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Biomedical subjects

W Reinhardt

Publications and source records attributed to W Reinhardt.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Thyroid hormone resistance: variable clinical manifestations in five patients].

AIM: The syndrome of thyroid hormone resistance (RTH) is characterised by elevated circulating thyroid hormones, unsuppressed TSH levels and peripheral refractoriness to hormone action. Patients with RTH may be clinically hyperthyroid if the pituitary gland is more insensitive than other tissues to thyroid hormones. More often, patients have peripheral tissue resistance as well and are euthyroid. RTH is related to point mutations in the T3-binding domain of the beta-receptor gene. We report the variable clinical and biochemical features of five patients with RTH. METHODS: Five patients with RTH were clinically and biochemically evaluated: thyroid tests were done at baseline, after TRH stimulation and after T3-suppression test. Thyroid ultrasound was performed as well. Individual exons of the thyroid hormone receptor beta gene were amplified from leucocyte DNA in these patients using the polymerase chain reaction (PCR). RESULTS: Sequence analysis identified a single point mutation at a certain nucleotide position. This corresponds to aminoacids substitutions at one position in the predicted aminoacid sequence. RTH was familial in three individuals and sporadic in two. Three of the patients underwent thyroid surgery or radioiodine treatment because of recurrent goiter and/or "refractory hyperthyroidism". Moreover, one of our patients with RTH developed also hyperthyroidism due to Graves disease and underwent thyroid surgery for the third time. Her brother, besides RTH, demonstrated strongly positive TPO-antibodies and a hypoechogenic pattern on ultrasound. So the diagnosis of Hashimoto's thyroiditis was made. CONCLUSIONS: RTH has to be considered in all patients with inappropriate TSH secretion. The clinical manifestation of patients with RTH is heterogenous. Thyroid antibody measurements should be performed regularly in order to detect the development of coexisting autoimmune thyroid disease.

Adult↗
PubMed1996

Pharmacokinetics and pharmacodynamics of subcutaneous testosterone implants in hypogonadal men.

OBJECTIVE: There are advantages and disadvantages with all of the presently available types of testosterone replacement for hypogonadal men. We performed this investigation to establish detailed data about the pharmacokinetics, pharmacodynamics, feasibility and side-effects of subcutaneously implanted testosterone (T) pellets. DESIGN AND MEASUREMENT: In a single-dose, open-label, non-randomized study, 6 T-pellets, each containing 200 mg of fused crystalline T, were implanted in the subdermal fat tissue of the lower abdominal wall of 14 hypogonadal men. Blood samples for determination of T, LH, FSH, 5 alpha-dihydrotestosterone (DHT), sex hormone binding globulin (SHBG) and oestradiol (E2) were obtained at 0, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hours and on day 21 after implantation and then every 3 weeks until day 189, and on days 246 and 300 during follow-up. In another 36 hypogonadal men the feasibility and side-effects of T-pellets were evaluated. PATIENTS: Fourteen patients participated in the detailed pharmacokinetic study and another 36 patients in the assessment of feasibility and side-effects. All patients (age range 18-61 years) suffered from primary or secondary hypogonadism (T < 3.6 nmol/l). RESULTS: The pharmacokinetic study in 14 hypogonadal men revealed an initial short-lived burst release of T with a peak concentration of 49.0 +/- 3.7 nmol/l at 0.5 +/- 0.13 days which was followed by a stable plateau lasting until day 63 (day 2, 35.2 +/- 2.3; day 63, 34.8 +/- 2.6 nmol/l). Thereafter serum T gradually declined and was close to baseline concentrations on day 300. Apparent terminal elimination half-life (t1/2) was 70.8 +/- 10.7 days and apparent mean residence time 87.0 +/- 4.5 days. On average, serum T was below 10 nmol/l after 180 days. Absorption of T followed a zero-order release kinetic with an absorption half-time of 74.7 days (95% confidence interval: 71.1-78.5) and was almost complete by day 189 (95.9 +/- 0.84%). Serum DHT and E2 were significantly elevated from day 21 to day 105 and correlated significantly with T (DHT, r = 0.65, P < 0.0001, E2, r = 0.67, P < 0.0001). SHBG was significantly decreased from day 21 to day 168. In 6 men with primary hypogonadism T suppressed LH and FSH to the eugonadal range from day 21 to 126 and 42 to 105, respectively, with nadirs occurring at day 84 (LH) and day 63 (FSH). LH and FSH were highly inversely correlated with T (r = -0.47 and -0.57). The only side-effect observed during 112 implantations in the total group of 50 men were 6 local infections (5.4%) leading to extrusion of 5 pellets in 3 men. When given the choice, all patients except one preferred T-pellets to their previous T medication for permanent substitution therapy. CONCLUSION: T-pellets are the androgen formulation with the longest biological action and strongest pharmacodynamic efficacy in terms of gonadotrophin suppression. The pharmacokinetic features are advantageous compared to other T preparations and the patient acceptance is high.

