One year temporal pattern of neurohumoral factors and natriuretic peptides compared with clinical variables in patients with dilated cardiomyopathy.

BACKGROUND: Elevated levels of neuroendocrine peptides and hormones are some of the compensatory mechanisms activated in patients with congestive heart failure. The aim of this study was to describe their time related variability in clinically stable patients and to compare hormones and peptides levels to clinical variables. METHODS: Nineteen patients with history of congestive heart failure due to dilated cardiomyopathy and in sinus rhythm were recruited. At baseline, after 3 months, and at 1 year they underwent 6-min walk test, Minnesota Living with Heart Failure Questionnaire, and blood measurements of ANP, BNP, plasma renin activity, aldosterone, norepinephrine and epinephrine. RESULTS: After 1 year, 17 patients remained clinically stable, and did not change their therapy and functional class. Also echocardiographic data and neurohormonal parameters did not change significantly except for epinephrine that decreased significantly after 3 months and returned to a value similar to the basal one at 1 year. Two outliner values were observed for norepinephrine belonging to the only 2 patients that spontaneously withdrew the ace-inhibitor therapy during the follow-up. CONCLUSIONS: This study indicates that plasma concentration of neurohormones and peptides were fairly stable over 1 year interval in stable patients with mild-moderate heart failure due to dilated cardiomyopathy and that norepinephrine could be considered as the most sensible parameters to monitor therapy compliance.

Atrial fibrillation and mitral prolapse in a subject affected by Refetoff syndrome.

Inappropriate secretion of TSH (IST) refers to a heterogeneous group of syndromes in which patients show unsuppressed TSH levels in spite of high serum free thyroid hormone concentrations. It has been recognised that IST can be due to both thyroid hormone resistance (RTH) and pituitary TSH-secreting tumours. The former can be generalised (GRTH) or pituitary (PRTH) if the resistance is more severe in the pituitary than in the remaining tissues. This case report describes a peculiar coexistence of atrial fibrillation and mitral valve prolapse in a patient affected by generalized resistance to thyroid hormone. This finding is suggestive for a major and almost physiological sensitivity of the myocardium to the thyroid hormones activity which in the course of years may determine the modifications responsible for the pathologies described.

Prevalence of thyroid disorders in untreated adult celiac disease patients and effect of gluten withdrawal: an Italian multicenter study.

OBJECTIVES: Many afflictions have been associated with celiac disease, but chance associations may exists. The aim of this study was to establish, by means of a multicenter prospective study, the prevalence of thyroid impairment among adult patients with newly diagnosed celiac disease and to evaluate the effect of a 1-yr gluten withdrawal on thyroid function. METHODS: A total of 241 consecutive untreated patients and 212 controls were enrolled. In 128 subjects a thorough assessment, including intestinal biopsy, was repeated within 1 yr of dietary treatment. Thyroid function was assayed by measuring the levels of TSH, free T3, free T4, thyroperoxidase, and thyroid microsome antibodies. RESULTS: Thyroid disease was 3-fold higher in patients than in controls (p < 0.0005). Hypothyroidism, diagnosed in 31 patients (12.9%) and nine controls (4.2%), was subclinical in 29 patients and of nonautoimmune origin in 21. There was no difference regarding hyperthyroidism, whereas autoimmune thyroid disease with euthyroidism was present in 39 patients (16.2%) and eight controls (3.8%). In most patients who strictly followed a 1-yr gluten withdrawal (as confirmed by intestinal mucosa recovery), there was a normalization of subclinical hypothyroidism. Twenty-five percent of patients with euthyroid autoimmune disease shifted toward either a subclinical hyperthyroidism or subclinical hypothyroidism; in these subjects, dietary compliance was poor. In addition, 5.5% of patients whose thyroid function was normal while untreated developed some degree of thyroid dysfunction 1 yr later. CONCLUSIONS: The greater frequency of thyroid disease among celiac disease patients justifies a thyroid functional assessment. In distinct cases, gluten withdrawal may single-handedly reverse the abnormality.

Abnormally high TSH in subject with thyrotoxicosis affected by congenital hypothyroidism. Case report.

Inappropriate secretion of TSH (IST) refers to a heterogeneous group of syndromes in which patients show unsuppressed TSH levels in spite of high serum free thyroid hormone concentrations. It has been recognised that IST can be due to both thyroid hormone resistance (RTH) and pituitary TSH-secreting tumours. The former can be generalised (GRTH) or pituitary (PRTH) if the resistance is more severe in the pituitary than in the rest of the tissues. This case report points out the persistence of this patient's TSH resistance to the inhibition of high concentrations of circulating thyroid hormones with clear symptoms of thyrotoxicosis even after many years of replacement therapy; it also suggests that in this case FT4 is the parameter to evaluate the therapy's effectiveness.

