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Steroidogenesis of gonadal cells is tightly regulated by gonadotropins. However, certain polycyclic aromatic hydrocarbons, including Benzo[a]pyrene (BaP), induce reproductive toxicity. Several existing studies have considered higher than environmentally relevant concentrations of BaP on male and female steroidogenesis following long-term exposure. Also, the impact of short-term exposure to BaP on gonadotropin-stimulated cells is understudied. Therefore, we evaluated the effect of 1 nM and 1 µM BaP on luteinizing hormone/choriogonadotropin (LH/hCG)-mediated signalling in two steroidogenic cell models, i.e. the mouse tumor Leydig cell line mLTC1, and the human primary granulosa lutein cells (hGLC) post 8- and 24-h exposure. Cell signalling studies were performed by homogeneous time-resolved fluorescence (HTRF) assay, bioluminescence energy transfer (BRET) and Western blotting, while immunostainings and immunoassays were used for intracellular protein expression and steroidogenesis analyses, respectively. BaP decreased cAMP production in gonadotropin-stimulated mLTC1 interfering with Gαs activation. Therefore, decrease in gonadotropin-mediated CREB phosphorylation in mLTC1 treated with 1 μM BaP was observed, while StAR protein levels in gonadotropin-stimulated mLTC1 cells were unaffected by BaP. Further, BaP decreased LH- and hCG-mediated progesterone production in mLTC1. Contrastingly, BaP failed to mediate any change in cAMP, genes and proteins of steroidogenic machinery and steroidogenesis of gonadotropin-treated hGLC. Our results indicate that short-term exposure to BaP significantly impairs steroidogenic signalling in mLTC1 interfering with Gαs. These findings could have a significant impact on our understanding of the mechanism of reproductive toxicity by endocrine disruptors., (© 2024. The Author(s).)

Bisphenol A (BPA) is a ubiquitous, synthetic chemical proven to induce reproductive disorders in both men and women. The available studies investigated the effects of BPA on male and female steroidogenesis following long-term exposure to the compound at relatively high environmental concentrations. However, the impact of short-term exposure to BPA on reproduction is poorly studied. We evaluated if 8 and 24 h exposure to 1 nM and 1 µM BPA perturbs luteinizing hormone/choriogonadotropin (LH/hCG)-mediated signalling in two steroidogenic cell models, i.e., the mouse tumour Leydig cell line mLTC1, and human primary granulosa lutein cells (hGLC). Cell signalling studies were performed using a homogeneous time-resolved fluorescence (HTRF) assay and Western blotting, while gene expression analysis was carried out using real-time PCR. Immunostainings and an immunoassay were used for intracellular protein expression and steroidogenesis analyses, respectively. The presence of BPA leads to no significant changes in gonadotropin-induced cAMP accumulation, alongside phosphorylation of downstream molecules, such as ERK1/2, CREB and p38 MAPK, in both the cell models. BPA did not impact STARD1 , CYP11A1 and CYP19A1 gene expression in hGLC, nor Stard1 and Cyp17a1 expression in mLTC1 treated with LH/hCG. Additionally, the StAR protein expression was unchanged upon exposure to BPA. Progesterone and oestradiol levels in the culture medium, measured by hGLC, as well as the testosterone and progesterone levels in the culture medium, measured by mLTC1, did not change in the presence of BPA combined with LH/hCG. These data suggest that short-term exposure to environmental concentrations of BPA does not compromise the LH/hCG-induced steroidogenic potential of either human granulosa or mouse Leydig cells.

We report the synthesis and pH dependent emission spectral behaviour of four emissive iridium(III) complexes (Ir1-Ir4) with two isomeric pairs of bis-trifluoromethyl appended benzimidazole ligands. The imidazolyl hydrogen(N-H) has been replaced by phenyl groups (N-Ph) in two ligands to understand the impact of hydrogen bonding on the photophysical properties of the complexes and it indeed plays interesting role in the charge-transfer dynamics. The pH dependent electronic spectral change is observed for two of the complexes. The enhancement of emission intensity is observed at different wavelength for pH<7 and pH>7 for Ir1 and Ir3. The emission sensing of biogenic amines with pk a values ranging from 5.80-9.74 is reported along with cellular imaging. The complex Ir1 specifically localizes within lysosome (pH=4.5-5) and thus image this organelle with great precision. The detail electronic spectra and electrochemical behaviour were reported here along with TDDFT results., (© 2024 Wiley-VCH GmbH.)

Objective: To evaluate the usefulness of submitting children with thyroid cancer secondary to nuclear accidents to a completion total thyroidectomy., Design: A case series consisting of patients living and operated on in Belarus whose parents had asked for a clinical evaluation in a western European center., Setting: A tertiary care referral center., Patients: The conditions of 47 children from Gomel, Belarus, with differentiated thyroid carcinoma following the nuclear accident at Chernobyl, Ukraine, were evaluated at the University of Pisa, Pisa, Italy. In approximately half of the cases, the treatment in Belarus consisted of a hemithyroidectomy. After a complete evaluation, the decision was made to reoperate on 19 of them by performing a completion total thyroidectomy. The preoperative evaluation revealed that 5 (26%) of the 19 patients who had undergone a hemithyroidectomy had unilateral recurrent nerve palsy and that 2 (10.5%) had hypoparathyroidism., Interventions: Neck ultrasonography was used for the preoperative localization of thyroid residuals, thyroid nodules, suspicious lymph nodes, and a guided fine-needle aspiration biopsy specimen. The circulating thyroglobulin measurement was obtained before reoperation. An iodine 131 whole-body scan (WBS) was performed and circulating thyroglobulin levels were obtained after completion of the thyroidectomy during withdrawal of levothyroxine sodium therapy., Main Outcome Measure: The number of patients with a recurrence of thyroid cancer and lung or lymph node metastases after the completion total thyroidectomy., Results: The results of the histologic examination were positive for papillary thyroid cancer in 6 (28.6%) of 21 patients, 3 with residual cancer in the remaining thyroid lobe and 3 with metastatic lymph node disease. A posttherapy WBS demonstrated lung metastases in 5 (28%) of 18 patients and lymph node metastases in 6 (33%) of 18 patients; the results of a posttherapy WBS were negative for metastases in 7 (39%) of 18 patients. Hypoparathyroidism developed in 4 (21%) of 19 patients who underwent a completion total thyroidectomy; unilateral laryngeal nerve palsy developed in 1 (5.2%) of these 19 patients. Among 22 children who previously underwent total thyroidectomy in Belarus, a diagnostic WBS showed lung metastases in 10 (45%) of the children and lymph node metastases alone in 3 (14%) of the children; the results of a diagnostic WBS were negative for metastases in 9 (41%) of the children. Statistical analysis showed a nonsignificant (P>.05) difference in the prevalence of lung and lymph node metastases in patients who previously underwent total thyroidectomy compared with patients who underwent completion total thyroidectomy., Conclusion: Completion total thyroidectomy allowed for the diagnosis and treatment of recurrent thyroid cancer and lung or lymph node metastases in 61% (11/18) of the patients in whom residual differentiated thyroid carcinoma was not previously recognized.

