[Change in the course of drug therapy of hyperthyroidism?].
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Antithyroid Agents↗
Biomedical subjects
D Reinwein
Publications and source records attributed to D Reinwein.
[Asymptomatic primary hyperparathyroidism. Treatment or observation?].
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Bone and Bones↗
Treatment of prolactinoma patients with the new non-ergot dopamine agonist roxindol: first results.
We studied the effects of the new non-ergot D2-dopamine agonist roxindol for the treatment of human prolactinomas. Roxindol is a non-ergot drug with additional 5-hydroxytryptamine type 1 A agonist and serotonin reuptake inhibitory activity. Ten patients with prolactin-secreting pituitary adenomas received roxindol three times daily at a dosage of 7.5-30 mg/day for at least 4 weeks according to a prospective protocol. All patients but one had received oral bromocriptine previously without normalization of prolactin levels. Serum prolactin profiles were analyzed once a week during the first month of therapy and at 4-week intervals thereafter. Mean baseline serum prolactin was suppressed from 23,000 +/- 13,600 mU/l (range 1500-141,000 mU/l; 20 mU/l = 1 microgram/l) by 37 +/- 11% after 1 week, by 49 +/- 9% after 4 weeks, and by 65 +/- 11% (n = 8) after 24 weeks of treatment. Serum prolactin was normalized in two patients. A tumor volume reduction of 20-25% was obtained in two subjects. Compared with previous treatment with oral bromocriptine the decrease in serum prolactin was comparable. In contrast, tolerance of roxindol was superior in five of seven patients with major side effects with bromocriptine, including three subjects who had discontinued bromocriptine because of adverse reactions. Four subjects spontaneously reported improvement of psychological and physical performance. One patient had a transient increase of serum transaminases. Thus, for the first time we could show a suppressive effect of roxindol on prolactin secretion in human prolactinomas. Due to its good tolerance roxindol may provide a useful alternative to bromocriptine.
Adult↗
The long-acting somatostatin analogue octreotide alleviates symptoms by reducing posttranslational conversion of prepro-glucagon to glucagon in a patient with malignant glucagonoma, but does not prevent tumor growth.
A 52-year-old female with metastatic glucagonoma secreting glucagon and chromogranin A was treated with the somatostatin analogue octreotide for 2 years without any additional tumor-reducing interventions. Before therapy plasma glucagon was above 8 micrograms/l (normal < 0.2) and within 2 days 3 x 200 micrograms octreotide daily suppressed plasma glucagon to 2.2-2.5 micrograms/l. Concomitantly, chromogranin A dropped from 0.85 mg/l (normal < 0.1) to 0.2. After 3 weeks the preexisting disabling necrolytic migratory erythema had vanished completely, and weight loss was temporarily stopped. During therapy chromogranin A and plasma glucagon rose, exceeding pretreatment levels after 3 and 14 months, respectively. After 1 year the erythema recurred, responding only transiently to increasing doses of octreotide. The patient died after 2 years of therapy of tumor cachexy despite very high doses of octreotide (4 x 600 micrograms/day). Throughout treatment octreotide did not prevent tumor growth, as demonstrated by computed tomography and sonography. Determination of immunoreactive glucagon before and during octreotide therapy in fractions of plasma samples subjected to gel chromatography revealed a reduction in the ratio of glucagon to preproglucagon from 1.83 (before) to 0.56 (during therapy), indicating inhibition of posttranslational processing of preoproglucagon by octreotide, thereby reducing circulating bioactive glucagon. In summary, octreotide induced a remission of clinical symptoms by inhibiting posttranslational conversion of preproglucagon to glucagon but did not prevent tumor growth. Therefore, octreotide is a valuable therapy for rapid relief of clinical symptoms, thereby improving the possibilities for other tumor-reducing therapies.
Cell Division↗
Low interleukin-2 receptor levels in serum of patients with insulin-dependent diabetes.
