Thyroid Radioiodine Research Articles

The variation in serum triiodothyronine (T3) achieved during suppression testing in thyrotoxicosis.

SUMMARYRegular measurement of thyroidal radioiodine uptake has been widely used as a means of monitoring continued extrapituitary stimulation of the thyroid during the treatment of thyrotoxicosis with carbimazole and triiodothyronine (T3). However, it is unclear to what extent the serum T3 level may vary at the time of testing, nor what effect this might have on the uptake of radioiodine. Two studies have been undertaken. In the first, serum T3 levels in twenty‐four thyrotoxic patients were measured at intervals during an 18‐month course of carbimazole combined with T3, 20 μg qid. Considerable variations in the highest and lowest levels of serum T3 were found both between and within individuals. The second study was on twenty‐three thyrotoxic patients thought to be entering remission because the iodine uptake after 5 months of drug treatment had fallen to less than 50% of the pretreatment value (suppressors). The changes in uptake of radioiodine after 5 and then 6 months of treatment were compared in seven patients, who received carbimazole and T3 throughout, with the corresponding changes in the remaining sixteen patients, whose T3 alone was withdrawn prior to the uptake test at month 6. The mean degree of suppression remained unchanged by month 6 in the first group. In the second group, however, the mean uptake rose significantly, and nine of the sixteen patients would have been classified as non‐suppressors at the sixth month (i.e. uptake greater than 50% the pretreatment value) had their failure to maintain high serum levels of T3 gone undetected. The first study indicated this could well happen in routine circumstances, and it is suggested that the reliability of suppression tests be checked with simultaneous measurement of serum T3.

Thyroglobulin and Calcitonin in Patients With Nontoxic Goiter

THE SERUM thyroglobulin (Tg) concentration is elevated in some patients with differentiated thyroid carcinoma.¹Plasma calcitonin (CT) measurement is a specific screening test for medullary carcinoma of the thyroid.²The purpose of our study was to assess the clinical value of measuring plasma thyroglobulin and calcitonin levels in the evaluation of nontoxic goiter. <h3>Patients and Methods</h3> Patients with goiter who attended the endocrine clinics of the Wadsworth Veterans Administration Hospital or the University of California, Los Angeles, Hospital had blood samples drawn during routine visits. All patients had been examined for goiter by standard techniques, including thyroid function tests, antithyroid antibodies, and radioiodine thyroid scans. Thyroid size was estimated by palpation, and nodules were measured with a plastic ruler. In patients with single nodules discovered by palpation, the thyroid size was estimated by adding the mass of the nodule to that of the normal gland, which was assumed

Inhibition of TSH-stimulated radioiodine turnover and release of T 4 and T 3 in vivo by somatostatin

With respect to the hypothalamic-pituitary-thyroid axis, it has been demonstrated that somatostatin blocks the pituitary thyrotropin (TSH) release stimulated by thyrotropin-releasing hormone (TRH). 1,2 Recently, somatostatin has been shown to be present in the thyroid gland. 3,4 To elucidate the role of somatostatin in the regulation of thyroid function, the effect of somatostatin on TSH-stimulated thyroidal radioiodine turnover and thyroid hormone release in vivo were studied in euthyroid volunteers.

Comparison of pituitary-thyroid maturation in the fetuses of rats fed an iodine-deficient or normal diet.

From the earliest detectable development of fetal pituitary-thyroid function (day 18-19 of gestation) through the first postnatal day, there was a higher degree of stimulation of the pituitary-thyroid axis in the fetuses of rats fed a low iodine diet (LID) than in those of rats fed a high iodine diet (HID). Significant differences between the two groups were consistently observed in relative thyroid size, plasma TSH, 4-h thyroid radioiodine uptake, and the labeled iodoamino acid composition of thyroid digests. Plasma T4 concentration was lower in both LID and HID fetuses and pups than in the HID mothers. Plasma T3 was not detectable (less than 20 ng/dl) in the fetuses of either group, nor was labeled T3 in the thyroid digests. Body weight, plasma T4, and pituitary TSH content were usually lower in the LID than the HID animals of comparable age; however, these differences were not consistently statistically significant (P less than 0.05). We conclude that iodine deficiency causes a marked stimulation of TSH secretion and, consequently, of thyroid growth and metabolism from the earliest development of fetal pituitary-thyroid function.

