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Biomedical subjects

J Orgiazzi

Publications and source records attributed to J Orgiazzi.

At least 91 records · Page 5Linked to original sources
PubMed1986

[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↗
PubMed1986

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↗
PubMed1986

[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↗
PubMed1984

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↗
PubMed1984

Paradoxical response of thyrotropin to L-dopa and presence of dopaminergic receptors in a thyrotropin-secreting pituitary adenoma.

We studied the dopaminergic control of TSH secretion in a patient with hyperthyroidism due to a TSH-secreting pituitary adenoma. A 34-yr-old previously thyroidectomized woman had mild clinical hyperthyroidism and a diffuse goiter without exophthalmos. She complained of headaches and had bitemporal hemianopsia. Serum T4 and T3 by RIA were elevated, and TSH was 112 microU/ml (normal range, 1.1-7.2). The alpha-subunit to TSH molar ratio was 1.7 (normal, less than 1), as reported in other patients with tumoral TSH hypersecretion. After TRH, a marked increase in TSH occurred. There was no evidence of pituitary deficiency. Skull x-rays and computerized axial tomography revealed an intrasellar tumor with suprasellar extension. Selective transsphenoidal adenomectomy was performed, and a pituitary tumor was removed. The tumor was almost entirely composed of cells reactive with antihuman beta TSH serum by indirect immunofluorescence. A unique feature of this patient was the marked increase in TSH levels after L-dopa administration. To our knowledge, this paradoxical response has never been reported previously in such patients. Using [3H]domperidone as ligand, dopaminergic receptors were demonstrated in the membranes of the adenomatous thyrotroph cells. The reason for the paradoxical response of TSH to dopaminergic agents is not known.

Adenoma↗
PubMed1983

[Detection of thyrostimulating immunoglobulins in whole serum. Value of the culture of human thyroid cells].

TSAb was assayed in whole serum using a human thyroid cell culture system. Sera (20.% final concentration) were added to each well (10(6) cells) at the initiation of the culture. After 48 h of incubation, total AMPc was assayed and results, when significantly different, were expressed as per cent of basal values. Among 67 untreated patients with Graves' disease, TSAb was detected in 64 (95.5%), with activity varying from 135 to 1000%. No correlation was found between TSAb activity and clinical presentation or thyroid hormones levels. None of the 7 patients with Hashimoto's thyroiditis, or of the 12 with simple goiter or of the 25 normal subjects tested was positive. One of the 10 patients with proven toxic adenoma was weakly positive. When compared under the same conditions, activities of whole sera or of corresponding ammonium sulfate precipitates were similar. Reproducibility averaged 15% and 25% within an assay and between assays respectively. Prolongation of incubations for 48 h instead of 2 h markedly increased the sensitivity of TSAb detection. This culture system provides a relatively simple, sensitive and reliable bioassay for TSAb.

Adolescent↗
PubMed1983

[Serum lipids in diabetes mellitus. Relation to equilibration and microangiopathy].

We have determined in 128 diabetic (57 non insulin-dependent (NIDDM) and 71 insulin-dependent (IDDM) patients) and in control subjects, serum total cholesterol, HDL cholesterol, triglycerides and Hb Alc levels. Presence of macroangiopathy was assessed by clinical findings. In IDDM increasingly poor control of diabetes was associated with significant increases in total cholesterol (p less than 0.001) and triglycerides (p less than 0.01). HDL cholesterol (1.19 +/- 0.39 mM/l) did not differ from control subjects (1.30 +/- 0.35 mM/l) and was not related to Hb Alc levels. NIDDM had increased total cholesterol (5.91 +/- 1.45 vs 5.38 +/- 0.93 mM/l, p less than 0.05) and triglycerides (2.06 - 0.32 to 8.80- vs 1.03 - 0.22 à 2.20 mM/l, p less than 0.01) and decreased HDL cholesterol (1.08 +/- 0.44 vs 1.31 +/- 0.36 mM/l, p less than 0.01). These differences could be explained only in part by the overweight of the NIDDM patients. There was no significant correlation in NIDDM between Hb Alc and serum lipids levels but overweight and triglycerides were positively correlated (p less than 0.02) and triglycerides and HDL cholesterol negatively correlated (p less than 0.05). IDDM with macroangiopathy had higher total cholesterol levels than those without (6.44 +/- 1.60 vs 5.29 +/- 1.22 mM/l, p less than 0.01). IDDM and NIDDM with macroangiopathy had slightly decreased HDL cholesterol; however, the diabetic subjects with macroangiopathy were older and had a longer duration of diabetes than subjects without macroangiopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

Abnormalities of heart rate and arterial blood pressure regulation in diabetes mellitus. Relation with age, duration of diabetes and presence of peripheral neuropathy.

