T3 Resin Uptake Research Articles

TRH (Thyroid-Releasing Hormone) Tests

I have read with great interest "Goiter in Children" by Foley (PIR 1984;5:259). The author stated: "In patients with thyromegaly and mild symptoms of hyperthyroidism, a TRH test will help to discriminate hyperthyroxemia secondary to increased or abnormal serum thyroxine binding proteins from early Graves disease, factitious hyperthyroidism, toxic thyroiditis, and TSH-mediated hyperthyroidism." I would suggest the use of a triiodothyronine (T3) resin uptake as a base-line test. An elevated serum thyroxine (T4) value in conjunction with a diminished T3 resin uptake suggests thyroxine-binding globulin (TBG) excess, which can be confirmed by specific quantitation of TBG. Patients with familial dysalbuminemic hyperthyroxinemia (FDH) have elevated levels of serum T4 and free thyroxine index (FT4l) values but normal T3 resin uptake and TBG levels.

TSH secretion in thalassemia

Thyroid function has been evaluated in 6 prepubertal male and 9 female thalassemic patients. Four of the latter were sexually immature (Group I), with very low estradiol levels and the remainder had more advanced sexual development (Group II). Subjects were challenged with TRH and the response compared to adult controls and a group of 15 males aged 13-18 years with constitutional delayed adolescence. All patient groups and controls had normal levels of T4, T3 and T3 resin uptake. When compared to adult controls or males with constitutional delayed adolescence, the male thalassemic patients had increased basal TSH levels with an exaggerated response to TRH. Long term testosterone enanthate led to a decrease in integrated TSH secretion, showing that androgens may decrease the TSH response to TRH. The more sexually mature females of Group II also had increased basal and stimulated TSH levels; however, the sexually immature females of Group I had basal TSH and TSH responses to TRH equivalent to female controls. In Group I patients there were, moreover, no changes in TSH response during administration of estradiol valearate for 3 months and conjugated estrogens for 8 months. The high basal and stimulated TSH levels in the males and Group II females are most likely due to subclinical primary hypothyroidism. This has been previously described in thalassemia. On the other hand, failure of estrogens to increase the TSH response to TRH in Group I females is evidence of pituitary involvement, which is also well documented in this clinical condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired pituitary thyrotroph function in uncontrolled type II diabetes mellitus: normalization on recovery.

Altered thyroid hormone metabolism with decreased serum T3 and increased rT3 concentrations in patients with uncontrolled diabetes mellitus has been well documented. However, data regarding TSH secretion are sparse, especially the influence of glycemic control. Therefore, we examined serum T4, free T4, T3, rT3, T3 resin uptake, and TSH as well as the TSH response to TRH administration [expressed as TSH increment (delta TSH) and area under the curve (theta TSH)] in 29 newly discovered type II diabetic patients (DM) before treatment and in 12 normal subjects. The study was repeated in the DM patients after attainment of euglycemia and normalization of glycosylated hemoglobin (HbA1C) following therapy with diet and tolazamide for 8-12 weeks. Serum T4, free T4, and T3 resin uptake were not significantly different in DM compared to those in normal subjects. Serum T3 was low and rT3 was high in DM before treatment, and both normalized on achieving the euglycemic state. Basal TSH in uncontrolled DM was not significantly different from that in normal subjects and remained unchanged during treatment. However, delta TSH and theta TSH were significantly reduced (P less than 0.01) in uncontrolled DM. Both fasting plasma glucose (FBS) and HbA1C levels correlated inversely with delta TSH as well as theta TSH (FBS vs. delta TSH, r = -0.42; FBS vs. theta TSH, r = -0.38; HbA1C vs. delta TSH, r = -0.40; HbA1C vs. theta TSH, r = -0.42; P less than 0.05 for all correlations). Finally, TSH responses returned to normal on attainment of euglycemia and normal HbA1C concentrations. These studies indicate that regulation of TSH secretion is altered in DM during the decompensated state and normalizes when euglycemia is achieved.

High concentrations of furosemide inhibit serum binding of thyroxine.

