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Biomedical subjects

J Orgiazzi

Publications and source records attributed to J Orgiazzi.

At least 73 records · Page 4Linked to original sources
PubMed1990

Antithyroid drugs and Graves' disease: a prospective randomized evaluation of the efficacy of treatment duration.

A prospective randomized study was performed in patients with hyperthyroid Graves' disease (GD) in order to compare long (18 months) and short term (6 months) antithyroid drug treatment on the remission rate. A therapeutic protocol was offered to all GD patients who had not been treated for this disease previously. All patients studied who followed the protocol were rechecked 2 yr after treatment was withdrawn, or earlier in the case of relapse. Of the patients having undergone long term treatment, 61.8% still were in remission 2 yr after treatment withdrawal, whereas only 41.7% of the patients treated for 6 months were in remission (P less than 0.05). Such findings clearly establish that treatment duration has a direct beneficial incidence on the remission rate. These results were confirmed by the fact that treatment for 18 months resulted in remission in 7 of 15 patients who had previously relapsed after a 6-month course of therapy. This improvement in relation to treatment duration might be due to the immunosuppressive action of carbimazole. No significant difference was observed between relapse and remission groups, regardless of treatment duration, for HLA ABDr, serum T3 and T4, and T3/T4 ratio determined before treatment. Only the thyroid-stimulating antibody levels determined at the time of diagnosis and at the end of treatment were higher in the relapse group, a difference that was relevant only globally, due to value scattering. Furthermore, thyroid-stimulating antibody levels at the end of treatment may indicate remission or, conversely, continuance of the pathological process.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[Pseudomyasthenic pre-Basedow ophthalmoplegia].

A 67-year old woman presented with isolated and bilateral external ophthalmoplegia of the myasthenic type following a subacute course and resistant to anticholesterinases and corticosteroids. A biological hyperthyroidism with immunological markers was discovered. An intensive care of corticosteroids was partially effective, but fatal bone marrow aplasia attributed to carbimazole developed. Pure ophthalmoplegia without local signs of inflammation may be the sole manifestation of dysthyroid orbitopathy.

Aged↗
PubMed1989

Rapid effectiveness of prednisone and thionamides combined therapy in severe amiodarone iodine-induced thyrotoxicosis. Comparison of two groups of patients with apparently normal thyroid glands.

Treatment of amiodarone iodine-induced thyrotoxicosis is often unsuccessful. Nevertheless, severe forms require a rapidly efficient therapy. Twelve patients with severe amiodarone iodine-induced thyrotoxicosis, as demonstrated on clinical and biological findings, were studied. After amiodarone withdrawal, 6 patients (group A) were treated with thionamides alone (carbimazole 60 mg daily and benzylthiouracile 1.5 g daily), and 6 patients (group B) received in addition to the same antithyroid drugs prednisone, 0.50 to 1.25 mg/kg/day for 40 days; in group A, T4 levels did not change over the study period of 40 days; T3 levels decreased only after 30 days; clinical status did not improve. In group B: T3 and T4 levels decreased dramatically at 10 days of treatment, to values significantly lower than in group A; clinical improvement occurred mainly in patients treated with high doses of prednisone; elevated thyroglobulin levels diminished rapidly. Improvement was maintained after cessation of prednisone. The rapid effect of prednisone suggests an impairement of proteolysis of thyroglobulin possibly due to a lysosomal action.

Adult↗
PubMed1989

[TSH receptors].

It is a paradox that thyroidology often initiates new biological concepts but lags behind in the characterization of the molecular mechanisms involved, the latter progressing more rapidly in other systems. The question of the TSH receptor is an illustration of this. This paper reviews the main aspects of the biochemistry and functions of the TSH receptor. It is stressed that the classical biochemical approach has failed in the elucidation of the structure of the receptor which should benefit from molecular biology methodologies. Experimental difficulties in the study of the TSH binding function of the receptor are also described. Functional pathways activated by the receptor are discussed, especially within the frame of current researches on the thyroid growth effect of TSH. Another important feature concerning the TSH receptor is its implication in the physiopathology of Graves' disease. Auto-anti-TSH receptor antibodies are the hallmark the disease and are responsible for the hyperfunction of the gland. Characterization of the antigenic epitopes of the receptor and biological effects of the various anti-TSH receptor antibodies, both natural polyclonal and experimental monoclonal, is also an area of active research. It is hoped that understanding of Graves' disease will benefit from improvement in our knowledge of the TSH receptor structure and functions.

