A Case of Pituitary Apoplexy and Cavernous Sinus Syndrome during Hemodialysis.

Background: Pituitary apoplexy (PA) is a clinical syndrome of pituitary hemorrhage or infarction and can result in hypopituitarism as well as compression of adjacent brain structures. Visual loss occurs frequently, as a result of tumor expansion and compression of the optic chiasm and optic nerves. Additionally, with pituitary tumor invasion into the fixed space of the cavernous sinus, compression of multiple cranial nerves can result in cavernous sinus syndrome (CSS). We describe a case of an undiagnosed pituitary tumor manifesting as abrupt PA with CSS during hemodialysis (HD). Clinical Case. A 77-year-old male with end-stage renal disease (ESRD) presented with acute onset of severe headache, decreased vision, ophthalmoplegia of the left eye, and hypotension during HD. MRI of the brain revealed a 2.5 cm pituitary adenoma with acute hemorrhage, compression of the left prechiasmatic optic nerve, and invasion into the left cavernous sinus (CS). The hormonal profile was consistent with multiple pituitary hormone deficiencies. The patient was treated with glucocorticoids and underwent transsphenoidal resection of the tumor. He had an uneventful postoperative hospital course, and his left visual acuity stabilized, although there was no immediate improvement in his other ocular symptoms. Conclusion: Our case highlights a rare constellation of a pituitary adenoma with CS invasion complicated by PA and CSS during HD. The pathophysiology of PA is not well understood, and there are very limited data regarding PA in patients with end-stage renal disease (ESRD) on HD. Prompt recognition of PA in a patient presenting with CSS, particularly in the HD setting, is essential to ensure appropriate care is provided for this medical emergency.

New-onset persistent hyperglycemia with initiation of brentuximab treatment.

INTRODUCTION: The addition of brentuximab vedotin (BV) to adriamycin, vinblastine, and dacarbazine (AVD) has become the standard-of-care approach for advanced stage Hodgkin lymphoma (HL). This case describes a rare presentation of new-onset diabetes mellitus one month after initiation of BV + AVD therapy in a patient with HL. CASE REPORT: A 41-year-old woman with pre-diabetes and obesity was started on BV + AVD for classical HL, nodular sclerosing type. Six weeks after initiating therapy, she was admitted for abdominal pain, at which time her blood glucose was noted to be 357 mg/dL. Her Hba1c was 8.1%. She required rapid acting insulin, and throughout admission, her glucose ranged from 132 to 263 mg/dL. After discharge, a fasting glucose of over 250 mg/dL deemed her ineligible to have a PET/CT performed to assess disease status. MANAGEMENT AND OUTCOME: She was started on basal insulin, a DPP4-inhibitor, and a meglitinide analog. After initiation of therapy, her glucose levels were better controlled, and she was able to have her PET scan. Repeat Hba1c was 6.2% three months after initiation of glucose-lowering medications. She completed 6 cycles of BV + AVD therapy, with improving finger stick blood glucose (FSBG), and repeat Hba1c 1 month after completion of therapy was 5.2% on metformin monotherapy. DISCUSSION: Reports of brentuximab-induced hyperglycemia are rare in the literature, noted in just a few studies and one case report. Our case demonstrates a need to monitor blood glucose levels carefully during the initiation of BV therapy, especially in individuals with risk factors such as obesity, pre-diabetes mellitus, or diabetes mellitus.

Thyrotoxicosis after COVID-19 Infection with a Delay in Graves' Disease Antibody Positivity.

