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Thyrotropin (TSH) secretion was evaluated in a group of patients with chronic renal failure (CRF) undergoing regular maintenance hemofiltration and in normal controls. The study group included 68 patients (39 males and 29 females, age range 39-73 years, mean: 53 years). In all patients blood was drawn at 08:30-09:00 h; in 20 patients the nocturnal (24:00-02:00 h) serum TSH peak was also evaluated; 12 patients underwent stimulation test with synthetic TSH-releasing hormone (TRH). TSH was measured by an ultrasensitive immunoradiometric assay. CRF patients showed a significant decrease in serum total and free thyroxine and triiodothyronine concentrations, which in a substantial proportion of subjects were below the lower normal limit. Serum reverse triiodothyronine and thyroxine-binding globulin values did not differ in the two groups. Despite this trend of thyroid hormones to decrease, no patient had supranormal TSH values as in primary hypothyroidism. While the mean morning TSH concentrations of CRF patients did not differ from those of controls, the mean nocturnal values were significantly reduced in CRF (1.0 +/- 0.2 vs 3.2 +/- 0.4 mU/l, p less than 0.0005) and the nocturnal serum TSH surge was not observed in 18 of the 20 patients (90%) in whom it was evaluated. The mean serum TSH peak value after TSH-releasing hormone (TRH) administration was also reduced in CRF patients, and the TSH response to TRH was blunted in 3 out of 12 patients (25%). The results of this study demonstrate a major impairment of TSH secretion in CRF, which baseline TSH measurements in the morning and the evaluation of the TSH response to TRH may not reveal.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to demonstrate the suggested failure of the serotoninergic system in human obesity and to evaluate the role of central serotoninergic activity in prolactin (PRL) and thyroid stimulating hormone (TSH) release in this condition, 13 euthyroid obese and 9 healthy women of normal weight were studied. A TRH test (200 micrograms i.v.) was performed before and after administration of fenfluramine (FF) 60 mg b.d. for 14 days. In the controls, FF did not modify the expected significant increase in PRL induced by TRH. In obese patients, however, the PRL levels was significantly increased after TRH, but the increase was less than in the controls. After FF, the PRL response to TRH was larger than in the pretreatment phase, with values similar to those observed in normal subjects. In neither group FF did change the TSH-stimulating effect of TRH, but the hormonal response in obese patients was greater than in the controls. The restoration of the responsiveness of PRL to TRH after central serotoninergic stimulation confirms the hypothesis that a failure of the serotoninergic system may occur in human obesity. Since FF does not interfere with the secretory pattern of basal and stimulated TSH in normal or obese subjects, the serotoninergic system does not seem to play a major role in the control of TSH secretion.

Endemic cretinism (EC) is one of the most severe iodine deficiency disorders, leading to typical symptoms such as neurodevelopmental impairments or mental deficits. In addition to environmental factors, the pathogenesis of its genetic contribution remains unclear. The study revealed the differential expression profiles of long non-coding RNA(lncRNA) and messenger RNA(mRNA) based on high-throughput RNA-seq. GO and KEGG analyses were used to annotate the function and pathway of differentially expressed (DE) mRNA and co-expressed mRNA. The protein-protein interaction(PPI) network was established. The expression levels of three lncRNAs and six mRNAs were validated by quantitative real-time PCR analysis (qRT-PCR) and subjected to correlation analysis. Compared to controls, a total of 864 lncRNAs and 393 mRNAs were differentially expressed. The PPI network had 149 nodes and 238 edges, and three key protein-coding genes were observed. Levels of LINC01220 and target mRNA IDO1 were statistically elevated in EC patients. Differentially expressed lncRNA may be a new potential player in EC. LINC01220 and IDO1 might interact with each other to participate in EC. The biological process of regulation of postsynaptic membrane potential and the Rap1 signaling pathway might exert a regulating role in the pathophysiological process of EC. Our findings could provide more theoretical and experimental evidence for investigating the pathophysiological mechanisms of EC., Competing Interests: Declarations. Ethics Approval: All procedures performed in studies involving human participants were by the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study protocol was approved by the Ethics Review Committee of Harbin Medical University (No. hrbmuecdc20201201). Consent to Participate: Written informed consent was provided by all control participants and guardians of all patients. Consent for Publication: Consent to publish from the participant was obtained to report individual participant data. Competing Interests: The authors declare that they have no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Environmental factors are linked to aging and age-related diseases. Emerging evidence suggests that enhancing body's resistance to xenobiotics might be an anti-aging strategy. The constitutive androstane receptor (CAR) regulates drug-metabolizing enzymes and transporters, coordinating metabolism and immune responses to adapt to stress triggered by exogenous exposure. However, the impact of activating CAR on aging remains unknown. In this study, Caenorhabditis elegans (C. elegans), drug-induced premature aging mice, and senescence accelerated P8 (SAMP8) mice are used as models to explore the effects of CAR activation on lifespan and healthspan, along with the underlying mechanisms. The results showed that hCAR agonist CITCO and mCAR agonist TCPOBOP prolonged the lifespan and healthspan in model organism. The longevity effects of CITCO and TCPOBOP were attenuated in CAR homozygous nhr-8/daf-12 mutant C. elegans as well as CAR -/- mice. In C. elegans, CITCO activated both anti-stress and detoxification genes, and increased the resistance to environmental adversities. Additionally, the lifespan-extending and xenobiotic resistant effects of CITCO might be related to the regulation of age-related pathways. Furthermore, CITCO improved age-related neurodegeneration in C. elegans models. Taken together, the results suggest that the longevity effects of CAR agonists may be related to the enhancement of xenobiotic resistance of animals., (© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Cyclometalated iridium (Ir) complexes demonstrate impressive capabilities across a range of fields, including biology and photocatalysis, due to their tunable optical characteristics and structure flexibility. However, generating upconversion luminescence of Ir complexes under near-infrared light excitation is challenging. Herein, by employing lanthanide-doped upconversion nanoparticles (UCNPs) as the sensitizer, a new strategy is demonstrated to gain upconversion luminescence of Ir complexes via triplet energy transfer. This design relies on a rationally designed hybrid of core-shell structured NaYbF 4 :Tb@NaTbF 4 UCNPs and new Ir phosphonate complexes, in which UCNPs can migrate upconverted energy to the surface of nanoparticles through Tb 3+ -mediated energy migration and then sensitize the upconversion luminescence of Ir complexes upon 980 nm excitation. Both experimental and theoretical investigations highlight the significance of triplet energy transfer from excited Tb 3+ ions to the triplet state of Ir complexes in the sensitization of upconversion luminescence of Ir complexes. These findings may open exciting avenues for fabricating hybrid Ir materials with new functions and driving the development of UCNP-based nanomaterials., (© 2024 Wiley‐VCH GmbH.)

