Reverse T3 Concentrations Research Articles

Decrease of free thyroxin in serum of lactating women.

We measured thyroid hormones and thyroxin-binding proteins in serum from 62 normal lactating and 52 nonlactating women at three months postpartum, and compared these values with those for 42 nonpregnant control women of similar age. Mean thyroxin concentrations in the lactating and nonlactating women were significantly (P less than 0.001) lower than that of the nonpregnant controls, but there was no significant difference (P greater than 0.2) in triiodothyronine concentration among these three groups. Free T4 concentration was significantly (P less than 0.01) lower in lactating women than in controls. The reverse-T3 concentrations in both lactating and nonlactating women were significantly (P less than 0.001) lower than in controls, and were significantly (P less than 0.001) lower in lactating than in nonlactating women. The concentration of thyroxin-binding globulin was significantly higher in lactating women than in controls, and the albumin concentration was significantly lower in women postpartum than in controls. Evidently, regulation of thyroid hormone in women postpartum, especially during lactation, differs from that in nonpregnant women.

THYROID FUNCTION IN HOSPITALIZED CHILDREN

Serum concentrations of thyroxine (T4), triiodothyronine (T3), reverse T3 (rT3), and thyrotropin (TSH) were determined in 21 consecutively admitted children (ages 3 wk 63mo;10 M, 11 F) in April, 1986. In 14 children in whom thyroid function was assessed on the first and last days of hospitalization, the levels of T4 and T3 (X±SD) increased (T4 9.6±3.4 to 11.4 ±3.2 ug/dL, p<0.03) (T3 124.8±66.7 to 180.6±56.9 ng/dL, p<0.01) and that of rT3 decreased (444.1±165.3 to 369±156.9 ng/dL, p<0.02). Clinically children were grouped into those in (1) good, (2) fair, or (3) poor condition upon admission. Serum values of T4 and T3 were lowest in group 3 compared to group 1 and intermediate in group 2. Further grouping of children into those with (a) bacterial (n=4), (b) nonbacterial nonrespiratory (n=9), (c) nonbacterial respiratory (n=5), (d)others (n=3) revealed lower T3 values for group (a) versus groups (b, c, d) (p<0.04). T3: a)41.9%33.5 b)136.9±68.8 c)156.4±31.3 d)146.7±65.3 We conclude that thyroid function is altered primarily in the clinically very sick child with a bacterial illness. Measurement of serum T3 concentrations may provide a rapid method for identifying the acutely ill child with a bacterial infection.

Effect of changes in thyroid state on metabolism of thyroxine by rat placenta.

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

The effect of propranolol on circulating thyroid hormone measurements in thyrotoxic and euthyroid subjects.

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

Effect of a single injection of prolactin on the serum concentrations of thyroid hormones and corticosterone and liver monodeiodinase in the domestic fowl before and after hatching.

The influence of an intravenous injection of ovine prolactin on the liver monodeiodinase activity and serum concentrations of thyroid hormones and corticosterone was studied in Hisex embryos and chicks after hatching. An injection of 1 and 10 micrograms ovine prolactin into 18-day-old chick embryos increased serum concentrations of tri-iodothyronine (T3) five- and eightfold respectively after 2 h. At the same time serum concentrations of thyroxine (T4) and reverse T3 (rT3) were decreased in the chick embryo, but only with 10 micrograms prolactin. This was accompanied by a doubling of the liver monodeiodinase activity. Serum concentrations of corticosterone, however, were not influenced by the prolactin injections. In the 5-day-old chicken, serum concentrations of T3, rT3, T4 and liver T4-5'-monodeiodinase activity were not influenced by 1 or 10 micrograms prolactin. Serum concentrations of corticosterone after injection of 1 or 10 micrograms prolactin were doubled compared with controls. These results are compatible with a prolactin-induced shift from a T4-5-monodeiodination into a T4-5'-monodeiodination in the liver at the end of incubation. This effect, however, is not mediated through a prolactin-induced corticosterone release.

