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Biomedical subjects

G Benker

Publications and source records attributed to G Benker.

At least 19 recordsLinked to original sources
PubMed1995

Response to methimazole in Graves' disease. The European Multicenter Study Group.

OBJECTIVE: A variety of regimens continue to be used in the treatment of Graves' disease with antithyroid drugs. We have investigated the factors which determine the initial response to methimazole (time until euthyroidism is achieved) in Graves' disease. PATIENTS: Five hundred and nine patients with Graves' disease in different European countries with normal and subnormal iodine supply. Patients were randomized to treatment with either 10 or 40 mg of methimazole per day for one year, with levothyroxine supplementation as required to maintain euthyroidism. Investigations were carried out before treatment and at 3 and 6 weeks and 3, 6, 9 and 12 months. MEASUREMENTS: Response was assessed by serial measurements of serum thyroid hormones. TSH receptor antibodies, thyroid autoantibodies and urinary iodide excretion were measured centrally. Twenty-minute thyroid uptake was measured by standard techniques. Data were collected and analysed centrally. Standard techniques as well as a stepwise logistic regression model were used to examine the relations between methimazole dose, age, goitre size, presence of endocrine eye signs, thyroid hormone levels, urinary iodide excretion, thyroid uptake, index of disease severity (Crooks), presence of TSH receptor antibodies and duration of the hyperthyroid phase. RESULTS: Within 3 weeks, 40.2% of patients responded to 10 mg of methimazole and 77.5% responded within 6 weeks. The corresponding figures for 40 mg of methimazole were 64.6 and 92.6%. Significant associations were found between duration of hyperthyroidism and the following variables: goitre size, urinary iodide excretion, methimazole dose, presence of TSH receptor antibodies (TBIAb), index of disease severity (Crooks) and pretreatment thyroid hormone levels. Response to methimazole was delayed in patients with large goitres, iodine excretion of > or = 100 micrograms/g creatinine, high pretreatment thyroid hormone levels, elevated levels of TBIAb and treatment with only 10 mg of methimazole. In the 10-mg group, 46% of patients were euthyroid within 3 weeks when urinary iodide was < 50 microgram/g of creatinine, and only 27% when iodide was above 100 micrograms/g. By stepwise logistic regression, the main factors for the response to methimazole were daily dose, pretreatment T3 levels, and goitre size. CONCLUSION: Methimazole dose, pretreatment serum T3 levels, and goitre size are the main determinants of the therapeutic response to methimazole in Graves' disease, at least in areas comprising low, subnormal and normal iodine supply.

Adult↗
PubMed1995

Hip fractures and the thyroid: a case-control study.

OBJECTIVE: To investigate the prevalence of thyroid illness - especially hyperthyroidism - and exposure to thyroid hormones in patients with hip fracture. DESIGN: A case-control study. SETTING: Two surgical/orthopaedic hospital units and 22 facilities for the aged in a moderately iodine-deficient region of Germany. SUBJECTS: A total of 116 postmenopausal females with hip fracture and 402 postmenopausal female controls. MAIN OUTCOME MEASURES: Hip fracture; thyroid disease confirmed by measurement of serum thyrotropin, total and free thyroxine and triiodothyronine; history of thyroid disease and thyroid medication obtained by a questionnaire. RESULTS: Of the hip fracture patients 4.3% had overt untreated hyperthyroidism, and 6.9% gave a history of past hyperthyroidism (total, 11.2%). The corresponding figures for the controls were 2.0 and 2.7%, respectively (total, 4.7%). 7.8% of the cases had been exposed to levo-thyroxine for 3-29 years, compared to 11.2% of the controls. The odds ratio for hyperthyroidism (present and past) was 2.5 (1.2-5.3, 95% confidence interval), and the odds ratio for levo-thyroxine exposure was 0.67 (0.32-1.41) in the hip fracture patients. CONCLUSIONS: Hyperthyroidism is found 2.5-fold more often in hip fracture patients than in controls. Hence, hyperthyroidism appears to be a significant risk factor for hip fracture and should be investigated by clinical and, when necessary, laboratory means in hip fracture patients. In contrast, no increased risk for hip fracture could be detected after exposure to levothyroxine.