Carbohydrates are natural, renewable, chemical compounds that play crucial roles in biological systems. Thus, efficient and stereoselective glycosylation is an urgent task for the preparation of pure and structurally well-defined carbohydrates. Photoredox catalysis has emerged as a powerful tool in carbohydrate chemistry, providing an alternative for addressing some of the challenges of glycochemistry. Over the last few decades, Ir- and Ru-based organometallic photocatalysts have attracted significant interest because of their high stability, high-energy triplet state, strong visible-light absorption, long luminescence lifetime, and amenability to ligand modification. This review highlights the recent progress in the organometallic photocatalyst-promoted synthesis and modification of carbohydrates under photoirradiation, as well as the related benefits and drawbacks., (© 2024 The Chemical Society of Japan and Wiley-VCH GmbH.)

Anticipating intramolecular excited-state proton-coupled electron transfer (PCET) process within dinuclear Ir 2 -photocatalytic system via the covalent linkage is seminal, yet challenging. Indeed, the development of various dinuclear complexes is also promising for studying integral photophysics and facilitating applications in catalysis or biology. Herein, this study reports dinuclear [Ir 2 (bis{imidazo-phenanthrolin-2-yl}-hydroquinone)(ppy) 4 ] 2+ (1 2+ ) complex by leveraging both ligand-centered redox property and intramolecular H-bonding for exploring dual excited-state proton-transfer assisted PCET process. The vital role of covalently placed hydroquinone in bridged ligand is investigated as electron-proton transfer (ET-PT) mediator in intramolecular PCET and validated from triplet spin density plot. Moreover, bimolecular photoinduced ET reaction is studied in acetonitrile/water medium, forging the lowest energy triplet charge separated ( 3 CS Phen-Im ) state of 1 2+ with methyl viologen via favorably concerted-PCET pathway. The result indicates strong donor-acceptors coupling, which limits charge recombination and enhances catalytic efficiency. To showcase the potential application, this bioinspired PCET-based photocatalytic platform is studied for phototherapeutics, indicating significant mitochondrial localization and leading to programmed cell death (apoptosis) through futile redox cycling. Indeed, the consequences of effective internalization (via energy-dependent endocytosis), better safety profile, and higher photoinduced antiproliferative activity of 1 2+ compared to Cisplatin, as explored in 3D tumor spheroids, this study anticipates it to be a potential lead compound., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Ferroptosis is a cell death mechanism based on extensive cellular membrane peroxidation, implicated in neurodegenerative and other diseases. The essential oil component γ-terpinene, a natural monoterpene with a unique highly oxidizable pro-aromatic 1,4-cyclohexadiene skeleton, inhibits peroxidation of polyunsaturated lipid in model heterogeneous systems (micelles and liposomes). Upon H-atom abstraction, an unstable γ-terpinene-derived peroxyl radical is formed, that aromatizes to p-cymene generating HOO⋅ radicals. As HOO⋅ are small and hydrophilic radicals, they quickly diffuse outside the lipid core, blocking the radical chain propagation of polyunsaturated lipids. This unprecedented antioxidant "slingshot" mechanism explains why γ-terpinene shows a protective activity against ferroptosis, being effective at submicromolar concentrations in human neuroblastoma (SH-SY5Y) cells., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Heteroatoms are essential to living organisms and present in almost all molecules with medicinal usage. The catalytic functionalization at the carbon-centered radical with an adjacent heteroatom provides an effective way to value added moiety while retaining the unique physicochemical and pharmacological properties of heteroatoms, which can promote the development of pharmaceutical and fine chemical production. Carbonylative transformation was discovered nearly a century ago which is an efficient method for the synthesis of carbonyl-containing molecules with potent applications in both industry and academia. Despite numerous advances in new reaction development, carbonylative transformation involving adjacent heteroatom carbon radical remain a subject that deserves to be discussed. In this minireview, we systematically summarized and discussed the recent advances in carbonylative transformations involving carbon-centered