TRH test as an index of suppression compared with the thyroid radioiodine uptake in euthyroid goitrous patients treated with thyroxine.

To determine an index of adequate suppression of pituitary TSH secretion in euthyroid goitrous patients treated with sodium levothyroxine (T4), TSH responses to 500 micrograms TRH given iv were compared with thyroid 24-h radioiodine uptakes during therapy with T4 in 12 euthyroid goitrous patients. The patients received sequentially 100, 150, 200, 250, and 300 micrograms T4 with the doses increased at 4-6 week intervals. The mean dose of T4 that reduced the peak TSH response to TSH to the lower limit of normal (TSH = 5 microU/ml) was 130 micrograms; the mean T4 dose that suppressed the TSH response to one-half the lower limit of normal (TSH = 2.5 microU/ml) was 165 micrograms. The mean T4 dose that nearly obliterated the TSH response was 200 micrograms; this degree of suppression occurred with doses of 100-300 micrograms T4 in individual patients. Suppression of thyroid uptake correlated closely with suppression of the TSH response to TRH. The goiter diminished in size significantly in 6 of the 12 patients during the 6 months of observation adn did not enlarge in any patient. The data indicate that suppression of the TSH response to TRH is a convenient technique to assess the adequacy of suppressive therapy of goiter.

Studies on the mechanism of goitrogenic action of diphenylthiohydantoin.

Diphenylthiohydantoin (DPTH) is a potent goitrogenic compound and produces goiters in rats. Like methimazole, DPTH depresses plasma T4 and T3 concentrations and elevates plasma T4 and T3 concentrations and elevates plasma TSH concentration. Unlike methimazole, however, DPTH does not suppress thyroidal radioiodine uptake and thyroid hormone synthesis, although the monoiodotyrosine to diiodotyrosine ration is elevated by DPTH. DPTH does not inhibit thyroidal radioiodine release or augment the degradation of thyroid hormone. DPTH depresses an increase of plasma T4 and T3 in thyroidectomized rats maintained on T4 or T3 by augmenting fecal excretion of hormones. In addition, DPTH decreases conversion of T4 to T3 in vitro. It is suggested that DPTH is a unique goitrogen which acts at two different extrahyroidal sites, viz. fecal loss of thyroid hormone and conversion of T4 to T3.

Contamination of the home environment by patients treated with Iodine-131: initial results.

We have employed twin sodium iodide radiation detectors to analyze iodine-131 transfer from thyroid patients to their families. Unlike previous studies of this problem, we measured thyroid radioiodine activity directly and are able to detect as little as 92 pCi of iodine 131 in adult thyroids. As in previous studies, we have also measured direct radiation exposures of family members with wristband thermoluminescent dosimeters. Thus far, we have studied seven families with 17 persons. Eleven of these are children under age 16. Direct radiation exposure of family persons from proximity of these radioactive patients ranged from 0.17 to 126 mR per day (natural background radiation amounts to approximately 0.35 mR per day). The maximum activity of iodine-131 in family thyroids ranged from less than 92 pCi to as high as 110,000 pCi and resulted in thyroid dose equivalents of 4 to 1330 mrem. Based on recent estimates of thyroid cancer, the latter dose equivalent could possibly double the risk of thyroid malignancy in children over what is expected normally. Such a risk implies the addition of 10 induced cases to the 10 naturally occurring cases per million people per year.

Dietary iodine and accumulation of radioiodine in thyroids of chickens.

Groups of hatchling white leghorn cockerels were fed a basic, semisynthetic low-iodine diet to which various amounts of iodide were added: 0 up to 100 microgram I/g feed. Growth rates were unaffected by the range of dietary iodine content. A transitory goiter occurred only in the group fed the basic low-I diet. Half-life of 131I in the thyroid increased directly and fractional turnover rate inversely with increase of dietary iodine. Trichloroacetic acid-soluble iodine in serum did not accurately reflect variation of dietary iodine. However, effective clearance and binding rate constants did decrease proportionally to dietary iodine increase beyond the first 3-5 days. Concentration of iodine in thyroid was directly proportional to dietary iodine after 10 days. There was no consistent correlation between thyroxine or triiodothyronine and dietary iodine except in general terms of high and low dietary iodine groups. The avian thyroid exhibits great lability in adjusting functionally to a wide range of dietary iodine contents.

