Longer-term recurrence rate after low versus high dose radioiodine ablation for differentiated thyroid Cancer in low and intermediate risk patients: a meta-analysis.

BACKGROUND: Regarding the longer-term recurrence rate the optimal activity for the remnant thyroid ablation in patients with differentiated thyroid cancer (DTC) is discussed controversially. For the short-term ablation success rate up to 12 months there are already several meta-analyses. In this study we performed the first meta-analysis regarding the longer-term recurrence rate after radioactive 131-I administration. METHODS: We conducted an electronic search using PubMed/MEDLINE, EMBASE and the Cochrane Library. All randomized controlled trials (RCTs) assessed the recurrence rate after radioactive iodine ablation in patients with DTC, with a follow-up of at least two years were selected. Statistics were performed by using Review Manager version 5.3 and Stata software. RESULTS: Four RCTs were included in the study, involving 1501 patients. There was no indication for heterogeneity (I2 = 0%) and publication bias. The recurrence rate among patients who had a low dose 131-iodine ablation was not higher than for a high dose activity (odds ratio (OR) 0.93 [95% confidence interval (CI) 0.53-1.63]; P = 0.79). The mean follow-up time was between 4.25 and 10 years. The subgroup analysis regarding the TSH stimulated thyroglobulin values (< 10 ng/mL versus < 2 ng/mL versus ≤1 ng/mL) showed no influence on recurrence rate. CONCLUSIONS: For the first time we showed that the longer-term, at least 2-year follow-up, recurrence rate among patients who had 131-iodine ablation with 1.1 GBq was not higher than with 3.7 GBq.

Correction for hyperfunctioning radiation-induced stunning (CHRIS) in benign thyroid diseases.

PURPOSE: Radioiodine-131 treatment has been a well-established therapy for benign thyroid diseases for more than 75 years. However, the physiological reasons of the so-called stunning phenomenon, defined as a reduced radioiodine uptake after previous diagnostic radioiodine administration, are still discussed controversially. In a recent study, a significant dependence of thyroid stunning on the pre-therapeutically administered radiation dose could be demonstrated in patients with goiter and multifocal autonomous nodules. A release of thyroid hormones to the blood due to radiation-induced destruction of thyroid follicles leading to a temporarily reduced cell metabolism was postulated as possible reason for this indication-specific stunning effect. Therefore, the aim of this study was to develop dose-dependent correction factors to account for stunning and thereby improve precision of radioiodine treatment in these indications. METHODS: A retrospective analysis of 313 patients (135 with goiter and 178 with multifocal autonomous nodules), who underwent radioiodine uptake testing and radioiodine treatment, was performed. The previously determined indication-specific values for stunning of 8.2% per Gray in patients with multifocal autonomous nodules and 21% per Gray in patients with goiter were used to modify the Marinelli equation by the calculation of correction factors for hyperfunctioning radiation-induced stunning (CHRIS). Subsequently, the calculation of the required activity of radioiodine-131 to obtain an intra-therapeutic target dose of 150 Gy was re-evaluated in all patients. Furthermore, a calculation of the hypothetically received target dose by using the CHRIS-calculated values was performed and compared with the received target doses. RESULTS: After integrating the previously obtained results for stunning, CHRIS-modified Marinelli equations could be developed for goiter and multifocal autonomous nodules. For patients with goiter, the mean value of administered doses calculated with CHRIS was 149 Gy and did not differ from the calculation with the conventional Marinelli equation of 152 Gy with statistical significance (p = 0.60). However, the statistical comparison revealed a highly significant improvement (p < 0.000001) of the fluctuation range of the results received with CHRIS. Similar results were obtained in the subgroup of patients with multifocal autonomous nodules. The mean value of the administered dose calculated with the conventional Marinelli equation was 131 Gy and therefore significantly below the CHRIS-calculated radiation dose of 150 Gy (p < 0.05). Again, the fluctuation range of the CHRIS-calculated radiation dose in the target volume was significantly improved compared with the conventional Marinelli equation (p < 0.000001). CONCLUSIONS: With the presented CHRIS equation it is possible to calculate a required individual stunning-independent radioiodine activity for the first time by only using data from the radioiodine uptake testing. The results of this study deepen our understanding of thyroid stunning in benign thyroid diseases and improve precision of dosimetry in radioiodine-131 therapy of goiter and multifocal autonomous nodules.

Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: what is up, what is down?

The incretin hormones gastric inhibitory polypeptide and especially glucagon-like peptide (GLP) have an important physiological function in augmenting postprandial insulin secretion. Since GLP-1 may play a role in the pathophysiology and treatment of type 2 diabetes, assessment of meal-related GLP-1 secretory responses in type 2 diabetic patients vs healthy individuals is of great interest. A common view states that GLP-1 secretion in patients with type 2 diabetes is deficient and that this applies to a lesser degree in individuals with impaired glucose tolerance. Such a deficiency is the rationale for replacing endogenous incretins with GLP-1 receptor agonists or re-normalising active GLP-1 concentrations with dipeptidyl peptidase-4 inhibitors. This review summarises the literature on this topic, including a meta-analysis of published studies on GLP-1 secretion in individuals with and without diabetes after oral glucose and mixed meals. Our analysis does not support the contention of a generalised defect in nutrient-related GLP-1 secretory responses in type 2 diabetes patients. Rather, factors are identified that may determine individual incretin secretory responses and explain some of the variations in published findings of group differences in GLP-1 responses to nutrient intake.

[Computer program for retinopathy of prematurity screening]. / Computerprogramm für das Screening auf Retinopathia praematurorum.

BACKGROUND: The goal of retinopathy of prematurity (ROP) screening is complete detection of all preterm infants with threshold ROP. AIM: We wanted to develop software to facilitate registration of ROP findings, checking due dates of re-examination, and evaluation of screening data. By means of complete and faultless registration and evaluation of the data of preterm infants, the effectiveness and safety of the screening should increase. METHODS: We developed software that runs under Microsoft Windows 3.1 or Windows 95 and is programmed in Microsoft Access Basic and Microsoft Visual Basic. The software allows all screening data to be registered and evaluated. Intuitive handling, third level of normalization in database architecture, and automatic plausibility checks guarantee the utmost integrity of data and efficacy of database. RESULTS AND CONCLUSION: To date, the software has been used routinely in 2000 examinations in 1000 preterm infants. Our software facilitates clinical management and evaluation of ROP screening, which therefore becomes more safe.

Transscleral vs transpupillary diode laser photocoagulation for the treatment of threshold retinopathy of prematurity.

OBJECTIVE: To evaluate the efficacy and safety of transscleral diode laser photocoagulation for the treatment of threshold retinopathy of prematurity (ROP). PATIENTS: Fifty eyes of 25 preterm infants (birth weight, 510-1200 g [864+/-178 g ¿mean+/-SD¿]; gestational age, 24-29 weeks [26.7+/-1.7 weeks]) with threshold ROP were treated with diode laser photocoagulation (wavelength, 810 nm). One eye of each infant was treated transsclerally while the fellow eye had transpupillary coagulation using the laser indirect ophthalmoscope. Follow-up ranged from 2 to 22 months (10.0+/-5.3 months). MAIN OUTCOME MEASURE: The regression of acute ROP and the incidence of adverse treatment effects. RESULTS: In 25 (100%) of the eyes treated transpupillarly and in 24 (96%) of the eyes treated transsclerally, ROP regressed after a single or a second laser treatment and the outcome was a flat, attached retina. One eye (4%) with disease in zone I failed to improve after transscleral laser treatment and ROP progressed to stage 4B with a partially attached retina, although additional retinal detachment surgery with an encircling band was performed. No adverse side effects as a result of diode laser treatment were noted except for a small amount of retinal-preretinal bleeding in the ridge in 9 (36%) of the transsclerally and in 5 (20%) of the transpupillarly coagulated eyes. There were no adverse side effects (eg, cataract formation) in the anterior segments of the eyes. CONCLUSIONS: The results suggest that transscleral diode laser coagulation is as effective in the treatment of threshold ROP as transpupillary diode laser photocoagulation. Only minor side effects were noted. Transscleral diode laser photocoagulation seems to be an advantageous treatment method if transpupillary treatment bears an increased risk of cataract formation.

[Diode laser coagulation of stage 3+ retinopathy of prematurity]. / Diodenlaserkoagulation der Retinopathia praematurorum Stadium 3+.