We compared the effectiveness of systemic corticosteroids with the use of high-dose intravenous immunoglobulin (IVIG) in the treatment of Graves' ophthalmopathy. This was performed as a prospective, nonrandomized study including a blinded ophthalmological and orbital computed tomographic (CT) evaluation. The two groups of patients were not significantly different in relation to sex composition, age distribution, duration of Graves' disease, and ophthalmopathy and previous hyperthyroidism. All patients were followed up by endocrinologic evaluation and blinded ophthalmological (before therapy = B, at the end of therapy = E, and 6 months after the end = 6M) and orbital CT (B and E) evaluations. Twenty-seven patients treated with IVIG were followed up after the end of treatment for an average of 21 months (range 12 to 48 months). Soft tissue involvement (NOSPECS) improved or disappeared in 32 of 35 (90%) patients treated with IVIG and in 25 of 27 (92.5%) patients treated with corticosteroids. Diplopia improved or disappeared in 22 of 29 (75%) patients treated with IVIG and in 16 of 20 (80%) patients treated with corticosteroids. The results observed by clinical evaluation were confirmed with orbital CT score in 30 IVIG patients and in the corticosteroid-treated patients; a significant reduction of extraocular muscle thickness was observed after treatment in both groups. Proptosis improved or disappeared in 20 of 31 (65%) patients treated with IVIG and in 15 of 24 (62%) patients treated with corticosteroids. Mean values of proptosis evaluated by Hertel's exophthalmometer showed a slight reduction both in IVIG as well as in corticosteroid-treated patients. It is interesting to observe that in 28 IVIG-treated patients in whom it was possible to evaluate soft tissue involvement, proptosis and diplopia in the period between the fifth and sixth month from the start of therapy, the most important part of the amelioration (if responders) was already obtained at that time. Responder patients were defined in relation to the decrease in the highest NOSPECS class or grade. Among IVIG-treated patients 26 of 34 (76%) responded; while in the corticosteroid group 18 of 27 (66%) responded to treatment. The prevalences of patients who responded to the treatments were not significantly different in the two groups (Chi-square). The initial values of the subjective eye score were similar in the two groups, and a significant reduction was observed in both. Major side effects requiring discontinuation of the corticosteroid therapy were observed in two patients with hemorrhagic gastritis and in one patient with manic-depressive psychosis. Among 15 patients submitted to the evaluation of bone mineral content before and after corti-costeroid therapy, 4 presented signs of osteoporosis and 3 a reduction of bone mineral content. Moderate and minor side effects were more frequently noted in steroid-treated patients than in the IVIG group. These data suggest that IVIG is safe and effective in reducing the eye changes in patients with Graves' ophthalmopathy.

To evaluate the presence of asbestos-related pleural and parenchymal abnormalities and their correlation with pulmonary function and smoking habits, 119 asbestos-exposed asymptomatic workers (mean age, 46.2 years; mean duration of asbestos exposure, 8.6 years; mean latency time, 21.6 years) with normal standard P.A chest radiographs were submitted to HRCT, CO-diffusing capacity and pulmonary function tests. HRCT scans were normal only in 31 (26%) examined workers; 31 (26%) subjects showed both pleural and parenchymal involvement, and 50 (42%) and seven (6%) had exclusively pleural and parenchymal abnormalities, respectively. Based on CO-diffusing capacity and pulmonary function tests, no significant difference was demonstrated between workers with pleural lesions and subjects with normal pleura; however, lower values of FVC were observed in the nonsmoking workers with parenchymal abnormalities in comparison with nonsmoking subjects with normal parenchyma (78.2 vs. 89.7% of predicted values; p = 0.03 by student's two-tailed t test), and lower values of FEV1/FVC in the smokers with parenchymal lesions with respect to smokers with normal parenchyma (93.7 vs. 100.2% of predicted values; p = 0.005 by students' two-tailed t test). In conclusion, our results demonstrate that HRCT may detect early parenchymal abnormalities which correlate with exposure to asbestos and respiratory function impairment, including a reduction in obstructive indices in smokers occupationally exposed to asbestos, without any clinically evident disease.

This study reviews the epidemiology of thyroid cancer during childhood from the environs of Gomel in Belarus and the clinical data of 64 children aged 4 to 16 years from this area who had been diagnosed with differentiated thyroid carcinoma following the nuclear accident of Chernobyl. One case of thyroid cancer in children (aged < 15 years at diagnosis) was observed during the period 1981-1985 (rate = 0.5; expressed as annual averages per million children under age 15 years in the region of Gomel and period identified) before the Chernobyl accident. Twenty-one cases of thyroid cancer in children were observed during 1986-1990 (rate = 10.5) and 143 (rate 97) during 1991-1994 after the Chernobyl accident. During the first 7 months of 1995, there were 33 more cases of thyroid cancer observed in children. Three children with thyroid cancer were born since 1986 in the Gomel region. A total of 64 children aged 4 to 16 years from this area who had been diagnosed with differentiated thyroid carcinoma had been reviewed by us during the period May to November 1994. The female/male ratio was 1.4:1.0. At the time of the first diagnosis the mean age of the children was 9.4 +/- 2.8 years, and at the time of the accident their mean age was 3.8 +/- 2.4 years. More than 90% of the patients were less than 6 years of age and 3 were still in utero at the time of the accident. The period of latency between the accident and the first diagnosis was 5.6 +/- 1.5 years. Their ages at the time of the first diagnosis and their ages at the time of the accident were significantly correlated (p = 0.001); there was no significant correlation between the age of each child at the time of the accident and the latent period before the onset of carcinoma. The aggressiveness of the tumor, evaluated on the basis of T stage, lymph node status, and lung metastases, did not correlate with age at the time of the first diagnosis or with the age at the time of the accident. The susceptibility of the thyroid to the carcinogenetic effects of radiation, particularly during the first years of life (< 5 years) has clearly been demonstrated. However, there appears to be no correlation between the aggressiveness of the tumor and the age of the patients.

