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Editorial. Discusses prospects and problems in the treatment of disseminated Hodgkin's disease. Use of the mechlorethamine, vincristine, procarbazine and prednisone (MOPP) program in the treatment of the disease; Long-term complications after MOPP treatment of patients; Drug therapies proposed to improve complete remission induction rates and assure the durability of remissions.

Objectives: Graves' hyperthyroidism (GH) interferes with iron metabolism and elevates ferritin. The precise mechanisms remain unclear. The influence of thyroid hormones on the synthesis/regulation of hepcidin, an important regulator of iron metabolism, remains uncharacterized., Design: Prospective observational study., Patients: We included patients (n = 31) with new-onset and untreated GH., Measurements: Laboratory parameters indicative of iron metabolism (ferritin, transferrin, hepcidin), inflammatory markers/cytokines and smoking status were assessed at the diagnosis of GH (T0) and at euthyroidism (T1) in the same patients using multivariable analyses. Hepcidin was measured by mass spectrometry (hepcidin MS ) and ELISA (hepcidin EL ). The impact of T3 on hepatic hepcidin expression was studied in a cell culture model using HepG2 cells., Results: Median ferritin levels were significantly lower and transferrin significantly higher at T1 than at T0. Hepcidin MS levels were lower in males and females at T1 (statistically significant in males only). No statistically significant difference in hepcidin EL was detected between T0 and T1. Plasma levels of inflammatory markers (high-sensitive CRP, procalcitonin) and cytokines (interleukin 6, interleukin 1ß, tumour necrosis factor α) were not different between T0 and T1. Smokers tended to have lower fT3 and fT4 at T0 than nonsmoking GH patients. T3 significantly induced hepcidin mRNA expression in HepG2 cells., Conclusions: Iron metabolism in patients with GH undergoes dynamic changes in patients with GH that resemble an acute-phase reaction. Inflammatory parameters and cytokines were unaffected by thyroid status. Gender and smoking status had an impact on ferritin, hepcidin and thyroid hormones., (© 2017 The Authors. Clinical Endocrinology Published by John Wiley & Sons Ltd.)

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.

A 69 years old female patient was admitted to the hospital with anemia, loss of appetite and weight since three months. The physical examination showed extended cutaneous bleedings. Laboratory tests revealed a hemolytic anemia with fragmented erythrocytes. The bone marrow examination was characterized by erythroid hyperplasia and an invasion by mucin-producing adenocarcinoma cells. Upper endoscopy detected a small hiatal hernia with mucosal erosions between esophagus and stomach. The histology of the mucosal biopsy identified a poorly differentiated mucin-producing adenocarcinoma with portions of signet-ring cells. X-ray examination revealed osteoplastic bone metastases of the vertebrae and of the pelvis. We diagnosed a disseminated, mucin-producing adenocarcinoma of the stomach, associated with microangiopathic hemolytic anemia. In spite of rapidly begun chemotherapy with adriamycin and daily blood transfusions the woman died after four weeks.

In 1981, the Swiss Medical Association (FMH) set up an expert medical evidence office, from which patients or their dependents could request an extra-judicial expert report in cases of suspected error in diagnosis or treatment. Up to the year 1995, this office issued a total of 1675 expert reports, of which 109 were for the specialty of Internal Medicine. Since the office was founded, the number of expert witnesses called upon has continued to increase. The most common accusation was "failure to investigate or delay in investigation" (41 times, 48.2%) followed by the accusation of a "diagnostic error" (35 times, 41.2%). In 13 cases (20%) the expert report confirmed there had been a medical error, 46 (70.8%) negated such a finding, and no firm conclusion was reached in 6 expert reports (9.2%). Expert reports are very often requested by patients with malignant neoplasms, particularly if the disease is first diagnosed at an advanced stage, and these are associated with the most frequent accusation of delayed investigation. Communication problems between doctor and patient are a recurrent theme throughout the expert reports and this shows the importance of taking the patient's concerns seriously, of a well-founded explanation, and of being ready to discuss matters.

We describe a case of Niemann-Pick disease type B. A 13-year-old female adolescent of Turkish origin suffered from abdominal pain for several months, finally leading to hospitalisation. The investigations revealed splenomegaly and interstitial pneumopathy. The bone marrow contained giant foam cells typical of Niemann-Pick disease. Enzymatic analysis of a fibroblast culture confirmed the diagnosis of Niemann-Pick disease type B, with reduced activity of acid sphingomyelinase. Niemann-Pick disease is an inherited autosomal recessive lysosomal storage disorder of sphingolipids, resulting in an accumulation of sphingomyelin in the cells of the reticulo-histiocytic system due to an enzymatic defect. In Niemann-Pick disease type B the spleen and lung are the main organs affected. At present no treatment exists for this disorder.

