Serum Iodothyronine Concentrations Research Articles

Thyroid hormone responses to endurance exercise

Limited information exists about changes in circulating thyroid hormone concentrations during prolonged endurance exercise in horses. To examine the effects of prolonged exercise on serum iodothyronine concentrations in horses performing endurance exercise of varying distances. Serum concentrations of iodothyronines were measured in horses before and after completion of 40, 56, 80 and 160 km endurance rides (Study 1); daily during a 5 day, 424 km endurance ride (Study 2); and before and for 72 h after completion of a treadmill exercise test simulating a 60 km endurance ride (Study 3). In Study 1, 40 and 56 km of endurance exercise had little effect on serum iodothyronine concentrations with the exception of a 10% decrease (P<0.05) in free thyroxine (FT4) concentration after the 56 km ride. In contrast, total thyroxine (T4), total triiodothyronine (T3), FT4 and free triiodothyronine (FT3) concentrations all decreased (P<0.05) after successful completion of 80 and 160 km rides, with decreases ranging from 13-31% and 47-54% for distances of 80 and 160 km, respectively. Further, pre-ride T4 concentration was lower (P<0.05) and FT3 concentration was higher (P<0.05) in horses competing 160 km as compared to horses competing over shorter distances. In Study 2, serum concentrations of T4, T3 and reverse triiodothyronine (rT3) progressively decreased (P<0.05) over the course of the multi-day ride. In Study 3, the greatest decrease (P<0.05) in all iodothyronines was observed at 12 h of recovery, ranging from 25% for FT4 to 53% for FT3, but all thyroid hormone concentrations had returned to the pre-exercise values by 24 h of recovery. Endurance exercise results in transient decreases in serum iodothyronine concentrations. These data are important to consider when thyroid gland function is assessed by measurement of serum iodothyronine concentrations in endurance horses.

Serum iodothyronine concentrations in intestinally decontaminated rats treated with a 5′-deiodinase type I inhibitor 6-anilino-2-thiouracil

Enteric bacteria have been postulated to have a role in thyroid economy by promoting the hydrolysis of thyroid hormone conjugates of biliary origin, thus permitting the absorption and recycling of thyroxine (T4) and triiodothyronine (T3). An enterohepatic circulation of T3 might be more pronounced under conditions in which type I iodothyronine deiodinase activity (5'D-I) is inhibited, because this augments the accumulation of T3 sulfate conjugates in bile. This potential of increased gut reabsorption of T3 might explain, at least in part, the failure of serum T3 values to decrease appreciably when marked reductions in peripheral 5'D-I activity are induced by selenium deficiency or 6-anilino-2-thiouracil (ATU) administration. Thus, studies were performed to determine the effect of intestinal decontamination, in the absence and in the presence of 5'D-I inhibition, on plasma T4 and T3 concentrations. Groups of adult male rats received either enteric antibiotics or no antibiotics for 12 days and then, in half of the rats in each group, treatment for 10 days with ATU, a 5'D-I inhibitor that does not affect thyroid hormone synthesis. The activity of intestinal arylsulfatase and arylsulfotransferase, enzymes that catalyze hydrolysis of thyroid hormone conjugates, was reduced markedly by approximately 87% in rats that received antibiotics, regardless of whether or not they also received ATU. The ATU treatment markedly inhibited liver 5'D-I activity in antibiotic-treated as well as in non-antibiotic-treated rats (control = 399 +/- 32 U/mg protein (mean +/- SEM); ATU = 152 +/- 17: antibiotics = 351 +/- 29; antibiotics + ATU = 130 +/- 10; p < 0.01) and significantly increased plasma T4 and T3 sulfate (T4S, T3S) concentrations (control: T4S = 2.8 +/- 0.4 and T3S = 6.7 +/- 1.3 ng/dl; ATU: T4S = 6.2 +/- 1.4 and T3S = 10.6 +/- 2.1 ng/dl; antibiotics: T4S = 1.8 +/- 0.2 and T3S = 3.6 +/- 1.0 ng/dl; antibiotics + ATU: T4S = 6.8 +/- 0.7 and T3S = 9.7 +/- 1.8 ng/dl; p < 0.05). The ATU treatment was associated with a significant increase in plasma T4 and rT3 concentrations but did not affect plasma T3 concentrations, and intestinal decontamination did not alter these ATU-associated effects on circulating thyroid hormones. These results suggest that anaerobic enteric bacteria in the rat do not have an important role in recycling of thyroid hormones, either under normal conditions or in circumstances where 5'D-I activity is markedly reduced, and that increased gut absorption of T3 from T3S cannot explain the near-normal serum T3 values found when peripheral 5'D-I activity is markedly decreased.