Background and Objective. Mounting evidence implicates COVID-19 as a cause of thyroid dysfunction, including thyrotoxicosis due to both thyroiditis and Graves' disease (GD). In this report, we present a case of thyrotoxicosis following COVID-19 infection that was ultimately found to represent GD with significantly delayed diagnostic serum antibody positivity. Case Report. A 65-year-old woman with a history of uncomplicated COVID-19 infection one month prior, presented to the Emergency Department with exertional dyspnea and palpitations, and was found to be in atrial fibrillation with rapid ventricular response (AF with RVR). Labs showed subclinical hyperthyroidism and the patient was started on a beta-blocker and methimazole. One month later, thyroid-stimulating immunoglobulin (TSI) resulted negative and thyroid function tests had normalized. The clinical picture suggested thyroiditis, and methimazole was stopped. One month later, the patient again presented in AF with RVR, with labs showing overt biochemical thyrotoxicosis. Antibodies were re-tested, and the thyrotropin receptor antibody (TRAb) and TSI resulted positive, confirming GD. Discussion. Most notable in this case is the feature of delayed GD antibody positivity: the diagnostic immunoassay for GD resulted negative one and two months after infection, but was ultimately positive three months after infection. To the authors' knowledge, this represents the longest delayed antibody positivity reported to date, amongst cases of new-onset GD following COVID. Conclusion. The clinical course of GD following COVID-19 infection is highly variable. This case underscores the need for vigilance in monitoring for delayed GD antibody positivity due to the important therapeutic implications of distinguishing thyroiditis from GD.

Tirzepatide for Weight Loss: Can Medical Therapy "Outweigh" Bariatric Surgery?

The worldwide prevalence of obesity has been increasing progressively over the past few decades and is predicted to continue to rise in coming years. Unfortunately, this epidemic is also affecting increasing rates of children and adolescents, posing a serious global health concern. Increased adiposity is associated with various comorbidities and increased mortality risk. Conversely, weight loss and chronic weight management are associated with improvements in overall morbidity and mortality. The pathophysiology of obesity is multifactorial with complex interactions between genetic and environmental factors. The foundation of most weight loss plans is lifestyle modification including dietary change and exercise. However, lifestyle modification alone is often insufficient to achieve clinically meaningful weight loss due to physiological mechanisms that limit weight reduction and promote weight regain. Therefore, research has focused on adjunctive pharmacotherapy to enable patients to achieve greater weight loss and improved chronic weight maintenance compared to lifestyle modification alone. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin hormone analogs that have proven effective for the management of type 2 diabetes mellitus as well as obesity and overweight. Tirzepatide is a novel "twincretin" that functions as a dual glucose-dependent insulinotropic polypeptide and GLP-1 RA. Tirzepatide was recently approved by the Food and Drug Administration for the management of type 2 diabetes. Similar to previously approved GLP-1RAs, weight loss is a common side effect of tirzepatide which prompted research focused on its use as a primary weight loss therapy. Although this drug has not yet been approved as an antiobesity medication, there are several phase 3 clinical trials that have demonstrated superior weight loss efficacy compared with previously approved medications. This review article will discuss the discovery and mechanism of tirzepatide, as well as the completed and ongoing trials that may lead to its approval as an adjunctive pharmacotherapy for weight loss.

Weight-loss response to naltrexone/bupropion is modulated by the Taq1A genetic variant near DRD2 (rs1800497): A pilot study.

Naltrexone/bupropion (NB) is a US Food and Drug Administration-approved antiobesity medication. Clinical trials have shown variable weight loss, with responders and non-responders. NB is believed to act on central dopaminergic pathways to suppress appetite. The Taq1A polymorphism near DRD2 (rs1800497) is associated with the density of striatal dopamine D2 receptors, with individuals carrying the A allele (AA or AG; termed A1+) having 30%-40% fewer dopamine binding sites than those who do not carry the A allele (GG; termed A1-). We performed a pilot study to assess the association of the rs1800497 ANKK1 c.2137G > A (p.Glu713Lys) variant with weight loss with NB treatment in 33 subjects. Mean (SD) weight loss was 5.9% (3.2%) for the A1+ genotype group (n = 15) and 4.2% (4.2%) for the A1- genotype group (n = 18). The mean weight loss for the A1+ genotype group was significantly greater than the predefined clinically significant 4% weight-loss target (one-sample t-test, P = .035), whereas the mean weight loss for the A1- genotype group was not (P = .85). Individuals with the A1+ genotype appear to respond better to NB than A1- individuals.

Sleeve Gastrectomy and Roux-en-Y Gastric Bypass Achieve Similar Early Improvements in Beta-cell Function in Obese Patients with Type 2 Diabetes.

