Abstract A 54-year-old female admitted for nausea and vomiting found to have hypernatremia. Four months prior to this admission, patient had undergone emergent craniotomy for an intraparenchymal hemorrhage. Found to have a 7.8 cm hemorrhagic and partially necrotic mass. Pathology consistent with anaplastic oligodendroglioma. She began radiation and temozolomide 2 months after surgery. On this admission for nausea and vomiting, sodium noted to be elevated at 154 mmol/L (136-145 mmol/L). Initially thought to be due to dehydration and started on intravenous fluids. Urine output noted to increase to 2-3 liters/day with persistently elevated sodium. Urine studies and labs collected while sodium 155 mmol/L significant for urine osmolality 128 mOsm/kg (50-1200 mOsm/kg), serum osmolality 330 mOsm/kg (280-295), and urine sodium 34 mmol/L. Given patient's history of prior craniotomy, radiation, and temozolomide, suspected central diabetes insipidus but DDAVP challenge with 4 mcg did not result in a lower urine output and urine osmolality remained <300 mOsm/kg. Repeat DDAVP challenge produced similar results. Evaluation of other central axis deficiencies revealed normal Free T4 (1.21 ng/dL). Unable to assess for adrenal insufficiency due to patient already on high-dose steroids for malignancy. Workup was turned to potential nephrogenic etiology as patient had been started on pantoprazole during her initial diagnosis 4 months prior. Co-peptin while sodium 148 mmol/L returned at 27.6 pmol/L (<13.1 pmol/L), indicative for nephrogenic diabetes insipidus. Patient was started on amiloride 5 mg twice a day and hydrochlorothiazide 25 mg twice a day with improvement noted in both sodium and urine output. Did discuss renal biopsy to rule-out interstitial nephritis from pantoprazole but given patient was on anti-coagulation for sub-massive pulmonary embolism, biopsy was deferred. Ultimately patient was discharged on amiloride 10 mg and hydrochlorothiazide 25 mg daily with sodium 142 mmol/L. She continued to receive temozolomide but eventually both amiloride and hydrochlorothiazide were held during a subsequent admission about a month later due to hyponatremia from poor oral intake. Sodium remained stable for about 5 months off medication at which time patient was re-started on amiloride for hypernatremia. Unfortunately patient passed due to complications from thrombosis. Review of PubMed revealed only 1 additional case report of a patient on temozolomide who developed nephrogenic diabetes insipidus but that patient was also on sulfamethoxazole-trimethoprim which was most likely the cause. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

An 81-year-old woman presented to the emergency department for evaluation of shortness of breath, dysphagia and chest tightness. In the emergency department, imaging was obtained, with CXR showing complete opacification of R hemithorax. Follow up imaging with CT Chest showed large mediastinal mass contingent with the right lobe of the thyroid, along with large volume (transudative) pleural effusion. Patient underwent thoracentesis with improvement in her shortness of breath, but chest tightness persisted. IR biopsy was obtained, which confirmed the mass was indeed thyroid in origin. At this time, Endocrinology was consulted for concerns of thyrotoxicosis, along with the goiter, as lab work returned with suppressed TSH (<0.01 mcIU/mL), normal Free T4 (1.14 ng/dL). On examination, the Endocrinology team found the patient to be clinically euthyroid, with normal vital signs and only ongoing complaints of chest tightness with deep inspiration. Decision was made to go forward with resection of the mass, with a multidisciplinary approach involving ENT and Cardiothoracic Surgery. The ENT team began the procedure by dissecting the right lobe from the remaining thyroid tissue. The gland was noted to track inferiorly and posteriorly into the chest, and the decision was made to truncate the portion of the gland superior to the clavicle. At the time it was felt that further manipulation of the gland was a high risk from this position. The patient was then handed off to the cardiothoracic surgery team who, using robotic assistance, took a transdiaphragmatic approach. After roughly 3 hours of dissection, the goiter was placed in an endo-catch bag and was able to be removed through a transabdominal/diaphragmatic incision. The remainder of the left lobe was safely left in place. In the end the removed portion of the goiter was found to be 13.7 cm in length and weighed 532 g. Average thyroid weight in iodine replete populations remains roughly 20 g. Pathology returned as adenomatoid hyperplasia in all 4 specimens. Postoperatively the patient did well and follow up with Endocrinology was scheduled. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

