[Diagnostic workup of adrenal masses].

With the increasing use of abdominal imaging, adrenal masses are more frequently detected. Depending on the clinical context, the detection of an adrenal mass has different consequences for downstream testing and therapy. As adrenal masses comprise various benign and malignant aetiologies, all lesions >1 cm need further diagnostic workup.

Medullary thyroid cancer with ectopic Cushing's syndrome: A multicentre case series.

Objective: Ectopic Cushing's syndrome (ECS) induced by medullary thyroid cancer (MTC) is rare, and data on clinical characteristics, treatment and outcome are limited.

Design: Retrospective cohort study in three German and one Swiss referral centres.

Patients: Eleven patients with MTC and occurrence of ECS and 22 matched MTC patients without ECS were included.

[Causes, diagnosis and differential diagnosis of hyponatremia].

Hyponatremia is a common electrolyte disorder that arises from disturbances in water metabolism. In cases of acute advanced hyponatremia, serious symptoms are predominant, while chronic mild hyponatremia causes minor symptoms such as slowness, depression or unsteadiness of gait. Any therapy of hyponatremia depends on the severity of its symptoms and on its specific etiology and diagnosis.

Analysis of IL2/IL21 gene variants in cholestatic liver diseases reveals an association with primary sclerosing cholangitis.

Background/aims: The chromosome 4q27 region harboring IL2 and IL21 is an established risk locus for ulcerative colitis (UC) and various other autoimmune diseases. Considering the strong coincidence of primary sclerosing cholangitis (PSC) with UC and the increased frequency of other autoimmune disorders in patients with primary biliary cirrhosis (PBC), we investigated whether genetic variation in the IL2/IL21 region may also modulate the susceptibility to these two rare cholestatic liver diseases.

Methods: Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block were genotyped in 124 PBC and 41 PSC patients.

ABCB4 deficiency: A family saga of early onset cholelithiasis, sclerosing cholangitis and cirrhosis and a novel mutation in the ABCB4 gene.

Gallstones are very common. However, there is a small group of patients with low phospholipid-associated cholelithiasis (LPAC) that is characterized by symptomatic cholelithiasis at a young age (<40 years), recurrence of biliary symptoms despite cholecystectomy and concrements or sludge in the intra- and extrahepatic biliary system. The LPAC syndrome is associated with mutations of the adenosine triphosphate-binding cassette, subfamily B, member 4 (ABCB4) gene encoding the hepatobiliary phospholipid translocator multidrug resistance protein 3 (MDR3).

Long-term LDL apheresis does not stably improve hemorheology in hypercholesterolemic patients with coronary artery disease.

Hemorheological abnormalities are independent cardiovascular risk indicators and adversely affect the outcome of cardiovascular disease. Single LDL apheresis treatment was shown to improve blood and plasma viscosity, red cell aggregation and deformability. However, the long-term effects of LDL apheresis on hemorheology are still unknown.

Pathogenesis and treatment of pruritus in cholestasis.

Pruritus is an enigmatic, seriously disabling symptom accompanying cholestatic liver diseases and a broad range of other disorders. Most recently, novel itch-specific neuronal pathways, itch mediators and their relevant receptors have been identified. In addition, new antipruritic therapeutic strategies have been developed and/or are under evaluation.

Medical treatment of primary sclerosing cholangitis: a role for novel bile acids and other (post-)transcriptional modulators?

Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic disease of the liver and bile ducts that is associated with inflammatory bowel disease, generally leads to end-stage liver disease, and is complicated by malignancies of the biliary tree and the large intestine. The pathogenesis of PSC remains enigmatic, making the development of targeted therapeutic strategies difficult. Immunosuppressive and antifibrotic therapeutic agents were ineffective or accompanied by major side effects.

Primary biliary cirrhosis following Lactobacillus vaccination for recurrent vaginitis.

Background/aims: Antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex, PDC-E2, and other mitochondrial 2-oxoacid dehydrogenases (AMA-M2) are the hallmark for diagnosis of primary biliary cirrhosis (PBC). AMA-M2 formation as an early step in the pathogenesis of PBC has recently been assumed to be triggered by bacterial mimics of the E2 subunit and certain reactant xenobiotics. We report a case of symptomatic PBC diagnosed after sequential immunization with a lactobacillus vaccine for recurrent vaginitis over years.

