Search PubMed⌕ Search

Biomedical subjects

J Orgiazzi

Publications and source records attributed to J Orgiazzi.

At least 109 records · Page 6Linked to original sources

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↗

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↗

[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↗

Evidence for circadian variations in serum thyrotropin, 3,5,3'-triiodothyronine, and thyroxine in the rat.

We previously observed that under a 12-h light, 12-h dark schedule (lights off at 1900 h), male Sprague-Dawley rats showed a circadian rhythm for serum TSH with a zenith near midday. In the present work we further characterized the serum TSH rhythm by appropriate mathematical analysis. The peak of serum TSH occurred at 1130 +/- 0105 h (mean of five experiments), with an amplitude of 0.2 +/- 0.1 microgram/ml, while the TSH level was minimum at the beginning of the dark period; the period of the TSH rhythm was 24.5 +/- 0.6 h. A circadian rhythm was also demonstrated for serum T3 and T4; these rhythms were characterized by peaks occurring 1.5 and 2.2 h after that of TSH, respectively. As expected, characteristics of the rhythm were more narrowly defined for T3 than for T4. Serum concentrations peaked at 1256 +/- 0206 and 1346 +/- 0308 h for T3 and T4, respectively; the serum T3 concentration varied from 78.7 +/- 7.8 to 54.2 +/- 2.7 ng/100 ml (P < 0.001) and serum T4 varied from 7.3 +/- 1.1 to 5.1 +/- 0.5 microgram/100 ml (P < 0.05) for zenith and nadir values, respectively. It is suggested that the diurnal peaks of thyroid hormones might be related to TSH-induced changes in thyroid secretion.

Animals↗

Regulation of TSH secretion in rats chronically exposed to heat (34 degrees C).

Previous studies have shown that in heat exposed rats, a decreased plasma T4 concentration was associated with a normal biologically active TSH concentration. This study was designed to clarify this apparent discrepancy in the regulation of TSH secretion. In experimental rats (34 degrees C for 25 days) and controls (25 degrees C), plasma total T4 was 3.2 vs. 5.7 x 10(-8) mol/l. (P less than 0.01), plasma total T3: 2.4 vs. 5.7 x 10(-10)mol/l. (P less 0.01) and plasma TSH: bioassay 0.34 vs 0.29 mU/ml (ns), radioimmunoassay: 1.04 vs. 0.87 microgram RP1/ml (ns). After TRH, plasma TSH increased identically in the two groups. In heat-exposed rats, the dialysable fraction of T4 and T3 were were increased: 0.032 vs. 0.020% (P less than 0.05) and 0.102 vs. 0.086% (P less than 0.05), respectively; accordingly, free T4 concentration was normal and that of free T3 was low; total plasma proteins were slightly increased. It is concluded that in heat-exposed rats: (1) plasma thyroid hormone binding activity was decreased as shown by the association: decreased plasma total T4--elevated free T4 fraction. The normality of the free T4 concentration accounted for the normal plasma TSH. (2) the combination of normal plasma TSH, normal plasma free T4, low plasma free T3 concentrations would suggest that T4 is predominantly involved in the regulation of TSH secretion.

Animals↗

Normal pregnancies after treatment of hyperprolactinemia with bromoergocryptine, despite suspected pituitary tumors.

Bromocryptine treatment was administered to 15 patients with amenorrhea and galactorrhea (AG) and to 1 patient with amenorrhea. All of them had increased plasma PRL levels. Of these 16 patients, 4 had a normal sella turcica (ST; group STO), 4 had a slight enlargement (group ST+), and 7 had a clear enlargement of ST (ST++) but no evidence of suprasellar extension. Ovulation was restored in 15 patients by bromocryptine treatment only. In one patient, ovulation resumed only after human pituitary gonadotropin treatment in combination with bromocryptine. There was no correlation between basal prolactinemia, PRL stimulability or suppressibility, the size of ST, or the efficiency of bromocryptine treatment. Every patient with normal LH response to either LRH or clomiphene or both resumed ovulation. Ovulation resumed in 3 patients among the 4 with abnormal LH response to either LRH or clomiphene or both. Among the 14 who desired pregnancy, 13 became pregnant. To date, 12 patients (ST++, 5; ST+, 3; STO, 4) have delivered normal babies. The courses of pregnancy were normal. During pregnancy, no change of ST was noted on lateral and frontal skull x-ray performed in every patient at trimonthly intervals. There was no change in the sellar index in 10 patients after pregnancy, as compared to the pretreatment status. In the presence of a pituitary adenoma or in patients with hyperprolactinemia and amenorrhea and galactorrhea, bromocryptine treatment may cure sterility without pituitary complication during pregnancy.

Adult↗

Approach to the mechanism of androgen overproduction in a case of Krukenbery tumor responsible for virilization during pregnancy.

Virilization may occur during pregnancy as the result of an ovarian Krukenberg tumor. mechanism of the androgen overproduction in this exceptional condition is still poorly understood. A new case is reported in which only in the postpartum clinical, endocrine, and endoscopic studies led to the diagnosis of an ovarian Krukenberg tumor secondary to a gastric carcinoma. In the mother, basal hormonal studies were done 1 and 4 weeks after delivery, then after gastric and ovarian surgery. Three months after delivery, ovarian steroid response to hCG (priming dose, 5000 IU; then 1500 IU every other day for 12 days) and a study of progesterone (P) metabolism at a steady state after a constant infusion of [3H]P and cold P (92 micrograms/min leads to blood production rate (BPR) of 152 mg/day designed to reproduce the BPR of P usually seen in pregnancy) were successively performed. Hormones were measured by specific RIAs after chromatographical purification. Basal hormonal levels were normal in the child. In the mother, on the 5th day postpartum, mean hormone levels (in nanograms per dl) were: testosterone (T), 4181; androstenedione (delta 4), 8876; 17 alpha-hydroxyprogesterone (17-OHP), 9746; P 1075; estrone (E1), 195; and estradiol (E2), 151. One month later, levels were normal for the follicular phase; T, 40; delta 4, 146; P, 52; E2, 9; and E2, 4.5. At both times, dehydroepiandrosterone was normal (703-750). Hormone levels increased progressively during hCG stimulation but their time course was different between hormones. At the end of the test, T. 144; delta 4, 746;' 17-OHP, 789; P, 723; E1, 37; and E2, 20. The MCR of P was decreased, 1450 liters/day (normal, 2020). Conversion ratios between products and precursor during constant infusion were normal. From these data, obtained in four different conditions (postpartum period, hCG stimulation, progesterone infusion, and after oophorectomy), the following can be concluded: adrenal production of dehydroepiandrosterone was normal; the ovarian overproduction of androgens likely resulted from the excessive reductive metabolism of both placental and ovarian P along the delta 4 steroid biosynthetic pathway by an hypertrophic stromal compartment; and HCG stimulation seems to be the necessary stimulus for this condition. The enhancement by T on its own peripheral production is also discussed.

Androgens↗