The worldwide prevalences of diabetes mellitus (DM) and of heart failure (HF) have collectively been on the rise. HF accounts for a large portion of the cardiovascular mortality and morbidity associated with DM. DM increases the risk of developing heart failure by promoting atherosclerosis and exerting direct deleterious effects on the myocardium. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are agents approved for the treatment of DM; they exert their anti-hyperglycemic effects by blocking renal reabsorption of glucose and inducing glycosuria. SGLT-2 inhibitors have consistently decreased the hospitalization rate of HF and cardiovascular mortality in several clinical trials. SGLT-2 inhibitors also possess anti-inflammatory, anti-fibrotic, and antihypertensive in addition to beneficial effects on the myocardial metabolism, which may account for their heart failure benefits. However, further research still needs to be done to evaluate the use of SGLT-2 inhibitors in non-diabetic patients and their efficacy in preventing or treating different heart failure phenotypes.

Purpose of Review Heart failure is responsible for a significant part of diabetes-associated cardiovascular mortality and morbidity. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are novel agents approved for the treatment of diabetes mellitus; in recent clinical trials, these agents have shown a significant reduction in cardiovascular death and hospitalization secondary to heart failure. Recent Findings Clinical trials with specific heart failure outcomes have shown the benefit of SGLT-2 inhibitors in reducing the mortality and morbidity associated with heart failure. The guidelines for the management of diabetes mellitus recommend the preferential use of SGLT-2 inhibitors in patients with a history of cardiovascular disease. SGLT-2 inhibitors are potential game changers in the treatment of heart failure. Guidelines for prescription of these agents help assess risk-benefit analysis and personalize treatment for maximal benefit.

A 47-year-old female patient with type 1 diabetes, end-stage renal disease (ESRD), and congestive heart failure was admitted with chest pain and dyspnea. Physical examination was significant for bibasilar crepitation, jugular venous distention, and pedal edema consistent with volume overload.

Sodium-glucose cotransport protein-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to reduce cardiovascular events in high-risk patients with type 2 diabetes mellitus (T2DM). We examined real-world use of these agents at a US academic medical center in the state of Mississippi. Prescriptions, provider specialty, and insurance status of users of SGLT2is and GLP-1RAs in patients with T2DM, and T2DM and cardiovascular disease (CVD) seen from 1st January 2013 to 30th June 2019 were obtained by electronic health records review. We identified 21,173 patients with T2DM and CVD. Overall, 306 (1.4%) and 349 (1.6%) patients received a SGLT2i and GLP-1RA, respectively. After the US Food and Drug Administration (FDA) expanded empagliflozin and liraglutide indications, a mean difference of 19.2 and 12.7 greater quarterly new prescriptions was noted, respectively, whereas no such rise in canagliflozin was observed. Primary care physicians accounted for 53.4% SGLT2i prescriptions, endocrinology for 30.3%, and cardiology for 6.0%. Primary care physicians accounted for 45.1% GLP-1RA prescriptions, endocrinology for 45.0%, and cardiology for 1.4%. Prescription patterns did not largely differ by patient insurance status. In conclusion, prescription of evidence-based therapies to improve CVD outcomes in high-risk patients with T2DM remains very low after several years of evidence generation. Low uptake was evident across insurance types. Modest increases in use were observed after regulatory expansions in labeling; however, cardiologists rarely engaged in prescription, underscoring the need for widespread implementation strategies across health care systems.