Aged↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1992

An autoimmuno-dominant thyroglobulin epitope characterized by a monoclonal antibody.

It has become evident in recent years that autoimmune thyroglobulin (Tg) antibodies of Graves disease and Hashimoto's thyroiditis show a restricted epitope repertoire compared to Tg heteroantibodies. We have produced monoclonal antibodies (Mab) against human Tg by the hybridoma technique and the epitope specificity was determined by crossblocking experiments. Six noncrossreactive Mabs were used in a double determinant IRMA system for plasma Tg measurements. Sensitivity of the assays was between 1 and 2 ng/ml, intraassay variation less than 5%. Recovery experiments with added Tg were performed in 25 Graves sera with elevated Tg autoantibodies. Monoclonal antibody Tg13 showed an unusual strong interference with autoantibodies resulting in a very low recovery in all sera (median: less than 10%). In further studies Tg was digested by trypsin and after Western blotting, the resulting fragments were incubated with different Mab antibodies, a polyclonal antibody and 10 different Graves sera with high Tg autoantibodies. In contrast to all other mabs only Mab Tg13 showed several low molecular weight bands between 17 and 50 KD. The major bands recognized by Mab Tg13 corresponded to bands obtained by the autoimmune sera, which showed a very homogeneous band pattern. We conclude that Mab Tg13 is specific for an autoimmunodominant B cell epitope of human Tg.

Antibodies, Monoclonal↗
PubMed1992

Conservative and surgical management of incidentally discovered adrenal tumors (incidentalomas).

Of 50 patients with incidentalomas (INC), 18 were adrenalectomized and in 18 patients the INC was left in place. For 14 patients clinical data were insufficient for evaluation. Follow-up investigation of the 18 unoperated subjects 11-101 months (median 32.2) after the diagnosis had been made revealed unchanged size of the INC [initially 2.1 +/- 0.8 cm (mean +/- SD) at follow-up 2.0 +/- 1.0 cm]. Cushing's syndrome developed in one patient, which was not evident at the initial discovery of the INC 32 months before. "Pre-Cushing's Syndrome" was detected in 1 patient and confirmed in a second who had displayed a pathologically high dose dexamethasone suppression test 101 months before. In addition, 3 male patients with a hitherto unknown mild subclinical defect of 21-hydroxylase activity were identified. The remaining 12 patients had normal endocrine activity of their adrenals. Eighteen patients were adrenalectomized with an average tumor size of 3.96 +/- 1.88 cm. Histologically, 10 (52%) adenomas were observed, including 3 with signs of hypercortisolism. Adrenal hyperplasias were observed in 2 patients, metastasis in 1 patient. 31.5% of the INC which were removed were nonmalignant tumors of other than adrenal origin. We conclude that initially endocrinologically inactive adrenal tumors can eventually develop autonomous endocrine activity and therefore need to be reexamined at regular intervals. Conservative management with regular follow-up investigations is the preferable treatment for small incidentalomas when endocrine over-activity has been excluded and no indications of malignancy exist. Based on these observations and the literature a diagnostic and therapeutic strategy is presented.

Adrenal Cortex Function Tests↗
PubMed1992

Treatment of juvenile goitre with levothyroxine, iodide or a combination of both: the value of ultrasound grey-scale analysis.