Serum samples taken from four patients who had low serum T4 concentrations (less than 2 micrograms/dl) during severe non-thyroidal illness were found to contain a heat-stable, dialyzable inhibitor of 125I T4 binding to plasma proteins. Inhibitory activity coincided with high dose furosemide treatment for oliguric renal failure. Inhibition was proportional to the serum furosemide concentration and the effect was reproduced in vitro by addition of furosemide to normal serum. The inhibitory effect diminished with serum dilution while maintaining the same relative concentration of furosemide. A time-course study in one patient demonstrated a close temporal relationship between high serum concentrations of furosemide and subnormal T4, associated with T3 resin uptake values compatible with increased occupancy of T4-binding globulin by a competitor. These findings demonstrate that furosemide in high concentrations can inhibit T4 binding in plasma and may be a factor contributing to the development of the low T4 state in critical illness.

Thyroidal changes associated with endurance training in women

The associations between endurance training, body composition, and the pituitary-thyroid axis were studied in 17 healthy, young women. Body composition and plasma concentrations of T4, T3, rT3, resin T3 uptake, TSH, and TRH-stimulated TSH were examined at baseline and after each subject's weekly distance had increased 48 km (delta 48) and 80 km (delta 80) above baseline. Total body weight did not change at delta 48 or delta 80. Mean (+/- SE) lean weight in kg increased from 42.9 +/- 1.2 at baseline to 44.8 +/- 1.2 at delta 80 (P = 0.002). We have reported previously that at delta 48 the subjects had evidence of mild thyroidal impairment, which consisted of decreased T3 and rT3, and an exaggerated TSH response to TRH. With more prolonged training (delta 48 to delta 80) there were significant increases in T4, rT3, and unstimulated TSH, while the ratios of T4/rT3 and T3/rT3 and the TSH response to TRH decreased significantly. Some of the thyroidal changes that occurred between delta 48 and delta 80 are similar to those seen in other stressful non-thyroidal conditions.

Decreased thyroid gland volume in alcoholic cirrhosis of the liver.

Thyroid function and thyroid gland volume were studied in 40 consecutive alcoholic patients with histologically proven cirrhosis of the liver, and compared with data obtained from 40 sex-, age-, and weight-matched normal subjects. Thyroid volume, measured ultrasonically, was significantly decreased in the patients with cirrhosis: median, 11 ml (range, 6-16 ml); compared to normal subjects: median, 20 ml (range, 10-31 ml) (P less than 0.001). Serum T3 concentrations were significantly reduced: median, 1.5 nmol/liter (range, 0.1-2.5 nmol/liter); compared to normal subjects: median, 2.2 nmol/liter (range, 1.5-2.8 nmol/liter) (P less than 0.001). The free T3 index was reduced accordingly. Serum TSH levels were significantly increased in cirrhosis: median, 2.1 microU/ml (range, 0.4-5.3 microU/ml); compared to normal subjects: median, 1.1 microU/ml (range, 0.3-3.8 microU/ml) (P less than 0.05). No significant differences were found in T3 resin uptake, free T4 index, or serum T4 levels between the two groups. No significant correlations could be demonstrated between thyroid gland volume and biochemical indices of liver function or thyroid function tests. It is suggested that alcohol might have a direct effect on the thyroid gland.

Lowering effect of diphenylhydantoin on serum free thyroxine and thyroxine binding globulin (TBG).

To evaluate the effect of anticonvulsants on serum levels of free thyroxine (FT4) and thyroxine-binding globulin (TBG), 32 patients with epilepsy receiving long-term anticonvulsant treatment (mean duration 81.8 +/- 8.9 months) were employed in the present study. The serum levels of total thyroxine (TT4), total triiodothyronine (TT3), T3 resin uptake (T3U) and thyrotrophin (TSH) were also measured. Free thyroxine index (FT4I) was calculated from TT4 and T3U. Mean levels of these thyroid function tests were as follows: 5.52 +/- 1.51 micrograms/dl (TT4), 1.16 +/- 0.32 ng/dl (FT4), 101.5 +/- 16.2 ng/dl (TT3), 27.5 +/- 2.6% (T3U), 19.64 +/- 3.97 micrograms/ml (TBG), 1.50 +/- 0.36 (FT4I) and 2.21 +/- 0.18 microU/ml (TSH). These values except for T3U and TSH were significantly lower than normal values (P less than 0.01). Using correlation analysis, a significant dose-dependency (daily doses) was found between diphenylhydantoin (DPH) and TT4, FT4 and TBG. Other anticonvulsants (barbiturates, carbamazepine, primidone) or duration of treatment were not significantly correlated with thyroid function tests. Therefore serum levels of DPH were also measured in 19 out of 32 patients receiving anticonvulsant treatment. Significant negative correlation was found between serum levels of DPH and FT4 (r = -0.65) and DPH and TBG (r = -0.61).