Interleukin-2 receptors are released in the circulation in response to antigenic ro mitogenic stimulation of T-lymphocytes. Abnormal serum interleukin-2 receptor levels have been found in young children with type 1 diabetes and "prediabetes." We measured interleukin-2 receptor levels in 17 patients with newly diagnosed type 1 diabetes, 21 patients with long-standing type 1 diabetes, 19 patients with long-standing type 2 diabetes, 19 islet-cell antibody positive nondiabetic polyendocrine patients, 12 islet-cell antibody-positive first-degree relatives of patients with type 1 diabetes and compared the results to age- and sex-matched normal controls. We found significantly lower interleukin-2 receptor levels in patients with newly diagnosed and long-standing type 1 diabetes compared to normal controls (87 +/- 11 and 93 +/- 11 vs. 142 +/- 25 and 132 +/- 40 U/ml, P < 0.001 and P < 0.01). There were no significant differences in interleukin-2 receptor levels between prediabetic groups and normal controls or patients with long-standing type 1 or type 2 diabetes. There was no correlation between glycosylated hemoglobin, blood glucose levels, and interleukin-2 receptor in the groups with long-standing type 1 or type 2 diabetes. We conclude that patients with type 1 diabetes have low interleukin-2 receptor serum levels. This phenomenon is acquired close to disease onset and is unlikely to be an early markers of type 1 diabetes.
Adolescent↗
Effectiveness of prophylactic therapy on goiter recurrence in an area with low iodine intake--a sonographic follow-up study.
There is no agreement as to whether or not drug treatment after surgery for nodular goiter is effective in preventing recurrence of goiter. Data about recurrences in areas of marginally low iodine intake (like Germany) vary widely. Therefore, we performed a retrospective study in 104 patients who had been treated surgically because of benign uninodular or multinodular goiter. The mean follow-up period was 6.4 years (minimal 1 year) with at least three examinations. Thyroid ultrasound with volumetric analysis was recorded in each patient. Thirty-two patients did not receive any prophylaxis, 50 patients were treated with L-thyroxine, 17 patients with a combination of L-thyroxine and iodine and 5 patients with iodine alone. Recurrence of goiter was documented in 28.0% of the untreated patients and in 8.9% of the patients on prophylaxis (P < 0.05). The mean increase of thyroid volume was 7.3 ml versus 3.1 ml in patients without versus with prophylactic drug treatment (not significant). No significant correlation was found between the increase of thyroid volume and age of the patients, follow-up time, or initial thyroid volume, respectively. These data clearly demonstrate the effectiveness of prophylactic drug therapy to prevent recurrence of goiter after thyroid surgery in an iodine-deficient area.
Adult↗
Antithyroid drug-induced agranulocytosis: clinical experience with ten patients treated at one institution and review of the literature.
The frequency, predisposing factors and course of agranulocytosis (granulocytes < 250/microliter) secondary to antithyroid drugs were studied in a cohort of 1256 continuously treated outpatients with hyperthyroidism during the 15 year period from 1973 to 1987. Two cases of agranulocytosis were detected; the frequency was 0.18% (95%-confidence intervals, 0.0-0.44%). This prevalence appears to be lower than reported in previous studies (up to 1.8%). For other adverse drug reactions, there was a clear-cut relationship to initial thionamide dose and to the body mass index; most reactions occurred during the first weeks of treatment. In addition, eight patients referred for thionamide drug- induced agranulocytosis were studied, and the following results obtained: Methimazole dose in patients with agranulocytosis was almost twice as in other patients (63.3 +/- 19.7 vs 34.3 +/- 29.7 mg daily) suggesting that this complication was related to dose. The interval between start of antithyroid drug treatment and first symptoms of agranulocytosis was 33 days (median; range, 23-55 days); hence, prolonged treatment beyond this period would appear relatively safe. Withdrawal of the causative agent and treatment of infection led to recovery of leukocyte counts within 15 days (median; range, 5-31 days). Two fatal outcomes were seen in referred patients. In one severely hyperthyroid patient with methimazole-induced agranulocytosis, recombinant human granulocyte/macrophage colony stimulating factor induced clinical and hematologic recovery within a few days of administration. In conclusion, agranulocytosis is the most severe side effect of antithyroid drugs. According to our results and a literature review, it occurs almost exclusively during the first ten weeks of treatment and is probably related to the drug dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[An unusual course of severe osteoporosis].
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Biopsy↗
[Immune activity and serum interleukin-2-receptor concentration in autoimmune thyroid diseases].
