triiodothyronine--reverse and Hyperthyroidism

Topics: Biomarkers; Humans; Hyperthyroidism; Hypothyroidism; Immunoassay; Reagent Kits, Diagnostic; Reference Values; Specimen Handling; Thyroid Function Tests; Triiodothyronine; Triiodothyronine, Reverse

Changes in thyroid function and structure during pregnancy, including abnormalities in thyroid ultrasonography. Levels of thyroid stimulating hormone (TSH), free thyroxine (FT4), total thyroxine (TT4), total triiodothyronine (TT3), reverse triiodothyronine (rT3), thyroxin binding globulin (TBG) and thyroglobulin (Tg) as well as the changes in metabolism have been presented. Difficulties in the diagnostics of hyperthyroidism and hypothyroidism in pregnant women have been described. In addition modern ideas about the treatment of thyroid dysfunction in this period of woman life have been presented. Furthermore thyroid physiology and pathology in fetus and newborn have been described.

Topics: Female; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Pregnancy; Pregnancy Complications; Thyroglobulin; Thyroid Diseases; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

Topics: Chemical Phenomena; Chemistry; Diiodothyronines; Diiodotyrosine; Glucuronates; Humans; Hyperthyroidism; Iodine; Kinetics; Phenyl Ethers; Radioimmunoassay; Sulfates; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Modern day evaluation of thyroid disorders requires a combination of accurate clinical judgement and reliable, sensitive, and specific thyroid functions tests. Principle among the latter are thyroxine (T4) 3, 5, 3'-triiodothyronine (T3), and thyroid-stimulating hormone (TSH). Also playing an important role in special situations are free thyroxine, an assessment of bound and unbound thyroid-binding globulin, TRH stimulation, long-acting thyroid stimulator (LATS), antibodies to thyroid hormone and to thyroid receptors. Basic to interpretation of these tests in the clinical setting is a comprehension of the relationship of the hypothalamus, the pituitary, and the thyroid gland as well as a knowledge of the peripheral metabolism of thyroxine and triiodothyronine. The role of each of these laboratory tests in the evaluation of hyper- and hypometabolic states, their alteration in nonthyroid and other endocrine disorders, and the effects of environmental and physiological factors on these tests are reviewed.

Topics: Adult; Aged; Autoantibodies; Calcitonin; Choriocarcinoma; Female; Fetus; Hepatitis; Humans; Hyperthyroidism; Hypothalamo-Hypophyseal System; Hypothyroidism; Infant, Newborn; Kidney Diseases; Male; Mental Disorders; Middle Aged; Pregnancy; Stress, Physiological; Thyroglobulin; Thyroid Diseases; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Several alterations in thyroid function are found in diabetes mellitus (see Table I). The most profound changes occur in patients with insulin-dependent diabetes. Plasma T4 is normal whereas plasma T3 is diminished, and the plasma level of rT3 is elevated in diabetic ketoacidosis or in patients with severely uncontrolled diabetes. These changes arise from alterations in the monodeiodination pathways of T4. Both hypo- and hyperthyroidism occur with increased frequency in diabetes. There is an increased prevalence of thyroid autoantibodies in insulin-dependent diabetics. Animals studies suggest a defect in the hypothalamic regulation of the thyroid-pituitary feedback system and an impaired response of the thyroid gland to TSH. Clinical studies are not yet available to confirm the occurrence of these regulatory disturbances in human diabetic patients. It is not clear whether the deiodination and regulatory changes in thyroid hormone economy that are associated with diabetes result in hypothyroidism at the cellular level.

Topics: Animals; Autoantibodies; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Humans; Hyperthyroidism; Hypothalamo-Hypophyseal System; Hypothyroidism; Insulin; Receptors, Cell Surface; Receptors, Thyroid Hormone; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Animals; Fetus; Humans; Hyperthyroidism; Hypothyroidism; Syndrome; Thyroid Hormones; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The purpose of this study was to determine differences in 131I biokinetics after oral or intravenous treatment of hyperthyroidism (0.81 GBq) or differentiated thyroid cancer (1.85 GBq) following thyroidectomy. 20 patients with differentiated carcinoma and 20 patients with hyperthyroidism were studied. In each group 10 patients were treated perorally and 10 patients intravenously. The integrated whole-body activities during therapy were significantly lower, by an average 23% (cancer) and 45% (hyperthyroidism) than after oral application. It is most likely that these differences between oral and intravenous application are due to the higher serum activity after intravenous therapy. It is concluded that a higher activity dose of 131I must be given orally to achieve the same target dose as after intravenous application.

Topics: Administration, Oral; Aged; Humans; Hyperthyroidism; Injections, Intravenous; Iodine Radioisotopes; Middle Aged; Thyroid Neoplasms; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The purpose of this study is to determine whether there is a difference in treatment of hyperthyroidism using either the D- or L-isomer of propranolol. Two groups of 20 patients with overt hyperthyroidism received either 120 mg L- or D-propranolol each for a period of 5 days. In the D-propranolol administered group there was a significant decrease in TT3 and fT3 plasma levels and in the ratio of TT3 to TT4; however, a significant increase occurred in rT3 values up to day 5. On the other hand, L-propranolol treatment resulted in a less pronounced decrease in TT4 and TT3 values, while all other thyroid hormone levels remained unchanged as, above all, did the T3/T4 ratio. The well known effect of D,L-propranolol upon peripheral conversion of T4 to T3 is thus not due to the beta-blocking action of L-propranolol but is mainly conditioned by the D-isomer which has no beta-blocking action itself.

Topics: Adult; Aged; Basal Metabolism; Female; Humans; Hyperthyroidism; Male; Middle Aged; Propranolol; Sex Hormone-Binding Globulin; Stereoisomerism; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Amiodarone; Benzofurans; Humans; Hyperthyroidism; Iodine; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Administration of the anti-inflammatory drug fenclofenac (600 mg bd) for 28 days to four females with thyrotoxicosis resulted in a rapid decline in thyroid hormone levels. The mean total thyroxine (T4) level of 173 +/- 8.6 (SEM) nmol/l before therapy was normalized to 70 +/- 6.4 nmol/l after administration of the drug for 7 days. Free T4 levels also decreased significantly but not to within the reference range in all subjects. Mean total triiodothyronine (T3) and reverse T3 levels declined from 6.2 +/- 0.9 nmol/l and 0.63 +/- 0.2 nmol/l respectively before therapy to 3.8 +/- 0.5 nmol/l and 0.52 +/- 0.1 nmol/l after 7 days' treatment but remained consistently elevated in all subjects. Clinical thyroid status remained unchanged despite these marked reductions in circulating thyroid hormone levels, suggesting that fenclofenac was of no therapeutic benefit.

Topics: Adult; Anti-Inflammatory Agents; Clinical Trials as Topic; Female; Humans; Hyperthyroidism; Middle Aged; Phenylacetates; Thyroid Gland; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Treatment for one month with propranolol or atenolol, a selective beta-1-adrenoceptor blocking agent, was evaluated in 20 hyperthyroid patients. The patients improved to the same extent on either drug, as shown by a clinical diagnostic index. Basal metabolic rate decreased by 11% during both treatments, while it was unchanged in seven untreated hyperthyroid controls. Thyroxine concentration did not change during any treatment. During propranolol treatment T3 decreased from 4.6 to 3.9 nmol/l, while no changes were observed during atenolol treatment or in the control group. No significant changes were seen in free T4, free T3 or rT3 concentrations on any treatment, although free T3 was observed to decrease slightly during propranolol treatment. Thus, the improvement of the clinical symptoms of hyperthyroidism cannot be explained by diminished thyroid hormone concentrations in serum, since the reduction was small during propranolol and absent during atenolol treatment.

Topics: Adolescent; Adult; Atenolol; Drug Evaluation; Female; Humans; Hyperthyroidism; Male; Middle Aged; Propanolamines; Propranolol; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

To fully investigate the thyroid hormonal function in patients with the most common arrhythmia - atrial fibrillation.. 120 patients (aged 55-85 yrs) with symptoms of congestive heart failure exacerbation and no other concomitant disorders (inclusion criteria: normal cardiac troponin T at admission and 12 hours after, normal renal, hepatic and respiratory function; exclusion criteria: inflammatory state, history of myocardial infarction). Depending on the presence of permanent atrial fibrillation (PAF), patients were divided into two groups: PAF (34 females, 26 males) and regular sinus heart rhythm (43 females, 17 males), the groups did not differ in terms of heart rate, blood pressure, presence of overt/subclinical thyroid dysfunction, and medical therapy used. In all subjects thyroid stimulating hormone, free thyroxine, free triiodothyronine, reverse triiodothyronine were measured; echocardiography was performed.. PAF group showed higher FT4 and rT3 (1.41 vs. 1.27 ng/dl, p=0.0007; 0.61 vs. 0.32 ng/ml, p<0.0001, respectively). With ROC curve analysis the biochemical thyroid related factor of the highest prognostic value for PAF occurrence (with the highest sensitivity and specificity: 77% and 72%, respectively) was rT3 with the cut-off of above 0.3 ng/ml. Also, a positive correlation between rT3 levels and left ventricular posterior wall diameter was observed (Spearman's correlation coefficient 0.33, p=0.0093).. PAF is another condition where an increase in rT3 is observed. rT3 concentration above 0.3 ng/ml may be a novel biochemical sign associated with the presence of PAF in patients with chronic heart failure.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Case-Control Studies; Cohort Studies; Female; Heart Failure; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; ROC Curve; Thyroid Function Tests; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Inhabitants living in areas with endemic dietary iodine intake deficiency develop nodular goitre. The aim of our study was to evaluate thyroid morphology and function among adults residing in Lower Silesia and to assess the effect on the thyroid gland of an iodine-based contrasting agent administered during a cardiac intervention procedure.. The first part of the study (evaluation of thyroid gland) was carried out on 120 subjects (78 men and 42 women). From among this group, invasive cardiac procedures were performed on 60 subjects (38 men and 22 women) during the second part of the study. Endocrine tests were repeated one, three, and six months after the invasive procedure.. 1) Within the studied group, pathological changes in thyroid morphology were found in 49.1%, and thyroid function disturbances in 9.3%, of all subjects. 2) A decrease in TSH concentration with a corresponding increase in fT3 concentration was seen at the second visit (four weeks after iodine administration) leading to the diagnosis of hyperthyroidism in 15% of subjects.. 1) Considering the multitude of silent thyroid pathologies, particular care is required before administering an iodine-based medium. 2) It is reasonable and advisable to monitor TSH and fT3 levels before and at four weeks after administration of an iodine-containing contrast agent. 3) Thyroid morphology and function disturbances after iodine administration do not necessitate treatment, as they are of transient character and only require monitoring.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Cardiac Catheterization; Contrast Media; Coronary Angiography; Dose-Response Relationship, Drug; Female; Humans; Hyperthyroidism; Iodine; Male; Middle Aged; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Human extraocular muscles (EOM) are preferentially susceptible to thyroid eye disease. Although the specific cause of this autoimmune disorder is unknown, it is often associated with elevated thyroid hormone levels. Thus, the effect of elevated thyroid hormone levels on cross-sectional area, myofiber size, satellite cells, and myosin heavy chain (MyHC) isoform expression was examined in adult rabbit EOMs, to determine how elevated thyroid hormone alters EOM biology.. After 1 month of elevated thyroid hormone levels, the EOMs were removed and prepared for histologic examination. Total muscle mass, myofiber size, patterns of MyHC isoform expression, and the number of satellite cells were determined.. Elevated thyroid hormone levels significantly decreased muscle mass, total number of myofibers, and mean cross-sectional area of the myofibers. Alterations in MyHC isoform expression were extremely complex, but several basic patterns emerged. The percentages of neonatal- and developmental-positive myofibers decreased in almost all EOM regions examined, and the percentages of slow-positive myofibers significantly increased. In contrast to normal EOMs, which retain a population of activated satellite cells throughout life, elevated thyroid hormone levels resulted in the virtual disappearance of MyoD-positive cells and a decrease in Pax7-positive cells.. The reductions in EOM size, number of fibers expressing developmental and neonatal MyHC, and number of MyoD- and Pax7-positive satellite cells suggest that elevated thyroid hormone levels decrease the ongoing myofiber remodeling normally seen in the EOM. These catabolic changes have important implications for maintenance of function in the EOMs.

