Lipoprotein Insulin Resistance Index: A Simple, Accurate Method for Assessing Insulin Resistance in South Asians.

Context: Identification of insulin resistance (IR) in South Asians, who are at a higher risk for type 2 diabetes, is important. Lack of standardization of insulin assays limits the clinical use of insulin-based surrogate indices. The lipoprotein insulin resistance index (LP-IR), a metabolomic marker, reflects the lipoprotein abnormalities observed in IR. The reliability of the LP-IR index in South Asians is unknown. Objective: We evaluated the predictive accuracy of LP-IR compared with other IR surrogate indices in South Asians. Methods: In a cross-sectional study (n = 55), we used calibration model analysis to assess the ability of the LP-IR score and other simple surrogate indices (Homeostatic Model Assessment of Insulin Resistance, Quantitative insulin sensitivity check index, Adipose insulin resistance index, and Matsuda Index) to predict insulin sensitivity (SI) derived from the reference frequently sampled intravenous glucose tolerance test. LP-IR index was derived from lipoprotein particle concentrations and sizes measured by nuclear magnetic resonance spectroscopy. Predictive accuracy was determined by root mean squared error (RMSE) of prediction and leave-one-out cross-validation type RMSE of prediction (CVPE). The optimal cut-off of the LP-IR index was determined by the area under the receiver operating characteristic curve (AUROC) and the Youden index. Results: The simple surrogate indices showed moderate correlations with SI (r = 0.53-0.69, P < .0001). CVPE and RMSE were not different in any of the surrogate indices when compared with LP-IR. The AUROC was 0.77 (95% CI 0.64-0.89). The optimal cut-off for IR in South Asians was LP-IR >48 (sensitivity: 75%, specificity: 70%). Conclusion: The LP-IR index is a simple, accurate, and clinically useful test to assess IR in South Asians.

Metastatic Grade 3 Neuroendocrine Tumor in Multiple Endocrine Neoplasia Type 1 Expressing Somatostatin Receptors.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) may occur in 30% to 90% of patients with multiple endocrine neoplasia type 1 (MEN1). However, only 1% of GEP-NETs are grade 3 (G3). Given the rarity of these aggressive tumors, treatment of advanced G3 GEP-NETs in MEN1 is based on the treatment guidelines for sporadic GEP-NETs. We report a 43-year-old male with germline MEN1 followed at our institution, with clinical features including hyperparathyroidism, a nonfunctional pancreatic NET, and Zollinger-Ellison syndrome. On routine surveillance imaging at age 40, computed tomography/positron emission tomography imaging showed 2 arterially enhancing intraluminal masses on the medial aspect of the gastric wall. Anatomical imaging confirmed 2 enhancing masses within the pancreas and a rounded mass-like thickening along the lesser curvature of the stomach. The gastric mass was resected, and pathology reported a well-differentiated G3 NET with a Ki-67 >20%. The patient continued active surveillance. Eighteen months later cross-sectional imaging studies showed findings consistent with metastatic disease within the right hepatic lobe and bland embolization was done. On follow-up scans, including 68Ga-DOTATATE (68Ga-DOTA(0)-Tyr(3)-octreotate) imaging, interval increase in number and avidity of metastatic lesions were compatible with disease progression. Given a paucity of treatment recommendations for G3 tumors in MEN1, the patient was counseled based on standard NET treatment guidelines and recommended 177Lu-DOTATATE treatment. PRRT (peptide receptor radionuclide therapy) with 177Lu-DOTATATE (177Lu-tetraazacyclododecanetetraacetic acid-octreotide) is an important therapeutic modality for patients with somatostatin receptor-positive NETs. However, prospective studies are needed to understand the role of PRRT in G3 NETs.

A Case of Undiagnosed Functional Gonadotroph Adenoma Leading to Ovarian Hyperstimulation Syndrome.

A functional gonadotroph adenoma is a very rare endocrinopathy, and only a few cases have been reported in the literature. We present a case of a woman in her early 50s with a past medical history of recurrent ovarian cysts who developed bilateral hemianopsia and was referred to the endocrinology clinic after a magnetic resonance imaging (MRI) identified a pituitary mass. Anterior pituitary hormone workup confirmed hypersecretion of follicle-stimulating hormone (FSH), which suggested ovarian hyperstimulation syndrome (OHSS) as the etiology of recurrent ovarian cysts. The patient underwent transsphenoidal resection of the pituitary tumor with improvement in visual symptoms. Our case illustrates that functional gonadotroph adenoma can be a potential cause of OHSS apart from the setting of assisted reproductive technology and hence warranting a meticulous endocrine evaluation to rule out this rare disease.

Gastrointestinal Complications of COVID-19 Vaccines.