Thyroid hormone abnormalities at diagnosis of insulin-dependent diabetes mellitus in children

Comprehensive evaluation of thyroid hormone indices was performed in 58 children with insulin-dependent diabetes mellitus (IDDM) at the time of diagnosis and prior to insulin therapy. Two patients were found to have primary hypothyroidism, with markedly elevated TSH and very low T4, free T4, T3, and reverse T3 concentrations. The remaining 56 patients had the transient alterations in thyroid hormone indices that are characteristic of "euthyroid sick" or "low T3" syndrome. Mean TSH and reverse T3 values were significantly higher and the mean T3, T4, and free T4 levels were significantly lower than those observed in the control population. Ten of the diabetic patients had elevated TSH concentrations and normal or low free T4 values; eight had normal TSH levels and low T4 and free T4 values. The remainder of the group had thyroid indices compatible with abnormal peripheral metabolism of thyroid hormones. Elevated titers of antimicrosomal antibodies were found in 16% of the children with IDDM. We conclude that abnormal peripheral metabolism and altered hypothalamic-pituitary function are responsible for the transient changes in thyroid hormone indices in patients with untreated IDDM. The most reliable indicators of concomitant primary hypothyroidism in untreated IDDM are markedly elevated TSH and low reverse T3 values.

Circulating thyroid hormones in progressive renal failure in the baboon (Papio ursinus).

In order to examine the effects of developing renal failure on circulating thyroid hormones, serum concentrations of thyroxine (T4), free T4 (FT4), triiodothyronine (T3) and reverse T3 (rT3) and TBG capacity were measured in 9 baboons before and during the progress of acute (mean survival 12 days), subacute (32 days) and chronic (120 days) renal failure following allogeneic renal transplantation. Irrespective of the rate of development of renal failure, there were significant, non linear (power functions) negative correlations between serum creatinine or urea concentrations and levels of T4, FT4 and T3; rT3 levels remained unchanged, but the T4: rT3 molar ratio fell from 236.5 +/- 61 (+/- SE) to 121.8 +/- 30.9 (p less than 0.05). T4 and T3 levels were invariably subnormal at creatinine concentrations greater than 250 mumol/l (2.8 mg/dl), but FT4 was subnormal only in chronic renal failure. Thyroxine binding globulin (TBG) capacity did not change significantly; thus the TBG: T4 ratio increased from 3.4 +/- 0.2 (basal) to 10.4 +/- 3.4 before death (p less than 0.05). In animals which survived for greater than 25 days after transplantation, a significant linear correlation between FT4 and T3 was found as uremia progressed. Polyacrylamide gel electrophoresis (pH 7.4) of (125I)-T4 labelled preoperative and uremic serum showed a consistent decline in the proportion of tracer bound to TBG, from 67.0 +/- 0.8% to 58.9 +/- 1.0% (p less than 0.001), with a 48% reduction in TBG saturation (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy.

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

Antagonism of serum tri-iodothyronine changes after injections of prolactin in the domestic fowl before and after hatching.

The influence of an intravenous injection of ovine prolactin on circulating levels of thyroid hormones was studied in Rhode Island Red embryos and chicks after hatching. In the chick embryo, 2 h after injection of 0.1 microgram prolactin (on incubation day 19), serum triiodothyronine (T3) increased threefold; after 10 or 100 micrograms prolactin (on incubation day 18) serum T3 increased 15- to 25-fold. These profound increases were not observed in chicks after hatching. Serum concentrations and thyroid content of thyroxine (T4) in embryos and chicks of all ages studied were not influenced by the prolactin injections. Maximal serum concentrations of reverse T3 (rT3) were found on incubation day 18 (110.25 +/- 23.36 pmol/l; 71.66 +/- 15.18 pg/ml; n = 8), whereas after hatching no rT3 could be detected. An injection of 10 micrograms prolactin on day 18 depressed serum rT3 after 2 h to 5.68 +/- 3.20 pmol/l (3.69 +/- 2.08 pg/ml; n = 8; P less than 0.001); the effect of 100 micrograms prolactin was less pronounced. After hatching, chronic administration of prolactin resulted in decreased serum levels of T3, but not of T4, and hypertrophy of the follicles in the thyroid gland. It is concluded that prolactin plays a major role in the maturation of embryonic thyroid metabolism by changing the T4-5-monodeiodination into a T4-5'-monodeiodination. The hypertrophy of the thyroid gland observed after hatching following prolonged prolactin administration may be due to decreased negative feedback of T3 on the hypophysis.

Thyroid function in nonthyroidal illnesses.