CORD SERUM THYROID STIMULATING HORMONE (THS) AND THYROGLOBULIN (Tg) LEVELS DO NOT DECLINE WITH INCREASING WEIGHT IN NORMAL NEWBORNS WITH mean ± SD BIRTH WEIGHT OF 3685 ± 623 GRAMS OR GREATER

Tg, TSH, free T4 index, and free T3 index were determined in cord serum and related to birth weight and sex in normal newborns, 12 females and 12 males. Free index values are the product of the T3 resin uptake ratio and the appropriate thyroid function indice. Mean ± SD birth weight of female infants (3685 ± 623 grams) was significantly (p <0.025) less than that of male infants (4104 ± 248 grams). In contrast, the mean ± SD free T4 index value of female infants (8.4 ± 0.7 μg/dl) was significantly (p < 0.025) greater than that of male infants (7.3 ± 1.6 μg/dl). Free T3 index values (58.1 ± 4.2 vs 60.5 ± 6.0 ng/dl), TSH values (7.0 ± 3.8 vs 8.4 ± 3.2 μU/ml, and Tg values (39.1 ± 8.1 vs 38.3 ± 12.0 ng/ml) of female and male infants did not differ significantly (p >0.1). Free T4 index values of female (r = 0.804, p < 0.005) and male (r = 0.704, p <0.01) infants correlated positively with free T3 index values. The log of TSH levels did not correlate with birth weight in female infants (r = -0.291, p >0.1). However, male infants showed a positive correlation between the log of TSH levels and birth weight (r = 0.539, p <0.05). Tg levels of female (r = -0.282, p >0.1) or male (r = 0.254, p >0.2) infants did not correlate with birth weight. These data, together with our prior observations, are consistent with a hypothesis that body composition may influence cord serum Tg and TSH levels.

CORD SERUM THYROID STIMULATING HORMONE (TSH) AND THYROGLOBULIN (Tg) LEVELS DECLINE WITH INCREASING WEIGHT IN LOW BIRTH WEIGHT NEWBORNS

Tg, TSH, free T4 index, and free T3 index were determined in cord serum and related to birth weight and sex in infants with weights of less than 2500 grams, 19 males and 19 females. Free index values are the product of the T3 resin uptake ratio and the appropriate thyroid function indice. Mean ± SD birth weight of male (1850 ± 413 grams) and female (2032 ± 301 grams) infants did not differ significantly (p >0.05). Similarly, mean ± SD cord serum Tg (124 ± 49 vs 107 ± 55 ng/ml), TSH (9.2 ± 6.5 vs 7.1 ± 2.7 μU/ml), free T4 index (6.2 ± 1.6 vs 6.1 ± 1.0 μg/dl), and free T3 index (47 ± 12 vs 47 ± 5 ng/dl) values of male and female infants did not differ significantly (p >0.1). Free T3 index values of male (r = 0.570, p <0.01) and female (r = 0.443, p <0.05) infants correlated positively with the free T4 index values. Tg levels and the log of TSH levels correlated negatively with birth weight in male (Tg, r = -0.849; log TSH, r = -0.660) and female (Tg, r = -0.891; log TSH, r = -0.600) infants (p <0.005). Also, Tg levels correlated positively with the log of TSH levels in male (r = 0.412, p <0.05) and female (r = 0.554, p <0.01) infants. These data are consistent with a hypothesis that changes in body composition accompanying increasing birth weight are associated with an increase in thyroid gland responsiveness to TSH or a decrease in T4 clearance.

