Gastric peroxidase — localization, catalytic properties and possible role in extrathyroidal thyroid hormone formation

1981 ◽  
Vol 96 (2) ◽  
pp. 208-214 ◽  
Author(s):  
Ranajit K. Banerjee ◽  
Asoke G. Datta
Keyword(s):  
Thyroid Hormone ◽  
Mitochondrial Membrane ◽  
Catalytic Properties ◽  
Proteolytic Enzymes ◽  
Antithyroid Drugs ◽  
Highly Active ◽  
Hormone Formation ◽  
Gastric Peroxidase

Abstract. A highly active peroxidase (EC 1.11.1.7) has been found to be localized in the mitochondria isolated from the fundic region of mouse stomach. The stomach has also the property of concentrating iodide significantly. Evidence has been presented to show that the peroxidase is orientated outside the mitochondrial membrane. The enzyme is strongly inhibited by antithyroid drugs like methimazole and thiouracil. Azide and cyanide completely inactivate the enzyme. The activity is inhibited by SH-blocking reagents like mersalyl or pchloromercuribenzene sulphonate, but not by N-ethylmaleimide. The enzyme is also sensitive to the action of some proteolytic enzymes. It can catalyse the formation of mono- or diiodotyrosine from tyrosine or monoiodotyrosine as substrate, respectively. The enzyme is capable of synthesizing thyroxine and triiodothyronine on the backbone of a protein, such as thyroglobulin or albumin.

Early change of thyroid hormone concentration after 131I treatment in patients with solitary toxic adenoma

2002 ◽  
Vol 41 (04) ◽  
pp. 178-183 ◽  
Author(s):  
V. Fidler ◽  
K. Zaletel ◽  
S. Gaberšček ◽  
S. Hojker ◽  
E. Pirnat
Keyword(s):  
Thyroid Hormone ◽  
Antithyroid Drugs ◽  
Prospective Clinical Study ◽  
Hormone Concentration ◽  
Toxic Adenoma ◽  
Free Triiodothyronine ◽  
Thyroid Cells ◽  
131I Treatment ◽  
Before And After ◽  
Thyroid Hormone Concentration

Summary Aim: In spite of extensive use of 131I for treatment of hyperthyroidism, the results of early outcome are variable. In our prospective clinical study we tested whether 131I induced necrosis causing clinical aggravation of hyperthyroidism and increasing the free thyroid hormone concentration in the serum of patients with solitary toxic adenoma not pretreated with antithyroid drugs. Patients and methods: 30 consecutive patients were treated with 925 MBq 131I. Serum concentration of thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), thyroglobulin (Tg), and interleukin-6 (IL-6) were measured before and after application of 131I. Results: After application of 131I no clinical worsening was observed. FT4 and fT3 concentration did not change significantly within the first five days, whereas both of them significantly decreased after 12 days (p <0.0001). Slight and clinically irrelevant increase in the level of the two thyroid hormones was observed in 9 patients. Furthermore, we observed a prolonged increase in Tg concentration and a transient increase in IL-6 concentration. Conclusion: Neither evidence of any clinical aggravation of hyperthyroidism nor any significant increase in thyroid hormone concentration by 131I induced necrosis of thyroid cells was found. Therefore, the application of 131I may be considered as a safe and effective treatment for patients with hyperthyroidism due to toxic adenoma.

scholarly journals Lipid abnormalities in elderly patients with subclinical hyperthyroidism

2003 ◽  
Vol 56 (11-12) ◽  
pp. 564-567 ◽  
Author(s):  
Zorica Caparevic ◽  
Dragos Stojanovic ◽  
Vesna Ilic ◽  
Gradimir Bojkovic ◽  
Mirjana Stojanovic
Keyword(s):  
Atrial Fibrillation ◽  
Thyroid Hormone ◽  
Elderly Patients ◽  
Cardiac Hypertrophy ◽  
Ldl Cholesterol ◽  
Hdl Cholesterol ◽  
Antithyroid Drugs ◽  
Subclinical Hyperthyroidism ◽  
Cholesterol Levels ◽  
Lipid Abnormalities

