL receptor on the surface of the liver, inhibiting clearance of LDL-C. Therefore, our study assessed serum PCSK9 concentrations at parturition (Maternal) compared to a nonpregnant (Control) cohort, as well as between mother and newborn (Maternal and Newborn). Methods. Blood was collected from women at parturition and from umbilical cords. Serum lipids and PCSK9 were measured and data were analysed for significance by Mann-Whitney U test at P < 0.05 and presented as median levels. Spearman's correlations were made at a 95% confidence interval. Results. Serum PCSK9 was significantly higher in Maternal versus Control cohorts (493.1 versus 289.7 ng/mL; P < 0.001, resp.), while the Newborn cohort was significantly lower than Maternal (278.2 versus 493.1 ng/mL; P < 0.0001, resp.). PCSK9 was significantly correlated with TC and HDL-C in Maternal and with TC, LDL-C, and HDL-C in Newborn cohorts. Conclusions. Our study provides the first quantitative report on PCSK9 in pregnancy (at parturition) and in umbilical cord blood. Further research will determine how these changes may affect lipoprotein levels during this physiological state.

Pro-protein convertase subtilisin-kexin 9 (PCSK9) is known to affect low-density lipoprotein (LDL) metabolism, but there are indications from several lines of research that it may also influence the metabolism of other lipoproteins, especially triglyceride-rich lipoproteins (TRL). This review summarizes the current data on this possible role of PCSK9. A link between PCSK9 and TRL has been suggested through the demonstration of (1) a correlation between plasma PCSK9 and triglyceride (TG) levels in health and disease, (2) a correlation between plasma PCSK9 and markers of carbohydrate metabolism, which is closely related to TG metabolism, (3) an effect of TG-lowering fibrate therapy on plasma PCSK9 levels, (4) an effect of PCSK9 on postprandial lipemia, (5) an effect of PCSK9 on adipose tissue biology, (6) an effect of PCSK9 on apolipoprotein B production from the liver and intestines, (7) an effect of PCSK9 on receptors other than low density lipoprotein receptor (LDLR) that are involved in TRL metabolism, and (8) an effect of anti-PCSK9 therapy on serum TG levels. The underlying mechanisms are unclear but starting to emerge.

Objective: To report the case of a female patient who was diagnosed with Gordon syndrome causing chronic hyperkalemia with normal renal function and clinical implications during pregnancy. Methods: The pertinent clinical features, laboratory data, and clinical course of the patient, both during and after pregnancy, are reported along with a brief literature review. Results: The patient was a 28-year-old female who had a history of multiple visits to the emergency department due to muscle twitching and generalized weakness since 2007. During these visits, she was found to have hyperkalemia without apparent cause. She was not on any culprit medications. Laboratory work-up showed hyperkalemia ranging between 5.5 to 6.4 mmol/L and hyperchloremic metabolic acidosis but normal renal function. Adrenal insufficiency was ruled out with normal morning cortisol and appropriate cortisol response to a stimulation test with 250 μg adrenocorticotropic hormone. Renin was low at 2.5 ng/L (normal range is 3.2 to 59.3 ng/L), aldosterone was inappropriately normal at 250 pmol/L (normal range is 103 to 1,197 pmol/L). The fludrocortisone challenge test failed to decrease her potassium levels. Genetic testing confirmed mutation in the kelch-like family member 3 gene (c.254A>T, p.Glu85Val) confirming the diagnosis of Gordon syndrome. Hydrochlorothiazide was initiated which reversed her biochemical abnormalities. She became pregnant, and her potassium levels normalized throughout pregnancy without the need for thiazides. Her blood pressure remained normal. Her pregnancy was uneventful. Following delivery, her potassium levels increased requiring re-initiation of thiazides. Conclusion: We report the seventh case describing the clinical course of Gordon syndrome during pregnancy and postpartum. All other cases reported show continued need for treatment during pregnancy whereas our patient had resolution of the metabolic defects. (AACE Clinical Case Rep. 2018;4:e235-e239) Abbreviations: CUL3 = cullin 3 gene; GS = Gordon syndrome; HCTZ = hydrochlorothiazide; KLHL3 = kelch-like family member 3 gene; NCC = sodium-chloride cotransporter channel; WNK = with-no-lysine kinase

We report the case of a 75-year-old female with an intrapulmonary smooth, round 2-cm nodule that contained heterotrophic thyroid tissue with no malignant or teratomatous features. She also had a normally located multinodular goiter. Ultrasound examinations of the thyroid and CT-scans of the pulmonary nodule done 7 years apart showed no significant change. Thyroid/whole body scans using TC-99m done 7 years apart also provided similar findings. The lack of change in the thyroid and pulmonary nodules makes a thyroid malignancy highly unlikely.Intrapulmonary heterotrophic thyroid tissue is a very rare entity, with only 2 reported cases in the literature. Our case is different from the other 2 in that they did not have a co-existing goiter.This case report draws attention to the occurrence of intrapulmonary heterotrophic thyroid tissue. Although rare, it needs to be considered in the differential diagnoses of a pulmonary nodule.