Giant prolactinomas are rare and constitute only 2-3% of prolactinomas. They are defined as prolactinomas greater than 4 cm in size with a prolactin level of > 1,000 µg/L. Unlike prolactinomas, giant prolactinomas have a male preponderance and present a decade earlier in men as compared to women. Giant prolactinomas may present with galactorrhea, irregular periods or decreased libido. Due to their large size, they can involve surrounding brain structures and may present with hydrocephalus, dizziness, seizures, deafness, and cognitive dysfunction. Laboratory assessment may reveal a falsely low prolactin level secondary to “hook effect” which is due to saturation of the capture and detection antibodies used in the assay. Dilution of the sample would show a paradoxical increase in prolactin levels confirming the hook effect. Magnetic resonance imaging (MRI) is warranted to assess the extent of the tumor. Dopamine agonists are the treatment of choice in giant prolactinomas and lead to rapid resolution of symptoms, normalization of prolactin levels, and reduction in the size of the tumors. Refractory giant prolactinomas may be treated with surgery, temozolomide or radiotherapy. Giant prolactinomas can pose unique diagnostic and management challenges because of atypical presentations and confounding laboratory assessments. We present four cases of giant prolactinomas each presenting in a unique manner and discuss the diagnostic and management dilemmas associated with them. J Endocrinol Metab. 2020;10(6):182-189 doi: https://doi.org/10.14740/jem652

Abstract Introduction: Adrenal adenomas are incidentally noted during nonadrenal disease imaging at a rate up to 4%. Frequency of incidentalomas increases with age, most being adrenocortical adenomas. This case highlights an uncommon etiology of such an adrenal mass finding. Case Description: A 37-year-old with a history of hypertension, hypothyroidism, and tobacco use was admitted after post-operative complication. Prior to surgery, she had been experiencing right upper quadrant pain along with 70 lb weight loss and diarrhea. She otherwise had frequent palpitations. Patient had undergone cholecystectomy and common hepatic duct injury was noted. Imaging revealed a 5.3 x 3.5 cm right adrenal mass previously unknown prior to surgery. Hormonal workup was negative for overproduction of aldosterone, cortisol, DHEA-S or metanephrines. Discussion: Patient underwent successful resection of adrenal mass, revealing adrenal adenoma with osseous metaplasia and hematopoiesis. Extramedullary hematopoiesis is a usually discovered incidentally as in this case. Typical sites are the spleen and liver. Cases of adrenal gland manifestations have been reported in the presence of hemoglobinopathies (thalassemia, hereditary spherocytosis) or myelofibrosis. At four-month follow-up, laboratory testing on this patient didn’t suggest any erythrocytic or leukocytic disorder. Conclusion: This case highlights an uncommon finding of hematopoiesis in an adrenal incidentaloma without any underlying hematologic defect or disease. References: Motta, I., Boiocchi, L., Delbini, P., Migone De Amicis, M., Cassinerio, E., Dondossola, D., Rossi, G. and Cappellini, M. D. (2016), A giant adrenal myelolipoma in a beta-thalassemia major patient: Does ineffective erythropoiesis play a role?. Am. J. Hematol., 91: 1281-1282. doi:10.1002/ajh.24446. Stewart P, Newell-Price J. (2016). The Adrenal Cortex. In Melmed S, Polonsky K, Larsen P, Kronenberg H, Williams Textbook of Endocrinology. (13th ed., pp 489-555). Philadelphia, PA: Elsevier

Since the 2008 FDA guidance restructuring the design of trials for the approval of novel glucose-lowering agents, 13 medications have now been evaluated by dedicated cardiovascular outcome trials. All of the completed trials have included data (though with varying definitions) on rates of hospitalization for heart failure. This review is aimed at summarizing current heart failure outcome data available from cardiovascular safety trials for novel glucose-lowering agents in patients with type 2 diabetes mellitus. There appears to be growing evidence for the benefit of sodium–glucose cotransporter-2 inhibitors, and there are still not enough data to fully support the safety of glucagon-like peptide 1 receptor agonists in heart failure. Increased rates of hospitalization for heart failure were seen with both saxagliptin and alogliptin, and this has led to a class warning for all dipeptidyl peptidase-4 inhibitors. Future studies should have a standardized definition of “hospitalization for heart failure,” should consider including hospitalization for heart failure as a component of the primary composite endpoint, and should provide a more detailed description of the baseline characteristics of enrolled study participants with heart failure.