radicals with an adjacent heteroatom, including oxygen (O), nitrogen (N), phosphorus (P), silicon (Si), sulfur (S), boron (B), fluorine (F), and chlorine (Cl). The related reaction mechanism was also discussed., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Objective: The objective of this study is to clarify the clinical features of thyroid dysfunction observed in patients with autoimmune pancreatitis (AIP)., Methods: We repeatedly examined thyroid function in 74 patients with type 1 AIP (58 males, 16 females; average onset age of AIP 67 years). Clinical and serological findings in patients with thyroid dysfunction were analyzed., Results: During follow-up, clinical and subclinical hypothyroidism were observed in 3 and 17 patients, respectively. Clinical and subclinical hyperthyroidism were observed in 5 and 1 patients, respectively. One patient showed clinical hyperthyroidism followed by subclinical hypothyroidism. All patients with clinical and subclinical hypothyroidism were asymptomatic and required no medical treatment, whereas four patients with clinical hyperthyroidism were symptomatic and received treatment with thiamazole., Conclusion: Frequent hypothyroidism in AIP, which was previously reported, was confirmed. Moreover, in this study, the association between hyperthyroidism and AIP was demonstrated. Hyperthyroidism in AIP may be more clinically significant than hypothyroidism because patients frequently require medical treatment., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Platinum(II) metalla-N-heterocyclic carbene complexes featuring pyridyl heterocyclic moiety demonstrate remarkable catalytic efficiency in alkyne hydrosilylation under green light irradiation. The photocatalytic properties of complexes are rationalised by the photo-induced charge transfer occurring in extended condensed system identified with the help of various experimental (UV/vis and emission spectroscopy, cyclic voltammetry) and theoretical methods (DFT/TD-DFT, IFCT analysis)., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Measurements of serum thyroglobulin (hTg) were performed using a specific radioimmunoassay. Sera with detectable anti-thyroglobulin (anti-Tg) antibody titers (> or = 1:10) as assessed by passive hemagglutination were discarded. Assays were carried out under conditions in which anti-Tg titers less than 1:10 produced no interference. The assay sensitivity was 1.25 ng/ml and the mean +/- SE concentration of serum hTg in 58 control subjects was 9.5 +/- 0.9 ng/ml (range < 1.25-27 ng/ml). A slight but significant (p < 0.025) increase in the mean hTg level was observed in 12 pregnant women at delivery (25.7 +/- 5.2 ng/ml). Moderate to marked elevations of serum hTg were observed in patients with nontoxic goiter (61.4 +/- 15 ng/ml; n = 23), subacute thyroiditis (138 +/- 67 ng/ml; n = 5), toxic adenoma (129 +/- 47 ng/ml; n = 13), untreated (424 +/- 101 ng/ml; n = 35) or treated (328 +/- 222 ng/ml; n = 14) toxic diffuse goiter. 88 patients with thyroid carcinoma and 10 with nonthyroidal malignancies were studied. The mean level of serum hTg was increased in untreated differentiated thyroid carcinoma (89.5 +/- 19 ng/ml; n = 13) but not in undifferentiated (10 +/- 2.9 ng/ml; n = 6) or medullary (0.8 +/- 0.2 ng/ml; = 3) carcinoma. In treated differentiated thyroid carcinoma the mean hTg levels were normal (8.2 +/- 0.2 ng/ml) in patients (n = 24) with no evidence of either a thyroid residue or metastatic disease, moderately increased (56.6 +/- 16 ng/ml) in patients (n = 27) with residual thyroid tissue, markedly elevated in patients with lymph node metastases (199 +/- 50 ng/ml; n = 5) and extremely elevated in those with bone (4004 +/- 982 ng/ml; n = 8) or lung (2520 +/- 620 ng/ml; n = 5) metastases. There was no significant difference in serum hTg between functioning (n = 23) and nonfunctioning (n = 5) metastases as assessed by 131I whole body scan. A slight but significant (p < 0.0005) increase in the mean concentration of hTg was observed in nonthyroidal malignancies (21.7 +/- 4.5 ng/ml; n = 10). Serial measurements showed a transient increase of serum hTg after 131I therapy of differentiated thyroid carcinoma, toxic diffuse goiter or toxic adenoma, with peak values usually occurring within the first three days. A fall of serum hTg after administration of suppressive doses of thyroid hormone to patients with nontoxic goiter and a rise after discontinuation of thyroid suppressive therapy in patients with metastatic differentiated thyroid carcinoma was observed.(ABSTRACT TRUNCATED AT 400 WORDS)