Topics: Animals; Hyperthyroidism; Muscle Fibers, Skeletal; MyoD Protein; Myosin Heavy Chains; Oculomotor Muscles; PAX7 Transcription Factor; Protein Isoforms; Rabbits; Satellite Cells, Skeletal Muscle; Triiodothyronine, Reverse

The aims of this work were to determine the effect of hypothyroidism on insulin-stimulated glucose turnover and to unravel the potential mechanisms involved in such an effect.. Hypothyroidism was induced by administration of propylthiouracil, with partial T4 substitution. Euglycaemic-hyperinsulinaemic clamps, associated with the labelled 2-deoxy-D-glucose technique for measuring tissue-specific glucose utilisation, were used. To assess a possible involvement of leptin in the modulation of glucose metabolism by hypothyroidism, leptin was infused intracerebroventricularly for 6 days. A group of leptin-infused rats was treated with rT3 to determine a potential role of T3 in mediating the leptin effects.. Compared with euthyroid rats, hypothyroid animals exhibited decreased overall glucose turnover and decreased glucose utilisation indices in skeletal muscle and adipose tissue. Leptinaemia in hypothyroid rats was lower while resistin mRNA expression in adipose tissue was higher than in euthyroid animals. Intracerebroventricular leptin infusion in hypothyroid rats partially restored overall, muscle and adipose tissue insulin-stimulated glucose utilisation and improved the reduced glycaemic response observed during insulin tolerance tests. The leptin effects were due neither to the observed increase in plasma T3 levels nor to changes in the high adipose tissue resistin expression of hypothyroid rats. The administration of leptin to hypothyroid animals was accompanied by increased expression of muscle and adipose tissue carnitine palmitoyl transferases, decreased plasma NEFA levels and reduced muscle triglyceride content.. Hypothyroidism is characterised by decreased insulin responsiveness, partly mediated by an exaggerated glucose-fatty acid cycle that is partly alleviated by intracerebroventricular leptin administration.

Topics: Adipose Tissue; Animals; Blood Glucose; Carnitine O-Palmitoyltransferase; Energy Metabolism; Fatty Acids, Nonesterified; Gene Expression; Glucose; Glucose Clamp Technique; Hormones, Ectopic; Hyperthyroidism; Insulin; Insulin Resistance; Iodide Peroxidase; Iodothyronine Deiodinase Type II; Leptin; Male; Muscle, Skeletal; Propylthiouracil; Rats; Rats, Wistar; Resistin; Thyrotropin; Thyroxine; Triglycerides; Triiodothyronine; Triiodothyronine, Reverse

Hyperthyroidism is known to affect multiple organ functions, and thyroid hormone has been known to improve myocardial function in a failing heart. The purpose of this study is to elucidate the functional and metabolic effects of thyroid hormone on myocardium in a rat model exposed to long-term excess thyroid hormone, particularly focusing on the SR Ca(2+)-ATPase (SERCA2) function. 3,5,3'-Triiodo-L-thyronine (T3), or the vehicle, was subcutaneously given for 4 weeks (T3 and control [C] group). Bolus I.V. Thapsigargin (TG) was used to test the SERCA2 function (C-TG and T3-TG) in Langendorff perfused heart. Myocardial functions such as LV-developed pressure (LVDP; mmHg), +/- dP/dt (mmHg/s), tau (ms), and oxygen consumption (MVO(2); ml/min/g wt) were measured. SERCA2 and GLUT4 protein level were also evaluated by Western immunoblotting. Left ventricle to body weight (LV/BW) ratio was significantly higher in the T3 group. Both negative dP/dt and tau were significantly decreased by TG. It is interesting that the decrement of negative dP/dt and tau attained by TG was significantly larger in the hyperthyroid group (T3-TG) than in a normal heart (C-TG). SERCA2 and GLUT4 protein levels were not significantly different between control and the T3 group. We conclude that prolonged exposure to thyroid hormone causes hypertrophy of the myocardium and an augmentation of the SR Ca(2+) ATPase activity. Care must be taken in hyperthyroid heart during the ischemia-reperfusion process where the SRECA2 function is inhibited.

Topics: Animals; Calcium-Transporting ATPases; Disease Models, Animal; Heart Ventricles; Hyperthyroidism; Myocardial Contraction; Myocardium; Rats; Rats, Wistar; Reperfusion Injury; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Thyroid Hormones; Triiodothyronine, Reverse

Liver uptake of thyroxine (T4) is mediated by transporters and is rate limiting for hepatic 3,3',5-triiodothyronine (T3) production. We investigated whether hepatic mRNA for T4 transporters is regulated by thyroid state using Xenopus laevis oocytes as an expression system. Because X. laevis oocytes show high endogenous uptake of T4, T4 sulfamate (T4NS) was used as an alternative ligand for the hepatic T4 transporters. Oocytes were injected with 23 ng liver mRNA from euthyroid, hypothyroid, or hyperthyroid rats, and after 3-4 days uptake was determined by incubation of injected and uninjected oocytes for 1 h at 25 degrees C or for 4 h at 18 degrees C with 10 nM [125I]T4NS. Expression of type I deiodinase (D1), which is regulated by thyroid state, was studied in the oocytes as an internal control. Uptake of T4NS showed similar approximately fourfold increases after injection of liver mRNA from euthyroid, hypothyroid, or hyperthyroid rats. A similar lack of effect of thyroid state was observed using reverse T3 as ligand. In contrast, D1 activity induced by liver mRNA from hyperthyroid and hypothyroid rats in the oocytes was 2.4-fold higher and 2.7-fold lower, respectively, compared with euthyroid rats. Studies have shown that uptake of iodothyronines in rat liver is mediated in part by several organic anion transporters, such as the Na+/taurocholate-cotransporting polypeptide (rNTCP) and the Na-independent organic anion-transporting polypeptide (rOATP1). Therefore, the effects of thyroid state on rNTCP, rOATP1, and D1 mRNA levels in rat liver were also determined. Northern analysis showed no differences in rNTCP or rOATP1 mRNA levels between hyperthyroid and hypothyroid rats, whereas D1 mRNA levels varied widely as expected. These results suggest little effect of thyroid state on the levels of mRNA coding for T4 transporters in rat liver, including rNTCP and rOATP1. However, they do not exclude regulation of hepatic T4 transporters by thyroid hormone at the translational and posttranslational level.

Topics: Animals; Binding, Competitive; Blotting, Northern; Carrier Proteins; Enzyme Activation; Hyperthyroidism; Hypothyroidism; Iodide Peroxidase; Iodine Radioisotopes; Ligands; Liver; Male; Microinjections; Oocytes; Rats; Rats, Wistar; Receptors, Thyroid Hormone; RNA, Messenger; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse; Xenopus laevis

Familial dysalbuminemic hyperthyroxinemia (FDH) is the most common cause of euthyroid hyperthyroxinemia, although a rare example of albumin polymorphism. FDH is inherited in an autosomal dominant manner and is characterized by enhanced binding of thyroxine to a mutant form of albumin, probably at Site 1, subdomain 11A. Previous laboratory tests of FDH have been cumbersome, rarely available, and required demonstration of anti-albumin precipitable T4, isoelectric focusing of serum for albumin in presence of labeled T4 and, occasionally, comparison of the concentrations of metabolites of T4 that have different binding affinities to the abnormal albumin. Recent studies have shown that the same mutation in the albumin gene that results in FDH has been found in 13 unrelated families. A G-->A transition in codon 218 of the albumin gene resulted in the replacement of arginine with histidine. An intragenic Sac-1 polymorphic site was found in association with the specific FDH mutation, suggesting a founder effect. FDH in our Hispanic family was confirmed by isoelectric focusing of serum. Results of thyroid function tests in our affected patients were typical for the phenotype: high total T4 and normal total T3. Genomic DNA was amplified by PCR using a mismatched oligonucleotide primer that produced a unique restriction site (Dra III) only if the DNA sample contained the mutation in codon 218: CGC (Arg) to CAC (His). In affected individuals of this family expression of the FDH phenotype was associated with the presence of His218 in one of the two alleles. Analysis linking the FDH mutation to the Sac-1 polymorphism in this family was not informative. DNA analysis is a rapid and simple method to diagnose FDH in individuals with euthyroid hyperthyroxinemia.

Topics: Adolescent; Adult; Alleles; Child; DNA; Female; Humans; Hyperthyroidism; Isoelectric Focusing; Leukocytes; Male; Mutation; Pedigree; Polymorphism, Genetic; Reverse Transcriptase Polymerase Chain Reaction; Serum Albumin; Thyroid Function Tests; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

In a prospective study, thyroid metabolism in 102 patients undergoing diagnostic coronary angiography was investigated, stratified for thyroid morphology. The thyroid function serum parameters "TT3, rT3, TT4, fT4 and TSH" and the urinary iodine excretion were measured before and three weeks after diagnostic intraarterial administration of the iodine-containing contrast agent. Only patients with euthyroid function were included in order to answer the questions whether or not the administration of non-ionic iodine containing contrast medium leads to significant thyroid function changes in euthyroid patients and whether thyroid morphology is a prognostic factor for the risk of developing hyperthroidism. Serum concentrations of thyroid autoantibodies (TPO-Ab, Tg-Ab, TSH-receptor-Ab) were measured and thyroid ultrasound was performed. According to the ultrasound findings, 4 morphologic groups were formed: normal thyroid glands (n = 37), normal sized but nodular glands (n = 16), diffuse goiter (n = 15) and nodular goiter (n = 34). Twenty-five patients were positive for Tg-Ab; TPO-Ab were found in 13 patients. TSH-receptor-Abs were not detected in all patients. TT3 levels did not significantly change after iodine application (p = 0.30). TT4 and fT4 levels showed significantly different alterations in the 4 groups (fT4 p < 0.001). The amount of iodine given did not influence alteration of serum concentrations of TSH (p = 0.67), TT3 (p = 0.68), TT4 (p = 0.37), fT4 (p = 0.92) and rT3 (p = 0.81). Elevated levels of urinary iodine excretion correlated with the amount of contrast medium given (p = 0.087). Albeit there was a high number of nodular transformed glands and goitrous patients included, and our cohort was recruited in an iodine deficient area, we did not observe hyperthyroidism in any patient. However, thyroid function parameters are significantly altered after coronary angiography independent of antibody status and the amount of contrast agent given, but dependent on thyroid morphology.

Topics: Angioplasty, Balloon, Coronary; Autoantibodies; Cardiac Catheterization; Contrast Media; Coronary Angiography; Data Interpretation, Statistical; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Hyperthyroidism; Immunoenzyme Techniques; Iodine; Iohexol; Male; Middle Aged; Prospective Studies; Radioimmunoassay; Risk Factors; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine; Time Factors; Triiodothyronine; Triiodothyronine, Reverse; Ultrasonography

A prospective study was carried out using a combination of propranolol and potassium iodate to assess whether there were beneficial effects in preparing hyperthyroid cats for surgical thyroidectomy. Group A (n = 11) received propranolol from days 1 to 10, followed by propranolol and potassium iodate from days 11 to 20; group B (n = 10) received the reverse regimen. Blood samples were taken daily for subsequent determination of serum total L-thyroxine (TT4), L-triiodothyronine (TT3) and reverse T3 (rT3) concentrations. The signs of hyperthyroidism improved in all cats over the treatment period. At surgery, 36 per cent of the cats in group A had reference range serum TT4 concentrations, while 89 per cent with initially elevated TT3 concentrations had reference range concentrations. In group B, 10 per cent of the cats had reference range TT4 concentrations, while 75 per cent with initially elevated TT3 concentrations had reference range concentrations. The drug regimen used in group A was better tolerated and more effective and offers an alternative before thyroidectomy in cats that cannot tolerate carbimazole.

Topics: Animals; Cat Diseases; Cats; Drug Administration Schedule; Female; Hyperthyroidism; Liver; Male; Potassium Iodide; Preoperative Care; Propranolol; Prospective Studies; Reference Values; Sympatholytics; Thyroid Gland; Thyroidectomy; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

In systemic nonthyroidal illness (NTI), peripheral production of T3 from T4 is decreased, resulting in a decreased serum T3 concentration. We investigated whether factors in serum of NTI patients may play a role in this energy-saving adaptation mechanism. Metabolism of T4 and T3 by rat hepatocytes in primary culture was measured in the presence of 10% serum of normal subjects or of patients with NTI and related to the severity of disease. Patients with NTI were grouped according to serum thyroid hormone abnormalities: group I, serum rT3, T3, and T4 normal; group III, rT3 elevated, T3 decreased, T4 normal; group IV, rT3 elevated, T3 and T4 decreased. Compared with metabolism in the presence of normal serum, metabolism of T4 and to a lesser extent of T3 was progressively decreased in the presence of serum of patients of groups I-IV. A decreased net deiodination of T4 and T3 (corrected for differences in free hormone concentration) without an increase in conjugated T4 and T3 (corrected for differences in free hormone concentration) was observed, similar to results in experiments with compounds inhibiting transport into the cells and not the metabolic processes (5' deiodination) per se. Deiodination of T4 in vitro was correlated with serum T3 concentration of the patient (r = 0.69). Serum of patients with NTI influences thyroid hormone handling by hepatocytes comparable to the effect of transport inhibitors and not to that of the 5'-deiodinase inhibitor propylthiouracil, suggesting that decreased thyroid hormone transport over the cell membrane may play a role in lowered T3 production in NTI.

