[Iodine-induced hyperthyroidism after cadexomer iodine treatment of leg ulcers]. / Jodinducerad tyreotoxikos efter cadexomerjodbehandling av bensår.

The article consists in two case reports of eldery patients who developed hyperthyroidism after cadexomer iodine treatment of small leg ulcers. The first was an 87-year-old woman who developed anxiety, hoarseness and tachycardia after five months treatment of a 12 cm2 leg ulcer with 350 g cadexomer iodine. Her serum level of free thyroxine (FT4) was 23.1 pmol/l (normal range, 11.7-28.0), and that of thyroid-stimulating hormone (TSH) 0.01 mIU/l (normal range, 0.1-3.0). She had had a nodular goitre for thirty years. The second was an 86- year-old woman who developed depression and confusion after three months' treatment of an 8 cm2 leg ulcer with 170 g cadexomere iodine. Her serum level of FT4 was 30.0 pmol/l, and that of TSH 0.005 mIU/l. Both patients underwent Tc99m pertechnetate scanning and iodine uptake measurement with a view to treating the hyperthyroidism with radio-iodine. However, as iodine uptake was inhibited in both cases, radio-iodine treatment was impossible, and symptomatic treatment and antithyroid drugs had to be used. Thus, it is concluded that topical treatment with cadexomer iodine can induce hyperthyroidism difficult to manage clinically as the treatment options are limited, which should be borne in mind when cadexomer iodine treatment is considered.

Systemic radionuclide therapy using indium-111-DTPA-D-Phe1-octreotide in midgut carcinoid syndrome.

A 55-yr-old woman with a midgut carcinoid syndrome due to metastatic spread of an ileal tumor to the liver, paraortic and mediastinal lymph nodes and to the skeleton was given systemic radionuclide therapy with 111In-DTPA-D-Phe1-octreotide. Before therapy, dosimetric calculations were performed on whole-body scintigraphs and 111In retention was shown to be long-lasting. Excretion was mainly seen during the first 24 hr after injection; thereafter whole-body retention remained stationary at 30%. Indium-111 activity in tumor biopsies and blood was measured using a gamma counter. Very high tumor-to-blood ratios were obtained: 150 for the primary tumor and 400-650 for liver metastases, which further justified radiation therapy. Indium-111-DTPA-D-Phe1-octreotide treatment was given on three separate occasions (3.0, 3.5 and 3.1 GBq) 8 and 4 wk apart. After each therapy, the patient experienced facial flush and pain over the skeletal lesions followed by symptomatic relief, even though no objective tumor regression was found radiologically after 5 mo. After initiation of octreotide treatment, there was a 14% reduction of the main tumor marker, urinary 5-HIAA. After three subsequent radionuclide therapies, there was a further 31% reduction of 5-HIAA levels. No adverse reactions, other than a slight decrease in leukocyte counts, were seen. The mean absorbed radiation dose after the three treatments was estimated to be about 10-12 Gy in liver metastases and 3-6 Gy in other tumors, depending on the size and location of the metastases. Assuming internalization of 111In into tumor cells and a radiobiological effect from short range Auger and conversion electrons, there might be a therapeutic effect on the tumor.

Clinical outcome of radioiodine treatment of hyperthyroidism: a follow-up study.

OBJECTIVES: To study the clinical outcome of treatment of hyperthyroid patients with radioiodine. DESIGN: Records of patients treated for hyperthyroidism with radioiodine from 1989 to 1992 were examined in 1994, and a questionnaire was sent to patients < or = 70 years with Graves' disease (GD) and toxic nodular goitre (TNG) to obtain information regarding thyroxine substitution, smoking habits and present state of health. SETTING: Outpatients in a thyroid unit; follow-up by primary care. SUBJECTS: Seven hundred and fifty-four patients with hyperthyroidism treated with radioiodine, 327 receiving the questionnaire, 72% response rate. INTERVENTION: Radioiodine treatment using a delivered absorbed dose method, aiming at an absorbed dose to the thyroid of 100-120 Gy. MAIN OUTCOME MEASURES: Statistical analysis of clinical records and results from questionnaire. RESULTS: Only 10% of the patients needed more than one treatment. At the time of follow-up, thyroxine supplementation was given to 178 (93%) of the GD and to 21 (47%) of the TNG patients. Smoking was more common in GD patients than in the general population (44% vs. 26%; P < 0.001). Smoking GD patients experienced eye discomfort more often than smoking TNG patients (53% vs. 7%; P < 0.001). Weight gain after therapy was a problem in 79% of the hyperthyroid individuals. CONCLUSIONS: Few patients needed retreatment and most of the GD patients had thyroxine after 1-5 years after therapy. Smoking patients, especially those with GD, had more eye symptoms. At follow-up, the euthyroid patients still consider themselves having a poorer health than individuals in the general population.