Autoimmune thyroid diseases and coeliac disease.

BACKGROUND: Coeliac disease may be associated with a wide variety of diseases of known or suspected immunological aetiology. OBJECTIVE: To screen for both (a) the prevalence of coeliac disease in adults with autoimmune thyroid diseases, and (b) thyroid impairment among adults with coeliac disease, as compared to sex- and age-matched controls. DESIGN: Prospective cohort study. SETTING: University teaching hospital. PATIENTS: A total of 152 consecutive adults with autoimmune thyroid diseases, 185 consecutive coeliac disease patients (53 newly diagnosed and 132 already on a gluten-free diet) and 170 sex- and age-matched controls. METHODS: Screening for coeliac disease was done by means of IgA anti-endomysium antibodies, detected by indirect immunofluorescence on monkey oesophagus. Patients with positive sera underwent duodenal biopsy for diagnostic confirmation. Thyroid function was assessed by measuring the levels of serum thyroid-stimulating hormone, free T3, free T4, thyroperoxidase and thyroid microsome antibodies. Autoimmune thyroid diseases were classified according to the American Thyroid Association guidelines. RESULTS: Anti-endomysium antibodies were positive in five of 152 autoimmune thyroid disease patients (3.3%) and coeliac disease was histologically confirmed in all: this prevalence is 10-fold higher than expected. Only one patient presented with gastrointestinal complaints, but iron deficiency was found in three and alterations at bone mineralometry in all. The overall prevalence of autoimmune thyroid diseases was significantly higher (38/185, 20.5%) in coeliac patients than in controls (19/170, 11.2%). The prevalence of both hypo- and hyperthyroidism was not different from that of controls, while the prevalence of autoimmune thyroid disease with euthyroidism was 13% in patients and 4.7% in controls. CONCLUSIONS: The association of coeliac disease with autoimmune thyroid disease is not surprising as they share common immunopathogenetic mechanisms. It is advisable to screen autoimmune thyroid disease patients for coeliac disease as there is an increased risk for gluten intolerance. In contrast, thyroid function assessment in coeliac disease patients is probably less justified, although the need for a strict clinical follow-up of those patients with euthyroidism and autoimmune thyroid disease, who could develop overt thyroid impairment, remains an open question.

Initial treatment of thyrotoxic Graves' disease with methimazole: a randomized trial comparing different dosages.

We evaluated the efficacy of different doses of methimazole (MMI) as the initial therapy for Graves' disease. Fourteen patients were treated with 15 mg/die of the drug (group A) and 14 with 30 mg/die (group B). Blood samples for T3, T4, FT3 and FT4 were obtained before beginning therapy, every 48 h during the first 12 days and on the 45th day of treatment. All these hormonal parameters fell significantly from the 2nd day of therapy in both groups. All the patients, except for one in group B, had normal or subnormal levels of thyroidal hormones on the 45th day of treatment. The comparison between the two groups of regression coefficients over the first 12 days showed no significant differences. The absolute decrease of each examined parameter on day 12 was positively correlated with the relevant pretreatment value. These results demonstrate that doses of MMI (15 mg/die) much lower than those commonly recommended are able to rapidly control thyroidal overproduction as effectively as 30 mg/die.

Use of the thyroid 99Tcm scintiscan with lead-shield on the hot nodule in the diagnosis of autonomous adenoma.

Eighteen patients bearing a hot nodule, imaged by basal 99Tcm scintiscan and toxic in eight of them, were studied. All patients underwent 99Tcm thyroid scintiscan in basal conditions and after placing a lead-shield on the hot thyroid nodule, without other radioisotope administration. In eight cases the thyroid scintiscan after lead-shield overlapping the hot nodule, was compared to a second 99Tcm thyroid scintiscan after thyrotrophic hormone stimulation, TSH. This technique of nodule shielding was able to show the extranodular tissue in 15 patients; in the remaining three cases neither this approach nor the scintiscan after exogenous TSH were able to demonstrate any remainder thyroid parenchyma. Thus, this scintigraphic method can be considered excellent in the diagnosis of autonomous adenoma: it needs, in fact, a single radioisotope administration and does not present the adverse effects frequently induced by exogenous TSH.

Changes in insulin binding activity during myeloid differentiation.