Much of the control over the coronavirus disease 2019 (COVID-19) pandemic has been achieved by mass vaccination against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent that causes COVID-19. The COVID-19 mRNA (messenger RNA) vaccines are relatively newly approved and have been widely used in the US since they first became available. However, with passing time, data regarding adverse events associated with the mRNA vaccines have become clearer. Vaccines are safe in general, and the benefits outweigh the risks of adverse events. In this case report, we present the first documented case report of post-vaccination acute diverticulitis and colon micro-perforation following Moderna booster dose (Moderna Inc, Cambridge, USA) in a young adult. Vaccine recipients should be educated on vaccine-associated gastrointestinal (GI) adverse events in order to reduce morbidity and mortality. We also recommend that vaccine recipients with pre-existing GI disorders should be carefully monitored for the worsening of pre-existing conditions post-COVID-19 vaccination.

Clinical Effects of Sodium-Glucose Transporter Type 2 Inhibitors in Patients With Partial Lipodystrophy.

OBJECTIVE: Severe insulin resistance syndromes, such as lipodystrophy, lead to diabetes, which is challenging to control. This study explored the safety and efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in a series of 12 patients with severe insulin resistance due to partial lipodystrophy. METHODS: A retrospective chart review of the safety (N = 22) and efficacy (N = 12) of SGLT2is in patients with partial lipodystrophy was conducted at our institution. The efficacy outcomes included hemoglobin A1C level, insulin dose, fasting plasma glucose level, C-peptide level, lipid profile, 24-hour urinary glucose excretion, estimated glomerular filtration rate, and blood pressure before and after 12 months of SGLT2i treatment. RESULTS: The hemoglobin A1C level decreased after SGLT2i treatment (at baseline: 9.2% ± 2.0% [77.0 ± 21.9 mmol/mol]; after 12 months: 8.4% ± 1.8% [68.0 ± 19.7 mmol/mol]; P = .028). Significant reductions were also noted in systolic (P = .011) and diastolic blood pressure (P = .013). There was a trend toward a decreased C-peptide level (P = .071). The fasting plasma glucose level, lipid level, and estimated glomerular filtration rate remained unchanged. The adverse effects included extremity pain, hypoglycemia, diabetic ketoacidosis (in a patient who was nonadherent to insulin), pancreatitis (in a patient with prior pancreatitis), and fungal infections. CONCLUSION: SGLT2is reduced the hemoglobin A1C level in patients with partial lipodystrophy, with a similar safety profile compared with that in patients with type 2 diabetes. After individual consideration of the risks and benefits of SGLT2is, these may be considered a part of the treatment armamentarium for these rare forms of diabetes, but larger trials are needed to confirm these findings.

COVID-19 and chronic fatigue syndrome: An endocrine perspective.

Patients recovering from COVID-19 may have persistent debilitating symptoms requiring long term support through individually tailored cardiopulmonary and psychological rehabilitation programs. Clinicians need to be aware about the likely long-term complications and their diagnostic assessments to help identify any occult problems requiring additional help. Endocrinological evaluations should be considered as part of the armamentarium in the management of such individuals with diligent cognizance about the involvement of the hypothalamo-pituitary-adrenal (HPA) axis, adrenal and thyroid function. We here review the literature and potential pathophysiological mechanisms involved in and related to post COVID-19 symptoms with an emphasis on endocrine function.

Climate Change and Obesity.

Global warming and the rising prevalence of obesity are well described challenges of current mankind. Most recently, the COVID-19 pandemic arose as a new challenge. We here attempt to delineate their relationship with each other from our perspective. Global greenhouse gas emissions from the burning of fossil fuels have exponentially increased since 1950. The main contributors to such greenhouse gas emissions are manufacturing and construction, transport, residential, commercial, agriculture, and land use change and forestry, combined with an increasing global population growth from 1 billion in 1800 to 7.8 billion in 2020 along with rising obesity rates since the 1980s. The current Covid-19 pandemic has caused some decline in greenhouse gas emissions by limiting mobility globally via repetitive lockdowns. Following multiple lockdowns, there was further increase in obesity in wealthier populations, malnutrition from hunger in poor populations and death from severe infection with Covid-19 and its virus variants. There is a bidirectional relationship between adiposity and global warming. With rising atmospheric air temperatures, people typically will have less adaptive thermogenesis and become less physically active, while they are producing a higher carbon footprint. To reduce obesity rates, one should be willing to learn more about the environmental impact, how to minimize consumption of energy generating carbon dioxide and other greenhouse gas emissions, and to reduce food waste. Diets lower in meat such as a Mediterranean diet, have been estimated to reduce greenhouse gas emissions by 72%, land use by 58%, and energy consumption by 52%.

Nonseminomatous Germ-Cell Tumor Presenting as Bilateral Adrenal Masses.

