Roland Gärtner

Publications of Roland Gärtner

• [Hypothyroidism--diagnosis and therapy].

  Authors: Roland Gärtner

  MMW Fortschritte der Medizin. 11/2010; 152(44):67-9, 71; quiz 72.

• [48-year-old woman with pressure pain in the neck]

  Authors: Roland Gärtner

  Deutsche medizinische Wochenschrift (1946). 12/2009; 134(49):2515-6.

• Thyroid diseases in pregnancy.

  Authors: Roland Gärtner

  Current opinion in obstetrics & gynecology. 09/2009;

  PURPOSE OF REVIEW: Thyroid disorders are common in pregnancy and affect maternal and fetal outcome. RECENT FINDINGS: The reference values for normal thyroid function during first and second trimesterPURPOSE OF REVIEW: Thyroid disorders are common in pregnancy and affect maternal and fetal outcome. RECENT FINDINGS: The reference values for normal thyroid function during first and second trimester had been re-evaluated recently. Hypothyroxinemia affects the neuropsychological development of the child. Maternal thyroid dysfunction or only the presence of thyroid-specific antibodies is associated with increased risk for early abortion, preterm delivery and neonatal morbidity. Pregnant women under levothyroxine treatment are often undertreated or overtreated. Screening for thyroid dysfunction of pregnant women is recommended and cost-effective. SUMMARY: Recently, the recommended dose for iodine intake during pregnancy had been increased from 200 to 250 mug/day, because recent studies revealed that even mild-to-moderate iodine intake might affect the neuropsychological development of the child. About 5-18% of all pregnant women exhibit elevated thyroid-specific antibodies, but only 0.3% develop overt hypothyroidism and 0.1-0.4% overt hyperthyroidism. However, those pregnant women with autoimmune thyroiditis and normal thyroid function may have a restricted thyroid reserve, followed by hypothyroxinemia and/or thyroid-stimulating hormone increase during pregnancy. The incidence of miscarriage, preterm delivery and small for date offspring might be increased and probably a delayed neuropsychological development. Routine thyroid function testing at least as early as possible in all pregnant women is emphasized.

• Selenium and thyroid hormone axis in critical ill states: an overview of conflicting view points.

  Authors: Roland Gärtner

  Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 02/2009; 23(2):71-4.

  In critical ill states the plasma selenium levels are low and inversely correlated with the severity and outcome of the disease. The plasma selenium levels indicate the amount of circulatingIn critical ill states the plasma selenium levels are low and inversely correlated with the severity and outcome of the disease. The plasma selenium levels indicate the amount of circulating selenoproteins and selenoenzymes. These are important for the maintenance of the redox system, modulating the immune system and also for thyroid hormone metabolism. Not only all three deiodinases (D1-3) are selenoenzymes, but within the thyroid gland there are several other selenoenzymes, which are important for the maintenance of normal thyroid function. In critical ill states also triodothyronine (T3) is low and reverse T3 elevated, and also TSH and thyroxin (T4) are low, correlating like low plasma selenium with the severity of the disease. Subsequently, several intervention trials had been performed to evaluate whether an adjuvant selenium supplementation might attenuate the course of the disease and improve outcome. The selenium supplementation improved outcome and even reduced mortality in some but not all prospective randomized trials. A few prospective randomized intervention trials with selenium supplementation had also been performed to evaluate the hypothesis, whether low selenium is the cause of low-T3-syndrome, however, with conflicting results and no clear evidence that low D1 activity is due to the selenium deficiency in critical illness. Because D1 catalyses the conversion of T4 to T3 and also the clearance of reverse T3, low D1 activity would sufficiently explain low plasma T3 and elevated reverse T3. It had been, however, clearly shown that cytokines are responsible for the inhibition of D1 activity, but D2 and D3 are even higher during acute inflammation in critically ill patients. One of the most important effects of selenium on the immune system seems to be the reduction of cytokine release and therefore an indirect connection between low selenium and low D1 activity has to be postulated and not a lower D1 activity due to lower availability of selenium for the D1 expression.

• [Hyperthyroidism in the elderly: do not relay only on TSH and typical symptoms]

  Authors: Roland Gärtner

  MMW Fortschritte der Medizin. 10/2008; 150(36-37):29-31.

• Effects of Selenium Supplementation on TPOAb and Cytokines in Acute Autoimmune Thyroiditis.

  Authors: Roland Gärtner, Leonidas H Duntas

  Thyroid : official journal of the American Thyroid Association. 07/2008; 18(6):669-70.

• Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock.

  Authors: Matthias W A Angstwurm, Lothar Engelmann, Thomas Zimmermann, Christian Lehmann, Christoph H Spes, Peter Abel, Richard Strauss, Andreas Meier-Hellmann, Rudolf Insel, Joachim Radke, Jürgen Schüttler, Roland Gärtner

  Critical care medicine. 02/2007; 35(1):118-26.