Topics: Animals; Cells, Cultured; Culture Media; Disease; Humans; Hyperthyroidism; Hypothyroidism; Liver; Male; Monensin; Ouabain; Propylthiouracil; Rats; Rats, Wistar; Reference Values; Regression Analysis; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

This study was designed to assess both central and peripheral aspects of thyroid function in combat-related posttraumatic stress disorder (PTSD), with the particular purpose of finding a mechanistic explanation for an imbalance between serum levels of free thyroxine (T4) and total T4 previously observed in pilot work.. A total of 96 male combat veterans with PTSD diagnosed by DSM-III-R (72 from the West Haven, Conn, Veterans Affairs Medical Center and 24 from the Menlo Park, Calif, Veterans Affairs Medical Center) were compared with 24 male control subjects. One or more serum samples were analyzed by radioimmunoassays for levels of total T4, free T4, total triiodothyronine (T3), free T3, T4-binding globulin, and thyrotropin.. The pilot observation of moderately elevated total T4 levels with no elevation in free T4 levels in patients with PTSD was confirmed, suggesting the hypotheses that (1) there may be an increased peripheral conversion of free T4 by deiodination to T3 or (2) there may be an increased binding of T4 secondary to elevated T4-binding globulin levels. Our findings support both hypotheses. The PTSD groups all showed a marked and sustained elevation in levels of both total T3 and free T3, as well as elevated T3/T4 ratios, supporting the increased T3 conversion hypothesis. The PTSD groups also showed a marked and sustained increase in T4-binding globulin levels, supporting the increased binding hypothesis. Thyrotropin levels did not differ between PTSD and control groups.. These findings demonstrate an unusual pattern of thyroid alterations, featuring substantial elevations in total T3, free T3, and T4-binding globulin levels, in combat-related PTSD that differs from established endocrinopathies, such as classic hyperthyroidism, T3 thyrotoxicosis, or chronic T4-binding globulin elevation.

Topics: Adult; Combat Disorders; Comorbidity; Follow-Up Studies; Humans; Hyperthyroidism; Male; Pilot Projects; Protein Binding; Radioimmunoassay; Thyroid Gland; Thyrotoxicosis; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

A highly sensitive, specific, and reproducible RIA has been developed to measure T4 sulfate (T4S) in ethanol extracts of serum. rT3 sulfate (rT3S) cross-reacted 7.1%, and T3S cross-reacted 0.59% in the RIA; T4, T3, rT3, and 3,3'-diiodothyronine cross-reacted 0.004% or less. The recovery of nonradioactive T4S added to serum averaged 95%. The detection threshold of the RIA was 18 pmol/L. The coefficient of variation averaged 6.9% within an assay and 12% between assays. T4S was bound by T4-binding globulin and albumin in serum. The free fraction of T4S in four normal sera averaged 0.06% compared to a value of 0.03% for T4 (P < 0.001). The serum concentration of T4S was (mean +/- SE) 19 +/- 1.2 pmol/L in normal subjects, 33 +/- 10 in hyperthyroid patients with Graves' disease, 42 +/- 15 in hypothyroid patients, 34 +/- 6.9 in patients with systemic nonthyroidal illnesses, 21 +/- 4.3 in pregnant women at 15-40 weeks gestation, and 245 +/- 26 in cord blood sera of newborns; the value in the newborn was significantly different from normal (P < 0.001). The mean concentration of T4S in amniotic fluid samples at 15-38 weeks gestation was 106 +/- 22 pmol/L (cf. normal adults; P < 0.001). Administration of sodium ipodate (Oragrafin; 3 g, orally) to hyperthyroid patients was associated with a transient increase in serum T4S. The T4S content of the thyroid gland was less than 1/4000th that of T4. We conclude that 1) T4S is a normal component of human serum, and its levels are markedly increased in newborn serum and amniotic fluid; and 2) the sulfation pathway plays an important role in the metabolism of T4 in man.

Topics: Blood Proteins; Cross Reactions; Female; Fetal Blood; Humans; Hyperthyroidism; Hypothyroidism; Immune Sera; Infant, Newborn; Pregnancy; Protein Binding; Radioimmunoassay; Reference Values; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

To clarify the duration and the extent of the antithyroid effect of iodides in hyperthyroidism, and to investigate whether iodides have an additional peripheral effect on the metabolism of thyroid hormones, as has been reported for some organic iodine compounds.. The effect on the peripheral thyroid hormone levels of 150 mg of potassium iodide daily (equivalent to 114 mg of iodide) for 3-7 weeks was compared in 21 hyperthyroid patients and 12 healthy controls. A possible effect of iodide on the peripheral metabolism of thyroid hormones was investigated by assessing the serum levels of thyroid hormone in 12 hypothyroid patients on thyroxine replacement for 2 weeks.. There were 21 thyrotoxic patients, 12 healthy hospital controls, and 12 patients with complete or near-complete hypothyroidism, on thyroxine replacement.. The following were measured before and at weekly intervals after iodide administration: (1) pulse rate, (2) serum T4, (3) serum T3, (4) serum TSH, (5) serum thyroxine-binding capacity (TBC), (6) serum rT3, (7) serum thyroxine-binding globulin (TBG), (8) the free-T4 Index, calculated as T4/TBC.. In the hyperthyroid patients serum T4, T3 and rT3 decreased, whereas serum thyroxine-binding globulin and thyroxine binding capacity increased. Serum T3, however, did not become completely normal in all cases. After 21 days, serum T4 and T3 started increasing again in some cases, but other patients remained euthyroid even after 6 weeks. In the normal controls there was a small but significant and consistent decrease in serum T4, T3 and rT3 and an increase in serum TSH. Finally, in the T4-treated hypothyroid patients there was no consistent change, except for an increase of serum T4 at 1 and 14 days and a decrease of serum TSH the first day.. Iodides in hyperthyroidism have a variable and unpredictable intensity and duration of antithyroid effect. Their antithyroid effect is smaller in normal controls. They have no important effect on the peripheral metabolism of thyroid hormones.

Topics: Adult; Aged; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Potassium Iodide; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Humans; Hyperthyroidism; Plasma Exchange; Plasmapheresis; Radioimmunoassay; Thyroglobulin; Thyroxine; Triiodothyronine, Reverse

We have evaluated an alternative method of preparation of hyperthyroid patients for surgery, using betamethasone, iopanoic acid and propranolol.. Betamethasone (0.5 mg every 6 hours), iopanoic acid (500 mg every 6 hours) and propranolol (40 mg every 8 hours) were given orally for 5 days; thyroidectomy was performed on the 6th day. We analysed patient acceptability, clinical and hormonal effects, ease of surgery and final outcome.. Thirteen females and 1 male, aged 16-59 years, ten with diffuse goitre and four with nodular goitre were submitted to subtotal thyroidectomy because antithyroid drugs had failed to control thyrotoxicosis or because hyperthyroidism coexisted with other conditions (pregnancy, hypertensive disease).. Daily clinical assessments were made together with T3, T4 and rT3 serum concentrations before and while on drug treatment, during the surgical procedure and post-operatively.. Daily assessment showed progressive clinical improvement so that on day 5 the patients were considered clinically euthyroid. Serum levels of T3 (mean +/- SD) showed significant decrease (by 38.2 +/- 24.9%, P less than 0.01) as early as 24 hours after medication was started, reaching almost euthyroid levels on day 3; on the day of operation T3 had diminished by 64.5 +/- 16.6% (P less than 0.0001). Serum T4 concentration showed a slight but significant decrement only from day 4 on and never reached euthyroid levels. Serum rT3 values exhibited a brisk increment at 24 hours (+333 +/- 194%, P less than 0.0001) and remained elevated between 8 and 10 nmol/l until medication was stopped. Drug tolerance was considered as excellent since no serious side-effects were noted, even in pregnant patients. There were no anaesthetic incidents or postoperative complications and patients were discharged 48-72 hours after operation. The final outcome has been satisfactory and pregnant patients continued their pregnancies without incident, bearing normal children.. Pharmacological combination of betamethasone, iopanoic acid and propranolol has proved to be safe and effective and is of low cost. Provided there is adequate supervision of the patients, it may be used in patients requiring urgent thyroidectomy or in those who for reasons of non-compliance need a short preoperative regime.

Topics: Adolescent; Adult; Betamethasone; Drug Administration Schedule; Female; Humans; Hyperthyroidism; Iopanoic Acid; Male; Middle Aged; Pregnancy; Pregnancy Complications; Preoperative Care; Propranolol; Thyroidectomy; Thyroxine; Time Factors; Triiodothyronine; Triiodothyronine, Reverse

The photoreactive compound p-nitrophenyl-2-diazo-3,3,3-trifluoropropionate (PAL) was coupled to [125I]rT3, T4, or T3 and incubated with liver and kidney microsomes of hypo-, hyper-, or euthyroid rats to identify the type I iodothyronine deiodinase. Various substrates or inhibitors of the enzyme, including rT3, T4, T3, 6-n-propylthiouracil (PTU), and iopanoic acid, were used as competitors to establish the specificity of protein labeling. The PAL derivatization enhanced the behavior of T4 and T3 as substrates for the type I enzyme. No specific labeling of microsomal proteins was observed with either rT3 or T4-PAL, presumably due to deiodination of the labeled compound. In contrast, T3-PAL labeled a 27-kDa band, the presence of which paralleled thyroid status. The labeling of only this protein was blocked by either substrates or enzyme inhibitors in a dose-dependent fashion, with a rank order of potency predicted by the activity of such compounds in type I enzyme assays. The specific nature of these competitions provides further evidence that this 27-kDa protein, identified in previous studies using N-bromoacetyl [125I]T3 or -T4, contains the active site of the rat type I deiodinase. This is in agreement with the mol wt of the rat type I deiodinase deduced from the recently identified cDNA coding for this protein.

Topics: Affinity Labels; Animals; Binding, Competitive; Diazonium Compounds; Hyperthyroidism; Hypothyroidism; Iodide Peroxidase; Iopanoic Acid; Male; Molecular Weight; Photochemistry; Propionates; Propylthiouracil; Rats; Rats, Inbred Strains; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Total and free concentrations of T4 and rT3 in serum and cerebrospinal fluid were estimated by ultrafiltration in 12 patients with unipolar endogenous depression before and after electroconvulsive treatment. Recovery from depression resulted in a decrease in CSF concentrations of free T4 (median) (26.2 to 21.4 pmol/l, p less than 0.02) and free rT3 (14.1 to 12.3 pmol/l, p less than 0.05). Concentrations of free T4 in the cerebrospinal fluid were lower than those in serum (p less than 0.02), the ratio being 0.6. In contrast, levels of free rT3 in the cerebrospinal fluid were considerably higher than those found in serum (p less than 0.01), the ratio being 25. These ratios did not change following recovery from depression. In 9 patients with nonthyroidal somatic illness, concentrations of free T4 and rT3 in the cerebrospinal fluid were similar to those found in patients with endogenous depression, whereas 4 hypothyroid patients and one hyperthyroid patient had considerably lower and higher, respectively, concentrations of both free T4 and rT3. In conclusion, levels of free T4 and free rT3 in the cerebrospinal fluid are increased during depression compared with levels after recovery, probably reflecting an increased supply of T4 from serum and an increased production of rT3 from T4 in the brain. The data also suggest that the transport of iodothyronines between serum and the cerebrospinal fluid is restricted.

Topics: Aged; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Amiodarone, an antiarrhythmic agent, is known to occasionally induce alterations in thyroid function because of its iodine content and ability to inhibit T4 5'-monodeiodination. We herein describe the drug-induced chemical hyperthyroidism in a diabetic patient with ventricular premature beats. A 46-year-old man with well controlled diabetes mellitus revealed neck swelling during a 4 months' treatment with amiodarone for his frequent occurrence of ventricular premature beats. Physical findings were unremarkable other than grade III diffuse struma. Routine laboratory studies were almost normal. The results of thyroid function studies showed hyperthyroidism, including increases in T4 and free T4, slight increases in T3 and free T3, a marked increase in reverse T3 and a decrease in 123I 24-h uptake. TSH was low and did not respond to TRH. Antithyroid antibodies and TSH receptor antibodies were negative. The findings of the thyroid biopsy were unremarkable except for a mild follicular hyperplasia. After cessation of the drug, T3 and free T3 were returned to normal within 2 weeks, T4 and free T4 within 2 months and reverse T3 after 6 months. These data suggest that the struma and chemical hyperthyroidism observed in our patient were induced by amiodarone treatment.

