Current role of pasireotide in the treatment of acromegaly.

"First-generation" somatostatin receptor agonists (SSTRAs) octreotide and lanreotide are the most commonly used first-line pharmacological therapy for patients with acromegaly. A subset of patients respond only partially or not at all to the first-generation SSTRA, necessitating the use of additional pharmacological agents or other modes of therapy. Pasireotide is a "second-generation" SSTRA that has multi-receptor activity. Prospective studies have shown promise in the use of pasireotide in patients with poor response to first-generation SSTRA. Here we elucidate the molecular pathways of resistance to first-generation SSTRA, the mechanism of action, pre-clinical and clinical evidence of the use of pasireotide in patients having incomplete / lack of response to first-generation SSTRA. We also discuss the clinical, pathological, and radiological markers predicting response to pasireotide, and the difference in side-effect profiles of pasireotide, compared to first-generation SSTRA.

Type B Insulin Resistance Syndrome: A Rare Cause of Hypoglycemia.

We describe a case of a Black female patient with a history of type 2 diabetes mellitus and systemic lupus erythematosus, who had a subacute onset of severe hypoglycemia that persisted after cessation of insulin therapy. Biochemical testing revealed hyperinsulinemic hypoglycemia, normal serum triglycerides, and high-normal serum adiponectin levels. Abdominal imaging demonstrated an 11-mm cystic pancreatic lesion. Her clinical history and biochemical test results raised suspicion for type B insulin resistance syndrome (TBIRS), which was confirmed on anti-insulin receptor antibody testing. The patient's hypoglycemia was managed with dietary modification therapy and continuous glucose monitoring. The severity and frequency of hypoglycemic episodes decreased spontaneously. We describe TBIRS and its uncommon hypoglycemic presentation, analyze factors that put TBIRS among the differential diagnosis, and discuss the treatment of TBIRS-associated hypoglycemia.

Acute heart failure with incidentally found cystic adrenal mass.

Summary: Pheochromocytomas are rare adrenal tumors characterized by excessive catecholamine secretion. Symptoms and signs associated with pheochromocytomas are usually intermittent and chronic but can rarely develop into life-threatening crises. We describe a case of acute severe congestive heart failure in a previously healthy female, who recovered rapidly (4 days after admission) with acute medical therapy. The etiology on evaluation was a spontaneous bleed in a previously undiagnosed pheochromocytoma, resulting in a pheochromocytoma crisis and transient stress cardiomyopathy, followed by quick recovery of cardiac function. Our aim is to describe pheochromocytoma as a rare cause of stress cardiomyopathy. We discuss the evaluation of pheochromocytoma during critical illness and triggers/treatment strategies for pheochromocytoma crises. Learning points: Hemorrhage in a pheochromocytoma can result in a pheochromocytoma crisis, with sudden release of excess catecholamines resulting in multisystem organ dysfunction and high mortality. Acute decompensated heart failure can be a rare presentation of pheochromocytoma, in a patient with no cardiac risk factors. Measurement of metanephrines in acutely stressful clinical situations can have considerable overlap with the biochemical picture of pheochromocytoma. Early imaging studies may help with the differential diagnosis. Pheochromocytoma should be ruled out before performing an adrenal biopsy. Emergent adrenalectomy in pheochromocytoma crisis results in high mortality. Medical management of the acute crisis followed by elective adrenalectomy after alpha-blockade results in better outcomes.

A Visual Diagnosis: Lipodystrophy.

Lipodystrophy syndromes are rare metabolic disorders characterized by local or generalized loss of adipose tissue, resulting in insulin resistance, dyslipidemia, and cosmetic disfiguration. The lipodystrophic phenotype is highly variable, with partial lipodystrophy often missed or misdiagnosed as other diseases from a lack of a proper physical examination and low physician awareness. Correct diagnosis is important for optimal treatment and follow-up strategies in these patients. The use of GLP-1 analogs has not been systematically evaluated in lipodystrophy and could be a potential precision medicine therapy. We aim to make the reader, particularly generalists or endocrinologists outside of tertiary referral centers, aware of the presentation and clinical features of partial lipodystrophy, emphasize the role of a full physical examination in diagnosis, and discuss therapeutic options, including GLP-1-based glycemic management illustrated by our clinical case.

Obesity and Aging.

The obesity epidemic in aging populations poses significant public health concerns for greater morbidity and mortality risk. Age-related increased adiposity is multifactorial and often associated with reduced lean body mass. The criteria used to define obesity by body mass index in younger adults may not appropriately reflect age-related body composition changes. No consensus has been reached on the definition of sarcopenic obesity in older adults. Lifestyle interventions are generally recommended as initial therapy; however, these approaches have limitations in older adults. Similar benefits in older compared with younger adults are reported with pharmacotherapy, however, large randomized clinical trials in geriatric populations are lacking.

Omega-3 Fatty Acids in Cardiovascular Disease and Diabetes: a Review of Recent Evidence.