  OBJECTIVE: Sepsis is associated with an increase in reactive oxygen species and low endogenous antioxidative capacity. We postulated that high-dose supplementation of sodium-selenite would improveOBJECTIVE: Sepsis is associated with an increase in reactive oxygen species and low endogenous antioxidative capacity. We postulated that high-dose supplementation of sodium-selenite would improve the outcome of patients with severe sepsis and septic shock. DESIGN: Prospective randomized, placebo-controlled, multiple-center trial. SETTING: Eleven intensive care units in Germany. PATIENTS: Patients were 249 patients with severe systemic inflammatory response syndrome, sepsis, and septic shock and an Acute Physiology and Chronic Health Evaluation (APACHE) III score >70. INTERVENTIONS: Patients received 1000 microg of sodium-selenite as a 30-min bolus injection, followed by 14 daily continuous infusions of 1000 microg intravenously, or placebo. MEASUREMENTS AND MAIN RESULTS: The primary end point was 28-day mortality; secondary end points were survival time and clinical course of APACHE III and logistic organ dysfunction system scores. In addition, selenium levels in serum, whole blood, and urine as well as serum glutathione-peroxidase-3 activity were measured. From 249 patients included, 11 patients had to be excluded. The intention-to-treat analysis of the remaining 238 patients revealed a mortality rate of 50.0% in the placebo group and 39.7% in the selenium-treated group (p = .109; odds ratio, 0.66; confidence interval, 0.39-1.1). A further 49 patients had to be excluded before the final analysis because of severe violations of the study protocol. In the remaining 92 patients of the study group, the 28-day mortality rate was significantly reduced to 42.4% compared with 56.7% in 97 patients of the placebo group (p = .049, odds ratio, 0.56; confidence interval, 0.32-1.00). In predefined subgroup analyses, the mortality rate was significantly reduced in patients with septic shock with disseminated intravascular coagulation (n = 82, p = .018) as well as in the most critically ill patients with an APACHE III score > or =102 (>75% quartile, n = 54, p = .040) or in patients with more than three organ dysfunctions (n = 83, p = .039). Whole blood selenium concentrations and glutathione peroxidase-3 activity were within the upper normal range during selenium treatment, whereas they remained significantly low in the placebo group. There were no side effects observed due to high-dose sodium-selenite treatment. CONCLUSIONS: The adjuvant treatment of patients with high-dose sodium-selenite reduces mortality rate in patients with severe sepsis or septic shock.

• Dose-related influence of sodium selenite on apoptosis in human thyroid follicles in vitro induced by iodine, EGF, TGF-beta, and H2O2.

  Authors: Petra Lehmann, Petra Rank, Klaus L J Hallfeldt, Bjarne Krebs, Roland Gärtner

  Biological trace element research. 08/2006; 112(2):119-30.

  Apoptosis of thyroid follicular cells is induced by high doses of iodide, epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), as well as H2O2 and might be attenuated byApoptosis of thyroid follicular cells is induced by high doses of iodide, epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), as well as H2O2 and might be attenuated by antioxidants. Therefore, we examined the apoptotic index induced by these substances in selenium-treated vs untreated human thyroid follicular cells. Reconstituted human thyroid follicles were incubated with sodium selenite (10 or 100 nM) for 72 h; controls received none. The follicles were then distributed to 24-well plates and incubated with potassium iodide (5, 10, or 20 nM), EGF (5 ng/mL), TGF-beta (5 ng/mL), or H2O2 (100 muM). Apoptosis was determined by a mitochondrial potential assay and the number of apoptotic cells counted by two independent, experienced technicians and the glutathione peroxidase (GPx) activity was determined. Asignificant increase of apoptic cells was obtained in control thyroid follicles treated with iodine (5, 10, or 20 microM), thyroidstimulating hormone (TSH) 1, or 10 mU/mL in combination with 5 and 10 microM iodine, EGF (5 ng/mL) and TGF-beta (5 ng/mL), or H2O2 (100 microM) (p < 0.001). In contrast, in thyroid follicles preincubated with 10 or 100 nM sodium selenite, the apoptototic index was identical to the basal rate. In H2O2-treated follicles, the apoptotic index was still significantly elevated but 50% lower compared to control cells. The GPx activity increased from 1.4 +/- 0.2 to 2.25 +/- 0.4 mU/microg DNA with 10 nMselenite and 2.6 + 0.4 mU/microg DNA with 100 nM selenite. Sodium selenite might increase the antioxidative potential in human thyroid follicles in vitro and therefore diminish the apoptosis induced by TGF-beta, EGF, iodide, and even H2O2.

