Radioiodine Treatment Of Hyperthyroidism Research Articles

Secretion and metabolism of monomeric human calcitonin: effects of age, sex, and thyroid damage.

Some data suggest that human calcitonin (CT) secretion is lower in women than in men, decreases with age and the menopause, and is absent in thyroidectomized persons. To further explore CT secretory physiology, we have studied basal and calcium-stimulated plasma immunoreactive CT (iCT) and silica-extractable monomeric CT concentrations in 148 healthy volunteers and 33 patients with a history of thyroid damage (total or subtotal thyroidectomy, radioiodine treatment for thyrotoxicosis). Both whole-plasma iCT and extractable CT levels were lower basally and after calcium infusion in women than in men, basal levels being reduced about 50% and calcium-stimulated values about 75% from those of male subjects. There were no significant changes in basal iCT or extractable CT concentrations with age, and CT secretory capacity (CT response to calcium infusion) likewise did not change with age. Infusion of monomeric CT to constant concentration in 27 persons permitted estimates of CT metabolic clearance rates (MCRs) and secretion rates (SRs). Calculated MCRs of about 9 ml/min.kg-1 (persons aged 21-30 yr) and 6 ml/min.kg-1 (persons aged 54-70 yr) were in good agreement with published data, and did not differ between the sexes. SRs were dependent upon the assay method used to estimate basal plasma CT concentrations, being highest when whole-plasma iCT values were used. Based on estimates of plasma monomeric CT from the silica extraction procedure, the SR of CT was 59 +/- 6 (SE) ng/d.kg-1 in men, and 22 +/- 3 ng/d.kg-1 in women. Thyroid damage reduced, but did not abolish, apparent CT immunoreactivity, even in silica extracts of plasma. However, all subsets of thyroid-damaged patients had absent-to-markedly-impaired CT secretion in response to calcium infusion. We conclude that CT secretion is substantially lower both basally and after stimulation in women than in men, and that this difference in CT immunoreactivity probably reflects differences in circulating CT bioactivity. The sex difference in plasma CT concentrations probably results from lower rates of CT secretion in women, not increased MCR. There is no age-related decrease of plasma CT concentrations (or CT secretory reserve), calling into question the concept that a progressive deficiency of CT is partly responsible for age-related ("senile") osteoporosis. Surgical or radiation damage to the thyroid gland commonly abolishes C-cell response to calcium; such CT-deficient patients form a population suitable for determining whether or not reduced CT secretion can impair skeletal homeostasis.

8 Radio-iodine treatment of hyperthyroidism— a more liberal policy?

The main and most valid evidence we have is that on direct follow-up of treated patients. This has been well done in thousands of patients in two countries with very good medical care and over long periods--10 to 15 years or more. On the other hand there is no doubt about radiation carcinogenesis, and thyroid cancer has been caused in children by low-dose x-ray therapy. The possibility of other cancer and of leukaemogenesis is also real. The evidence for this is reviewed and risk estimates given. Experimental work and radiation biology is reviewed and it is suggested that the risk of thyroid cancer from the usual radio-iodine doses given for treatment is low because of cell killing or sterilization, and animal evidence is discussed that supports this. The final position appears to be that no risk has yet been demonstrated in man and evidence in general suggests that if there is indeed a cancer risk it will be less than about 0.1%. It is suggested that this is not dissimilar to surgical risks, except that these are more immediate as compared with the long latent period for development of radiation-induced cancer. Genetic risks are also discussed and again have not been demonstrated in man from this treatment and should in any case be low. The risk to children is also considered; there is no direct evidence of risk but only small numbers have been treated--nevertheless the hypothetical risk may be counterbalanced by the benefits. Administration of radio-iodine therapy to pregnant or lactating women must be scrupulously avoided; both cause significant risks. Finally, if a more liberal policy be accepted it is worth while giving optimum treatment, and evidence is given suggesting low-dose treatment similar in effect to surgical thyroidectomy and followed temporarily if need be by anti-thyroid drug treatment.