Serum interleukin-2 receptor (IL-2R) concentrations were compared in 55 patients with thyrotoxicosis (14 men, 41 women, mean age 43.5 +/- 17 years), 18 patients with Hashimoto's thyroiditis (5 men, 13 women, mean age 47 +/- 15 years) and 28 healthy subjects (12 men, 16 women, mean age 30 +/- 10 years). The patients with thyrotoxicosis were divided into three groups depending on the activity or stage of the disease: 17 patients with florid untreated hyperthyroidism, 23 euthyroid patients receiving treatment with antithyroid drugs and 15 patients with thyrotoxicosis in remission after completing one year's antithyroid treatment. The patients with untreated thyrotoxicosis had significantly higher IL-2R values than the euthyroid patients receiving treatment or those in remission (207 +/- 112 vs 139 +/- 66 and 91 +/- 26 U/ml, P < 0.05 and P < 0.01). The IL-2R values of patients with thyrotoxicosis in remission were, however, significantly lower than those of the 28 healthy subjects (126 +/- 34 U/l; P < 0.01) or the euthyroid patients receiving treatment (P < 0.05). The 18 patients with Hashimoto's thyroiditis had significantly lower serum IL-2R values (70 +/- 39 U/ml) than the healthy controls. These data show that the serum IL-2R level depends on the state of thyroid metabolism and on the activity phase of the thyrotoxicosis. The low serum levels of IL-2R in patients with Hashimoto's thyroiditis could signify a genetically determined decrease in IL-2R production or might be linked with the destruction of thyroid tissue by the chronic autoimmune process.
Adult↗
[The therapy of hyperthyroidism. Its current status].
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Antithyroid Agents↗
Long-term treatment of acromegalic patients with repeatable parenteral depot-bromocriptine.
We studied the efficacy and tolerability of a repeatable long-acting parenteral depot-bromocriptine preparation (Parlodel LAR) in 14 acromegalic patients, 10 of whom had received oral bromocriptine therapy previously, 2 of them showing intolerance to oral bromocriptine. Patients received i.m. injections of 50-100 mg depot-bromocriptine at 4-week intervals for 3-24 months (median 6). Growth hormone profiles were assessed by four daily samples at 4-week intervals. Main daily growth hormone levels decreased from 52.1 +/- 12.3 micrograms/l (mean +/- SEM) to 19.4 +/- 4.7 micrograms/l on the day of injection. In 6 patients, growth hormone values were lowered by more than 50%, whereas IGF-I levels decreased only slightly and growth hormone values during the oral glucose tolerance test remained non-suppressible. Tumour sizes were not affected. Two women became pregnant and were delivered of healthy babies. Side-effects typical of bromocriptine occurred frequently on the days of injection and diminished in most patients after 2 months of therapy despite increasing dosage. Compared with previous oral bromocriptine therapy, 9 of 10 patients preferred the depot preparation, whereas the reduction of growth hormone levels was similar during both treatments. In conclusion, depot-bromocriptine should be considered for acromegalic patients intolerant to oral bromocriptine.
Acromegaly↗
Prognostic factors in medullary thyroid carcinoma: evaluation of 741 patients from the German Medullary Thyroid Carcinoma Register.
A retrospective study of 741 patients with medullary thyroid carcinoma diagnosed between 1967 and 1991 was carried out by members of the German Medullary Thyroid Carcinoma Study Group to evaluate prognostic factors. A total of 559 patients (75%) were considered to have sporadic disease, and 182 (25%) had the familial type. The sex ratio (male to female) was 1:1.4 in sporadic disease patients, and the mean age at diagnosis was 45.9 years (range 5-81 years). For familial disease patients the sex ratio was 1:1.1, and the mean age at diagnosis was 33.4 (range 5-77 years). The follow-up time for 630 patients ranged from 1 month to 20.8 years (mean 13.0 years). The overall adjusted survival rate was 86.7% at 5 years and 64.2% at 10 years. In a univariate analysis the stage of disease at diagnosis, age, sex, and type of disease (sporadic, familial) were relevant prognostic factors, with a better prognosis for young female patients with familial disease and diagnosed at an early stage. In a multivariate proportional hazards analysis, the difference in the survival rate of patients with familial disease versus those with the sporadic form disappeared, while prognostic information provided by age and sex was still significant. The poorer prognosis of patients with sporadic medullary thyroid carcinoma may be related to the patients' older age at detection and more advanced tumor stage at diagnosis. There seems to be no difference in biological behavior between tumors of the sporadic and those of the familial type.
Adolescent↗
Basophilic leukocytes in hypothyroidism.
