Abiraterone-Induced Endocrinopathies.

Abiraterone, a CYP17A1 inhibitor, is used along with prednisone in patients with castration-resistant and castration-sensitive prostate cancer, yielding improved overall and disease-free survival. However, little is documented in the endocrinology literature about the incidences of the endocrine side effects of abiraterone. In this case series, we discuss the diagnosis and management of 3 prostate cancer patients who experienced mineralocorticoid excess and secondary adrenal insufficiency related to abiraterone and prednisone use.

Identifying patients with type 2 diabetes who might benefit from insulin pump therapy: Literature review, clinical opportunities, potential benefits and challenges.

The global prevalence and increasing incidence rates of type 2 diabetes (T2D) have rippling effects on healthcare costs and diminishing quality of life. Despite advances in technology, continuous subcutaneous insulin infusion (CSII), or insulin pump therapy, is rarely being recommended by healthcare professionals and is underutilized in T2D management. This review analyses the available literature on CSII use in T2D patients. In addition, it discusses which groups of patients may benefit from CSII, identifies potential challenges associated with CSII use, and suggests future directions for research to expand the applicability of this technology to the broader T2D population.

Increase in hematocrit with SGLT-2 inhibitors - Hemoconcentration from diuresis or increased erythropoiesis after amelioration of hypoxia?

BACKGROUND AND AIMS: The SGLT2-inhibitors significantly reduce heart failure hospitalization and progression to end-stage kidney disease. An increase in hemoglobin/hematocrit is seen with SGLT2i-inhibitor treatment. This increase has been attributed to hemoconcentration resulting from a diuretic effect. In this review, we present evidence suggesting that the hematocrit increase is not due to hemoconcentration, but to an increase in erythropoiesis due to amelioration of hypoxia and more efficient erythropoietin production with SGLT2-inhibitor treatment. METHODS: We performed a detailed review of the literature in PubMed for articles describing various mechanisms linking hematocrit increase with SGLT2-inhibitor use to their cardio-renal benefits. RESULTS: The best predictor of cardio-renal benefits with SGLT2-inhibitors is an increase in hematocrit and hemoglobin. If this hemoconcentration is a results of diuresis, this would be associated with volume contraction and a deterioration in renal function, as seen with long-term diuretic use. This is the opposite of what is seen with the use of SGLT2-inhibitors, which are associated with long-term preservation of renal function. There is now growing evidence that the increase in hematocrit can be attributed to an increase in erythropoiesis due to amelioration of renal hypoxia and more efficient erythropoietin production with SGLT2-inhibitor treatment. Increased erythropoiesis leads to an increase in RBC count which improves myocardial/renal tissue oxygenation and function. CONCLUSION: The increase in hematocrit with SGLT2i treatment is not due to hemoconcentration, but to an increase in erythropoiesis due to amelioration of hypoxia and more efficient erythropoietin production with SGLT2i treatment.

A novel hypothesis linking low-grade ketonaemia to cardio-renal benefits with sodium-glucose cotransporter-2 inhibitors.

The cardio-renal benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors are well established. In 2016, we postulated that these benefits are attributable, in part, to the occurrence of chronic low-grade ketonaemia and a shift in myocardial and renal fuel metabolism away from fat oxidation, which is energy inefficient, towards ketone oxidation, which is more energy efficient. This shift improves myocardial and renal function and can potentially translate into lower rates of progression to heart failure and end-stage kidney disease in patients with and without diabetes. There is now evidence that, in addition to being an efficient fuel substrate, ketones also have antiinflammatory and antioxidative benefits on the heart and the kidney. In addition, ketones have positive effects on mitochondrial biogenesis and function, and on erythropoiesis, and thereby are potentially able to further ameliorate the proinflammatory and hypoxic milieu in those with heart and kidney failure, independent of hyperglycaemia. In the present review, we propose a novel hypothesis to link the pleiotropic effects of low-grade ketonaemia to the cardio-renal benefits seen with SGLT2 inhibitors.

Sodium-Glucose Cotransporter Type 2 (SGLT-2) Inhibitors and Ketogenesis: the Good and the Bad.