Alterations in thyroid physiology and thyroid function tests occur in some patients with nonthyroidal illnesses. Low concentrations of serum triiodothyronine (T3) usually occur in nonthyroidal illnesses and are attributable largely to reduced extrathyroidal conversion of thyroxine (T4) to T3. Concentrations of serum total T4 may be low, normal, or high; alterations in serum binding of T4 explain the abnormality in most cases. Concentrations of serum reverse T3 are usually high because metabolic clearance is reduced. Whether patients with nonthyroidal illnesses with low T4 or T3, or both, are hypothyroid is uncertain; concentrations of free T4 have been estimated as low, normal, or high using different methods. Serum thyroid-stimulating hormone is typically normal. Low concentrations of T3 or T4, or both, in nonthyroidal illnesses may have a homeostatic significance. Low serum concentrations of T4 correlate with poor prognosis in nonthyroidal illnesses. Inhibitors of thyroid hormone binding and phagocytosis are present in normal tissues. Leakage of the inhibitors into the circulation may lower serum concentrations of T4 on one hand and compromise critical host defenses on the other.

Foetal head growth retardation due to antiepileptic drugs: with reference to GH, TSH, T4, T3 and reverse T3 concentrations.

To study the mechanisms of inhibitory action of antiepileptic drugs on foetal head growth, determinations were made of the growth hormone, thyrotropin and thyroid hormone levels in the sera of pregnant women, and the correlations between each hormone concentration and the foetal head circumference were studied. The thyroxine level decreased in the maternal serum and in the cord blood, and the thyrotropin level also became lower in the epileptic mother taking antiepileptic drugs. The growth hormone level in the umbilical vein sample of the epileptic mother was lower than that in the controls. The correlations between the head circumference of an infant at delivery and the decreased levels of the hormones seemed to indicate that a decrease in the thyroxine level, caused by antiepileptic drugs, produced the foetal head growth retardation.

Elevation of postmortem triiodothyronine in sudden infant death syndrome and in infants who died of other causes: A marker of previous health

We measured serum concentrations of thyroxine (T4), triiodothyronine (T3), reverse T3, free T4, thyroid-stimulating hormone, and cortisol in 62 victims of sudden infant death syndrome (SIDS) in 30 infants who died of known causes and in 15 living controls. The mean T3 value was elevated in 69% of those with SIDS. 37% of the others who died, and in no control infants. After excluding those who died of known cause who had abnormal thyroid function (abnormal postmortem concentrations of T4, free T4, or reverse T3), the T3 values were elevated in 63% of those remaining. When the data were analyzed on the basis of case histories and autopsy findings, those infants who were in good health and died suddenly of accidental causes had an elevation in mean T3 similar to that seen in SIDS victims; those who died under conditions known to alter thyroid metabolism did not. The T4, free T4, reverse T3, thyroid-stimulating hormone, and cortisol values were not useful in differentiating those with SIDS from the living controls, or those who were healthy at the time of death. We were unable to find any difference in T3 serum concentrations between the total group who had SIDS and those who had SIDS with minor infections, with petechiae on intrathoracic organs, with premature birth, or those who were resuscitated. Our data point out the importance of using appropriate controls when evaluating SIDS. The normal reverse T3 values in SIDS, as well as confirmation of the normal T4 and free T4 values, constitute evidence against chronic persistent alveolar hypoventilation or prolonged episodes of hypoxia immediately preceding death from SIDS.

Endocrinology and metabolism: an annotated bibliography of recent literature. References to journal articles and other papers.

Endocrinology and metabolism: an annotated bibliography of recent literature. References to journal articles and other papers.

Effects of dexamethasone on the hypothalamic-pituitary-thyroid axis in rats.

