Pituitary function in patients with newly diagnosed untreated systemic lupus erythematosus.

OBJECTIVES: To determine whether hormonal dysfunction involving the hypothalamic-pituitary-adrenal (HPA) axis, prolactin (PRL) secretion, and sex hormone status contribute to development of systemic lupus erythematosus (SLE). METHODS: 11 patients with SLE and 9 healthy controls were tested for their total anterior pituitary gland reserve by simultaneous injection of corticotropin-, growth hormone- (GH), thyrotropin-, and gonadotropin-releasing hormone (GnRH). Serum concentrations of adrenocorticotropin (ACTH), cortisol, GH, thyroid stimulating hormone (TSH), PRL, luteinising hormone (LH), and follicle stimulating hormone (FSH) were measured at baseline and after injection. Baseline values of oestradiol, testosterone, and thyroxine were determined. RESULTS: Basal and stimulated serum concentrations of ACTH, cortisol, GH, and PRL were similar in both groups. In contrast, despite similar basal thyroxine levels the TSH response to TRH was significantly higher in patients than in controls. LH and FSH levels in premenopausal female patients of both groups were identical. In contrast, two of the three male patients were hypogonadal without compensatory increases of basal LH and FSH levels, but they retained excessive stimulatory capacity in response to GnRH. CONCLUSION: No significant alteration of the HPA axis was found in patients with SLE, which is inadequate in view of the continuing inflammation. GH and PRL secretion were normal. The pituitary-thyroid and pituitary-gonadal axes were affected in patients with newly diagnosed, untreated SLE.

[Spontaneous healing of retroperitonea fibroasis after successful therapy of sigmoid carcinoma]. / Spontanheilung einer Retroperitonealfibrose nach erfolgreicher Therapie eines Sigmakarzinoms.

In a 64 year old man sigma cancer was diagnosed unexpectedly during an operation for retroperitoneal fibrosis (histologically benign fibrosis), that had caused unilateral hydronephrosis. In the following hemicolectomy this tumor of the colon turned out to be a medium high grade adenocarcinoma (tumor staging pT2, pN1, DUKES C). Chemotherapy with 450 mg/m2 5-FU once a week and a concomitant therapy with laevamisol was added for 6 months. Computer-tomography revealed a significant reduction of the retroperitoneal masses already before induction of chemotherapy. One year after termination of chemotherapy retroperitoneal fibrosis was no longer detectable. The course of events makes us assume that the retroperitoneal fibrosis of our patient was paraneoplastic and therefore completely reversible by successful removal of the underlying tumor.

Successful symptomatic management of a patient with Ménétrier's disease with long-term antibiotic treatment.

We present the case of a 79-year-old female patient with criteria typical for Ménétrier's disease, i.e. enlargement of the gastric folds due to foveolar hyperplasia associated with severe protein-loss along with epigastric pain, nausea, vomiting and weight loss. Gastrin levels were within the normal range, but elevated Helicobacter pylori antibody titers (83 microg/ml) were indicative of a recent infection. Histologic examination of a gastric polyp, which was removed in toto, revealed the presence of early gastric cancer of the mucosal type. After initiation of antibiotic treatment with clarithromycin (3 x 250 mg/day) and metronidazole (2 x 500 mg/day) in combination with lansoprazole (30 mg/day), the patient's condition improved rapidly along with abrogation of protein loss. Under maintenance treatment as indicated above, the patient has been free of symptoms now for a period of more than 2 years. On repetitive endoscopic follow-up, there was no change in gastric mucosa morphology either endoscopically or histologically, and also no evidence of recurrence of a malignant lesion. We conclude that this therapeutic regimen represented an effective alternative to surgical intervention in this patient and should be considered in similar cases.

[Ethylene glycol poisoning and brain injury--a dangerous combination]. / Athylenglykolvergiftung und Schädel-Hirn-Trauma--Eine gefährliche Kombination.

We report on a patient after brain injury additionally showing signs of ethylene glycol intoxication. CT-scan showed a subdural hematoma, which in spite of increasing neurological deficit didn't show any enlargement. Metabolic acidosis with an increased anion gap and osmolar gap led to the diagnosis of ethylene glycol intoxication. Then intensive hemodialysis and i.v. ethanol were administered and the intoxication could be treated successfully.

Culture of human insulinoma cells: development of a neuroendocrine tumor cell- and human pancreatic islet cell-specific monoclonal antibody.