OBJECTIVE: Many tumors can metastasize to the adrenal glands, making the diagnosis of adrenal masses challenging. Awareness that rare primary tumors can metastasize to the adrenals and consideration of biopsy for their diagnosis, sometimes at extra-adrenal sites, is essential to prevent unnecessary adrenalectomies and facilitate the right treatment. We report a rare case of bilateral adrenal masses due to metastasis from a nonseminomatous germ-cell tumor of a retroperitoneal lymph node origin. METHODS: The diagnosis of the adrenal masses from the nonseminomatous germ-cell tumor of a retroperitoneal lymph node origin was based on a retroperitoneal lymph node core biopsy. An initial core biopsy of the adrenal gland revealed necrotic tissue and inflammatory cells without evidence of malignancy. Due to nondiagnostic findings, the core biopsy was repeated, which showed degenerating cells with a high mitotic index and immunohistochemical staining positive for vimentin, suggesting the possibility of a high-grade sarcoma. A retroperitoneal lymph node biopsy was performed. The patient was started on chemotherapy. RESULTS: A 34-year-old man presented with acute left upper-abdominal pain of 2 weeks and tenderness on the left upper quadrant of the abdomen, and he was found to have bilateral adrenal masses. Laboratory results showed the following: adrenocorticotropic hormone 41 pg/mL (7-69 pg/mL), metanephrine <0.1 nmol/L (0-0.49 nmol/L), normetanephrine 0.99 nmol/L (0-0.89 nmol/L), and morning cortisol 3.1 µg/dL after a 1-mg dexamethasone-suppression test. His dehydroepiandrosterone sulfate level was 62 µg/dL (120-520 µg/dL), and 17OH progesterone level was 36 ng/dL (<138 ng/dL); androstenedione and serum estradiol levels were normal. Laboratory tests for tumor markers revealed the following: testosterone 21 ng/dL (241-827 ng/dL), prostate-specific antigen 0.57 ng/mL (0-4 ng/mL), alpha-fetoprotein 1.9 IU/mL (0.6-6 IU/ml), and beta-human chorionic gonadotropin 134 mIU/mL (0-1 mIU/mL). CONCLUSION: We report a rare case of rapidly progressing adrenal masses in a young man, found to have metastasized from nonseminomatous germ-cell tumors. Histopathologic confirmation of the metastatic tumor was done, which prevented unnecessary adrenalectomy. The patient received appropriate chemotherapy.

The looming storm: Blood and cytokines in COVID-19.

A novel coronavirus termed as COVID-19 by WHO has been the causative agent of an unprecedented pandemic in the history of humanity. The global burden of mortality and morbidity associated with this pandemic continues to increase with each passing day as it is progressively leading to multiorgan dysfunction. In most cases, the cause of death has been attributed to respiratory failure, sepsis, cardiac failure, kidney injury, or coagulopathy. As more knowledge is being unfolded, an in-depth understanding of various systemic manifestations and complications of SARS-CoV2 is vital for optimum management of these patients. This novel virus is known to spread faster than its two ancestors, the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), demonstrating a case fatality ranging from 5 to 8% [1]. Hematological abnormalities such as lymphopenia, thrombocytopenia, elevated D-Dimer, elevated fibrinogen, elevated fibrinogen degradation products as well as cytokines such as IL-6 are emerging as important prognostic marker for worse outcome of COVID-19. Among various systemic manifestations, hematological complications such as venous thrombosis causing pulmonary embolism or deep vein thrombosis, and arterial thrombosis causing myocardial infarction, strokes or limb ischemia are being noted to be directly linked to high mortality from COVID-19. An attempt to understand the pathophysiology of various hematological abnormalities including cytokine storm, hypercoagulable state and some rare presentations of this disease hence becomes imperative. Through this review, we aim to provide an up-to-date summary of current evidence-based literature of hematological manifestations, their consequences and management including role of anticoagulation and drugs targeting cytokine storm in patients with SARS-CoV-2.