Introduction Sensitive thyroid-stimulating hormone (TSH) assays provide identification of many patients with subclinical hyperthyroidism resulting from excessive production or excessive replacement of thyroid hormone. Subclinical hyperthyroidism is defined by a TSH below normal (suppressed) with normal serum T3 and T4 levels. Subclinical hyperthyroidism is the goal of thyroid hormone therapy in patients with thyroid cancer, solitary thyroid nodules, multinodular or diffuse goiters, or a history of head and neck irradiation. Benefits of TSH suppression in these patients, were thought to exceed the risks of subclinical hyperthyroidism. Subclinical hyperthyroidism also occurs in patients with thyroiditis and those with autoimmune thyroid disease. Other causes of TSH suppression, such as use of glucocorticoids, severe illness and pituitary dysfunction should be excluded. Material and methods This investigation included 55 elderly patients with subclical hyperthyroidism in order to establish the type and degree of lipid abnormalities and effects of therapy with antithyroid drugs (methimazole 10 mg/day) during three months. These patients presented with no or minimal symptoms of thyroid hormone excess, but 56% of patients experienced atrial fibrillation and cardiac hypertrophy. Results Levels of serum cholesterol, LDL-cholesterol and HDL-cholesterol were decreased. We found a significant increase of serum cholesterol, LDL-cholesterol and HDL-cholesterol levels after treatment. Discussion and Conclusion Subclinical hyperthyroidism in elderly individuals is difficult to diagnose because it may present only with cardiac manifestations including atrial fibrillation and cardiac hypertrophy. There is general agreement that measurement of serum TSH is the most sensitive indicator of thyroid hormone activity in its target tissues. Patients with subclinical hyperthyroidism tend to have low serum total cholesterol, LDL-cholesterol anf HDL-cholesterol levels. These values increase after treatment. Most patients with subclinical hyperthyroidism should be treated with antithyroid drugs to prevent cardiovascular complications and bone loss, particulary among postmenopausal women.

scholarly journals Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative Damage in Mice

2020 ◽  
Vol 36 (10) ◽  
pp. 1158-1170
Author(s):  
Xun Wu ◽  
Wenxing Cui ◽  
Wei Guo ◽  
Haixiao Liu ◽  
Jianing Luo ◽  
...  
Keyword(s):  
Brain Injury ◽  
Oxidative Damage ◽  
Mitochondrial Membrane ◽  
Molecular Mechanisms ◽  
Mitochondrial Fission ◽  
Secondary Brain Injury ◽  
Functional Deficits ◽  
Highly Active ◽  
Neural Apoptosis ◽  
Mitochondrial Oxidative Damage

Abstract Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury.

scholarly journals SAT-434 Phenotype and Genotype Analysis of Patients with Resistance to Thyroid Hormone β: A Single-Center Experience

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Karn Wejaphikul ◽  
Prapai Dejkhamron ◽  
Stefan Groeneweg ◽  
W Edward Visser ◽  
Kevalee Unachak ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Mutation Analysis ◽  
Novel Mutation ◽  
Family Members ◽  
Antithyroid Drugs ◽  
Thyroid Function Tests ◽  
Resistance To Thyroid Hormone ◽  
The Mean ◽  
The Impact