The effects of oral iodide, levothyroxine and of iodide and levothyroxine in combination were studied in three groups of 30 children, age 13-15 years, with euthyroid goitre. As endpoints of this study, we used thyroid volume reduction, thyroid hormones, thyrotropin and thyroid grey-scale histograms by computerized analysis. The three groups were well matched with respect to mean age, body weight and pretreatment thyroid volumes and thyroid hormones. Mean urinary iodide excretion before treatment was in the range of 30 micrograms/g creatinine, since the study was conducted in an iodine-deficient area. All three treatment regimens led to significant reductions in thyroid volume within one month. After six months on 100 micrograms of levothyroxine, thyroid volume had decreased from 14.1 +/- 4.2 ml to 8.3 +/- 2.6 ml (mean +/- SD); on 150 micrograms of iodide, from 18.5 +/- 6.2 ml to 8.8 +/- 2.7 ml; and on 100 micrograms of iodide plus 50 micrograms of levothyroxine, from 17.2 +/- 3.1 ml to 8.3 +/- 2.0 ml. When treatment was discontinued for three months, or the dosage reduced, thyroid volume increased again in the levothyroxine (to 11.3 +/- 2.5 ml) but not in the iodide group. Grey-scale values (by ultrasound, computer-aided estimation) after nine months were significantly different between the three treatment groups; no change was observed with levothyroxine, but after 150 micrograms of iodide as well as after combined treatment with levothyroxine and iodide there were marked decreases of grey-scale values; this is interpreted as reflecting a decrease in follicle size and colloid content of the thyroid which takes place after iodide supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

[The concentration of atrial natriuretic peptides (ANP). ANP in different sections of the circulation during atrial volume load with and without anesthesia].

We studied the effect of a volume load induced by a 45 degrees Trendelenburg position on atrial natriuretic peptide (ANP) secretion in awake and anaesthetized patients with coronary artery disease undergoing aortocoronary bypass surgery. ANP was measured in different parts of the circulation before and after induction of high dose fentanyl anaesthesia at fixed times prior to and after extracorporeal circulation. METHOD. In eight patients with coronary artery disease (NYHA classification II-III), who received neither diuretic nor positive inotropic therapy, ANP was measured in the various parts of the circulation: in a peripheral vein, a radial artery, in the pulmonary artery and in the coronary sinus. The measurements were made in the supine and 45 degrees Trendelenburg position. Measurements of mean arterial pressure (MAP), central venous pressure (RAP), pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), cardiac index (CI) and heart rate (HR) were taken simultaneously. The measurements were taken in the awake patient, during steady-state high-dose fentanyl anaesthesia with 50% O2 in N2O and after extracorporeal circulation. RESULTS. Compared to measurements in a control group, ANP levels were significantly higher in all parts of the circulation in patients with coronary artery disease, although clinical symptoms of heart failure were absent. After extracorporeal circulation, significantly higher levels of ANP were found at all measurement sites; however the concentration gradient of ANP between coronary sinus and arterial or venous blood was reduced. In awake and anaesthetized patients a change in body position, causing a significant increase in filling pressures, did not produce an increase in ANP levels at all measurement sites. The induction of high-dose fentanyl anaesthesia did not have an influence on plasmatic ANP levels. CONCLUSION. The results of this study lead to the following conclusions: 1. ANP levels in patients with CAD are increased, even if clinical heart failure symptoms are absent. 2. ANP is secreted in the coronary vessels. Following dilution in the atrial blood, it is metabolized to inactive compounds in the periphery. 3. Basic ANP levels are not changed by high-dose fentanyl anaesthesia. Marked increases of the filling pressures do not correlate with atrial ANP levels either before or after induction of anaesthesia. 4. After extracorporeal circulation ANP levels are significantly increased in all parts of the circulation. The concentration gradient between coronary sinus blood, on the one hand, and arterial and venous blood on the other hand is reduced. This phenomenon is probably caused by an alteration in the metabolism of ANP during hypothermic extracorporeal circulation.

Aged↗
PubMed1991

[Coincidence of non-medullary thyroid cancer and hyperparathyroidism].

Hyperparathyroidism (HPT) and non-medullary thyroid carcinoma are not related by a common embryologic origin. In a 5-years period (1985-1989) 163 patients were operated for HPT at our hospital. Of these, 54 patients had concurrent thyroid disease, which was operated simultaneously. In 6 cases, thyroid carcinoma was found, e.g. 3.7% of all patients. This prevalence compares well to reports of different authors in the literature. The most probable explanation is the early diagnosis of asymptomatic occult papillary carcinomas; this was true in 4 of our 6 patients with thyroid malignancy.