Patients With MEN1 Are at an Increased Risk for Venous Thromboembolism.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder predisposing the development of multiple functional and nonfunctional neuroendocrine tumors (NETs). Only uncommon MEN1-associated functional NETs such as glucagonomas (<1%) and adenocorticotropic hormone-producing tumors (<5%) are known to be associated with hypercoagulability. It is unknown if patients with MEN1 generally have an increased risk of venous thromboembolism (VTE). METHODS: We queried a prospective natural history study of germline mutation-positive MEN1 patients (n = 286) between 1991 and 2019 for all lifetime events of VTE. The search terms were: DVT, thromb, embol, PE, pulmonary embolism, clot, hematology consult, anticoagulant, coumadin, lovenox, xarelto, warfarin, aspirin, rivaroxaban, and apixaban. Incidence rates were calculated, accounting for age and sex. Comparisons were made to published incidence rates in healthy populations, different types of cancer, and Cushing's syndrome. RESULTS: Thirty-six subjects (median age 45 years, range 16-75) experienced a VTE event, yielding a prevalence rate of 12.9%. The age-sex adjusted incidence rate of VTE is 9.11 per 1000 patient-years, with a sex-adjusted lifetime incidence rate of 2.81 per 1000 patient-years. MEN1-associated lifetime incidence rates are ~2-fold higher than the estimated annual incidence rate in the general population and are comparable to the known risk in the setting of various types of cancer. Approximately 80% of patients who had a VTE were diagnosed with pancreatic NETs, of which 24% were insulinomas. Fourteen patients (42%) experienced perioperative VTE events. CONCLUSIONS: MEN1 patients have an increased risk of VTE. Further mechanistic investigation and validation from other MEN1 cohorts are needed to confirm the increased prevalence of VTE in MEN1.

Metabolic Syndrome and COVID 19: Endocrine-Immune-Vascular Interactions Shapes Clinical Course.

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Individuals with metabolic syndrome are at increased risk for poor disease outcomes and mortality from COVID-19. The pathophysiologic mechanisms for these observations have not been fully elucidated. A critical interaction between SARS-CoV-2 and the angiotensin-converting enzyme 2 (ACE2) facilitates viral entry into the host cell. ACE2 is expressed in pancreatic islets, vascular endothelium, and adipose tissue, and the SARS-CoV-2 -ACE2 interaction in these tissues, along with other factors, governs the spectrum and the severity of clinical manifestations among COVID-19 patients with metabolic syndrome. Moreover, the pro-inflammatory milieu observed in patients with metabolic syndrome may contribute toward COVID-19-mediated host immune dysregulation, including suboptimal immune responses, hyperinflammation, microvascular dysfunction, and thrombosis. This review describes the spectrum of clinical features, the likely pathophysiologic mechanisms, and potential implications for the management of metabolic syndrome in COVID-19 patients.

ADRENAL INSUFFICIENCY SECONDARY TO BILATERAL ADRENAL HEMORRHAGE ASSOCIATED WITH ANTIPHOSPHOLIPID SYNDROME.

OBJECTIVE: Antiphospholipid syndrome (APS) can involve multiple organ systems but endocrine manifestations are rare. In most cases adrenal insufficiency (AI) is the first endocrine manifestation of APS. The prompt diagnosis of AI is critical as this disorder is a life-threatening disease that may lead to fatal outcomes if left untreated. We present a case of AI associated with APS the patient was diagnosed promptly and managed successfully. METHODS: The diagnosis of APS was based on a combination of clinical features (deep venous thrombosis and pulmonary embolism) and laboratory findings (lupus anticoagulant, anticardiolipin antibody, anti-beta-2 glycoprotein-I antibody), without alternative diagnosis to explain the clinical findings. AI was diagnosed by low morning serum cortisol with elevated adrenocorticotropic hormone (ACTH) level as well as an ACTH stimulation test. RESULTS: A 50-year-old male presented with deep venous thrombosis of the left extremity diagnosed by compressive ultrasound, and was subsequently diagnosed with a pulmonary embolism by computed tomography angiography and treated with heparin. Two days later, he developed hypotension and bilateral flank pain, and an abdominal computed tomography scan revealed bilateral adrenal hemorrhage. Laboratory results showed a serum cortisol of 3.3 mcg/dL (stress normal, 25 to 35 mcg/dL) and ACTH of 319 pg/mL (stress normal, 128 to 218 pg/mL), consistent with primary AI. Symptoms improved quickly with hydrocortisone therapy. The patient still required glucocorticoid therapy for at least 4 years thereafter. CONCLUSION: In all cases of adrenal hemorrhage and infarction with unknown etiology, screening with lupus anticoagulant and anticardiolipin antibodies is imperative. Recognition of this high-mortality condition allows for appropriate screening and confirmatory tests leading to a prompt diagnosis and timely management.

Nanomedicine in coronary artery disease.

Nanomedicine is one of the most promising therapeutic modalities researchers are working on. It involves development of drugs and devices that work at the nanoscale (10-9m). Coronary artery disease (CAD) is responsible for more than a third of all deaths in age group >35 years. With such a huge burden of mortality, CAD is one of the diseases where nanomedicine is being employed for preventive and therapeutic interventions. Nanomedicine can effectively deliver focused drug payload at sites of local plaque formation. Non-invasive strategies include thwarting angiogenesis, intra-arterial thrombosis and local inflammation. Invasive strategies following percutaneous coronary intervention (PCI) include anti-restenosis and healing enhancement. However, before practical application becomes widespread, many challenges need to be dealt with. These include manufacturing at the nanoscale, direct nanomaterial cellular toxicity and visualization.