Bariatric surgery is a treatment option for obese patients with type 2 diabetes mellitus (T2DM). Although sleeve gastrectomy (SG) is growing in favor, some randomized trials show less weight loss and HbA1c improvement compared with Roux-en-Y gastric bypass (RYGB). The study objective was to compare changes in beta-cell function with similar weight loss after SG and RYGB in obese patients with T2DM. Subjects undergoing SG or RYGB were studied with an intravenous glucose tolerance test before surgery and at 5-12% weight loss post-surgery. The primary endpoint was change in the disposition index (DI). Baseline BMI, HbA1c, and diabetes-duration were similar between groups. Mean total weight loss percent was similar (8.4% ± 0.4, p = 0.22) after a period of 21.0 ± 1.7 days. Changes in fasting glucose, acute insulin secretion (AIR), and insulin sensitivity (Si) were similar between groups. Both groups showed increases from baseline to post-surgery in DI (20.2 to 163.3, p = 0.03 for SG; 31.2 to 232.9, p = 0.02 for RYGB) with no significant difference in the change in DI between groups (p = 0.53). Short-term improvements in beta-cell function using an IVGTT were similar between SG and RYGB. It remains unclear if longer-term outcomes are better after RYGB due to greater weight loss and/or other factors.

Geometry-independent inclusion of basal myocardium yields improved cardiac magnetic resonance agreement with echocardiography and necropsy quantified left-ventricular mass.

OBJECTIVES: Left-ventricular mass (LVM) is widely used to guide clinical decision-making. Cardiac magnetic resonance (CMR) quantifies LVM by planimetry of contiguous short-axis images, an approach dependent on reader-selection of images to be contoured. Established methods have applied different binary cut-offs using circumferential extent of left-ventricular myocardium to define the basal left ventricle (LV), omitting images containing lesser fractions of left-ventricular myocardium. This study tested impact of basal slice variability on LVM quantification. METHODS: CMR was performed in patients and laboratory animals. LVM was quantified with full inclusion of left-ventricular myocardium, and by established methods that use different cut-offs to define the left-ventricular basal-most slice: 50% circumferential myocardium at end diastole alone (ED50), 50% circumferential myocardium throughout both end diastole and end systole (EDS50). RESULTS: One hundred and fifty patients and 10 lab animals were studied. Among patients, fully inclusive LVM (172.6±42.3g) was higher vs. ED50 (167.2±41.8g) and EDS50 (150.6±41.1g; both P<0.001). Methodological differences yielded discrepancies regarding proportion of patients meeting established criteria for left-ventricular hypertrophy and chamber dilation (P<0.05). Fully inclusive LVM yielded smaller differences with echocardiography (Δ=11.0±28.8g) than did ED50 (Δ=16.4±29.1g) and EDS50 (Δ=33.2±28.7g; both P<0.001). Among lab animals, ex-vivo left-ventricular weight (69.8±13.2g) was similar to LVM calculated using fully inclusive (70.1±13.5g, P=0.67) and ED50 (69.4±13.9g; P=0.70) methods, whereas EDS50 differed significantly (67.9±14.9g; P=0.04). CONCLUSION: Established CMR methods that discordantly define the basal-most LV produce significant differences in calculated LVM. Fully inclusive quantification, rather than binary cut-offs that omit basal left-ventricular myocardium, yields smallest CMR discrepancy with echocardiography-measured LVM and non-significant differences with necropsy-measured left-ventricular weight.

Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations.

BACKGROUND: Patients with long QT syndrome (LQTS) who harbor multiple mutations (i.e. ≥ 2 mutations in ≥ 1 LQTS-susceptibility gene) may experience increased risk for life-threatening cardiac events. OBJECTIVES: The present study was designed to compare the clinical course of LQTS patients with multiple mutations to those with a single mutation. METHODS: The risk for life-threatening cardiac events (comprising aborted cardiac arrest, implantable defibrillator shock, or sudden cardiac death) from birth through age 40 years, by the presence of multiple vs. single mutations, was assessed among 403 patients from the LQTS Registry. RESULTS: Patients with multiple mutations (n=57) exhibited a longer QTc at enrollment compared with those with a single mutation (mean ± SD: 506 ± 72 vs. 480 ± 56 msec, respectively; P=0.003) and had a higher rate of life threatening cardiac events during follow-up (23% vs. 11%, respectively; p=0.031). Consistently, multivariate analysis demonstrated that patients with multiple mutations had a 2.3-fold (P=0.015) increased risk for life threatening cardiac events as compared to patients with a single mutation. The presence of multiple mutations in a single LQTS gene was associated with a 3.2-fold increased risk for life threatening cardiac events (P=0.010) whereas the risk associated with multiple mutation status involving >1 LQTS gene was not significantly different from the risk associated with a single mutation (HR 1.7, P=0.26). CONCLUSIONS: LQTS patients with multiple mutations have a greater risk for life-threatening cardiac events as compared to patients with a single mutation.