The prevalence of thyroid nodules was studied with ultrasonography in a group of male hospital workers (n = 44) who had been exposed occupationally to x-rays. This group was compared with a group of nonexposed workers (n = 88) who were age- and sex-matched with the exposed workers. Thyroid nodules were detected in 18 (41%) of the exposed workers, compared with 11 (13%) of the nonexposed controls. Both groups were subdivided with respect to age (i.e., 30-39 y, 40-49 y, 50-59 y), and there was a higher and significant relative risk for thyroid nodule formation in the exposed group. We also divided the groups into subgroups according to levels of exposure (i.e., nonexposed, exposed for < 20 y, and exposed for > 20 y), and a significant result was obtained with the linear-trend chi-square test. The preliminary results of our study suggest that occupationally induced exposure to radiation may be a risk factor for thyroid nodule formation.

Objective: To study the involvement of antibodies in the extrathyroidal manifestations of autoimmune Graves' disease, we determined the presence of IgG, IgA and IgM antibodies and C3c in connective tissue samples from patients with Graves' disease and pretibial myxedema (PTM) or thyroid associated ophthalmopathy (TAO)., Methods: Connective orbital tissue samples were obtained from 12 patients undergoing orbital decompression for TAO, and skin samples from lesions on the pretibial area were obtained in 7 patients with PTM. Sections from each tissue sample were stained with fluorescin-isothiocianate conjugated anti-human IgG, IgA, IgM and C3c and were examined by a fluorescence optical instrument. Other serial sections from each sample were incubated with human IgG solutions (concentration 6 mg/ml or 20 mg/ml), human albumin (40 mg/ml), PBS, myoglobin (40 mg/ml), or IgA (20 mg/ml), and were then processed by a standard direct immunofluorescence staining procedure., Results: Among the samples from TAO patients 8/12 (67%) were positive for IgG deposition, 4/9 (44%) were positive for IgA, 1/9 (11%) was positive for IgM and 4/9 (44%) were positive for C3c deposition. Orbital connective samples from 3 non-TAO patients were all negative. Among samples from PTM patients 4/7 (57%) were positive for IgG deposition, 3/ 4 (75%) were positive for IgA, 0/4 was positive for IgM and 3/7 (43%) were positive for C3c deposition. Skin samples from 5 control patients undergoing skin biopsy for non-autoimmune diseases were all negative. Incubation with human IgG (20 mg/ml) resulted in the complete disappearance of IgG and C3c deposition in all positive patients. No significant variation in IgG fluorescent staining after incubation with either 6 mg/ml of IgG solution, human albumin, PBS, myoglobin or IgA was observed., Conclusion: The results of our study suggest that different classes of antibodies, mainly IgG and IgA, may be implicated in the disease process in autoimmune TAO and PTM. Activation of the complement cascade, via the classic or the alternative pathway, could take place in about 40% of these patients. IVIG in vitro may solubilize, by a specific mechanism, IgG and complement immune complex deposition in the extrathyroidal manifestations of autoimmune Grave's disease.

Objectives: To examine, by ultrasonography the prevalence of thyroid nodules in a cross sectional study of male medical workers occupationally exposed to chi radiation at the Pisa hospital, in comparison with controls matched for age and sex., Methods: 50 male medical workers exposed to radiation were randomly matched for age (+/- 2 years) with 100 male workers not occupationally exposed to ionising radiation who lived in a slightly iodine deficient area of Tuscany (Lunigiana) (control group 1), and with 100 male workers not exposed to radiation who lived in the same area (Pisa) (control group 2)., Results: Of the occupationally exposed subjects, thyroid nodules were detected in 19/50 (38.0%). Among controls, thyroid nodules were detected in 19/100 subjects of control group 1 and in 13/100 of control group 2. Comparison of exposed and control groups, stratified into 30-39, 40-49, and 50-59 year old age subgroups, showed a higher significant relative risk for thyroid nodules in the exposed subjects., Conclusion: The results suggest that occupational exposure to radiation may be a risk factor for thyroid nodules.

The aim of the study was to evaluate the role of neck ultrasonography in follow-up of patients with differentiated thyroid cancer. Sixty-three patients had total thyroidectomy and 131I ablation for differentiated thyroid cancer and had a negative whole body scan during follow-up. They were admitted for a high resolution neck ultrasound examination. Sixteen of 63 patients presented images suspicious for lymph node metastasis and/or for local recurrences (4 cases). Fine needle aspiration confirmed the suspicion of malignancy in 12 patients: only lymph node metastasis in 8 cases, local recurrence and lymph node metastasis in 3 cases, and in one case only local recurrence. Fine needle aspiration was suspicious for lymphadenitis in 4 cases. Thyroglobulin levels were very high in all patients with local recurrence and/or lymph node metastasis but undetectable in 2 cases presenting node metastasis and in 4 cases with lymphadenitis. All but one patient were admitted for surgery and the cytological diagnosis was confirmed. Early identification of a pathologic mass in the neck is a desirable goal; high resolution echography can play an important role in the follow-up of these patients and can detect local recurrences even when there is a negative whole body scan or undetectable thyroglobulin level.

Seven patients affected by Graves' ophthalmopathy and pretibial myxedema (four patients with nodular form, two with diffuse, and one with elephanthiasic form) have been treated with high-dose intravenous immunoglobulins. We have observed (a) clinical improvement of pretibial myxedema and Graves' ophthalmopathy in all patients, (b) a reduction of pretibial skin thickness, by ultrasonography evaluation, in four patients, (c) a reduction of mucopolysaccharide skin content in three patients, (d) disappearance of lymphocytic skin infiltration and IgG deposition in two patients, and (e) a parallel reduction of the titer of circulating autoantibodies as antithyroglobulin, antimicrosomal, anti-TSH receptor, and of non-organ-specific antibodies as antinuclear, anti-smooth muscle cells, and anti-mitochondrial. In comparison two patients with Graves' ophthalmopathy and pretibial myxedema treated with systemic corticosteroids did not present any improvement of the cutaneous ailment. Therefore, this study suggests that intravenous immunoglobulins are effective in the treatment of pretibial myxedema and may have an immunomodulant action in patients with Graves' disease and related disorders.