Free fatty acids sensitize hepatocytes to bile acid-induced apoptosis.

Delivery of free fatty acids to the liver in nonalcoholic fatty liver disease (NAFLD) may render hepatocytes more vulnerable to glycochenodeoxycholic acid (GCDCA)-induced apoptosis. Fat overloading was induced in HepG2-Ntcp cells and primary rat hepatocytes by incubation with palmitic or oleic acid. Apoptosis was quantified by measuring caspase 3/7 activity and transcription of interleukin (IL) 8 and IL-22 by quantitative real-time PCR.

Medical treatment of cholestatic liver disease.

In most cholestatic liver diseases the cause of the disease is not known and therapy can only be directed toward suppression of the pathogenetic processes and amelioration of the consequences of cholestasis. The recognition of adaptive-compensatory responses to cholestasis has become of major importance. They tend to minimize retention of bile acids and other potentially toxic solutes in the hepatocyte by limiting hepatocellular uptake, reducing bile acid synthesis, stimulating detoxification, and up-regulating alternative pathways for excretion.

Tauroursodeoxycholic acid reduces bile acid-induced apoptosis by modulation of AP-1.

Ursodeoxycholic acid (UDCA) is used in the therapy of cholestatic liver diseases. Apoptosis induced by toxic bile acids plays an important role in the pathogenesis of liver injury during cholestasis and appears to be mediated by the human transcription factor AP-1. We aimed to study if TUDCA can decrease taurolitholic acid (TLCA)-induced apoptosis by modulating AP-1.

Intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is a cholestatic disorder characterized by (i) pruritus with onset in the second or third trimester of pregnancy, (ii) elevated serum aminotransferases and bile acid levels, and (iii) spontaneous relief of signs and symptoms within two to three weeks after delivery. ICP is observed in 0.4-1% of pregnancies in most areas of Central and Western Europe and North America, while in Chile and Bolivia as well as Scandinavia and the Baltic states roughly 5-15% and 1-2%, respectively, of pregnancies are associated with ICP.

Plasma separation and anion adsorption transiently relieve intractable pruritus in primary biliary cirrhosis.

Background/aims: Pruritus can be a severely disabling symptom in patients with primary biliary cirrhosis who do not respond to treatment with ursodeoxycholic acid, anion exchangers, enzyme inducers, or opiate antagonists. The aim of this study was to assess the clinical efficacy of plasma separation and anion adsorption in the treatment of intractable pruritus of cholestasis.

Methods: Three patients with primary biliary cirrhosis and intractable pruritus defined by severity of pruritus 7 on a rating scale between 0 (no pruritus) and 10 (maximal pruritus) on at least 4 of 7 days despite medical treatment were treated with plasma separation and anion adsorption on three consecutive days.

Ursodeoxycholic acid treatment of vanishing bile duct syndromes.

Vanishing bile duct syndromes (VBDS) are characterized by progressive loss of small intrahepatic ducts caused by a variety of different diseases leading to chronic cholestasis, cirrhosis, and premature death from liver failure. The majority of adult patients with VBDS suffer from primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Ursodeoxycholic acid (UDCA), a hydrophilic dihydroxy bile acid, is the only drug currently approved for the treatment of patients with PBC, and anticholestatic effects have been reported for several other cholestatic syndromes.

Malacoplakia in a renal transplant recipient.

Malacoplakia is a rare, inflammatory condition characterized histologically by distinct histiocytes with pathognomonic inclusion calcospherules called Michaelis-Gutmann bodies. It most often affects the urinary tract of immunocompromised patients. We describe a case of renal allograft parenchymal malacoplakia in a transplant recipient.

Extrahepatic manifestations of cholestatic liver diseases: pathogenesis and therapy.

Pruritus, fatigue, and metabolic bone disease are frequent complications of cholestatic liver diseases, which can be quite distressing for the patient and can considerably reduce the quality of life. The molecular pathogenesis of these extrahepatic manifestations of cholestasis is poorly understood, and hypotheses to explain these symptoms are being discussed. This article provides treatment recommendations for the complications of cholestasis based on putative pathomechanisms and summarizes recent experimental and clinical data involving management options.