BACKGROUND: Laser photocoagulation in retinopathy of prematurity (ROP) appears to have fewer adverse effects and to be at least as effective as cryotherapy. METHODS: To evaluate the efficacy and safety of diode laser photocoagulation we examined 50 eyes affected by stage 3+ ROP in 30 very low birth weight infants (gestational age 24-29 weeks, mean +/- SD 26.5 +/- 1.4 weeks; birth weight 480-1400 g, 898 +/- 208 g) in a prospective (uncontrolled) clinical study. Photocoagulation treatment was performed using a diode laser (810 nm) with a laser indirect ophthalmoscope delivery system. Follow-up ranged from 3 to 23 months (10.5 +/- 6.4 months). RESULTS: In 46 (92%) of the 50 eyes ROP regressed after a single laser treatment and the outcome was a flat, attached retina. Two eyes (4%) had a second laser session and one other eye (2%) had additional retinal detachment surgery, resulting in the regression of ROP and a flat, attached retina. Thus, the success rate was 98% (49 out of 50 eyes). In 1 (2%) of the 50 eyes treatment failed and ROP progressed to stage 5, although additional retinal detachment surgery was performed. No adverse side effects of diode laser treatment were noted, except for a small amount of retinal/preretinal bleeding in the ridge in 8 eyes (16%) and slight postoperative anterior chamber bleeding in 1 eye (2%) with dense tunica vasculosa lentis. There were neither lenticular opacities nor cataract formation. CONCLUSION: Diode laser photo coagulation using the laser indirect ophthalmoscope for stage 3+ ROP was easy to administer. Laser treatment had only minor side effects and was at least as effective as cryotherapy.

Diode laser photocoagulation for stage 3+ retinopathy of prematurity.

BACKGROUND: Laser photocoagulation in retinopathy of prematurity (ROP) appears to have fewer adverse effects than cryotherapy and seems to be at least as effective. METHODS: To evaluate the efficacy and safety of diode laser photocoagulation, we included 42 eyes with stage 3+ ROP of 24 preterm infants (gestational age 24-29 weeks, mean +/- SD 26.6 +/- 1.3 weeks; birth weight 480-1400 g, 896 +/- 196 g) in a prospective clinical study. Photocoagulation treatment was performed using a diode laser (810 nm) with a laser indirect ophthalmoscope delivery system. Follow-up ranged from 3 to 16 months (8.8 +/- 4.0 months). RESULTS: In 39 (93%) of 42 eyes ROP regressed after a single laser treatment and the outcome was a flat, attached retina. One eye (2%) had a second laser session and another eye (2%) had additional retinal detachment surgery, resulting in the regression of ROP and a flat, attached retina. Thus, the success rate was 41 (98%) out of 42 eyes. In one (2%) of the 42 eyes treatment failed and ROP progressed to stage 5, although additional retinal detachment surgery was performed. No adverse side effects of diode laser treatment were noticed except for a small amount of retinal/preretinal bleeding in the ridge in five eyes (12%) and a small postoperative anterior chamber hemorrhage in one eye (2%) with dense tunica vasculosa lentis. Neither lenticular opacities nor cataract formation were encountered. CONCLUSION: Diode laser photocoagulation for stage 3+ ROP showed only minor side effects and was at least as effective as cryotherapy treatment.

Diode laser photocoagulation for threshold retinopathy of prematurity in eyes with tunica vasculosa lentis.

