The Journal of Clinical Endocrinology & Metabolism, 2012
A functional thyroid-stimulating autoantibodies (TSAb) assay using a thyroid-stimulating hormone ... more A functional thyroid-stimulating autoantibodies (TSAb) assay using a thyroid-stimulating hormone receptor chimera (Mc4) appears to be clinically more useful than the commonly used assay, a binding assay that measures all the antibodies binding to the thyroid-stimulating hormone receptor without functional discrimination, in diagnosing patient with Graves' disease (GD). The objective of the study was to investigate whether an Mc4 assay can predict relapse/remission of hyperthyroidism after antithyroid drug (ATD) treatment in patients with GD. An Mc4 assay was used to prospectively track TSAb activity in GD patients treated with ATD over a 5-yr period. GD patients from the Chieti University participated in this study. Interventions included the assessment of patients' sera using the Mc4 assay, the Mc4-derivative assay (Thyretain), and a human monoclonal thyroid-stimulating hormone receptor antibody, M22 assay. The Mc4 assay, a sensitive index of remission and recurrence, was used in this study. The TSAb levels significantly decreased only in the remitting group as evidenced by Mc4 assay values at the end of ATD (0.96 ± 1.47, 10.9 ± 26.6. and 24.7 ± 37.5 arbitrary units for the remitting, relapsing, and unsuspended therapy groups, respectively). Additional prognostic help was obtained by thyroid volume measurements at the end of treatment. Although not statistically significant, the Mc4 assay has a trend toward improved positive predictive value (95.4 vs. 84.2 or 87.5%), specificity (96.4 vs. 86.4 and 90.9%), and accuracy (87.3 vs. 83.3 and 80.9%) comparing the Mc4, Thyretain, and M22 assays, respectively. Thyretain has a trend toward improved negative predictive value (82.6 vs. 81.8 and 76.9%) and sensitivity (80 vs. 77.8 and 70%) comparing Thyretain, Mc4, and M22 assays, respectively. The Mc4 assay is a clinically useful index of remission and relapse in patients with GD. Larger studies are required to confirm these findings.
Abstract ASDEX Upgrade has recently finished its transition towards an all-W divertor tokamak, by... more Abstract ASDEX Upgrade has recently finished its transition towards an all-W divertor tokamak, by the exchange of the last remaining graphite tiles to W-coated ones. The plasma start-up was performed without prior boronization. It was found that the large He content in the plasma, resulting from DC glow discharges for conditioning, leads to a confinement reduction. After the change to D glow for inter-shot conditioning, the He content quickly dropped and, in parallel, the usual H-Mode confinement with H factors close to one was ...
A 24-year-old woman was admitted to hospital because of hirsutism, virilism and amenorrhea, which... more A 24-year-old woman was admitted to hospital because of hirsutism, virilism and amenorrhea, which had appeared 6 months earlier. Endocrinological evaluation showed a slightly elevated serum level of testosterone (1.2 +/- 0.05 ng/ml), normal plasma levels of dehydroepiandrosteronesulfate (DHEA-S) (2,070 +/- 6 ng/ml), androstenedione (1.8 +/- 0.5 ng/ml) and sex hormone-binding globulin (SHBG)(42 +/- 3 nM/L); there was normal urinary 17-ketosteroid (17-KS) excretion (11.7 mg/24 h), low urinary estrogen (E) excretion (3 +/- 0.4 micrograms/24 h), suppressed basal gonadotropin concentrations (LH 0.9 microUI/ml; FSH 3.2 microUI/ml) and an exaggerated response to the LH-RH test. At laparotomy, a monolateral ovarian tumor was found, which was proved histologically to be a Sertoli-Leydig cell tumor. After tumor ablation, a regular menstrual cycle followed and progressive reduction of virilism was noted. This was followed within 4 months by complete normalization of LH, FSH, estrogen and progesterone serum levels. The responsiveness to LH-RH also became normalized. Two years after this operation, the patient had a normal pregnancy. This case of virilization in a woman affected by a benign Sertoli-Leydig cell tumor was primarily characterized by an unusual response of the hypothalamopituitary axis against an endocrinological background of notable alteration of the androgen/estrogen ratio, where the androgens were slightly increased and the estrogens greatly reduced.
The Journal of Clinical Endocrinology & Metabolism, 1968
... Seconda Clinica Medica, Università di Roma, Policlinico Umberto I Rome, Italy. Present addres... more ... Seconda Clinica Medica, Università di Roma, Policlinico Umberto I Rome, Italy. Present address: State University of New York, Downstate Medical Center, Department of Pathology, 450 Clarksorf Ave., Brooklyn, NY 11203. ABSTRACT. ...