Effects of dexamethasone on the hypothalamic-pituitary-thyroid axis in rats were studied. Rats given saline (group A), 25 micrograms of dexamethasone/100 g body weight (group B) or 500 micrograms o dexamethasone/100 g body weight (group C) were serially decapitated and brain tissues and blood were obtained. TRH contents in the hypothalamus, plasma concentrations of TRH, TSH, T4, T3 and reverse T3 were measured by specific radioimmunoassay. TRH contents in the hypothalamus were significantly increased at 3 h in group B after dexamethasone treatment. In group C, however, they significantly increased for 1 to 3 h, but then decreased with the minimum at 20 h. TRH plasma levels significantly increased with the maximum at 4 h in group B and at 24 h in group C. TSH plasma levels were significantly decreased initially and then significantly increased with the maximum at 5 h in group B and at 24 h in group C. TSH responsiveness to TRH was significantly decreased at 1 to 3 h in group B, but in group C it was significantly decreased initially and the significantly increased. T3 plasma levels significantly decreased at 1 to 3 h in group B and at 1 to 18 h in group C. Reverse T3 plasma levels were significantly increased with the maximum at 3 h in group B and at 6 h in group C. The results demonstrate that dexamethasone may act on multiple sites of the hypothalamic-pituitary-thyroid axis in rats and that its effect depends on the dose used or the time interval after dexamethasone treatment.

The role of sex hormones in the mechanism of inhibited LH release in female patients with anorexia nervosa.

In order to elucidate the mechanism of impaired LH secretion, 60 female patients with anorexia nervosa were investigated. A control group consisted of 14 women of the same age, examined in the follicular phase of the menstrual cycle. The serum LH, FSH, prolactin, TSH, testosterone, dihydrotestosterone, dehydroepiandrosterone, delta 4-androstenedione, oestrone, oestradiol, oestriol, progesterone, thyroxine, triiodothyronine, reverse T3 and serum sex hormone binding globulin (SHBG) concentrations were measured. The results showed a significant increase in serum dehydroepiandrosterone, testosterone, oestriol and reverse T3 concentrations. However, oestrone, oestradiol, progesterone, SHBG and triiodothyronine levels were significantly lower than those of the control group. The mean serum LH concentration in patients with anorexia nervosa before and after LRH stimulation was significantly lower than that in the control group, but FSH secretion in response to LRH was normal. All hormonal changes in anorexia nervosa disappeared after weight gain during cyproheptadine treatment. Dramatically increased dehydroepiandrosterone levels suggest that the high testosterone in women with anorexia nervosa is derived from adrenal rather than from gonadal steroids. There was no correlation between serum testosterone, dehydroepiandrosterone, oestriol and LH concentrations indicating that steroid hormone disturbances do not cause impaired LH release in anorexia nervosa.

Prolactin, estradiol, and thyroid hormones in umbilical cord blood of neonates with and without hyaline membrane disease: A study of 405 neonates from midpregnancy to term

Concentrations of prolactin (PRL), estradiol (E2), thyroxine (T4), triiodothyronine (T3), and reverse T3 in umbilical cord blood were measured by radioimmunoassay in neonates with (n = 60) and in a control group without (n = 345) hyaline membrane disease. Mean levels of all hormones assayed were not significantly different between the two groups at various stages of gestation. In the control group, gestational age correlated positively with PRL and inversely with reverse T3, whereas birth weight correlated positively with PRL, T4, and T3, but inversely with reverse T3 levels. Thus, larger, more mature neonates tended to have higher cord levels of PRL, T4, T3 and lower concentrations of reverse T3. The data also suggest that, in the premature neonate, various obstetric complications and exposure in utero to beta-mimetic drugs and glucocorticoids may be important determinants of the concentrations of E2 and thyroid hormone in cord blood.

Effect of dietary carbohydrates during hypocaloric treatment of obesity on peripheral thyroid hormone metabolism.

The effect of different hypocaloric carbohydrate (CHO) intakes was evaluated in 8 groups of obese patients in order to assess the role of the CHO and the other dietary sources in modulating the peripheral thyroid hormone metabolism. These changes were independent of those of bw. Serum T3 concentrations appear to be more easily affected than those of reverse T3 by dietary manipulation and CHO content of the diet. A fall in T3 levels during the entire period of study with respect to the basal levels occurred only when the CHO of the diet was 120 g/day or less, independent of caloric intake (360, 645 or 1200 calories). Moreover, reverse T3 concentrations were found increased during the entire period of study when total CHO were very low (40 to 50 g/day) while they demonstrated only a transient increase when CHO were at least 105 g/day (with 645 or more total calories). Indeed, our data indicate that a threshold may exist in dietary CHO, independent of caloric intake, below which modifications occur in thyroid hormone concentrations. From these results it appears that the CHO content of the diet is more important than non-CHO sources in modulating peripheral thyroid hormone metabolism and that the influence of total calories is perhaps as pronounced as that of CHO when a "permissive" amount of CHO is ingested.