La fonction thyroïdienne dans le syndrome néphrotique

Serum Total Thyroxine (T4), Triiodothyronine (T3), Free Thyroxine (FT4), Free Triiodothyronine (FT3) Reverse Triiodothyronine and T3 Resin Uptake (T3RU) as well as basal and post stimulating TSH were measured in twenty clinically euthyroid patients with the nephrotic syndrome. In comparison with control values, our patients showed (1) significantly lowered mean serum TBG levels (p less than 0,05) (2) unmodified mean serum T3, FT3 and rT3 values (3) significantly lowered mean serum T4 and FT4 levels (p less than 0,001 and p = 0,027 respectively) (4) significantly higher mean basal TSH, and increased TSH response to TRH. We found a significant correlation between proteinemia and T4 or FT4 (p less than 0,001; p less than 0,01 respectively). In summary, our study: Shows that the low Total T4 observed in the Nephrotic Syndrome is not only due to a decreased protein bound T4, but also to a decreased FT4; And brings evidence for mild hypothyroidism in nephrotic patients.

Pituitary-thyroid hormone economy in healthy aging men: basal indices of thyroid function and thyrotropin responses to constant infusions of thyrotropin releasing hormone.

In order to assess the effects of aging, as distinct from those of thyroid disease or extrathyroidal illness, on certain indices of thyroid function, we studied 74 healthy, ambulatory men recruited from the Baltimore Longitudinal Study on Aging. We determined basal serum values of T4, T3, rT3, thyroxine-binding globulin (TBG), and T3 resin uptake (T3RU) and calculated the free T4 index (FT4I = T4 X T3RU/100), free T3 index (FT3I = T3 X T3RU/100), and T4/TBG ratio for each subject. We used an ultrasensitive RIA to measure variations in basal concentrations of TSH within the normal range. We then infused TRH at a constant rate (0.4 microgram/min iv) for 240 min into 63 of the same men; serum samples, collected at 15-min intervals during the infusion, were analyzed for TSH by routine RIA. Subjects were divided into 3 groups according to age; A (n = 26, mean age = 39.4), B (n = 23, mean age = 60.0), and C (n = 25, mean age = 79.6). Analysis of variance with Duncan's multiple range test and regression analysis were used to evaluate data. There was no significant (P greater than 0.05) variation with age of basal serum values of T4, TBG, or T3RU. Comparison of groups A and C showed significant decreases of mean values of serum T3 (-11%, P less than 0.05), FT3I (-13%, P = 0.02), FT4I (-11%, P less than 0.01), and T4/TBG ratio (-12%, P less than 0.01) and an increase in serum TSH (+38%, P less than 0.05). For these variables, the mean values for group B were intermediate between, but not significantly different from, those of A and C. Regression analysis showed significant correlations of age with T3, FT3I, FT4I, T4/TBG, and TSH at P levels similar to those obtained by Duncan's test. No elderly individual exhibited a baseline elevation of TSH (greater than 7 microU/ml) or depression of T4 (less than 5 micrograms/dl), suggesting that primary hypothyroidism was not present in our old group. The basal TSH concentration did not correlate significantly with any index of thyroid function except with FT3I in group C (r = -0.43, P less than 0.05). In all age groups the TSH responses to TRH exhibited a biphasic pattern with early and late peaks.(ABSTRACT TRUNCATED AT 400 WORDS)

Influence of diazepam on thyroid function tests in normal Nigerians

It has often been reported that certain drugs, in particular benzodiazepines, significantly depress the results of thyroid function studies. 1–4 In spite of the significance of this side effect very few systematic and conclusive studies have been reported in the literature. One of the benzodiazepine drugs, Diazepam, is the most commonly prescribed in our environment. A number of patients referred to our thyroid function laboratory are usually placed on this drug. In most cases a complete drug history is unobtainable. It was decided therefore to evaluate the effect of this drug on the thyroid function tests we most routinely carry out viz. T3 resin uptake T 4 and 131I uptake.

The thyrotropin (TSH) profile in isolated gonadotropin deficiency: a model to evaluate the effect of sex steroids on TSH secretion.