The Journal of Clinical Endocrinology & Metabolism, 2011
Graves&am... more Graves' disease (GD) is caused by persistent, unregulated stimulation of thyrocytes by thyroid-stimulating antibodies (TSAbs) that activate the TSH receptor (TSHR). We previously reported the first small-molecule antagonist of human TSHR and showed that it inhibited receptor signaling stimulated by sera from four patients with GD. Our objective was to develop a better TSHR antagonist and use it to determine whether inhibition of TSAb activation of TSHR is a general phenomenon. We aimed to chemically modify a previously reported small-molecule TSHR ligand to develop a better antagonist and determine whether it inhibits TSHR signaling by 30 GD sera. TSHR signaling was measured in two in vitro systems: model HEK-EM293 cells stably overexpressing human TSHRs and primary cultures of human thyrocytes. TSHR signaling was measured as cAMP production and by effects on thyroid peroxidase mRNA. We tested analogs of a previously reported small-molecule TSHR inverse agonist and selected the best NCGC00229600 for further study. In the model system, NCGC00229600 inhibited basal and TSH-stimulated cAMP production. NCGC00229600 inhibition of TSH signaling was competitive even though it did not compete for TSH binding; that is, NCGC00229600 is an allosteric inverse agonist. NCGC00229600 inhibited cAMP production by 39 ± 2.6% by all 30 GD sera tested. In primary cultures of human thyrocytes, NCGC00229600 inhibited TSHR-mediated basal and GD sera up-regulation of thyroperoxidase mRNA levels by 65 ± 2.0%. NCGC00229600, a small-molecule allosteric inverse agonist of TSHR, is a general antagonist of TSH receptor activation by TSAbs in GD patient sera.
Activation of the hypothalamic–pituitary–adrenal axis usually occurs after physical and/or psycho... more Activation of the hypothalamic–pituitary–adrenal axis usually occurs after physical and/or psychological stress with a magnitude modulated by both intensity of the stress episodes and individual variability. Competitive sport activities can be considered as a stressor, and many studies have investigated the dynamic relationships of the hypothalamic–pituitary–adrenal axis finding different results. The aim of our study was to evaluate cortisol and testosterone levels in salivary samples from 16 soccer players over six training sessions and 18 matches. Resting levels of cortisol show pre-match levels greater than pre-training levels, with both increasing through the season. Cortisol changes following training and match sessions show lower variations for training sessions than matches. Through the season, training sessions show reduced increases in cortisol levels. For testosterone, pre-match and pre-training levels decrease through the season. Testosterone responses to training sessio...
The Journal of Clinical Endocrinology & Metabolism, 2012
A functional thyroid-stimulating autoantibodies (TSAb) assay using a thyroid-stimulating hormone ... more A functional thyroid-stimulating autoantibodies (TSAb) assay using a thyroid-stimulating hormone receptor chimera (Mc4) appears to be clinically more useful than the commonly used assay, a binding assay that measures all the antibodies binding to the thyroid-stimulating hormone receptor without functional discrimination, in diagnosing patient with Graves' disease (GD). The objective of the study was to investigate whether an Mc4 assay can predict relapse/remission of hyperthyroidism after antithyroid drug (ATD) treatment in patients with GD. An Mc4 assay was used to prospectively track TSAb activity in GD patients treated with ATD over a 5-yr period. GD patients from the Chieti University participated in this study. Interventions included the assessment of patients' sera using the Mc4 assay, the Mc4-derivative assay (Thyretain), and a human monoclonal thyroid-stimulating hormone receptor antibody, M22 assay. The Mc4 assay, a sensitive index of remission and recurrence, was used in this study. The TSAb levels significantly decreased only in the remitting group as evidenced by Mc4 assay values at the end of ATD (0.96 ± 1.47, 10.9 ± 26.6. and 24.7 ± 37.5 arbitrary units for the remitting, relapsing, and unsuspended therapy groups, respectively). Additional prognostic help was obtained by thyroid volume measurements at the end of treatment. Although not statistically significant, the Mc4 assay has a trend toward improved positive predictive value (95.4 vs. 84.2 or 87.5%), specificity (96.4 vs. 86.4 and 90.9%), and accuracy (87.3 vs. 83.3 and 80.9%) comparing the Mc4, Thyretain, and M22 assays, respectively. Thyretain has a trend toward improved negative predictive value (82.6 vs. 81.8 and 76.9%) and sensitivity (80 vs. 77.8 and 70%) comparing Thyretain, Mc4, and M22 assays, respectively. The Mc4 assay is a clinically useful index of remission and relapse in patients with GD. Larger studies are required to confirm these findings.
Abstract ASDEX Upgrade has recently finished its transition towards an all-W divertor tokamak, by... more Abstract ASDEX Upgrade has recently finished its transition towards an all-W divertor tokamak, by the exchange of the last remaining graphite tiles to W-coated ones. The plasma start-up was performed without prior boronization. It was found that the large He content in the plasma, resulting from DC glow discharges for conditioning, leads to a confinement reduction. After the change to D glow for inter-shot conditioning, the He content quickly dropped and, in parallel, the usual H-Mode confinement with H factors close to one was ...