We compared the results of ethanol sclerotherapy in thyroid cysts with emptying of cysts and instillation of saline. Twenty-six patients with recurrent thyroid cysts were treated with cyst aspiration and subsequent ethanol sclerotherapy. A control group of 44 patients was submitted to cyst aspiration and subsequent injection with isotonic saline; among them 20 had previously been treated with repeated aspirations of the cyst fluid. The patients were followed up clinically and ultrasonically 1 and 12 months after treatment. Cure was defined as the absence of any residual cystic lesion or an ultrasonic cyst volume less than 50% of basal after 12 months from the start of treatment. Cytological study showed all of the lesions to be benign. Of the 44 patients in the saline group 16 (36%) were cured, among whom 6 of 20 had previously been submitted to repeated aspirations. Among the 26 patients treated with ethanol sclerotherapy 20 (77%) were cured. Statistical analysis revealed a significantly higher effectiveness of treatment with ethanol than that with emptying and saline instillation (chi-square, P = 0.002) or with repeated aspiration and saline instillation (chi-square, P = 0.003). Slight pain was observed in two patients treated with saline and five treated with ethanol sclerotherapy. Three patients treated with ethanol sclerotherapy presented severe pain and one transitory hyperthyroidism. We conclude that ethanol sclerotherapy is effective and safe in the treatment of thyroid cysts.

The possibility to detect initial "preclinical" pulmonary lesions related to asbestos is under debate. The aim of this study is to report our experience. We have submitted to HRCT 70 shipyard workers with chest X-ray judged "normal" by "outside" readers (mean age 44.5 +/- 6.1 ys) with a similar grade of (low-level) exposure to amosite (mean duration of "direct"/"heavy" exposure was 4.2 +/- 4.9 ys; "environmental"/"light" exposure was 8.4 +/- 5.9 ys). Among the 70 workers, in 34 pleural plaques were shown, in 6 subjects parenchymal abnormalities alone and in 13 parenchymal and pleural abnormalities were found; in the last 17 workers no pathological finding was shown. In six subjects the presence of a combination of parenchymal abnormalities permitted us to diagnose asbestosis. The difference in the duration of exposure to asbestos for the subjects with both pleural and parenchymal involvement compared to all other groups of workers was statistically significant; also the difference in duration of exposure between workers with or without parenchymal involvement resulted significant. In a control group (20 subjects without any known professional exposure to asbestos) HRCT permitted us to identify 5 cases with small pleural plaques while only one case presented parenchymal bands; lesion frequency was significantly lower in comparison with the exposed group. Calcified plaques have been proved to be more common in the workers with heavier exposure, and no one of the reference group had calcified plaques. The CT-determined emphysema score was found to optimally correlate with smoking habit (pack/years). In conclusion our study suggests that pulmonary or pleural involvement can be shown by HRCT before the onset of any clinical symptomatology with high sensitivity and specificity. Furthermore the results seem to indicate that the prevalence of HRCT-shown parenchymal lesions and the severity of lung involvement among asbestos-exposed workers are related to the duration of exposure, as in most of clinically evident asbestos-related lung disorders, in contrast with previous observations.

We have reexamined a series of 1119 patients consecutively submitted to fine needle aspiration of nodules of the neck. Among these in 166 cases ultrasonography combined with aspiration suggested the presence of cysts. 60 patients were submitted to cyst aspiration and 34 were aspirated and submitted to cyst injection with tetracycline hydrochloride. The patients were followed up clinically and ultrasonically 3 and 12 months after treatment. Cure was defined as the absence of any residual cystic lesion and an ultrasonic cyst volume less than 50% with respect to basal after 12 months from the start of treatment. 18 of the 60 (30%) patients only aspirated and 24 of the 34 patients (70%) in the tetracycline group were cured (statistically significant; p < 0.005). We conclude that tetracycline seems an effective sclerotherapy in treatment of thyroid cysts.

The lungs of 50 symptom free workers exposed to amosite and with normal pulmonary function tests were examined by high resolution computed tomography (HRCT). Twenty five had normal standard chest radiographs whereas the other 25 had radiographs interpreted as near normal (International Labour Office profusion score < 0/1 or suspected pleural plaques). In 13 of the workers the results of HRCT were negative; in 22 pleural plaques were found, in five there was only parenchymal involvement, and 10 had both pleural and parenchymal changes. The mean duration of exposure to amosite was significantly longer for the subjects with parenchymal signs than for those with normal parenchyma and for the workers with pleural plaques than for those with normal pleura and lung parenchyma. The prevalence of identified pleural and parenchymal abnormalities in the 50 workers was also significantly higher than in a reference group without exposure to asbestos. It is concluded that HRCT may detect initial lung and pleural involvement in symptom free workers exposed to amosite and the mean duration of exposure is longer for subjects with parenchymal or pleural involvement.

Benign thyroid cysts often recur after aspiration; the effectiveness of tetracycline instillation in the case of recurrence has been questioned. We, therefore, tested the efficacy of percutaneous ethanol injection in 20 patients with "pure" cyst relapsing after aspiration. After evacuation, 95% ethanol was instilled under sonographic guidance and re-aspirated 5 min later. The procedure was performed twice for larger cysts. Follow-up studies were carried out after 1, 3, 6, and 12 months. In case of recurrence at 1 month, patients (n = 5) were submitted to a second session. A slight burning sensation was the only adverse effect. No recurrences were observed at 3 and 6 month follow-up; only one patient with recurrence after 1 month had relapsed at 12 months. A significant shrinkage (P < 0.0001 vs. pretreatment) was observed in all other cases at 12 months; cysts were not detectable in seven patients (35%). No significant variations in thyroid hormone levels were detected during treatment or follow-up. Serum thyroglobulin levels markedly increased 3 h after ethanol injection. One month after treatment, thyroglobulin returned to pretreatment levels, thus excluding progressive thyroid damage. Percutaneous ethanol injection may prove a safe and effective tool for the therapy of thyroid cysts.

Sonographically guided percutaneous ethanol injection (PEI) has been recently used with excellent results in the treatment of toxic and pretoxic thyroid adenoma. The aim of the present study was to assess the efficacy of PEI also in the treatment of "cold" thyroid nodules. Twenty patients, each with a single thyroid nodule, underwent PEI. In all cases the nodules were found to be cold by thyroid scintiscan. A total of 16.1 mL +/- 3.1 mL of ethanol was injected once a week. No adverse effects were observed during therapy. A striking nodular shrinkage was obtained in all cases, ranging from 72.8% to 97.6% (mean 84.5%, p < 0.001 vs pretreatment volume). These preliminary results suggest that PEI is an effective and safe therapy that may be useful in the treatment of thyroid nodules as an alternative to other therapies (surgery, L-thyroxine).