Animals↗
PubMed1988

Blocking anti-thyrotropin receptor antibodies desensitize cultured human thyroid cells.

Stimulating anti-TSH receptor antibodies (TSAb) mimic TSH in the induction of refractoriness in cultured thyroid cells; TSAb and TSH desensitize one another. We investigated whether blocking anti-TSH receptor antibodies (TBkAb) have the same desensitizing effects in cultured human thyroid cells. Prolonged exposure of cells (20 h) to TBkAb followed by antigen-antibody dissociation by an acid wash step was required to induce refractoriness to subsequent stimulation of cAMP accumulation with TSH and TSAb. Cycloheximide prevented this desensitization effect. The cAMP response to forskolin was not reduced in cells pretreated by TBkAb and was increased in cells desensitized by TSH or TSAb. The pattern of the TSH dose-response curves suggested that desensitization by TSH or TSAb involved only a postreceptor mechanism but both receptor and postreceptor phenomena in the case of TBkAb. In conclusion, like TSH or TSAb, TBkAb may induce a homologous desensitization in human thyroid cells which is not mediated by cAMP.

Animals↗
PubMed1988

Lasting remissions in patients treated for Graves' hyperthyroidism with propranolol alone: a pattern of spontaneous evolution of the disease.

Twenty-six patients with Graves' hyperthyroidism treated only with propranolol for 1-21 months have been followed up to 5 years. The patients were evaluated before treatment, at 15, 30, and 90 days during treatment, and then at 90-day intervals during propranolol treatment by clinical examination and measurement of serum free T3, free T4, rT3, TSH, and sex hormone-binding globulin concentrations and serum anti-thyroglobulin, antithyroid microsomal, antithyroid peroxidase, and thyroid-stimulating autoantibodies. Eighteen patients who had no biochemical improvement during propranolol therapy or relapsed after initial improvement were treated conventionally. In contrast, eight patients had a biochemical remission, which has lasted 30-48 months after propranolol withdrawal. The biochemical values before and during treatment did not differ among the two groups of patients, except for the initial serum free T3 levels which were significantly higher in the patients who had no remission. Serum TSH levels returned to normal only in patients who had a long-lasting remission. While thyroid autoantibodies decreased or disappeared during follow-up, the evolution of thyroid-stimulating autoantibody values was grossly related to the clinical outcome. Long-lasting remissions may occur in patients with hyperthyroidism due to Graves' disease not given ablative or antithyroid drug therapy. Since propranolol is devoid of antithyroid and immunosuppressive actions, these remissions are probably spontaneous. Although they tended to occur in patients with less severe disease, no biological parameter was found that predicted the outcome.

Adult↗
PubMed1988

Hyperthyroidism due to selective pituitary resistance to thyroid hormones in a 15-month-old boy: efficacy of D-thyroxine therapy.

A 15-month-old boy had clinical features of hyperthyroidism. In spite of elevated serum thyroid hormone levels (mean serum T4, 230 nmol/L; T3, 4.2 nmol/L), serum TSH levels ranged between 3.3-5.6 mU/L and rose to 35.4 mU/L after TRH stimulation. There was no abnormal serum thyroid hormone binding or any evidence of a pituitary tumor. The boy was treated with carbimazole for 6 months and became euthyroid. However, his thyroid size enlarged, and serum TSH rose to 45 mU/L. In an attempt to suppress TSH secretion, 3,5,3'-triiodothyroacetic acid was added to carbimazole in daily doses from 0.7-1.4 mg. This combined therapy failed to suppress TSH secretion (serum TSH, 10.2 mU/L) and led to recurrence of symptoms of hyperthyroidism. A trial using highly purified dextrothyroxine (contamination by L-T4, 0.05%) as sole therapy then was carried out. Serum TSH levels promptly declined to normal, both basally and after TRH stimulation (basal, 2.4 mU/L; peak, 13.8 mU/L). During a 24-month follow-up period, the boy remained euthyroid. Serum TSH levels remained in the normal range, as did his serum L-T4 levels (93 nmol/L). Complete remission was achieved using a 5-mg daily dose of D-T4. Temporary discontinuation of D-T4 led to prompt relapse of hyperthyroidism. Our patient's TSH hypersecretion appears to be due to selective pituitary resistance to thyroid hormones. Purified D-T4 effectively inhibited TSH secretion in this patient, without inducing significant side-effects, even when the daily dose was high. The cause of partial pituitary unresponsiveness to thyroid hormones is not known. We suggest that transport of thyroid hormones into the thyrotroph cells could be deficient in our patient.

