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Biomedical subjects

G Benker

Publications and source records attributed to G Benker.

At least 73 records · Page 4Linked to original sources

Diagnostic problems and operative treatment of pituitary microadenomas.

Over an average observation period of 53 months 26 patients with endocrinological active microadenoma of the hypophysis (12 M. Cushing, 14 acromegaly) were retrospectively examined. Only in 11 cases did the CT-examination demonstrate intrasellar tumour expansion. Both the problems of and the criteria for CT-diagnosis of microadenoma were demonstrated. In 22 cases (84%) the microsurgical transsphenoidal exstirpation of the adenoma led to an adequate reduction in both ACTH and HGH. No postoperative deterioration of the other hypophysial functions was seen. It could be further demonstrated that where the surgical therapy failed local radiation therapy with high voltage radiation of the hypophysis region led to a reduction of the abnormal hormone secretion. The comparism of our results with those reported in the literature led us to suggest a combined therapy concept in which the indication for operative, conservative and radiation therapy is delineated.

Acromegaly↗

Selective bilateral and simultaneous catheterization of the inferior petrosal sinus: CRF stimulates prolactin secretion from ACTH-producing microadenomas in Cushing's disease.

Bilateral, selective and simultaneous catheterization of the inferior petrosal sinus with measurements of ACTH after stimulation with ovine corticotrophin-releasing factor (CRF) is now frequently used to establish the differential diagnosis in patients with Cushing's disease and to determine the side of the microadenoma in the pituitary. To investigate whether CRF has any effect on other pituitary hormones, we also determined prolactin (PRL) concentrations in the samples obtained during this procedure. Fourteen patients under evaluation for Cushing's syndrome and one patient with a hormonally inactive pituitary tumour were catheterized. Baseline PRL levels in the peripheral veins were within the normal range before and after CRF in all patients (3.7-16.0 ng/ml). In 10 patients ACTH- and PRL concentrations lateralized to one side of the pituitary and could both be stimulated by CRF. The gradient of PRL between inferior petrosal sinus and periphery ranged from 7 to 147 ng/ml after CRF. There was no correlation between ACTH and prolactin increase in response to CRF. In three patients with no ACTH-gradient but a positive response to CRF, no tumours could be found during transsphenoidal surgery; they had no PRL-gradient and showed no PRL response to CRF. One patient with the ectopic ACTH syndrome had no ACTH- and no PRL response to CRF. The patient with the inactive pituitary tumour showed a normal ACTH-, but no PRL response to CRF. These data demonstrate for the first time that in normo-prolactinaemic patients with Cushing's disease, in contrast to patients bearing no microadenoma, PRL is secreted in response to CRF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

The sonographical and functional sequelae of de Quervain's subacute thyroiditis: long-term follow-up.

Fifty-three patients with subacute thyroiditis (SAT) were seen during the acute stage of the disease. HLA-Bw 35 was positive in 33 out of 39 tested patients. At first presentation, all examined patients (N = 23) had ultrasound abnormalities (generalized hypodensity, single or multiple hypodense areas). Serum T4 and/or T3 were increased in 24/52, free T4 in 11/23, and the TSH response to TRH was flat in 8/11 patients. Six of 12 in whom volumetry was performed had goitres. Thirty-seven patients were re-examined after a mean follow-up interval of 46.5 months. At this follow-up, serum T4, free T4 and T3 levels as well as the sonographically determined thyroid volume had decreased, but there was still abnormalities by ultrasound detected in 14/36 patients; 19.4% had focal sonolucent lesions, whereas the prevalence of such lesions was only 3.1% in asymptomatic controls. Three patients were subclinically hypothyroid at the follow-up, whereas all others were euthyroid. Patients with abnormal ultrasound findings were of the same age and had a similar thyroid size, but a slightly higher TSH and a significantly (P less than 0.02) lower free T4 than those with normal ultrasound findings. They also had a higher prevalence of thyroid autoantibodies in low titres. Serum thyroglobulin was elevated in more than half of the patients during the acute phase, but only in 1 out of 11 patients during follow-up. Thyroglobulin at the follow-up was not related to TSH, but there was a correlation with thyroid volume (r = 0.57).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Simultaneous bilateral catheterization of the inferior petrosal sinus in Cushing's syndrome. ACTH determination for the diagnosis and location of the side of a hypophyseal microadenoma before and after administration of corticotropin-releasing hormone].