Background: Levothyroxine has often been given to patients operated on for nodular goiter to prevent recurrence. The rationale is that suppression of thyroid-stimulating hormone (TSH), considered to be the main growth factor in this disease, can be obtained by administration of levothyroxine., Methods: Sixty patients undergoing operation for nontoxic nodular goiter were randomized in two groups: (1) thirty-two were administered levothyroxine at substitutive dosage (100 micrograms) or placebo and (2) twenty-eight were given levothyroxine at suppressive dosage (2.2 to 3 micrograms/kg/day). Levels of thyroid hormones and TSH were evaluated every 6 months. Recurrences detected by echography were then considered., Results: After a 3-year follow-up we observed 25 of 32 recurrences in group 1 and 6 of 28 in group 2 (p < 0.005). Subjects with endemic goiter problems responded better to therapy. Patients with a multinodular goiter responded better than patients with a uninodular goiter. No difference was found regarding the type of surgical treatment (subtotal thyroidectomy vs lobectomy)., Conclusions: The results confirmed suppressive therapy as actually being effective in preventing recurrences at least in iodine-deficient regions like Italy. Thus for these patients it may be suggested as a prophylactic treatment after operation.

C cells of the thyroid probably exert a paracrine control on follicular cells through secretion of peptides such as calcitonin and somatostatin. The aim of the present study was to investigate the expression of different peptides produced by C cells in rat thyroid and in the different morphological and pathological conditions of the human thyroid. Therefore we employed the immunohistochemical double-staining method using anti-calcitonin and anti-somatostatin antibodies. The results of this study show the presence of C cells containing calcitonin and C cells containing somatostatin exclusively in the rat and the human thyroid. This distinction with prevalence of one peptide on the other is maintained in the different morphological and pathological conditions of the human thyroid.

Frank hypothyroidism is known to induce neurological and mental dysfunction. The aim of this study was to assess selected neuropsychological and behavioral features by means of standardized tests in a group of 14 patients with subclinical hypothyroidism who were free from neuropsychological complaints and to evaluate the possible effects of L-thyroxine treatment on their performance. Patients were submitted to the Crown and Crisp Experiential Index and to the Wechsler Memory Scale; their ratings on the neurobehavioral tests and their thyroid hormone profile were compared to those of a control group of 50 age- and sex-matched subjects. Comparison was also carried out between pretreatment ratings and those obtained following a 6-month L-thyroxine course (0.1-0.15 mg/day). The Wechsler Memory Scale ratings showed a significant impairment in patients' memory-related abilities [memory quotient (MQ) = 89.1 +/- 2.9; P = 0.002 (patients versus controls)]; the Crown and Crisp Experiential Index ratings demonstrated moderate differences between untreated patients and controls with respect to hysteria (P = 0.03), anxiety (P = 0.05), somatic complaints (P = 0.0005), and depressive features (P = 0.002) scales; the total score was also significantly higher (42.0 +/- 3.8; P = 0.005). After L-thyroxine treatment the patients' performances showed an improvement in memory skills, as evaluated by the Wechsler Memory Scale [MQ = 99.9 +/- 4.0; P = 0.002 (treated versus untreated)]; somatic complaints (P = 0.02) and obsessionality (P = 0.04) ratings and the Crown and Crisp Experiential Index total score (P = 0.04) significantly decreased with respect to untreated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Concentration of C cells in the thyroid of rats treated with Mercaptoimidazole or Levo-thyroxine. The aim of the present study was to elucidate the possible functional relationship between follicular and parafollicular cells of the thyroid gland; therefore we have investigated the behaviour of calcitonin producing cells and serum calcitonin concentration in rats both in resting and hyperstimulation conditions of follicular cells. Our results showed that with regard to follicular mass the concentration of the C cells was reduced in the two groups of rats treated compared to control rats. C cell concentration decrease was associated with reduced serum calcitonin concentration. In conclusion C cell activity is independent of TSH and thyroid hormones circulating levels.

Thyroid adenoma is commonly associated with surgery and radiometabolic treatment; recently, according to previous successful reports, percutaneous ethanol injection therapy under sonographic guidance, has been introduced as an alternative. This technique has already been favourably used in the treatment of focal lesions, such as liver cancer and hyperparathyroidism. In our experience, we have treated with such therapy 69 patients affected by thyroid adenoma (55 females, 14 males; 28 pretoxic, 41 toxic). Ethanol (0.5-2.8 mL/mL nodular tissue) was injected, under sonographic guidance, in 4-9 sessions (1 weekly). Thyroid hormone profile was assessed during treatment and at 3 and 6 months follow-up. Apart from local transient pain in 21% sessions, two cases of pyrexia (38.5 degrees-1 day) and 3 cases of transient dysphonia, no relevant adverse effects were observed. A slight thyroid hormone increase was seen in both groups immediately following treatment. Six months after therapy a biochemical and clinical remission of hyperthyroidism was observed in 33 out of 41 toxic patients (80%); a significant increase of TSH levels was seen in both groups (p < 0.001). With follow-up, significant volume shrinkage (70-80% volume reduction--p < 0.0001) as well as structural alterations of the nodule, were consistently recorded at sonography, in both groups; a linear relationship (p < 0.0001) between pretreatment volume and volume reduction was found. At scintiscan functional activity of extranodular parenchyma was found in 75% of patients affected by pretoxic adenoma and in 63.1% of patients with toxic adenoma. These data confirm that percutaneous ethanol injection therapy is effective in obtaining functional ablation and in inducing remission of hyperthyroidism, when present; so it represents a valid and safe alternative to standard therapeutic tools of thyroid adenoma.

We report a case of phosphate diabetes in a patient with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with sarcoidosis. Our patient was affected by systemic sarcoidosis and he fits the criteria of Schwartz for the diagnosis of SIADH. He presented with phosphate diabetes which appeared during demeclocycline (DMC) therapy and persisted for about 1 month from the end of DMC. It constitutes the fourth case of phosphate diabetes induced by tetracycline described in the literature and it is the third case of SIADH associated with sarcoidosis.

A 72-year-old woman was referred to our hospital for diarrhea, abdominal and back pain, weight loss, low serum potassium level. Pathological findings and high circulating Vasoactive Intestinal Peptide (VIP) levels allowed us to diagnose "VIPoma syndrome". The patient underwent a treatment with SMS 201-995 with improvement of symptomatology and reduction of circulating VIP levels. After a wash-out period the patient was treated with salmon calcitonin with a net improvement of diarrhea, normalization of potassium serum level and reduction of VIP level. The symptomatology recurred after calcitonin withdrawal. These data confirm the effectiveness of SMS 201-995 in the VIPoma syndrome and suggest that calcitonin may ameliorate symptomatology and reduce circulating VIP level in patients with VIPoma tumor.

