thyronines and Hyperthyroidism

Topics: Anorexia Nervosa; Biomarkers; Brain Neoplasms; Diiodothyronines; Humans; Hyperthyroidism; Hypothyroidism; Liver Diseases; Radioimmunoassay; Reference Values; Thyroid Function Tests; Thyronines

The presence of antithyroid hormone autoantibodies in the sera of patients with thyroid and nonthyroid disorders is a well-known condition. When circulating thyroid hormones bind to the patients' immunoglobulins, serum levels of total and free thyroid hormones are often in discordance with clinical features. This problem occurs because the autoantibodies can interfere with radioimmunoassays. To avoid inappropriate treatment of such patients, it is clinically important to consider the presence of autoantibodies in patients with unexpectedly high or low total and free thyroid hormone values. We have reviewed the English and Japanese literature, both case reports and basic works, and summarize the incidence of antithyroid hormone autoantibodies, clinical features, effects on appropriate testing of the hypothalamic-pituitary-thyroid axis, diagnostic methods for confirming their presence of autoantibodies, treatment of patients with these disorders, and possible pathogenetic mechanisms.

Topics: Autoantibodies; Cross Reactions; False Positive Reactions; Goiter; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Immunoglobulin G; Immunoglobulins; Radioimmunoassay; Thyroid Diseases; Thyroid Function Tests; Thyroid Hormones; Thyroiditis, Autoimmune; Thyronines

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

Topics: Diiodothyronines; Humans; Hyperthyroidism; Kinetics; Liver Cirrhosis; Metabolic Clearance Rate; Thyronines; Thyroxine; Triiodothyronine

Topics: Benzoates; Binding Sites; Cross Reactions; Diet; Ethylmercury Compounds; Evaluation Studies as Topic; Geography; Humans; Hyperthyroidism; Hypothyroidism; Immune Sera; Iodine; North America; Phenytoin; Radioimmunoassay; Sulfides; Thyronines; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine

Topics: Autoradiography; Basal Metabolism; Blood; Blood Protein Electrophoresis; Female; Humans; Hyperthyroidism; Hypothyroidism; Iodine Isotopes; Pregnancy; Thyroid Function Tests; Thyronines; Thyroxine

Topics: Blood; Body Fluids; Calcium; Congenital Hypothyroidism; Drug Therapy; Hyperthyroidism; Hypothyroidism; Myxedema; Nitrogen; Pharmacology; Phosphorus; Thyronines; Thyroxine; Toxicology; Urine

Animal studies have shown thyroid dysfunction affects salivary gland functioning, however conclusive human studies are lacking. We sought to assess the qualitative and quantitative changes in saliva among subjects with thyroid dysfunction prior to and following treatment.. A longitudinal observational study of 153 newly diagnosed subjects who had hypothyroidism (n = 107) or hyperthyroidism (n = 46), aged 18-45 years, fulfilling the inclusion/exclusion criteria was conducted. Analysis of salivary parameters (stimulated salivary flow rate (SSFR), pH and buffering capacity) was performed at diagnosis (baseline), on attaining euthyroid state and 3 months thereafter.. Subjects were 86% females, and at baseline 13% of subjects had hyposalivation. Mean SSFR, pH, buffering capacity as well as percentage of hypothyroid subjects having normal salivation increased following thyroid treatment.. Thyroid dysfunction affects salivary gland function. Subjects with chronic hyposalivation should have thyroid function assessment if the known established causes are excluded.

Topics: Adolescent; Adult; Antibodies; Antithyroid Agents; Autoantigens; Buffers; Carbimazole; Female; Follow-Up Studies; Humans; Hydrogen-Ion Concentration; Hyperthyroidism; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Iodide Peroxidase; Iron-Binding Proteins; Longitudinal Studies; Male; Middle Aged; Receptors, Thyrotropin; Saliva; Salivary Glands; Secretory Rate; Thyroglobulin; Thyronines; Thyrotropin; Thyroxine; Triiodothyronine; Xerostomia; Young Adult

Thyroid-stimulating hormone (TSH)-binding inhibitory immunoglobulin (TBII) is thought to be one of the essential causes of Graves' disease, and most cases of neonatal hyperthyroidism can be explained by transplacental passage of TBII. Because surgery is often indicated for patients of childbearing age, it is important to elucidate how surgery reduces TBII levels. Between 1988 and 1991 a total of 946 female patients with Graves' disease underwent subtotal thyroidectomy. Follow-up examination was undertaken at 1, 2, 3, and 4 to 5 years after surgery. At 4 to 5 years after surgery, 76.8% of patients without recurrent overt hyperthyroidism had TBII < 20%. In patients with recurrent hyperthyroidism, TBII increased gradually during follow-up, and they had higher TBII levels than nonrecurrence patients. There were a few euthyroid and hypothyroid patients who had TBII > 60%, and the number of such patients decreased annually. In most of the patients, immunologic remission was obtained by subtotal thyroidectomy except for their having recurrent hyperthyroidism. To acquire immunologic remission, hormonal remission, at least, would be necessary. Because no definite factor other than the size of the thyroid remnant related to postoperative thyroid function was elucidated, near-total thyroidectomy rather than subtotal thyroidectomy is expected to be induced not only hormonal remission but also immunologic remission. It should be noted that a few patients achieved hormonal remission but not immunologic remission.

Topics: Adult; Autoantibodies; Female; Follow-Up Studies; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Patient Care Planning; Postoperative Complications; Radiopharmaceuticals; Receptors, Thyrotropin; Recurrence; Retrospective Studies; Thyroidectomy; Thyronines; Thyrotropin; Thyroxine

The effects of hyperthyroidism and hypothyroidism on the immune function were assessed in rats by the changes in lymphocyte subsets in peripheral blood and spleen. Hyperthyroidism was induced in rats by intraperitoneal injection of large doses of T4. Hypothyroid rats were prepared by total thyroidectomy followed by 131I administration. In the hyperthyroid rats, the peripheral blood helper/suppressor T cell ratio was decreased, while in hypothyroidism this ratio was increased. However, in spleen cells, this ratio was increased in hypothyroid rats as compared to normal controls. The most striking finding was an augmentation of activated T cells (transferrin receptor positive lymphocytes) in both peripheral blood and spleen cells in the hypothyroid rat. These results suggested that thyroid hormone suppressed the immune response and that a deficiency of this hormone was associated with an increase of activated T cells. These effects of thyroid hormone on the lymphocyte subsets in rats were at variance with the abnormalities that have been observed in humans with such autoimmune thyroid disease as Graves' disease.