Risks from radioiodine treatment for thyrotoxicosis

Risks from radioiodine treatment for thyrotoxicosis

RAISED PLASMA-THYROID-STIMULATING-HORMONE LEVELS IN THYROTOXIC PATIENTS TREATED WITH IODINE-131

69 euthyroid patients who had raised plasma - thyroid - stimulating - hormone (T.S.H.) levels (>7·4 μU. per ml.) in February, 1972, after 131I therapy for thyrotoxicosis between 1954-66 were reassessed fifteen months later. The initial mean plasma-T.S.H. level ± S.E. in the 66 patients who remained euthyroid (25·0±2·0 μU. per ml.) was unchanged (22·6±1·8 μU. per ml.) at the end of the study. Overt hypothyroidism developed in only 3 patients with initial plasma-T.S.H. levels of 34·6, 45·6, and 90·4 μU. per ml. At follow-up these patients had plasma-T.S.H. levels of 67·3, 28·2, and 92·8 μU. per ml., respectively. Since raised plasma-T.S.H. concentration occurring after radioiodine treatment of thyrotoxicosis does not alter for a considerable period, it cannot be used as an indication of impending overt hypothyroidism.

Surgical treatment of thyrotoxicosis.

A retrospective study of thyrotoxic patients treated by subtotal thyroidectomy between 2 and 21 years ago in the north-east of Scotland showed that 20% of the patients could not be identified or traced at the time of the survey. The thyroid status of 40% of patients followed up was abnormal.It is now accepted that radioiodine treatment of thyrotoxicosis is followed by a significant incidence of late onset hypothyroidism, and life-long follow-up is regarded as obligatory. The findings in this study indicate that similar methods of aftercare are required for surgically treated patients and for all patients receiving thyroxine-replacement therapy.

Cellular Autoimmune Reactions Following Radioiodine Treatment for Hyperthyroidism

Cellular Autoimmune Reactions Following Radioiodine Treatment for Hyperthyroidism

Organ antibodies after local irradiation.

Radioiodine treatment for hyperthyroidism is followed by an increase in the thyroid humoral antibodies (2). This increase is temporary (3, 11, 16), lasting about one year, after which there is a gradual drop to below the pretherapy values (3). The increase is due to the radiotherapy, since it is not found after other forms of treatment for hyperthyroidism, such as subtotal thyroidectomy (3, 7). The rise in humoral thyroid antibodies after radioiodine therapy has also been observed in euthyroid patients (4). The question is whether this increase in thyroid antibodies is a manifestation of a general nonspecific increase in the humoral antibodies or a sign of a specific immunologic reaction directed only against the irradiated tissue. It should be possible to decide which of these two explanations is the correct one if it were known whether radioiodine therapy produces an increase in antibodies also against other tissues than the thyroid and whether there is an increase in the thyroid antibodies also after intensive, local irradiation of other tissues. The object of the present study was to elucidate these problems. Material The study was performed in 129 consecutive cases of hyperthyroidism and 47 euthyroid patients, who were examined before radioiodine therapy and two to twelve months afterward, and on 86 cases of carcinoma of the cervix or corpus uteri, who were examined before and two to twelve months after intracavitary application of radium. No patients with known auto-immune disease were included in the group given radioiodine therapy, and no patients with known auto-immune or thyroid disease were included in the radium-treated group. Methods The methods used for radioiodine therapy were the same as described previously (3, 4). In radium treatment for tumors of the corpus or cervix uteri, as in radioiodine therapy, an extremely large radiation dose is supplied to a small area and only a small dose to the rest of the body. Irradiation with radium was given in two local applications at intervals of about three weeks. The total dose on the surface of the mucous membrane was 20,000 to 30,000 R and at 2 cm depth 4,000 to 5,000 R. Some of the patients had also received external 60CO therapy. The method has been described by Kottrneier (12). Antibodies to bovine gamma globulin and to human 7S gamma globulin were examined by the tanned-cell passive hemagglutination test (1). Antibodies to parietal cells were examined with the indirect immunofluorescent test (10, 19, 20), using unfixed sections of rat gastric mucosa. Antibodies to nuclear antigens were examined by the same technic (8, 9), with acetone-fixed sections of human thyroid. The test sera were heated to 56°C for thirty minutes and diluted one to five before incubation on the tissue sections.

Complications in Radioiodine Treatment of Hyperthyroidism

Complications in Radioiodine Treatment of Hyperthyroidism

ISOLATION AND IDENTIFICATION OF THE LONG-ACTING THYROID STIMULATOR AND ITS RELATION TO HYPERTHYROIDISM AND CIRCUMSCRIBED PRETIBIAL MYXEDEMA.