Endemic cretinism is still present in an endemic goiter area of the central Apennines (Montefeltro) (goiter prevalence 55%; mean urinary iodine level 39 micrograms/g creatinine). Clinical and biochemical features of patients with myxedematous, neurologic, and mixed cretinism were studied. Also, in this area, as in most other, neurologic cretinism is more prevalent than myxedematous and mixed forms. The hormonal profiles of the three types of cretinism were clearly different. Nevertheless, all myxedematous cretins had some neurologic disorders (hyperreflexia, increased muscle tone, disorder of gait, Babinski sign, hypoacusia) that were similar to those present in neurologic cretins. These findings suggest that neurologic damage is very similar in all forms of endemic cretinism, reflecting a diffuse insult to the developing fetal nervous system. Furthermore, these data support the hypothesis that the primary pathophysiologic event in the different types of endemic cretinism is represented by maternal and fetal hypothyroidism, while differences may be explained by the extent and duration of postnatal hypothyroidism. All the cretins were over 35 of age, suggesting a severe iodine deficiency in the past decades, and a progressive improvement of nutritional status resulted in "silent iodine prophylaxis." However, recent studies have revealed the persistence of a moderate iodine deficiency, a high prevalence of neurologic hypoacusia, and reduction of mental performance in normal schoolchildren of this area. These findings constitute strong evidence in favor of adequate iodine prophylaxis.

A 59 year old man presenting fever, serum hyponatremia and hypoosmolality in association with hyperosmotic urine was hospitalized in our unit in February 1988. We demonstrated evidence of systemic sarcoidosis and inappropriate secretion of antidiuretic hormone (ADH). The patient was treated with corticosteroid therapy for a period of about 1 year, with regression of signs of the inappropriate vasopressin secretion as well as the symptomatology related to systemic sarcoidosis. This study identified systemic sarcoidosis as a definite cause of "syndrome of inappropriate ADH secretion".

Three patients affected with Graves' ophthalmopathy and pretibial myxoedema have been treated with high dose intravenous immunoglobulins. We have observed in all patients clinical improvement of pretibial myxoedema and a parallel reduction or negativization of the titre of circulating thyroglobulin, microsomal, TSH receptor autoantibodies and of non organ-specific antibodies (antinuclear, anti smooth muscle cells and antimitochondrial autoantibodies). In conclusion the results of this study suggest that intravenous immunoglobulin are effective in the treatment of pretibial myxoedema and probably act by an immunomodulation of autoimmune phenomena.

We report the effect of "intravenous gamma-globulin treatment" (IVIG) in a patient with autoimmune polyglandular syndrome type II, with circulating organ specific autoantibodies, preclinical hypothyroidism, amenorrhea and Addison syndrome. During IVIG treatment we observed a normalization of thyroid function, the appearance of some non ovulatory menses, reduction of thyroglobulin, thyroidal microsomal, anti-parietal cell, adrenal and ovary antibodies. These data confirm that intravenous immunoglobulin may represent a new tool for treatment of autoimmune disorders and show, for the first time, an immunosuppressive effect of intravenous gammaglobulin treatment in immunological phenomena direct against ovary, adrenal and gastric mucosa.

The aim of this study was to evaluate the variations of thyroid autoantibodies titre in a group of 15 patients affected with "Graves' disease" (G. D.) during the treatment with antithyroid drug (ATD) and "high dose intravenous immunoglobulin" (IVIG) for "Graves' ophthalmopathy". Before the starting of treatment thyroglobulin antibodies (TgAb) were positive in 10/15 patients, microsomal antibodies (MAb) were positive in 13/15 patients and TRAb were positive in 5/9 patients. At the end of treatment TgAb titre was decreased or negative in 7/10 patients, MAb titre was decreased or negative in 7/13 patients, TRAb titre was diminished or negativized in 5/5 patients. Anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) were positive in 3/15 and 3/15 patients before the treatment and in all these we observed a reduction or negativization of circulating titre during IVIG treatment. Anti-extractable nuclear antigen (ENA)m anti-mitochondrial antibodies (AMA) and rheumatoid factors were negative in all the patients. Also in the 3 patients not treated with ATD we have observed a reduction or a negativization of circulating thyroid autoantibodies. In conclusion these data suggest that the reduction of thyroid and non organ specific autoantibodies might be due to a stable immunosuppressive action of IVIG treatment in patients with Graves' disease.

Recent reports of transmission by intravenous gamma-globulin preparations of A, B, C and non-A non-B hepatitis (NANBH), including several cases that progressed to severe liver damage and death, have raised concerns about the safety of intravenous gamma-globulins. To assess this issue 15 patients treated with high-dose "intravenous immunoglobulin" (IVIG) for Graves' Ophthalmopathy had serial determination of glutamic pyruvic transaminase (GPT), glutamic oxalacetic transaminase (GOT), gamma glutamyltranspeptidase (gamma-GT), alkaline phosphatase and bilirubin that were performed regularly at interval of 3 weeks during IVIG treatment and 6 months after the end of the treatment. Hepatitis A, B, C and HIV markers were determined before, during and 6 months after the end of the treatment. The standard dosage was 400 mg per Kg body weight IVIG (3 cycles of 5 days and 12 of 1 day, every 21 days). Transient minor elevations were observed for GPT, for GOT, for gamma-GT and alkaline phosphatase. None of the elevations were considered indicative of NANBH or of any chronic hepatic disease. Transient presence of hepatitis A, B and C antibodies were observed in 6 patients. All patients remained negative for hepatitis B antigens throughout the study. HIV antibodies resulted always negative in all patients. In conclusion this study suggests the hepatitis and HIV safety of IVIG.