Topics: Animals; Dose-Response Relationship, Drug; Female; Flow Cytometry; Hyperthyroidism; Hypothyroidism; Immune System; Lymphocyte Activation; Lymphocyte Subsets; Male; Phenotype; Rats; Rats, Wistar; Thyroid Gland; Thyronines; Thyroxine

Experiments on albino male rats have demonstrated that a single subcutaneous isoprenaline injection produces cardiac calpaine activation and lysosomal labilization in euthyroidized animals. A 10 micrograms/kg triiodothyronine dose and a 50 micrograms/kg L-thyroxin inhibit calpaines and stabilize myocardial lysosomal membranes in intact rats. The effects following myocardial damage do not occur or become less pronounced in hyperthyroidism. Triiodothyronine proved to be more effective.

Topics: Animals; Calpain; Cathepsin D; Heart; Hyperthyroidism; Isoproterenol; Male; Myocardium; Rats; Thyronines; Thyroxine; Triiodothyronine

In the present study, we report the uncommon case of a 9.6-yr-old girl with circulating anti-T3 autoantibodies (T3-Ab) and hyperthyroidism due to inappropriate secretion of TSH (IST). The diagnosis of IST was based on the findings of normal TSH levels (2.4 mU/L) in the presence of high free T4 (28.2 pmol/L) and free T3 (FT3) levels, as measured by direct measurement methods based on "one-step" analog tracer (28.0 pmol/L) and "two-step" Lisophase (13.3 pmol/L) techniques. The discrepancy between the two measurements suggested a methodological interference due to T3-Ab in "one-step" technique, being the "two-step" methodology unaffected by the presence of such autoantibodies. T3-Ab were documented by high nonspecific binding of serum to labeled T3 (38.0% vs 4.3 +/- 2.1% in controls). The clinical picture of hyperthyroidism, the qualitatively normal TSH responses to TRH and T3 suppression tests, the normal pituitary imaging and the values of some parameters of peripheral thyroid hormone action compatible with hyperthyroidism indicated that the patient was affected by pituitary resistance to thyroid hormones (PRTH). Chronic treatment with dopaminergic agent bromocriptine (7.5 mg/day) did not cause TSH secretion to be suppressed, while the administration of thyroid hormone analog TRIAC (1.4 mg/day) inhibited TSH release (from 2.4 to 0.2 mU/L). As a consequence, circulating thyroid hormone levels normalized and euthyroidism was restored. During TRIAC administration, FT3 levels, measured by "one-step" analog tracer technique, gave spuriously high values due to the methodological interference of T3-Ab (15.2 vs 4.3 pmol/L as measured by "two-step" Lisophase technique).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Autoantibodies; Child; Drug Resistance; Female; Humans; Hyperthyroidism; Pituitary Gland; Thyroid Hormones; Thyronines

Administration of triiodothyronine (liothyronine, 15 micrograms, q 8 h, for 6 treatments) caused marked decrease in serum concentration of thyroxine (T4) and estimates of free T4 (fT4) concentration in clinically normal cats. A prospective clinical study was done to evaluate the use of this suppression test for diagnosis of hyperthyroidism in cats with clinical signs suggestive of the disease, but lacking high serum concentration of iodothyronines. Twenty-three cats were confirmed as hyperthyroid on the basis of histologic changes in the thyroid gland or clinical improvement in response to administration of methimazole. Mean +/- SD serum concentration of T4 (34.3 +/- 12.7 to 31.3 +/- 11.5 nmol/L) and estimate of fT4 concentration (26.6 +/- 6.4 to 25.6 +/- 6.9 pmol/L) did not change after administration of liothyronine to these cats. Twenty-three cats were classified as nonhyperthyroid by histologic confirmation of other disease, abnormal results of other diagnostic tests that strongly supported primary disease other than hyperthyroidism, or spontaneous remission of weight loss without treatment. Mean +/- SD serum concentration of T4 (27.9 +/- 10.3 to 11.7 +/- 6.4 nmol/L) and estimate of fT4 concentration (21.7 +/- 5.4 to 10.4 +/- 4.4 pmol/L) decreased significantly (P less than 0.001) in response to administration of liothyronine. Discriminant analysis was used to identify variables from iodothyronine assays (eg, absolute concentration of T4 or absolute estimate of fT4 concentration, or changes of T4 or fT4 concentration) that provided the best diagnostic sensitivity and specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cat Diseases; Cats; Discriminant Analysis; Evaluation Studies as Topic; False Negative Reactions; False Positive Reactions; Female; Hyperthyroidism; Male; Predictive Value of Tests; Prospective Studies; Thyronines; Thyroxine; Triiodothyronine

Topics: Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Radioimmunoassay; Thyronines

Topics: Anorexia Nervosa; Diiodothyronines; Female; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Liver Cirrhosis; Male; Pregnancy; Radioimmunoassay; Reference Values; Thyronines

A sensitive and specific RIA has been developed to measure thyronine (To) in urine. The RIA used an anti-To antibody obtained from a rabbit immunized with a L-To-human serum albumin conjugate and [3H]To as the radioligand. The acetic acid analog of To (ToAc), that is the diphenyl structure with an acetic acid side-chain, cross-reacted strongly with the antibody. Relative to To, it cross-reacted 160% in phosphate-buffered saline, pH 7.4, and 100% in 0.075 mol/L barbital buffer, pH 8.6, containing sodium salicylate (final concentration, 8 mg/mL). The latter conditions were employed for the RIA, and the results reported thus reflect the presence of To and/or ToAc. 3-Monoiodothyronine, 3'-monoiodothyronine, 3',5'-diiodothyronine, and 3,5-diiodothyronine cross-reacted with the anti-To antibody 1.9%, 1.7%, 0.3%, and 0.2%, respectively; the cross-reactivity of other To derivatives and tyrosine and its derivatives was less than 0.05%. Urinary To and/or ToAc excretion in 12 normal subjects averaged 16 +/- 2 (+/- SE) micrograms/day (59 +/- 9 nmol/day) or 14 +/- 2 micrograms/g creatinine (5.9 +/- 0.6 nmol/mmol creatinine). Treatment of urine from normal subjects with beta-glucuronidase or sulfatase did not significantly alter the To content. Column and thin layer chromatographic studies revealed that 83% and 61%, respectively (range, 37-100%), of urinary To immunoreactivity was attributable to ToAc. The mean daily excretion of To in 20 patients with nonthyroidal illness [NTI; 22 +/- 4 micrograms/day (82 +/- 17 nmol/day)] was similar to that in normal subjects, but was elevated when expressed as nanomoles per mmol creatinine (20 +/- 2; P less than 0.001), because creatinine excretion was reduced in the NTI patients. The mean daily urinary To excretion in 13 patients with hyperthyroidism due to Graves' disease was slightly elevated [29 +/- 6 micrograms/day (108 +/- 21 nmol/day); P less than 0.1], but was clearly elevated when expressed as nanomoles per mmol creatinine (37 +/- 8; P less than 0.001), again because creatinine excretion was reduced in these patients. The mean urinary To excretion was subnormal in 13 patients with hypothyroidism and was significantly (P less than 0.005) less than that in the NTI patients regardless of the manner in which the results were expressed. Analysis of pronase hydrolysates of thyroid glands obtained at autopsy from euthyroid patients suggested that the To content of the thyroid approximates only 1.2% that of T4, supporting the thes