Insulin binding activity and its changes in relation to terminal differentiation were studied in the HL60 human promyelocytic cell line, and in myeloid cells from both normal bone marrow and chronic myeloid leukemia (CML) patients. After treatment with dimethylsulfoxide, the HL60 line began to differentiate into more mature myeloid cells. Treated and untreated HL60 cells were found to possess specific insulin receptors with characteristics similar to those of monocytes and granulocytes. Dimethylsulfoxide induced a progressive decrease in insulin binding, parallel to the increase in the proportion of differentiated cells. Myeloid cells from CML patients were used to study insulin binding characteristics during spontaneous differentiation. They were separated on Ficoll Hypaque into a light fraction, containing mostly undifferentiated cells, and a dense fraction, containing mostly granulocytes, with similar specific insulin receptor characteristics. Insulin binding capacity, however, was twice as high in the light fraction. To compare binding activity during normal and leukemic myeloid differentiation, cells from normal bone marrow and CML peripheral blood were fractioned by BSA density gradient into enriched fractions of one predominant cell type. Insulin binding decreased in the course of both differentiations. These findings indicate that leukemic immature myeloid cells possess a high number of specific insulin receptors, and that insulin binding decreases during both spontaneous and chemically induced terminal differentiation.

Kinetic analysis of the response of plasma glucose, insulin, and C-peptide to glucagon injection in normal and diabetic subjects.

A compartmental model formed by plasma glucose, proinsulin, insulin, and C-peptide was proposed to allow a quantitative evaluation of the interrelationship among the different components of the system and to obtain a better discrimination between normal and pathologic subjects. In 11 control subjects, in 6 mild diabetics, and in 9 severe diabetics (insulin-dependent), the kinetics of plasma glucose, insulin, and C-peptide after an i.v. injection of glucagon (sampling for about 120 min) were fitted to the model which was solved with digital computing techniques. Since biphasic plasma insulin and C-peptide kinetics were demonstrated in many normals and mild diabetics, the effect of glucagon in the model was represented by a differential plus a proportional effect. The model (formed by 6 compartments and 14 transfer constants) takes into account the fact that insulin and C-peptide derive monomolecularly from proinsulin and that liver inactivates insulin. The values of the parameters obtained were submitted to stepwise discriminant analysis in order to obtain their relative importance in discriminating among the three groups of subjects. With respect to normal subjects, we found in diabetics an increased inflow of glucose into plasma; a decreased effect of glucagon in promoting the proinsulin response; a decreased effect of glucose in promoting the proinsulin response; a decreased glucose utilization; a lower coupling effect of insulin on glucose; and a higher disappearance rate of C-peptide. We observed a lower formation of insulin and C-peptide from proinsulin in severe diabetics.

[Insulin receptors in the HL60 human promyelocytic leukemic cells line]. / Recettori insulinici nelle cellule della linea promielocitaria umana HL60.

The insulin binding characteristics of human promyelocitic HL60 cell line was studied by the use pf I(125) insulin. The binding activity was found to increase linearily both with the number of cells and with the incubation time. The competition curve with increasing concentration of unlabeled insulin demonstrated of specific receptors. The number of receptors was estimated to be 6.36 . 10(6) per cell.

[Decrease of insulin binding to human acute leukemic cells during chemically induced differentiation]. / Modificazioni dell'attivita' legante l'insulina di cellule leucemiche umane durante la differenziazione indotta da sostanze chimiche.

The specific insulin binding activity of human promyelocitic HL 60 cell line during the myeloid and macrophagic differentiation induced by chemical compounds was investigated. Dimethyl sulfoxide (DMSO) and retinoic acid myeloid induced differentiation in HHL 60 cells was accompanied by a marked decrease of insulin receptors. In K 562 cell line, where DMS O has no effect on differentiation, the number of insulin receptors was only slightly affected. 12-0-tetradodecanoil phorbol 13-acetate (TPA) induced macrophagic differentiation of HL 60 cell line was also accompanied by a decrease of insulin binding activity. Our results support the hypothesis that during the process of terminal differentiation a decrease of insulin receptors occurs.

[Serum levels and kinetics of digoxin in patients with hyperthyroidism (author's transl)]. / Livelli sierici e cinetica della digossina in pazienti con sindromi ipertireosiche.

The mechanism of reduced sensitivity to digitalis in patients with hyperthyroidism has been attributed to a change of intrinsic myocardial function and/or to altered pharmacokinetics of cardiac glycosides. Digoxin kinetics have been studied in hyperthyroid and 8 euthyroid patients after a single oral and i.v. dose at steady-state. Plasma and urinary digoxin concentrations were determined by radioimmunoassay. A significantly mean lower serum digoxin concentration was found in hyperthyroid patients, both after a single oral drug administration and at the steady-stage. A decreased digoxin absorption could not account for this finding, since both the percentage of gastrointestinal uptake of the drug and maximal serum concentration did not differ in hyperthyroid patients as compared to controls. Hyperthyroid subjects showed, on the contrary, an expended distribution volume and a significantly higher excretion, as documented by a lower drug half-life, by the increase of the elimination constant and urinary digoxin output.