This study evaluated the effect of estrogens and androgens on TSH secretion in hypogonadal male and female patients with isolated gonadotropin deficiency (IGD). The IGD subjects were clinically euthyroid and had normal circulating levels of thyroid hormones and T4-binding globulin (TBG). The patients were challenged with TRH (200 micrograms) in the untreated state, during treatment, and 1 month after cessation of hormonal replacement therapy. For the study, five females were treated with ethinyl estradiol (0.05 mg twice daily) for 21 days; after stopping for 7 days, the treatment schedule was repeated for another two cycles. The remaining female was given a similar regimen with conjugated estrogens (0.625 mg daily). Five males were treated with hCG (5000 IU twice weekly) for 3 months; two were treated with hCG and Pergonal. The female patients had significantly decreased basal TSH levels as well as impaired TSH responses to TRH. After 3 months of ethinyl estradiol treatment, there was a rise in TBG, total serum T4 and T3 levels and a decrease in T3 resin uptake; the free T4 index was unchanged. During estrogen administration, there was no change in basal TSH, but there was an increase in the peak TSH response to TRH, which became identical to that of the controls. Cessation of estrogen was associated with a reduction in releasable TSH, and the profile reverted to the pretreatment state. In addition, serum TBG levels, with the associated changes in thyroid hormones, also returned to normal. The male patients had TSH responses to TRH identical to those of the male controls. After 3 months of hCG treatment, there was a marked rise in serum estradiol as well as testosterone. Serum T4 was reduced without a change in T3, T3 resin uptake, or TBG. Furthermore, there was no alteration in the TSH response to TRH. On the other hand, the administration of ethinyl estradiol (0.1 mg daily for 2 weeks) to two male IGD subjects produced an increase in TBG. This was associated with elevation of serum T4 and T3 levels and reduction of T3 resin uptake. During estradiol administration, there was an increase in the TSH response to TRH. These data are compatible with the hypothesis that estrogens are required to maintain a normal TSH response to TRH in the female. However, testosterone may counteract the effect of estradiol, which may explain why normal males tend to have a lower TSH response to TRH than females.

Low serum 3,3',5-triiodothyronine (T3) and reciprocally high serum 3,3',5'-triiodothyronine (reverse T3) concentration in spinal cord injury patients.

Thyroid function tests were performed on 115 spinal cord injury patients. Serum thyroxine, thyroid stimulating hormone, and T3 resin uptake were within normal range in all patients. Serum T3 levels tended to be low in paraplegic and quadriplegic patients, even though they were clinically euthyroid and other thyroid functions were normal. Serum reverse T3 levels were reciprocally higher in these patients.

Biochemical hypothyroidism in Nigerian children with nephrotic syndrome.

The nephrotic syndrome in Nigerian children is known to be largely associated with the endemicity of quartan malaria. Routine thyroid function studies were carried out on 24 children with clinical and biochemical evidence of the nephrotic syndrome. The children, aged four to 14 years, were all in the active phase of their disease, presenting with facial and pedal oedema and ascites. There was severe hypoalbuninaemia [mean (S.E.); 19.2 (1.1) g/l], hypercholesterolaemia; 10.5 (1.0) mmol/l and severe albuminuria ranging from 1 to 10 g/l. There was no clinical evidence of thyroid disease. The results of thyroid function tests in these children were compared with those of 181 apparently healthy children of the same age range. The mean total serum thyroxine levels (S.E.) were 118.3 (2.6) and 50.0 (6.4) nmol/l in controls and patients, respectively; T3 resin uptake values were 29.8 (0.2)% and 33.1 (1.2)%; the free thyroxine index (FTI) was 34.7 (0.8) and 16.7 (1.9) while thyrotropin (TSH) levels were 4.8 (0.2) and 10.6 (1.0) mU/l (IRP. MRC 68/38), respectively. The findings of low levels of thyroxine and FTI in association with high levels of TSH suggest that a state of primary hypothyroidism exists in these nephrotic children.

Impotence in Medical Clinic Outpatients

One thousand one hundred eighty men in a medical outpatient clinic were screened as to the presence of impotence. Four hundred one men (34%) were impotent, and of those, 188 (47%) chose to be examined for their problem. After a comprehensive evaluation the following diagnoses were obtained: medication effect, 25%; psychogenic, 14%; neurological, 7%; urologic, 6%; primary hypogonadism, 10%; secondary hypogonadism, 9%; diabetes mellitus, 9%; hypothyroidism, 5%; hyperthyroidism, 1%; hyperprolactinemia, 4%; miscellaneous, 4%; and unknown causes, 7%. The mean age of the impotent patients was 59.4 years, and the prevalence of alcoholism was 7%. Luteinizing hormone, follicle-stimulating hormone, testosterone, thyroxine, triiodothyronine (T3), T3 resin uptake, and prolactin studies were necessary to diagnose individual cases. We conclude that erectile dysfunction is a common and often overlooked problem in middle-aged men followed in a medical clinic.