Adolescent↗
PubMed1993

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↗
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↗
PubMed1991

Variable prevalence of lymphocytic thyroiditis among diabetes-prone sublines of BB/W or rats.

The BB/Wor rat develops spontaneous autoimmune insulin-dependent diabetes mellitus (DM) and lymphocytic thyroiditis (LT). Six different inbred sublines of this rat model have been selected for studying the pathogenesis of DM and, thereby, the prevalence of DM has been carefully monitored and found to be relatively constant. In contrast, we have observed a striking difference in the prevalence and intensity of LT in these six sublines, varying from 100% in NB subline rats to 4.9% in BE subline rats at 105-110 days of age. Excess iodide administration frequently increases the prevalence of LT but did not do so in the two sublines (BB and BE) with the lowest frequency of spontaneous LT. In view of this variable prevalence of LT in the different BB/Wor sublines, it is imperative that investigators studying the pathogenesis and modulation of LT in this rat model select those sublines which express a desired frequency of spontaneous LT.

Aging↗
PubMed1990

TSH secretion in Cushing's syndrome: relation to glucocorticoid excess, diabetes, goitre, and the 'sick euthyroid syndrome'.

Thyrotrophin (TSH) secretion was studied in 63 patients with Cushing's syndrome (53 patients with pituitary dependent Cushing's disease, eight with adrenocortical tumours, and two with the ectopic ACTH syndrome). Prior to treatment, TSH response to 200 micrograms of TRH intravenously was significantly decreased compared to controls; TSH response was 'flat' (increment less than 2 mU/l) in 34 patients (54%). Patients with a flat response to TRH had significantly higher morning and midnight cortisol levels than patients with a TSH response of 2 mU/l and more; this was not due to differences in serum thyroid hormone levels. Basal TSH, TSH increment after TRH, and stimulated TSH value, but not serum triiodothyronine, were correlated with cortisol measurements (0800 h serum cortisol, midnight cortisol, and urinary free corticoid excretion). After exclusion of 40 patients with additional disease (severe systemic disease, diabetes mellitus, or goitre), cortisol-TSH correlations were even more pronounced (r = -0.73 for midnight cortisol and stimulated TSH levels), while in the patients with additional complications, these correlations were slight or absent. Successful treatment in 20 patients was associated with a rise in thyroid hormone levels and the TSH response to TRH. These results indicate that (1) the corticoid excess but not serum T3 is the principal factor regulating TSH secretion in Cushing's syndrome, (2) a totally flat response to TRH is rare, and (3) TSH suppression and lower than normal serum thyroid hormone levels are reversible after treatment. Since factors like severe systemic disease, diabetes mellitus and goitre also affect TSH secretion, they tend to obscure the statistically significant correlations between cortisol excess and TSH secretion.

Adult↗
PubMed1990

Effect of thalidomide on the incidence of iodine-induced and spontaneous lymphocytic thyroiditis and spontaneous diabetes mellitus in the BB/Wor rat.

Thalidomide, a derivative of glutamic acid, has immunosuppressive effects and suppresses graft-vs-host disease in the rat and following bone marrow transplantation in man. It is effectively used in the treatment of erythema nodosum leprosum and has a potential therapeutic effect in a variety of autoimmune diseases. In view of these observations, we evaluated the effect of thalidomide on the incidence of spontaneous and iodine-induced lymphocytic thyroiditis and spontaneous insulin dependent diabetes mellitus in the BB/Wor rat. Thalidomide did not suppress the incidence of lymphocytic thyroiditis and serum anti-thyroglobulin antibodies or affect the serum concentrations of T4, T3 and TSH in this rat model. Thalidomide also did not affect the incidence of insulin dependent diabetes mellitus. In contrast to preliminary studies in man and rat demonstrating efficacy in the therapy of autoimmune diseases, thalidomide did not prevent or suppress autoimmune lymphocytic thyroiditis or insulin-dependent diabetes mellitus in the BB/Wor rat.

Animals↗
PubMed1990

[Speckle photographic studies--a supplementary method for instrumental occlusive analysis].

A new three-dimensional method--speckle photography--introduced into stomatology. For judgement of occlusive and functional interests we examined 20 young adults (10 male and 10 female) aged from 21 to 25. The clinical results together with speckle-photographic model evaluations yield useful hints about morphological and functional connections in the orofacial system.

Adult↗
PubMed1989

The inhibitory effect of large doses of methimazole on iodine induced lymphocytic thyroiditis and serum anti-thyroglobulin antibody titers in BB/Wor rats.