Topics: Acetates; Adult; Antibodies; Antibody Specificity; Female; Glucuronidase; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Radioimmunoassay; Sulfatases; Thyronines; Triiodothyronine

Seventy-five elderly patients with atrial fibrillation (41 males and 34 females with a mean age of 75.6 years) were studied to evaluate the incidence of masked thyroid dysfunction. A thyrotropin (TSH)-releasing-hormone (TRH) test (intravenous injection of 250 micrograms of synthetic TRH) was performed in the patients and 30 age matched controls without atrial fibrillation. In the controls, no abnormal TRH stimulated TSH response was observed. In the patients with atrial fibrillation, no response of TSH to TRH (hyperthyroidism) was found in 5 cases (6.6%), while hyperresponse of TSH to TRH (hypothyroidism) was found in 6 cases (8.0%). Thyroid dysfunction (hyper or hypothyroidism) was more frequently observed in the patients than in the controls (p less than 0.05). Two of 5 hyperthyroid patients had normal thyroid hormone levels. All patients with hyperthyroidism were treated with antithyroid drugs or 131I. Unfortunately, atrial fibrillation persisted in all but 1 case. It is concluded that the TRH test is a useful screening test for detecting those patients with abnormal thyroid function among elderly patients with atrial fibrillation, and that hypothyroidism should be considered as a cause of atrial fibrillation in the elderly.

Topics: Aged; Antibodies; Atrial Fibrillation; Female; Humans; Hyperthyroidism; Injections, Intravenous; Male; Thyroid Gland; Thyronines; Thyrotropin; Triiodothyronine

A radioimmunoassay for the estimation of 3,5-diiodothyronine (3,5-T2) in human urine has been established. The urinary excretion of both glucuronide and sulfate conjugates of 3,5-T2 were estimated after enzymatic deconjugation. In 19 healthy controls the median excretion of unconjugated 3,5-T2 was 276 pmol/d, whereas the median excretion of glucuronidated and sulfated 3,5-T2 in 7 healthy subjects was 448 and 451 pmol/d, respectively. The median excretion of 154 pmol/d in 9 hypothyroid patients did not differ from that found in controls. In contrast 12 patients with hyperthyroidism had an enhanced excretion, 1312 pmol/d (P less than 0.01). Compared with previous data on the daily degradation of 3,5-T2, it is concluded that approximately one-sixth of degradated 3,5-T2 is excreted in the urine.

Topics: Adult; Aged; Diiodothyronines; Female; Glucuronates; Goiter; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Radioimmunoassay; Sulfates; Thyronines

When 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) (10 ng/(g X day] was administered to pregnant rats, their infants showed signs of hyperthyroidism with suppressed body weight, tachycardia, and tremor at the day of birth. The brain weight did not change but the wet weight of the cerebral cortex was increased in the infants. Tubulin content (per wet weight and per whole tissue) was increased in the cerebral cortex and cerebellum but remained unchanged in the hypothalamus in the DIMIT-treated group. DIMIT-induced hyperthyroidism was shown to affect the development of the fetal brain.

Topics: Animals; Brain; Female; Hyperthyroidism; Maternal-Fetal Exchange; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Inbred Strains; Thyronines; Tissue Distribution; Tubulin

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

We studied the effect of T3-induced hyperthyroidism on the outer ring (5' or 3') monodeiodination of T4 (to T3) and 3',5'-diiodothyronine [3',5'-T2; to 3'-monoiodothyronine (3'-T1)] and on the inner ring (3 or 5) monodeiodination of 3,5-T2 (to 3-T1) by various rat tissues. Weight-matched pairs of male Sprague-Dawley rats were given either saline or T3 (20 micrograms/100 g BW daily) ip for 3 days. The metabolism of the iodothyronines was studied on day 4 in homogenates of the tissues in the presence of 25 mM dithiothreitol. Hyperthyroidism was associated with a significant (P less than 0.05) increase in T4 to T3 monodeiodinating activity in the liver (mean, 95%), kidney (mean, 60%), and heart (mean, 153%), but not in skeletal muscle, small intestine, spleen, testis, cerebral cortex, or cerebellum. The monodeiodinating activity converting 3',5'-T2 to 3'-T1 was greatly increased (P less than 0.05) in the heart (mean, 750%), spleen (mean, 462%), and skeletal muscle (mean, 167%), but not in liver, kidney, small intestine, testis, cerebral cortex, or cerebellum. In the case of liver and kidney, however, there was evidence of an activation of 3',5'-T2 monodeiodinating activity, as suggested by a significant increase in the activity in the absence of added dithiothreitol. The monodeiodination of 3,5-T2 to 3-T1 increased significantly only in the cerebral cortex (mean, 525%) and liver (mean, 69%) and not in any other tissue. The time course of the above-mentioned changes in iodothyronine metabolism was studied in groups of rats (five per group) given T3 (20 micrograms 100 g BW-1 day-1) 6-72 h before death. Significant increases in 3',5'-T2 (to 3'-T1) monodeiodination in the heart and 3,5-T2 (to 3-T1) monodeiodination in the cerebral cortex were evident within 6 h of T3 administration. Changes in T4 to T3 monodeiodinating activity in the kidney and liver, however, did not become statistically significant until 24 and 72 h, respectively. The various effects of T3 on the tissues became maximal between 48 and 72 h after the initiation of T3 treatment. Our data suggest that most tissues, including some that have been considered unresponsive to thyroid hormones, e.g. brain and spleen, demonstrate substantial metabolic changes after T3 administration. The tissue responses are variable in degree; in some instances, they are specific for the substrate and type of tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Diiodothyronines; Hyperthyroidism; Kinetics; Male; Rats; Rats, Inbred Strains; Thyronines; Thyroxine; Triiodothyronine

The splanchnic extraction of 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) was studied in 7 hyperthyroid patients and 20 normal subjects employing the hepatic venous catheterization technique. A significant net uptake by splanchnic tissues was found for both diiodothyronines . The fractional splanchnic extraction calculated as the arterio-hepatic venous plasma concentration difference divided by the arterial concentration was unaffected by hyperthyroidism as compared to normal values. There was a close positive correlation between the arterio-hepatic venous concentration difference and arterial concentration, 3,3'-T2: r = 0.988, and 3',5'-T2: r = 0.932 (P less than 0.001). The splanchnic extraction was nonsaturable at endogenous plasma concentrations of 3,3'-T2 up to at least 17.0 ng/dl and of 3',5'-T2 up to at least 15.2 ng/dl. The data suggest that the splanchnic extraction of 3,3'-T2 and 3',5'-T2 obeys first order kinetics, the fractional extraction being unaffected by hyperthyroidism. Furthermore, changes in the net splanchnic extraction of 3,3'-T2 and 3',5'-T2 do not seem to contribute to changes in circulating levels of these iodothyronines. It is suggested that tissues other than the liver contribute significantly to the deiodination process both in normal and in hyperthyroid man.