Dextrothyroxine↗
PubMed1988

Monoclonal antibody approach to the relationship between immunological structure and biological activity of thyrotropin.

In order to locate the domains involved in the biological activity of TSH and to get some insight in the relationship between immunological and biological properties of TSH, 24 monoclonal antibodies (mAb) to 11 different antigenic regions of hTSH were tested for both binding to hTSH and inhibition of hTSH stimulation of adenylate cyclase in human thyroid membranes. These mAb were also investigated for binding to bovine TSH (bTSH), and interference with bTSH binding to the receptor and stimulation of adenylate cyclase. Radioiodinated human TSH (hTSH) was incubated with increasing concentrations of mAb. Maximum hTSH binding by the various mAb ranged from 15-75% and was not related to the apparent affinity of the mAb for hTSH. Maximum inhibition by the mAb of hTSH stimulation of adenylate cyclase ranged from 3-92%. As compared to the antigenic map of hTSH, it was observed that mAb reacting with the same antigenic regions might display varying inhibition of hTSH. Nevertheless, it was clearly shown that the most potent inhibitors of hTSH stimulatory activity interacted with epitopes located on the alpha- and beta-subunits or expressed only by holo hTSH. Only 11 of the 24 mAb cross-reacted significantly with bTSH. Seven exhibited the same inhibition of hTSH and bTSH stimulatory activity; the four remaining mAb rather than to inhibit adenylate cyclase stimulation as observed with hTSH, did not interfere or even increased adenylate cyclase stimulation by bTSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1987

[Biological criteria of isolated Graves' ophthalmopathy].

The diagnostic value of biological tests, especially the thyroid stimulating immunoglobulin (TSI) assay, was studied in 29 patients with endocrine Graves' ophthalmopathy without hyperthyroidism. In 21 patients the presence of biological abnormalities (L-T3 suppression test, TRH test, presence of antithyroid antibodies) indicated that the ophthalmopathy was related to Graves' disease. The remaining 8 patients were free of any biological abnormality. The contribution of the TSI assay to the pathophysiological diagnosis of ophthalmopathy is poor. These immunoglobulins were detected in 12 out of 29 cases, but they were associated with the above-mentioned abnormalities in all but 3 of these 12 cases.

Adolescent↗
PubMed1987

Selective enrichment of phytosphingosine in glycosphingolipids of isolated human thyrocytes as compared to the whole thyroid.

The glycosphingolipids of isolated human thyrocytes have been analyzed. As compared to the total thyroid gland, the pattern of gangliosides was found to be similar, whereas the neutral glycolipid profile was quite different, with glucosylceramide as the major glycosphingolipid of thyrocytes. Moreover, this glucosylceramide contains almost exclusively phytosphingosine (4-D-hydroxy-sphinganine) which is only a minor component in the long-chain bases of the glycosphingolipids extracted from the whole thyroid gland.

Cell Separation↗
PubMed1987

[Extrarenal synthesis of calcitriol in sarcoidosis].

Mean plasma calcitriol was significantly increased in a patient with sarcoidosis and hypercalcemia without elevation of PTH. Recent studies provided evidence for an extrarenal production of calcitriol. To investigate this possibility, the conversion of calcidiol by a sarcoid lymph node homogenate was studied. After 2-hour incubation, a product was present in the incubation, which comigrated with synthetic calcitriol on two high performance liquid chromatography systems, was detected by ultraviolet absorption spectrometry and was bound with high affinity by the chick intestinal receptor for calcitriol. These results provide further evidence for an extrarenal synthesis of calcitriol, contributing to the excessive amounts of this metabolite found in the plasma of patients with sarcoidosis.

Adult↗
PubMed1987

Immunological parameters in Graves' disease: are they useful for indication and monitoring of antithyroid drug treatment?

This paper reviews the available published data on studies of a correlation between the presence or intensity of measurable immunological abnormalities or markers in Graves' disease and the outcome after a course of antithyroid drug. The following parameters are discussed: circulating anti-thyroid-stimulating hormone receptor antibodies; antitubulin antibodies; human lymphocyte antigens, and repartition of T-lymphocyte subsets. At the present time no single parameter has any real practical value for individual patients either to indicate or monitor antithyroid drug therapy. The more useful information remains the anti-thyroid-stimulating hormone receptor level at the end of treatment which, if elevated, is predictive of relapse. Several areas of research, however, appear promising.

Antithyroid Agents↗
PubMed1987

High voltage orbital radiotherapy and surgical orbital decompression in the management of Graves' ophthalmopathy.

