triiodothyronine--reverse and Graves-Disease

We have evaluated three regimens for the rapid control (10 days' therapy) of thyrotoxicosis in hyperthyroid Graves' disease: methimazole (MMI, 40 mg/day), MMI and sodium ipodate (MMI + Na Ipodate, 1 g/day and MMI and saturated solution of potassium iodide (MMI + SSKI, 6 drops twice daily). When serum T4 and T3 concentrations were analysed as the percent change from pre-treatment values, the following results were observed. Serum T4 concentration decreased in the three treatment groups and the decrease was similar in the MMI and MMI + SSKI groups but significantly lower than in the MMI + Na ipodate group. The serum T3 concentration decreased to the normal range in all seven MMI + Na Ipodate treated patients by the fourth day of treatment and the per cent decrease in serum T3 from pre-treatment values was significantly greater than in the MMI and MMI + SSKI treated patients. The decrease in serum T3 was similar in the latter two groups. Heart rate decreased in all three groups, but the decrease was significantly more in the MMI + Na Ipodate-treated patients. The present findings suggest that the rapid control of hyperthyroid Graves' disease is similar in patients treated with MMI and MMI + SSKI and that the combination of MMI + Na Ipodate is more efficacious since the decrease in serum T3 concentrations and heart rate was significantly greater in the MMI + Na ipodate-treated patients.

Topics: Adult; Blood Pressure; Drug Evaluation; Drug Therapy, Combination; Female; Graves Disease; Heart Rate; Humans; Ipodate; Male; Methimazole; Middle Aged; Potassium Iodide; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The clinical implications of nuclear T3R alterations of circulating lymphocytes in hyperthyroidism, hypothyroidism and nonthyroidal diseases were investigated. Nuclear T3R in lymphocytes was determined by radio-ligand binding analysis. The results showed that in hyper- and hypothyroid patients the nuclear affinity (Ka) for T3 was similar to that of normal subjects. In hyperthyroidism nuclear T3 maximal binding capacity (MBC) was unaltered, whereas in hypothyroidism the MBC was significantly increased. In the patients with diabetes mellitus, chronic renal failure and hepatic cirrhosis, the nuclear T3R MBC of lymphocytes was about 1.5-1.6 times of the normal controls. It was concluded that there existed hormonal regulation of nuclear T3R, and up-regulation was seen in hypothyroidism and low T3 syndrome.

Topics: Diabetes Mellitus; Graves Disease; Humans; Hypothyroidism; Kidney Failure, Chronic; Lymphocytes; Receptors, Thyroid Hormone; Triiodothyronine, Reverse

Topics: Adult; Female; Graves Disease; Humans; Male; Middle Aged; Propranolol; Triiodothyronine, Reverse

Concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) in the placenta were measured in 7 patients with abortion, in 9 patients with premature delivery, in 16 normal pregnancies and in 4 pregnant women with Graves' disease. The placentas, obtained at delivery, were homogenized and centrifuged at 800 X g. T4, T3 and rT3 concentrations in the supernatants were extracted with 3 vol. of 99% ethanol and measured by RIAs. In normal pregnancy, placental T4, T3 and rT3 concentrations were 18.8 +/- 5.9 (mean +/- SD), 0.026 +/- 0.012, and 1.70 +/- 0.49 ng/g tissue, respectively. Ratios of rT3/T3 and rT3/T4 in the placenta were about 12 and 2.3 times as high as those in the fetal sera, respectively. There was a significant positive correlation between the placental T4 and the maternal or cord serum T4 concentrations. However, no correlation was found between the placental T3 or rT3 concentrations and the maternal or cord T3 or rT3 concentrations. In 4 patients with Graves' disease, the placental T4 concentration was elevated. These results indicate that the placental T4 concentration is influenced by both the maternal and fetal serum T4, and elevated ratios of rT3/T3 and rT3/T4 in the placenta might be due to the active placental 5-monodeiodination.