Long QT syndrome in African-Americans.

BACKGROUND: We evaluated the risk factors and clinical course of Long QT syndrome (LQTS) in African-American patients. METHODS: The study involved 41 African-Americans and 3456 Caucasians with a QTc > or = 450 ms from the U.S. portion of the International LQTS Registry. Data included information about the medical history and clinical course of the LQTS patients with end points relating to the occurrence of syncope, aborted cardiac arrest, or LQTS-related sudden cardiac death from birth through age 40 years. The statistical analyses involved Kaplan-Meier time to event graphs and Cox regression models for multivariable risk factor evaluation. RESULTS: The QTc was 29 ms longer in African-Americans than Caucasians. Multivarite Cox analyses with adjustment for decade of birth revealed that the cardiac event rate was similar in African-Americans and Caucasians with LQTS and that beta-blockers were equally effective in reducing cardiac events in the two racial groups. CONCLUSIONS: The clinical course of LQTS in African-Americans is similar to that of Caucasians with comparable risk factors and benefit from beta-blocker therapy in the two racial groups.

Influence of diabetes mellitus on outcome in patients over 40 years of age with the long QT syndrome.

Diabetes mellitus can affect ventricular repolarization, and we investigated the impact of diabetes on the risk for cardiac events in older patients with long QT syndrome (LQTS). The study population consisted of 1,152 patients with QTc interval >/=450 ms who were enrolled in the United States portion of the International Long QT Syndrome Registry and survived >40 years of age. Patients were categorized as having diabetes if they received oral diabetic medication or insulin. End points after 40 years of age included first cardiac event (syncope, aborted cardiac arrest, sudden cardiac death, whichever occurred first) and all-cause mortality. Follow-up extended from 41 to 75 years of age. Risk factors for end points were evaluated by the Cox model. During follow-up, 193 patients had a first cardiac event, and 99 patients died. Of patients with LQTS, development of diabetes in adult patients with LQTS was not associated with an increased risk of first cardiac events dominated by syncope. Risk factors for mortality were syncope before 41 years of age, QTc interval > or =500 ms, heart rate >80 beats/min, and diabetes; there was no mortality interaction involving diabetes and QTc interval > or =500 ms. In conclusion, diabetes and prolonged QTc interval contributed independent mortality risks in adult patients with LQTS, with no interaction between these 2 risk factors.

Clinical implications for patients with long QT syndrome who experience a cardiac event during infancy.

OBJECTIVES: This study was designed to evaluate the clinical and prognostic aspects of long QT syndrome (LQTS)-related cardiac events that occur in the first year of life (infancy). BACKGROUND: The clinical implications for patients with long QT syndrome who experience cardiac events in infancy have not been studied previously. METHODS: The study population of 3,323 patients with QT interval corrected for heart rate (QTc) > or =450 ms enrolled in the International LQTS Registry involved 20 patients with sudden cardiac death (SCD), 16 patients with aborted cardiac arrest (ACA), 34 patients with syncope, and 3,253 patients who were asymptomatic during the first year of life. RESULTS: The risk factors for a cardiac event among 212 patients who had an electrocardiogram recorded in the first year of life included QTc > or =500 ms, heart rate < or =100 beats/min, and female sex. An ACA before age 1 year was associated with a hazard ratio of 23.4 (p < 0.01) for ACA or SCD during ages 1 to 10 years. During the 10-year follow-up after infancy, beta-blocker therapy was associated with a significant reduction in ACA/SCD only in those with a syncopal episode within 2 years before ACA/SCD but not for those who survived ACA in infancy. CONCLUSIONS: Patients with LQTS who experience ACA during the first year of life are at very high risk for subsequent ACA or death during their next 10 years of life, and beta-blockers might not be effective in preventing fatal or near-fatal cardiac events in this small but high-risk subset.