Electrical and mechanical abnormalities in the heart of a schizophrenic patient with hyponatremia derived from water intoxication.

Electrical and mechanical abnormalities were studied in the heart of a schizophrenic male patient with severe hyponatremia and concomitant low plasma osmolarity induced by excessive water intake (so-called "water intoxication syndrome") by recording electrocardiography and echocardiography. There was a significant positive correlation between the plasma osmolarity and serum sodium concentration. The QRS duration of electrocardiography, an index of the ventricular electrical conduction velocity, tended to be prolonged and the left ventricular ejection fraction calculated by echocardiography decreased in proportion to the reduction of the serum sodium concentration. Lowering extracellular sodium concentration theoretically slows electrical conduction velocity, and was observed in this patient. On the other hand, low external sodium concentration should increase cardiac contractility via suppression of the forward mode operation of the sodium-calcium exchange mechanism, thereby increasing the intracellular free calcium concentration. However, this was not the case in our patient, because ejection fraction was not increased but rather significantly decreased with the lowering of serum sodium concentration. We speculate that in patients with water intoxication, the negative inotropism of the heart caused by low plasma osmolarity prevails over the positive inotropism caused by low serum sodium concentration.

Sensitivity of thyroids to endogenous thyrotrophin in patients with Graves' disease.

T3 nonsuppressibility and TSH nonresponsiveness to TRH are characteristics of untreated hyperthyroid Graves' disease. Although the tests are commonly restored to normal during antithyroidal drug therapy, dissociation of TRH and T3 suppression tests have been observed in euthyroid Graves' disease and during drug therapy. Abnormalities of pituitary-thyroidal regulation and persistence of thyroid autoimmune disease have been found in Graves' patients following various modalities of therapy. The present study investigated in vivo sensitivity to endogenous TSH of thyroids in 144 Graves' disease patients following treatment with subtotal thyroidectomy, 131I, or antithyroidal drugs. After administration of TRH, thyroidal sensitivity to TSH was determined by the following: delta T3 (peak T3 minus basal T3), % increase in T3 (peak over basal), and the ratio of delta T3 to delta TSH. Significant differences in sensitivity to TSH in T3 nonsuppressible patients were found compared to suppressible patients regardless of their TSH responses to TRH or modality of therapy. These data suggest that measurements of serum T3 and TSH following TRH administration to determine in vivo thyroidal sensitivity may be substituted for the T3 suppression test as a confirmatory test for Graves' disease or as a prognosticator of relapse following therapy.

Pancreatic abnormalities in patients with eating disorders.

In patients with eating disorders, we evaluated pancreatic abnormalities using serum elastase 1 measurement by RIA and the 50 g oral glucose tolerance test (50 g OGTT). Twenty-one patients had anorexia nervosa (AN) with bulimia and vomiting (AN-B group), 30 had AN without bulimia or vomiting (AN-R group), and 25 had bulimia with normal body weight (B group). The serum elastase 1 level was determined on admission and repeated after body weight gain in 43 anorectic patients. The 50 g OGTT was performed within 2 weeks after admission. The serum elastase 1 level in the AN-B group (363 +/- 47 ng/dl, M +/- SE), and in the AN-R group (352 +/- 37) were significantly higher than that in the B group (242 +/- 18) or in the healthy female controls (191 +/- 10; n = 13). A significant decrease of serum elastase 1 was observed before and after body weight gain; however, there was no significant correlation between the serum elastase 1 level and insulin response to the 50 g OGTT. Elevation of the serum elastase 1 level in AN suggests pancreatic abnormalities other than those related to endocrinological events.

Anorexia nervosa with elevated serum TSH.

Low or normal serum TSH concentration is common during fasting and in patients with anorexia nervosa. We report here four patients with anorexia nervosa who had elevated serum TSH, low T3 and low free T4 levels when the initial diagnosis was made. Also, an appearance of TSH peak in response to TRH was delayed, but T3 responsiveness to TRH was normal. All patients were clinically euthyroid with negative serum thyroid autoantibodies and without goiter. Following weight gain, basal levels of serum T3, free T4, and TSH, as well as TSH responsiveness to TRH, returned almost to normal. The data indicated that these patients with anorexia nervosa before refeeding had either a latent transient primary hypothyroidism or the low T3 syndrome associated with an inappropriately high secretion of TSH, probably a new condition that is related to their pretreatment nutritional state.

Production of anti-glucagon sera with a C-terminal fragment of pancreatic glucagon.

The C-terminal region-sepcific anti-glucagon sera were raised in rabbits using as immunogen, and conjugate of BSA and a C-terminal fragment of pancreatic glucagon. The hapten was prepared by trypsin digestion of the glucagon, which was proved to be a 1:3 mixture of glucagon (18--29) and (19--29). Six rabbits were immunized by subcutaneous injection of an emulsion of the conjugate with complete Freund's adjuvant and five of the rabbits produced antibodies to the glucagon (GC-1, GC-2, GC-3, GC-5 and GC-6). For comparison, rabbit antisera were also produced against glucagon polymer (GA-10) and syrupy glucagon fibrils (PGA-2). All these antisera as well as the pancreatic glucagon-specific antiserum 30 K were characterized with dog gut-extract (gut-GLI) and glucagon-related peptide fragments in the radioimmunoassay systems. The assay systems utilized 125 I-monosubstituted pancreatic glucagon as tracer and human mono-component glucagon as standard. All sera of the GC-series crossreacted with the dog gut-extract very weakly and antisera GC-5 and GC-6 exhibited the lowest crossreactivities with the extract, which were shown to be as low as that of 30k. Characterization of the antiserum GC-5 with purified glucagon related fragments indicated that the major antigenic determinant located exactly in the C-terminal region of glucagon. The present results clearly showed high efficiency of the use of the glucagon C-terminal fragment as hepatenic immunogen in obtaining the C-terminal region-specific, i.e., pancreatic glucagon-specific antisera.