We report on 2 groups of patients with Graves' ophthalmopathy. A group of 21 patients was treated by high voltage (18 MV) orbital radiotherapy combined with mean doses of corticoids. The results were good or excellent in 12 patients (mean score 6.62 before and 4.0 after, soft tissues greater than proptosis greater than extraocular muscle involvement), without any complications from irradiation. Patients undergoing surgery initially presented less severe symptoms, even 7 patients treated after corticoid and/or radiotherapy failure. The results were satisfactory in all patients (mean score 5.1 before and 2.4 after, proptosis greater than soft tissues greater than extraocular muscle involvement). Both methods showed results within 3 months, and they can be combined.

Eye Diseases↗
PubMed1987

Thyroid stimulating antibody: an index of thyroid stimulation in Graves' disease?

Early (20 min) thyroid radio-iodine uptake (ERU) and thyroid-stimulating antibodies (TSab) were determined in 27 untreated unselected patients with Graves' disease at the time of diagnosis. In 21 subjects the same tests were further performed in parallel during combined carbimazole-L-T3 therapy (mean duration of follow-up: 10.8 +/- 5.8 months; mean +/- SD). TSab was determined by a cAMP-human thyrocyte culture stimulation assay and expressed in microliter-equivalent of a TSab standard/ml (microliter-eq/ml). Before treatment, ERU, ranging from 15 to 54% of the injected dose (normal less than or equal to 8% dose) correlated with serum T3 (r: 0.54; P less than 0.01); TSab, ranging from 6 to 85 microliter-eq/ml was detected in 21/27 patients. There was a significant correlation between ERU and TSab (Spearman rank test: r: 0.57; P less than 0.01). During the first months of treatment, 5 of the 21 patients sequentially studied had undetectable TSab levels throughout the study and in these patients ERU decreased by 57% of its initial value; the remaining 16 subjects were divided into two groups according to ERU changes: in group A (9 patients), initial ERU decreased by 50% or more or the absolute value became less than 20% of the dose and TSab decreased from 10.9 +/- 4.8 microliter-eq/ml to 5.3 +/- 1.6 microliter-eq/ml (P less than 0.01); in group B (7 patients), the fall of ERU was less than 50% or the absolute value remained greater than 20% of the dose and TSab values remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Management of Graves' hyperthyroidism.

Management of Graves' disease hyperthyroidism, a life-long disease, hinges on a clear strategy and involves the patient's understanding and adherence. Antithyroid drug treatment is difficult to adapt to each patient's need; so far, the more efficient use of antithyroid drug remains on long-term courses of 18 months or more. Although a picture is evolving of patients more likely to go into remission after the medical treatment, its characteristics are not yet reliable. Radical (ablative) treatments are often necessary. In general, surgery might appear less appealing than 131I irradiation which, as compared to surgery, carries only the risk of later hypothyroidism. It is hoped that basic as well as clinical research is able to generate innovative, better adapted, and pathophysiologically oriented new therapeutic means.

Antithyroid Agents↗
PubMed1987

[Auricular fibrillation in hyperthyroidism. Incidence of associated cardiopathy and of dilatation of the left auricle].

In this study the mechanism responsible for atrial fibrillation (AF) in hyperthyroidism was investigated by standard cardiovascular exploration and echocardiography. Fifty four patients (43 women, 11 men, mean age 44 years) were examined during, and after successful treatment of a thyrotoxicosis episode associated with Graves' disease in 43 cases, with a secondarily toxic goitre in 7 cases and with a toxic adenoma in 4 cases. Nineteen patients presented with a heart disease: mitral valve prolapse (MVP) in 11 (including 4 with AF) and another cardiopathy in 8 (including 4 with AF). Among the 34 patients without heart disease, only 2 had AF during thyrotoxicosis. In all groups the antero-posterior diameter of the left atrium was greater in patients with AF than in those with normal sinus rhythm, but it remained within normal limits in patients with MVP. It may be assumed that in these cases AF resulted from synergism between the arrhythmogenic potential of MVP and that of the thyroid hormones. In contrast, prior dilatation of the left atrium seemed to play a predominant role in patients with another cardiopathy. The 4 patients with AF in the latter group remained with AF after the thyrotoxicosis was cured, whereas the 2 patients without heart disease and 3 of the 4 MVP patients reverted to sinus rhythm without anti-arrhythmic therapy or cardioversion. It is concluded that the presence of an underlying heart disease accounts for most cases of AF developed during thyrotoxicosis, but in 1 out of 2 cases the heart disease in a minor one, consisting of MVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