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[Follow-up and long-term results of radioiodine therapy in immune hyperthyroidism].

Follow-up and long-term results of 131-I treatment in Graves' disease are mainly influenced by the initial therapy. In Austria 131I-dose is estimated mostly as a result of thyroid uptake and volume, with the aim to restore euthyroidism. Methimazole or Propanolol pretreatment is performed in more than half of the patients. In Salzburg fixed dosis of 185 MBq 131-I are delivered until euthyroidism is achieved. Follow-up is done in 3 to 6 monthly intervals, later on once a year. Long-term results of 131-I-therapy are rare, because of the difficulty in discriminating Graves' disease from hyperthyroidism due to thyroid autonomy in the years before antibodies could be evaluated. Results are also quite uncertain, when obtained before the age of TSH- and TRH-test, because mild hyperthyroidism and hypothyroidism might have been overlooked. Early hyperthyroidism after 131-I-treatment can occur in 7% to 40% within the first year, raising with 2% to 5% each year. Hypothyroidism seems to depend on the dose, but may be caused even by low doses. This difficulty in finding the "ideal" dose might be due to stimulating, blocking and destroying antibodies with differences in the sensitivity of the thyroid tissue. The goal should be, to attain euthyroidism by radioiodine therapy, but hyperthyroidism should not be prolonged over a long period by delivering too small doses in order to avoid hypothyroidism.

Autoantibodies↗

[Effect of somatotropin on cathepsin D in the liver of hypo- and hyperthyroid rats].

In experiments on albino male rats the dependence of the cathepsin D activity on the thyroid hormone- and somatotropin levels in the organism was studied. It was demonstrated that the total cathepsin D activity in the liver of hypothyroid rats is lowered by 37% and that of hyperthyroid animals is augmented by 63%. Somatotropin injected to intact rats within 10 days in doses of 0.5 mg/100 g body weight enhanced the total enzyme activity by 19%. Hormone injection to hypothyroid animals returns to the normal cathepsin D activity, whereas in hyperthyroid rats the enzyme effect is significantly lowered under hormone action. Protein content in the nucleus-free homogenate of the hypothyroid rat liver does not differ from that of intact rats and is increased by 27% in hyperthyroid animals. Exogenous somatotropin returns to normal protein content in hyperthyroid rats.

Animals↗

Hyperthyroidism and familial hypertrophic cardiomyopathy.

A kindred with a high incidence of hypertrophic cardiomyopathy (HC) was studied to identify the presence of clinical hyperthyroidism. Two and possibly three members with HC had associated hyperthyroidism. In the propositus, clinical, ECG, and vectorcardiographic evidence for HC resolved after treatment of the hyperthyroidism. We hypothesize that the disproportionately high correlation of hyperthyroidism and HC and the resolution found in the propositus after treatment may indicate that antithyroid therapy should be considered in this form of cardiomyopathy.

Adolescent↗

Serum thyrotropin-binding inhibiting immunoglobulin and thyroperoxidase antibody in Graves' hyperthyroidism after 131I therapy.

Seventeen patients who received radioiodine (131I) therapy for Graves' hyperthyroidism had serial blood samples taken before therapy and after therapy for a period of at least 1 year. At 1 year post-therapy, six patients were hypothyroid. Seven patients were euthyroid, and four patients were hyperthyroid. Prior to isotope administration, 14 patients had detectable serum thyrotropin-binding inhibiting immunoglobulin (TBII) and 16 patients had detectable serum thyroperoxidase antibody (TPOAb). Three to 6 months after therapy, 11 of 14 TBII-positive patients demonstrated a marked increase (> 10%) in serum TBII activity. Four patients out of 11 developed hypothyroidism and six of the 11 developed euthyroidism. A decrease in TBII was observed in three patients who developed hyperthyroidism. In the three patients with undetectable TBII prior to therapy, two had high titers of TPOAb. Seven patients demonstrated a marked increase in TPOAb 3 to 6 months after therapy. Of these, four developed hypothyroidism and three developed euthyroidism, whereas three of the four patients who had a marked decrease in TPOAb developed hyperthyroidism. This study demonstrated that an increase in serum TBII and TPOAb activity 3 to 6 months after 131I therapy, may be useful in predicting which patients may develop euthyroidism or hypothyroidism after 1 year of 131I therapy.