Topics: Adolescent; Adult; Diiodothyronines; Female; Humans; Hyperthyroidism; Kinetics; Liver; Male; Mesentery; Middle Aged; Thyronines

The mass spectral properties of four classes of derivatives of thyronine are discussed ( oxazolidinone , O-methyl oxazolidinone , O-acetyl oxazolidinone and N,O- diheptafluorobutyryl methyl ester). An assay for thyronine in human urine is described based on the N,O- diheptafluorobutyryl methyl ester. Results of T0 excretion in euthyroid humans were compared with those obtained previously using an assay based on the O-acetyl oxazolidinone derivative. Patients with frank hyperthyroidism had significantly higher T0 excretion than euthyroid subjects (2 alpha less than 0.002) and hypothyroid patients lower T0 excretions than euthyroid subjects (2 alpha less than 0.002). Some overlap between the two pathological ranges and the normal euthyroid range was evident.

Topics: Humans; Hyperthyroidism; Hypothyroidism; Mass Spectrometry; Thyronines

To investigate the thyroid hormone metabolism in altered states of thyroid function, serum concentrations of 3, 3'-diiodothyronine (3, 3'-T2), 3', 5'-T2 and 3, 5-T2 as well as T4, T3 and rT3 were determined by specific radioimmunoassays in 17 hyperthyroid and 10 hypothyroid patients, before and during the treatment. Serum T4, T3, rT3, 3, 3'-T2 and 3', 5'-T2 concentrations were all higher in the hyperthyroid patients than in age-matched controls and decreased to the normal ranges within 3 to 4 months following treatment with antithyroid drugs. In the hypothyroid patients, these iodothyronine concentrations were lower than in age-matched controls and returned to the normal ranges after 2 to 3 months treatment with T4. In contrast, serum 3, 5-T2 concentrations in hyperthyroid patients (mean +/- SE : 4.0 +/- 0.5 ng/dl) were not significantly different from those in controls (3.9 +/ 0.4 ng/dl), although they tended to decrease in 3 of 6 patients after the antithyroid drug therapy. Serum 3, 5-T2 levels in the hypothyroid patients (3.8 +/- 0.6 ng/dl) were also within the normal range and showed no significant change following the T4 replacement therapy. However, serum 3, 5-T2 as well as 3, 3'T2 concentrations rose significantly with a marked rise in serum T3 following T3 administration, 75 micrograms/day for 7 days, in Graves' patients in euthyroid state.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Diiodothyronines; Humans; Hyperthyroidism; Hypothyroidism; Middle Aged; Thyronines; Thyroxine; Triiodothyronine

Topics: Animals; Humans; Hyperthyroidism; Hypothyroidism; Kidney; Liver; Rats; Thyroid Gland; Thyroid Hormones; Thyronines; Tissue Distribution

A RIA for 3-monoiodothyronine (3T1) using tritiated ligand, has been validated for measurement of extracted serum. The mean euthyroid level of serum 3T1 was 2.9 +/- 1.7 ng/dl. In thyrotoxic patients, the mean serum 3T1 was significantly higher: 6.2 +/- 3.9 ng/dl (P less than 0.001) and in hypothyroid patients, the mean level was 2.1 +/- 1.5 ng/dl, lower but not significantly lower than the mean euthyroid level (P greater than 0.05). The mean serum level in severely ill patients was 2.5 +/- 1.5 ng/dl (P greater than 0.05) and in cord blood was significantly higher at 9.1 +/- 2.6 ng/dl (P less than 0.001). The appearance of 3T1 within 5 min in two normal volunteers after iv injection of 3,3'-diiodothyronine was followed over 2 1/2 h. Thus 3T1 is a normal constituent of human plasma and is derived from 3,3'-diiodothyronine. Its concentrations appear to be severalfold higher than those reported for 3'T1.

Topics: Adult; Contraceptives, Oral; Diiodothyronines; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Radioimmunoassay; Thyronines

Topics: Adult; Aged; Diiodothyronines; Female; Humans; Hyperthyroidism; Hypothyroidism; Kinetics; Male; Metabolic Clearance Rate; Middle Aged; Thyronines

Simultaneous kinetic studies of 3,5-diiodothyronine (3,5-T2) and T3 were performed in 15 healthy controls (8 men and 7 women), 7 hyperthyroid patients (2 men and 5 women), and 6 hypothyroid women using the single injection, noncompartmental approach. The serum concentrations (picomoles per liter), MCRs (liters . day-1 . (70 kg)-1), and production rates (PRs; nmol . day-1 . (70 kg)-1) of 3,5-T2 in healthy men and women were (mean +/- SD): 100 +/- 23 vs. 80 +/- 23 (P = NS), 59 +/- 31 vs. 123 +/- 58 (P less than 0.025), and 5.6 +/- 1.9 vs. 9.1 +/- 2.6 (P less than 0.02). The conversion rate (CR) of T3 to 3,5-T2 was 12.0 +/- 3.8% in men compared to 18.5 +/- 3.7% in women (P less than 0.01). Serum 3,5-T2 levels in five mildly hyperthyroid women were elevated to 123 +/- 33 pmol/liter (P less than 0.05), whereas the MCR and PR were unchanged. However, two hyperthyroid men with more pronounced elevation of serum T3 had enhanced PRs (26.9 and 23.9 nmol . day-1 . (70 kg)-1). The CR in hyperthyroid women was significantly reduced to 5.6 +/- 2.9% (P less than 0.001). The serum levels, MCR, and PR of 3,5-T2 in hypothyroid women were: 58 +/- 25 pmol/liter (P = NS), 71 +/- 52 liters . day-1 . (70 kg)-1 (P = NS), and 3.4 +/- 2.4 nmol . day-1 . (70 kg)-1 (P less than 0.005). The CR was enhanced to 34.8 +/- 15.7% (P less than 0.05). Our data demonstrate that in euthyroid subjects, approximately 15% of T3 is deiodinated to 3,5-T2, and this 5'-deiodination of T3 is influenced by thyroid function.