200 workers of the pay-toll stations of a Tuscan motorway were examined for PbB, FEP and urinary delta-ALA. The mean value of PbB was 37 +/- mcg/100 ml R.B.C., but in 39 subjects (19.4%) it was over 50 mcg/100 ml R.B.C. FEP showed a mean value of 23.3 +/- 8.9 mcg/100 ml and in 8 subjects (4.4%) it exceeded 40 mcg/100 ml. Urinary delta-ALA was always in the normal range. There was a light difference in the mean value of PbB in comparison with a group of 50 normal subjects; no difference was found in FEP levels. The distribution of PbB and FEP values was also studied in workers and in non exposed subjects.

The outcome of the respiratory symptoms, pulmonary function tests and bronchial hyperresponsiveness was studied in forty-seven workers with respiratory disease due to toluene diisocyanate (TDI) (twenty-seven asthmatic and twenty non-asthmatic subjects) after about 2 years from the first examination. Eight of twelve asthmatic subjects who left the industry after the first examination complained at the follow-up of dyspnoea and wheezing, but pulmonary function tests were unchanged; bronchial hyperresponsiveness decreased in three, but most were still positive to challenge test with bethanechol at the follow-up. Fifteen subjects who continued their exposure to TDI showed at the follow-up a significant decrease of the spirometric parameters and an increase of the bronchial hyperresponsiveness, and symptoms of chronic bronchitis were more frequent at the second examination. Non-asthmatic subjects, both exposed and non-exposed to TDI at the second examination, showed a significant decrease of the pulmonary function tests but no relevant changes in bronchial hyperresponsiveness. Our data suggest that stopping occupational exposure to TDI frequently did not produce an improvement of the TDI bronchial asthma, and persistence of the occupational exposure causes a more rapid decline in the respiratory function.

Responsiveness to synthetic thyrotropin-releasing hormone (TRH), thyroid suppressibility by triiodothyronine (T3) and the outcome of hyperthyroidism following prolonged therapy with thionamides were studied in a group of 35 patients with toxic diffuse goiter. TRH and T3 suppression tests were performed 10 days to 24 months (mean 4 months) after withdrawal of antithyroid drugs. Nineteen patients were euthyroid and had a normal thyrotropin (TSH) response to TRH, while 4 were recovering from mild hypothyroidism due to overtreatment and had an exaggerated response. No response was observed in 12 patients with recurrent hyperthyroidism. Positive T3 suppression tests were found only in 10 of the 30 cases examined. Peak and net 2 h secretion responses of TSH to TRH exhibited a significant inverse correlation with the levels of serum thyroxine and serum triiodothyronine, but were unrelated to the degree of thyroid suppressibility. Relapse or recurrence of thyrotoxicosis occurred in at least 9 of the 23 patients having no evidence of hyperthyroidism at the time of TRH test. Each of them was found to be responsive to TRH, while the T3 suppression test was negative in 8 and had to be discontinued in one because of thyrotoxic symptoms. The present data indicate that during the early period after completion of a prolonged course of antithyroid drug therapy responsiveness to TRH in toxic diffuse goiter is: a) correlated with circulating thyroid hormones, b) unrelated to the degree of thyroid suppressibility by T3 and c) of little value in predicting the long-term results of treatment.

It is now well accepted that serum thyroglobulin (Tg) determination is a specific marker of disease activity in well-differentiated thyroid cancer after total thyroidectomy. In this study we examined 15 thyroidectomized patients with metastases from medullary thyroid cancer and 10 patients with metastases from undifferentiated thyroid cancer, to determine whether serum Tg measurement could be useful also in these types of thyroid tumors. In contrast with differentiated thyroid cancer, which had high levels of circulating serum Tg, patients with medullary and undifferentiated thyroid cancer had undetectable or low levels of serum Tg. Thus, serum Tg measurements are not useful in the diagnosis of metastatic disease in these patients.