We have evaluated the variations of thyroid function, of thyroid autoantibodies titer, of non-organ specific autoantibodies and of other autoimmunity indices in 3 patients affected with Hashimoto's thyroiditis treated with "high dose intravenous gammaglobulin" (IVIG) (400 mg/Kg/day for 3 cycles of 5 days and subsequently 9-12 cycles of 1 day every 21 days). Before the starting of IVIG treatment patient 1 presented clinically evident hypothyroidism while patients 2 and 3 presented a preclinical form of hypothyroidism. At the end of IVIG treatment patients presented no variation of thyroid function, while patients 2 and 3 presented a normalization of T3, T4 and TSH circulating levels. Before the starting of IVIG treatment thyroglobulin antibodies (TgAb) were positive in 3/3 patients, microsomal antibodies (MAb) were positive in 3/3 patients adt TRAb were positive in 2/3 patients and MAb titre was decreased or negative in 0/3 patients. At the end of IVIG treatment Tg Ab titre was decreased or negative in 2/3 patients and MAb titre was decreased or negative in 2/3 patients. Anti-nuclear antibodies (ANA) 1/3 patients before the titre and in all these we observed a reduction or negativization of circulating titre during IVIG treatment. Anti-extractable nuclear antigen (ENA), anti-mitochondrial antibodies (AMA), C3, C4, CH50 and rheumatoid factors were negative or in the normal range in all the patients. In conclusion these data suggest that IVIG is effective in the treatment of preclinical hypothyroidism in patients with Hashimoto's thyroiditis and determine a stable immunosuppressive action on circulating thyroid and non organ specific autoantibodies.

Twenty-five patients with solitary autonomous thyroid nodules (15 nontoxic, 10 toxic) received percutaneous ethanol injection treatment (PEIT) under sonographic guidance in 4-7 sessions (1-2 weekly). To test different doses, smaller nodules (volume less than 15 mL) were given 0.75-2.8 mL ethanol/mL nodular tissue while larger nodules received 0.5-1 mL/mL. Except for 1 patient who developed hyperpyrexia, no relevant adverse effects were observed. A slight, asymptomatic increase in serum thyroid hormone levels was observed in both groups during the treatment. Three months after treatment, a biochemical and clinical remission of hyperthyroidism was observed in 8 of 10 patients with toxic nodules. A significant increase of TSH level was seen in both groups (p less than 0.01). Significant shrinkage of volume (p less than 0.001) as well as structural alterations of nodules were consistently recorded at sonography. A linear relationship (r = 0.98; p less than 0.0001) between pretreatment volume and volume reduction was found both for large and small nodules, thus suggesting that even limited ethanol doses may be therapeutically effective. A recovery of extranodular parenchyma activity at scintiscan occurred in 16 (64%) of 25 patients. These data confirm that PEIT is effective in obtaining functional ablation and in inducing remission of hyperthyroidism. Adverse effects are infrequent. In spite of the small patient sample, a 0.5-1 mL ethanol dose per each mL of tissue appears as effective as larger doses and seems appropriate for treatment.

Human ovarian preovulatory follicular fluids (FF) from 10 women were analysed for their complement contents. Functionally active complement was detected in all the fluids studied in amounts similar to those present in normal human serum. Pooled FF was challenged by seminal plasma in order to determine whether seminal plasma could activate FF complement, the pattern of such an activation and the possible consequences on the reproductive function. FF complement activation occurred during the incubation with seminal plasma with features including alternative pathway activation, factor B and C3 conversion and reduction in total haemolytic complement, as well as an inhibition by seminal plasma of the FF complement response to a new activating challenge. Possible consequences for fertilization, implantation of a fertilized ovum and local defence mechanisms against viruses and bacteria are discussed.

Crohn's disease with acute abdomen in pregnancy is described. The Authors evaluate Crohn's disease together with the diagnostic, prognostic and therapeutic problems and relationships between this disease and pregnancy. They conclude as underlining the rarity of Crohn's disease beginning in pregnancy and so the importance of symptoms related to this disease in fertile age woman to make diagnosis and therapy before pregnancy.

Objective: We have evaluated the efficacy of percutaneous ethanol injection as an alternative to surgery and iodine-131 treatment in solitary autonomous thyroid adenoma., Design: Percutaneous ethanol injection (0.5-2.8 ml ethanol/ml nodular tissue) was performed under sonographic guidance in 3-5 (1-2 weekly) sessions; a 7.5 MHz linear real-time scanner (Toshiba, mod. 32B) was used for sonographic studies. The thyroid hormone profile was assessed during treatment and for the next 6 months., Patients: Fifty-six patients (40 females, 16 males, mean age 46 +/- SD 9 years; 30 pretoxic, 26 toxic) were included in the study: their pretreatment technetium-99 m thyroid scan showed a single hot nodule with total suppression of extranodular tissue in 45 and near-total suppression in 11., Measurements: Thyroid hormones, antithyroglobulin and antiperoxidase antibodies were measured by specific radioimmunoassay, while thyrotrophin was evaluated by ultrasensitive immunoradiometric assay., Results: Apart from a case of transient pyrexia, no relevant adverse effects were observed. A slight thyroid hormone increase was seen in both groups immediately following a treatment. Six months after therapy a biochemical and clinical remission of hyperthyroidism was observed in 18 out of 22 toxic patients (81.8%); a significant increase of TSH levels was seen in both groups (P less than 0.01). With follow-up, significant volume shrinkage (P less than 0.001) as well as structural alterations of the nodule were consistently recorded at sonography; a linear relationship (r = 0.98; P less than 0.0001) between pretreatment volume and volume reduction was found. At scintiscan, functional activity of extranodular parenchyma was found in 40 out of 56 patients (71.4%), 16/26 (61.5%) in the hyperthyroid group, 24/30 (80.0%) in the pretoxic group., Conclusions: These data confirm that percutaneous ethanol injection is effective in obtaining functional ablation and in inducing remission of hyperthyroidism, when present; adverse effects seem infrequent.

A group of 248 asymptomatic postmenopausal patients was evaluated using transvaginal echography. Thirty-five patients with endometrial echopatterns which were larger than 8 mm and/or irregular then underwent hysteroscopy and endometrial biopsy. Results show that 31.4% of cases in which there was a thickening of the endometrial echopattern correspond to the presence of polyp, myoma, synechia with atrophic endometrium. In conclusion, the Authors affirm the inappropriateness of the term "endometrial echopattern" in menopause, since this term should be reserved to describe the typical appearance of the endometrium during the reproductive phase. They stress that ultrasonography can reveal anomalies of the internal echostructure of the womb but that further tests (e.g. hysteroscopy, biopsy) are required to diagnose their nature.