Long-acting thyroid stimulator (LATS) was found in the plasma in each of 7 subjects with circumscribed, pretibial myxedema, which in every instance had developed after surgical or radioiodine treatment of thyrotoxicosis. Using a potent plasma from one of these subjects, a bio-assay method for the quantitative measurement of LATS was developed which was used in subsequent fractionation and recovery experiments. By fractional precipitation of the proteins of LATS plasma by acid potassium phosphate, followed by gel filtration of the active fraction through diethylaminoethyl-Sephadex, LATS was eluted with a single protein moiety and was recovered in 60–80% yield with an 8-fold increase in purity. Analysis by the methods of ultracentrifugation, paper electrophoresis, immunoelectrophoresis, double diffusion in agar, and sucrose gradient separation confirmed the presence of a single protein which was identified as a 7S gamma globulin. Incubation of LATS with antihuman-7S antibody or digestion of LATS by papain d...

Leukemia following radioidine therapy of hyperthyroidism.

POCHIN has recently analyzed the incidence of leukemia in patients previously given I¹³¹(an internal source of beta and gamma rays) for the therapy of hyperthyroidism.¹The data were collected by questionnaire from those clinics in Great Britain which used the isotope therapeutically. Information was included which had been assembled by others in several additional countries where I¹³¹therapy is extensively employed. Eighteen cases of leukemia in hyperthyroid patients previously treated with I¹³¹were collected through May, 1960. Three cases were also recorded in which the onset of leukemia had preceded I¹³¹therapy and which might erroneously have been considered to have followed I¹³¹therapy had not a preliminary blood count been performed. Pochin concluded, "The present evidence, while giving no support to the idea that leukemia is induced by the radioiodine treatment of thyrotoxicosis, neither excludes such induction nor sets any upper

Leukaemia following radioiodine treatment of thyrotoxicosis.

Leukemia is known to have developed in 18 patients who had previously been treated with radioiodine for thyrotoxicosis, three cases having occurred in the United Kingdom, ten in the United States, four in Canada, and one in Austria. About 60,000 thyrotoxic patients have been treated with radioiodine in these four countries alone, with an estimated total of over 220,000 patient-years since treatment until mid-1960. Application of natural leukemia rates appropriate to the sex, age, and nation of these patients suggests that approximately 21 cases of leukemia would be expected to have occurred fortuitously among them whether radioiodine had been given or not. The numbers of patients treated in those countries in which cases of leukemia have not been observed would raise this total considerably. The intervals between radioiodine treatment and diagnosis of leukemia are consistent with a change distribution. Of the 17 cases in which the type of leukemia is known, l3 were diagnosed as acute, a proportion somewhat, but not strikingly, higher than that to bc expected on the basis of data for England and Wales on the frequency of acute leukemia in a normal population of corresponding age and sex. These estimates are held to indicate that themore » present known records of cases in which leukemia has followed radioiodine treatment of thyrotoxicosis gives no indication that this treatment is inducing leukemia. At the same time they clearly do not exclude this possibility, since the total number of cases of leukemia might greatly exceed the number at present known to have occurred. (auth)« less

Leukaemia following radioiodine treatment of hyperthyroidism.

A patient died of acute leukaemia 28 months after her hyperthyroidism had been effectively treated with 7·1 mc of radioiodine. This dose is unlikely to have caused radiation of more than 100 reps in relevant extrathyroid tissues.

Impaired organic binding of radioiodine by the thyroid following radioiodine treatment of hyperthyroidism.

THERE have been several attempts to demonstrate a change in thyroid physiology following irradiation with radioiodine. Skanse (1) was able to show in chicks that the thyroid lost its ability to retain large doses of radioiodine and that its growth response to thiouracil and thyrotropic hormone was diminished following large doses of the isotope. On the other hand, Salter (2), using the thyroidal radioiodine uptake, serum protein-bound iodine concentration, and the rate of turnover of radioiodine into thyroxine, came to the conclusion that no appreciable change in thyroid function occurs in humans following therapeutic dosage with radioiodine. Evidence will be presented here of a specific change in thyroid function following such therapy. The work of McGinty and Sharp (3) in 1946 showed that radioactive iodine trapped by a thyroid gland which is under the effect of thiouracil remains in the inorganic form. Organic binding of the trapped iodide does not occur. This work was later confirmed by VanderLaan and...