Acta endocrinologica. Supplementum最新文献

Sandostatin (SMS 201-995) was evaluated in the treatment of variceal bleeding in 9 patients with liver cirrhosis and portal hypertension who were undergoing injection sclerotherapy following a variceal haemorrhage. SMS 201-995 reduced directly recorded intravariceal pressure by 38%, whereas reductions in the wedged hepatic venous pressure were around 17%. These observations suggest that SMS 201-995 may prove useful in treating bleeding oesophageal varices in the acute situation. Preliminary, promising data are shown in the results of a randomized controlled clinical trial in which SMS 201-995 plus injection sclerotherapy vs injection sclerotherapy are compared in patients with bleeding oesophageal varices. Furthermore, in experimental work associated stimulating effects of SMS 201-995 are shown on the function of the reticulo-endothelial system both in the liver and peripherally. These effects may prove useful by reducing the effects of endotoxaemia and possibly result in arresting further liver damage.

Twelve patients with active acromegaly were treated with the long-acting somatostatin analogue SMS 201-995 (SMS), at a dose of 50 micrograms sc twice daily in the first 2 weeks of treatment and 100 micrograms sc thereafter. Four h after the first injection of SMS, GH levels became normal in 8 of the 12 patients. Basal glucose levels were significantly lower at the 28th day of treatment. This glucose lowering effect was stronger in the diabetic than in the nondiabetic patients. The postprandial rise of insulin levels was reversed by SMS, leading to a more pronounced postprandial rise of glucose, whereas the postprandial secretion of glucagon was also reversed by SMS. The rise of glucose levels during oral glucose loading was similar before and during SMS, despite a strong inhibitory effect of the drug on the insulin rise after glucose loading. Basal TSH levels were not influenced by SMS, the TRH-induced TSH response, however, was significantly blunted. Although the basal PRL levels were significantly reduced by SMS, the TRH-induced PRL rise was similar before and during administration of the analogue. Paradoxical GH responses to TRH disappeared in 7 out of 8 patients during SMS. Paradoxical GH responses to GnRH, however, persisted in 4 out of 4 patients. Paradoxical responses of GH after glucose loading disappeared in 2 out of 2 patients. The GH response after GHRH administration was strongly suppressed by SMS. During long-term treatment (up to 2 years), the GH level obtained within 5 h after the last injection of SMS remained normal in the patients whose GH levels normalized at the first day of treatment. There was a good response of the disease to this treatment, and no serious adverse reactions were observed. We conclude that SMS normalizes most anomalous growth hormone kinetics in acromegaly. The drug offers a new tool in the treatment of this disease.

In severe cases of e.o. IV to VI combined treatment with Cyclosporin A and corticosteroids is most effective whereas Ciamixon alone appears to be less effective. Patients who received Ciamexon some time after termination of Cyclosporin A treatment showed slight ophthalmological improvement or stabilization of the status (judged after short time of therapy). Patients with e.o. III (IV), treated ineffectively with only corticosteroids before, showed a tendency of improvement under Ciamexon treatment.

TSH is a trophic factor for cultured rat thyroid cells (FRTL-5). In the present study we have investigated the mechanism by which TSH promotes cell growth and evaluated the possible role of the adenylate cyclase (AC)-cAMP system in this process. The mitogenic activity of several agents was evaluated by measuring their effect on cell number or 3H-thymidine incorporation into DNA. Forskolin and cholera toxin, two potent and specific activators of the AC, induced a dose dependent increase of 3H-thymidine incorporation. The maximal stimulation, observed at concentrations of 10 microM and 10 ng/ml, respectively, was beta 80% of that obtained with optimal concentrations of TSH. A similar effect was obtained with a Graves' IgG preparation (0.2 mg/ml) able to stimulate the thyroid AC or with 3-isobutyl-1-methyl-xanthine (IBMX, 0.5 mM), a phosphodiesterase inhibitor. 8-bromo cAMP (0.5 mM), a cAMP analog, also stimulated 3H-thymidine incorporation, and its potency was approximately 60% of that of TSH. Similar results were obtained when the mitogenic activity of these compounds was evaluated by cell number. Norepinephrine (NE, 10 microM), although devoid of AC stimulatory activity in these cells, also stimulated 3H-thymidine incorporation, but its potency was only 20-30% of that of TSH. Indomethacin (100 microM), an inhibitor of phospholipid and arachidonic acid metabolism, was able to inhibit the stimulatory effect of NE (84%), and to a lesser extent of TSH (63%) and cholera toxin, had minor effect on forskolin (24%), IBMX (16%) and Graves' IgG (8%), and no effect on 8-bromo cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