A 24-year-old woman was admitted to hospital because of hirsutism, virilism and amenorrhea, which... more A 24-year-old woman was admitted to hospital because of hirsutism, virilism and amenorrhea, which had appeared 6 months earlier. Endocrinological evaluation showed a slightly elevated serum level of testosterone (1.2 +/- 0.05 ng/ml), normal plasma levels of dehydroepiandrosteronesulfate (DHEA-S) (2,070 +/- 6 ng/ml), androstenedione (1.8 +/- 0.5 ng/ml) and sex hormone-binding globulin (SHBG)(42 +/- 3 nM/L); there was normal urinary 17-ketosteroid (17-KS) excretion (11.7 mg/24 h), low urinary estrogen (E) excretion (3 +/- 0.4 micrograms/24 h), suppressed basal gonadotropin concentrations (LH 0.9 microUI/ml; FSH 3.2 microUI/ml) and an exaggerated response to the LH-RH test. At laparotomy, a monolateral ovarian tumor was found, which was proved histologically to be a Sertoli-Leydig cell tumor. After tumor ablation, a regular menstrual cycle followed and progressive reduction of virilism was noted. This was followed within 4 months by complete normalization of LH, FSH, estrogen and progesterone serum levels. The responsiveness to LH-RH also became normalized. Two years after this operation, the patient had a normal pregnancy. This case of virilization in a woman affected by a benign Sertoli-Leydig cell tumor was primarily characterized by an unusual response of the hypothalamopituitary axis against an endocrinological background of notable alteration of the androgen/estrogen ratio, where the androgens were slightly increased and the estrogens greatly reduced.
The Journal of Clinical Endocrinology & Metabolism, 1968
... Seconda Clinica Medica, Università di Roma, Policlinico Umberto I Rome, Italy. Present addres... more ... Seconda Clinica Medica, Università di Roma, Policlinico Umberto I Rome, Italy. Present address: State University of New York, Downstate Medical Center, Department of Pathology, 450 Clarksorf Ave., Brooklyn, NY 11203. ABSTRACT. ...
The Journal of Clinical Endocrinology & Metabolism, 2011
Graves&am... more Graves' disease (GD) is caused by persistent, unregulated stimulation of thyrocytes by thyroid-stimulating antibodies (TSAbs) that activate the TSH receptor (TSHR). We previously reported the first small-molecule antagonist of human TSHR and showed that it inhibited receptor signaling stimulated by sera from four patients with GD. Our objective was to develop a better TSHR antagonist and use it to determine whether inhibition of TSAb activation of TSHR is a general phenomenon. We aimed to chemically modify a previously reported small-molecule TSHR ligand to develop a better antagonist and determine whether it inhibits TSHR signaling by 30 GD sera. TSHR signaling was measured in two in vitro systems: model HEK-EM293 cells stably overexpressing human TSHRs and primary cultures of human thyrocytes. TSHR signaling was measured as cAMP production and by effects on thyroid peroxidase mRNA. We tested analogs of a previously reported small-molecule TSHR inverse agonist and selected the best NCGC00229600 for further study. In the model system, NCGC00229600 inhibited basal and TSH-stimulated cAMP production. NCGC00229600 inhibition of TSH signaling was competitive even though it did not compete for TSH binding; that is, NCGC00229600 is an allosteric inverse agonist. NCGC00229600 inhibited cAMP production by 39 ± 2.6% by all 30 GD sera tested. In primary cultures of human thyrocytes, NCGC00229600 inhibited TSHR-mediated basal and GD sera up-regulation of thyroperoxidase mRNA levels by 65 ± 2.0%. NCGC00229600, a small-molecule allosteric inverse agonist of TSHR, is a general antagonist of TSH receptor activation by TSAbs in GD patient sera.
Activation of the hypothalamic–pituitary–adrenal axis usually occurs after physical and/or psycho... more Activation of the hypothalamic–pituitary–adrenal axis usually occurs after physical and/or psychological stress with a magnitude modulated by both intensity of the stress episodes and individual variability. Competitive sport activities can be considered as a stressor, and many studies have investigated the dynamic relationships of the hypothalamic–pituitary–adrenal axis finding different results. The aim of our study was to evaluate cortisol and testosterone levels in salivary samples from 16 soccer players over six training sessions and 18 matches. Resting levels of cortisol show pre-match levels greater than pre-training levels, with both increasing through the season. Cortisol changes following training and match sessions show lower variations for training sessions than matches. Through the season, training sessions show reduced increases in cortisol levels. For testosterone, pre-match and pre-training levels decrease through the season. Testosterone responses to training sessio...
Uploads
Papers by F. Monaco