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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

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↗

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↗

[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↗

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↗

[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↗

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↗

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↗

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↗

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↗

[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↗

[Hyperthyroidism induced by amiodarone].

The incidence of amiodarone-induced thyrotoxicosis remains unclear, partly due to the difficulties encountered in making a firm diagnosis based on thyroid hormone levels. Amiodarone is known to inhibit thyroxine (T4) metabolism, thus bringing plasma T4 concentrations up to levels that may simulate T4 toxicosis. On the other hand, the iodine overload due to the drug itself may create true hyperthyroidism. The purpose of this paper is to suggest practical means of detecting thyrotoxicosis in patients on amiodarone and to discuss the treatment of this side-effect.

Amiodarone↗

T lymphocyte subsets at various stages of hyperthyroid Graves' disease: effect of carbimazole treatment and relationship with thyroid-stimulating antibody levels or HLA status.

Markers of autoimmunity in hyperthyroid Graves' disease were studied at various stages of the disease in connection with HLA status. The 148 patients studied were included in a long term prospective evaluation of antithyroid drug treatment. The proportions of total T lymphocytes and OKT4 and OKT8 positive cells in peripheral blood and circulating thyroid-stimulating antibodies were determined before treatment (M0; 46 patients), after 6 (M6; 50 patients), and 18 months (M18; 22 patients) of carbimazole treatment, at relapse (15 patients) and after 2 yr of euthyroidism after drug withdrawal (remission; 23 patients). Twenty-seven patients were sequentially studied between M0 and M6, and M6 and M18. As compared to matched normal subjects, the mean proportion of OKT8 positive cells was significantly decreased in every group of patients, even in those in remission, and the mean OKT4/OKT8 cell ratios were increased in all groups except the patients in remission. However, OKT4/OKT8 cell ratios in individual M0 patients were widely distributed, being normal in 50%. No correlation was found between the proportions of T cell subsets and thyroid-stimulating antibody values, and the two measures varied independently in patients studied sequentially. OKT8 lymphocyte subset was dependent on HLA status. In DR3-positive patients, the mean OKT4/OKT8 cell ratio was high at all stages of the study; in DR3-negative patients it decreased significantly at M18 and was normal in those patients who had a remission. However, in the DR3-positive and -negative groups of patients, the mean OKT4/OKT8 ratios at M0 and at relapse were similar. In conclusion, the proportions of circulating OKT8 positive lymphocytes reflect only poorly the activity of the immune abnormalities in Graves' disease, but do correlate with HLA-DR3 status.

Adolescent↗

[Transient neonatal hypothyroidism in a neonate born of a mother with Hashimoto's thyroiditis].

Transient neonatal hypothyroidism was found in a boy whose mother was treated for hypothyroidism due to Hashimoto's thyroiditis. During the neonatal period the infant had antithyroid microsomal and antithyroglobulin antibodies and immunoglobulins inhibiting cyclic AMP production by thyroid cells in vitro. After one year of treatment, all antibodies disappeared. Thyroid scintiscan and fixation in the neonatal period was negative and became positive 2 months after stopping treatment with normal fixation and cervical thyroid picture. The mother's serum contained the same antibodies: they crossed the placental barrier and were responsible for neonatal pathological manifestations.

Autoantibodies↗

Thyroid stimulating antibodies: an aid to the strategy of treatment of Graves' disease?

In 1976 we initiated a prospective study to specify the usefulness of thyroid stimulating antibody (TSAb) determinations in predicting the outcome of post-antithyroid drug treatment for Graves' disease. This study was carried out on 55 patients, who were either treated for six (n = 16) or 18 months (n = 39) and followed up for an additional two-year period. TSAb was determined on whole serum in 29 patients before and at the end of treatment, and in 26 patients at the end of treatment only. These determinations were carried out using a sensitive and reproducible microassay based on cAMP accumulation in human thyroid cell cultures. Before treatment, TSAb ranging from 170 to 1529% was present in 28/29 patients and reached significantly low levels at the end of treatment whatever its duration. TSAb was undetectable in 24/55 patients at the end of treatment. 8/16 'short-treated' and 18/39 'long-treated' patients remained in remission. As expected, initial TSAb levels had no predictive value. End-treatment TSAb values, when low (less than 350%) or negative did not correlate with later evolution: in these 39 patients, relapse rate was 41%. In contrast, 13/16 patients with end-treatment TSAb greater than 350% relapsed. Relapses tended to occur earlier in patients with the highest TSAb levels. TSAb determined again during follow-up was negative in each of the 18 patients in remission, and positive in 8/10 patients at the time of relapse, whatever its level at the end of the drug course. This study confirms that only end-treatment TSAb levels are predictive of relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