Iodine-131 treatment of hyperthyroidism: significance of effective half-life measurements.

UNLABELLED: Our goals were to evaluate the effect of half-life determination and differences in the half-life of 131I between patients with Graves' disease and toxic nodular goiter, and the influence of antithyroid drugs on iodine uptake. METHODS: We reviewed the records of 555 patients who had received radioiodine treatment for Graves' disease and toxic nodular goiter to analyze iodine uptake, half-life values and pretreatment with antithyroid drugs. Two different methods of dose calculation were compared: one using repeated uptake measurements at 24 and 48 hr and 4 or 6 days to define the effective half-life. The other method assumed a half-life of 5 days and uptake at 24 hr only. All patients were treated according to the first method. A follow-up questionnaire was sent to 327 patients (238 responders) to assess the treatment outcome. RESULTS: After comparing the results of the two methods, we found that repeat uptake measurements and determination of effective half-life results in administered activities that differ considerably from those calculated when an assumed, fixed half-life and a single uptake measurement are used. The simpler method would lead to over- as well as undertreatment of the patient. There was a functional difference between patients with Graves' disease and toxic nodular goiter, as reflected by the shorter 131I half-life in Graves' disease (mean 5.0 days) than toxic nodular goiter (mean 6.0 days) and a skewed distribution in toxic nodular goiter. Patients pretreated with antithyroid drugs had shorter 131I half-lives in both categories. Ten percent of the patients required more than one treatment; 94% of the patients with Graves' disease and 45% with toxic nodular goiter had thyroxine substitution 1-5 yr after treatment. CONCLUSION: A dose calculation method that uses three uptake measurements provides sufficient data about the effective half-life of 131I in the thyroid. There is considerable difference in the half-life based on the disease being treated (Graves' disease or toxic nodular goiter). The 131I half-life also is shorter after pretreatment with anti-thyroid drugs. Thus, the simpler method leads to significant uncertainty, leading to over- as well undertreatment of the patient.

Overweight--a common problem among women treated for hyperthyroidism.

We sent out a questionnaire to 112 women treated for diffuse toxic goitre 2-5 years earlier to evaluate the prevalence of problems with overweight after the disease. Of 87 responders, about 50% (irrespective of surgical or radioiodine treatment) reported weight problems, and we randomly selected 40 of these women (20 with and 20 without reported weight problems) for a clinical follow-up (32 appearing). At the follow-up examination (mean 4 years after treatment for hyperthyroidism), 27 women had a higher weight than their estimated premorbid weight. The weight gain correlated with the estimated premorbid body mass index (BMI; P < 0.005), indicating that excess weight gainers may have had a premorbid problem now exaggerated in the post-hyperthyroid period. However, many women with a BMI within the limits stated to be ideal (21-25 kg/m2) also showed dramatic increases in weight. In contrast, the average middle-aged woman in our region did not appear to have gained in weight during a corresponding time period as judged from a longitudinal population study. Women with reported weight problems (mean weight increase 15.6%, n = 16) did not differ from women without (mean weight increase 6.7%, n = 16) as regards pretreatment hormone levels, method of treatment, (change of) smoking habits or post-treatment levothyroxine administration, or in serum concentrations of thyroid hormones, thyrotrophin, cortisol, procollagen-III-peptide, cholesterol, HDL cholesterol or triglycerides. Women with hyperthyroidism should be informed about the risk of gaining weight after therapy and given early support as to dietary and lifestyle change.

Influence of estrogen and progesterone on behavioral effects of apomorphine and amphetamine.