Cord blood screening for congenital hypothyroidism

Top of pageAbstract A regionalised screening programme for neonatal hypothyroidism using umbilical cord blood has been developed. An initial serum thyroxine (T4) was performed on all infants and supplementary thyrotropin (TSH) measurements were made only on those samples where T4 was 50 μU/ml were recalled. In 38,000 births 14 detected cases had thyroid dysfunction (TD) confirmed by thyroidal radioiodine uptake (RAI). Primary TD occurred in 13:- Athyrosis 4, Dyshormonogenesis 3, Hypoplasia 3, Lingual thyroid 2, Iodide induced 1; and secondary in 1 case. Without the hypoplasia cases (where “subclinical hypothyroidism” was present on follow up: normal T4, abnormal RAI, and elevated TSH) and the secondary case, the incidence of significant primary hypothyroidism (SPH) was 1 in 4,000. Treatment with L-thyroxine 5.0 μg/kg/day was begun day of life 25-83 in the 10 SPH cases with 8 treated before 5 weeks and 5 before 4 weeks of age. A high incidence of congenital hypothyroidism has been documented, and the effectiveness of cord blood screening for its early detection and treatment demonstrated.

The effects of prolactin and TSH on thyroid function in Fundulus heteroclitus

Treatment with ovine prolactin significantly reduces serum T 4 in Fundulus heteroclitus, both in control ( P < 0.05) and TSH-stimulated fish ( P < 0.01), without affecting thyroidal radioiodine uptake. Prolactin also reduces the loss of radioiodine from F. heteroclitus ( P < 0.001). This loss is markedly increased by ovine TSH ( P < 0.001), but only in the absence of prolactin. Although other explanations are possible, prolactin is probably goiterogenic in F. heteroclitus, lowering thyroidal secretion of T 4 as well as inhibiting the peripheral effects of this hormone.

Congenital Defect in Iodothyronine Synthesis. Clinical Aspects of Iodine Metabolism in Goats with Congenital Goitre and Hypothyroidism

SUMMARY Iodine metabolism was studied in seven normal goats and six goats with congenital hypothyroidism and goitre. The goitrous goats were greatly retarded in growth, their skin was thick and scaly, and they had a sparse haircoat. Thyroidal turnover of radioiodine was markedly increased and was not influenced by the administration of KCNS or methimazole. There was no apparent defect in deiodination of iodotyrosines. Column chromatography of plasma revealed that most of the thyroidal radioiodine was released into the circulation as an iodopolypeptide. No free MIT or DIT could be detected in the plasma or urine. These findings suggest that the goitrous goats had a defect, comparable to those found in man and sheep, in thyroglobulin synthesis, with the release of abnormal iodinated proteins into the circulation.

Abnormalities in Thyroid Function in Relatives of Patients with Graves' Disease and Hashimoto's Thyroiditis: Lack of Correlation with Inheritance of HLA-B8

Thyroid function, antithyroid antibodies and human major histocompatibility locus (HLA) antigens were studied in first-degree relatives (parents, siblings and children) of patients with Graves' disease and Hashimoto's thyroiditis. The particularly common abnormalities in Graves' relatives were positive antithyroid antibodies (25 of 74 cases, 34%) and supranormal thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) (12 of 44 cases, 27%). Less common abnormalities were goiter (10 of 92 cases, 11%), ophthalmopathy (1 of 92 cases, 1.1%), non-suppressibility of 24 h thyroid radioiodine uptake (2 of 48 cases, 4.2%), elevated baseline serum TSH (4 of 80 cases, 5.0%), subnormal TSH response to TRH (2 of 44 cases, 4.5%) and detectable LATS-protector (3 of 47 cases, 6.4%). Thyroid uptake was non-suppressible in two of the three cases with LATS-protector; the remaining one had ophthalmopathy and normally suppressible thyroid uptake. Of the 14 relatives of patients with Hashimoto's thyroiditis included i...