The intraperitoneal administration to rats of 500 mg/kg body weight of 2-deoxy-D-glucose, an analog of glucose which produces intracellular glucopenia with rise in extracellular fluid glucose concentration, is followed by a significant though transient reduction of hypothalamic TRH content, observed at 15 and 25 minutes after drug administration. A subsequent increase in serum thyrotropin followed by that of triiodothyronine concentration was also observed. These findings indicate that the neuroglucopenia induced by 2-deoxy-D-glucose may play a role in the regulating the hypothalamic-pituitary-thyroid axis.

We have studied the in vitro TSH secretion and the adenylate cyclase (AC) activity of a human pituitary adenoma surgically removed from a hyperthyroid patient showing high serum TSH levels. The tumor appeared almost homogeneously constituted by cells positive for an anti-TSH-beta antiserum and showing the ultrastructural characteristics of the adenomatous thyrotrophs. Adenoma fragments released in vitro a large amount of TSH (148.4 microU/mg prot/30 min), alpha-subunit (35.5 ng/mg prot/30 min) and TSH-beta (10.1 ng/mg prot/30 min). The effects of somatostatin (GHRIH) and dopamine (DA) on the hormone release have been tested in vitro. Both agents markedly inhibited the release of intact TSH and TSH-beta whereas the release of alpha-subunit was less affected. The two agents were effective at concentrations higher than 10(-8)M. The ability of GHRIH and DA in modulating the AC activity was investigated in membrane fraction preparations. GHRIH inhibited AC at concentrations higher than 10(-7)M. The maximal inhibition was 32% at 10(-5)M. Conversely, DA slightly stimulated AC activity. This effects was not mimicked by the dopaminergic ergot CH 29-717, which was completely ineffective on the enzyme. These results suggest that: 1) in this TSH-secreting pituitary adenoma a normal secretory response to the inhibiting agents (GHRIH and DA) is present; 2) different mechanisms of transduction of the GHRIH and DA signals (cAMP dependent and cAMP independent) could be operating in this tumor.

Measurements of serum thyroxine binding globulin (TBG) by a ligand partitioning sandwich assay were performed in 173 healthy subjects between three months and 92 yr of age. Significant sex-related differences were observed in subjects aged 21 to 50 yr. In males, serum TBG declined progressively reaching a nadir in the fourth decade and then increased with advancing age. In contrast, no significant age-related variation was observed in females.

Hypothyroidism is often observed after radioiodine treatment in Graves' disease, but it is considered a rare complication in single hyperfunctioning thyroid nodule ('hot' nodule). This concept has been recently challenged, but the available data are conflicting. In the present study we therefore assessed the development of permanent hypothyroidism in 126 patients with thyroid hot nodule treated with 131I (180 muCi/g of estimated nodule weight, total dose 5.5-28.9 mCi). Follow-up ranged between 1 to 11 years. Hypothyroidism was observed in 5 (4%) patients, corresponding to a cumulative incidence by life-table analysis of 4.8% ten years after treatment. No relationship was found between the development of hypothyroidism and the size of the nodule or the total amount of administered dose. Fifty-six patients with euthyroid hot nodule at the time of treatment had higher cumulative incidence of hypothyroidism after 10 years (9.7%) than those with toxic adenoma (1.5%) (0.1 greater than P greater than 0.05 by logrank test). When the patients were analyzed according to the presence or absence of serum antithyroglobulin and/or antithyroid microsomal autoantibodies, the prevalence of hypothyroidism after 131I treatment was higher (4/25 = 16%) in patients with significant serum antibody titres (greater than or equal to 1/400 by passive haemagglutination), when compared to that observed in subjects with negative antibody tests (1/101 = 1.0%). Life-table analysis showed in antibody positive patients a cumulative incidence of hypothyroidism after 10 years of 18.0% vs 1.4% in antibody negative patients (P less than 0.001 by logrank test).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of the administration of oral glucose with or without a simultaneous intravenous somatostatin infusion on blood glucose, immunoreactive insulin, C-peptide, and glucagon levels in seven patients with idiopathic postprandial hypoglycemia was studied. Oral glucose alone induced an excessive insulin response and hypoglycemia, whereas a slight suppression in glucagon levels without any increase at the hypoglycemic nadir was observed. The simultaneous administration of somatostatin significantly reduced the insulin response and induced a slower rise of blood glucose; no hypoglycemia developed. Only minor variations in glucagon were observed with respect to the basal test. A rebound in insulin, C-peptide, and glucagon levels was observed at the end of the somatostatin infusion. These data show that somatostatin can suppress glucose-induced hypoglycemia in these subjects, thus suggesting that its long-acting analogues might be worth a therapeutic trial in severe idiopathic postprandial hypoglycemia.

Thyrotropin-releasing hormone (TRH)-like material was found in human retina obtained at autopsy from eyes used for corneal grafts. The TRH-like material was extracted with methanol and was found to be indistinguishable from synthetic TRH in its immunoreactivity and bioreactivity and in its proteolytic degradation by fresh human serum. The TRH concentration in human retina was similar to that reported in human cerebral cortex. These data are in keeping with the notion that the retina is an extension of the central nervous system. The physiological function of human retinal TRH in unknown: probably it acts as a neurotransmitter.