Topics: Amiodarone; Cardiac Complexes, Premature; Diabetes Complications; Humans; Hyperthyroidism; Male; Middle Aged; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Tachycardia and tachyarrhythmias are frequent in patients with thyrotoxicosis, especially in the elderly. Since myocardial calcium uptake is increased in thyrotoxic rats, the efficacy of the calcium channel-blocking drug diltiazem in decreasing heart rate and the incidence of arrhythmias was evaluated in 11 hyperthyroid patients. All patients were studied with a 24-hour Holter monitor prior to the beginning of sole diltiazem therapy (120 mg given every eight hours), on the tenth day of therapy, and five days after therapy was discontinued. Heart rate significantly decreased by 17% during diltiazem treatment (96.5 +/- 3.7 systoles/min vs 79.9 +/- 3.2 systoles/min [mean +/- SE]) and returned to baseline values five days after the therapy was discontinued (100.7 +/- 3.4 systoles/min). Similarly, the number of premature ventricular extrasystoles per hour was significantly decreased (18 +/- 7 vs 2 +/- 1). In three patients, asymptomatic bouts of supraventricular tachycardia, paroxysmal atrial fibrillation, or ventricular tachycardia disappeared during diltiazem therapy. These findings suggest that calcium-blocking drugs may be extremely useful as adjunctive therapy for thyrotoxicosis in the presence of angina, congestive failure, and tachyarrhythmias.

Topics: Adult; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Diltiazem; Drug Administration Schedule; Drug Evaluation; Female; Heart Rate; Humans; Hyperthyroidism; Male; Middle Aged; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Alterations in thyroid hormone status and the administration of radiographic contrast agents can markedly influence iodothyronine metabolism and, in particular, the activity of type I 5'-deiodinase (5'DI). In the present studies, the mechanisms responsible for these effects have been reassessed. As previously reported, the addition of iopanoic acid (IOP) to broken cell preparations resulted in a competitive pattern of 5'DI inhibition. However, the in vivo administration to rats of IOP or 3,3',5'-triiodothyronine (rT3) resulted in a noncompetitive pattern of inhibition of 5'DI in the liver, kidney, and thyroid gland, whereby marked decreases in maximal enzyme velocity (V max) were noted, with no change in the value of the Michaelis-Menten constant. In rats rendered hyperthyroid by the injection of 3,5,3'-triiodothyronine (T3), 5'DI activity was significantly increased in the liver and the kidney. The administration of IOP to these thyrotoxic animals resulted in a rapid loss of enzyme activity characterized by an approximate 80% decrease in 5'DI V max values in both tissues. Furthermore, this inhibitory effect persisted for longer than 60 h after a single IOP injection. IOP administration also decreased 5'DI V max levels in the thyroid gland by 52%. In other experiments, treatment of intact Reuber FAO hepatoma cells with IOP or rT3 induced a rapid decrease in 5'DI V max levels. In cells treated with cycloheximide, these agents enhanced the rate of disappearance of enzyme activity by greater than 12-fold, indicating a predominant effect on accelerating the rate of enzyme inactivation and/or degradation. These studies demonstrate that iodothyronines and other iodinated compounds have complex regulatory effects on 5'DI that entail alterations in the rates of both enzyme activation and inactivation. The previously accepted concept that rT3 and IOP impair thyroxine (T4) to T3 conversion in vivo by acting as competitive inhibitors is an oversimplification. Rather, the clinically beneficial effects of administering these agents to patients with hyperthyroidism may result primarily from the rapid and prolonged inactivation of 5'DI which occurs in the thyroid gland and peripheral tissues.

Topics: Animals; Carcinoma, Hepatocellular; Contrast Media; Hyperthyroidism; Iodide Peroxidase; Iopanoic Acid; Kidney; Liver; Liver Neoplasms; Male; Rats; Thyroid Gland; Triiodothyronine, Reverse; Tumor Cells, Cultured

Thyroid function in individuals from a representative population of 79-year-olds was evaluated clinically and from measurements of serum thyrotropin (TSH) and 3,5,3'-triiodothyronine (T3). High TSH concentrations (greater than or equal to 10 mU/l) were found in 16 of 320 women (5%) and 2 of 204 men (1%). Signs and symptoms which traditionally are regarded as related to hypothyroidism were as common in subjects with high TSH concentration as in the remaining population and occurred in 10-50% of the subjects. In the 16 women with high TSH, free thyroxine (free T4) concentrations were low in 10, whereas only one subject had low thyroxine (T4) and T3 concentrations, indicating that free T4 is a more sensitive parameter for thyroid hypofunction in the elderly. Based on the T3 assay, there was no evidence for hyperthyroidism in this population. The results indicate that high TSH concentrations are common in elderly women, less common in men. The results show that classical symptoms of thyroid dysfunction are quite common in 79-year-olds, but do not correlate with biochemical indicators of thyroid dysfunction, indicating that defining "clinically euthyroid" in an elderly may be almost impossible.

Topics: Aged; Female; Humans; Hyperthyroidism; Hypothyroidism; Longitudinal Studies; Male; Mass Screening; Thyrotropin; Thyroxine; Triiodothyronine, Reverse

We describe the effect of administration of repeated doses of sodium ipodate in a newborn infant with hyperthyroidism due to transient Graves' disease. Pretreatment (day 3) serum T4 and T3 concentrations were 49 micrograms/dl and 590 ng/dl, respectively. With 24 h after the first dose of ipodate, serum T3 fell by 40%, and it subsequently ranged from 209-278 ng/dl throughout the 39-day ipodate treatment period. Serum T4 also decreased after ipodate administration to 69% and 41% of the pretreatment value after 72 h and 7 days of treatment, respectively; values thereafter during treatment ranged from 19-22 micrograms/dl. These plateau values are in the upper range of normal for the neonatal period. Rapid clinical improvement occurred as the hyperiodothyroninemia abated. Serum rT3 concentrations increased from 468-672 ng/dl to greater than 1400 ng/dl 24 h after each ipodate dose. Thyroid-stimulating immunoglobulin was present in maternal and cord sera, and the half-life of serum thyroid-stimulating immunoglobulin in the infant was approximately 12 days. Antithyroglobulin and antimicrosomal antibodies were present in the infant at 10 days of age, and the titers decreased progressively thereafter; the half-life for the antimicrosomal antibody titer was 3 weeks. The data suggest that sodium ipodate can be useful for treatment of neonatal hyperthyroidism due to Graves' disease.

Topics: Antibodies; Female; Graves Disease; Humans; Hyperthyroidism; Infant, Newborn; Ipodate; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Methods to identify the plasma T4-binding abnormalities that can cause euthyroid hyperthyroxinemia were evaluated in patients with excess T4-binding globulin, familial dysalbuminemic hyperthyroxinemia, prealbumin-associated hyperthyroxinemia, and autoantibody binding of T4. Familial dysalbuminemic hyperthyroxinemic serum showed a unique persistence of abnormal [125I]T4 binding when diluted 1:100 in phosphate buffer with added 1000-fold excess of unlabeled T4 (10(-6) M T4). Immunoprecipitation of [125I]T4 by antibody to prealbumin, precipitation of [125I]T4 by polyethylene glycol 6000 19%, and in vitro resin uptake of T3 were specific for prealbumin-associated hyperthyroxinemia, autoantibody binding of T4, and T4-binding globulin excess, respectively. These simple methods facilitate investigation of patients with euthyroid hyperthyroxinemia and will identify individuals and families at risk of misdiagnosis by standard methods. Use of these techniques rules out the known binding abnormalities in hyperthyroxinemic patients and may make the diagnosis of generalized hormone resistance more specific.

Topics: Humans; Hyperthyroidism; Protein Binding; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

The "euthyroid sick syndrome", representing the changes of thyroid hormone metabolism in disease, embraces the following hormonal changes: 1) A decrease in serum T3 levels which is often accompanied by an increase in rT3 levels. Serum T4 levels remain normal. These changes are extremely frequent in many varied diseases. 2) In very severe disease, serum T4 levels may also decrease. The free T4 index is often decreased and the free T4 may either be normal or decreased. These changes reflect alterations of thyroid hormone metabolism and can be distinguished from primary hypothyroidism by a normal serum TSH level. 3) Occasionally there are transient increases of total and free T4. This disturbance of serum thyroid hormone levels is mostly due to drug interference with thyroid hormone metabolism (amiodarone etc.). Differentiation from hyperthyroidism is difficult. It is important to diagnose the "euthyroid sick syndrome" since this will avoid erroneous diagnosis and treatment or hypo- and hyperthyroidism.

Topics: Diagnosis, Differential; Disease; Humans; Hyperthyroidism; Hypothyroidism; Thyroid Hormones; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

We assessed the sensitivity, specificity, predictive value of a positive result, and efficiency of tests for total thyroxin, free thyroxin index, free thyroxin, total triiodothyronine, free triiodothyronine index, and free triiodothyronine in serum from 1619 consecutive new patients with suspected thyroid dysfunction. Multivariate discriminant analysis was also used. Free thyroxin index and free thyroxin were clearly the most sensitive indicators of hypothyroidism. In contrast, all of these tests identified hyperthyroidism with similar efficiencies. By stepwise discriminant analysis, the free thyroxin index was the most efficient test for distinguishing between euthyroidism and hyperthyroidism and between euthyroidism and hypothyroidism. The combination of tests for total thyroxin, free thyroxin index, triiodothyronine, and free triiodothyronine was optimal for separating euthyroidism, hyperthyroidism, and hypothyroidism. We conclude that the free thyroxin index, despite the introduction of newer technologies, is still the best thyroid hormone test for screening for thyroid disease.

Topics: Adult; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Thyroid Diseases; Thyroid Function Tests; Thyroid Hormones; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

The clinical and laboratory findings are described in three patients who ingested large amounts of L-thyroxine (two cases) and L-thyroxine together with L-triiodothyronine and who were treated with propranolol. Serum concentrations of thyroxine (maximum values 75 micrograms/dl, 64 micrograms/dl, and 20 micrograms/dl, respectively; normal range 4-12 micrograms/dl), triiodothyronine (maximum values 837 ng/dl, 453 ng/dl, and 566 ng/dl, resp.; normal range 80-180 ng/dl), reverse triiodothyronine (maximum values 235 ng/dl, 190 ng/dl, and 65 ng/dl, resp.; normal range 10-40 ng/dl) as well as free thyroxine equivalent and free triiodothyronine equivalent were monitored daily until they reached the normal range. Statistical analysis of the kinetics of these parameters indicated that the extreme thyroxine conversion was directed toward reverse triiodothyronine, partly due to the treatment with the beta-adrenergic blocker propranolol. The striking discrepancy between the high concentrations of the active hormones and the moderate clinical symptoms was most likely caused by peripheral effects of propranolol.

Topics: Adolescent; Adult; Dose-Response Relationship, Drug; Factitious Disorders; Female; Humans; Hyperthyroidism; Male; Propranolol; Suicide, Attempted; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

We studied the effect of the state of the thyroid on T4 monodeiodination in the rat placenta, and it was compared with those in the liver and kidney. The tissues, maternal serum, and amniotic fluid were obtained from pregnant rats. The tissues were homogenized in cold 50 mM Tris-HCl buffer, pH 7.5. The homogenate (1 mg protein) was incubated at 37 degrees C for 60 min with 1 microgram T4 in the presence of 5 mM DTT. The T3 and reverse T3 generated in the reaction mixture were extracted into cold ethanol and measured by RIAs. The conversion of T4 to reverse T3 in rat placenta was not significantly changed in MMI-induced hypothyroidism or T4 induced hyperthyroidism. On the other hand, conversion of T4 to T3 in the liver and kidney were changed in parallel with the thyroid state. The concentration of reverse T3 in the amniotic fluid was increased in accordance with the increase in the maternal serum T4 concentration. These results indicate that the placental T4 inner ring deiodination is not affected by the thyroid state, and that the change in the amniotic fluid reverse T3 concentration in this study is mainly dependent upon the change in maternal thyroid function.