A 55-year-old female patient was presented with severe dyspnea due to sudden onset of heart failure (ejection fraction (EF) <10%). Echocardiogram showed a takotsubo pattern with an akinetic apical segment. Coronary angiography did not reveal any obstructive disease. She became hypotensive which was refractory to conventional pressor agents. Catecholamine-induced cardiomyopathy was suspected after the CT scan of the abdomen showed a 4 cm necrotic right adrenal mass consistent with pheochromocytoma (PHEO). Venous arterial extracorporeal membrane oxygenation and α blockers were initiated. There was a rapid improvement in cardiac function with EF normalising in 1 week. Subsequently, β-blockers were added and right adrenalectomy was done 3 weeks after the admission. She did extremely well after surgery with her blood pressure normalising without the need for antihypertensive therapy. Genetic evaluation revealed no pathogenic mutations implicated in the development of PHEO.

The impact of dietary factors on metabolism in general and glycemia in particular is well established in animal models [1–4]. For example, Surwit et al. in 1988 noted that the obese (C57BL/6J ob/ob) mouse only develops significant hyperglycemia in the presence of stress [5]. Initially, the background strain (C57BL/6J) was used as a normal control animal. However, when data using both the C57BL/6J animal and another strain (A/J) were compared, it became clear that the former mouse strain was always mildly hyperglycemic and hyperinsulinemic compared to the latter. This raised the possibility that the ob/ob mutation was an obesity mutation, exacerbating the genetic predilection to hyperglycemia already present in the background strain. Thus, Surwit and Feinglos developed a nutritional experiment to explore the effect of a high-fat, high-calorie diet on the development of obesity and hyperglycemia in these mice. This would serve as a model of the development of type 2 diabetes induced by diet in human populations with a similar genetic predisposition. Both A/J and C57BL/6J mice were studied. For each strain, 10 mice were fed a control diet of ad libitum water and Purina Rodent Chow, whereas 10 mice were fed a high-fat, high-simple-carbohydrate diet ad libitum. (For more detailed nutrient composition of the diets, please see Table 13.1). The control diet and the high-fat, high-simple-carbohydrate diet were administered for 6 months. Both strains of mice developed obesity after 16 weeks, but the C57BL/6J mice were significantly more obese. Furthermore, the diet-induced obesity led to moderate glucose intolerance and insulin resistance in the A/J mice, but obesity in the C57BL/6J mice led to clear-cut diabetes with markedly increased fasting glucose and insulin levels: glucose 248 ± 8 mg/dL versus 162 ± 6 mg/dL in C57BL/6J mice versus A/J mice, respectively. The authors concluded that, on this "diabetogenic" diet, C57BL/6J 217mice appear to develop diabetes in a manner that is analogous to most cases of human type 2 diabetes in predisposed individuals [5].

Heart failure (HF) is an important comorbidity in individuals with diabetes. Most commonly, the condition is secondary to ischaemia and hypertension. Diabetic cardiomyopathy is becoming increasingly recognised as a cause of HF and blood glucose control plays a pivotal role in the prevention and treatment of HF. Since the US Food and Drug Administration regulatory guidance in 2008, new glucose-lowering agents are evaluated routinely by cardiovascular outcome trials. These trials offer a wealth of knowledge and allow better understanding of the risks and benefits of contemporary diabetes medications. In this review, we will focus on the risks of HF with emerging glucose-lowering therapies and the safety of these medications in patients with established HF. We will summarise the guidance that is available for the treatment algorithm of diabetes in those with HF and highlight future areas of research.

Diabetes mellitus (DM) and chronic kidney disease (CKD) are two chronic diseases whose prevalence and coprevalence are on the rise. CKD is also the most debilitating and expensive complication of DM while management of DM in CKD is most challenging. CKD is developing in much younger patients with DM, and its presentation is also changing. Various methods of glycemic assessment are affected by CKD and dosage of DM medications needs to be adjusted according to the kidney function. One of the significant barriers to glycemic control in DM patients with CKD is hypoglycemia; close monitoring of glucose levels is essential. Dialysis affects the glucose homeostasis and insulin pharmacokinetics; therefore diabetic medication regimen needs to be adjusted accordingly. Kidney transplants are being increasingly performed as an alternative to dialysis. With the increased survival of transplants secondary to improved immunosuppressive regimen, the prevalence of post-transplant diabetes mellitus is on the increase. Good glycemic control is necessary for the survival of the transplant.

