Non-uraemic calciphylaxis (NUC) postliver transplantation.

Calciphylaxis is a rare and life-threatening disease characterized by cutaneous arteriolar stenosis and vascular thrombosis leading to skin ischaemia and necrosis. While calciphylaxis occurs mostly in patients with end-stage renal disease, the disorder has been described in patients with normal renal function, namely non-uraemic calciphylaxis (NUC). A 41-year-old African-American woman presented with a painful ulcerative rash on her thighs and right buttock 2 months after undergoing an orthotopic liver transplantation. She underwent debridement of the lesions and an excisional biopsy of one of the lesions, which revealed calciphylaxis. She was treated with sodium thiosulfate, cinacalcet and hyperbaric oxygen with complete resolution of the lesions 4-5 months after presentation. While she was treated with a course of high-dose glucocorticoids after the transplant, she did not have other risk factors for calciphylaxis. NUC should be considered in the differential diagnosis of necrotic skin lesions in postliver transplant patients.

Posaconazole-Induced Adrenal Insufficiency in a Case of Chronic Myelomonocytic Leukemia.

INTRODUCTION: Posaconazole is an azole used in treatment and prophylaxis of a broad spectrum of fungal infections. Antifungals such as ketoconazole have been shown to cause primary adrenal insufficiency (AI) as a result of direct inhibition on the steroidogenesis pathway. There is only one reported case of primary AI induced by posaconazole in a patient with mucormycosis. We report a case of posaconazole-related primary AI. CASE: A 63-year-old man with chronic myelomonocytic leukemia was admitted for fatigue and intermittent nausea and vomiting. He had recently discontinued prophylactic posaconazole 300 mg daily. He was assessed for AI with a morning cortisol of 1.9 mcg/dL followed by a failed cosyntropin stimulation (CS) test. Adrenocorticotropic hormone (ACTH) level was 154.6 pg/mL with negative 21-hydroxylase antibodies. The patient's symptoms improved with initiation of hydrocortisone and fludrocortisone. One year after discontinuation of posaconazole, he underwent a repeat CS test which showed normal adrenal function with normal ACTH at 34.1 pg/mL. CONCLUSION: In this case, we demonstrate that prolonged use of posaconazole is associated with primary AI. As use of posaconazole increases, knowledge of the potential risk of AI is important and must be included in the differential diagnosis when these patients present with hypotension, hypoglycemia, and failure to thrive.

Gestational Diabetes Mellitus: Post-partum Risk and Follow Up.

BACKGROUND: Women with gestational diabetes mellitus (GDM) are at an increased risk for developing metabolic syndrome, type 2 diabetes mellitus (T2DM), and cardiovascular disease. In this review, we will discuss postpartum cardiovascular and diabetes risk in women with a history of GDM and different ways to improve postpartum screening. METHODS: This review involves a comprehensive literature review on gestational diabetes and postpartum risk for cardiovascular disease and diabetes mellitus as well as post-partum screening methods. RESULTS: Cardiovascular risk post-partum is potentiated by increased inflammatory markers leading to worsening atherosclerosis and cardiovascular events downstream. Decreased insulin sensitivity and ß cell compensation, recurrent GDM, maternal factors such as pre and post-partum weight gain and lactation may contribute to T2DM risk. Postpartum glucose testing is essential in screening women as hyperglycemia in pregnancy has long term effects on both cardiovascular disease and diabetes risk on the mother. CONCLUSION: Long and short term improvement to post-partum glucose testing is essential to decreasing cardiometabolic and diabetes risk in women with gestational diabetes mellitus.

THE PHYSIOLOGY BEHIND DIABETES MELLITUS IN PATIENTS WITH PHEOCHROMOCYTOMA: A REVIEW OF THE LITERATURE.

OBJECTIVE: This paper reviews the physiologic mechanisms responsible for glucose intolerance and diabetes mellitus in patients with pheochromocytoma. METHODS: Google Scholar and PubMed were searched using the following key words: "diabetes," "pheochromocytoma," "adrenoreceptors," and "hyperglycemia." All the articles that were retrieved and reviewed were in the English language. RESULTS: Glucose intolerance and diabetes mellitus, resulting from high circulating levels of catecholamines, are mainly the product of compromised insulin secretion from the ß-cells in the pancreas, decreased glucose uptake in the peripheral tissues, and increased insulin resistance. CONCLUSION: As pheochromocytomas mainly present with cardiovascular and autonomic hyperfunctioning, it is important to understand the metabolic disorders associated with this rare disease. Hyperglycemia is an associated metabolic abnormality which can drastically improve after tumor resection, and significant downscaling of anti-hyperglycemic therapy is often required. ABBREVIATIONS: GLUT4 = glucose transporter type 4 HbA1c = hemoglobin A1c IL = interleukin OGTT = oral glucose tolerance test.

Gadd34 functional domains involved in growth suppression and apoptosis.

Gadd34 (also known as MyD116) was originally described as a growth arrest and DNA damage-inducible gene. Increased expression of Gadd34 was subsequently found to correlate with apoptosis, and forced overexpression of the protein leads to apoptosis. Gadd34 protein modulates protein phosphatase type 1 activity through both direct binding to the protein, as well as through binding to other proteins that also modulate phosphatase activity. In addition, Gadd34 has a region of homology with the herpes simplex virus type 1 ICP34.5 protein that is involved in the prevention of apoptosis in infected cells. Recently it was reported that a novel rat Gadd34-related gene, PEG-3, was upregulated in transformed cells, and that forced expression of this gene led to increased tumorigenic potential of cells implanted into nude mice and increased angiogenesis of these tumors. We have found, however, that PEG-3 does not exist in normal rat cells, which have a single diploid complement of Gadd34. Sequence analysis of the rat Gadd34 gene and comparison with PEG-3 indicates that PEG-3 is most likely a mutant of Gadd34 that perhaps arose as a result of transformation. This finding suggests that truncated Gadd34 may interfere with normal Gadd34 function in transfected cells. However, human Gadd34 lacking the viral homology domain does not interfere with normal Gadd34-induced apoptosis in cultured cells. This suggests that viral similarity sequences may be required for Gadd34-mediated functions other than apoptosis.