Amiodarone, an iodine containing drug, may induce thyrotoxicosis by an uncertain mechanism. In this study the role of thyroid autoimmunity was evaluated in 28 consecutive patients referred to us because they had become hyperthyroid during long-term amiodarone administration. Titres of thyroglobulin and thyroid microsomal antibodies, TSH binding-inhibitory and thyroid stimulating antibodies were evaluated. Underlying thyroid disorders were demonstrated in 20 patients (9 of them had toxic diffuse goitre, seven toxic multinodular goitre and four toxic adenoma), while eight patients did not show any apparent thyroid gland abnormality. Circulating thyroid autoantibodies could be found in all amiodarone iodine-induced hyperthyroid patients with toxic diffuse goitre and in one with toxic multinodular goitre, whilst they were absent in the other patients. These studies suggest that thyroid autoimmunity has little if any role in the development of thyrotoxicosis in amiodarone treated patients without underlying thyroid disorders. Furthermore, in amiodarone-iodine-induced thyrotoxicosis associated with various thyroid diseases, the humoral markers of thyroid autoimmunity show an incidence similar to that observed in spontaneous hyperthyroidism.

51 male patients with mild degree chronic airway obstruction underwent detailed evaluation of pulmonary function tests, blood gas analysis and exercise tolerance test before and after a short-term therapy. The patients were randomly assigned to medical therapy alone or to medical and rehabilitative therapy. 23 patients treated with medical and rehabilitative therapy showed a significant decrease of respiratory rate and PaCO2 and a significant increase of TV, FEV 1.0, FEV 0.75 x 40, PaO2, SaO2 and exercise tolerance after a month of therapy. 28 patients treated with medical therapy alone showed a significant increase of VC and FEV 0.75 x 40. These data suggest that rehabilitative therapy is a valid adjunct to medical therapy in the short-term treatment of chronic airway obstruction.

Serum thyroglobulin (Tg) was measured in the cord blood of 635 newborns and serum thyroxine (T4) reverse triiodothyronine (rT3), TSH and T3 were measured in about 200 of them. Cord Tg was detectable in all newborns with a mean +/- SE value (50 +/- 1.3 ng/ml) higher than that found in the serum of adult subjects (n = 144; Tg = 13 +/- 1.1; p less than 0.0001). Cord Tg had a log-normal distribution. A low, but positive correlation was found between cord Tg and cord TSH (n = 242; r = 0.17; p less than 0.05) but not with cord T4 or cord rT3. Gestational age was negatively correlated with cord Tg or cord rT3 (rS = 0.97; p less than 0.01; rS = -0.89; p less than 0.02, respectively) while was positively correlated with cord T4 or cord TSH (rS = 0.85; p less than 0.05; rS = 0.86; p less than 0.01, respectively). Birth weight, maternal diabetes, induction of labor with oxitocin, cesarian section and newborns' illness showed no influence on cord Tg levels when considered alone, but decreased cord Tg levels were found in ill newborns delivered by cesarian section. On the contrary, increased cord Tg levels were present in cord blood of newborns who developed hypoglycemia soon after birth and in small for gestational age newborns. In 24 newborns studied daily for the first 6 days of life, serum Tg was always detectable with mean values not different from those found in the cord blood.(ABSTRACT TRUNCATED AT 250 WORDS)

We have evaluated neuropsychic development in 70 normal schoolchildren in an area of severe endemic goitre and cretinism in the Central Apennines (Montefeltro). In each subject we have studied auxological, psychometric and audiometric parameters, together with tympanograms and stapedial reflexograms. Auxological data were in the normal range, as were the stapedial reflexograms and tympanograms. On the contrary, 54.8% of the sample performed below the 25th percentile in psychometric tests (Raven test PM-47), being also 22.8% below the 5th percentile. Audiometric data showed a neurological hearing impairment in 3.1% of the children tested, as compared with 0.28% in the area of Pisa. These data point out that an impairment of central nervous system function still persists in this area of severe endemic goitre.

The effects of lithium carbonate on thyroid was evaluated in 40 consecutive psychiatric patients on long-term treatment with this drug. Five patients had clinical and/or biochemical hypothyroidism. Twenty four (60%) subjects showed goiter of different size, including very large glands. A very high prevalence of goiter (87%) was observed in the 15 patients coming from a moderate endemic area. A lower incidence of goiter (44%) was found in subjects coming from non endemic areas. Goiter was associated with significantly elevated serum thyroglobulin concentration similar to that reported in endemic or sporadic nontoxic goiter. None of 25 psychiatric patients not receiving lithium therapy was hypothyroid and only three (12.5%) of them showed a small size goiter. These data indicate a very high prevalence of thyroid enlargement in patients on lithium therapy and suggest the opportunity to institute a prophylactic thyroid hormone treatment at least in subjects coming from endemic areas.