Abstract Introduction Resistance to thyroid hormone β (RTHβ) is caused by mutations in THRB, the gene that encodes thyroid hormone receptor β. The clinical phenotype is variable and may include goiter, tachycardia, and learning disability with or without hyperactive behavior. The biochemical hallmark of RTHβ is elevated T4 and T3 with non-suppressed TSH concentrations. We here describe the phenotype and genotype of three Thai patients diagnosed with RTHβ in a pediatric referral center. Patients had previously been misdiagnosed and inappropriately treated with antithyroid drugs (ATDs). Methods Clinical features and thyroid function tests (TFTs) of three unrelated RTHβ patients were retrospectively reviewed. Genomic DNA of the RTHβ patients and affected family members was amplified for exon 7-10 of the THRB gene and sequenced to identify mutation by Sanger sequencing. The impact of the p.L341V novel mutation on the affinity for T3 and T3-induced transcriptional activity was previously determined in vitro. Results Three female patients were diagnosed with RTHβ. All of them had been misdiagnosed with hyperthyroidism and treated with ATDs prior to referral. The mean age at diagnosis was 8 years. The main presenting symptoms were diffuse goiter and tachycardia. The mean duration of ATD treatment was 3 years. During the treatment, patients had fluctuating thyroid hormone and increased TSH levels. An older sister and mother of one patient also had similar TFTs abnormalities, for which the mother had undergone a subtotal thyroidectomy. RTHβ was diagnosed based on the high FT3 and FT4 with normal (non-suppressed) TSH concentrations and confirmed by mutation analysis. Anti-thyroid peroxidase, anti-thyroglobulin, and TSH receptor antibody (TRAb) were negative, excluding autoimmune thyroid disease. Heterozygous missense mutations of the THRB gene were identified in all patients and affected family members. Two mutations had been previously reported (p.R243W and p.L456F), and one mutation was novel (p.L341V). In vitro studies confirmed an important role of Leu341 in T3 binding of the TRβ and functional impairment of the p.L341V novel mutation and were reported separately. According to available literature, only nine Thai RTHβ patients (in three families) carrying three different mutations (p.G251V, p.M313T, and p.A317T) had been previously reported. Goiter was the most common clinical finding, and almost all patients had a history of receiving unnecessary treatment with ATDs. Conclusion We report a series of RTHβ patients carrying THRB gene mutations, including one novel mutation (p.L341V). Clinicians should be alert that RTHβ can be found in patients with goiter and tachycardia. Elevated T4 and T3 with non-suppressed TSH concentration is the main diagnostic clue for this disease. Mutation analysis allows definitive diagnosis of RTHβ and may help to avoid potential misdiagnosis and improper treatment.

scholarly journals Challenging diagnosis of resistance to thyroid hormone in a patient with pituitary adenoma

2019 ◽  
Vol 12 (7) ◽  
pp. e229430
Author(s):  
Nelson Carvalho Cunha ◽  
Leonor Gomes ◽  
Margarida Bastos
Keyword(s):  
Pituitary Adenoma ◽  
Thyroid Hormone ◽  
Correct Diagnosis ◽  
Pituitary Surgery ◽  
Pituitary Hormones ◽  
Young Female ◽  
Left Lobe ◽  
Antithyroid Drugs ◽  
Resistance To Thyroid Hormone ◽  
Normal Ranges

The elevation of thyroid hormone with a normal or elevated thyroid-stimulation hormone (TSH) occurs uncommonly. This set a diagnosis challenge between TSH-secreting pituitary adenoma and resistance to thyroid hormone (RTH). We report a case of a young female patient with palpitations, with elevated thyroid hormone and non-suppressed TSH. TSH receptor antibody was undetectable. Thyroid ultrasound revealed mild heterogeneous goitre, and MRI revealed a microadenoma with 7.5 mm length in pituitary’s left lobe. Pituitary hormones were within normal ranges. The thyrotropin-releasing hormone stimulation test showed normal TSH elevation, consistent with RTH. The genetic test revealed a mutation in heterozygosity in THRB gene (G344R) confirming RTH-beta. No pituitary surgery or thyroidectomy was performed nor were prescribed any antithyroid drugs. Inappropriate secretion of TSH requires a high level of clinical suspicion and the proper laboratory, genetic and radiological studies to conduct a correct diagnosis and prevent unnecessary and potential harmful therapies.

scholarly journals ASPERMATOGENESIS, ANAPHYLAXIS, AND CUTANEOUS SENSITIZATION INDUCED IN THE GUINEA PIG BY HOMOLOGOUS TESTICULAR EXTRACT