Adult↗

Management of hyperthyroidism due to Graves' disease: a retrospective analysis of 1,000 inpatient cards.

There are three different modalities to treat hyperthyroidism due to Grave's disease: anti-thyroid drugs (ATD), radioiodine and surgery, each of them having its own advantages and disadvantages. The option for one of the three therapeutical approaches has both subjective and objective components. In Europe, a screening on the therapeutical options in Graves' disease was performed at the European Thyroid Association (ETA) initiative, being based on a questionnaire. In the Thyroid Department of the Endocrinology Institute in Bucharest, w analysed the managements of hyperthyroidism due to Graves' disease on 1,000 cards of hyperthyroid patients admitted there during the last five years. In order to diagnose Graves' disease, in vivo tests radioiodine uptake (RIU) at 2 and 24 hrs, 93.39% scintigram (92.93%), thyroid ultrasonography (15%) and reflexogram (98.06%), were carried out. Out of the in vitro tests, PBI (protein bound iodine) was performed prioritarily, while T4, T3 (variable), TSH (13.91%) were performed according to the economic factors. For the patient with moderate hyperthyroidism, antithyroid therapy was alternative with the radioiodine one (51.61% and 48.35%, respectively). The age of the patient played a major role in the decision to take. The frequency of cases treated with radioiodine was considerably higher in the patients with recurrence and in the elderly. The initial dose of antithyroid treatment was high (50-60 mg), and was reduced according to the thyroid function. The therapy duration was not pre-determined. The ATD treatment was prolonged for a time-interval ranging between 2 and 5 years, depending of the clinical status (age, sex, goiter size, exophthalmic syndrome) and the social conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

[Radioiodine therapy of recurrent hyperthyroidism in patients previously treated for diffuse toxic goiter with subtotal surgery].

Radioiodine therapy is often employed for treatment of patients with relapse of hyperthyroidism due to Graves' disease, after previous thyroid surgery. Little is known about the outcome of this treatment compared to patients with no previous surgery. A total of 20 patients, who had received surgical treatment for Graves' hyperthyroidism 1-46 years previously and with relapse of hyperthyroidism, and 25 patients with hyperthyroidism due to Graves' disease and no previous thyroid surgery were treated with radioiodine, following the same protocol. Early after treatment the previously operated patients showed a higher sensitivity to radioiodine, with more cases of early hypothyroidism than non-operated patients. However, after 50 months of follow-up the outcome was identical. The results indicate that frequent assessment is necessary after radioiodine treatment of patients with previous thyroid surgery, since some patients develop early hypothyroidism.

Adult↗

Diagnosis and successful treatment of fetal goitrous hyperthyroidism caused by maternal Graves disease.

BACKGROUND: Intrauterine diagnosis and treatment of fetal goitrous hyperthyroidism due to maternal Graves disease has not been reported. CASE: A case of fetal goitrous hyperthyroidism caused by maternal Graves disease was diagnosed and treated in the second trimester. High concentrations of both thyroid-stimulatory immunoglobulins (Igs) and thyrotropin-binding inhibitory Igs were detected in both maternal and fetal umbilical venous blood. Maternal propylthiouracil (PTU) treatment resulted in normalization of fetal thyroid function and a decrease in the size of the fetal thyroid goiter. Although euthyroid immediately after birth, the infant later became hyperthyroid and required treatment with PTU. CONCLUSION: The relatively high frequency of fetal thyroid disorders in maternal Graves disease warrants complete maternal and fetal evaluation. Fetal diagnosis and treatment of either hyperthyroidism or hypothyroidism are feasible and necessary to prevent fetal morbidity and mortality.