Rapid adaptation of pituitary responsiveness to TRH in the post-surgical state. The role of free T3.

In eight clinically and biochemically euthyroid patients undergoing routine major non-thyroidal surgery preoperative and daily postoperative serum concentrations of total and free thyroid hormones were measured. Thyrotrophin-releasing hormone (TRH) tests were performed preoperatively and on the first 3 postoperative days. There was a significant fall in mean serum total and free triiodothyronine (T3) concentrations on the postoperative days and mean reverse T3 concentrations rose reciprocally. There was no significant change in mean basal thyroid-stimulating hormone (TSH) values, but there was a significant increase in the mean TSH-response to TRH on the first postoperative day. The mean TSH response than declined sequentially until day 3 while mean free T3 concentrations remained significantly depressed. Mean serum free thyroxine(T4)concentrations remained normal during the study. Intrapituitary conversion of T4 to T3 or other down regulatory mechanisms could explain this rapid adaptation of the pituitary axis.

The effect of fenclofenac on thyroid function.

The non-steroidal anti-inflammatory agent fenclofenac competitively inhibits the binding of thyroxine(T4) and triiodothyronine (T3) by thyroxine-binding globulin(TBG). Eight male volunteers completed a 4-week study during which they took fenclofenac 600 mg twice daily. The concentration of fenclofenac in serum reached a plateau after 1 week of therapy after which the mean concentration(+/SEM) of the drug in serum was 78.6 o.2 mg/1. During the steady state period on treatment there were reductions of the mean serum concentrations of total T4 to 35% (P less than 0.001), total T3 to 55% (P less than 0.001), free T4 to 69% (P less than 0.001) and free T3 to 90% (NS) of the respective pretreatment values. There were also significant changes in the concentrations of thyrotropin and reverse T3 in serum. After starting treatment with fenclofenac serum concentrations of thyrotrophin fell to a nadir after 2-4 days at which time the mean concentration was 34% (P less than 0.01) of the pretreatment value, whilst reverse T3 values increased to a maximum of 136% (P less than 0.001) of the pretreatment values over 1-2 days. There was subsequently an increase of the thyrotrophin and a reduction in reverse T3 concentrations to normal by 2 weeks of pretreatment. Transient pituitary suppression was also suggested by the response to to thryotrophin-releasing hormone (TRH): 7 days after starting fenclofenac the mean thyrotrophin response was 62% (P less than 9.001) of the pretreatment value. After 4 weeks of fenclofenac the response of TRH had returned to normal. After discontinuing fenclofenac there was a transient increase in the mean concentration of thyrotrophin in serum, to 129% of the pretreatment value (P less than 0.001), with a subsequent return to normal. Four weeks after discontinuing fenclofenac the serum concentrations of thyroid hormones and thyrotrophin were normal.

Thyroid function and thyroid hormone metabolism in elderly people. Low T3-syndrome in old age?

T4-, T3- and reverse-T3 concentrations were measured in the sera of 365 subjects beyond the age of 65 in order to evaluate if the decrease of serum T3 frequently observed in old age can be attributed to old age per se or to concomitant nonthyroidal disease. The results obtained from a carefully selected healthy group of elderly people show that 1) total and free T3 levels are lower in senescence but well within the range for euthyroidism in younger healty controls;2) the decrease of serum T3 is more pronounced and occurs earlier in healthy old males than in females, so that for subjects over the age of 75, the upper limit for euthyroidism has to be adjusted by 10% in women and by 20% in men; and 3) there is no low T3 syndrome characterized by decreased serum T3 and increased serum reverse T3, solely due to old age. Turnover kinetics have shown the daily production of T4 and T3 in old age to decrease by 20 micrograms and 10 micrograms, respectively, and an increased T3 metabolic clearance not to account for the reduction of serum T3 concentrations. Combined stimulation tests with TSH and TRH showed that the functional reserve of the thyroid gland to produce T3 is maintained in old age. The first step in the sequence of events may be seen in an impairment of TSH secretion leading to an adaptation of the amount of thyroid hormones to a reduced mass of metabolically active body tissue in old age.