Topics: Adult; Diiodothyronines; Female; Humans; Hyperthyroidism; Hypothyroidism; Kinetics; Male; Metabolic Clearance Rate; Thyronines; Triiodothyronine

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

RIAs for the estimation of 3',5'-diiodothyronine (3',5'-T2) and 3,3'-diiodothyronine (3,3'-T2) in human urine have been established. The urinary excretion of both glucuronide and sulfate conjugates of T2 and of T4, T3, and rT3 were estimated by means of enzymatic deconjugation. In healthy controls, the mean excretion (picomoles per 24 h) of free T4 was 1820, that of free T3 was 813, that of free rT3 was 77, that of free 3',5'-T2 was 13, and that of free 3,3'-T2 was 674. The total excretion of free and conjugated T4 was 2941, that of T3 was 1283, that of rT3 was 791, that of 3',5'-T2 was 709, and that of 3,3'-T2 was 2688. Significant amounts of sulfated T4 and T3 could not be demonstrated, amounts of sulfated T4 and T3 could not be demonstrated, whereas the excretion of sulfated rT3 was higher than that of glucuronidated rT3 (P less than 0.001). In contrast, glucuronidated and sulfated 3',5'-T2 as well as glucuronidated and sulfated 3,3'-T2 were found in the urine in equal amounts. In hyperthyroidism, the excretions of free and glucuronidated iodothyronines were increased, whereas the increase of the excretions of sulfated iodothyronines were less pronounced, only reaching statistical significance for 3,3'-T2 (P less than 0.02). In hypothyroidism, the excretions of both free, glucuronidated and sulfated iodothyronines were reduced. Significant amounts of sulfated T4 and T3 could not be demonstrated in urine from hyperthyroid or hypothyroid patients. Our data demonstrate that the amounts of free iodothyronines excreted in the urine vary considerably, suggesting active renal handling. The amounts of urinary glucuronidated and sulfated conjugates of the different iodothyronines studied vary considerably and are affected by thyroid function.

Topics: Cross Reactions; Diiodothyronines; Glucuronates; Humans; Hyperthyroidism; Hypothyroidism; Radioimmunoassay; Sulfuric Acids; Thyroid Gland; Thyronines

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

An heterologous radioimmunoassay for measurement of 3'-monoiodothyronine (3'T1) has been developed using pure 3'T1 as standard, (125I)DL3'T1 and an anti 3,3'L-diiodothyronine antiserum. The assay utilizes Sephadex G25F minicolumns to separate 3'T1 from other endogenous iodothyronines. 8-anilino-1-naphthalene sulphonic acid was used to inhibit binding of 3'T1 to serum binding proteins. Sensitivity was approximately 3.2 pmol/l. The mean serum 3'T1 concentration was 7.4 pmol/l in normal subjects, 30.8 pmol/l in thyrotoxic patients, 4.1 pmol/l in hypothyroid patients, 23.2 pmol/l in patients with severe non-thyroidal illness and 109.8 pmol/l in cord blood. Increased levels of 3'T1 were found in two normal volunteers who were injected with 3,3'T2, demonstrating that 3'T1 is derived from 3,3'T2 in extrathyroidal tissues. These studies suggest that 3'T1 is a minor iodothyronine metabolite in the human. It is unlikely to have significant biological relevance.

Topics: Adult; Diiodothyronines; Female; Fetal Blood; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Male; Middle Aged; Radioimmunoassay; Reference Values; Thyronines

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

The measurements of circulating total thyroxine (T4) and total triiodothyronine (T3) depend on the concentrations of thyroid hormone binding proteins, especially TBG. A simple approach, the calculation of free T3 index (FT3I) and augmented FT3I (aFT3I) from total T3 and T3-resin uptake, corrects the total serum T3 for variation in thyroid hormone binding capacity. In a group of 95 patients with borderline elevated T3 levels (3.0-4.5 nmol/l) we have correlated the results of FT3I and aFT3I with clinical, biochemical and radioisotope findings: in a subgroup of 23 euthyroid females taking oestrogens (group A1) and in 22 other patients with TBG elevations (independent of oestrogens, group A2) the results for total T3 were within the slightly hyperthyroid range (3.32 +/- 0.3 and 3.26 +/- 0.24 nmol/l respectively), but FT3I was always within the normal range. In contrast, FT3I was clearly elevated in 50 hyperthyroid patients (group B) compared to the total T3 (4.6 +/- 0.6 and 3.9 +/- 0.4 nmol/l respectively). An even better discrimination was obtained by calculation of augmented FT3I. It is concluded that in patients with moderate elevations of T3 the FT3I and aFT3I are capable of distinguishing clearly between the euthyroid and hyperthyroid range. The estimation is thus indicated in all patients with changes in thyroid hormone binding protein concentration and is of great value in confirming or ruling out the diagnosis of T3-toxicosis, T4-toxicosis and in all cases of "preclinical" or borderline hyperthyroidism.

Topics: Diagnosis, Differential; Female; Humans; Hyperthyroidism; Thyronines; Thyroxine; Thyroxine-Binding Proteins

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

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

Topics: Cross Reactions; Diiodothyronines; Fasting; Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Radioimmunoassay; Reference Values; Thyronines; Thyroxine; Triiodothyronine

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

Conversion of thyroxine (T(4)) to 3,5,3'-triiodothyronine (T(3)) in rat brain has recently been shown in in vivo studies. This process contributes a substantial fraction of endogenous nuclear T(3) in the rat cerebral cortex and cerebellum. Production of T(4) metabolites besides T(3) in the brain has also been suggested. To determine the nature of these reactions, we studied metabolism of 0.2-1.0 nM [(125)I]T(4) and 0.1-0.3 nM [(131)I]T(3) in whole homogenates and subcellular fractions of rat cerebral cortex and cerebellum. Dithiothreitol (DTT) was required for detectable metabolic reactions: 100 mM DTT was routinely used. Ethanol extracts of incubation mixtures were analyzed by paper chromatography in t-amyl alcohol:hexane:ammonia and in 1-butanol:acetic acid. Rates of production of iodothyronines from T(4) and T(3) were greater at pH 7.5 than at 6.4 or 8.6 and greater at 37 degrees C than at 22 degrees or 4 degrees C. Lowering the pH, reducing the protein or DTT concentrations, and preheating homogenates to 100 degrees C all increased excess I(-) production but reduced iodothyronine production. In cerebral cortical homogenates from normal rats, products of T(4) degradation were as follows (percent added T(4)+/-SEM in nine experiments): T(3), 1.9+/-0.5%; 3,3',5'-triiodothyronine (rT(3)), 34.0+/-2.4%; 3,3'-diiodothyronine (3,3'-T(2)), 5.8+/-1.6%; 3'-iodothyronine (3'-T(1)),

Topics: Animals; Brain; Dithiothreitol; Hydrogen-Ion Concentration; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Iodine; Iopanoic Acid; Male; Rats; Subcellular Fractions; Temperature; Thyronines; Thyroxine; Time; Triiodothyronine

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

Topics: Adolescent; Adult; Aged; Cross Reactions; Diiodothyronines; Female; Humans; Hyperthyroidism; Hypothyroidism; Liver Cirrhosis; Male; Middle Aged; Radioimmunoassay; Thyroid Neoplasms; Thyronines

Topics: Amniotic Fluid; Diiodothyronines; Female; Fetal Blood; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Pregnancy; Radioimmunoassay; Thyroglobulin; Thyroid Gland; Thyronines; Thyroxine; Triiodothyronine

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

Topics: Acute Disease; Diiodothyronines; Humans; Hyperthyroidism; Hypothyroidism; Liver Cirrhosis; Myocardial Infarction; Thyronines; Uremia

A specific radioimmunoassay for measurement of 3,3'-diiodothyronine (T2') is presented. With the method described (ethanol extraction of native serum and lyophilisation of the extract) the application of 400 microliter serum equivalent in the assay is possible. Standards and sera are treated similarly. The detection limit is 0.625 ng/dl, comparison between direct assay and dried extract assay shows good correlation. Mean normal T2' serum concentration in man is 7.2 ng/dl (range 3 to 11 ng/dl), hypothyroid: below 3.0 ng/dl, hyperthyroid: 11-64 ng/dl (range). T2' level in cord-blood of newborns: 16.5 ng/dl. The urinary excretion of free T2' of normal man is 0.49 microgram/24 h (mean), a relatively high excretion rate in comparison to the low serum level.