The ontogeny of nyctohemeral variations of hypothalamic TRH content was determined in male rats from 7-45 days after birth, exposed to a daily 12-h light, 12-h dark cycle (0600-1800 h light; 1800-0600 h dark) or maintained in complete darkness until 45 days. TRH was extracted from whole hypothalami with 90% methanol and assayed by specific RIA. Hypothalamic TRH extracted from rats at different ages showed immunological, chromatographic, and biological properties identical to those of synthetic TRH. No significant variations in hypothalamic TRH content during the day were observed in 7-, 10-, and 17-day-old rats; a significant change, with a maximal value at 1800 h, was observed in 23-day-old rats, while an adult pattern with a maximal value at 1200 h and a minimal value at 2400 h was found in rats of 31 days of age and became more evident in 45-day-old rats. In animals maintained in complete darkness for 45 days after birth, no significant changes in hypothalamic TRH content at 1200 and 2400 h were observed. These findings indicate that environmental cyclic light-dark exposure is required for the development of diurnal changes in hypothalamic TRH content. Furthermore, any study involving hypothalamic TRH determination should take into account the age of animals and the diurnal variations of TRH.

Serum tissue polypeptide antigen, (TPA), carcinoembryonic antigen (CEA), calcitonin (CT) and thyroglobulin (Tg) have been measured by specific radioimmunoassays in 174 patients with various types of thyroid cancer previously submitted to thyroidectomy. Elevated serum TPA concentrations were found in 12 of 13 patients with local invasion or distant metastases from undifferentiated thyroid cancer or thyroid lymphosarcoma, while serum Tg and CEA values were normal or undetectable. In 123 patients with well differentiated thyroid cancer serum TPA was usually normal regardless of the presence or absence of functioning metastases. On the contrary, 14 of 15 patients with "dedifferentiated" metastases from previously differentiated thyroid cancer had elevated serum TPA values, while serum CEA was normal and serum Tg variable. Serum CT was confirmed as the most sensitive marker of metastatic medullary thyroid carcinoma, but elevated serum TPA values were also found in most of these cases. The present data indicate that serum TPA provides a new humoral marker in the follow-up of undifferentiated and "dedifferentiated" thyroid carcinoma and may also be usefully employed as an additional marker for medullary thyroid carcinoma.

The thyrotropin-releasing hormone (TRH) content in whole hypothalamus was measured by specific radioimmunoassay in rats exposed to a daily light-dark cycle (06:00-18:00 light, 18:00-06:00 dark) and in animals exposed to constant light or constant darkness for 12 days. A nyctohemeral variation of hypothalamic TRH was observed in light-dark exposed animals, while this variation was abolished by exposure either to constant light or constant darkness. These data indicate that any study involving hypothalamic TRH determination should be carried out taking into account the diurnal variation and the effect of environmental light exposure.

The goitrogenic role of autoimmune phenomena in endemic goiter is still uncertain. Scanty and discrepant results have been reported in different areas of the world. This prompted us to evaluate the prevalence of circulating thyroid antibodies in an area of North-Western Tuscany during a survey for endemic goiter. The survey was carried out according to the P.A.H.O. criteria in a stable community. In all schoolchildren (n = 142, age range 7-15 yr) and in most of their parents (n = 159), thyroid size was evaluated and urine was collected for iodine determination. Blood was drawn for determination of circulating thyroid microsomal (MAb) and thyroglobulin antibodies (TgAb), TT3, TT4 and TSH. Prevalence of goiter in schoolchildren was 77.9% and 94.8% in their parents. Mean (+/- SD) urinary iodine excretion was 55.0 +/- 2.1 micrograms/24 h. The overall frequency of TgAb and MAb in the adult population was 14.4%, statistically higher than that of control subjects matched for sex and age. The frequency in schoolchildren was 4.3%. The presence of goiter in children was unrelated to the presence of thyroid antibodies in parents, whether goitrous or nongoitrous. A higher prevalence of goiter was found in children with goitrous parents as compared to children with nongoitrous parents (p less than 0.005). In conclusion, the frequency of thyroid autoantibodies in the adult population of the endemic area studied was increased, but showed no relation with the presence of goiter. The prevalence of goiter in children was associated with the presence of goiter but not of thyroid autoantibodies in parents. These data suggest that autoimmune phenomena are of limited importance in the development of endemic goiter.