Adult↗

ATYPICAL MANIFESTATIONS OF HYPERTHYROIDISM.

Patients with hyperthyroidism usually present with symptoms of hypermetabolism with or without goitre and/or eye signs. Occasionally, however, the chief complaints are not immediately suggestive of hyperthyroidism. Patients with hyperthyroidism are described who presented with such atypical manifestations as periodic muscular paralysis, myasthenia, myopathy, encephalopathy, psychosis, angina pectoris, atrial fibrillation, heart failure without underlying heart disease, skeletal demineralization, pretibial myxedema, unilateral eye signs, and pitting edema of the ankles.

Asian People↗

Chemical hyperthyroidism: serum triiodothyronine levels in clinically euthyroid individuals treated with levothyroxine.

We have observed many patients treated with levothyroxine sodium who have elevated serum thyroxine (T4) levels but appear clinically euthyroid. Such patients generally have normal serum triiodothyronine (T3) values. A retrospective review at The Johns Hopkins Hospital, Baltimore, comparing the correlation of T3 and T4 values in levothyroxine-treated patients with that in patients not so treated was carried out from 1977 to 1979. Mean free thyroxine index (FTI) value in 104 levothyroxine-treated patients was 4.70 +/- 0.2 and mean T3 value was 177 +/- 9 ng/dL. In a group of 50 hyperthyroid patients, mean FTI value was 7.26. +/- 0.5, with a mean T3 value of 389 +/- 26 ng/dL. In 71 euthyroid patients, mean FTI value was 2.36 +/- 0.1, with a T3 value of 137 +/- 3 ng/dL. Computed ratios of T3 to FTI and T3 to T4 were significantly lower in the group treated with levothyroxine than in either the hyperthyroid or euthyroid nontreated groups. Levothyroxine-treated patients with high T4 levels but normal T3 levels were clinically euthyroid. Patients not treated with levothyroxine with similarly elevated T4 levels had elevated T3 levels and were clinically hyperthyroid. It is concluded that lower relative T3 levels in levothyroxine-treated patients may explain why these patients appear clinically euthyroid despite elevated T4 values. Serum T3 determination is the procedure of choice for evaluation of levothyroxine-treated individuals. Furthermore, an elevated FTI value in such an individual does not, in itself, dictate need to reduce dosage.

Drug Administration Schedule↗

Update on the management of hyperthyroidism and hypothyroidism.

Clinical aspects, laboratory investigation, and treatment of hyperthyroidism and hypothyroidism are reviewed in light of recent information. Special circumstances, such as hyperthyroidism during pregnancy, Graves ophthalmopathy, iodine-induced hyperthyroidism, and subclinical hypothyroidism, are also considered.

Female↗

Recurrent hyperthyroidism after thyroidectomy.

For 53 patients with toxic recurrent goiter (TRG), the interval between thyroidectomy and recurrent hyperthyroidism range from six months to 50 years (average, 12.4 +/- 11.9 years). Recurrent hyperthyroidism may occur in older patients for whom cardiac decompensation may be the initial manifestation. Reports on surgically treated hyperthyroid patients may underestimate the incidence of TRG unless follow-up is extended for many years.

Adolescent↗

Thyroid morphology and function after subtotal resection for hyperthyroidism.

Two main patterns of hyperplasia of the thyroid epithelium are seen in hyperthyroidism--toxic diffuse hyperplasia and toxic nodular hyperplasia. Toxic diffuse hyperplasia may affect the entire gland or it may arise in the extranodular tissue in a gland with nodular lesions. A series of patients treated by subtotal thyroidectomy for hyperthyroidism were classified into three morphological groups of goitre: 98 had a toxic diffuse goitre (TDG), 58 toxic nodular goiter with diffuse hyperplasia (TNGDH), and 105 toxic nodular goitre with nodular hyperplasia (TNGNH). The type of goitre was correlated to the development of disturbed thyroid function 1-6 years after surgery. Twenty-two patients with TDG and 18 (31 per cent) with TNGDH developed hypothyroidism; only 3 (3 per cent) with TNGNH showed hypofunction. Six patients with recurrent hyperthyroidism were found; all showed diffuse hyperplasia of the gland. It is concluded that the development of disturbed thyroid function after surgery is closely related to the histopathological type of goitre.