Topics: Adult; Cross Reactions; Fetal Blood; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Protein Binding; Radioimmunoassay; Reference Values; Thyronines; Thyroxine-Binding Proteins

The present report describes a RIA for 3',5'-diiodothyronine (T2) that can be performed on unextracted serum and which has a lower limit of detectability of 2 ng/dl. Cross-reactivity with other iodothyronines was negligible, except for rT3 which began to demonstrate cross-reactivity when rT3 levels were elevated to 180 ng/dl. Employing this RIA for T2, we have determined that 83 healthy individuals had a mean (+/-SE) serum T2 concentration of 5.0 +/- 0.3 ng/dl, thyrotoxic subjects (n = 12) had a mean T2 level that was elevated to 10.8 +/- 0.8 ng/dl, and each of 6 hypothyroid subjects had undetectable (less than 2 ng/dl) concentrations. Athyreotic patients (n = 8), receiving 0.4 mg T4 daily, had serum T2 concentrations of 15.0 +/- 3.0 ng/dl. Fasting in obese subjects was associated with an increase in serum T2 to 6.9 +/- 0.6 ng/dl from a basal level of 4.4 +/- 0.4 ng/dl in the fed state (P less than 0.01). Despite the fact that rT3 levels may be elevated in amniotic fluid and that rT3 is expected to represent the major source from which extrathyroidal T2 arises, T2 levels were low in amniotic fluid, being undetectable (less than 2 ng/dl) in 9 of 19 samples; the mean (+/-SE) T2 concentration in the 10 detectable samples was 5.4 +/- 1 ng/dl. These data indicate T2 is a normal component of serum and that the majority of serum T2 is probably derived from peripheral conversion. Furthermore, these observations suggest that situations associated with elevated rT3 levels (e.g. thyrotoxicosis and fasting) may also have increased T2 values.

Topics: Amniotic Fluid; Diiodothyronines; Female; Fetal Blood; Humans; Hyperthyroidism; Hypothyroidism; Immune Sera; Obesity; Pregnancy; Radioimmunoassay; Reference Values; Thyronines

A simple, reproducible, and highly specific RIA has been developed for measurement of 3',5'-diiodothyronine ((3',5'-T2) in unextracted serum. Interference in binding of radioactive 3',5'-T2 to anti-3',5'-T2 by serum proteins was minimized by using 0.4 M phosphate buffer (pH 6.2) and merthiolate. The detection threshold of the RIA was 2.5 ng/100 ml. Recovery of nonradioactive 3',5'-T2 added to serum averaged 99%. T4, T3, and rT3 cross-reacted with 3',5'-T2-binding sites on anti-3',5'-T2 antibody only to the extent of 0.0025, less than 0.0004, and 0.22%, respectively. 3'-Monoiodothyronine cross-reacted 1.7%. Serum 3',5'-T2 concentrations were (mean +/- SD) 6.4 +/- 2.4 ng/100 ml in 53 normal subjects, 4.2 +/- 3.5 ng/100 ml in 7 hypothyroid patients, 14.9 +/- 7.7 ng/ml in 25 patients with hepatic cirrhosis, and 14.3 +/- 5.3 ng/100 ml in 31 newborns' cord blood sera. The values in each of the latter four groups were significantly different from normal. The mean serum 3',5'-T2 concentration of 7.7 +/- 2.5 ng/ml in eight subjects in the third trimester of pregnancy did not differ significantly from normal at a time when serum T4 and T3 were clearly elevated. Oral administration of 300 microgram rT3 to 9 normal subjects led to a mean maximal increase in serum 3',5'-T2 concentration of 45% at 1 h. Total fasting in 3 obese subjects was associated with a significant increase in serum 3',5'-T2 from 8.6 to 16.3 ng/100 ml at 6-8 days; serum rT3 increased similarly, while serum T3 decreased and T4 did not change. Administration of dexamethasone (2 mg also associated with nearly parallel increases in serum 3',5'-T2 and rT3 and a decrease in serum T3. 3',5'-T2 concentrations were also measured in amniotic fluids at different stages of gestation; the mean value of 15.2 ng/100 ml at 15-20 weeks gestation was significantly higher than that of 5.8 ng/ml at 33-40 weeks gestation. Pronase hydrolysates of 9 autopsy specimens of normal thyroid glands contained (mean +/- SD) 350 +/- 144 microgram T4 and 0.24 +/- 0.15 microgram 3',5'-T2/g wet wt. On the basis of these data and those available for MCRs of 3',5'-T2 and T4, it was estimated that thyroidal secretion contributes less than 1% of 3',5'-T2 measured in serum of normal man. The various data suggest that: 1) 3',5'-T2 is a normal component of human serum; 2) almost all 3',5'-T2 in human serum derives from extrathyroidal sources; and 3) changes in serum 3',5'-2 generally parallel those in rT3.

Topics: Adolescent; Adult; Aged; Amniotic Fluid; Antibodies; Antibody Specificity; Diiodothyronines; Fasting; Female; Fetal Blood; Graves Disease; Humans; Hyperthyroidism; Hypothyroidism; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Pregnancy; Radioimmunoassay; Thyroid Gland; Thyroid Hormones; Thyronines

