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Biomedical subjects

D Reinwein

Publications and source records attributed to D Reinwein.

At least 91 records · Page 5Linked to original sources

[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↗

Parenteral bromocriptine in the treatment of hormonally active pituitary tumours.

Eleven patients with PRL and three with GH-secreting pituitary adenomas were treated with a single intramuscular injection of 50 mg of bromocriptine retard (Parlodel, LA (long-acting)). There was a marked PRL suppression in 9 prolactinoma patients, in four for a period of at least 6 weeks. In one patient with acromegaly GH plasma levels decreased into the normal range. The size of the pituitary adenoma diminished considerably, as shown by CT scan, in three out of the 9 responding patients with prolactinoma and in the above acromegalic patient. Visual fields normalized within 14 d in one patient with a PRL-secreting macroadenoma and bitemporal hemianopsia who also had CT scan-documented shrinkage of the tumour. There were no side-effects except slight hypotension in two and local tenderness at the injection site in one patient; these symptoms disappeared without treatment. It is concluded that bromocriptine retard is a safe and effective therapeutic tool for shrinking hormonally active pituitary tumours in selected patients. Due to its good tolerance and the rapid hormonal and clinical improvement it may be also considered as the best therapeutic approach to initiate the treatment of PRL- and/or GH-secreting pituitary tumours.

Acromegaly↗

Continuous infusion of growth hormone releasing hormone does not alter the growth hormone response to different stress stimuli.

Continuous infusion of GHRH, as well as a bolus injection of GHRH, specifically stimulates the release of GH by the anterior pituitary. However, repetitive bolus injections of GHRH result in diminished responses of GH, while a constant infusion of GHRH cannot maintain high serum GH levels. To investigate whether different GH-releasing stimuli are able further to challenge the somatotroph being exposed to continuous infusion of GHRH, we determined the GH response to insulin-induced hypoglycaemia and bicycle exercise. Six normal volunteers received a bolus of 50 micrograms GHRH or vehicle followed by a continuous infusions of GHRH 1-29 amide (1 microgram/kg/h) or vehicle for 2.5 h. GHRH bolus and infusion resulted in elevated GH levels, but GH levels fell to values not significantly different from baseline levels after 150 min, GH plasma levels rose again, however, in response to insulin hypoglycaemia and bicycle exercise after both GHRH or vehicle infusion. Thus, the somatotroph's responsiveness to GHRH remains intact to respond to stress stimuli after continuous GHRH infusion.

Adult↗

Response of total and 'free' thyroid hormones and diiodotyrosine to bovine TSH in subclinical hypothyroidism.

Thirty-three patients with Addison's disease were studied. Twenty-two had idiopathic Addison's disease; within this group, 14 patients had clinical or subclinical hypothyroidism, and 16 had increased titres of thyroid autoantibodies. Five patients had tuberculous, and eight had unclassifiable Addison's disease; only one patient in the latter group had evidence of thyroid autoimmunity. A stimulation test with 15 mU bTSH/kg was performed in three patients with Schmidt's syndrome (coexisting Addison's disease and manifest primary hypothyroidism), 15 patients with either subclinical hypothyroidism or increased titres of thyroid autoantibodies, 10 patients without thyroid involvement, and 10 normal controls. There was no detectable increase of 'free' and total thyroid hormones in Schmidt's syndrome. The mean increases after 3-4 h of T4, fT4, T3 and fT3 were 22, 35, 63 and 66%, respectively, in patients without thyroid involvement, and 13, 24, 46 and 45% in patients with subclinical hypothyroidism. 'Free' but not total thyroid hormones rose significantly (P less than 0.01) higher in patients without signs of thyroid involvement than in patients with subclinical hypothyroidism and/or thyroid autoantibodies. Thyroid hormone response to bTSH in Addison's disease with apparently healthy thyroid glands was not different from normal controls. Serum diiodotyrosine rose in all groups except in hypothyroidism; hypothyroid patients had, however, basal levels well within the normal range. Thus, thyroid hormone synthesis appears to be blocked at a point distal to diiodotyrosine formation in this particular situation. These results support the assumption that TSH elevation in idiopathic Addison's disease is due to coexisting thyroid autoimmunity and that it reflects incipient thyroid failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Addison Disease↗

[Sonographic volumetry of the thyroid gland in the control o thyroxin and iodide treatment of non-toxic goiter].

In a prospective study 39 patients with diffuse euthyroid goitre were treated for one year with 100 micrograms levothyroxine (n = 19) or 500 micrograms iodide (n = 20). Efficacy of treatment was assessed by sonographic thyroid volumetry . In both forms of treatment maximum volume decrease was already seen within the first six months. After treatment for one year the mean decrease of thyroid volumes was 27.5% in the thyroxine group and 22% in the iodide group. This difference was statistically not significant. There was no difference in the extent of goitre size reduction within the thyroxine group among patients with complete TSH suppression and with still positive TRH test. Significant increases of T4 and of fT4 values within the normal range were observed already after one month with thyroxine treatment and only after 3 months with iodide treatment. There were no changes of the T3 values. In one female patient iodine-induced hyperthyroidism occurred. However, there were no further side effects in both treatment groups. This randomised study documents for the first time that both 500 micrograms of iodide and 100 micrograms of levothyroxine have a comparable efficacy for reduction of goitres.

Adolescent↗