Thyroid function tests and characterization of thyroxine-binding globulin in the carbohydrate-deficient glycoprotein syndrome type I.

Carbohydrate-deficient glycoprotein (CDG) syndrome is a newly recognized hereditary disorder that presents with psychomotor retardation, cerebellar ataxia, peripheral sensorimotor neuropathy, and, variably, skeletal abnormalities, lipodystrophy, and retinitis pigmentosa. These abnormalities appear to be produced by a defect that causes reduced carbohydrate content in glycoproteins. We studied seven patients with CDG type I belonging to five unrelated families. The concentration of serum TBG, a glycoprotein of hepatic origin, was measured by RIA and T4 saturation and was found to be below the normal range in three of the seven patients and normal in four of them. More than half of the total serum TBG had reduced sialic acid content and localized on isoelectric focusing (IEF) as two prominent bands cathodal to the three major bands of normal TBG. The latter two bands are responsible for the characteristic IEF pattern or CDG syndrome. TBG in patients with CDG had immunoreactivity indistinguishable from that of normal TBG and had normal affinity for T4, T3, and rT3. Serum total T4, T3, and rT3 were below the normal range in seven, five, and seven patients, respectively. The free T4 index was also below normal in four patients, but the free T4 concentration, measured by equilibrium dialysis at low dilution, and serum TSH were in the midnormal range. The serum total T4 and rT3 levels were disproportionately reduced relative to the serum TBG concentration and compared to the concentrations of these iodothyronines in matched subjects with inherited partial TBG deficiency. Chronic illness cannot explain these changes, because, contrary to patients with nonthyroidal illness, those with CDG had significantly higher serum total T3/T4 and lower rT3/T4 ratios. It is concluded that IEF of TBG is a rapid and simple method for the diagnosis of CDG type I and that the abnormal pattern can be detected as early as 5 days postpartum. Patients with CDG are chemically euthyroid, and it is postulated that the reduction in serum iodothyronine concentrations beyond that explained on the basis of low TBG levels may be due to the interference with binding to TBG by an unidentified substance.

Pitfalls in the interpretation of thyroid function tests in old age and non-thyroidal illness.

In hyperthyroidism, measurement of the serum thyroxine (T4) index or free concentration often suffices to establish the diagnosis. In hyperthyroidism, including 3,3',5-triiodothyronine (T3) toxicosis, thyrotrophin (TSH) response to thyrotrophin-releasing hormone (TRH) is blunted. Sensitive measurement of serum TSH may in the future be the first-line screening test not only for primary hypothyroidism but also for hyperthyroidism. In non-thyroidal illness serum T4, reverse T3 and T3 levels change in relation to severity of disease. In mild disease, T4 is initially increases as the severity of the non-thyroidal illness increases. Reverse T3 increases and serum T3 decreases when the patients become more ill. Serum TSH response to TRH is often blunted. In old age similar changes in serum iodothyronine concentrations may take place, probably related to existing non-thyroidal illness. Also many drugs may have different effects on serum parameters of thyroid function. In acute psychiatric diseases increased serum total and free T4 levels and a blunted TRH test may be encountered.

Transient Hyperthyroxinemia in Symptomatic Hyponatremic Patients

Twenty-two patients with severe hyponatremia were divided into 12 patients with and ten without associated neurologic manifestations (groups 1 and 2, respectively). Marked hyperthyroxinemia was demonstrated in seven patients in group 1 but in none in group 2. The triiodothyronine concentration was also higher than normal in two patients in group 1. All serum iodothyronine concentrations in group 1 were significantly higher than in group 2. Thyrotropin and thyroxine-binding globulin levels were normal in both groups. The differences between groups were apparent only in the acute phase, and there were no clinical manifestations of hyperthyroidism. All iodothyronine concentrations returned to normal within two weeks after the correction of the hypo-osmolar disorder. Our results indicate that a transient asymptomatic increase in serum iodothyronine levels occurs during hyponatremia. Thus, thyroid test results should be interpreted cautiously in patients with acute, severe, symptomatic hyponatremia.