PURPOSE OF REVIEW: Omega-3 fatty acids (n-3 FA) lower triglycerides, have anti-inflammatory properties, and improve metabolism. Clinical evidence of cardiovascular benefit with omega-3 fatty acids is mixed. We discuss mechanisms providing biological plausibility of benefit of omega-3 fatty acids in cardiovascular risk reduction and review clinical trials investigating the benefits of prescription omega-3 fatty acids in dyslipidemia, atherosclerotic cardiovascular disease (ASCVD), and diabetes. RECENT FINDINGS: Although early trials showed no benefit of omega-3 fatty acids in ASCVD, the REDUCE-IT trial noted significant risk reduction in ASCVD events with highly purified EPA (icosapent ethyl) use which has changed the landscape for currently available therapeutic options. However, other large trials like STRENGTH and VITAL, which used different formulations of prescription omega-3 fatty acids, did not note significant cardiovascular risk reduction. Thus the effectiveness of omega-3 fatty acids for cardiovascular disease prevention is an ongoing topic of debate. A relative paucity of studies examining benefits for glycemic outcomes in persons with diabetes exists; however, few studies have suggested lack of benefit to date. Significant residual cardiovascular risk exists for individuals with hypertriglyceridemia. Prescription omega-3 fatty acids are more commonly used for CV risk reduction in these patients. Clinical guideline statements now recommend icosapent ethyl use for selected individuals with hypertriglyceridemia to reduce cardiovascular events given recent evidence from the REDUCE-IT trial. Nonetheless, data from other large scale trials has been mixed, and future research is needed to better understand how different preparations of omega-3 may differ in their cardiovascular and metabolic effects, and the mechanisms for their benefit.

Time-Restricted Eating in Metabolic Syndrome-Focus on Blood Pressure Outcomes.

PURPOSE OF THE REVIEW: Time-restricted eating (TRE) is a promising dietary intervention for weight loss and improvement of cardiometabolic risk factors. We aim to provide a critical review of blood pressure outcomes reported in clinical TRE studies in adults with metabolic syndrome, in the context of the proposed mechanisms that underlie the relationship between timing of eating and blood pressure. RECENT FINDINGS: Clinical TRE studies report mixed results pertaining to blood pressure outcomes, likely due to significant heterogeneity in study design and TRE protocols. Mechanistically, TRE's metabolic benefits have been speculated to be mediated by alignment of meal timing with circadian regulation of metabolic processes and/or enhancement of catabolism as a result of prolonging the fasting period. TRE protocols that start and end earlier appear to have more pronounced blood pressure lowering effects. Blood pressure also tends to be lower with narrower eating windows. Concurrent weight loss is not consistently linked to blood pressure reduction, while lower insulin levels may be an important factor for blood pressure reduction. Notably, no published studies have reported 24-h blood pressure profiles or data on blood pressure variability. Blood pressure has only been examined in limited TRE studies, measured at a single time point. Given the clinical relevance of blood pressure's diurnal variability and the mechanistic evidence underlying timing of eating and blood pressure effects, more studies are needed to investigate TRE's effects on the diurnal variability of blood pressure.

Testosterone Replacement Therapy: A Narrative Review with a Focus on New Oral Formulations.

Male hypogonadism affects 10-30% of the male population and is often under-recognized and under-treated. Different replacement formulations exist, each with specific benefits and limitations. These replacements include gels, patches and short- and long-acting injectables. JATENZO® (oral testosterone undecanoate; Clarus Therapeutics Inc., Northbrook, IL, US) is the first oral formulation of testosterone approved by the US Food and Drug Administration. TLANDO® (oral testosterone undecanoate; Lipocine Inc., Salt Lake City, UT, US), another oral testosterone formulation, has also recently been approved by the US Food and Drug Administration. Based on unique chemistry using a self-emulsifying drug delivery system and lymphatic absorption, JATENZO and TLANDO address some of the limitations of other dosing routes while providing a safe option without evidence of liver dysfunction. This review discusses various testosterone treatment options, focusing on the role and pharmacokinetics of the new oral formulations.

Coronary revascularization in patients with stable coronary disease and diabetes mellitus.

PURPOSE OF STUDY: Diabetes mellitus accelerates the development of atherosclerosis. Patients with diabetes mellitus have higher incidence and mortality rates from cardiovascular disease and undergo a disproportionately higher number of coronary interventions compared to the general population. Proper selection of treatment modalities is thus paramount. Treatment strategies include medical management and interventional approaches including coronary artery bypass graft (CABG) surgery and percutaneous coronary interventions (PCI). The purpose of this review is to assimilate emerging evidence comparing CABG to PCI in patients with diabetes and present an outlook on the latest advances in percutaneous interventions, in addition to the optimal medical therapies in patients with diabetes. KEY METHODS: A systematic search of PubMed, Web of Science and EMBASE was performed to identify prospective, randomized trials comparing outcomes of CABG and PCI, and also PCI with different generations of stents used in patients with diabetes. Additional review of bibliography of selected studies was also performed. MAIN CONCLUSIONS: Most of the trials discussed above demonstrate a survival advantage of CABG over PCI in patients with diabetes. However, recent advances in PCI technology are starting to challenge this narrative. Superior stent designs, use of specific drug-eluting stents, image-guided stent deployment, and the use of contemporary antiplatelet and lipid-lowering therapies are continuing to improve the PCI outcomes. Prospective data for such emerging interventional technologies in diabetes is however lacking currently and is the need of the hour.