Topics: Abortion, Spontaneous; Female; Fetal Blood; Graves Disease; Humans; Obstetric Labor, Premature; Placenta; Pregnancy; Pregnancy Complications; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

A new type of serum albumin, that shows a markedly enhanced binding activity for 3,3', 5-triiodothyronine (T3), a somewhat increased activity for thyroxine (T4), and a normal activity for 3,3', 5-triiodothyronine (rT3) is described. This albumin was found in a patient with Graves' disease. After successful subtotal thyroidectomy, the existence of abnormal binding activity for T3 was suspected in this patient because of persistently increased total T3 concentrations in spite of elevated thyrotropin levels. Although free T3 and T4 concentrations measured by radioimmunoassay using commercial tracer analogue kits were markedly increased, those measured by equilibrium dialysis were within normal ranges. Electrophoretic studies revealed that these abnormalities were due to the markedly increased T3 binding activity by the serum albumin; that for T4 was also slightly increased. Scatchard plot analysis revealed that the association constant (Ka) for T3 of the patient's albumin was 5.1 X 10(6)/M (normal pooled albumin; 6.2 X 10(5)/M), and those for T4 and rT3 were 5.2 X 10(6)/M and 2.7 X 10(6)/M, respectively (normal pooled albumin; 2.1 X 10(6)/M for both T4 and rT3). The increased binding of albumin to T3 and T4 was markedly inhibited by barbitone, and 8-anilino-1-naphthalene-sulfonic acid. These characteristic features, and erroneously high values of free T3 and T4 concentrations measured by tracer analogue kits were similar to those seen in patients with familial dysalbuminemic hyperthyroxinemia, which have been previously reported. These findings strongly suggest that this albumin is a new variant in various dysalbuminemic syndromes, and the abnormal binding of iodothyronines moieties in these syndromes are not biochemically identical.

Topics: Adult; Binding Sites; Female; Graves Disease; Humans; Protein Binding; Radioimmunoassay; Serum Albumin; Thyroid Function Tests; Thyroxine; Triiodothyronine; 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

Patients with thyrotoxic Graves' disease were treated daily for 10 d with 1 g sodium ipodate, an iodine rich X-ray contrast agent which impairs outer ring (5'-) deiodination of T4 to T3, or with 12 drops of a saturated solution of potassium iodide (SSKI). T4, T3 and reverse T3 (rT3) concentrations were measured before, during, and 5 and 10 d after the administration of each drug. SSKI therapy induced a decrease in the serum T4 concentration from 14.7 +/- 1.3 microgram/dl (mean +/- SE) to a nadir of 7.9 +/- 0.9 on days 9 and 10 of therapy, all values reaching the normal range by day 9; a decrease in the serum T3 concentration from 402 +/- 43 ng/dl to a nadir of 143 +/- 20 on day 10, remaining elevated in all patients until day 5 and decreasing into the normal range in all except one patient on days 9 and 10; and no change in the serum rT3 concentration. Serum T4 and T3 concentrations returned to baseline values 10 d after withdrawal of SSKI. In contrast sodium ipodate therapy induced only a modest decrease in the serum T4 concentration from 15.1 +/- 0.7 micrograms/dl to a nadir on day 9 of 11.3 +/- 1.0 and serum T4 remained above the normal range in most patients until day 8; a striking and rapid decrease (within 12 h) in ther serum T3 concentration from 340 +/- 36 ng/dl to mean values ranging from 79 to 85 during the last 5 d of therapy, with most values below the normal range during the last 3 d; and a marked increase in the serum rT3 concentration from 111 +/- 15 ng/dl to a peak value of 376 +/- 59 on day 5.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Female; Graves Disease; Humans; Ipodate; Male; Potassium Iodide; Thyroid Hormones; 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