Three patients with the carcinoid syndrome received intravenous somatostatin (3.5 micrograms/min) for one day; intravenous salmon calcitonin (8 IU/hr) for one day; subcutaneous salmon calcitonin (100 IU three times daily) for ten days; and subcutaneous octreotide (150 micrograms three times daily) for ten days. Octreotide (SMS-201.995) is a stable analogue of somatostatin. There was a five-day washout period between each treatment. During each of these treatments, reductions in the numbers of daily flushes and bowel movements, stool weight, and urinary 5-hydroxyindoleacetic acid (5-HIAA) levels were observed. Relief of cramping abdominal pains was also reported. Patients 1 and 3 chose to continue receiving the subcutaneous calcitonin and patient 2 chose the octreotide. Patient 1 (aged 67 years) reported relief of symptoms for five months until she developed an intestinal obstruction as a result of tumor infiltration. Patient 3 (aged 67 years) has received the calcitonin for about 16 months with relief of symptoms and reduced urinary 5-HIAA levels. Patient 2 (aged 57 years) has continued octreotide treatment for one year and reports relief of symptoms.

We have evaluated the efficacy of high-dose intravenous immunoglobulin treatment in Graves' ophthalmopathy, and have carried out a prospective randomized clinical trial, including a single-blind evaluation, whereby 14 patients were assigned to two different treatment groups: 7 patients were treated with intravenous immunoglobulin and orbital radiotherapy (Group 1) and 7 patients were given intravenous immunoglobulin alone (Group 2). The results of the intravenous immunoglobulin treatment were also compared with those obtained in a Historical Control Group (12 patients) treated with systemic methylprednisolone and orbital irradiation. Degree of ocular involvement and response to treatment were assessed by ophthalmopathy index. The mean initial and final ophthalmopathy index showed no significant difference among the three groups. Comparison between the mean initial and final ophthalmopathy index showed a statistically significant reduction (p less than 0.005) in all three groups, the observed changes being confirmed by orbital computerized tomography in Groups 1 and 2. Corticosteroid treatment was associated with major and minor side effects, while no important adverse reactions were observed during intravenous immunoglobulin treatment. Even considering our results as preliminary, we conclude that intravenous immunoglobulin treatment is effective and safe in improving Graves' ophthalmopathy.

The most frequently used medical treatment of Graves' ophthalmopathy is the combination of orbital irradiation and systemic corticosteroid. In this study the effectiveness of "high dose intravenous immunoglobulin" (IVIG) in Graves' ophthalmopathy treatment is explored. 11 patients were treated with orbital radiotherapy combined with systemic corticosteroid (Group 1), while 10 patients were treated with the combination of orbital irradiation and IVIG (Group 2). The therapeutic effect was assessed by an ophthalmopathy index based on the American Thyroid Association, classification of ocular changes of Graves' ophthalmopathy. All signs and symptoms of endocrine ophthalmopathy improved significantly in both groups. The mean ophthalmopathy index decreased from 7.0 +/- 1.3 to 3.4 +/- 1.5 in Group 1, and from 7.0 +/- 1.8 to 3.0 +/- 2.1 in Group 2. Statistical analysis showed no significant difference between Group 1 and 2 mean initial and final ophthalmopathy index, and a significant difference between initial and final ophthalmopathy index both in Group 1 and 2. While side effects were present in Group 1 treated with systemic corticosteroid, no side effect was observed in patients treated with IVIG. These preliminary results suggest that IVIG is safe and effective in the treatment of Graves' ophthalmopathy.

The three-dimensional architecture of the human isthmic myosalpinx is directly visualized by means of scanning electron microscopy after removal of interstitial connective tissue through NaOH maceration and ultrasound microdissection. These investigations show that the myosalpinx is composed of irregularly running bundles of smooth muscle cells, changing their orientation within the myosalpinx and displaying longitudinal, oblique and circular directions. The muscular bundles anastomose and intermingle with other bundles running at different levels in the oviduct wall, and actually give rise to a wide and complex muscular network in which no distinct layers are readily discernible. These morphological data are consistent with the physiological findings that the transport of gametes and embryo in very early stages in the isthmic portion of the oviduct tube is the result of a discontinuous pattern of forward and backward movements.

Subclinical hypothyroidism in characterized by elevated TSH levels in the face of normal thyroid hormone concentrations. The purpose of this study was to evaluate whether these subjects show alterations of neuropsychological and behavioural features and of myocardial contractility as patients with overt hypothyroidism do. We evaluated in 14 subjects the hormonal profile (total and free T3 and T4, TSH), memory ability (Wechsler Memory Scale), behavioural reactivity (Crown & Crisp Experimental Index) and the pre-ejection period (isometric systole). We found an evident impairment of some cognitive functions correlated to memory and a behavioural alteration, perhaps secondary to the disease state, and moreover an early defect of myocardial contractility, represented by prolonged pre-ejection period. These results suggest that these patients should be treated with adequate doses of L-Thyroxine, like in overt hypothyroidism.

A case of sonographic diagnosis of single umbilical artery associated with hypoplastic left heart syndrome and left renal agenesis is reported. Umbilical artery Doppler waveforms are presented and discussed for the first time.

A 14-year-old girl presented with classic McCune-Albright syndrome. She underwent the ablation of several cysts during a laparotomy performed on the basis of persistent and intense pelvic pain and recurrent episodes of menometrorrhagia not responsive to pharmacologic therapy. Granulosa cells obtained from an isolated follicle and a cyst were cultured and estradiol (E2) secreted in the culture medium measured. Granulosa cells, obtained from the follicle, produced much higher levels of estradiol compared to those of cells coming both from follicles of equivalent size and preovulatory follicles of normal patients. Secretion of E2 by granulosa cells from the cyst was comparable to that of normal preovulatory follicles. We conclude that in this patient, ovaries are hyperfunctioning in terms of E2 production. This high production of estradiol and the fact that several cysts were found in the ovaries can justify the high levels of estradiol found in the serum of this patient at the moment of the operation.

We studied the effects of long-term (30 days) refracted daily intramuscular administration of 4 mg TRH tartrate (TRH-T) on the pituitary-thyroid axis in 20 euthyroid patients affected by cerebrovascular disease (CVD). All subjects were assayed for T4, T3, FT4, FT3, TSH and TBG plasma levels before treatment (D0), after 15 and 30 treatment days (D15, D30), and after a 15-day washout (D45). In addition, TSH response to 200 micrograms intravenous TRH was assessed at D0, D30 and D45. We observed a significant increase in T4, FT4 and FT3 levels in the face of decreased TSH concentrations. A blunted TSH response to TRH bolus persisted at D30. These data demonstrate that the down-regulation mechanism may be partially overcome in vivo when thyrotrophs are chronically exposed to pharmacological TRH-T doses and that TSH pattern is mainly due to the negative feedback of thyroid hormones, even though pituitary TSH reserves may become depleted. Furthermore, prolonged TRH-T administration does not produce hyperthyroidism in euthyroid CVD patients.