Serum thyroid hormones and blood folic acid during monotherapy with carbamazepine or valproate. A controlled study.

Studies investigating the influence of antiepileptic drugs on thyroid hormones usually have compared patients chronically treated with antiepileptic drugs to controls. To date, this type of designs has produced divergent results both with regard to individual drugs and individual thyroid hormones. The present study comprised 31 patients with newly diagnosed epilepsy, commencing treatment with either carbamazepine or valproate. T3, T4, FT4, FT3, rT3, TSH, T3 resin uptake and blood folic acid, were determined before and during antiepileptic monotherapy, thus making the patient his own control. During treatment with carbamazepine, a significant decrease in T4, FT4, FT3, rT3 and TBG was observed. Valproate caused a decrease in T4, FT4 and T3. Neither of the drugs caused any changes in blood folic acid concentrations or persistent increases in the TSH values. None of the patients developed overt symptoms of hypothyreoidism. Conceivable mechanisms underlying these hormonal changes are reviewed.

Different effects of propranolol, alprenolol, sotalol, atenolol and metoprolol on serum T3 and serum rT3 in hyperthyroidism.

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

The role of 99 mTc pertechnetate uptake in the evaluation of thyroid function

To investigate the usefulness of the 20 min 99 m Tc-per-technetate uptake test, the records of 246 consecutive patients were reviewed. Of these, 192 patients (151 females, 41 males; 10 weeks to 78 years) had at least one year clinical follow-up or a confirmed diagnosis by biopsy or surgery and were included in our study. In these patients, the 99 m Tc pertechnetate uptake and hormonal values (T3 resin uptake, T4 RIA, T-index) were obtained. These results were then compared to the clinical diagnosis at the time of the uptake and one year later. All patients received an i.v. injection of 5 mCi of 99 m Tc pertechnetate. Imaging was performed using a pinhole collimator and a scintillation camera interfaced to a computer. Regions of interest for the thyroid and the background were used to calculate the 20 min 99 m Tc pertechnetate uptake as a percentage of the injected dose. 99 m Tc uptake and hormonal values were confirmatory in 158 patients (82.3%): 138 were euthyroid, 18 were hyperthyroid and 2 were hypothyroid. In 29 other patients (15.1%) the pertechnetate uptake provided useful additional information and helped to identify Hashimoto's thyroiditis (8 patients); thyroid suppression by exogenous iodide, steroids or T4 (7 patients); overtreated hyperthyroidism (1 patient); persistent hyperthyroidism (5 patients); different stages of Grave's disease (4 patients); and toxic nodular goiter (4 patients). The 99 m Tc uptake was misleading in 5 euthyroid patients (2.6%). We have found the 99 m Tc pertechnetate uptake a useful adjunct to measurement of hormonal levels in patients with suspected thyroid disease.

A link between liver microsomal enzyme activity and thyroid hormone metabolism in man.

1 The effect of different combinations of liver microsomal enzyme inducing drugs on thyroidal hormone steady state concentrations was investigated. Three groups of healthy volunteers were given daily either antipyrine 1200 mg together with phenobarbitone 100 mg, antipyrine 1200 mg combined with rifampicin 600 mg or rifampicin 600 mg alone for a period of 14 days. 2 Before and after each treatment the total body clearance of antipyrine, gamma-glutamyl transferase (gamma-GT), 6 beta-OH-cortisol as in vivo parameters of liver microsomal enzyme activity were measured. In addition, thyroxine (T4), free thyroxine (FT4), T3 resin uptake, tri-iodothyronine (T3) reverse T3 (rT3) and TSH were estimated. 3 After rifampicin administration there was a 60% increase in antipyrine clearance while following combinations of antipyrine-phenobarbitone or antipyrine-rifampicin an 80% and 128% increase respectively occurred. 4 A marked decrease of T4, FT4 and rT3 was seen in all groups while T3 remained stable in all groups investigated. This effect may be partly due to an increase in extrathyroidal metabolism of T4 as found previously by a kinetic turnover study using 125I-T4. It also depends on the extent of the liver microsomal enzyme inducing capacity rather than on the nature of the drugs used. The striking disparity of liver enzyme induction of T4 and rT3 disposal on the one hand and T3 metabolism on the other is a unique phenomenon whose pathogenesis is not clear at the present time.