To investigate the long term usefulness of sodium ipodate (Oragrafin) in the management of Graves' hyperthyroidism, we studied the effects of ipodate (500 mg, orally, daily for 23-31 weeks) on serum T3, T4, rT3, and some clinical parameters in five newly diagnosed Graves' hyperthyroid patients. Mean pretreatment serum T3, T4, and rT3 concentrations were 780 ng/dl, 25.4 micrograms/dl, and 118 ng/dl, respectively. One day after the first dose of ipodate, serum T3 decreased by 62% (P less than 0.01), and it was within the normal range thereafter throughout treatment. The serum T4 concentration decreased by 20% (P = 0.09) at 24 h and by 43% (P less than 0.05) at 14 days. Subsequently, serum T4 was 41-65% lower than before treatment throughout the study; rT3 increased 24 h after the first dose of ipodate (118% above baseline; P = 0.1), remained elevated (97-109%) for 10 weeks, and then gradually decreased to the pretreatment level. A marked gain in body weight [5.1 +/- 1.1 (+/- SEM) kg] occurred in all patients. After discontinuation of ipodate, mean thyroid radioiodine (RAI) uptake values increased serially in four patients and were similar to pretreatment values: pretreatment, 74 +/- 6% (+/- SEM); after 7 days, 66 +/- 8%; after 14 days, 71 +/- 7%; after 28 days, 69 +/- 7%. The fifth patients's RAI uptake was 12-16% (vs. a pretreatment value of 48%) from 7-28 days after the end of a 31-week course of ipodate. He remained euthyroid without further treatment for the subsequent 4 months. We conclude that 1) ipodate (500 mg daily) reduces serum T4 and T3 levels as fast and as much as does the 1-g daily dose studied previously; 2) long term use (for 23-31 weeks) of ipodate for the treatment of Graves' hyperthyroidism is clinically feasible; no adverse effects occurred during or after ipodate treatment; and 3) RAI uptake returns to pretreatment levels as early as 7 days after the discontinuation of ipodate. Hence, use of ipodate does not prevent use of 131I therapy for those patients for whom it is otherwise desirable.

Topics: Adult; Female; Graves Disease; Humans; Ipodate; Long-Term Care; Male; Middle Aged; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Eleven euthyroid patients with severe exophthalmos of Graves' disease who had been treated with antithyroidal drugs for one to three years prior to total thyroidectomy were studied. All patients were clinically and biochemically euthyroid at the time of operation. According to their responses of TSH to TRH prior to operation, the patients were divided into two groups: (1) five responders and (2) six nonresponders. In group 1, serum TSH levels increased significantly on the third day after thyroidectomy (from 1.5 +/- 0.3 to 8.6 +/- 1.4 microU/mL: P less than 0.05); serum T4 concentrations decreased significantly and were in the hypothyroid range by the third day. In group 2, serum TSH levels rose from 0.5 +/- 0.01 to 3.2 +/- 0.5 microU/ml (P less than 0.05) on the ninth postoperative day; serum T4 concentrations decreased on the third day after operation but did not attain hypothyroid levels until the 12th day. Thus after total thyroidectomy the following are concluded: (1) serum TSH levels even in treated euthyroid patients with Graves' disease, rose more gradually in TRH-nonresponders in comparison with TRH responders; (2) the time when serum TSH elevation occurs is dependent upon serum concentrations of thyroid hormones (serum T3 and T4).

Topics: Adult; Female; Graves Disease; Humans; Male; Middle Aged; Thyroid Hormones; Thyroidectomy; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