1955 ◽  
Vol 101 (6) ◽  
pp. 591-604 ◽  
Author(s):  
Jules Freund ◽  
George E. Thompson ◽  
Murray M. Lipton
Keyword(s):  
Acetic Acid ◽  
Guinea Pig ◽  
Ammonium Sulfate ◽  
Guinea Pigs ◽  
Anaphylactic Shock ◽  
Proteolytic Enzymes ◽  
Trichloracetic Acid ◽  
Oil Emulsion ◽  
Highly Active ◽  
Water In Oil Emulsion

Guinea pig testicles were extracted with acetic acid; the extract was purified by removing material in consecutive precipitations with 30 per cent saturated ammonium-sulfate, trichloracetic acid, and chloroform. The solution so purified, when administered with complete adjuvants, was highly active in inducing impairment of spermatogenesis in guinea pigs. The activity resisted autoclaving at 15 pounds' pressure for 20 minutes, proteolytic enzymes, and formamide. Anaphylactic shock and cutaneous reaction to the purified homologous extract occurred in guinea pigs sensitized by the extract combined with adjuvants. For the production of aspermatogenesis it was essential to incorporate killed mycobacteria into the water-in-oil emulsion containing the antigen; but anaphylactic sensitization did not require the presence of mycobacteria.

scholarly journals Psychoses associated with thyrotoxicosis - 'thyrotoxic psychosis.' A report of 18 cases, with statistical analysis of incidence

2000 ◽  
pp. 438-444 ◽  
Author(s):  
BE Brownlie ◽  
AM Rae ◽  
JW Walshe ◽  
JE Wells
Keyword(s):  
Statistical Analysis ◽  
Thyroid Hormone ◽  
Clinical Picture ◽  
Psychiatric Inpatient ◽  
Antithyroid Drugs ◽  
Affective Psychosis ◽  
Nodular Goitre ◽  
Affective Psychoses ◽  
Hormone Levels ◽  
Thyroid Hormone Levels

OBJECTIVE: To report a series of newly diagnosed thyrotoxic patients with concurrent acute psychosis, and to assess the association between the two disorders. DESIGN: Retrospective study of thyrotoxic patients with associated psychosis ('thyrotoxic psychosis'; TP) requiring inpatient psychiatric care. New Zealand thyrotoxicosis annual incidence figures and first psychiatric admission rates for affective psychosis were utilised to statistically assess the co-occurrence of thyrotoxicosis and affective psychosis. PATIENTS AND METHODS: During the 20-year study period, 18 inpatients (16 women and 2 men), mean age 54 years, with TP were identified. No patient had a past history of thyrotoxicosis, but four had required psychiatric inpatient care many years earlier. Thyrotoxicosis was documented by radioimmunoassay of thyroid hormone levels, and thyroid scintiscan. Psychiatric manifestations were classified using ICD9 criteria. RESULTS: Thyroid hormone levels were markedly elevated in more than half of our TP patients. All younger patients had Graves' disease, and most older patients toxic nodular goitre. All patients were treated with antithyroid drugs, and all but one subsequently received (131)I therapy. Two patients were not mentally ill when thyrotoxicosis was diagnosed, but suffered major mood swings when thyroid hormone levels were falling. There was no specific psychiatric clinical picture but affective psychoses were commonest - seven depression, seven mania. The other diagnoses were two schizophreniform, one paranoid, and one delirium. Initially, neuroleptic medication was used in all but one patient, and during long-term follow-up (median 11 years) more than half our series had remained well with no further psychiatric problems. Statistical analysis was restricted to thyrotoxic patients with first psychiatric hospital admission for affective psychosis. During the 20-year period, there were nine thyrotoxic patients (95% confidence interval 4.5-17.1) with concurrent affective psychosis requiring first admission, and the calculated expected number was only 0.36. These findings indicate a clear association well above chance co-occurrence. CONCLUSION: TP is not a specific clinical picture, but affective psychoses are commonest. Statistical analysis of thyrotoxic patients with concurrent affective psychoses showed an incidence well above chance co-occurrence. It appears that thyrotoxicosis may be a precipitant of acute affective psychosis.

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