A 64 year old patient developed severe hepatocellular damage with jaundice and coagulopathy during ingestion of a combination of paracetamol and chlorzoxazone in therapeutic dosage. The risk factors for the development of liver cell necrosis following ingestion of paracetamol in therapeutic dosage are discussed. In particular in patients with risk factors (e.g. alcoholics and patients with heart failure) paracetamol-induced liver failure has to be considered in the presence of high transaminases, even when paracetamol was ingested in therapeutic dosage. Chlorzoxazone itself rarely can induce an idiosyncratic hepatocellular damage.

A 65 year old female developed right thoracic pain, productive cough and fever four weeks after hemicolectomy because of a cancer of the sigmoid. In spite of antibiotic treatment the condition of the patient deteriorated and she was admitted to the hospital with pneumonia of an upper lobe. Chest X-ray visualized prominent proximal pulmonary arteries. Progressive respiratory failure developed and blood gas analysis revealed hypocapnic hypoxemia. The patient had to be intubated and ventilated mechanically. Later, left arm blood pressure measurements could no longer be taken and the radial pulse was missing. Thereafter, an ischemic syndrome of the right leg developed. Embolectomy from the superficial femoral artery was carried out the same day. The patient died five days later. Autopsy revealed an almost complete occlusion of the pulmonary arteries. The organization of thrombotic material indicated recurrence. Emboli were also found in the systemic circulation. A large patent foramen ovale together with signs of pulmonary arterial hypertension are indicative of paradoxical thromboembolism.

A formerly healthy 14-year old boy with difficulties at school was admitted after two generalized seizures. Blood samples taken in the emergency room revealed normal serum-values for glucose and magnesium, but low calcium and elevated phosphorus. First evaluations showed normal age-related psychophysical development, serum-PTH was elevated and serum-1,25(OH)2D was normal. A CT-scan disclosed symmetric intracerebral calcifications. Further investigations confirmed the diagnosis of pseudohypoparathyroidism type 1B. Adequate treatment with calcium and calcitriol normalized serum-calcium, phosphorus and serum-PTH. Interestingly, school performance improved, as did personal activity.

A 33-year-old man was admitted because of jaundice. Five months ago a reconstruction of the mitral valve was performed because of mitral valve insufficiency. There was a history of heroin dependence until three years ago. Laboratory tests showed normochromic normocytic anemia, increased nonconjugated serum bilirubin, decreased plasma haptoglobin, hemoglobinuria and hemosiderinuria. The peripheral blood smear contained numerous fragmented red cells, and the bone marrow showed a markedly increased erythropoiesis and absent iron stores. The clinical examination as well as echocardiography revealed severe mitral valve insufficiency; therefore, a mitral valve replacement was performed. Introperatively the mitral valve showed ruptured chordae tendineae of the posterior leaflet and a leaking stitch of the anterior leaflet. We diagnosed a macrovascular hemolytic anemia with subsequent mechanical injury and fragmentation of red cells on a dysfunctioning mitral valve.

A 51-year-old engineer was admitted with progressive lower back pain which had started 4 months before. We found an elevated ESR and anemia. Chest X-ray showed bilateral polycyclic thickening of the pleura, and abdominal CT examination revealed a paraaortic tumorous lesion and a solid kidney tumor with a diameter of 5 cm on the left side. During the course of the disease we also observed an infiltration in the apex of the upper lobe of the left lung. Histological examination showed fibrotic tissue typical of Ormond's disease in the kidney tumor as well as in the pulmonary infiltrate. We diagnosed a systemic form of retroperitoneal fibrosis. Treatment with cyclophosphamide (combined with prednisone during the first 4 months) resulted in complete remission of the disease.

A 60-year-old woman was admitted because of impairment of consciousness, vomiting and urinary incontinence. The CT-scan of the brain (without contrast agent) showed slight hypodensities in the areas of the basal ganglia. The great cerebral vein produced a very high intensity signal. We diagnosed an aseptic venous thrombosis of the great cerebral vein. The neurologic deficits increased, and an apallic syndrome was diagnosed in spite of heparin treatment. Causes of aseptic cerebral venous thrombosis are discussed.

The QBC Autoread System is based on fully automatic, electro-optical linear measurements of the discrete layers of packed blood cells in a microhematocrite tube. The layering results from differing cell densities during high-speed centrifugation. The determination of hemoglobin, hematocrit, leucocytes, platelets and of the percentual share of granulocytes and lymphocytes/monocytes with the QBC Autoread System was evaluated concerning reliability and precision in comparison with the conventional analytical methods. We used a Coulter Counter System and the manual differentiation of the stained blood smears as reference methods. The evaluation of the first 400 blood samples showed a close correlation for all hematological parameters examined, but no significant deviation relative to the reference methods. Only 83 of totally 1000 (8.3%) examined venous blood samples could not be evaluated completely by the QBC Autoread System. For the analysis of very pathological cell populations, especially of hematological oncological diseases, the QBC System is not qualified. The extreme portability, the quick practicability and the good accordance with the conventional analytical methods make the QBC Autoread System a qualified screening method for practice and emergency laboratories.