In spite of the long-established use of antithyroid drugs, there are many unsettled questions connected with this treatment of Graves' disease. There is a lack of controlled prospective trials studying the results of antithyroid drug therapy while considering the many variables such as disease heterogeneity, regional differences, drug dosage and duration of treatment. Therefore, a multicenter study has been set up in order to compare the effects of two fixed doses of methimazole (10 vs 40 mg) with thyroid hormone supplementation on the clinical, biochemical and immunological course of Graves' disease and on remission rates. Experience accumulated so far suggests that treatment is safe using either 10 or 40 mg of methimazole. While there is a tendency for an advantage of the higher dose within the first weeks (higher effectiveness in controlling hyperthyroidism), this difference is not significant. The impact of dosage on remission rates remains to be shown.

SMS 201-995 (Sandostatin) is an octapeptide which differs in its action from native somatostatin in four ways: 1) it inhibits GH hormone secretion in preference to insulin secretion; 2) it can be administered subcutaneously or even orally; 3) it is long-acting (t1/2 after sc administration 113 min), and 4) there is no rebound hypersecretion of hormones when the effect of the analogue lingers off. In this paper a guide is offered for the use of Sandostatin in the treatment of acromegaly (after unsuccessful operation and/or radiotherapy) and of metastatic endocrine pancreatic tumours and carcinoids. A dose regimen for these two types of patients is suggested and the adverse reactions which can be expected are summarized. In addition, preliminary data are shown and the limitations are discussed of possible future indications of the analogue in the treatment of cancer, diabetes mellitus and gastrointestinal diseases.

Thyroid lymphocytes synthesize thyroid autoantibodies in close proximity to thyroid cells and consequently soluble mediators such as TSH and interleukins (IL) 1 and 2 may have unforeseen effects on lymphocytes and thyrocytes, respectively. Investigations of thyroid autoantibody synthesis by thyroid lymphocytes in vitro showed that TSH did not affect microsomal (Mic) antibody production, but thyroglobulin (Tg) antibody synthesis was decreased, probably as a result of complexing between Tg antibody and Tg secreted by small numbers of thyrocytes in the cell suspension. IL-1 and IL-2 partially mimicked the inhibitory effects on spontaneous autoantibody synthesis induced by Pokeweed mitogen (PWM) in cultures of thyroid lymphocytes. This inhibition may require a number of soluble mediators released by T cells in response to the mitogen; however, depletion studies indicated that the cell type responsible for PWM inhibition is unlikely to be a suppressor T cell and may be an NK cell. IL-1 and IL-2 had little effect on the viability of thyrocyte monolayers in an 18 h assay, but antibody dependent cells cytotoxicity (ADCC) using blood lymphocytes and thyroid autoantibody positive sera was demonstrated; further, the cytotoxicity appeared to be due to Mic antibodies. It is possible that IL-1 and/or IL-2 (as well as other cytokines) may affect thyroid cells after longer periods of exposure, either by altering them functionally or by direct damage. However, assuming that NK cells are present in sufficient numbers in the gland, ADCC could play a major role in the development of hypothyroidism in Hashimoto's disease.