Permissive role of thyrotropin on thyroid radioiodine uptake during the recovery phase of subacute thyroiditis

Serial measurements of serum triiodothyronine (T 3), thyroxine (T 4), thyrotropin (TSH), and 4-hr thyroidal 131I uptake were carried out in nine patients with subacute thyroiditis. In the acute phase, suppressed TSH and 131I uptake were observed simultaneously with the elevations of T 3 and T 4. Thyrotropin-releasing hormone (TRH) failed to increase TSH in all patients studied. The mean value of an increment in serum TSH was only 1.8 μU/ml during the recovery phase when 131I uptake was normal or hyper-normal. In addition, and elevated 131I uptake was not necessarily associated with an immediate increase in the serum T 3 and T 4. These observations suggest that the resumption of the iodide pump may be more important than an increment in TSH in producing normal or hypernormal 131I uptake during the recovery phase. There appears to be a dissociation between the reestablishment of 131I uptake and the resumption of the mechanism of hormonal synthesis and secretion in the thyroid.

GLYCEROL RELEASE IN VITRO FROM ADIPOSE TISSUE OF OBESE (ob/ob) MICE TREATED WITH THYROID HORMONES

Glycerol release from adipose tissue of adult genetically obese (ob/ob) mice was greater than that from adipose tissue of lean litter-mates. However, a higher concentration of adrenaline was required to stimulate lipolysis in ob/ob adipose tissue. Since oxygen consumption and the uptake of radioactive iodine by the thyroid were reduced and the biological half-life of thyroidal radio-iodine was lengthened, it is suggested that ob/ob mice are hypothyroid. The poor sensitivity of ob/ob adipose tissue to low doses of adrenaline was improved by treatment with either tri-iodothyronine or thyroxine. The lipolytic responses to both dibutyryl 3':5'-cyclic adenosine monophosphate and aminophylline were enhanced in thyroid hormone-treated lean and ob/ob mice. A higher dose of tri-iodothyronine was required to enhance lipolysis in ob/ob mice than in lean controls. The possibility that hypothyroidism is responsible for the change in response of ob/ob adipose tissue to lipolytic hormones is discussed.

The thyroidal response to chronic goitrogenic stimulation and the persistence of effects of early goitrogenic stimulation

The effects of overstimulation of the thyroid gland induced by the feeding or rapeseed meal or thiouracil during the growing period persisted for as long as 75 weeks after withdrawal of the source of goitrogen from the diet. Thyroid weight, thyroid iodine content and radioiodine uptake were all increased in birds which had received goitrogen during the growing period. Follicle diameter was greater and the height of epithelial cells was lower than in control birds. The thyroid changes in these birds were deduced to be compensatory because production characteristics were normal and distribution of a dose of radioiodine into thyronines (T3 + T4) was similar in the birds which had received goitrogen during the growing period and in the control birds. Birds which were being fed rapeseed meal at the time the thyroid gland were examined showed effects which varied in magnitude according to the length of time over which rapeseed meal had been fed. Thyroid weight, follicle diameter, amount of epithelial tissue present and the total amount of iodine in the thyroid glands increased, whereas coupling efficiency (radioiodine-labelled T3 + T4)/(monoiodotyrosine/diiodotyrosine) declined with time.

Factors increasing the probability of malignancy in thyroid nodules

A series of 348 patients undergoing operative intervention because of thyroid masses is reviewed. The incidence of primary malignancy among these patients is 16.4 per cent. Male sex and the presence of cervical adenopathy significantly increase the probability of malignancy. The presence of multiple nodules or a functional nodule on radioiodine thyroid scan significantly reduces the probability of cancer. A rational approach to thyroid nodules is presented based on these findings and new modalities that have become available.

Abnormal thyroid function in spontaneously hypertensive rats.

Thyroid weight, thyroidal radioiodide uptake, and cyclic AMP-dependent protein kinase activity of a thyroid supernatant fraction were increased significantly in spontaneously hypertensive rats (SHR), apparently because of increased secretion of pituitary TSH. However, the thyroids of SHR did not make supernormal amounts of thyroxine (T4), and thyroidal radioiodine release was apparently impaired. In the SHR, proteolytic enzyme activity was less than normal and the thyroglobulin was more resistant to normal proteolytic enzyme than was control thyroglobulin. Presumably because of these abnormalities, plasma T4 was significantly lower than normal, but triiodothyronine (T4) was normal, as a result of compensatory processes occurring in T3 synthesis and hydrolysis of thyroglobulin. T4 and T3 were less effective in depressing pituitary TSH synthesis and secretion in SHR than in controls, possibly because of an abnormal setting of the "hormostat." Although the hypothalamic content of TRH was normal in SHR, the exact site of the abnormality in the "hormostat" is not delineated in the present study.