We report on the culture of human insulinoma cells derived from a 32-year-old male patient with hyperinsulinism due to an insulinoma of the pancreas. A single-cell suspension was made by passing insulinoma fragments through a fine-gauge stainless-steel mesh. Cluster-forming insulinoma cells resembling pancreatic islets grew in the presence of fibroblasts. The insulinoma cell clusters could be differentiated from fibroblasts by using in situ pan optic staining and specific immunocytochemical staining (anti-human insulin and anti-human insulinoma monoclonal antibody (mAb) D24). mAb D24 was generated using insulinoma cells as antigen for immunization of a Balb/C mouse and cell fusion by the hybridoma cell technique. The anti-insulinoma cell mAb recognized a 32 kDa protein on immunoblot analysis of neuroendocrine tumor cells. D24 mAb also reacted immunohistochemically with normal pancreatic beta-cells and tumors such as vipoma, gastrinoma and carcinoid. Insulinoma cell clusters separated from fibroblasts by micromanipulation and plated into multiwell culture dishes exhibited an insulin-secretion rate of approximately 30 U/100 cells per 24 h with no insulin-secretory response to elevated glucose concentration. Purified insulinoma cells incubated with 1 ng/ml human nerve growth factor expressed neurofilament and neurite extension. These findings together with earlier observations in animal models suggest that human pancreatic beta-cells share some properties with neurons and are related to other neuroendocrine cells in the gastrointestinal tract.

Anterior pituitary function in patients with newly diagnosed rheumatoid arthritis.

Hormonal dysfunction involving the hypothalamic-pituitary-adrenal (HPA) axis, prolactin (PRL) secretion and sex hormone status has been supposed to contribute to the development or persistence of rheumatoid arthritis (RA). In addition, a reduced number of glucocorticoid receptors on circulating lymphocytes has been found in patients with RA. However, so far most studies have been performed in pre-treated patients. A combined test for total anterior pituitary reserve was performed in 10 patients with newly diagnosed untreated RA. Before and after stimulation with the respective hypothalamic releasing hormones, RA patients showed no difference in plasma concentrations of adrenocorticotrophic hormone (ACTH), cortisol, prolactin (PRL) and thyroid-stimulating hormone (TSH) when compared to healthy controls. In contrast, the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) was blunted in RA patients. The hypothalamic-pituitary-thyroid/gonadal and adrenal axes seem to be unaltered in RA. However, if one considers the presence of chronic inflammation, normal plasma ACTH and cortisol concentrations must be considered as inappropriately low. The observed blunted GH release could be mediated by cytokines (e.g. IL-1), which are known to be elevated in RA.

Endocrine stress reaction to surgery in brain-dead organ donors.

We studied the course of plasma levels of the stress markers adrenocorticotropic hormone (ACTH), cortisol, human growth hormone (h-GH), beta-endorphin, and prolactin during retrieval surgery in eleven brain-dead organ donors scheduled for multiple organ explantation. Donors were divided into two groups according to hemodynamic stability. Hormones demonstrated a great variability in plasma levels and in the pattern of reaction, revealing a different degree of remaining pituitary function. Beta-Endorphin was the only stress hormone that showed a response to surgical stimuli in six patients. Only three of them developed a concomitant rise in ACTH. Cortisol, prolactin, and h-GH plasma levels did not change during the observation period. In the three cases with a slight elevation in ACTH, no subsequent change in cortisol was detectable. Beta-Endorphin showed greater variability and a tendency to higher levels in the group presenting with a higher arterial pressure, which resulted in a significant difference (P < 0.005) when distributions were compared using the Mann-Whitney U-test. No correlation was found between hypotensive episodes and deficiencies of other stress hormones. We conclude that pituitary function varies considerably in brain-dead organ donors without demonstrating a correlation to the onset of hypotension. Thus, we feel no need for a substitution treatment with any of the hormones investigated prior to organ explanation.

Cardiovascular and catecholamine response to surgery in brain-dead organ donors.

Eleven brain-dead organ donors were studied during surgery. Plasma levels of adrenaline and noradrenaline were measured before and after skin incision, upon sternotomy and 15, 30 and 45 min thereafter. Haemodynamic changes were measured continuously throughout the observation period. Blood pressure and heart rate increased after skin incision, remained high at sternotomy then decreased towards the end of the observation period in six of the 11 patients. Plasma catecholamines increased promptly with the onset of surgical stimuli. We conclude that surgical stress can evoke an excessive rise of plasma adrenaline and noradrenaline and thus could impair allograft function.

[Interferon-alpha-induced disorders of thyroid function. A retrospective analysis of the literature and personal experiences]. / Interferon-alpha-induzierte Störungen der Schilddrüsenfunktion. Eine retrospektive Analyse der Literatur und eigener Erfahrungen.

This paper tries to evaluate the importance of IFN-alpha induced thyroid dysfunction. Based on our own experience and reported data we present the results obtained in a total of 588 patients, in whom thyroid function and thyroid antibody occurrence was monitored during therapy with IFN-alpha: About 10% of these patients developed thyroid dysfunction during IFN-alpha treatment. Half of them reacted with hypothyroidism, 3% with hyperthyroidism and in 2% a biphasic (hyperthyroidism followed by hypothyroidism) pattern of reaction was observed. The frequency of these thyroid dysfunctions was increased in female patients and in patients with preexisting thyroid antibodies. The risk to develop thyroid dysfunction is reduced to 7% in patients with no pretherapeutic thyroid antibodies. The evolution of the thyroid ailment is variable and therefore unpredictable. In many patients there is no need to stop treatment with IFN-alpha nor to treat the thyroid dysfunction specifically. IFN-alpha induced autoimmune- phenomena seem to be etiologically important for the development of thyroid disease during IFN-alpha. The reported data allow in our view some basic recommendations for the clinician: thyroid function and thyroid antibodies should be evaluated before the start of treatment with IFN-alpha. During therapy with IFN-alpha these parameters should be regularly (eg every 4 months) monitored. In patients with thyroid autoantibodies or dysfunction already before IFN-alpha the control intervals should not be longer than every two months.