Topics: Amnion; Animals; Female; Hyperthyroidism; Hypothyroidism; Kidney; Liver; Organ Specificity; Placenta; Pregnancy; Rats; Rats, Inbred Strains; Thyroid Gland; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Inner ring (-5) monodeiodination of T4 was studied by incubating T4 (approximately 0.26 mumol/L) with rat cerebral cortical homogenate (approximately 4 mg protein) in the presence of dithiothreitol (up to 400 mmol/L) and quantifying the amount of the product, rT3, by a specific radioimmunoassay. The production of rT3 was dependent on duration of incubation (up to 2 hours), amount of tissue protein (up to 8 mg), temperature (optimal at 37 degrees C) and pH (optimal, 7.0) of the incubation mixture and the concentration of DTT (maximally stimulated at 400 mmol/L). The apparent Km and Vmax of the T4-inner ring monodeiodinating activity were 36 nmol/L and 1.75 pmol/mg protein/h, respectively. The activity was inhibited by T3 and 3,5-T2, but not by 3'5'-T2, PTU, methimazole, sodium salicylate, or 8-anilino-I-naphthalene sulfonic acid. Ipodate weakly inhibited T4-to-rT3 monodeiodination. Hyperthyroidism induced by T4 (100 micrograms/d IP X 3 days), T3 (80 micrograms/d IP X 3 days) or DIMIT (45 micrograms/d IP X 3 days) significantly stimulated T4-to-rT3 conversion; DIMIT was the most potent agent. Hypothyroidism inhibited T4-to-rT3 converting activity in cerebral cortex. Fasting for three days had no appreciable effect on T4-to-rT3 conversion in cerebral cortex. Cerebral cortical T4 5-deiodinase activity in the pregnant rat at term was about 50% of that in the adult nonpregnant rat, whereas that in the fetus was about three-fold higher than that in the nonpregnant adult.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aging; Animals; Cerebral Cortex; Dithiothreitol; Fasting; Female; Fetus; Hydrogen-Ion Concentration; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Iodine; Kinetics; Male; Pregnancy; Rats; Rats, Inbred Strains; Thyroxine; Triiodothyronine, Reverse

Topics: Aging; Humans; Hyperthyroidism; Hypothyroidism; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

We propose a mathematical model of the human hypothalamus-anterior pituitary-thyroid system regulating basal metabolism, and practice computer simulation concerning primary thyropathy such as Graves' disease, hypothyroidism, T4-toxicosis and T3-toxicosis by use of this model. In order to throw light on properties of the system, indicial responses of the hormones, T4, T3, rT3, and TSH, and the function of the thyroid gland are computed. Medical treatments for Graves' disease and for hypothyroidism are simulated with a view to enhancing clinical significance. Performance of the simulation leads to an interesting result that when the convertion rate of blood T4 to blood T3 increases, explicit T3-toxicosis occurs, although the function of the thyroid gland is normal.

Topics: Computers; Graves Disease; Humans; Hyperthyroidism; Hypothalamo-Hypophyseal System; Hypothyroidism; Mathematics; Models, Biological; Thyroid Diseases; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Circulating concentrations of total and free thyroid hormones and thyroid hormone binding proteins were measured in thyrotoxic and euthyroid subjects treated with propranolol. In the thyrotoxic group, total triiodothyronine (T3) concentration fell after propranolol therapy, suggesting an effect of the drug on the peripheral conversion of thyroxine (T4) to T3. In euthyroid subjects, a rise in circulating concentrations of free T4 and reverse T3 (rT3) was observed, while only a small decrease in free T3 was evident. Thyroxine binding globulin (TBG) concentration fell during propranolol treatment while thyroxine binding prealbumin (TBPA) concentration rose. The changes observed in the euthyroid state are consistent with inhibition of peripheral deiodination of T4 and rT3; an additional effect of propranolol on binding protein metabolism was evident.

Topics: Humans; Hyperthyroidism; Propranolol; Thyroid Hormones; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

The use of amiodarone, a drug which is prescribed increasingly as an anti-anginal and anti-arrhythmic agent, necessitates a high index of suspicion for the development of thyroid disorders, especially thyrotoxicosis. Two cases, which illustrate the diagnostic dilemma of hyperthyroxinaemia and the poor response to antithyroid medication, are described. During amiodarone therapy, the clinical features of thyrotoxicosis may be masked or atypical, and the choice of therapy is complicated by a delayed response to thioamide drugs and possible contraindication for beta-blocking agents which necessitates the use of glucocorticoid drugs in some patients.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Carbimazole; Coronary Disease; Humans; Hyperthyroidism; Male; Prednisone; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adolescent; Adult; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Radioimmunoassay; Thyroid Diseases; Thyroiditis; Triiodothyronine, Reverse

Topics: Adolescent; Adult; Aged; Female; Humans; Hyperthyroidism; Male; Middle Aged; Nadolol; Propanolamines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

T4 (0.26 microM) was incubated in 0.1 M phosphate buffer (pH 7.4) containing 10 mM EDTA with homogenates (3-5 mg protein) of various rat tissues and up to 400 mM dithiothreitol (DTT) for 1 h at 37 C; the rT3 generated was measured by RIA of ethanol extracts of the incubation mixture. Among the various tissues of the male rat, homogenates of skin and cerebral cortex were very active in the conversion of T4 to rT3; other tissues demonstrated little or no T4 5-monodeiodinating activity (MA). The tissue content of rT3 was also greatest in these two tissues. The MA in skin increased linearly with incubation period (up to 4 h) and with increasing concentration of protein (up to 5 mg), substrate (up to 10 microM) and DTT (up to 400 mM); its optimal pH was 7.4, and optimal temperature was 37 C. Its Km and maximum velocity approximated 0.29 microM and 9.6 pmol/h X mg protein, respectively, in the presence of 400 mM DTT. There was no appreciable difference in T4 to rT3 MA of skin from different parts of the body. The MA was most abundant in microsomes and least in cytosol. The MA was unaffected by propylthiouracil (up to 25 microM), methimazole (up to 100 microM), sodium salicylate (up to 80 microM), or 8-anilino-1-naphthalene sulfonic acid (up to 75 microM). Ipodate (up to 80 microM) weakly inhibited the MA. T3 and 3,5-diiodothyronine inhibited dermal T4 to rT3 MA in a dose-dependent manner; T3 was 3-12 times more potent than 3,5-diiodothyronine on a molar basis in different experiments. Treatment of euthyroid rats with 3,5-dimethyl-3'isopropylthyronine (45 micrograms/day, ip) for 3 or 5 days significantly increased dermal T4 to rT3 MA. Similar treatment of rats with T4 (100 micrograms/day, ip) or T3 (20 or 80 micrograms/day, ip) did not change with MA appreciably. Hypothyroidism markedly inhibited the MA, and fasting inhibited it modestly. Pregnancy was associated with marked reduction in the MA of skin in the mother [0.30 +/- 0.11 (+/- SE) vs. 7.2 +/- 2.2 ng/h X mg protein; P less than 0.02] and fetus (0.67 +/- 0.075; P less than 0.025).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Dithiothreitol; Fasting; Female; Hydrogen-Ion Concentration; Hyperthyroidism; Hypothyroidism; Male; Microsomes; Pregnancy; Propylthiouracil; Rats; Skin; Temperature; Thyroxine; Time Factors; Tissue Distribution; Triiodothyronine, Reverse

A new method for the estimation of the bioavailability of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) is described based on gel separation followed by antibody extraction of labelled T4 and T3 from serum, and using the area under the curve of disappearance of the tracer (AUC) for the calculations. The peak serum concentrations of radioactive labelled T4 and T3 were reached approximately 90 min after oral administration of both tracers. The relative difference of duplicate estimations was below 10% (n = 3). The bioavailability of T4 in 6 euthyroid controls was in median 65% (range 64-75%), and it was significantly increased both in hyperthyroidism (88% (75-99%), n = 6, P less than 0.01) and hypothyroidism (84% (67-100%), n = 6, P less than 0.02). The bioavailability of T3 in 6 euthyroid controls was in median 78% (69-99%) and significantly greater than that of T4 (P less than 0.02). The bioavailability was unaffected by hyperthyroidism (79% (61-98%), n = 9) and hypothyroidism (77% (66-97%), n = 7). No significant difference between T4 and T3 bioavailabilities was found in hyper- or hypothyroidism. The clinical implication of the present study is that the bioavailability of T4 and T3 is almost identical and approximately 80% in patients with severe hypothyroidism.

Topics: Adult; Aged; Biological Availability; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Thyroxine; Triiodothyronine, Reverse

Amiodarone, an iodine-containing drug used frequently in the treatment of cardiac arrhythmias and angina pectoris, has many effects on thyroid hormone metabolism, including decreasing the production of triiodothyronine (T3) and decreasing the clearance of thyroxine and reverse T3. These effects result in elevated serum thyroxine and reverse T3 concentrations and decreased serum T3 concentrations. In addition, iodine-induced hyperthyroidism or hypothyroidism may occur in patients chronically treated with amiodarone. This study is a retrospective analysis of the incidence of thyroid dysfunction in Lucca and Pisa, West Tuscany, Italy, and in Worcester, Massachusetts. Hyperthyroidism was a more frequent (9.6%) complication of amiodarone therapy in West Tuscany, where iodine intake is moderately low; hypothyroidism was more frequent (22%) in Worcester, where iodine intake is sufficient. In patients receiving chronic amiodarone therapy, clinically suspected hyperthyroidism is best confirmed by showing elevations in serum T3 or free T3 concentrations; hypothyroidism is best diagnosed by showing an elevated serum thyrotrophin concentration. Thyroid function should be carefully monitored in patients receiving amiodarone chronically, especially if they have goiter or Hashimoto's thyroiditis.

Topics: Adult; Aged; Amiodarone; Benzofurans; Female; Goiter; Heart Diseases; Humans; Hyperthyroidism; Hypothyroidism; Iodine; Italy; Long-Term Care; Male; Massachusetts; Middle Aged; Retrospective Studies; Thyroglobulin; Thyroid Diseases; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Serum determinations of total T4, total T3, reverse T3, free T3 index, free T4, free T4 index, TBG, T4/TBG ratio, TSH and cholesterol were carried out on 18 euthyroid patients with coronary heart disease. Serum samples were obtained before treatment and after 15 days, 2, 4, 6, 8, 10, 12, 14 and 16 months of treatment with amiodarone (400 mg/day). Patients were divided into two groups, according to patterns of TSH response to thyrotrophin-releasing hormone (TRH): (I) patients with normal responses (n = 12), and (II) patients with subnormal responses (n = 6). Patients of group I showed total T4, free T4 and reverse T3 increments and total T3 and free T3 index decreases, whereas patients of group II were distinguished by the absence of T3 decreases and a rise in free T4 levels that showed a significant correlation with a drop in serum cholesterol (r = -0.767; p. less than 0.001). No patient of either group showed clinical signs of thyroid dysfunction. These results show that the appearance of hormonal patterns of hyperthyroidism is unpredictable and very frequent in patients with no previous thyroid abnormalities undergoing long-term treatment with the drug.

Topics: Aged; Amiodarone; Benzofurans; Female; Humans; Hyperthyroidism; Long-Term Care; Male; Middle Aged; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine, Reverse

A patient with severe hyperthyroidism (thyroid storm?) and thyroid encephalopathy is described. During her illness only a slightly raised level of total thyroxine and a normal level of total triiodothyronine was found in contrast with very high levels of free thyroid hormones. Very low levels of thyroxine binding globulin, albumin and low levels of thyroxine binding prealbumin in contrast with nearly normal values of T3 resin uptake were observed. All parameters of thyroid function returned to normal after therapy.

Topics: Adult; Coma; Humans; Hyperthyroidism; Hypothyroidism; Prealbumin; Thyroid Crisis; Thyroid Hormones; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

An open randomized study involving 57 subjects, 40 euthyroid and 17 hyperthyreotic, was undertaken to compare the effect of two beta-adrenergic blocking drugs, propranolol (120 mg/day) and acebutolol (600 mg/day), on the thyroid hormones serum level. In hyperthyreotic as well as in euthyroid subjects, propranolol evoked a fall in T3, an increase in reverse T3 and therefore a decrease in the T3/rT3 ratio. Acebutolol caused a decrease in T3 and in the T3/rT3 ratio only in euthyroid subjects. The only significant variation in the hyperthyroid acebutolol treated group was a decrease in reverse T3, perhaps spontaneous. TBG and TSH concentrations remained stable under treatment in all the groups. The relation of these effects with the existence of a membrane stabilizing activity displayed by propranolol as well as by acebutolol is discussed.

Topics: Acebutolol; Adult; Aged; Female; Humans; Hyperthyroidism; Male; Middle Aged; Propranolol; Random Allocation; Thyroid Hormones; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

In order to clarify the conversion of thyroxine (T4) to triiodothyronine (T3) or to reverse T3 (rT3), serum concentrations of T4, T3, rT3, thyrotropin (TSH), thyroxine-binding globulin (TBG) and values of T3 uptake (T3 U) were measured in 61 hyperthyroid and 31 hypothyroid patients, 8 patients with subacute thyroiditis, and 40 normal subjects. Then, free T4 index (FT4I), T3/T4, rT3/T4, and rT3/T3 ratio were calculated. The rT3/T3 ratio was high in the hyperthyroid patients and low in the hypothyroid patients compared with that in the normal subjects. The ratio was positively related to serum T4, T3, rT3 levels, and FT4I in the patients and normal subjects. The regression equation was represented by rT3/T3 = 0.015[T4] + 0.083. No influences of serum TBG and age on the rT3/T3 ratio were observed. Our results indicated that thyroid hormones themselves could regulate the conversion of T4 to T3 or rT3 by activating 5-monodeiodinase in hyperthyroidism and by activating 5'-monodeiodinase and suppressing 5-monodeiodinase in hypothyroidism. Serum rT3 level was a more sensitive parameter than serum T4 or T3 for evaluating thyroid dysfunction. During the treatment with methimazole (MMI) or L-thyroxine and the natural course of subacute thyroiditis, serum T4 levels and rT3/T3 ratios changed parallel to the regression line. However, once adverse effects of MMI occurred, those changed out of the line. From these results, we concluded that the relationship between serum T4 level and rT3/T3 ratio should be examined for adequate information concerning the peripheral conversion of thyroid hormones under various thyroid diseases.