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

To investigate the effect of the combination of dexamethasone (Dex) and sodium ipodate (SI) on hyperthyroidism, we studied 24 patients with typical Graves' disease, divided into four groups of six persons each. Three groups (Study I) were studied acutely (24 h) to determine the effects of Dex (5 mg every 12 h intramuscularly), SI (one oral dose of 3 g) and both drugs at the same doses, upon T4, T3, and rT3 at 0900 h before therapy was started and 24 h later. The group on Dex and that on SI had a similar T3 decrement of 25.9 +/- 4.0% and 35.8 +/- 5.0%, respectively, (P less than 0.05), whereas the effect of both drugs combined was greater (64.2 +/- 3.6%; P less than 0.01, Dex, and P less than 0.01, SI, respectively). The increment of rT3 was markedly greater in those patients on SI than in those on Dex (561.3 +/- 149.2% and 58.9 +/- 11%, respectively, P less than 0.025). A fourth group (Study II) was studied for seven days while receiving both Dex (1 mg orally three times per day) and SI (500 mg orally three times per day). Both T4 (from 18.8 +/- 1.1 to 13.1 +/- 1.1 micrograms/dl, P less than 0.02) and T3 (from 593 +/- 41 to 136.3 +/- 12.7 ng/dl, P less than 0.001) decreased at day 8. The initial brisk increment of rT3 at 24 h (808 +/- 149%, P less than 0.005) then diminished concomitantly with the fall of its precursor, T4.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Dexamethasone; Drug Therapy, Combination; Female; Graves Disease; Humans; Ipodate; Male; Middle Aged; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adult; Female; Graves Disease; Humans; Iodine; Iodine Radioisotopes; Kinetics; Male; Perchlorates; Potassium; Potassium Compounds; Propylthiouracil; Thyroid Gland; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adult; Blood Pressure; Body Weight; Female; Graves Disease; Humans; Ipodate; Kinetics; Male; Middle Aged; Propylthiouracil; Pulse; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The inner ring monodeiodination [T4 to rT3, T3 to 3,3'-diiodothyronine(3,3'-T2)] as well as the outer ring monodeiodination (T4 to T3, rT3 to 3,3'-T2) was demonstrated with thyroid tissues obtained from patients with Graves' disease by measuring the products by RIAs. Sequential deiodination of T4 to 3,3'-T2 was also recognized in normal human thyroid glands. These iodothyronine deiodinations were dependent on incubation time, tissue volume, temperature, pH, and concentration of dithiothreitol. The monodeiodination of rT3 to 3,3'-T2 proceeded very rapidly and the maximal production of 3,3'-T2 was obtained at about 5 min. In the other reactions, the products accumulated in an almost linear fashion during the period of 60 min. The optimal pH for 5-monodeiodination was 9.0, while that for 5-monodeiodination was 5.5-6.5. In the absence of dithiothreitol, all of these reactions were abolished. Propylthiouracil and iopanoic acid inhibited the reactions, whereas methimazole and potassium iodide had no effect. Kinetic study revealed that the apparent Km and maximum velocity of the conversion of T3 to 3,3'-T2 were 10.9 microM and 19 pmol 3,3'-T2/mg protein.min, respectively, and that those of rT3 to 3,3'-T2 were 0.37 microM and 80 pmol 3,3'-T2/mg protein.min, respectively. There was a significant difference in the conversion of T4 to rT3 between normal [0.56 +/- 0.04 pmol/mg protein.min (mean +/- SE)] and Graves' thyroids 0.88 +/- 0.06 pmol/mg protein min). Moreover, a significant difference was found between 3,3'-T2 production rate from T3 or rT3 in the Graves' thyroids and that in the normal thyroids. The overall reaction from T4 to 3,3'-T2 in the Graves' thyroids (4.04 +/- 0.70 pmol/mg protein.min) was significantly higher than that in the normal thyroids (0.63 +/- 0.11 pmol/mg protein.min; P less than 0.001). The results indicate the existence of 5-deiodinase that produces rT3 from T4 and 3,3'-T2 from T3, and 5'-deiodinase that produces T3 from T4 and 3,3'-T2 from T3, and 5'-deiodinase that produces T3 from T4 and 3,3'-T2 from rT3 in human thyroids. Accelerated conversion of T4 to 3,3'-T2 via either T3 or rT3 was observed in Graves' thyroid glands.