Inhibitory effect of large doses of propylthiouracil and methimazole on an increase of thyroid radioiodine release in response to thyrotropin.

Thyroidal radioiodine release increased shortly after a single injection of small doses of PTU, while moderate doses of MMI produced a similar increase of thyroidal radioiodine release with a latency of 7-9 hr. Large doses of PTU and MMI failed to augment thyroidal radioiodine release for at least 29 to 34 hr after the initial administration of goitrogens, although plasma TSH increased significantly because of goitrogen administration. An increase of thyroid hormone release in response to exogenous TSH was depressed by PTU and MMI in rats and mice treated with T4. Since this depression of TSH action only continued for a short period in spite of continuous administration of goitrogens, and since final thyroidal radioiodine release rate was similar to that produced by small doses of PTU, the effects mentioned were not simply due to general toxic action of goitrogens. It is suggested that large doses of PTU and MMI not only block thyroid hormone synthesis but also interfere with the action of TSH on thyroid hormone secretion.

Safety evaluation studies on oxisuran, a differential inhibitor of cell-mediated hypersensitivity

Preclinical toxicity studies were conducted on oxisuran, 2-[(methylsulfinyl) acetyl]-pyridine, an immunosuppressant with selective inhibition of cell-mediated hypersensitivity. Oral LD50 values were 5280 and 6610 mg/kg in female mice and rabbits, respectively, and 6550 mg/kg in female and male rats. An LD50 could not be established in dogs because of emesis at a dose of 5000 mg/kg. Intravenous LD50 values were 2510 mg/kg for mice and 1800 mg/kg for female and male rats. Feeding the drug in the diet to rats at dosages of 20, 100, 300, and 1000 mg/kg for 13 weeks caused a slight reduction in food consumption and body weight gain at the higher dosages. At doses of 100, 300, and 1000 mg/kg, cloudy swelling and fatty infiltration of the liver and hyperplasia of the thyroid occurred in dose-related patterns (mild to moderate) in many animals. No significant changes were found in thyroid function studies which included thyroid uptake ( 125I) and T 3 and T 4 determinations. The thyroid hyperplasia seen at 13 weeks disappeared within a few days of drug withdrawal. Oral daily administration of 20, 125, 500, and 2000 mg/kg of oxisuran to dogs for 13 weeks produced a decrease in food consumption and body weight in the latter phase of the study in the males treated with the high dose. Serum glutamic-pyruvic transaminase was mildly elevated in dogs given 2000 mg/kg. At this dose, some animals showed slightly increased thyroid and liver weights. Histologically, thyroid hyperplasia was moderate in females (2000 mg/kg) and mild to moderate in males (125, 500, and 2000 mg/kg). The liver, in the animals of the high-dose group showed a slight degree of vacuolar changes and bile retention. Thyroidal radioiodine uptake ( 125I), PBI, TI, and serum cholesterol were slightly below normal values. The histology and function tests of the thyroid were within normal ranges at 4 weeks post-treatment.

STUDIES ON THE MECHANISM OF GOITROGENIC ACTION OF DIPHENYLTHIOHYDANTION

Diphenylthiohydantoin (DPTH) is a potent goitrogenic compound and produces a large goiter in rats. Like methimazole, DPTH depresses plasma thyroxine (T4) and triiodothyronine (T3) concentrations and elevates plasma TSH concentration. Unlike methimazole, however, DPTH does not suppress thyroidal radioiodine uptake and thyroid hormone synthesis. DPTH does not depress thyroidal radioiodine release nor augment the degradation of thyroid hormone. DPTH depresses an increase of plasma T3 and T4 in thyroidectomized, T4- and T3-maintained rats by augmenting fecal excretion of hormones. In addition, DPTH depresses peripheral conversion of T4 to T3 in vitro.It is suggested that DPTH is an unique goitrogen which acts on 2 different extrathyroidal sites, viz. fecal loss of thyroid hormone and conversion of T4 to T3.