A study was made of the influence of apomorphine. D- and L-amphetamine on the effects of different hormonal treatments used to induce copulatory behavior in female rats. Female copulatory behavior, (lordosis response), which has been shown to be inhibited by increased DA and 5-HT neuronal activity, was depressed by apomorphine, D- and L-amphetamine in ovariectomized rats treated with estrogen + progesterone. When lordosis behavior was activated by estrogen alone the inhibitory action of the drugs, especially that of apomorphine was considerably less pronounced. However, the effect of D-amphetamine on stereotype activity was not greater after treatment with estrogen + progesterone than after administration of estrogen alone. Estrogen had a slight stimulatory effect on stereotype activity in non-drug-treated rats, while progesterone had an inhibitory effect. Possible mechanisms underlying the observed interactive effect of progesterone and monoamines on lordosis behavior, such as a progesterone-induced alteration of monoaminergic transmission, are discussed.

Potentiation of D- and L-amphetamine effects on copulatory behavior in female rats by treatment with alpha-adrenoreceptor blocking drugs.

The influence of noradrenergic mechanisms on the effects of D- and L-amphetamine on lordosis behavior and stereotype activity was studied in ovariectomized estrogen + progesterone treated rats. Phenoxybenzamine, phentolamine and prazosin, which all block alpha-adrenergic receptors potentiated the inhibitory effect of D-amphetamine on lordosis behavior. Phenoxybenzamine and prazosin also potentiated the effect of L-amphetamine, while phentolamine did not increase the effect. No augmented effect of D- or L-amphetamine was obtained on stereotype activity after pretreatment with phenoxybenzamine or phentolamine. L-propranolol, which blocks beta-adrenergic receptors and pimozide, a dopamine receptor blocker did not influence the effect of D- or L-amphetamine on lordosis behavior. Clonidine an alpha-receptor stimulant drug inhibited lordosis response in estrogen treated rats. This is probably due to a presynaptic effect, decreasing the release of NA from nerve terminals. The possibility that D- and L-amphetamine activates a NA system which influences lordosis behavior either by a direct facilitation or by decreasing the activity of an inhibitory serotonergic system is discussed.

The effects of different amphetamines on copulatory behaviour and stereotype activity in the female rat, after treatment with monoamine depletors and synthesis inhibitors.

The effects of treatment with alpha-methyl-p-tyrosine (alphaMPT), parachlorophenylalanine (pCPA) and reserpine in combination with D- or L-amphetamine on copulatory behaviour and stereotype activity was studied in estrogen + progesterone treated ovariectomized rats. In doses which clearly prevented D- and L-amphetamine-induced stereotype activity alphaMPT or pCPA did not influence the effect of D- and L-amphetamine on lordosis response. Reserpine treatment decreased the enhanced stereotype activity after D- and L-amphetamine but did not decrease the effect on the copulatory behaviour. Pretreatment with pCPA or reserpine clearly reduced the effect of fenfluramine on the lordosis response. It is suggested that different mechanisms of action are involved in the D-amphetamine effect on the lordosis response and on stereotype activity. The present data give further evidence that the lordosis inhibitory effect of fenfluramine is mediated by 5-HT-mechanisms. The mechanism by which L-amphetamine inhibits the lordosis response seems to be different from both the action of fenfluramine and the effect of D-amphetamine.

A comparative study of different amphetamines on copulatory behavior and stereotype activity in the female rat.

The influence of D- and L-amphetamine, fenfluramine, and p-chloroamphetamine on female copulatory behavior (lordosis response) and the induction of stereotype activity was compared. Lordosis response in the female rat has been shown to be inhibited by increased central nervous serotonergic (5-HT) as well as dopaminergic (DA) activity. A dose-dependent inhibitory effect on the estrogen- + progesterone-induced lordosis response in ovariectomized rats was demonstrated after treatment with the four amphetamines. In contrast, only D- and L-amphetamine induced a stereotype activity, which is considered to be mediated by DA mechanisms. A decrease in DA receptor activity, achieved by pimozide pretreatment, abolished the effect of D-amphetamine on lordosis behavior, but the effect of L-amphetamine was only slightly diminished and the action of fenfluramine and p-chloroamphetamine was unaffected. On the other hand, both L- and D-amphetamine-induced stereotype activity was prevented by pimozide treatment. The data suggest that the D-amphetamine effect on lordosis behavior is mediated by increased DA receptor activity. Although it induces stereotype activity by increased DA activity, L-amphetamine, like fenfluramine and p-chloroamphetamine, inhibits the lordosis response by some other action presumably related to serotonergic mechanisms.