Topics: Adolescent; Adult; Aged; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Radioimmunoassay; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

A simple and accurate method for estimation of the free fractions (FFT) of T4, T3, rT3, 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) in serum is presented. The method is based on ultrafiltration of serum pre-incubated with tracers of high specific activity, followed by purification of the ultrafiltrate on small Sephadex columns. The addition of tracer only dilutes serum negligible (about 5%) and the ultrafiltration procedure only removes about 7% of the volume of serum, thus probably not disturbing the equilibrium between the free and protein bound fraction of iodothyronine. Progressive reduction of tracer to less than 10% of the amount usually used did not reduce the FFT of any of the iodothyronines. In contrast, addition of T4 to serum led to an increase of all FFTs except that of 3',5'-T2. These data suggest that FFT of T4, T3, rT3 and 3,3'-T2 primarily is determined by the amount of T4 present in serum and that significant amounts of these iodothyronines are bound to TBG, whereas 3',5'-T2 possibly primarily is bound to albumin. The median FFT of T4, T3, rT3, 3,3'-T2 and 3',5'-T2 in serum from euthyroid subjects (n = 38) was: 0.030, 0.29, 0.14, 1.10 and 1.07%, respectively. The corresponding median free concentrations in pmol/l were: 30, 4.79, 0.59, 0.44 and 0.77, respectively. Pregnant women in 3rd trimester had normal levels of free T4, free T3 and free rT3, whereas the median free 3,3'-T2 was reduced in contrast to elevated median free 3',5'-T2.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Diiodothyronines; Female; Humans; Hyperthyroidism; Kidney Failure, Chronic; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Pregnancy; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse; Ultrafiltration

Radioactivities of endogenously labelled thyroid hormones following in vivo application of 131 I and extraction from serial blood samples, show that T4 secretion is enhanced in T3-hyperthyroidism as it is in T4-T3-hyperthyroidism. In an extreme case of T3-hyperthyroidism with serum concentrations (SC) of T3 nearly equal to T4 (1000 ng/dl and 1800 ng/dl, respectively) tracer studies revealed a very short half life of T4 when compared to T3 (21.8 and 20.2 hrs., respectively). In 110 cases with both types of hyperthyroidism, regression analysis showed that T3/T4 ratio as an indicator of T4 conversion, as well as T3/rT3 ratio as an indicator of the direction of the conversion, are related to T4SC (r = -0.84 and -0.72, respectively, p less than 0.001). T3-hyperthyroidism is described by high values of these ratios. For the definition of T3-hyperthyroidism it is suggested that both T4 and rT3SC are within the normal range (T4 less than or equal to 11.5 micrograms/dl, rT3 less than or equal to 43.0 ng/dl) and according to this definition, T3/rT3 is higher than in T4-T3-hyperthyroidism and in an undefined group (24.8 +/- 4.5 vs. 6.3 +/- 0.4 or 7.5 +/- 0.4, respectively). By means of the ratios the undefined group may be allocated to T4-T3-hyperthyroidism. The T3/rT3 ratio is value of greater than 10 has a frequency of 88% in thus defined T3-hyperthyroidism and a ratio of less than or equal to 10 is found in 90% of the other cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Granulocytes; Humans; Hyperthyroidism; Iodine Radioisotopes; Kinetics; Subcellular Fractions; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Serum T4, T3, rT3 and T3 resin uptake (T3 RU) were measured before and after 7 days of treatment with either propranolol, alprenolol, sotalol, atenolol or metoprolol in hyperthyroid patients. We found a significant decrease in serum T3 after propranolol, alprenolol, atenolol and metoprolol but no change in the sotalol treated group. A significant increase in rT3 was found in the propranolol and alprenolol treated groups whereas a significant fall in rT3 was found in the atenolol and metoprolol treated groups. No change was found in the sotalol treated group. The changes observed in serum T3 and in rT3 could be explained by an inhibition of the 5'deiodinase enzyme by propranolol and alprenolol and an inhibition of both the 5'deiodinase and 5 deiodinase enzymes caused by atenolol and metoprolol.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Alprenolol; Atenolol; Humans; Hyperthyroidism; Metoprolol; Middle Aged; Propranolol; Sotalol; Triiodothyronine; Triiodothyronine, Reverse

The effect of different thyroid states on glucose homeostasis was investigated during metabolic adaptation to starvation in the conscious unrestrained miniature pig. Moderate hyperthyroidism increased the rate of glucose turnover, whereas hypothyroidism was without effect. Glucose recycling was elevated in hyperthyroid pigs, and reduced after thyroidectomy. Supplementary doses of T4 normalized total glucose recycling. Glucose metabolic clearance rate and pool size were unaffected by thyroid hormones. During starvation serum insulin showed a similar decrease in all thyroid states; glucagon increased in euthyroid and hypothyroid pigs, although it was already elevated in the hyperthyroid fed state. Serum cortisol levels although varying were enhanced in hyperthyroid and hypothyroid-T4-treated pigs. Glucogenic precursor concentration and cumulative urinary N-excretion were increased in hyperthyroid pigs. It is concluded that 1) even a moderate hyperthyroidism produces an increase in glucose turnover and a concomitant acceleration in protein breakdown, and 2) thyroid hormone is essential for the starvation-induced total glucose recycling.

Topics: Animals; Blood Glucose; Glucagon; Hyperthyroidism; Hypothyroidism; Insulin; Kinetics; Lipids; Male; Starvation; Swine; Swine, Miniature; Thyroid Gland; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Amiodarone, an iodinated benzofuran derivative, has electrophysiologic effects on cardiac muscle akin to those of hypothyroidism. It is possible that the drug exerts its salutary effect, at least in part, by selectively inhibiting the action of triiodothyronine (T3) on the myocardium. The drug produces complex changes in thyroid hormones, with significant elevations in thyroxine (T4) and reverse T3 (rT3), with minor decreases in T3, and with minor and transient increases in thyroid-stimulating hormone, but without effect on thyroid-binding globulin. These changes may interfere with the biochemical evaluation of thyroid function. Rarely, hypothyroidism or hyperthyroidism may develop during the course of amiodarone therapy, a complication caused by the iodine contained in the drug rather than by the direct pharmacologic actions of the compound. The incidence of altered thyroid function induced is likely to vary with populations susceptible to iodine-induced goiter. Under the action of amiodarone, serum rT3 levels increase as a function of dose and duration of therapy and therefore provide a basis for judging the magnitude of in vivo drug cumulation. It was found that therapeutic efficacy was usually predictable on the basis of the attainment of a defined range of serum values, established by a correlation of rT3 levels with therapeutic responses both during loading and maintenance phases as well as after withdrawal of treatment of steady-state drug effects. Serious adverse effects occurred nearly always in association with four- to fivefold increases of rT3 above baseline values, and disappeared when such levels fell as a result of dosage reduction or after temporary drug discontinuation. The data suggest that the determination of serum rT3 levels during amiodarone therapy provides a simple and reliable technique for monitoring the drug's antiarrhythmic efficacy and toxicity, thereby enhancing its clinical utility. The use of rT3 levels may permit the development of a safe but optimal therapeutic regimen for the control of a wide spectrum of refractory atrial and ventricular tachyarrhythmias. The use of this technique, however, presupposes the allowance that must be made for variations in the methods for the serum assay of rT3 and of the systemic conditions in which the rT3 levels fluctuate relative to severity of the illness.

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Hyperthyroidism; Hypothyroidism; Iodides; Male; Middle Aged; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adolescent; Adult; Aged; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Thyroid Diseases; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The sequential clinical and laboratory (serum T4, T3 and rT3 concentrations) effects of propranolol were studied in 21 hyperthyroid patients. The amount of propranolol required to achieve clinical compensation ranged from 240 to 400 mg/day. For two patients, 480 mg/day, the maximal dose used, did not produce clinical compensation. The only significant changes in serum iodothyronines was detected in the 9 patients compensated with 240 mg/day. T3 decreased from 362 to 299 ng/dl (P less than 0.05) and the rT3/T3 molar ratio increased from 3.4 to 6.5 (P less than 0.025). The increases of rT3 from 113 to 168 ng/dl and of the rT3/T4 molar ratio from 6.7 to 10.8 were not statistically significant (P = 0.052). A slight decrease of serum T3 and increase of serum rT3 occurred during the first or second week in the other patients but the changes were not sustained over the whole period of treatment. These results show that the effects of propranolol on hyperthyroidism were independent of its transitory effects on the peripheral metabolism of thyroid hormones, thus providing further support for the current view that the clinical improvement of hyperthyroid patients on propranolol therapy is probably due to beta-adrenergic receptor blockade. A small percentage of thyrotoxic patients may not show clinical improvement even when propranolol doses of more than 400 mg/day are used.

Topics: Adolescent; Adult; Female; Humans; Hyperthyroidism; Male; Middle Aged; Propranolol; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adult; Aged; Diagnosis, Differential; Female; Graves Disease; Humans; Hyperthyroidism; Male; Middle Aged; Pregnancy; Pregnancy Complications; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

We studied various tests of thyroid function in sick patients with nonthyroidal illness (NTI) in order to determine the utility of each test for differentiating these patience from a group with hypothyroidism. We evaluated each test in 22 healthy volunteers who served as controls, 20 patients with hypothyroidism, 14 patients admitted to medical intensive care unit whose serum T4 was less than 5 micrograms/dl, 13 patients with chronic liver disease, 32 patients on chronic hemodialysis for renal failure, 13 ambulatory oncology patients receiving chemotherapy, 16 pregnant women, 7 women on estrogens, and 20 hyperthyroid patients. On all samples, we measured serum T4, the free T4 index by several methods, free T4 by equilibrium dialysis, free T4 calculated from thyronine-binding globulin (TBG) RIA, free T4 by three commercial kits (Gammacoat, Immophase, and Liquisol), T3, rT3, and TSH (by 3 different RIAs). Although all of the methods used for measuring free T4 (including free T4 index, free T4 by dialysis, free T4 assessed by TBG, and free T4 assessed by the 3 commercial kits) were excellent for the diagnosis of hypothyroidism, hyperthyroidism, and euthyroidism in the presence of high TBG, none of these methods showed that free T4 was consistently normal in patients with NTI; with each method, a number of NTI patients had subnormal values. In the NTI groups, free T4 measured by dialysis and the free T4 index generally correlated significantly with the commercial free T4 methods. Serum rT3 was elevated or normal in NTI patients and low in hypothyroid subjects. Serum TSH provided the most reliable differentiation between patients with primary hypothyroidism and those with NTI and low serum T4 levels.

Topics: Alpha-Globulins; Chronic Disease; Female; Humans; Hyperthyroidism; Hypothyroidism; Kidney Failure, Chronic; Liver Diseases; Neoplasms; Pregnancy; Radioimmunoassay; Reagent Kits, Diagnostic; Renal Dialysis; Thyroid Function Tests; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

The ability of 10 muM epinephrine or isoproterenol to stimulate cyclic AMP accumulation was decreased in hepatocytes isolated from hyperthyroid (triiodothyronine treated) as compared to euthyroid rats. In the presence of methylisobutylxanthine, epinephrine or isoproterenol-stimulated cyclic AMP accumulation was approximately 65% lower in hyperthyroid as compared with euthyroid rat hepatocytes. The ability of glucagon to stimulate a cyclic AMP response was also decreased in the hyperthyroid state, when assayed in either the absence or presence of a methyl xanthine. The character of the catecholamine-stimulated cyclic AMP response was beta adrenergic in both the hyperand euthyroid states. No evidence for an alpha(2) adrenergic mediated component of catecholamine action on cyclic AMP levels was noted. Cyclic AMP phosphodiesterase activity of hepatocyte homogenates was not altered in the hyperthyroid state. Hormone-stimulated, guanine nucleotide- and fluoride-activatable adenylate cyclase activity was reduced in subcellular fractions obtained from hyperthyroid as compared with euthyroid rat hepatocytes. Beta adrenergic receptor binding was reduced approximately 35% and glucagon receptor binding reduced approximately 50% in the hyperthyroid as compared with euthyroid rat hepatocyte membrane fractions. The status of the regulatory components of adenylate cyclase were examined by in vitro treatment of subcellular fractions with cholera toxin. The ability of cholera toxin to modulate adenylate cyclase was not altered by hyperthyroidism. Cholera toxin catalyzed AD[(32)P]ribosylation of hyperthyroid and euthyroid rat hepatocyte proteins separated electrophoretically displayed nearly identical autoradiograms. Studies of the reconstitution of adenylate cyclase activity of S49 mouse lymphoma cyc(-) mutant membranes by detergent extracts from rat hepatocyte membranes, indicated that hyperthyroidism was associated with a reduced capacity of regulatory components to confer fluoride, but not guanine nucleotide activatability to catalytic cyclase. Thyroid hormones regulate the hormone-sensitive adenylate cyclase system of rat hepatocytes at several distinct loci of the system.

