SGLT2 inhibitors.

Diabetes mellitus is a serious health issue and an economic burden, rising in epidemic proportions over the last few decades worldwide. Although several treatment options are available, only half of the global diabetic population achieves the recommended or individualized glycemic targets. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents with a novel insulin-independent action. SGLT2 is a transporter found in the proximal renal tubules, responsible for the reabsorption of most of the glucose filtered by the kidney. Inhibition of SGLT2 lowers the blood glucose level by promoting the urinary excretion of excess glucose. Due to their insulin-independent action, SGLT2 inhibitors can be used with any degree of beta-cell dysfunction or insulin resistance, related to a very low risk of hypoglycemia. In addition to improving glycemic control, SGLT2 inhibitors have been associated with a reduction in weight and blood pressure when used as monotherapy or in combination with other antidiabetic agents in patients with type 2 diabetes mellitus (T2DM). Treatment with SGLT2 inhibitors is usually well tolerated; however, they have been associated with an increased incidence of urinary tract and genital infections, although these infections are usually mild and easy to treat. SGLT2 inhibitors are a promising new option in the armamentarium of drugs for patients with T2DM.

Sodium glucose co-transporter 2 inhibitors: blocking renal tubular reabsorption of glucose to improve glycaemic control in patients with diabetes.

BACKGROUND: The kidney plays a central role in the regulation of plasma glucose levels, although until recently this has not been widely appreciated or considered a target for therapeutic intervention. The sodium glucose co-transporter type 2 (SGLT2) located in the plasma membrane of cells lining the proximal tubule mediates the majority of renal glucose reabsorption from the tubular fluid, which normally prevents the loss of glucose in the urine. Competitive inhibitors of SGLT2 that provoke the renal excretion of glucose have been discovered, thereby providing a unique mechanism to potentially lower the elevated blood glucose levels in patients with diabetes. OBJECTIVE: To explore the physiology of SGLT2 action and discuss several SGLT2 inhibitors that have entered early clinical development. METHODS: All publicly available data were identified by searching the internet for 'SGLT2' and 'SGLT2 inhibitor' through 1 November 2007. Published articles, press releases and abstracts presented at national and international meetings were considered. RESULTS/CONCLUSION: Sodium glucose co-transporter type 2 inhibition is a novel treatment option for diabetes, which has been studied in preclinical models and a few potent and selective SGLT2 inhibitors have been reported and are currently in clinical development. These agents appear to be safe and generally well tolerated, and will potentially be a beneficial addition to the growing battery of oral antihyperglycaemic agents.

Endocrine incidentalomas.

OBJECTIVES: Endocrine incidentalomas are very common in the practice of every physician, mostly primary care and family physicians. Incidentalomas are discovered in the thyroid, pituitary and adrenal glands during imaging studies performed for non-endocrine reasons. The aim of this review article is to familiarise health professionals with all three endocrine incidentalomas, and give some guidance on how to initiate the right endocrine workup. METHODS: We reviewed the most pertinent literature published on this topic through PubMed and Medline. We also discussed our own approach to incidentalomas in the endocrine clinic at Thomas Jefferson Hospital in Philadelphia. RESULTS/CONCLUSIONS: Thyroid incidentalomas are very common, with a prevalence close to 50% on imaging studies. Thyroid-stimulating hormone (TSH) is the first test to obtain; if not suppressed, next step is fine-needle aspiration biopsy of any nodule above 1 cm and/or with suspicious ultrasound characteristics. Adrenal incidentalomas have a prevalence of almost 5%. All adrenal nodules above 4 cm should be resected. Regardless of the size, a workup for pheochromocytoma should always be done. Only hypertensive patients should be screened for primary hyperaldosteronism. Pituitary incidentalomas are also common, with a prevalence of 10-20%. All patients with pituitary masses should have a workup for hormonal hypersecretion. Only patients with macroadenomas will have additional screening for hypopituitarism and visual field defects. All hyperfunctioning adenomas are resected except prolactinomas which are treated medically. Similarly, if a macroadenoma is causing hypopituitarism or visual deficit, surgery should also be considered.

Steroids and the surgical patient.

In patients undergoing surgery, a thorough history is important to obtain, including use of any steroid therapy within the previous year. If there is a history of steroid use, and if time permits, testing of the HPA axis should be performed. If adrenal unresponsiveness is documented or if clinical suspicion of [table: see text] adrenal insufficiency is high (without testing), a stress dose of steroids should be administered during the perioperative period to prevent an adrenal crisis.

Uncontrolled diabetes mellitus.

The conditions of DKA and NKH are life-threatening complications of poorly controlled diabetes mellitus. They have characteristic clinical and laboratory features. If not treated appropriately, they can result in a high mortality rate of 15% to 28% in DKA and 17% to 50% in NKH.

A case of the Carney triad.

OBJECTIVE: To report a case of mediastinal paraganglioma in the setting of the Carney triad (gastric leiomyosarcoma, extra-adrenal paraganglioma, and pulmonary chondroma). METHODS: A case of the Carney triad is presented, and the related literature is discussed. RESULTS: A 47-year-old woman with a history of gastric leiomyosarcoma and retroperitoneal paraganglioma sought medical attention because of progressive shortness of breath. She was found to have a mediastinal mass in the aortopulmonary window. The patient had normal blood pressure and normal urinary catecholamines, but metaiodobenzylguanidine scintigraphy showed an intense uptake in the region of the mass, consistent with paraganglioma. She subsequently underwent resection of the mediastinal mass, and the surgical pathology report indicated paraganglioma. CONCLUSION: Patients with the Carney triad can have multicentric paragangliomas. Metaiodobenzylguanidine scanning may be helpful in the diagnostic workup.