• [Modern diagnostic approach to autoimmune thyroiditis]

  Authors: Roland Gärtner

  MMW Fortschritte der Medizin. 05/2006; 148(16):41, 43-5.

  High-resolution ultrasonography of the thyroid gland is the major primarytechnical diagnostic procedure in suspected autoimmune thyroiditis (AIT). A diffusely echo-poor thyroid is proof of theHigh-resolution ultrasonography of the thyroid gland is the major primarytechnical diagnostic procedure in suspected autoimmune thyroiditis (AIT). A diffusely echo-poor thyroid is proof of the presence of AIT. Duplex sonography provides further information about the activity of the disease, and is of differential diagnostic importance for distinguishing postpartum thyroiditis from AIT, or for the investigation of an infiltrating carcinoma. Today, antibody determination serves merely to confirm the diagnosis, with TPO antibodies being the most specific for AIT. The TG antibodies may also be nonspecifically elevated in subacute thyroiditis (de Quervain) or irradiation or radioiodine treatment. For an evaluation of thyroid gland function in AIT, determination of basal TSH is needed.

• [Osteoporosis in the elderly--diagnosis and treatment]

  Authors: Roland Gärtner

  MMW Fortschritte der Medizin. 03/2005; 147(7):33, 35-6.

  In contrast to postmenopausal osteoporosis, the overriding objective in senior citizens older than 75 years is to avoid fractures of the hip, which are associated with a high mortality rate. BoneIn contrast to postmenopausal osteoporosis, the overriding objective in senior citizens older than 75 years is to avoid fractures of the hip, which are associated with a high mortality rate. Bone density measurement obtained at the neck of the femur using DXA provides reliable data on the risk of an individual patient of sustaining a fracture close to the hip joint. A physical examination can help to assess the patient's risk of falling, while diagnostic laboratory studies can help to exclude secondary osteoporosis. As a preventive measure, physical activity can increase bone density also in old age. Calcium and vitamin D improve muscular strength and coordination, and thus also may be helpful in preventing falls. In manifest osteoporosis, risedronate and alendronate reduce the risk of fractures close to the hip and of vertebrae by 50%. In addition, raloxifene can be employed to prevent vertebral fractures.

• Selenium in the treatment of autoimmune thyroiditis.

  Authors: Roland Gärtner, Barbara C H Gasnier

  BioFactors (Oxford, England). 02/2003; 19(3-4):165-70.

  We recently conducted a prospective, placebo-controlled clinical study, where we could demonstrate, that a substitution of 200 microg sodium selenite for three months in patients with autoimmuneWe recently conducted a prospective, placebo-controlled clinical study, where we could demonstrate, that a substitution of 200 microg sodium selenite for three months in patients with autoimmune thyroiditis reduced thyroid peroxidase antibody (TPO-Ab) concentrations significantly. Forty-seven patients from the initially 70 patients agreed to participate in a follow-up cross-over study for further six months. One group (n = 13), which initially received selenium continued to take 200 microg sodium selenite (Se-Se), one group stopped taking selenium (Se-0) ( n = 9), another group which received placebo started to take 200 microg selenium (n = 14) (Plac-Se) and the last group was without selenium substitution (Plac-0) (n = 11). TPO-Ab concentrations were measured at beginning and the end of the study. In the Se-Se group, the TPO-Ab concentrations further significantly p = 0.004) decreased from 625 +/- 470 U/ml to 354 +/- 321 U/ml, in the Se-0 group the TPO-Ab concentrations increased significantly p = 0.017) from 450 +/- 335 to 708 +/- 313 U/ml. In the placebo group, the TPO-Ab concentrations in those patients who were followed without selenium substitution were unchanged (1351 +/- 940 vs. 1724 +/- 1112 U/ml, p = 0.555). In contrast, the patients who received 200 microg sodium selenite after placebo, the TPO-Ab concentrations decreased significantly (p = 0.029) from 1182 +/- 723 to 643 +/- 477 U/ml.

• Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations.

  Authors: Roland Gärtner, Barbara C H Gasnier, Johannes W Dietrich, Bjarne Krebs, Matthias W A Angstwurm

  The Journal of clinical endocrinology and metabolism. 05/2002; 87(4):1687-91.