Since in the literature basophilia is frequently related to myxedema, we evaluated basophilic leukocytes in patients with hypothyroidism, applying routine techniques used in clinical laboratories. The study included normal persons, untreated patients with hypothyroidism, and euthyroid subjects with hyperlipidemia. The number of circulating basophils was determined by differential counts of Pappenheim stained blood smears. No difference in relative and total basophil counts was detected in patients with hypothyroidism as compared to healthy controls (1.0% and 58.1 basophils/microliters vs. 0.8% and 50.8 basophils/microliters, respectively). The percentage of basophils in myxedema associated with hypercholesterolemia amounted to 1.0%, their absolute number to 57.6/microliters; in hypothyroid patients presenting normal serum cholesterol levels, the relative and absolute numbers of basophilic leukocytes was not statistically different (0.83% and 61.1 basophils/microliters, respectively). We conclude that in patients with hypothyroidism the number of basophils is not statistically different from the values of basophils in healthy controls. Furthermore, the number of peripheral blood basophils in hypothyroidism is not related to the serum cholesterol level.
Adult↗
Clinical thyroidology 1992: "what do we really need'?
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Humans↗
Increased serum neopterin levels in patients with Graves' disease.
Neopterin (NPT) a marker of activation of the T-lymphocyte/monocyte axis has been measured in serum of 89 patients with autoimmune thyroid disease (72 patients with Graves' disease and 17 patients with autoimmune thyroiditis) and compared to a group of 24 normal controls and 24 patients with nontoxic goitre. There was a significant correlation between NPT levels and age in the patients with nontoxic goitre (r = 0.447, p < 0.001) but not in patients with autoimmune thyroid disease. Significantly higher NPT levels were found in all patients with Graves' disease (GD) compared to age and sex matched healthy controls, and patients with nontoxic goitre (5.7 +/- 2.4 vs 4.1 +/- 1.7, and 4.0 +/- 1.5, p < 0.01). However, there was no difference in NPT levels between each group of patients with GD when subdivided in: hyperthyroid newly diagnosed GD, treated GD, GD in remission and relapse. Patients with autoimmune thyroiditis did not have abnormal NPT levels compared to age and sex matched normal controls. Neopterin serum levels were not influenced by hyperthyroidism as no significant differences in NPT levels could be found in 24 patients with hyperthyroid Graves' disease and 13 patients with toxic goitre or toxic adenoma when compared to age and sex matched euthyroid patients with Graves' disease or normal controls. Moreover, there was no significant difference in mean NPT levels 1. before and after restoration of euthyroidism in 10 patients with hyperthyroid Graves' disease and 2. before and under T3 supplementation in 18 patients with Graves' disease in remission who underwent a T3 thyroid suppression test.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Control of prolactin-secreting macroadenomas with parenteral, long-acting bromocriptine in 30 patients treated for up to 3 years.
OBJECTIVE: We investigated the effect of intramuscular injections of long-acting bromocriptine in patients with macroadenomas. STUDY DESIGN AND PATIENTS: Thirty patients with PRL-secreting pituitary macroadenomas were treated with repeated 4-weekly intramuscular injections of 50 or 100 mg of a long-acting, repeatable bromocriptine formulation for six to 37 injections, amounting to a total of 473 injections. Twenty patients received parenteral bromocriptine as primary therapy, ten had persisting hyperprolactinemia after previous therapies including pituitary surgery (n = 7), oral bromocriptine (7), and pituitary irradiation (2). MEASUREMENTS: A PRL day profile was obtained and the patients' clinical status and history were documented, at intervals. Detailed clinical, laboratory, and radiological (pituitary nuclear magnetic resonance or computed tomography scan) evaluations were performed at baseline, after 1 injection and every 6th injection thereafter. RESULTS: In all patients PRL was suppressed from a mean +/- SEM pretreatment level of 32,620 +/- 8680 to 4480 +/- 1140 mU/I on the third day after the first injection. In 12 patients PRL levels normalized (< 400 mU/I) with the first to fourth injection, in three additional patients PRL levels normalized after 8-15 months. In 19 patients PRL was suppressed to less than 1000 mU/l. In three patients PRL did not decrease to less than 50% of pretreatment; in two of them on oral bromocriptine prior to this study there had been a comparable low efficacy. Of 28 patients with macroadenomas (median height 22 mm) tumour shrinkage was evident in 15 by nuclear magnetic resonance or computed tomography scan 28 days after the first injection, and in three additional patients after 6 months. There was further regression in seven cases after 12, 18 or 24 injections. Adenoma size (mean +/- SEM) decreased to 66 +/- 7% of the pretreatment value. The 40 adverse events noted in 20 of 30 patients during 24 hours after the first injection were similar to known side-effects of oral bromocriptine, nausea and postural hypotension being the most frequent. With repeated injections, on average 0.6 adverse events were noted per injection (mostly mild asthenia). There were no local adverse reactions at the injection site. CONCLUSION: We conclude that long-acting repeatable bromocriptine in patients with macroprolactinomas offers a safe and efficacious primary treatment that ensures compliance and gives long-term control. Adverse reactions are comparable to oral bromocriptine but subside with repeated injections.