The BB/Wor rat spontaneously develops autoimmune insulin dependent diabetes mellitus and lymphocytic thyroiditis (LT). Excess iodine ingestion enhances and low iodine diet decreases the incidence of LT in this rat model but does not affect the incidence of diabetes mellitus. The administration of a low dose of methimazole (MMI; 870 ng/gm bw ip daily) from 30-90 days of age had no significant effect on thyroid function or on the incidence of iodine induced LT and serum anti-thyroglobulin (Tg) antibodies measured by an ELISA assay. A large dose of MMI (0.05% in the drinking water) induced goiter and hypothyroidism. In addition, the incidence of LT was markedly attenuated (76% vs 6%, p less than 0.001) and reduced titers of serum anti-Tg antibodies (0.59 +/- 0.1 OD vs 0.08 +/- 0.01, p less than 0.001) were observed. This inhibitory effect of MMI on the occurrence of iodine induced LT in the BB/Wor rat may be due to the lower antigenicity of the poorly iodinated Tg secondary to MMI therapy and/or to an immunosuppressant effect of MMI itself.

Animals↗
PubMed1988

Effect of L-thyroxine administration on the incidence of iodine induced and spontaneous lymphocytic thyroiditis in the BB/Wor rat.

Chronic L-thyroxine administration (6 micrograms/100g BW, ip, daily) for 2 or 3 months suppressed serum TSH concentrations and decreased both the incidence of spontaneous lymphocytic thyroiditis (LT) and the serum levels of anti-thyroglobulin (anti-Tg) antibodies in the diabetes prone BB/Wor rat. This suggests that TSH may play a role in the occurrence of LT in this rat model. In contrast to these observations, L-thyroxine administration did not affect the markedly increased incidence of LT or the elevated serum anti-Tg antibodies in iodine supplemented BB/Wor rats, suggesting that TSH stimulation is not necessary for the development of iodine induced LT in this rat model. Other factors, such as the increased antigenicity of highly iodinated Tg, may be more important.

Animals↗
PubMed1988

Effect of mouth rinsing with two polyvinylpyrrolidone-iodine mixtures on iodine absorption and thyroid function.

A prospective study was conducted to investigate the effect of long term therapy with two iodine-containing mouth rinses on thyroid function. Two groups of subjects were treated daily for 6 months with either a 5% polyvinylpyrrolidone (PVPI)-1.5% H2O2 mixture (Perimed) or a 5% PVPI-water mixture. Thyroid function studies, serum iodine concentrations, and urinary iodine excretion were measured before treatment, at 6-week intervals during the 6-month treatment period, and 3 weeks after the last treatment. There was evidence of significant iodine absorption (elevated serum total iodine and inorganic iodide concentrations and urinary iodine excretion) from daily use of both Perimed and the PVPI-water mixture. Serum T3 and T4 concentrations and the free T4 index did not change. There was a small significant rise in serum TSH concentrations during mouth rinse therapy, but all values remained within the normal range. This small increase in serum TSH is a normal adaptive response to the antithyroid effect of increased iodine intake and accounts for the maintenance of normal serum T4 and T3 concentrations. While daily use of these iodine-containing mouth rinses does result in significant iodine absorption, there is no evidence for the development of thyroid dysfunction during a 6-month course of therapy.

Absorption↗
PubMed1987

Effect of iodine intake and methimazole on lymphocytic thyroiditis in the BB/W rat.

Spontaneous LT and elevated serum anti-Tg occur in the diabetes prone BB/W rat, but thyroid function is essentially normal in the rats with LT. Prolonged low dose MMI decreases the incidence of LT in BB/W rats. The administration of excess iodine beginning at 30 days of age markedly accelerates the occurrence of LT and anti-Tg at 90 days of age. Low iodine intake decreases the incidence of LT. Excess iodine intake did not induce LT in W-line, Wistar-Furth, and Sprague-Dawley rats. This suggests that iodine induced LT occurs only in genetically susceptible rats. Despite the increased incidence of LT during iodine administration, thyroid function remains essentially normal. This is in contrast to the frequent induction of hypothyroidism following iodine administration to euthyroid patients with Hashimoto's thyroiditis. In order to decrease thyroid reserve, rats were hemi-TX at 30 days of age. The administration of iodine markedly increased the incidence of LT and serum anti-Tg, increased the weight of the remaining lobe, and induced hypothyroidism as determined by significantly lower serum T4 and T3 concentrations and elevated serum TSH concentrations. Excess iodine administration to hemi-TX W-line rats (genetically equivalent, non-diabetes, non-LT prone BB/W rats) did not induce LT but did induce hypothyroidism, suggesting that BB/W and W-line rats are susceptible to iodine induced hypothyroidism, perhaps unrelated to the induction of LT. Excess iodine did not induce LT or affect thyroid function in hemi-TX Wistar-Furth and Sprague-Dawley rats.

Animals↗