PURPOSE: To determine possible side effects of diode laser photocoagulation for threshold retinopathy of prematurity in eyes with tunica vasculosa lentis. METHODS: In a prospective clinical study, threshold retinopathy of prematurity was treated in 14 eyes of seven consecutive preterm infants with tunica vasculosa lentis (birth weight, 480 to 980 g; mean +/- S.D., 777 +/- 175 g; gestational age, 24 to 27 weeks; mean +/- S.D., 25.7 +/- 0.9 weeks) by using the diode laser indirect ophthalmoscope. Main outcome measure was the incidence of adverse treatment effects. Follow-up included anterior segment examination with a hand-held slit lamp and ranged from seven to 17 months (12.6 +/- 3.5 months). RESULTS: The tunica vasculosa lentis did not interfere with photocoagulation in any of the 14 eyes. Laser power ranged from 200 to 400 mW (260 +/- 52 mW). Duration of a single spot was 200 msec. Number of burns ranged from 1,060 to 2,132 (1,556 +/- 315). Retinopathy of prematurity regressed in all eyes, and the outcome was a flat, attached retina. A small amount of postoperative anterior chamber bleeding was noticed in one eye (7% of the eyes, 14% of the patients). There were neither lenticular opacities nor cataract formation. CONCLUSION: Diode laser photocoagulation with the laser indirect ophthalmoscope can be used safely in eyes with tunica vasculosa lentis. At the laser energy levels used in our study, no transient lens opacities or cataract formation occurred. However, the results of this study are limited by a relatively small number of patients and a relatively short follow-up.

Mental and physical state in subclinical hyperthyroidism: investigations in a normal working population.

We investigated whether subclinically hyperthyroid individuals selected from a nonpatient working population exhibit similar impairments to those found in studies with patients. Sixteen subclinically hyperthyroid subjects without apparent reason (SH-0) and 15 subclinically hyperthyroid subjects on levothyroxine (SH-T4) were compared with 27 euthyroid controls with respect to signs and symptoms of hyperthyroidism, sleep, depressivity, ability to concentrate, anxiety, and other dimensions of well-being. We found that SH-T4 exhibited significantly higher TT4 levels, TT4/TBG ratios, and more palpitations than controls. Furthermore, they slept less. The SH-0 subjects reported being in a better mood and less touchy than controls. Psychometric results of all groups were within the normal range. A comparison of this study to previous studies reveals that TT4 levels or TT4/TBG ratios may play a crucial role in the development of the predominantly nervous symptoms in subclinical hyperthyroidism. Possible reasons for the discrepancies between results in hospital and nonhospital settings are discussed.

Subclinical hyperthyroidism: physical and mental state of patients.

We investigated whether subclinical hyperthyroidism [subnormal basal thyroid-stimulating hormone (TSH) level, attenuated TSH response to thyrotropin-releasing hormone (TRH) stimulation, peripheral thyroid hormones within normal range] is accompanied by physical and mental changes. Thirty-five subclinically hyperthyroid patients (27 female, 8 male) were compared with 60 overtly hyperthyroid patients (51 female, 9 male) and with 28 euthyroid control patients (18 female, 10 male) with respect to physical symptoms, affective state, short-term memory, ability to concentrate and psychomotor performance. Patients with subclinical hyperthyroidism ranged between the other two groups. The major difference between controls and subclinically hyperthyroid patients was an increase in frequency of nervous symptoms and symptoms due to an increase of metabolic rate and thermal regulation changes. The major differences between subclinically hyperthyroid and overtly hyperthyroid patients were psychomotor impairment and symptoms of increased metabolic rate. Self-ratings of affective state tended to be similar in patients with subclinical and overt hyperthyroidism. The ability to concentrate and short-term memory were not impaired in any group. Symptoms in patients with subclinical hyperthyroidism probably result from central changes which lead to attenuated TSH responses to TRH, or from elevated but still normal thyroxine levels, which possibly enhance the effect of catecholamines.

Sequential psychological testing during the course of autoimmune hyperthyroidism.

Although the psychological disturbances accompanying Graves' disease are well known, the time required for normalisation of these disturbances during antithyroid drug treatment is not known. Therefore sequential psychological testing during the course of Graves' disease was done. There are also contradictory results concerning the possible correlation of neurophysiological and psychological test results during the course of Graves' disease with thyroid hormone values. Finally, psychological disturbances have been proposed as possible etiologic factors in Graves' disease. In our study, a significant decrease in anxiety and irritability could be observed at the time euthyroidism was achieved. Self-evaluations of depressivity, activity, exhaustion, well-being, extraversion, introversion, and the ability to concentrate changed 1 or 2 months after euthyroidism was induced. Similar test results could be observed after induction of euthyroidism by antithyroid drugs and subtotal thyroid resection. Therefore the mode of therapy does not seem to influence the course of normalisation of psychological parameters. In contrast to other investigations there was hardly any correlation between thyroid hormone values and psychological test results or the ability to concentrate. Nontheless, patients with Graves' disease showing high scores for depression and anxiety exhibit abnormal peripheral helper/suppressor T-lymphocyte relations. Furthermore, patients suffering from Graves' disease tend to be more anxious than controls. It remains to be determined whether an increased susceptibility to psychological disturbances has led to these alterations of lymphocyte subsets in Graves' disease patients with severe depression and anxiety.