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

3,3'-Diiodothyronine (3,3'-T(2)) has been detected in human serum and in thyroglobulin. However, no quantitative assessment of its clearance rate (CR), production rate (PR), or of the importance of extrathyroidal sources of 3,3'-T(2) relative to direct thyroidal secretion is yet available. This study examines these parameters in seven euthyroid subjects, and in eight athyreotic subjects (H) eumetabolic due to thyroxine therapy (HT(4)) (n = 5) or triiodothyronine replacement (HT(3)) (n = 3). A highly specific radioimmunoassay for the measurement of 3,3'-T(2) in whole serum was developed. Serum 3,3'-T(2) concentrations were (mean +/- SD) 6.0+/-1.0 ng/100 ml in 13 normal subjects, 9.0+/-4.6 ng/100 ml in 25 hyperthyroid patients, and 2.7+/-1.1 ng/100 ml in 17 hypothyroid patients. The values in each of the latter two groups were significantly different from normal. 3,3'-T(2) was detected regularly in normal concentrations in 11 hypothyroid patients eumetabolic by treatment with synthetic T(4), in 10 eumetabolic patients suffering from nonthyroidal systemic illness, and in 2 subjects with elevated serum T(4)-binding globulin. The 3,3'-T(2) CR was assessed from data acquired from the (125)I-3,3'-T(2) constant infusion technique. The 3,3'-T(2) PR was calculated from CR and serum concentration of 3,3'-T(2) determined by radio-immunoassay. In the HT(4) subjects the 3,3'-T(2) CR averaged 840+/-377 liters/day and 3,3'-T(2) PR 33.9+/-12.5 mug/day. These results were not significantly different from those in the control group: 3,3'-T(2) CR 628+/-218 liters/day and 3,3'-T(2) PR 39.8+/-19.8 mug/day (all corrected to 70 kg body wt). In addition to 3,3'-T(2) PR, T(3), and reverse triiodothyronine (rT(3)) PR were determined in three of the HT(4) subjects. In each case studied, the 3,3'-T(2) PR was close to the combined triiodothyronine (T(3) + rT(3)) PR. The mean molar ratio of T(2) PR/(T(3) + rT(3)) PR was 1.08+/-0.10. The results obtained in the HT(4) subjects indicate that the production of 3,3'-T(2) is a major route of T(4) metabolism. The combined studies of 3,3'-T(2), T(3) and rT(3) PR in the HT(4) subjects indicate that both T(3) and rT(3) are major precursors of 3,3'-T(2). In the HT(3) subjects, the conversion of T(3) to 3,3'-T(2), determined as the molar ratio of 3,3'-T(2) PR to T(3) PR, ranged from 0.36 to 0.92, providing further evidence that T(3) is a precursor of 3,3'-T(2). From the close agreement between the mean values for 3,3'-T(2) PR in the euthyroid and

Topics: Humans; Hyperthyroidism; Hypothyroidism; Kinetics; Metabolic Clearance Rate; Radioimmunoassay; Thyroidectomy; Thyronines; Triiodothyronine

Topics: Adolescent; Adult; Aged; Animals; Anorexia Nervosa; Antibody Specificity; Bile; Binding Sites, Antibody; Child; Female; Glucuronidase; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Radioimmunoassay; Rats; Sulfatases; Thyronines; Thyroxine; Triiodothyronine

A sensitive, specific and reproducible radioimmunoassay (RIA) for measurement of 3,3'-L-diiodothyoride (T2) in concentrated ethanol extracts of serum and amniotic fluid is described. The T2 binding antiserum was prepared aby immunization of rabbits with T2-human serum albumin conjugate. Of various thyroid hormone derivatives tested, only 3-L-monoiodothyonine cross-reacted significantly with T2 binding sites on the antiserum...

Topics: Amniotic Fluid; Cross Reactions; Female; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Liver Cirrhosis; Pregnancy; Radioimmunoassay; Thyronines

Topics: Age Factors; Aged; Humans; Hyperthyroidism; Hypothyroidism; Middle Aged; Thyronines; Triiodothyronine

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Thyroid (USP); Thyronines; Thyrotropin

A highly specific antiserum to 3,3',5'-triiodothyronine (reverse T(3), rT(3)) was prepared by immunization of rabbits with D,L-rT(3)-human serum albumin conjugate. Of the various thyroid hormone derivatives tested, only 3,3'-diiodothyronine (3,3'-T(2)) cross-reacted significantly (10%) with rT(3)-binding sites on the antiserum, while thyroxine (T(4)) and triiodothyronine (T(3)) cross-reacted by less than 0.1%. The antiserum was used in a simple, sensitive, precise, and reproducible radioimmunoassay (RIA) for measurement of rT(3) in ethanolic extracts of serum. The dose-response curves of inhibition of the binding of [(125)I]rT(3) to antibody obtained by serial dilutions of serum extracts were essentially parallel to the standard assay curve. Recovery of nonradioactive rT(3) added to serum before extraction averaged 93%. Serum rT(3) concentrations were found to be (mean+/-SD) 41+/-10 ng/100 ml in 27 normal subjects, 103+/-49 ng/100 ml in 22 hyperthyroid patients, 19+/-9 ng/100 ml in 12 hypothyroid patients, and 54+/-7 ng/100 ml in five subjects with elevated serum thyroxine-binding globulin: the values in each of the latter three groups of individuals were significantly different from normal. Reverse T(3) was detected regularly in normal or supranormal concentrations in serum of 12 hypothyroid patients rendered euthyroid or mildly hyperthyroid by treatment with synthetic T(4). It is suggested that serum rT(3) values noted here should be taken to reflect the relative changes in serum rT(3) rather than its absolute values in health and thyroid disease. True serum rT(3) may be somewhat different because: (a) D.L-rT(3) employed in the standard curve and L-rT(3) present in human serum may react differently with anti-D,L-rT(2). (b) Even though 3,3'-T(2), which cross-reacted 10% in rT(3) RIA, has been considered unlikely to be present in human serum, it may circulate in low levels. (c) Cross-reaction of T(4) in rT(3) RIA of 0.06% although small, could contribute to RIA estimates of rT(2); the effect of T(4) would be particularly important in case of serum of hyperthyroid patients. Thus, serum rT(3) concentration in hyperthyroid patients averaged 89+/-48 mug/100 ml after correction for cross-reaction effects of T(4): this value was about 14% lower than that before correction (see above). Serum rT(3) concentration in cord sera of seven newborns averaged 136+/-19 ng/100 ml; it was clearly elevated and within the range of values seen in hyperthyroid patients. This wa

Topics: Adult; Animals; Blood; Cross Reactions; Female; Humans; Hyperthyroidism; Hypothyroidism; Immune Sera; Infant, Newborn; Iodine Radioisotopes; Male; Methods; Protein Binding; Rabbits; Radioimmunoassay; Serum Albumin; Thyroglobulin; Thyronines; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Umbilical Cord

Topics: Adult; Carbon Radioisotopes; Dopamine beta-Hydroxylase; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Thyroid Diseases; Thyronines; Triiodothyronine

Topics: Animals; Calcium; Carbimazole; Gerbillinae; Gluconates; Hyperthyroidism; Hypothyroidism; Kidney; Male; Nephrocalcinosis; Thyroid Diseases; Thyronines

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Aorta; Arteriosclerosis; Diet, Atherogenic; Dietary Fats; Enzyme Repression; Esterases; Female; Hyperthyroidism; L-Lactate Dehydrogenase; Malate Dehydrogenase; Nucleotidases; Oxidoreductases; Pyrophosphatases; Rats; Thyroid Hormones; Thyronines

Topics: Adult; Aged; Antithyroid Agents; Chemical Phenomena; Chemistry; Female; Humans; Hyperthyroidism; Imidazoles; Male; Methylthiouracil; Perchlorates; Propylthiouracil; Sympatholytics; Thiouracil; Thyroid Hormones; Thyronines