Adenoma↗
PubMed1990

Control of prolactin secretion.

1. Prolactin is a 21,500 Dalton single-chain polypeptide hormone but may occur in 50 kDa and 150 kDa molecular variants. 2. These large PRL variants may be secreted predominantly; this condition is termed "macroprolactinemia". It is characterized by high immunological and normal biological serum levels of prolactin, and lack of clinical symptoms of hyperprolactinemia. 3. The information on PRL is encoded on chromosome 6. Transcription can be enhanced and suppressed by a variety of hormonal factors. 4. PRL is secreted in a pulsatile fashion; it displays a circadian rhythm (with a maximum during sleep) and is stimulated by some amino acids. PRL also responds to mechanical stimulation of the breast. 5. PRL rises during pregnancy, and maintainance of hyperprolactinemia (and, thereby, physiological infertility) is dependent on the frequency and duration of breast feedings. 6. Hypothalamic regulation of prolactin mainly involves tonic inhibition via portal dopamine. The physiological importance of various stimulating factors present in the hypothalamus is still incompletely understood. In particular, there is still no place for TRH in PRL physiology. 7. PRL is released in response to stress; this response may be mediated by opioids. The low-estrogen, low-gonadotropin amenorrhea of endurance-training women is not mediated by prolactin, however. 8. Estrogens stimulate PRL gene transcription via at least two independent mechanisms. There are many clinical examples of this estrogen effect on prolactin serum levels, and also on the growth of prolactinomas. 9. Mild hyperprolactinemia remains an enigma which cannot satisfactorily be resolved by biochemical or radiological testing. The border between "normal" and "elevated" prolactin is ill-defined. The possibility of macroprolactinemia complicates this matter even further. 10. The number of drugs which suppress prolactin by acting on pituitary D2 receptors, and which are useful in the treatment of hyperprolactinemia, continues to increase. In the field of ergot alkaloids, parenteral application appears to be a logical solution to the problem of the high first-pass effect; in addition, this form of treatment is frequently better tolerated than the oral route. 11. Prolactinoma development is presently being studied employing molecular biological techniques; the question of whether tumorigenesis can be attributed to specific defects of gene regulation remains to be answered.

Adult↗
PubMed1990

Acromegaly and hypertension: prevalence and relationship to the renin-angiotensin-aldosterone system.

The prevalence of arterial hypertension was evaluated in a retrospective study of 158 patients with acromegaly, and results were compared to control populations, namely, the Munich Blood Pressure Study (MBPS) and the Framingham Study. The prevalence of hypertension (defined according to WHO criteria) was significantly increased in female patients but not in men; hypertensive acromegalics were older and tended to have higher body weight compared to normotensive patients. Hypertension was not related to serum concentrations of growth hormone. After successful treatment of acromegaly, growth hormone levels and systolic and diastolic blood pressure fell only in female hypertensive acromegalics; this did not occur in normotensives. The rise in plasma renin activity in response to upright posture was diminished in 57.9% of acromegalic patients. The prevalence of low-renin hypertension in our group of patients was 31.6%, which is similar to figures reported for unselected non-acromegalic subjects with essential hypertension. Orthostatic renin activity was weakly and inversely related (r = -0.3) to blood pressure. No relationship between plasma aldosterone concentration and blood pressure could be detected; however, in acromegalic women, aldosterone rose higher after ambulation than in men. In conclusion, hypertension is a common problem in acromegaly and at least in part related to similar risk factors in control populations. The association with abnormalities of the renin-angiotensin-aldosterone system is difficult to interpret and does not offer an explanation for the slight increase in the prevalence of hypertension.

Acromegaly↗
PubMed1990

[What is the recurrence rate for Basedow's disease treated with thyrostatic agents. Answers from a prospective study].