Topics: Adenylyl Cyclases; Animals; Benzyl Alcohols; Cholera Toxin; Cyclic AMP; Epinephrine; Female; Glucagon; Guanosine Triphosphate; Hormones; Hyperthyroidism; Isoproterenol; Liver; Pindolol; Prazosin; Propranolol; Rats; Rats, Inbred Strains; Receptors, Cell Surface; Triiodothyronine; Triiodothyronine, Reverse

Topics: Biotransformation; Diagnosis, Differential; Humans; Hyperthyroidism; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adult; Carbimazole; Female; Humans; Hyperthyroidism; Middle Aged; Propranolol; Thyroid Function Tests; Thyroid Gland; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

To study the effect of alterations in thyroid status on 5'-monodeiodinase activity, conversions of rT3 to 3,3'-diiodothyronine and 3',5'-diiodothyronine (3',5'-T2) to 3'-monoiodothyronine were examined in vitro. Rats were injected either with T4 (10 micrograms/100 g BW, ip, daily for 12 days) to make them thyrotoxic or thyroidectomized to render them hypothyroid, and liver and kidney homogenates were prepared. Liver homogenates from hyperthyroid animals demonstrated a 2-fold increase in 5'-monodeiodination of both rT3 and 3',5'-T2; both reactions were also significantly increased in the kidneys of hyperthyroid rats. Hypothyroidism produced a significant decrease in 5'-deiodination of both rT3 and 3',5'-T2 in liver and kidney homogenates. These data indicate that the in vitro 5'-deiodination of both rT3 and 3',5'-T2 is increased in hyperthyroidism and decreased in hypothyroidism and suggest that these two iodothyronines are metabolized in a similar fashion in rat liver and kidney homogenates in states of altered thyroid function.

Topics: Animals; Diiodothyronines; Hyperthyroidism; Hypothyroidism; Iodine; Kidney; Liver; Male; Rats; Thyroidectomy; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Female; Fetus; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Immunoglobulin G; Immunoglobulins, Thyroid-Stimulating; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyrotropin; Triiodothyronine; Triiodothyronine, Reverse

Serum 3,3',5'-triiodothyronine (rT3), 3,5,3'-triiodothyronine (T3), thyroxine (T4) and propylthiouracil (PTU) were measured before and at short intervals for 8 hours after oral administration of 200 mg PTU to six patients with untreated thyrotoxicosis. The study was repeated on the 4th day of treatment with 200 mg PTU every 8 hours. Six other patients with untreated thyrotoxicosis were studied after a single administration of 800 mg PTU. The results indicated that PTU inhibition of T4 deiodination to T3, evaluated by the fall in serum T3, was of the same duration as the PTU inhibition of rT3 deiodination, evaluated by the increase in serum rT3. After 200 mg PTU inhibition was maximal for only a few hours, and there was no cumulative effect of PTU during the first four days of treatment, when 200 mg PTU was given every 8 hours. After 800 mg PTU the full effect was maintained for the 9 hour period studied, after which serum T3 had fallen to 65 +/- 2% of the pretreatment level (mean +/- SE). Thus, to obtain a permanent full effect of PTU on iodothyronine deiodination during the treatment of thyrotoxicosis it is necessary to use large doses or frequent administration.

Topics: Adult; Female; Humans; Hyperthyroidism; Middle Aged; Propylthiouracil; Time Factors; Triiodothyronine; Triiodothyronine, Reverse

Serum 3'monoiodothyronine (3'-T1) levels were estimated by means of a specific radioimmunoassay (RIA) preceded by an ethanol extraction. The recovery of 3'T1 was in mean (+/-SEM) 110 +/- 9%, and the lower detection limit was 23 pmol/l. Serum levels of 3'T1 in 34 euthyroid healthy subjects were (median (range)) 55 pmol/l (less than 23 - 168 pmol/l), in 13 hyperthyroid patients 133 pmol/l (70 - 265 pmol/l) (P less than 0.01) and in 13 hypothyroid patients less than 23 pmol/l (less than 23 - 68 pmol/l) (P less than 0.01). In 11 patients with chronic renal failure serum 3'-T1 levels were highly increased 285 pmol/l (115 - 1538 pmol/l) (P less than 0.01) and correlated inversely to creatinine clearance (R = -0.68, P less than 0.05). In patients with liver cirrhosis serum 3'-T1 levels were unaffected, whereas in 19 patients with endogenous depression studied before and after recovery from the depression serum levels decreased from 70 pmol/l (less than 23 - 248 pmol/l) to 30 pmol/l (less than 23 - 95 pmol/l) (P less than 0.01). Administration of propranolol 40 mg b.i.d. for 2 weeks did not affect serum 3'-T1 levels. The study shows that 3'-T1 is present in serum from euthyroid man and varies with thyroid function. Further, it is suggested that 3'-T1 in contrast to other iodothyronines primarily is eliminated by the kidneys.

Topics: Adult; Depression; Female; Humans; Hyperthyroidism; Hypothyroidism; Kidney Failure, Chronic; Male; Middle Aged; Propranolol; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

A method for the determination of D- and L-thyroxine in human serum is described. The method involves extraction of thyroxine from serum and the separation of thyroxine enantiomers on a reversed-phase, high-performance liquid chromatographic column by use of a chiral eluent containing L-proline and cupric sulfate. Satisfactory resolution of the enantiomers of thyroxine, triiodothyronine, and reverse triiodothyronine can be achieved in 12 min and, employing amperometric detection to monitor the separation, the detection limit for serum thyroxine is in the range of 1--3 ng per injected sample.

Topics: Chromatography, High Pressure Liquid; Humans; Hyperthyroidism; Hypothyroidism; Isomerism; Microchemistry; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

In a number of hyperthyroid patients the serum gastrin level exceeds the normal range. Administration of beta-blocking agents results in a decrease of the hypergastrinaemia. The fall in the serum gastrin levels is unrelated to the effect of beta-blocking agents on peripheral thyroxine metabolism, but is associated with a decline of the plasma cAMP levels. It is suggested that, though beta adrenergic sensitivity is one of the factors of hypergastrinaemia in hyperthyroidism, other factors may be involved in its production, too.

Topics: Adrenergic beta-Antagonists; Cyclic AMP; Gastrins; Humans; Hyperthyroidism; Propranolol; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Antithyroid Agents; Atenolol; Humans; Hyperthyroidism; Metabolic Clearance Rate; Practolol; Propanolamines; Propranolol; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Thyrotoxicosis with a normal serum triiodothyronine (T3) concentration has been described with a variety of acute and chronic illnesses occurring in association with thyrotoxicosis. We describe the first case to our knowledge of thyroxine (T4) toxicosis in a 16-year-old boy with diabetic ketoacidosis. Although the clinical manifestations of hyperthyroidism were mild, thyromegaly and persistent tachycardia suggested thyrotoxicosis. Serum T4 levels were elevated; however, the serum T3 level was normal. Measurement of reverse T3 (rT3) initially revealed an elevated level that decreased over several days of T3 levels increased into the toxic range. Peripheral conversion of T4 to T3 was apparently inhibited by diabetic ketoacidosis and there was a concomitant increase in rT3 levels, suggesting that conversion of T4 to rT3 was increased during acute ketoacidosis. Assessment of thyroid function based on serum T3 levels in diabetics may be misleading during ketoacidosis or uncontrolled diabetes.

Topics: Acute Disease; Adolescent; Aged; Diabetic Ketoacidosis; Female; Humans; Hyperthyroidism; Male; Middle Aged; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Animals; Diiodothyronines; Dithiothreitol; Edetic Acid; Hyperthyroidism; Hypothyroidism; Iodide Peroxidase; Kinetics; Liver; Male; NADP; Peroxidases; Propylthiouracil; Rats; Starvation; Thyroidectomy; Thyronines; Triiodothyronine; Triiodothyronine, Reverse

A 60-year-old woman, free of other disease, with severe clinical hyperthyroidism had normal total serum T4 with elevated free T4 concentration and T3 resin uptake characteristic of hyperthyroidism, with thyroid binding globulin (TBG) deficiency. However, serum TBG concentration as determined by immunoassay was normal, suggesting that the biochemical defect affecting the T4 binding sites did not affect is antigenicity. Her total and free serum T3 levels were low-normal with a markedly elevated reverse T3 concentration. These findings, in the presence of clinical hyperthyroidism, are consistent with an impairment in peripheral conversion of T4 to T3, apparently, in this case, due only to long-standing severe hyperthyroidism.

Topics: Female; Humans; Hyperthyroidism; Middle Aged; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adult; Contraceptives, Oral; Diiodothyronines; Female; Fetal Blood; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Kinetics; Male; Thyroid Diseases; Thyroidectomy; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The effect of the beta-1-adrenoceptor blocking agent, atenolol, on serum levels of thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) was studied in twelve hyperthyroid patients. While all patients improved symptomatically after treatment with atenolol 100 mg twice daily for 2 weeks, there were no significant changes in the serum T3 or rT3 concentrations. The serum T4 level showed a small but statistically significant fall. These data do not support the hypothesis that the beneficial clinical effects of beta-adrenoceptor blocking drugs in thyrotoxicosis are mediated by an action on the peripheral metabolism of thyroid hormones.

Topics: Adult; Atenolol; Female; Humans; Hyperthyroidism; Male; Middle Aged; Propanolamines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adult; Age Factors; Female; Fetal Blood; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Infant, Newborn, Diseases; Male; Pregnancy; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Female; Humans; Hyperthyroidism; Middle Aged; Radioimmunoassay; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

In common forms of hyperthyroidism serum levels of triiodothyronin (T3) are higher than those of thyroxin (T4) and isolated elevations of serum T3 have even been noted. We report 9 cases of proven hyperthyroidism with normal or low levels of T3 and elevated T4 and reverse T3 (rT3). Most out of the patients were more than seventy years old and had associated diseases. Our data show that the low T3 with elevated rT3 syndrome--which has been noted in many metabolic and pathologic conditions--can coexist in hyperthyroidism. They emphasize the lack of diagnostic discrimination of T3 assays in thyroid dysfunction especially in the older patient or one with associated disease.

Topics: Adult; Aged; Female; Humans; Hyperthyroidism; Male; Middle Aged; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Aging; Diagnosis, Differential; Diiodothyronines; Humans; Hyperthyroidism; Thyroid Gland; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Tachycardia in both fetuses of a twin gestation was documented in a mother who had undergone subtotal thyroidectomy 8 years prior to her present pregnancy. Maternal and fetal plasma concentrations of long-acting thyroid stimulator (LATS) and amniotic fluid 3,3',5'-triiodothyronine (reverse T3) were determined. All values were consistent with the diagnosis of fetal thyrotoxicosis, as were cord blood studies performed on the fetuses post partum. Significant concentrations of LATS were present in fetal cord blood. The first fetus survived but suffered hyperthyroidism during the first 3 neonatal weeks. The second twin died, possibly of fetal thyrotoxicosis. These studies suggest that in women with a history of thyrotoxicosis, high levels of maternal LATS may in some instances provoke fetal thyrotoxicosis, which can be diagnosed by the measurement of amniotic fluid reverse T3.

Topics: Adult; Amniotic Fluid; Female; Fetal Diseases; Fetal Heart; Humans; Hyperthyroidism; Infant, Newborn; Long-Acting Thyroid Stimulator; Male; Pregnancy; Pregnancy Complications; Pregnancy, Multiple; Tachycardia; Triiodothyronine, Reverse; Twins

rT3 metabolism in patients treated for thyrotoxicosis with prophylthiouracil (PTU), or methimazole (MMI) was studied by infusion of rT3 and measurements of the increase in serum rT3 and serum 3,3'-diiodothyronine. The results indicate that the high serum rT3 observed during treatment with PTU is not due to an increase in rT3 production, but to a decrease in the metabolic clearance rate of rT3. rT3 infusion was followed by an increase in serum 3,3'-T2 which was similar whether PTU or MMI was given. However, after stopping rT3 infusion there was a more rapid fall serum 3,3'-T2 during MMI treatment, compatible with an inhibitory effect of PTU on 3,3'-T2 degradation.

Topics: Adult; Aged; Diiodothyronines; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Thyronines; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adolescent; Adult; Amniotic Fluid; Dexamethasone; Fasting; Female; Fetal Blood; Humans; Hyperthyroidism; Hypothyroidism; Ipodate; Middle Aged; Pregnancy; Radioimmunoassay; Thyroid Gland; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The relative discriminatory value of the estimation of the serum reverse-T3 levels for the laboratory diagnosis of hyperthyroidism was investigated in 47 patients with clinical signs or symptoms of hyperthyroidism. The results were compared with those from the determination of the total serum levels of T3 and T4 prior and after correction for the binding proteins. Twenty-three of the patients had normal thyroid function and 24 had hyperthyroidism. The estimation of the total serum T3 level was superior to both the determination of the total serum T4 and reverse-T3 levels even subsequent to correction for the binding proteins.