Effect of Iopanoic acid on the pituitary-thyroid axis: time sequence of changes in serum iodothyronines, thyrotropin, and prolactin concentrations and responses to thyroid hormones.

We have previously shown that some oral cholecystographic agents induce marked increase in basal and TRH-stimulated TSH concentrations in normal subjects. To define the relationship between circulating iodothyronines and pituitary secretion after oral cholecystography, temporal changes in the responses of serum TSH and PRL to a fixed dose of TRH (500 micrograms iv) and in serum T4, T3, and rT3 concentrations were assessed before, immediately after, and then at weekly intervals after the three daily doses of iopanoic acid (Ip). Both basal and TRH-stimulated TSH concentrations were significantly increased at the end of the period of Ip administration when the serum T3 concentration was decreased, were still above the pretreatment level 1 week after the course of Ip when the serum T3 had returned to pre-Ip levels, and returned toward normal 2 weeks after the course of Ip. The changes in serum T3 concentration were accompanied by reciprocal changes in rT3 concentration. PRL secretion was not significantly changed. To evaluate further the relationship between the enhanced TSH secretion and the changes in serum iodothyronine concentrations, subjects were given oral doses of T3 (5 micrograms every 4 h) or T4 (50 micrograms every 8 h) during the administration of Ip. In the subjects given Ip plus T3, serum T3 concentrations were maintained at pre-Ip levels, and both basal and TRH-stimulated TSH concentrations were not different from the control. Administration of T4 did not completely prevent the Ip-induced increment of TSH secretion. It is suggested that in subjects given Ip, 1) the serum T3 level is, at least partly, a determining factor for TSH secretion; and 2) the set-point of TSH secretion is appropriately tuned to either reduction or elevation of serum T3 concentration by a mechanism that is different from that in fasting subjects.

Altered serum levels of thyroxine, triiodothyronines and diiodothyronines in endogenous depression.

Serum levels of thyroxine (T4), 3,3',5-triiodothyronine (T3), 3,3',5-triiodothyronine (rT3), 3,5-diiodothyronine (3,5-T2), 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) were studied in 80 patients with endogenous depression before and after electroconvulsive treatment (ECT). Compared to the values found after recovery, the patients when depressed had significant increased serum levels of T4, rT3, 3,3'-T2 and 3',5'-T2. Serum concentrations of T3 and 3,5-T2 were not significantly altered. Similarly the free T4 index (FT4I) was increased, while the free T3 index (FT3I) was unaffected. Previous studies have shown a reduced TSH response to TRH in patients with endogenous depression and that the long-term outcome after ECT is strongly related to changes in the TSH response. However, patients with increased TSH response to TRH (n = 23) had a pattern of serum iodothyronine concentrations similar to those (n = 57) with an unchanged TSH response. A similar pattern was also found in 7 patients with nonendogenous psychosis, in whom the TSH response to TRH was unchanged after recovery. It is concluded that the alterations of the TSH response to TRH found in endogenous depression cannot be explained by changes of FT4I or FT3I.

Effect of anticonvulsant and antidepressant drugs on iodothyronines in serum.

Serum iodothyronine concentrations were measured in patients on long-term therapy with one or two anticonvulsant drugs. Diphenylhydantoin (DPH) and carbamazepine (CBZ) reduced the serum levels of thyroxine (T4) free T4 index, reverse triiodothyronine (rT3) and 3,3'-diiodothyronine (3,3'-T2), whereas the depressant effect on the serum levels of triiodothyronine (T3) and free T3 index was small but statistically significant. In patients administered DPH and phenobarbital (PB) or CBZ and primidone (PD) the serum iodothyronine levels were also depressed, except for normal T3 and free T3 index. Patients receiving only PB or PD had normal serum levels of total and free thyroid hormones, but decreased concentrations of rT3 and 3,3'-T2. Only supratherapeutic concentrations of DPH and CBZ added in vitro to control sera significantly reduced the number of T4 and T3-binding sites, as reflected in increased T4 and T3 uptake test results. This indicates that the DPH and CBZ-induced decrease in thyroid hormone concentrations in vivo is not due to a displacement of thyroid hormones from their binding sites on serum proteins. The antidepressant drugs amitriptyline and mianserin had no effect on the thyroid hormone levels in serum.