PURPOSE OF REVIEW: The micro/macrovascular complications of diabetes cause considerable morbidity and premature mortality. The SGLT2 inhibitors are the first diabetes medications with significant benefits on microvascular disease (nephropathy) and macrovascular cardiovascular disease. In this review, we evaluate one of the potential mechanisms for these cardiorenal benefits-the production of ketones, their benefits, and risks. RECENT FINDINGS: In recent cardiovascular outcome trials (CVOTs), the SGLT2 inhibitors demonstrated significant cardiorenal benefits and they are now approved to reduce CV events/death, heart failure hospitalization, and progression to end-stage renal disease. Glucosuria induced by the SGLT2 inhibitors leads to increased ketone production. Ketones are an efficient fuel source and can improve myocardial and renal function. Further, the ketone body beta-hydroxybutyrate exhibits anti-inflammatory/anti-oxidative actions, which favorably impact myocardial and renal remodeling/fibrosis. Uncontrolled ketogenesis leads to ketoacidosis, especially during conditions of acute illness and excessive insulin dose reductions. The SGLT2 inhibitors have demonstrated significant cardiorenal benefits in large CVOTs. Studies are in progress to elucidate whether SGLT2 inhibitor-induced low-grade hyperketonemia contributes to these benefits.

Review of Intravenous and Subcutaneous Electronic Glucose Management Systems for Inpatient Glycemic Control.

PURPOSE OF REVIEW: The goal of this review is to summarize current literature on electronic glucose management systems (eGMS) and discuss their benefits and disadvantages in the inpatient setting. RECENT FINDINGS: We review different versions of commercially available eGMS: Glucommander™ (Glytec, Greenville, SC), EndoToolR (MD Scientific LLC, Charlotte, NC), GlucoStabilizer™ (Medical Decision Network, Charlottesville, VA), GlucoCare™ (Pronia Medical Systems, KY), and discuss advantages such as reducing rates of hypoglycemia, hyperglycemia, and glycemic variability. In addition, eCGMs offer a uniform standard of care and may improve workflows across institutions as well reduce barriers. Despite ample literature on intravenous (IV) versions of eGMS, there is little published research on subcutaneous (SQ) insulin guidance. Although use of eGMS requires extensive training and institution-wide adoption, time spent on diabetes management is better facilitated by their use.

Neural expression and post-transcriptional dosage compensation of the steroid metabolic enzyme 17beta-HSD type 4.

BACKGROUND: Steroids affect many tissues, including the brain. In the zebra finch, the estrogenic steroid estradiol (E2) is especially effective at promoting growth of the neural circuit specialized for song. In this species, only the males sing and they have a much larger and more interconnected song circuit than females. Thus, it was surprising that the gene for 17beta-hydroxysteroid dehydrogenase type 4 (HSD17B4), an enzyme that converts E2 to a less potent estrogen, had been mapped to the Z sex chromosome. As a consequence, it was likely that HSD17B4 was differentially expressed in males (ZZ) and females (ZW) because dosage compensation of Z chromosome genes is incomplete in birds. If a higher abundance of HSD17B4 mRNA in males than females was translated into functional enzyme in the brain, then contrary to expectation, males could produce less E2 in their brains than females. RESULTS: Here, we used molecular and biochemical techniques to confirm the HSD17B4 Z chromosome location in the zebra finch and to determine that HSD17B4 mRNA and activity were detectable in the early developing and adult brain. As expected, HSD17B4 mRNA expression levels were higher in males compared to females. This provides further evidence of the incomplete Z chromosome inactivation mechanisms in birds. We detected HSD17B4 mRNA in regions that suggested a role for this enzyme in the early organization and adult function of song nuclei. We did not, however, detect significant sex differences in HSD17B4 activity levels in the adult brain. CONCLUSIONS: Our results demonstrate that the HSD17B4 gene is expressed and active in the zebra finch brain as an E2 metabolizing enzyme, but that dosage compensation of this Z-linked gene may occur via post-transcriptional mechanisms.