Alveolar-capillary diffusion of CO was evaluated in 48 silicotics with predominantly small irregular opacities at low profusion. The mean value of CO diffusion lay between 82 and 87% of the reference values, except for DLCOSS2 which was slightly reduced (74% of theoretical). There was no correlation between the functional data and duration of work but there was a significant reduction of the CO diffusion values according to smoking, which was greatest in those smoking more than 15 pack-years. Subjects with small irregular opacities presented lower values than those with small "p" or "q" opacities, but this difference was not apparent when only non-smokers were considered.

Six asthmatic subjects exposed to enzymatic detergents derived from B. Licheniformis were examined by means of a specific Bronchial Provocative Test (sBPT) with solutions of the enzyme. All subjects, except for one, were positive to prick tests with solutions of the "crude" enzyme and with Alcalase, and showed high levels of specific IgE by RAST. The sBPT with solutions of the enzyme, administered by means of a Bird Mark 7 nebulyzer in IPPB with measurement of the delivered dose, showed a positive response in all 6 subjects. No positive result was obtained in 5 normal subjects and in 5 non exposed asthmatic patients, even at much higher doses of the delivered enzyme. The occupational-type sBPT showed only two positive results out of the 6 examined. A good relationship was observed between bronchial hyperresponsiveness and provocative dose of the enzyme. Therefore, the sBPT with solutions of the enzyme is proved to be highly sensitive and specific in confirming the diagnosis of occupational asthma due to proteolytic enzymes.

Combined therapy with systemic corticosteroids and orbital cobalt radiotherapy has been shown to be an effective treatment of severe Graves' ophthalmopathy. The potentially serious side-effects of large doses of systemic corticosteroids prompted us to evaluate the use of retrobulbar corticosteroids instead of systemic corticosteroids. Forty-four patients with active Graves' ophthalmopathy were given orbital cobalt irradiation (total dose 2000 rads) and retrobulbar methylprednisolone acetate (14 bilateral injections at 20-30 d intervals). The degree of ocular involvement and responses to treatment were evaluated by numerical scoring (ophthalmopathy index, OI) and clinical assessment. Excellent or good responses were observed in 11 out of 44 patients (25%), 24 (55%) showed slight responses, and no change was found in 9 patients (20%). The initial OI mean score was 5.9; the final score was 3.2, with a change of -2.7 (P less than 0.001). Regression or partial improvement was observed in most cases (35/44, 80%) with soft tissue changes, and in all 9 cases with sight loss due to optic neuropathy. Proptosis, corneal lesions and extra-ocular muscle involvement were less responsive, since regression or partial improvement was observed in 39% (12/31), 50% (8/16) and 31% (13/42), respectively. No major side-effects were observed. The effects of this type of therapy and those obtained by combined therapy with systemic corticosteroids and orbital radiotherapy were compared in two groups of 30 patients each, randomly assigned to either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

The serum free thyroxine concentration was measured by direct radioimmunoassay in 38 untreated T3-thyrotoxic patients with elevated serum total and free triiodothyronine, normal serum thyroxine and free thyroxine index, no TSH response to TRH, and with clinical evidence of hyperthyroidism. An elevation of circulating free thyroxine values was observed in 58% of the patients, whereas total serum thyroxine concentration was within the normal range. It is suggested, therefore, that T3-thyrotoxicosis should be reserved for patients with elevated serum total T3 and free T3 concentrations and normal serum total T4 and free T4 concentrations. Serum thyroxine-binding globulin concentrations were significantly lower (P less than 0.025) in patients with an elevated serum free thyroxine (18.7 +/- 3.6 micrograms/ml: mean +/- SD) as compared with those in patients with a normal free thyroxine concentration (23.4 +/- 2.6 micrograms/ml). In addition, no daily fluctuations in total and free thyroxine concentration were observed in 6 patients over a 4-8 day period.

Thirty-six menopausal women and 18 women with surgically-induced menopause were treated with a daily oral dose of 100 mg of veralipride for a period of 20 days followed by 10 days without therapy. Following 2 or 3 treatment periods, the drug was effective in 27 women from the first group and in 13 women from the second group. Six women had to discontinue therapy because of adverse effects. There was no significant variation in FSH or LH serum levels.

A case of allergic oculorhinitis induced by toluene diisocyanate (TDI) exposure in a subject who two years later developed bronchial asthma due to TDI is described. A 55-year-old nonatopic spray painter developed symptoms of oculorhinitis two or three hours after direct occupational exposure to polyurethane varnish; at the first examination neither specific nor nonspecific bronchial hyperresponsiveness was present. Two years later the patient, who had remained in his job, developed episodic dyspnea, wheezing, and cough immediately after TDI exposure, with persistence of oculorhinitis; at this time a slight immediate-type response to a specific bronchial provocative test with polyurethane varnish and TDI was observed. Nonspecific bronchial hyperresponsiveness was mild. Specific IgE to TDI-HSA conjugate was present at both the first and second examinations. We conclude that, in some cases, TDI may cause "allergic" oculorhinitis and bronchial asthma, probably with an immunological IgE-mediated mechanism.