Glucose modulation of alterations in serum iodothyronine concentrations induced by fasting

In order to investigate the process by which dietary composition may regulate T4 conversion to T3 and reverse T3, iodothyronine levels were measured in the sera of seven obese subjects during consecutive study periods. These study periods included the ingestion of an approximate weight-maintaining diet (40% carbohydrate, 40% fat, 20% protein) during a control period of 4 days, a fast of 7 days thereafter, and then a 5-day period of glucose ingestion (50 g/day) only. The mean (±SE) serum T3 concentration was 117 ± 8 ng/dl on day 4 of the control period, and gradually decreased to 66 ± 11 ng/dl ( p < 0.01) on the last day of fasting. The subsquent administration of glucose was associated with an increase in the mean serum T3 level to 94 ± 10 ng/dl ( p < 0.01). Mean (±SE) serum levels of reverse T3 varied reciprocally and were 52 ± 9 ng/dl, 82 ± 12 ng/dl ( p < 0.005), and 65 ± 9 ng/dl (compared to fasting, p < 0.05) during the fed and fasting states and during glucose administration, respectively. Furthermore, employing a similar protocol in a different group of subjects, serum sampled during the administration of 100 g of fructose orally during days 8–12 of fasting also was associated with an increase in mean serum T3 and a decrease in mean serum reverse T3, as compared to values obtained on day 6 or day 7 of fasting (T3: 83 ± 6 ng/dl, fasting vs. 111 ± 10, fructose ( p < 0.05); rT3: 56 ± 9, fasting vs. 42 ± 6 ng/dl, fructose ( p < 0.025)). Serum T4 concentrations were not significantly altered in any study period either during glucose or fructose ingestion. Despite the decrement in serum T3 levels observed during fasting, the mean peak TSH in response to TRH stimulation in a group of 15 obese subjects was decreased during fasting as compared to the fed state (8.1 ± 1.2 μU/ml, fast vs. 12.8 ± 2.0 μU/ml, fed). These observations suggest that both glucose and fructose are capable of modulating serum T3 and reverse T3 levels and that administration of these hexoses in doses of only 100–200 g/day for 5 days may be effective in altering T4 degradative pathways. Furthermore, despite the decreased serum T3 levels, the TSH response to TRH stimulation is decreased, paradoxically, during fasting.

Effect of parturition on serum iodothyronine concentrations in fetal sheep.

T4, T3, and rT3 were determined by RIA on daily serum samples collected from five catheterized fetal sheep during the 2-week period before spontaneous vaginal delivery (PTD). Samples were also available from three newborn lambs during the first 4 h of life. T3 concentrations began to increase 4-6 days before spontaneous vaginal delivery, from a stable geometric mean concentration of 30 ng/dl to a mean concentration of 131 ng/dl on the day of delivery (day 0). T4 concentrations decreased in four of the animals and remained unchanged in one during this time interval. rT3 concentrations decreased from a stable mean of 472 to 249 ng/dl on day 0. The prenatal increase in serum T3 levels correlated temporally with increasing fetal serum cortisol concentrations. The mean T3 concentration increased further after delivery to a level of 487 ng/dl at 1 h of age without significant changes in T4 or rT3 levels. The following conclusions were reached: 1) fetal serum T3 concentrations increase while T4 and rT3 concentrations decrease during the 4-6 days preceding spontaneous labor, and 2) T3 concentrations increase further after delivery. Available evidence suggests that the prenatal increase in fetal serum T3 levels is mediated by a cortisol-induced increase in T4 to T3 conversion in fetal tissues. The mechanism(s) of the postnatal increase in serum T3 concentrations in the newborn is not clear.