Topics: Humans; Hyperthyroidism; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Female; Humans; Hyperthyroidism; Male; Radioimmunoassay; Reagent Kits, Diagnostic; Triiodothyronine; Triiodothyronine, Reverse

Topics: Amiodarone; Benzofurans; Depression, Chemical; Humans; Hyperthyroidism; Stimulation, Chemical; Thyroid Gland; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Diagnosis, Differential; Humans; Hyperthyroidism; Thyroid Function Tests; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

Topics: Acromegaly; Female; Growth Hormone; Humans; Hyperthyroidism; Menopause; Methimazole; Middle Aged; Prednisolone; Prolactin; Propylthiouracil; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

A 9-yr-old boy is described in whom increased serum T4 concentration, increased T3 uptake, and increased free T4 index were associated with a euthyroid clinical state with normal total serum T3. T4-binding globulin (TBG), measured by RIA, was decreased. Reverse flow paper electrophoresis of serum proteins after reaction with radioactively labeled T4 demonstrated increased binding of T4 to a protein with electrophoretic mobility corresponding to albumin. Displacement of serum protein-bo-nd [125I]T4 activity by increasing concentrations of T4 revealed the presence of a low affinity, high binding capacity system with an association constant similar to that of T4-binding prealbumin. This low affinity binding protein cochromatographed with TBG on a DEAE-Sephadex column which normally separates TBG from T4-binding prealbumin. At free T4 concentrations equivalent to those present in the plasma of normal individuals, the T4 bound to free ratio is higher in the patient than in normals and the total serum T4 level is increased in the presence of normal free T4 concentrations. The relative affinity of this abnormal T4-binding protein for T3 is low compared to that of TBG. The patient's father had the same abnormal binding protein, which was not found in his mother or fraternal twin brother. These data suggest an autosomal dominant mode of inheritance of an aberration leading to synthesis of a new protein instead of normal TBG. The new protein is different from TBG in electrophoretic mobility, T4 and T3 binding, and antigenic properties.

Topics: Child; Humans; Hyperthyroidism; Male; Methimazole; Methylphenidate; Thyroid Gland; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

One disadvantage of the TRH test is that an absent or blunted TSH response is seen not only in hyperthyroid patients but also in some normal subjects. The aim of the present study was to elucidate whether the discriminatory power between eu- and hyperthyroidism could be increased by determining the T3 and T4 levels before and after the TRH administration. The study population consists of 30 patients referred for evaluation of suspected hyperthyroidism. The results show that all but one of the patients (n=20) who had T3 levels within the normal reference limits increased these levels after TRH administration, whether their TSH response was normal or blunted. One patient's T3 levels decreased after TRH. All the patients (n=10) who had T3 levels within the hyperthyroid range showed a decrease after TRH. The decrease was significantly correlated (r=0.90) to the magnitude of the increase. No consistent T4 and no change in reverse-T3 response was obtained. The addition of T3, T4 or reverse-T3 determinations in connection with the TRH test does not seem to increase the discriminatory power of the test.

Topics: Adult; Aged; Female; Humans; Hyperthyroidism; Male; Middle Aged; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The responses of serum concentrations of TSH, thyroxine (T4), triiodothyronine (T3) and of reverse triiodothyronine (rT3) to i. v. administration of 0.4 mg THR were examined prior to (and after) i. m. administration of ACTH (2 mg Synacthen Depot) in 7 euthyroid women using estrogen-containing oral contraceptives and in 8 controls, with the following results: (1) an increase in endogenous glucocorticoid secretion is associated with a depression of the TSH response to TRH; (2) TSH formed in decreased amounts is still capable of stimulating thyroid secretion; (3) the increased serum corticoid levels fail to affect the secretory response of the thyroid to TSH; (4) control of the pituitary-thyroid axis remains normal in the presence of increased serum thyroxine-binding globulin (TBG) levels. In a further series the serum levels of TBG, T4, T3, rT3 and cortisol under the effect of ACTH-induced endogenous glucocorticoid hypersecretion were studied in 6 normal untreated controls, in 6 normal women using oral contraceptives and in 10 untreated hyperthyroid patients. During four days subsequent to treatment the serum TBG levels decreased, maximum decrease being found in the users of oral contraceptives, minimum decrease in the controls. Serum T4 was found to decrease during 2 to 4 days, serum T3 parallel with an increase in serum rT3, for 1 to 2 days, subsequent for ACTH loading. In the euthyroid cases also the serum TSH levels showed a transitory decline. It is concluded that in case of endogenous hyperproduction of glucocorticoids (1) T4 leads to T3 monodeiodination decreases and T4 leads to rT3 conversion increases parallel with the changes in the serum cortisol levels; (2) TBG synthesis is inhibited by endogenous glucocorticoids; (3) the changes in serum TBG levels are accompanied by a decrease in the serum T4 concentrations.

Topics: Adrenocorticotropic Hormone; Adult; Cosyntropin; Female; Humans; Hydrocortisone; Hyperthyroidism; Thyroid Hormones; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse; Zinc

Simple radioimmunoassays for 3,3',5-triiodothyronine (T3), 3,3',5'-reverse-triiodothyronine (r-T3) and 3,3'-diiodothyronine (r-T'2) in human serum are described. The princple of the methods is the same and based on a system using 8-anilino-1-naphthalene sulfonic acid as an inhibitor of nonspecific protein binding, a simultaneous addition of the antibody and the labelled hormone, an overnight incubation at room temperature and a separation of bound and free hormone with dextran-coated charcoal. The methods require 15 microliter, 50 microliter and 100 microliter (or 333 microliter for ethanol extraction) serum respectively. Serum concentrations (mean +/- SD) of T3, r-T3 and r-T'2 from normal subjects are 144 +/- 19 ng T3/100 ml (n = 52), 32 +/- 7 ng r-T3/100 ml (n = 36), 3.8 +/- 0.7 ng r-T'2/100 ml (ethanol extraction, n = 18) and 8.2 +/- 1.6 ng r-T'2/100 ml (unextracted, n = 16).

Topics: Diiodothyronines; Humans; Hyperthyroidism; Hypothyroidism; Radioimmunoassay; Reference Values; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Serum concentrations of T4, T3 and reverse T3 were studied in two hyperthyroid groups (n = 13 and 11), in a group of normals (n = 9) and in a group of L-T4 substituted patients (n = 7) with severe pretreatment hypothyroidism. Serum T4 did not change except in one of the hyperthyroid groups change to in which a slight decrease was found. In all groups a significant fall in serum T3 and a significant rise in serum reverse T3 were found. An expected increase in serum TSH in the normal and in the L-T4 substituted groups could not be demonstrated.

Topics: Adult; Female; Humans; Hyperthyroidism; Male; Middle Aged; Myxedema; Propranolol; Stereoisomerism; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Propranolol alone was given to sixteen hyperthyroid, and concomitantly with thyroxine therapy to ten hypothyroid patients. Following treatment of the hyperthyroid group for 1-2 weeks there was a significant decrease in serum triiodothyronine (T3) which correlated with the plasma propranolol steady state concentration. The serum reverse T3 (rT3) rose significantly. Weight loss ceased in this group while weight gain occurred in patients who had a marked fall in serum T3. One patient with T3 toxicosis went into remission. The reduction in serum T3 was maintained in six patients receiving propranolol for more than 1 month. In the hypothyroid group the mean serum T3 level achieved with 0.15 mg thyroxine per day was significantly lower than in a control group who did not receive propranolol. In five patients following propranolol withdrawal there was a significant rise in T3, a fall in rT3 and TSH, and weight loss. Propranol may therefore have a clinically significant and direct action on the peripheral conversion of thyroxine to T3 and rT3.

Topics: Adolescent; Adult; Aged; Body Weight; Humans; Hyperthyroidism; Hypothyroidism; Middle Aged; Propranolol; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Diiodothyronines; Humans; Hypertension; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Liver Cirrhosis; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adult; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Thyrotropin-Releasing Hormone; Triiodothyronine; Triiodothyronine, Reverse

Serial changes in thyroid hormone levels are described in two patients in whom hyperthyroidism was associated with transient non-thyroidal illness. In a 74-year-old woman with mild hyperthyroidism, two episodes of cholecystitis were associated with subnormal concentrations of serum T3 and increased concentrations of serum rT3; T3 became elevated during recovery, associated with a simultaneous fall in rT3. The TSH response to TRH was undetectable on three occasions. A cholecystectomy was performed after preparation with Lugol's iodine and subsequent tests showed evolution through T3 toxicosis to classical hyperthyroidism. In the second case, symptoms and signs of classical hyperthyroidism were noted during an undiagnosed illness characterized by severe abdominal pain and fever. Six days after the onset of this illness, an elevated level of serum T4 was associated with a normal total T3 concentration and increased concentration of rT3. After resolution of abdominal symptoms, serum T3 was markedly increased, associated with persistent T4 and rT3 excess. These findings indicate that the changes in T3 and reverse T3 described in non-thyroidal illness also occur in hyperthyroid patients, and suggest that the fall in T3 may be of sufficient magnitude to make T3 measurement diagnostically unreliable in the presence of non-thyroidal illness.

Topics: Adult; Aged; Cholecystitis; Female; Humans; Hyperthyroidism; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

To further elucidate the peripheral metabolism of rT3 and to determine if rT3 production rates vary directly with thyroid function, we measured the disappearance of [125I]rT3 in thyrotoxic and hypothyroid subjects as well as in athyreotic patients maintained eumetabolic on exogenous T4. Kinetic parameters were determined by noncompartmental analysis, and serum concentrations of rT3 and T4 were determined by specific RIAs. In six hyperthyroid, seven euthyroid, and six hypothyroid subjects, the MCRs were 190.7 +/- 15.7, 111.7 +/- 13.2, and 71.8 +/- 7.0 liters/day kg, respectively (mean +/- SE). Production rates (PR) for these same groups were 271.3 +/- 40.5, 51.7 +/- 9.1, and 4.3 +/- 0.6 micrograms/day/70 kg. The observed differences in MCR and PR among the three study groups were highly significant (P less than 0.002). These data indicate that in comparison to euthyroid subjects, rT3 PR and MCR are increased in thyrotoxic and decreased in hypothyroid individuals.

Topics: Adult; Female; Humans; Hyperthyroidism; Hypothyroidism; Kinetics; Male; Metabolic Clearance Rate; Middle Aged; Thyroid Gland; Triiodothyronine; Triiodothyronine, Reverse

A dose (3 g) of sodium ipodate used routinely in oral cholecystography caused a fall in serum 3,5,3'-triiodothyronine and a rise in serum 3,3',5'-triiodothyronine in three patients taking thyroxine (T4), four euthyroid subjects,and four hyperthyroid patients. Serum T4 fell in patients with hperthyroidism, whereas it rose in the other two groups. Sodium ipodate appears to alter peripheral T4 metabolism and, in addition, produces thyroid-inhibiting effects in hyperthyroidism.

Topics: Graves Disease; Humans; Hyperthyroidism; Ipodate; Kinetics; Male; Reference Values; Thyroiditis, Autoimmune; Thyronines; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adult; Aged; Female; Humans; Hyperthyroidism; Male; Middle Aged; Propranolol; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

A simple and sensitive radioimmunoassay for reverse T3 in urine using small Sephadex G25 fine columns is described. The recovery of rT3 added to urine was on average 101.0 +/- 4.2% (mean +/- SEM). Detection limit was 4 pg/column. Urine excretion of rT3 (mean +/- SD) was 72.0 +/- 32.1 ng/24 h in 61 healthy euthyroid subjects with a slight increase with age (P less than 0.05), 28.8 +/- 18.2 ng/24 h in 12 hypothyroid patients and 183.6 +/- 79.7 ng/24 in 25 hyperthyroid patients.

Topics: Adolescent; Adult; Aged; Chromatography, Gel; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Radioimmunoassay; Triiodothyronine; Triiodothyronine, Reverse

Topics: Energy Intake; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Reverse T3 (r-T3) was measured in unextracted human plasma under different clinical conditions. The mean normal concentration was 0.20 ng/ml. In thyreotoxic patients r-T3 was elevated in the majority of the cases, however, it was normal in three cases of T3-toxicoses. Thyrectomized patients during different hormon substitution showed r-T3 levels corresponding to the T4 concentrations measured. Patients with severe chronic illnesses and low T3 showed normal to considerably elevated r-T3 levels. According to these results r-T3 is not of additional value in the diagnosis of thyroid disorders.

Topics: Hyperthyroidism; Thyroid Gland; Thyroidectomy; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Animals; Hyperthyroidism; Hypothyroidism; Kidney; Liver; Male; Rats; Thyroidectomy; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Graves Disease; Humans; Hyperthyroidism; Triiodothyronine; Triiodothyronine, Reverse