Topics: Animals; Binding Sites; Cattle; Chromosome Aberrations; Chromosome Disorders; Dogs; Female; Graves Disease; Guinea Pigs; Haplorhini; Humans; Hyperthyroidism; Iodine Isotopes; Male; Methods; Pregnancy; Propylthiouracil; Protein Binding; Rabbits; Radioimmunoassay; Rats; Serum Albumin; Serum Globulins; Sheep; Thyronines; Thyroxine; Triiodothyronine

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Electrocardiography; Hyperthyroidism; Male; Methionine; Myocardium; Phonocardiography; Potassium; Rabbits; Sodium; Thyroid Hormones; Thyronines; Time Factors; Vectorcardiography

Topics: Amino Acids; Animals; Anxiety; Chromatography, Paper; Diiodotyrosine; Female; Humans; Hyperthyroidism; Iodine Isotopes; Male; Monoiodotyrosine; Rabbits; Thyroid Gland; Thyronines; Thyroxine; Triiodothyronine

Topics: Adult; Blood Protein Disorders; Female; Goiter; Humans; Hyperthyroidism; Kidney Failure, Chronic; Proteinuria; Radionuclide Imaging; Thyroglobulin; Thyronines; Thyroxine

Topics: Adolescent; Adult; Blood Urea Nitrogen; Edema; Exophthalmos; Eye Manifestations; Female; Humans; Hyperthyroidism; Kidney Failure, Chronic; Long-Acting Thyroid Stimulator; Male; Middle Aged; Nephrectomy; Ophthalmoscopy; Pituitary Gland; Pituitary Hormone-Releasing Hormones; Renal Dialysis; Thyroid Function Tests; Thyroid Gland; Thyronines; Thyrotropin; Thyroxine-Binding Proteins; Uremia

Topics: Ammonia; Ammonium Sulfate; Arsenic; Bromates; Bromides; Cerium; Chemistry, Clinical; Chromatography, Ion Exchange; Hydrogen-Ion Concentration; Hyperthyroidism; Hypothyroidism; Iodine; Methods; Sulfuric Acids; Thyronines; Thyroxine; Triiodothyronine

Topics: Colorimetry; Goiter; Humans; Hyperthyroidism; Hypopituitarism; Ion Exchange Resins; Thyroiditis; Thyronines; Thyroxine

Topics: Blood Proteins; Cell Membrane; Chemical Phenomena; Chemistry; Chromatography, Gel; Dialysis; Erythrocytes; Humans; Hyperthyroidism; Hypothyroidism; Iodine Isotopes; Protein Binding; Thyronines; Thyroxine; Thyroxine-Binding Proteins

Topics: Diiodotyrosine; Graves Disease; Humans; Hyperthyroidism; Male; Middle Aged; Monoiodotyrosine; Thyroid Gland; Thyroid Hormones; Thyronines; Thyroxine; Triiodothyronine

Topics: Adolescent; Adult; Aged; Chemical Phenomena; Chemistry, Physical; Chlorides; Chromatography, Paper; Cyanides; Drug Stability; Electrophoresis, Paper; Erythrocytes; Female; Goiter; Hot Temperature; Humans; Hyperthyroidism; Iodides; Iodine Isotopes; Iodine Radioisotopes; Kinetics; Leukocytes; Male; Mercury; Middle Aged; Oxygen; Potassium; Thyroid Function Tests; Thyroid Gland; Thyronines

Topics: Chromatography, Paper; Dialysis; Drug Contamination; Humans; Hyperthyroidism; Hypothyroidism; Iodine Isotopes; Thyronines; Thyroxine; Triiodothyronine

Topics: Chromatography, Gel; Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Serum Albumin, Radio-Iodinated; Thyronines

Topics: Adult; Autoradiography; Basal Metabolism; Chromatography, Paper; Diiodotyrosine; Electrophoresis; Female; Humans; Hyperthyroidism; Iodides; Iodine Isotopes; Male; Middle Aged; Sodium; Thyroid Function Tests; Thyronines; Thyroxine; Triiodothyronine

Topics: Adolescent; Adult; Barbiturates; Humans; Hyperthyroidism; Middle Aged; Reserpine; Thyronines

Topics: Adolescent; Adult; Autoradiography; Female; Goiter; Humans; Hyperthyroidism; Male; Middle Aged; Myxedema; Technetium; Thyroid Diseases; Thyroid Gland; Thyronines; Thyroxine; Tyrosine

Topics: Animals; Collagen; Glycosaminoglycans; Gossypium; Granuloma; Hydroxyproline; Hyperthyroidism; Neoplasms, Experimental; Rats; Thyroid Gland; Thyronines

Topics: Chemistry, Clinical; Chromatography, Paper; Diiodotyrosine; Humans; Hyperthyroidism; Iodides; Thyronines; Thyroxine; Triiodothyronine; Tyrosine

Topics: Goiter; Humans; Hyperthyroidism; Iodine; Thyroid Hormones; Thyronines; Thyrotropin; Thyroxine; Tissue Extracts; Triiodothyronine

Topics: Cardiovascular Diseases; Female; Heart Diseases; Humans; Hyperthyroidism; Male; Middle Aged; Thyroid Function Tests; Thyronines

Topics: Aging; Alanine; Amino Acids; Aminobutyrates; Animals; Aorta; Carbon Isotopes; Diabetes Mellitus, Experimental; Geriatrics; Glycine; Hyperthyroidism; Hypothyroidism; Insulin; Leucine; Propylthiouracil; Proteins; Rats; Research; Thyronines

Topics: Child; Diabetes Mellitus; Erythrocytes; Hyperthyroidism; Hypothyroidism; Iodine Isotopes; Pediatrics; Thyroid Function Tests; Thyronines

Topics: Biomedical Research; Brain; Electroencephalography; Hyperthyroidism; Light; Pharmacology; Thyroid Hormones; Thyronines; Triiodothyronine

Topics: Blood Chemical Analysis; Chromatography; Geriatrics; Goiter; Hyperthyroidism; Iodine Isotopes; Monoiodotyrosine; Myxedema; Neoplasms; Propylthiouracil; Thiourea; Thyronines; Thyroxine; Tyrosine

Topics: Drug Therapy; Goiter; Hyperthyroidism; Hypothyroidism; Iodine Isotopes; Myxedema; Thyroid Function Tests; Thyroidectomy; Thyronines; Thyroxine

Topics: Drug Therapy; Goiter; Graves Disease; Humans; Hyperthyroidism; Methylthiouracil; Thyroid Hormones; Thyronines

Topics: Diiodotyrosine; Humans; Hyperthyroidism; Male; Thyroid Hormones; Thyronines; Thyrotropin; Triiodothyronine

Topics: Hyperthyroidism; Iodine; Iodine Isotopes; Thyroid Function Tests; Thyronines; Thyrotoxicosis

Topics: Humans; Hyperthyroidism; Thyronines; Thyroxine

Topics: Graves Disease; Humans; Hyperthyroidism; Iodine; Thyroid Gland; Thyronines; Triiodothyronine