ACTH concentration was measured in simultaneously drawn blood samples from the left and right inferior petrosal sinuses before and after administration of corticotropin-releasing hormone (CRH). Such samples were successfully obtained in 20 of 21 patients with ACTH-dependent Cushing's syndrome on whom it was attempted. In 11 of the 20 patients there was no concentration difference between petrosal sinus and peripheral blood. But 13 of 19 patients had a unilateral central to peripheral concentration gradient greater than 1.4 after CRH administration. In the other six patients no ipsi- to contralateral gradient was demonstrable. Two of these patients had a proven ectopic ACTH-producing tumor; no adenoma was found at operation in three; on patient is awaiting operation. In 10 of 13 patients with unilateral gradient a microadenoma was found on the same side at operation. One patient had a hemi-hypophysectomy on the side of the higher gradient: hypocortisolemia developed in her postoperatively. Two other patients are awaiting operation. The results indicate that simultaneous bilateral catheterization of the inferior petrosal sinus with CRH stimulation is a highly informative examination with few side-effects and will contribute to better diagnosis and treatment of Cushing's syndrome.

Adenoma↗

[Clinical aspects of hyperthyroidism in areas of different supplies of iodine. Results of a European prospective study].

Clinical aspects of 924 unselected patients with hyperthyroidism from 17 thyroid centres of 6 European countries were investigated in a prospective study for exactly 1 year. Serum samples were centrally assayed for thyroid hormones, thyroid autoantibodies and TSH-binding inhibiting immunoglobulins (TBII), and urine samples for iodine. 26 items of information per patient were computerized and evaluated. Forming 2 groups from iodine-deficient areas (IDA) and iodine-sufficient (ISA) according to the urinary iodine, it was possible to elucidate some characteristics independently of local factors. The most important findings were: 1. Three types of hyperthyroidism were described: Graves' disease was defined as hyperthyroidism with eye symptoms and/or the presence of measurable TBII; autonomous adenomas were defined by a single hot nodule in the thyroid scan; the remainder included TBII negative hyperthyroid patients as well as non-immunogenic forms of hyperthyroidism (toxic multinodular goiter and other multifocal autonomies). These were termed "non-classifiable" patients. Graves' patients, representing an average of 60% of the patients, have an age peak between 40 and 49 years; they are 10 years younger than unclassified hyperthyroid patients and 20 years younger than patients with autonomous adenoma, who represented 9.2% of the patients. Surprisingly, there was no difference in the prevalence of Graves' disease between IDA and ISA. 2. An unexpectedly high rate of 10.5% of hyperthyroid patients (Graves' disease 8.5%, non-Graves' disease 14.2%) had no goiter, a figure increasing in the elderly to almost 17%. In IDA the thyroid was larger and the goiter more often nodular than in ISA. IDA are characterized by significantly higher rates (11.3%) of autonomous adenoma than ISA (3.2%). 3. 59.4% of 507 patients with Graves' disease had eye symptoms, 44.6% of at least grade II or higher using the Werner classification. There was no difference between patients from ISA and IDA. We found unilateral ophthalmopathy in 6.7% of Graves' patients. 4. The median iodine excretion was calculated from urinary iodine after exclusion of values over 250 micrograms iodine/g creatinine, arbitrarily defined as iodine contamination. In IDA the median iodine excretion was 63.6, and in ISA 105 micrograms/g of creatinine. 5. Surprisingly, proven iodine contamination was as frequent in IDA (14.5%) as in ISA (15.2%). In the survey protocol, however, this was noticed less often by physicians in ISA.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Determination of the metabolic condition in diabetics with renal insufficiency by means of the fructosamine test].

We determined HBA1 (microcolumn method) and glycosylated albumin (fructosamine) in 23 healthy subjects, 35 patients with renal insufficiency without diabetes and 14 patients with diabetes mellitus and renal insufficiency. All patients with renal insufficiency required dialysis. All diabetics were of type I and had been compensated on insulin. The HBA1 in the nondiabetic patients with renal insufficiency (9.4 +/- 1.4%) was significantly raised compared to that in the control group with healthy metabolism (7.3 +/- 0.6%). Irrespective of the quality of compensation, the diabetic patients had HBA1 values of more than 11% of average. On the other hand, the concentrations of glycosylated albumin in healthy nondiabetic patients and in diabetic patients with renal insufficiency did not differ (1.3 +/- 0.5 as compared to 1.1 +/- 0.4 mmol/l) and were all in the normal range. Well-adjusted diabetics with renal insufficiency had a fructosamine concentration of 1.9 +/- 0.7 mmol/l (theoretical value for a good compensation 2.0 to 2.8). We conclude that determination of HBA1 in pronounced renal insufficiency does not provide reliable values because carbamylated hemoglobin is also registered and determination of fructosamine (which only indicates the metabolic situation in the last three weeks, however) is to be preferred in this situation.