Adult↗

Late onset hypothyroidism after subtotal thyroidectomy for hyperthyroidism: implications for long term follow-up.

A follow-up register has been used in Aberdeen and Dundee to record early and late onset hypothyroidism occurring in a large population of post-thyroidectomy patients treated for hyperthyroidism. In one centre, in a total of 1170 patients, the prevalence of postoperative hypothyroidism, at the time of entry to the register, was 41 per cent. Of these early cases of hypothyroidism 93 per cent occurred within 18 months of operation. Results are presented from a 12-year prospective study of patients treated in two centres, who were euthyroid when entered on the follow-up register. In one centre, based on 683 patients, the 10-year incidence of late onset hypothyroidism estimated by actuarial methods was 7.4 per cent (95 per cent confidence limits, 3.8-11.1); in the other centre with 156 patients the 5-year incidence was 10.8 per cent (95 per cent confidence limits, 3-18.6). The minimum predicted annual incidence is 1 per cent. Large thyroid remnants do not protect some patients against early or late postoperative hypothyroidism but do lead to an increased risk of recurrent hyperthyroidism. Hypothyroidism after subtotal thyroidectomy for hyperthyroidism shows a bimodal pattern and this study emphasizes the need to maintain life-long follow-up.

Follow-Up Studies↗

Hyperthyroidism in men with germ cell tumors and high levels of beta-human chorionic gonadotropin.

A retrospective review was done on all high volume choriocarcinomas and other germ cell tumors of men with serum beta-human chorionic gonadotropin (beta-HCG) levels greater than 50,000 mIU/ml to determine the incidence and characteristics of hyperthyroidism in this setting. Nineteen patients were identified with high beta-HCG levels, but because 2 did not have thyroid function tests performed, the cases of only 17 patients were evaluable. Of these, 14 (82%) had primary testicular carcinoma and 3 (18%) had extragonadal tumors. Beta-HCG levels on presentation ranged from 80,000 to 3,058,000 mIU/ml, with a median of 243,500 mIU/ml. Seven of the 17 evaluable cases (41%) had T4 serum levels higher than 12 micrograms/dl (normal level 4 to 12 micrograms/dl) with a median value of 15.4 micrograms/dl (range, 12.6 to 33.5 micrograms/dl); serum T4 levels correlated with beta-HCG levels (r = 0.84). All seven patients with elevated T4 levels had beta-HCG values greater than 200,000 mIU/ml, and three of these seven had clinical manifestations that could be attributed to an elevated serum T4; only one patient required specific antithyroid treatment; and after control of primary disease, all other patients had normalization of thyroid function. The most common manifestations of hyperthyroidism in our series were tachycardia, hypertension, and a systolic flow murmur; none of the patients had thyroid gland enlargement. We conclude that subclinical hyperthyroidism is a relatively common phenomenon in germ cell tumors of men with high levels of beta-HCG and that control of the primary disease results in serum T4 level normalization.

Adolescent↗

Alterations in the maternal behavior of rats rearing hypothyroid and hyperthyroid offspring.

To determine whether maternal behavior could serve as a mediator for thyroid hormone effects on behavior, I assessed nesting, nursing, grooming, contact, and retrieval in mothers of hypothyroid, hyperthyroid, and control litters, as well as in mothers of litters receiving thyroxine replacement therapy. Females assigned to the hypothyroid and replacement therapy treatments were placed on a goitrogenic diet of .2% propylthiouracil from Day 15 of gestation to Day 22 postpartum. Hyperthyroid and replacement therapy pups were injected daily with thyroxine starting on the day of birth. The decline in nesting and nursing was delayed in hypothyroid litters whereas the decline in nesting was accelerated in hyperthyroid litters. Retrieval was not affected, but grooming of pups occurred less frequently in hypothyroid and replacement therapy litters. Maternal care received by hypothyroid pups was considered adequate. Maternal behavior may alleviate some of the effects of perinatal hypothyroidism,, but does not seem to be responsible for the more severe effects of hypothyroidism.