Purpose of Review This review aims to summarize and discuss heart failure outcomes for current glucose-lowering agents in patients with type 2 diabetes mellitus. Recent Findings Current regulations require cardiovascular outcomes trials for new glucose-lowering therapies to establish that there is no unacceptable increase in cardiovascular risk prior to approval. These cardiovascular outcomes trials include glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose cotransporter-2 inhibitors. Overall, 87,162 patients have been studied in 10 published cardiovascular outcomes trials. There was no significant increase in major adverse cardiovascular events including cardiovascular mortality, myocardial infarction, and stroke in any of these trials. Heart failure was a component of the secondary endpoint of all of these trials, but only two of these studies show a significant improvement in rates of hospitalization for heart failure. Summary Expanded regulatory labeling for reduction in cardiovascular mortality (empagliflozin) and reduction in major adverse cardiovascular events (liraglutide) has recently been established. Saxagliptin and to a lesser part alogliptin have been associated with an increased rate of hospitalization for heart failure. Canagliflozin and empagliflozin are the only two medications that have shown a clear benefit in rates of heart failure hospitalization in treatment of patients with type 2 diabetes mellitus.

Diabetes mellitus (DM) and chronic kidney disease (CKD) are intricately intertwined. DM is the most common cause of CKD. Adequate control of DM is necessary for prevention of progression of CKD, while careful management of the metabolic abnormalities in CKD will assist in achieving better control of DM. Two of the key organs involved in glucose production are the kidney and the liver. Furthermore, the kidney also plays a role in glucose filtration and reabsorption. In CKD, monitoring of glycemic control using traditional methods such as Hemoglobin A1c (Hba1c) must be done with caution secondary to associated hematological abnormalities in CKD. With regard to medication management in the care of patients with DM, CKD has significant effects. For example, the dosages of oral and non-insulin anti-hyperglycemic agents often need to be modified according to renal function. Insulin metabolism is altered in CKD, and a reduction in insulin dose is almost always needed. Dialysis also affects various aspects of glucose homeostasis, necessitating appropriate changes in therapy. Due to the aforementioned factors glycemic management in patients with DM and CKD can be quiet challenging.

Abbreviations: BG = blood glucose EMR = electronic medical record

A 60-year-old man with uncontrolled type 2 diabetes (A1C 8.2%) presented after 3 weeks of fevers and chills associated with chronic left foot ulcers that had progressed to wet gangrene. The patient reported poor compliance with his home diabetes medications: lispro 75–25 (30 units every morning and 36 units every evening), metformin, and Januvia. On admission he had a blood glucose (BG) of 400 mg/dL (22.2 mmol/L) and an anion gap of 11. He was admitted for a planned below-the-knee amputation (BKA) by the general surgical service and started on an intravenous (i.v.) insulin drip, i.v. fluids, and antibiotics. Between December 1, 2013, and December 6, 2013, the patient underwent several surgical procedures, ending with a left completion BKA on December 6, 2013.

The transition from intravenous (IV) to subcutaneous (SQ) insulin in the hospitalized patient with diabetes or hyperglycemia is a key step in patient care. This review article suggests a stepwise approach to the transition in order to promote safety and euglycemia. Important components of the transition include evaluating the patient and clinical situation for appropriateness, recognizing factors that influence a safe transition, calculation of proper SQ insulin doses, and deciding the appropriate type of SQ insulin. This article addresses other clinical situations including the management of patients previously on insulin pumps and recommendations for patients requiring glucocorticoids and enteral tube feedings. The use of institutional and computerized protocols is discussed. Further research is needed regarding the transition management of subgroups of patients such as those with type 1 diabetes and end-stage renal disease.