We have determined in 46 control subjects and 117 diabetic patients with or without peripheral neuropathy (PN) the blood pressure response to standing and the heart rate variations during deep breathing (HRV) and standing (T/B ratio). HRV was abnormal in 20% of diabetics and T/B ratio only in 8%. HRV and T/B ratio decreased with age both in control and diabetic group and significant alterations of these two tests in diabetic patients were found only for the youngest subjects; HRV and T/B ratio were not related to the duration of diabetes. Ten diabetics had orthostatic hypotension. Diabetics with PN had lower HRV and T/B ratio than the others and, excluding the 10 subjects with large orthostatic hypotension, a lack of increase in diastolic blood pressure and a transient fall in systolic blood pressure on standing. T/B ratio appears in our subjects of less value than HRV for the diagnosis of cardiac autonomic neuropathy; because of the spontaneous alterations with age of the response to these tests interpretation of the results in diabetics is possible only in the presence of appropriate data in control subjects. PN in diabetic patients is strongly associated with abnormalities of heart rate regulation suggestive of cardiac vagal neuropathy and with abnormalities of blood pressure regulation suggestive of peripheral sympathetic lesions.

Adolescent↗
PubMed1983

Anti-tubulin antibodies in autoimmune thyroid disorders.

The presence of circulating antibodies directed against a cytoskeletal element, microtubules, in patients with autoimmune thyroid disorders, has been studied using pure brain tubulin as antigen. Immune complexes were immunoprecipitated using a goat anti-human immunoglobulin antibody. Twenty sera among 48 (41%) from patients with Graves' disease and nine sera among 16 (56%) from patients with Hashimoto's thyroiditis had increased levels of anti-tubulin antibodies as compared to that of 26 sera from control subjects. Only one serum among 11 from patients with toxic adenoma was positive. Very similar results were obtained using protein A adsorbent to collect immune complexes. Specificity of the tubulin binding activity was ascertained by dilution of the sera and displacement of tracer tubulin by unlabelled pure tubulin from rat or human brain. Anti-tubulin antibody titres were variable; one serum was positive at dilution higher than 1:15,000, a titre similar to those obtained in animals experimentally immunized against tubulin. Binding of labelled and unlabelled tubulin to immunoglobulins from positive sera was strictly competitive. The apparent affinity constant for the binding of tubulin to human anti-tubulin autoantibodies determined on four sera was 0.2-0.6 X 10(9)/M. There was no significant association between anti-tubulin antibodies and anti-microsomal antibodies or anti-thyroglobulin antibodies or thyroid stimulating antibodies. In contrast, only five to six per cent of sera from patients with other autoimmune diseases: lupus erythematosis or pernicious anaemia, had increased levels of anti-tubulin antibodies. In conclusion, tubulin represents a new autoantigen which is expressed rather specifically in autoimmune thyroid disorders and probably independently from the classical thyroid antigens.

Adult↗
PubMed1982

Familial hyperthyroidism without evidence of autoimmunity.

Thirty-four members of a single family were studied and 9 of them were found to be suffering from hyperthyroidism associated with diffuse goitre. Exophthalmos was absent and transmission seemed to be independent of HLA type. Four of the 9 were studied prior to treatment but in all cases serum immunoglobulin levels were normal, antithyroglobulin and antimicrosomal antibodies absent, thyroid stimulating antibodies negative and the lymphocyte transformation responses to mitogens not different from those of controls. The results of testing the euthyroid family members were similarly negative, except in the case of a woman with type I diabetes mellitus who showed a low titre of antimicrosomal antibody. Seven of the patients underwent subtotal thyroidectomy. Lymphocytic infiltration of the excised portion was rarely present. Four of the glands were subjected to immunofluorescent and electron microscopy but neither immunosecreting cells nor immune complex deposits were found. These results point to the existence of a non-autoimmune form of goitrous hyperthyroidism, different from Graves' disease.

Adolescent↗
PubMed1982

[Thyroid stimulators other than TSH. Classification. Immunoglobulins of Basedow's disease: history, methodology, nomenclature].

Two families of thyroid stimulators can be described besides TSH: a) hormonal factors, b) Graves' IgGs. Hormonal factors include: biogenic amines (catecholamines, histamine, serotonine), prostaglandins E and LH and hCG. The stimulating effect of the latters is expressed only at very high concentration. Thyroid stimulating effect of GH, insulin, cortisol, NGF and FGF is probably ancillary. Thyroid stimulating IgG were first represented by the LATS. Graves' IgGs are currently detected by their interaction with human thyroid tissue in vitro: one either detects thyroid stimulation (cAMP or hormone production) or binding inhibition of LATS or TSH. These various activities are denominated: thyroid-stimulating IgG (TSI) or antibodies (TSAb), or LATS-Protector (LATS-P) or thyrotropin binding inhibitory (TBIA). TBIA IgGs are not necessarily TSI. Thyroid growth stimulatory IgGs (TGI) have also been described as well as TSAb or TGI blocking IgG, that also block TSH effects. Graves' IgGs probably include a mosaic of specificities directed against different parts of thyroid cell surface antigens constituting, or near, the TSH receptor complex. TSI represent only one or a few types of these specificities.

Autoantibodies↗