Animals↗

Generation of a transgenic animal model of hyperthyroid Graves' disease.

Graves' disease (GD) is an organ-specific autoimmune disease characterized by hyperthyroidism. Agonistic anti-thyrotropin receptor antibodies (thyroid-stimulating antibodies, TSAb), which mimic the thyrotropin (TSH) action, are thought to cause GD. The precise immunological mechanism of TSAb production, however, remains elusive. Previous immunization approaches using TSH receptor led to transient hyperthyroidism, but did not seem sufficient for comprehensive understanding of the development of autoimmune responses. To create GD-related autoimmunity in mice, we here generated TSAb-transgenic mice in which a patient-derived TSAb is expressed in B cells. Expression of the human TSAb in mice resulted in various manifestations of hyperthyroidism including increased free thyroxine levels with concomitantly decreased TSH levels, increased thyroid uptake of technetium pertechnetate, hyperthermia and thyroid hyperplasia. We found a correlation between the serum levels of human TSAb immunoglobulin and free thyroxine. In addition, conventional B cells expressing the TSAb were partially deleted in the periphery while B1 cells expressing the TSAb persisted and accumulated in the peritoneal cavity, a finding consistent with previous demonstrations that the maintenance of B1 cells plays an important role in the development of autoimmune diseases. Thus, our transgenic mouse may provide a novel and useful animal model for elucidating the pathogenesis and pathophysiology of GD.

Animals↗

Seroreactivity to A-type retrovirus proteins in a subset of cats with hyperthyroidism.

The thyroid gland is afflicted in several endocrine, autoimmune, and malignant diseases. Previous studies detected immunoreactivity against proteins of a human intracisternal A-type retroviral particle type-I (HIAP-I) in serum samples from the majority of patients with Graves' disease, an autoimmune disease of the thyroid that can also affect other organs, most prominently the eyes. To determine whether hyperthyroid animals might provide a model for the retroviral involvement in thyroid autoimmunity, serum samples from 32 cats (21 hyperthyroid and 11 controls) and 10 hypothyroid dogs were examined for immunoreactivity with HIAP-I using a Western blot technique. Of the 21 hyperthyroid cats 15 (71.4%) were HIAP-I positive, while only 2 of 11 (11.8%) control animals without endocrine pathology were positive. No significant correlations were seen between HIAP seroreactivity and serum thyroid hormone levels (T3 and T4), age, gender, treatment history, vaccination status, or weight. No seroreactivity to HIAP-I was detected in hypothyroid dogs. An examination of HIAP-I reactivity in feline leukemia virus (FeLV)-seroconverting cats found that 7/9 (78%) animals viremic for FeLV-A showed an alteration in HIAP serology, whereas only 1/7 (14%) nonviremic animals showed a change in HIAP-I serology. These results suggest that it may be possible to develop an animal (feline) model for the role of retroviruses in thyroid autoimmune diseases.

Animals↗

Muscle carnitine in hypo- and hyperthyroidism.

Weakness is common in both hyper- and hypothyroidism, and skeletal muscle L-carnitine may play a role in this regard, as suggested by studies indicating abnormal levels of carnitine in serum and urine of patients with thyroid dysfunction. Skeletal muscle samples were obtained for carnitine analysis from control subjects, and from hyperthyroid and hypothyroid patients before and after treatment. There was a significant reduction in carnitine, especially the esterified portion, in hyperthyroid individuals, with a return to normal as euthyroid status was regained. In hypothyroid patients, there was a trend for carnitine to be lower than normal and for improvement once euthyroid status was attained. Our data indicate that muscle carnitine levels are affected by both hypo- and hyperthyroidism. A decrease in muscle carnitine in both conditions may contribute to thyroid myopathy.

Adult↗