Topics: Diiodothyronines; Graves Disease; Humans; Hydrogen-Ion Concentration; Iodide Peroxidase; Iodine; Kinetics; Thyroid Gland; 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

Topics: Adolescent; Diabetic Ketoacidosis; Female; Graves Disease; Humans; Ketone Bodies; Thyroid Crisis; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Ten patients with hyperthyroidism due to Graves' disease were treated with sodium ipodate (1 g daily) in addition to propranolol (P) plus propylthiouracil (PTU; 100 mg every 8 h) and were compared with a control group of 8 patients treated with P and PTU. Patients on P and PTU had a mean (+/- SEM) basal free T3 index of 387 +/- 59 (normal, 70--160) compared with that of 409 +/- 47 (P greater than 0.05) in the sodium ipodate group. The respective basal free T4 index values (normal, 4.5-10.9) were 21.3 +/- 2.8 for the controls and 25.9 +/- 2.8 for the ipodate group (P greater than 0.5), and the basal rT3 values were 192 +/- 49 and 210 +/- 41 (normal, 16--50 ng/dl; P greater than 0.05). The average percent changes in each thyroid index and rT3 were calculated. The first 3 days on P and PTU served as the basal period for the control group, and comparisons were made to the following 9 days. The ipodate group received P and PTU for 2.7 +/- 3.0 days, and comparisons were made with the interval on ipodate, P, and PTU (mean, 9.1 +/- 0.9 days). For the free T3 index, the control group showed a mean decrement of 20.5 +/- 4.4% compared with 50.2 +/- 3.1% for the ipodate group (P less than 0.001). The respective free T4 index decrements were 14.5 +/- 4.4% and 18.5 +/- 2.7% (P greater than 0.05). The respective changes in rT3 were -13.4 +/- 7.6% and +140 +/- 26.9% (P less than 0.001). In patients with hyperthyroidism, short term daily therapy with sodium ipodate plus P and PTU produces a greater reduction of free T3 index values than that caused by P and PTU alone.

Topics: Female; Graves Disease; Humans; Ipodate; Kinetics; Male; Propranolol; Propylthiouracil; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The effects of long-term treatment with antithyroid drugs, carbimazole (CMI) or propylthiouracil (PTU), on serum reverse triiodothyronine (rT3) levels were studied in 23 patients with Graves' disease. Nineteen patients were given CMI and four PTU for a minimum of six months. After one month of treatment the serum levels of thyroxine (T4), triiodothyronine (T3) and rT3 had normalized in both groups. When L-thyroxine was added to the regimens after two months of therapy, both serum T4 and rT3 levels increased, whereas serum T3 level continued to fall. The serum levels of rT3 seemed to be dependent on and followed the T4 levels so closely that determinations of rT3 in the medical management of patients with Graves' disease will be of little clinical use.

Topics: Adult; Aged; Antithyroid Agents; Carbimazole; Female; Graves Disease; Humans; Male; Middle Aged; Propylthiouracil; Thyroid Hormones; Time Factors; Triiodothyronine; Triiodothyronine, Reverse

Topics: Carbimazole; Graves Disease; Humans; Male; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

This report describes the effect of administration of repeated doses of ipodate (Oragrafin; 3 g orally every third day for five doses) in six hyperthyroid patients. Baseline serum concentrations of immunoassayable T3, rT3, and T4, were 926 +/- 206 ng/100 ml, 165 +/- 31 ng/100 ml and 21 +/- 2.7 micrograms/100 ml (mean +/- SEM), respectively. Within 24 h after the first dose of ipodate, serum T3 fell by 54% and it remained between 66-77% below baseline until the third day after the fifth dose; subsequently, there was a gradual recovery from the effect of ipodate. Serum T4 also decreased after ipodate administration; it was 23-31% lower than baseline from the second day after the third dose to the sixth day after the fifth dose. Serum rT3 increased after each dose of ipodate; peak values of 97%-203% above baseline value were observed at 24-48 h after each dose. There was a subjective improvement in clinical symptoms of hyperthyroidism in all cases. Resting pulse rate and pulse pressure dropped significantly (P less than 0.02) by the ninth day of study and remained so thereafter. Body weight increased significantly by the ninth day of the study. The various data suggest that ipodate may serve as a useful adjunct in the early treatment of hyperthyroidism.

Topics: Adolescent; Adult; Body Weight; Drug Evaluation; Female; Graves Disease; Humans; Ipodate; Male; Middle Aged; Pulse; Thyroxine; 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: Graves Disease; Humans; Hyperthyroidism; Triiodothyronine; Triiodothyronine, Reverse