Bladder Paraganglioma Associated With Succinate Dehydrogenase A Mutation Presenting as Pelvic Pain.

A 21-year-old female presented to the hospital with acute onset left pelvic pain that began while urinating. Ultrasound of the pelvis revealed a 1.7 cm structure within the bladder wall. Follow-up imaging with magnetic resonance imaging confirmed a 1.9 cm mass in the urinary bladder wall. Cystoscopy with transurethral resection was performed. Histopathology of the obtained tissue confirmed the diagnosis of paraganglioma. Laboratory evaluation revealed evidence of catecholamine excess with elevated urine norepinephrine, urine normetanephrine, and plasma free normetanephrine. Functional imaging with Ga-DOTATATE positron emission tomography-computed tomography (PET-CT) revealed increased uptake in the region of the known mass without findings of metastasis. Genetic testing revealed succinate dehydrogenase A mutation, consistent with paraganglioma syndrome 5. The patient was treated with alpha-adrenergic blockade prior to partial cystectomy. Urinary bladder paraganglioma is a rare entity. The diagnosis requires a high index of clinical suspicion due to variable presentation. Hypertension and other signs of catecholamine excess, especially in relation to micturition, are important clues. Despite evidence of catecholamine excess in most patients with bladder paraganglioma, the majority are diagnosed after biopsy, indicating a need for improved diagnostic strategies in this patient population. Early diagnosis and treatment are essential to prevent potentially lethal cardiac complications and tumor metastasis.

Persistent Orthostatic Hypotension in a Patient With Acromegaly: Resolution With Transsphenoidal Hypophysectomy.

Acromegaly is a rare condition characterized by excessive secretion of growth hormone from a pituitary tumor. It can affect multiple systems and can be fatal with cardiac dysfunction being the most common cause of death in these patients. Autonomic dysfunction is a less studied subject in patients with acromegaly, and the exact pathophysiology is still unclear. Here we present a case of a patient with persistent orthostatic hypotension, who was found to have acromegaly and pituitary adenoma upon further evaluation. Her orthostatic symptoms failed to improve with conservative measures and medical management, but unexpectedly resolved after transsphenoidal hypophysectomy was performed.

Syndrome of inappropriate antidiuretic hormone secretion in a patient with pituitary apoplexy.

Pituitary apoplexy (PA) is an endocrine emergency presenting with headache, visual and hormonal disturbances. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is rare after PA. A 64-year-old woman presented with acute frontal headache and nausea with normal neurological examination. Labs included normal sodium and creatinine. Echo showed new-onset congestive heart failure (CHF) and MRI of the brain revealed PA. She had normal cortisol levels and low thyroid stimulating hormone with normal thyroxine (T4) levels. During her hospitalisation, patient developed hyponatraemia. Initially, this was attributed to CHF and she was treated with tolvaptan with normalisation of sodium. One week later, she was readmitted with diarrhoea and hyponatraemia. She was euvolaemic on examination indicating compensated CHF. Despite fluid challenge, patient had no improvement of sodium levels. The diagnosis of SIADH was made. Clinicians should suspect SIADH in patients with hyponatraemia in the setting of PA with normal T4 and cortisol levels.

Glucose control and cardiovascular outcomes in individuals with diabetes mellitus: lessons learned from the megatrials.

Glucose lowering should be approached by managing overall cardiovascular risk. Glycemic goals should be individualized based on duration of diabetes, preexisting cardiovascular disease, age, and life expectancy. Intensive glycemic control has consistently been shown to produce a substantial benefit for preventing long-term microvascular complications in both type 1 and type 2 diabetes mellitus. Although cardiovascular disease is the major cause of death in patients with diabetes, microvascular complications cause substantial morbidity and disability. Thus, it is apparent that additional strategies on multimodal treatment options are necessary to promote effective management and prevention of diabetic complications.

Effects of insulin detemir on balloon catheter injured carotid artery in Zucker fatty rats.

OBJECTIVE: We compared the effect of the long acting basal insulin analog detemir with neutral protamine Hagedorn (NPH) insulin, and normal saline on recovery from vascular injury (balloon catheter mediated) in an animal model of insulin resistance. METHODS: Female Zucker fatty rats were administered NPH/detemir/saline for 7 days following which, they underwent balloon catheter mediated injury of left carotid artery, and were continued on the respective regimen for an additional 21 days when they were sacrificed. We evaluated the injured carotid artery for intimal hyperplasia (Intima/Media ratio) and also, aortic arch protein for markers of oxidative stress and inflammation, in addition to expression and phosphorylation of eNOS using well established methods. RESULTS: There was a significant difference in intimal hyperplasia (Intima/Media ratio) between control and detemir treated rats (1.3±0.09, 0.82±0.08; p<0.001) whereas the IM ratio in NPH treated rats was not significantly different from saline (1.17±0.1). Expression of p-eNOS (ser-1177) in both NPH and insulin detemir (1.3±0.15, 1.11±0.12) was significantly higher than controls (0.56±0.13; p<0.05). We did not find significant differences in the expression of MnSOD, eNOS and NFκB-p65. CONCLUSION: We conclude that in insulin resistant states, treatment with Insulin detemir but not NPH is associated with less intimal hyperplasia, although both insulins increased eNOS phosphorylation.

Safety evaluation of colesevelam therapy to achieve glycemic and lipid goals in type 2 diabetes.

INTRODUCTION: Patients with hypercholesterolemia and type 2 diabetes mellitus often require multiple medications to attain their LDL-C and A1C goals. Colesevelam, a bile acid sequestrant (BAS), which was FDA approved 10 years ago for the reduction of LDL-C in patients with dyslipidemia is also the only BAS that is approved for glycemic control in adults with type 2 diabetes to date. From both the physician and patient standpoint, safety and tolerability are the most important factors when considering initiating pharmacological therapy. Several randomized controlled studies have examined the safety, tolerability and efficacy of colesevelam over the last decade. AREAS COVERED: This manuscript focuses on the safety and tolerability based on the evaluation of data obtained from several human randomized controlled studies. In addition, the pharmacology, pharmacodynamics and key clinical efficacy data are reviewed using research articles accessed through MEDLINE/PubMed (2000 - 2010). EXPERT OPINION: Current data suggest that colesevelam is safe, well tolerated and offers the potential for improved adherence. Colesevelam is a valid option for long-term therapy for patients with hypercholesterolemia and type 2 diabetes. It can be used in combination with HMG-CoA reductase inhibitors for hypercholesterolemia, not controlled at their cholesterol goals with HMG-CoA reductase inhibitors, and should be considered in patients with type 2 diabetes mellitus with concomitant hypercholesterolemia to improve both risk factors.