Graves' disease is an autoimmune disease whose development involves immunogenetic and exogenous factors such as viruses, bacteria and iodine excess. In a number of patients the disease follows a chronic recurrent course. A recurrence rate of 50% can be expected one year after the end of therapy. Based on the preliminary results of the prospective study presented here, this recurrence rate does not differ in groups where patients underwent long-term treatment with 10 or 40 mg thiamazole. Retrospectively obtained data suggest that the time at which euthyroidism occurs under low-dose treatment is dependent on the alimentary iodine supply. A number of groups have attempted to develop clinically applicable methods to identify patients at risk for recurrence at the end of treatment. All the studies yielded controversial results. A prospective multicenter study was undertaken to reinvestigate the importance of measuring TSH receptor antibodies and performing the TRH test and the suppression test at the end of therapy in connection with this problem. In 451 patients the recurrence rate was 50.3% one year after the end of treatment. The patients in the recurrence group had a significantly higher rate of persistent antibody activity, no increase in TSH after TRH (negative TRH test), no normal suppressibility of thyroid 123 iodine uptake (negative suppression test) and larger goiter. The calculation of sensitivities and specificities shows, however, that these differences are not large enough to be of clinical importance for the individual patient.

Autoantibodies↗
PubMed1990

Survival rates in patients with differentiated thyroid carcinoma. Influence of postoperative external radiotherapy.

Nine hundred thirty-two patients with papillary and follicular thyroid carcinomas were seen at the Departments of Medicine, Surgery, and Radiology of the University of Essen, Essen, Germany, between 1970 and 1986. In addition to standard treatment by surgery, radioactive iodine and medical thyroid stimulating hormone (TSH) suppression, 346 patients had received conventional external irradiation to the neck (mostly 40-60 Gy) before referral to our institutions, whereas 586 patients had not received radiotherapy. From the follow-up data of these patients, survival rates were calculated separately for tumor Stages T1 (n = 203), T2 (n = 552), and T3/T4 (n = 277) using life-table analysis. Distribution of risk factors (histologic type of tumor, grading of malignancy, presence of distant metastases, age and sex) was similar in all groups with the one exception, that the radiotherapy patients with Stage T3/T4 were older. There was no significant difference in the life expectancy of irradiated and not irradiated patients by Breslow and Mantel-Cox tests. In Stages T1, T2, and T3/T4, 75% of the radiotherapy patients survived for 10.6 +/- 0.32, 11.5 +/- 0.61, and 6.71 +/- 0.85 years, respectively; the figures for the nonirradiated patients were 9.4 +/- 0.17, 10.8 +/- 0.37, and 6.26 +/- 0.51 years, respectively. When survival rates were calculated separately for patients with Stage T3/T4 older and younger than 40 years, there was no obvious effect of radiotherapy in the younger group, whereas in the older patients, improvement of survival by radiation just failed to reach statistical significance (P less than 0.09). In conclusion, this retrospective analysis failed to prove that survival is prolonged in patients with differentiated carcinoma by administration of conventional external radiotherapy after surgery. A benefit to older patients with locally advanced tumors has still to be demonstrated.

Adenocarcinoma↗
PubMed1990

[A registry of medullary thyroid cancer in West Germany].

A register for medullary thyroid carcinoma (MTC) in FRG has been set up by the "German Medullary Thyroid Carcinoma Study Group" in 1988. The aim is to provide a basis for collaborative work on MTC especially in the hereditary forms (i.e. multiple endocrine neoplasia [MEN] type IIa, IIb). For these hereditary varieties reliable screening tests exist and, if the disease is detected by family screening in an early stage, curative surgery is possible. Until now 408 patients (234 female, 174 male) with MTC have been reported by 17 cooperative centers. The mean age at diagnosis was 45.5 years. 25% (n = 104) are hereditary forms, most of them MEN IIa (n = 86), 13 are MEN IIb and 18 belong to the familial variety without other endocrinopathy. The mean age at diagnosis for MEN IIa was 36.5 years, MEN IIb 26.9 and for the pure familial form 27.5 years. As 33 patients per year have been diagnosed since 1982, nearly 25% of all expected cases of MTC in FRG have been registered.

Adult↗