Adolescent↗
Effect of small doses of iodine on thyroid function during caloric restriction in normal subjects.
It is well recognized that starvation and malnutrition are associated with a low-T3 syndrome in man. A similar condition has been observed after intake of a low carbohydrate hypocaloric diet. However, little is known about the influence of iodine on these conditions. Therefore, we evaluated the effect of iodine supplementation on thyroid function before and after a short-term intake of a low carbohydrate diet in normal subjects residing in an iodine-deficient area. The study was performed in 16 young euthyroid, nonobese volunteers (11 males, 5 females). The subjects were placed on a low carbohydrate (800 kcal) diet for 4 days. Eight subjects received 500 micrograms iodine (oral) daily beginning 4 weeks before diet. The control group (n = 8) received no iodine. After iodine supplementation, iodine excretion increased from 52 to 405 micrograms iodine/g of creatinine. Total T4 showed a slight but significant increase (104.2 nmol/l vs. 115.8 micrograms/dl; p < 0.001); fT4 was unchanged. The intake of the hypocaloric low carbohydrate diet resulted in a striking decrease in both total and free T3 and an increase of rT3 irrespective of iodine supplementation. T4 and fT4 were not affected in either group. During diet, iodine administration resulted in a decrease of basal TSH from 2.3 to 1.2 mU/l (p < 0.05), delta TSH from 10.3 to 4.5 mU/l (p < 0.01) and delta T3 (T3 180 min after TRH) from 0.7 to 0.3 nmol/l (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
A prospective randomized trial of antithyroid drug dose in Graves' disease therapy. European Multicenter Study Group on Antithyroid Drug Treatment.
Some studies have suggested that increasing the daily dose of anti-thyroid drugs might improve long-term remission rates of Graves' disease. Therefore, this question was addressed in a prospective multicenter trial involving 18 thyroid clinics in Europe, mostly in iodine-deficient or moderately iodine-sufficient regions. Five hundred and nine patients with Graves' hyperthyroidism were enrolled in a prospective randomized trial comparing the remission rates after treatment with methimazole (MMI) at two fixed dosages (10 vs. 40 mg) with levothyroxine supplementation. The treatment and follow-up periods lasted 12 months each. Sixty and seven-tenths percent of the recruited patients (total, 309; 153 in the 10 mg, 156 in the 40 mg group) were finally evaluated, and comparison of the two groups showed that they were well matched with respect to a wide range of variables, including parameters of thyroid function. With 10 mg MMI daily, 68.4% of the patients were euthyroid after 3 weeks, and 84.9% after 6 weeks, compared to 83.1% and 91.6%, respectively, with the use of 40 mg MMI daily. TSH receptor antibodies decreased similarly in the two groups, 25% of patients in the 10 mg group, and 30% in the 40 mg group still being TSH receptor antibodies positive after 12 months. One hundred and ninety six (63.4%) of the 309 patients achieved remission of Graves' disease. The two MMI doses were equally effective; 35.9% compared to 37.2% of patients treated with 10 and 40 mg MMI, respectively, had relapses. There was no difference in the length of the time interval between stopping treatment and recurrence between the two groups. However, the rate of adverse drug reactions increased from 39/251 (15.5%) in the 10 mg group to 67/258 (26.0%) in the 40 mg group (P < 0.01). Under conditions of iodine deficiency or borderline sufficient iodine supply, 40 mg MMI daily will render more patients with Graves' disease euthyroid within the first 6 weeks of treatment than 10 mg daily, but at the expense of an increased rate of adverse reactions. However, patients treated with 40 mg MMI daily for 1 yr have no higher chance of remission than patients treated with 10 mg. It does not appear justified at present to recommend MMI doses higher than required for the control of hyperthyroidism (with the goal of immunosuppression).
Adult↗