Unsuspected Von Hippel-Lindau syndrome in acute-onset resistant hypertension.

The discovery of adrenal lesions during routine testing for hypertension requires focused consideration for adrenal overproduction of cortisol, aldosterone or metanephrines. An otherwise healthy 25-year-old woman presented with headaches, diaphoresis and hot flushes with grossly elevated urine catecholamines, normetanephrines and norepinephrine levels, yet normal metanephrines, epinephrine/epinephrine, cortisol and aldosterone levels. Subsequent functional uptake studies and scans identified bilateral adrenal adenomas consistent with phaeochromocytomas. There was no family history of phaeochromocytomas or familial syndromes; however, a targeted genetic analysis for causes of familial phaeochromocytomas identified a heterozygous germline mutation in the VHL gene consistent with Von Hippel-Lindau syndrome. In this case, the identification of the VHL mutation led to careful screening and detection of clinically occult central nervous system hemangioblastomas and pancreatic neuroendocrine tumours. Verified genetic mutations facilitated best practices for long-term surveillance protocols, preconception counselling and screening of blood relatives. The patient responded well to surgical treatment and has ongoing multidisciplinary long-term surveillance.

Structure-function relationship between corneal nerves and conventional small-fiber tests in type 1 diabetes.

OBJECTIVE: In vivo corneal confocal microscopy (IVCCM) has been proposed as a noninvasive technique to assess small nerve fiber structural morphology. We investigated the structure-function relationship of small fibers in diabetic sensorimotor polyneuropathy (DSP). RESEARCH DESIGN AND METHODS: Ninety-six type 1 diabetic subjects with a spectrum of clinical DSP and 64 healthy volunteers underwent IVCCM examinations to determine corneal nerve structure, including corneal nerve fiber length (CNFL), fiber density (CNFD), branch density (CNBD), and fiber tortuosity (CNFT). Small nerve fiber function was assessed by cooling detection thresholds (CDTs), axon reflex-mediated neurogenic vasodilatation in response to cutaneous heating by laser Doppler imaging flare technique (LDIFLARE), and heart rate variability (HRV). Linear associations between structural and functional measures in type 1 diabetic subjects were determined using Spearman correlation coefficients and linear regression analysis. RESULTS: Of the type 1 diabetic subjects, with a mean age of 38.2 ± 15.5 years and a mean HbA1c of 7.9 ± 1.4%, 33 (34%) had DSP according to the consensus definition. Modest correlations were observed between CNFL, CNFD, and CNBD and all functional small-fiber tests (rs = 0.25 to 0.41; P ≤ 0.01 for all comparisons). For example, quantitatively every 1 mm/mm(2) lower CNFL was associated with a 0.61°C lower CDT, a 0.07 cm(2) lower LDIFLARE area, and a 1.78% lower HRV. No significant associations were observed for CNFT and the functional small-fiber measures. CONCLUSIONS: Small nerve fiber structural morphology assessed by IVCCM correlated well with functional measures of small nerve fiber injury. In particular, CNFL, CNFD, and CNBD demonstrated clear structure-function relationships.

Vegfa protects the glomerular microvasculature in diabetes.

Vascular endothelial growth factor A (VEGFA) expression is increased in glomeruli in the context of diabetes. Here, we tested the hypothesis that this upregulation of VEGFA protects the glomerular microvasculature in diabetes and that therefore inhibition of VEGFA will accelerate nephropathy. To determine the role of glomerular Vegfa in the development and progression of diabetic nephropathy, we used an inducible Cre-loxP gene-targeting system that enabled genetic deletion of Vegfa selectively from glomerular podocytes of wild-type or diabetic mice. Type 1 diabetes was induced in mice using streptozotocin (STZ). We then assessed the extent of glomerular dysfunction by measuring proteinuria, glomerular pathology, and glomerular cell apoptosis. Vegfa expression increased in podocytes in the STZ model of diabetes. After 7 weeks of diabetes, diabetic mice lacking Vegfa in podocytes exhibited significantly greater proteinuria with profound glomerular scarring and increased apoptosis compared with control mice with diabetes or Vegfa deletion without diabetes. Reduced local production of glomerular Vegfa in a mouse model of type 1 diabetes promotes endothelial injury accelerating the progression of glomerular injury. These results suggest that upregulation of VEGFA in diabetic kidneys protects the microvasculature from injury and that reduction of VEGFA in diabetes may be harmful.