Diabetes Mellitus, Type 1↗

Pharmacokinetics of aldosterone in patients with Addison's disease: effect of rifampicin treatment on glucocorticoid and mineralocorticoid metabolism.

Treatment of tuberculosis with rifampicin in patients with pre-existing adrenal failure has been reported to induce adrenal crisis due to alteration of cortisol metabolism by induction of hepatic mixed liver oxygenase enzymes. To determine whether mineralocorticoid metabolism is altered by rifampicin treatment, we established the pharmacokinetics of immunoreactive aldosterone. The metabolic clearance rate (MCR) and plasma half-life of this material were measured before and after 6 days of rifampicin treatment (600 mg/day) in seven patients with Addison's disease due to tuberculosis. Antipyrine clearance and urinary 6-beta-hydroxycortisol excretion was determined to demonstrate induction of the cytochrome P450 dependent enzymes. Infusion of aldosterone at a constant rate of 0.17 mg/h over 4.5 h produced steady state concentrations after 2 h, with no difference before and after rifampicin treatment (mean +/- SD, 1649 +/- 144 vs 1586 +/- 80 pg/ml, respectively). The disappearance curve of IR-aldosterone from plasma was biexponential. No change could be observed in the plasma half-lives (alpha-phase 29 +/- 1.9 min vs 30 +/- 1.5 min, beta-phase 129 +/- 3.2 min vs 126 +/- 4.3 min), the MCR (1.47 +/- 0.1 l/h/kg vs 1.46 +/- 0.1 l/h/kg), and the volume of distribution (9.9 +/- 1.9 vs 10.2 +/- 0.3 l). The antipyrine half-life decreased significantly from 12.2 +/- 2.6 h to 7.6 +/- 0.9 h (P less than 0.05) with a rise in antipyrine clearance from 0.38 +/- 0.07 to 0.80 +/- 0.23 ml/min/kg (P less than 0.05) and no change in the volume of distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Addison Disease↗

Metabolism of GnRH in man: influence of estrogens.

UNLABELLED: To clarify the influence of estrogens on the metabolism of gonadotropin-releasing hormone (GnRH), we studied the metabolic clearance rate (MCR) of GnRH (MCRGnRH), and the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol and testosterone (total and free fraction) in 9 sexually mature men and 7 women under basal conditions and after treatment with the antiestrogen tamoxifen (2 X 10 mg/day p.o.) for 7 days. In women, the medication was started on day 7 +/- 1 of their menstrual cycles. To calculate the MCR, synthetic GnRH was continuously infused (1.53 micrograms/min) and its serum levels were measured by a radioimmunoassay. During tamoxifen treatment we observed a small but significant decrease in the MCR in men (455 +/- 48 to 357 +/- 46 ml/min/1.86 m2), whereas the known cyclic increase in the MCR in women was blunted (1,769 +/- 147 to 1,558 +/- 119 ml/min/1.86 m2). There was a small but significant increase in LH levels in women (8.3 +/- 2.1 to 11.5 +/- 2.5 mU/ml). LH and testosterone levels in men, and FSH and estradiol levels in both sexes did not change significantly. CONCLUSION: (1) estrogens regulate the MCRGnRH either directly or by changing gonadotropin levels, but the effect is only slight; (2) an enhanced metabolism of GnRH may contribute to the feedback of estrogens on the secretion of gonadotropins, and (3) the sex-specific difference of the MCR is presumably not caused by estrogens.

Adolescent↗

Effects of high and low doses of methimazole in patients with Graves' thyrotoxicosis.

In spite of the long-established use of antithyroid drugs, there are many unsettled questions connected with this treatment of Graves' disease. There is a lack of controlled prospective trials studying the results of antithyroid drug therapy while considering the many variables such as disease heterogeneity, regional differences, drug dosage and duration of treatment. Therefore, a multicenter study has been set up in order to compare the effects of two fixed doses of methimazole (10 vs 40 mg) with thyroid hormone supplementation on the clinical, biochemical and immunological course of Graves' disease and on remission rates. Experience accumulated so far suggests that treatment is safe using either 10 or 40 mg of methimazole. While there is a tendency for an advantage of the higher dose within the first weeks (higher effectiveness in controlling hyperthyroidism), this difference is not significant. The impact of dosage on remission rates remains to be shown.

Adult↗

Bilateral and simultaneous sinus petrosus inferior catheterization in patients with Cushing's syndrome: plasma-immunoreactive-ACTH-concentrations before and after administration of CRF.