Reactive oxygen product formation by human neutrophils as an early marker for biocompatibility of dialysis membranes.

Production of reactive oxygen intermediates (ROI) by neutrophils (PMN) in vivo was examined by a whole blood assay using dichlorofluorescein-diacetate (DCFH-DA) in 10 patients each dialysed consecutively with two different dialyser membranes. Haemodialysis (HD) with cuprophan membrane (CM) led to a significantly (P < 0.001) more pronounced ROI production by PMN (2.4 +/- 0.5-fold increase in intracellular oxidation of DCFH-DA) compared with HD with polysulfone membranes (PM; 1.5 +/- 0.2-fold). HD with CM induced a decrease in PMN count by about 90%, whereas PM induced a decrease by only 25% (P < 0.001). In CM patients maximal ROI production coincided with the nadir in PMN count. All patients dialysed with CM showed a clear increase in serum levels of Bb fragments, whereas PM-dialysed patients did not. In this respect, however, no clear time relationship was seen to the kinetics of ROI production, nor to the disappearance of neutrophils from the circulation. Evaluating a direct effect of the dialysis membranes on PMN demonstrated that incubation of neutrophils with hollow fibres of the CM but not of the PM in the absence of plasma induces significant ROI production by PMN. Our study thus indicates that ROI production by PMN during HD correlates to membrane biocompatibility. Furthermore, one might speculate that also independently from but perhaps in addition to complement activation, reactive oxygen products are critically involved in the generation of haemodialysis-associated neutrophil emigration.

The effects of lisinopril on renal function in proteinuric renal transplant recipients.

Renal transplantation is frequently accompanied by systemic hypertension. In the present study we evaluated the effect of 2.5 mg lisinopril in 12 hypertensive and proteinuric renal graft recipients with stable graft function over 3 months. Only patients with absence of renal artery stenosis, at least as judged by technetium-scan imaging, were included. Lisinopril was effective in lowering systemic blood pressure. Mean arterial pressure was unchanged despite reduction of concomitant antihypertensive medication. Mean serum creatinine was unchanged during the study (1.95 +/- 0.8 mg/dl in the pretreatment period vs. 1.77 +/- 0.76 mg/dl in the intervention period, n.s.). Glomerular filtration rate remained stable (62.75 +/- 21.96 vs. 60.17 +/- 18.27 ml/min/1.73 m2, n.s.) whereas renal plasma flow increased (224.75 +/- 91.66 vs. 244.92 +/- 94.13 ml/min/1.73m2, P < 0.01), leading to a drop in filtration fraction (31.4 +/- 12.4 vs. 26.8 +/- 8.6, n.s.). Renal vascular resistance was significantly reduced following angiotensin-converting enzyme (ACE) inhibitor therapy (26,447 +/- 14,574 vs. 23,425 +/- 12,430 dyne sec cm-5/1.73 m2, P < 0.01). Mean daily proteinuric decreased significantly (2.98 +/- 2.06 vs. 2.06 +/- 2.29 g, P < 0.01) whereas in a group of patients with comparable blood pressure but without ACE inhibitor therapy and similar degree of proteinuria, 24-hr proteinuria remained stable. No severe side effects were observed--in particular, mean serum potassium showed only a slight increase and no clinically significant hyperkalemic condition was observed. When lisinopril therapy was withdrawn after 3 months, blood pressure increased in all patients, requiring reinstitution of additional antihypertensive medication. Renal hemodynamic parameters and daily proteinuria returned to baseline values. We conclude that 2.5 mg lisinopril daily was safe and effective in this group of renal transplant recipients and showed a good antihypertensive as well as antiproteinuric effect.

Quantitation of circulating angiotensin II using commercial immunoassays.

The quantitation of circulating angiotensin (ANG) II is not consistent among various commercially available kits. We measured plasma concentrations with three radioimmunoassay kits (Bühlmann Laboratories, Basel, Switzerland; Immuno Technology Service Production, The Netherlands, and Amersham, UK). The antibody specificity and their cross-reactions with ANG I decapeptide and with fragments of ANG II, were evaluated. The antibodies of the three kits cross-reacted with nearly all immunoreactive fragments of ANG II with intact carboxyl end. Cross-reaction with ANG I was detected with the antibody of the Immuno Technology Service kit only.