Transient efficacy of octreotide and pasireotide (SOM230) treatment in GIP-dependent Cushing's syndrome.

We studied a 55-year old woman presenting with features of Cushing's syndrome associated with metabolic abnormalities including severe hypertension and type 2 diabetes. Urinary free cortisol excretion was within normal limits, but an unusual diurnal cortisol rhythm was observed with low morning and high postprandial levels, associated with the absence of cortisol suppression after dexamethasone, suggesting the possibility of GIP-dependent Cushing's syndrome. The diagnosis was confirmed by further investigations, showing significant plasma cortisol responses after a mixed meal test and after oral, but not intravenous glucose administration, as well as ACTH-independent bilateral macronodular adrenal hyperplasia (AIMAH). An aberrant increase in cortisol was also observed after glucagon and terlipressin injections. The patient was first treated with octreotide 100-250 µg thrice daily for 6 months, then with the new multi-ligand somatostatin analogue (SOM 230) 450-900 µg twice daily for 3 months. Although inducing a significant acute suppression of post-prandial cortisol response, both drugs had no effects on the clinical and metabolic abnormalities associated with Cushing's syndrome and new tests performed at the end of each treatment period confirmed escape of post-meal cortisol suppression to therapy. The patient finally underwent a bilateral adrenalectomy, which markedly improved her medical condition and allowed in vitro confirmation by real time RT-PCR quantification of a high aberrant expression of GIP receptor mRNA in adrenal tissue. This case report illustrates the lack of sustained efficacy of somatostatin analogues on GIP-dependent Cushing's syndrome, independent of their affinity for the different somatostatin receptor subtypes.

[Teaching of diabetics: evaluation of the questions put to patients by health care personnel and the usefulness of a pedagogic analysis]. / Enseignement des diabétiques: evalutation des questions posées aux malades par les soignants et utilité d'une analyse pédagogique.

In order to be fully therapeutic diabetes education should allow the patient to understand the mechanisms of the illness as well as the steps to be taken to achieve optimal treatment. In the course of their classes health care personnel ask diabetic patients questions with the intention of encouraging their participation. An education specialist has analysed the use of these questions: their number, their type and their functions' were noted. A) By type of question we refer to the various answers possible. Two groups can be distinguished: 1) limited number of answers possible as the result of a closed question, 2) multiple answers possible as the result of an open question. B) By function of question we refer to the cognitive effect a question may have on the patient. Again two categories can be described. In the first case numbers, terminology or facts learnt by heart; this being the result of questions of simple knowledge. In the second case, the establishment of relationships between facts as well as the solving of problem situations are encouraged by questions of understanding. The study shows that health care personnel tend to put forward closed rather than open questions. Regarding the function of the question most of them aim at simple repetition. Few activate the thinking process. As a result of the pedagogical training our team received concerning the use of questions in patient education an increase in the number of open questions and of questions of understanding was noted. These questions encourage the thinking process and the solving of problems encountered by the patient in the treatment of his/her diabetes.

Chronic lymphocytic leukemia with portal hypertension and without liver involvement: a case report underlining the roles of increased spleno-portal blood flow and "protective" sinusoidal vasoconstriction.

We report the case of a 72-year-old woman with well-controlled chronic lymphocytic leukemia (CLL) and splenomegaly who developed portal hypertension with bleeding oesophageal varices in the absence of liver fibrosis or regenerative nodular hyperplasia at surgical wedge liver biopsy. The hepatic venous pressure gradient (HVPG) was elevated and splenectomy resulted in both its normalisation and the regression of oesophageal varices. This case shows the potential for an increased spleno-poral flow to generate severe portal hypertension likely through a "protective" sinusoidal vasoconstriction.

Insulin resistance in Type 1 (insulin-dependent) diabetes: dependence on plasma insulin concentration.

Sensitivity to insulin in vivo was studied in six Type 1 diabetic patients without residual insulin secretion and without clinical insulin resistance, and in eight non-diabetic subjects, using the euglycaemic insulin clamp technique. Insulin was infused for four periods of 2 h sequentially at 0.5, 1.0, 2.0 and 5.0 mU X kg-1 X min-1; for each insulin infusion period the steady-state plasma free insulin levels were comparable in the diabetic and non-diabetic subjects. The mean +/- SEM plasma glucose concentration was 4.9 +/- 0.03 mmol/l in the diabetic subjects (coefficient of variation of plasma glucose values: 5.7 +/- 0.7%) and 4.6 +/- 0.01 mmol/l in the control subjects (coefficient of variation: 5.1 +/- 0.6%). Insulin-mediated glucose disposal was lower in the diabetic than in the non-diabetic subjects at the two lower insulin infusion rates (mean +/- SEM = 2.03 +/- 0.27 versus 4.8 +/- 0.64 mg X kg-1 X min-1 at the first insulin infusion rate, p less than 0.01, and 5.59 +/- 0.59 versus 8.36 +/- 0.61 mg X kg-1 X min-1 at the second insulin infusion rate, p less than 0.01). However, insulin-induced glucose uptake did not differ significantly between the two groups at the third and fourth rates of insulin infusion. These results show that impaired insulin sensitivity in Type 1 diabetes is dependent on insulin concentration.

[Epidemic of hantavirus disease in Entre-Sambre-et-Meuse: year 1992-1993. Clinical and biological aspects]. / Epidémie d'hantavirose dans l'Entre-Sambre-et-Meuse: année 1992-1993 Données cliniques et biologiques.

A multihospital study allowed us to follow a total of 62 serologically proven cases of Nephropathia epidemica (NE) in the Belgian region between Sambre and Meuse during the 1992-1993 period. The clinical picture consisted of sudden high fever (100% of the cases), headache (71%), abdominal or lumbar pains (80%) and, as a less frequent but very specific sign, acute myopia (24%). Non-specific respiratory symptoms such as a non-productive cough and an abnormal lung auscultation were found in 1 case out of 4. Frequent laboratory anomalies were thrombocytopenia (69%), left-shift leucocytosis (77%), abnormal LDH (69%) and an inflammatory syndrome (86%) with levels of C-reactive protein (CRP) elevated up to a mean of 102 mg/L, often accompanied by a marked fall of total serum cholesterol and a rise of triglycerides. Impaired kidney function is the rule (84%), nevertheless serum creatinine levels remain inferior to 150 mumol/L (1.7 mg%) in 25% of the patients. As for neurological signs, 1 case of encephalitis and 1 syndrome of Guillain-Barré were observed. Relative bradycardia (< 90 bpm) was noted in 50% of the cases with fever, whereas Doppler-echocardiography detected pericarditis in 1 case, and transient impairment of the left ventricle function in 3 cases. Frequent elevation of liver enzymes (46%) confirms the observation that from now on, Hantavirus infections should be considered in the differential diagnosis of viral hepatitis. One severe case was observed with shock, diffuse intravascular coagulation and adult respiratory distress syndrome (ARDS), followed by 5 other patients presenting with marked degrees of hypoxemia and hypocapnia. We conclude that not only the causative Hantaviral serotype, but also the degree of "systemic inflammatory response syndrome" (SIRS) seems to determine the clinical picture in Hantavirus infections.