The ACTH-producing microadenoma is by far the most common cause of hypercortisolism in patients with Cushing's syndrome. Selective transsphenoidal surgery is the treatment of choice for Cushing's disease, however, it is not uniformly successful. Aim of this study was to determine simultaneously the ACTH-concentration in the right and left sinus petrosus inferior in patients with Cushing's syndrome before and after stimulation with CRF. The procedure was attempted in 17, successfully carried out in 16 patients. In the 14 of whom Cushing's disease was diagnosed, 11 had a gradient greater than 1.4 (central versus peripheral ACTH) after administration of CRF, two patients had no gradient, yet responded to CRF. One patient had the ectopic ACTH-syndrome and showed no response to CRF and no gradient. One patient, found to have no Cushing's disease, had no gradient and responded normal to CRF. In 9 of the 11 patients with a gradient, the microadenoma was found on the side of the higher ACTH-level; one patient underwent hemihypophysectomy of the side where the gradient was directed towards and was cured. No complications occurred. We conclude, that selective, simultaneous and bilateral catheterization of the sinus petrosus inferior is a safe method to localize the side of the microadenoma preoperatively.

Adenoma↗

Clinical and biochemical aspects of the insulin autoimmune syndrome (IAIS).

A 44-year old patient presented with recurrent hypoglycemic attacks after ingestion of carbohydrates. High insulin levels in the range of 350 microU/ml (normal range less than 20 microU/ml) were detected which rose to peak levels of 2,460 microU/ml (normal range less than 300 microU/ml) after oral glucose. The apparently high insulin concentrations were caused by insulin autoantibodies interfering in the radioimmunoassay (RIA) system (and thus with correct insulin quantitation). 125I-insulin added to the patient's serum was not bound to dextran-coated charcoal but was precipitated with antihuman IgG serum. The antibodies bound human, porcine, and bovine insulin with similar affinity. Following Sephadex G-50 gel filtration, the patient's insulin eluted after the void volume. Free insulin was extracted from serum using Sep-Pak C 18 cartridges and characterized by high pressure liquid chromatography (HPLC); it eluted similarly to synthetic human insulin. Quantitation of free insulin during a hypoglycemic attack (3.5 h after oral glucose, with a blood sugar of 20 mg/dl) showed an increased insulin level of 50 microU/ml. Insulin receptor concentration on erythrocytes was near the lower normal limit. We believe that the insulin antibodies present in this patient's serum (who supposedly never received insulin) led to the formation of a large circulating insulin pool, binding the insulin released after glucose stimulation, and causing hypoglycemias by delayed postprandial liberation of bound insulin.

Adult↗

[Acromegaly due to a pancreatic tumor producing growth hormone releasing hormone: clinical picture and morphology].

Acromegaly due to ectopic production of growth hormone releasing hormone (GH-RH) by a tumor is rare, but several cases have been described after isolation and identification of GH-RH from a pancreatic tumor. The authors observed a patient with acromegaly caused by a pancreatic tumor in whom GH-RH production was demonstrated by measurements of GH-RH in peripheral plasma, tumor veins, tumor extracts and immunohistochemical identification. Endocrinological, histological and ultrastructural results are discussed. The problem of potential malignancy is investigated in the light of DNA measurements. This observation shows that GH-RH measurements can be a useful diagnostic procedure before surgery for acromegaly.

Acromegaly↗

[Comparative histologic and hormonal studies of the thyroid gland with special reference to sudden infant death (SIDS)].

In 53 cases of death - including 12 cases of sudden infant death syndrome (SIDS) - where blood samples could be taken within 18 h postmortem, the thyroxines T4, FT4, T3 and FT3 were determined (ELISA and RIA). These hormone values were compared with the corresponding histological thyroid findings in 43 cases (11 SIDS, 32 controls). Nearly identical T4 and FT4 mean values were found in both groups which were within the norms. In contrast to the average values of the control group, the T3 and FT3 concentrations of the SIDS group showed an increase of 3.7-fold and 1.9-fold. Accordingly, histological examination of the SIDS group showed highly activated and extensively released follicles whereas normal colloidal-containing follicle structures were observed in nearly all control cases. The present findings indicate that neither postmortem T4 T3 conversion nor intensified agonal hormone secretion is likely to be the only cause of the increasing T3 and FT3 values. In SIDS cases chronic or recurring chronic stress situations are supposed to be the cause for the hormonal and histological thyroid findings. Some differential diagnoses are discussed. Within 18 h after death, increased concentrations of T3 and FT3, together with simultaneous colloid release, represent a diagnosis of SIDS.

Adolescent↗