Significance of latent hyperthyroidism.

In euthyroidism the circadian rhythm and pulsatility of TSH is well known. With regard to hyperthyroidism only very preliminary data were described. In this study we investigated the secretion pattern of the pituitary-thyroid axis hormones during 24 h in latent and overt hyperthyroidism and in euthyroidism with regard to common and different properties. Blood was obtained for 24 h at 10-min intervals. In euthyroidism we found intraindividually three overlapping patterns of TSH, which are different in amplitude and frequency and can be found interindividually, too. These patterns are equal to the circadian rhythm, pulsatile secretion and lastly to the methodic rustle. The circadian rhythm in latent hyperthyroidism is distinctly suppressed and in overt hyperthyroidism totally. Whereas in latent hyperthyroidism pulsatile secretion is extant, in overt hyperthyroidism the TSH pulses are absent. To record the patients' TSH circadian rhythm with only three blood samples, we defined the TSH-Triplex. In young as well as in elderly healthy volunteers it demonstrated significantly higher TSH levels at midnight (at 24:00 h) than it did at 4 p.m. and 8 a.m. The present study shows a significantly different TSH pattern in latent hyperthyroidism compared to euthyroidism. It should be discussed whether latent hyperthyroidism could be defined as hyperthyroidism stage I. On the other hand, latent hyperthyroidism could be an illness with its own cause, different from hyperthyroidism. Our data suggest that the laboratory findings of latent hyperthyroidism in each age are non-physiological. However, the cause for this disorder is unclear until now; hence further investigations are necessary.

[The hypothalamo-hypophyseal thyroid axis, plasma protein concentrations and the hypophyseo-gonadal axis in low T3 syndrome following acute myocardial infarct]. / Hypothalamo-hypophysäre Schilddrüsen-Achse, Plasmaproteinkonzentrationen und die hypophysäre Gonaden-Achse im Low-T3-Syndrom nach akutem Myokardinfarkt (AMI).

In patients with severely acute diseases, a special relationship of thyroidal hormones with decreased T3 and increased rT3 levels is known, the so-called low T3 syndrome. The aim of this study was to elucidate the involvement of the hypothalamo-pituitary thyroid axis, the pituitary-gonadal axis, the altered hepatic function, the plasma proteins in the low T3 syndrome, and the evaluation of these parameters for prognosis in patients with acute myocardial infarction. Thirty-one patients (29 male, 2 female) with AMI entered the study for the determination of hypothalamo-pituitary thyroid axis and the plasma proteins. Besides routine laboratory determinations, TRH, TSH, T4, T3, rT3, CHE, albumin, total protein, TBG, and estradiol concentrations in plasma were measured daily for 5 days after AMI using immunological and other methods. Twelve male patients with AMI entered the study for the determination of pituitary-gonadal axis; the T3, rT3, estradiol, testosterone, FSH, and LH concentrations in serum were determined using immunological methods. We found that T3 and T4 decreased significantly to a minimum on the first and the second day, respectively, after admission and increased in the course of the observation period. In contrast, rT3 was elevated significantly within the first 2 days and decreased later. TSH and TRH decreased in the first 2 days and increased in the following days. CHE, albumin, and total protein levels significantly showed a minimum on day 4 and TBG significantly showed a minimum on the second day after AMI and increased to day 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of hypometabolism on cell injury.

Rats were given galactosamine 1 g/kg i.p. Pretreatment with propylthiouracil 14 days prior to intoxication and surgical thyroidectomy 10 days prior to intoxication significantly reduced the elevation of SGOT and GLDH activities and protected against hepatocellular necrosis 28 h after intoxication. T3 and T4 levels decreased significantly within the first 2 days in patients with acute myocardial infarction, while rT3 levels were found to be elevated within this period. TRH and TSH decreased during the first 2 days of the observation period and increased in course of time. The protective role of the "hypometabolic" state is discussed.