Extraadrenal pheochromocytoma presenting with severe hematuria and postmicturition cephalgia, a case report of a rare bladder tumor entity.

Paraganglioma (PGL) of the urinary bladder are a very rare tumor entity. Treatment of a PGL requires a multidisciplinary approach. We report on a case of a malignant pheochromocytoma (PHEO) of the bladder in a male adult due to a succinate dehydrogenase B (SDHB) subunit gene mutation where a partial cystectomy was perfomed after preoperative alpha blocking.

A rare case of an ACTH/CRH co-secreting midgut neuroendocrine tumor mimicking Cushing's disease.

Ectopic ACTH/CRH co-secreting tumors are a very rare cause of Cushing's syndrome and only a few cases have been reported in the literature. Differentiating between Cushing's disease and ectopic Cushing's syndrome may be particularly difficult if predominant ectopic CRH secretion leads to pituitary corticotroph hyperplasia that may mimic Cushing's disease during dynamic testing with both dexamethasone and CRH as well as bilateral inferior petrosal sinus sampling (BIPSS). We present the case of a 24-year-old man diagnosed with ACTH-dependent Cushing's syndrome caused by an ACTH/CRH co-secreting midgut NET. Both high-dose dexamethasone testing and BIPSS suggested Cushing's disease. However, the clinical presentation with a rather rapid onset of cushingoid features, hyperpigmentation and hypokalemia led to the consideration of ectopic ACTH/CRH-secretion and prompted a further workup. Computed tomography (CT) of the abdomen revealed a cecal mass which was identified as a predominantly CRH-secreting neuroendocrine tumor. To the best of our knowledge, this is the first reported case of an ACTH/CRH co-secreting tumor of the cecum presenting with biochemical features suggestive of Cushing's disease. LEARNING POINTS: The discrimination between a Cushing's disease and ectopic Cushing's syndrome is challenging and has many caveats.Ectopic ACTH/CRH co-secreting tumors are very rare.Dynamic tests as well as BIPSS may be compatible with Cushing's disease in ectopic CRH-secretion.High levels of CRH may induce hyperplasia of the corticotroph cells in the pituitary. This could be the cause of a preserved pituitary response to dexamethasone and CRH.Clinical features of ACTH-dependent hypercortisolism with rapid development of Cushing's syndrome, hyperpigmentation, high circulating levels of cortisol with associated hypokalemia, peripheral edema and proximal myopathy should be a warning flag of ectopic Cushing's syndrome and lead to further investigations.

Liraglutide as add-on therapy to insulin in type 2 diabetes mellitus: a retrospective, observational study from a daily clinical practice setting in Switzerland.

INTRODUCTION: In most patients with type 2 diabetes mellitus (T2DM) and progressive beta-cell insufficiency, insulin therapy is required to achieve sufficient glycemic control. However, insulin therapy may lead to weight gain and increasing risk of hypoglycemia. Glucagon-like peptide-1 receptor agonists are being used as add-on therapy to insulin with favorable metabolic effects. Nonetheless, to date only few studies exist reporting on the combination of liraglutide and insulin with a short follow-up period. The aim of this study was to evaluate the efficacy and safety of liraglutide as add-on to insulin in patients with T2DM over a time period of up to 24-28 months. METHODS: Data of patients with T2DM, treated with insulin and liraglutide at an outpatient clinic in a tertiary referral hospital from October 2009 until December 2011 were retrospectively examined (n = 36). Glycated hemoglobin (HbA1c), weight, total daily insulin dose and side effects were assessed 5-8 months prior to liraglutide, at baseline and at follow-up visits after 3, 6, 12-16 and 24-28 months. RESULTS: Median HbA1c decreased significantly from 7.7% [interquartile range (IQR) 7.0-8.6] at baseline to 6.8% (IQR 6.5-7.7, p = 0.001) at 3 months and 6.9% (IQR 6.3-7.6, p = 0.0001) at 6 months, but re-increased thereafter (at 24-28 months, median 7.5%, IQR 7.1-8.2, p = 1.0). Median weight decreased significantly from 99.8 kg (IQR 81-110) at baseline to 97.7 kg (IQR 81.2-108.2, p = 0.027) at 3 months, but rose again thereafter. Insulin dosage did not change significantly over time. No severe hypoglycemia or major side effects occurred. CONCLUSIONS: In this observational study, adding liraglutide to insulin in daily clinical practice reduced HbA1c significantly within 6 months, but there may be a non-sustainable effect during long-term treatment.

Management of von hippel-lindau disease: an interdisciplinary review.

Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited tumour predisposition syndrome with an incidence of 1:36,000 newborns, the estimated prevalence in Europe is about 1-9/100,000. It is associated with an increased risk of developing various benign and malignant tumours, thus affecting multiple organs at different time points in the life of a patient. Disease severity and diversity as well as age at first symptoms vary considerably, and diagnostic delay due to failure of recognition is a relevant issue. The identification of a disease-causing VHL germline mutation subsequently allows family members at risk to undergo predictive genetic testing after genetic counselling. Clinical management of patients and families should optimally be offered as an interdisciplinary approach. Prophylactic screening programs are a cornerstone of care, and have markedly improved median overall survival of affected patients. The aim of this review is to give an overview of the heterogeneous manifestations of the VHL syndrome and to highlight the diagnostic and therapeutic challenges characteristic for this orphan disease. A comprehensive update of the underlying genetic and molecular principles is additionally provided. We also describe how the St. Gallen VHL multidisciplinary group is organised as an example of interdisciplinary cooperation in a tertiary hospital in Switzerland.

Hyponatremia associated coma due to pituitary apoplexy in early pregnancy: a case report.

Pituitary apoplexy in pregnancy is rare. Its clinical features may range from unspecific complaints to panhypopituitarism resulting even in coma and death. Therefore, alertness to signs and symptoms of acute loss of pituitary function in pregnancy is mandatory. We report a woman in her 7th week of her first gestation presenting with sudden coma due to severe hyponatremia. Secondary adrenal insufficiency could be identified as the underlying cause. Panhypopituitarism including central diabetes insipidus and spontaneous abortion developed during the follow-up. Magnetic resonance imaging showed pituitary apoplexy without a pre-existing pituitary mass. The clinical course was notable for severe complications, including neurological deficits through cerebral ischemia, but eventual recovery could be achieved. We discuss the diagnostic difficulties in the evaluation of pituitary disease in pregnancy.

A novel succinate dehydrogenase subunit B gene mutation, H132P, causes familial malignant sympathetic extraadrenal paragangliomas.

We report a family with malignant sympathetic paragangliomas (PGL) exhibiting a new type of germline mutation in the succinate dehydrogenase subunit B (SDHB) gene. Two affected brothers, presenting with symptoms at the ages of 25 and 52 yr, suffered from malignant abdominal extraadrenal sympathetic PGL. They died of their disease at ages 43 and 61 yr. Their mother had the same history of signs and symptoms, suggesting a catecholamine-producing tumor at the age of 55 yr. Analysis of the germline DNA from these three patients revealed a novel mutation in exon 4 (H132P) of the SDHB gene. This mutation was absent in 160 control chromosomes. Loss of heterozygosity analysis of the tumors showed a loss of one SDHB allele, and RT-PCR-based expression analysis confirmed the exclusive expression of the mutated allele in both tumors. A review of the published PGL families revealed malignant tumors in seven of 12 well-documented families with SDHB mutation-associated extraadrenal PGL. These findings, as well as findings of the family reported here, suggest a strong causal relationship of SDHB germline mutations with malignant extraadrenal abdominal PGL and imply the necessity of a close follow-up of affected individuals and family members.