  In areas with severe selenium deficiency there is a higher incidence of thyroiditis due to a decreased activity of selenium-dependent glutathione peroxidase activity within thyroid cells.In areas with severe selenium deficiency there is a higher incidence of thyroiditis due to a decreased activity of selenium-dependent glutathione peroxidase activity within thyroid cells. Selenium-dependent enzymes also have several modifying effects on the immune system. Therefore, even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases. We performed a blinded, placebo-controlled, prospective study in female patients (n = 70; mean age, 47.5 +/- 0.7 yr) with autoimmune thyroiditis and thyroid peroxidase antibodies (TPOAb) and/or Tg antibodies (TgAb) above 350 IU/ml. The primary end point of the study was the change in TPOAb concentrations. Secondary end points were changes in TgAb, TSH, and free thyroid hormone levels as well as ultrasound pattern of the thyroid and quality of life estimation. Patients were randomized into 2 age- and antibody (TPOAb)-matched groups; 36 patients received 200 microg (2.53 micromol) sodium selenite/d, orally, for 3 months, and 34 patients received placebo. All patients were substituted with L-T(4) to maintain TSH within the normal range. TPOAb, TgAb, TSH, and free thyroid hormones were determined by commercial assays. The echogenicity of the thyroid was monitored with high resolution ultrasound. The mean TPOAb concentration decreased significantly to 63.6% (P = 0.013) in the selenium group vs. 88% (P = 0.95) in the placebo group. A subgroup analysis of those patients with TPOAb greater than 1200 IU/ml revealed a mean 40% reduction in the selenium-treated patients compared with a 10% increase in TPOAb in the placebo group. TgAb concentrations were lower in the placebo group at the beginning of the study and significantly further decreased (P = 0.018), but were unchanged in the selenium group. Nine patients in the selenium-treated group had completely normalized antibody concentrations, in contrast to two patients in the placebo group (by chi(2) test, P = 0.01). Ultrasound of the thyroid showed normalized echogenicity in these patients. The mean TSH, free T(4), and free T(3) levels were unchanged in both groups. We conclude that selenium substitution may improve the inflammatory activity in patients with autoimmune thyroiditis, especially in those with high activity. Whether this effect is specific for autoimmune thyroiditis or may also be effective in other endocrine autoimmune diseases has yet to be investigated.

• The role of tacrolimus (FK506)-based immunosuppression on bone mineral density and bone turnover after cardiac transplantation: a prospective, longitudinal, randomized, double-blind trial with calcitriol.

  Authors: Hans-Ulrich Stempfle, Christiane Werner, Uwe Siebert, Tanja Assum, Uli Wehr, Walter A Rambeck, Bruno Meiser, Karl Theisen, Roland Gärtner

  Transplantation. 02/2002; 73(4):547-52.

  BACKGROUND: Tacrolimus (FK506) is a new immunosuppressive drug in organ transplantation that has demonstrated experimentally to be more deleterious on bone mineral metabolism than cyclosporine. TheBACKGROUND: Tacrolimus (FK506) is a new immunosuppressive drug in organ transplantation that has demonstrated experimentally to be more deleterious on bone mineral metabolism than cyclosporine. The purpose of this clinical study was to evaluate the effects of a tacrolimus-based immunosuppression on the skeleton and to investigate in a prospective, longitudinal, randomized, double-blind, study the effect of 0.25 microg calcitriol (1,25-dihydroxyvitamin D3) versus placebo in the prevention of bone loss and fracture rate after heart transplantion (HTx). METHODS: A total of 53 patients (5 female, 48 male, mean age: 53+/-11 years) were randomized to the study medication. Basic therapy included calcium and sex hormone replacement in hypogonadism. Bone mineral density of the lumbar spine (LS) and femoral neck (FN) were performed at baseline, after 12 and 24 months. Biochemical indexes of mineral metabolism were measured every 3 months. RESULTS: Overall bone mineral density (BMD) was significantly decreased after HTx (T-score-LS: 89+/-13%; FN: 88+/-14%). LS-BMD (% change in g/cm2) increased significantly within the study period in the calcitriol group (12 months: 7.1+/-8.1%, P<0.01; 24 months: 14.0+/-10.1%, P<0.01) and showed a positive trend in the placebo group (12 months: 4.5+/-9.3%, NS; 24 months: 6.2+/-8.0%, NS). FN-BMD in the calcitriol group was stable (12 months: -2.1+/-4.2%; NS; 24 months: -0.9+/-3.2%, NS). FN-BMD in the placebo group decreased significantly within the first 12 month follow-up period (-7.3+/-5.4; P<0.05) and stabilized within 2 years (-8.0+/-4.1%; P < 0.05). Fracture incidence was low during the study interval (first year: 5.0%, second year: 0%). Bone resorption markers decreased significantly during calcitriol therapy. CONCLUSIONS: High dose tacrolimus-based immunosuppressive regimen is associated with a rapid bone loss early after cardiac transplantation. Beyond the first 6 months after HTx, calcium, vitamin D, and hormone supplementation in hypogonadism lead sufficiently to bone mineral recovery. Besides immunosuppression, both concomitant hypogonadism and secondary hyperparathyroidism play a major role for the bone loss and should be therefore monitored and treated adequately. Low dose calcitriol should be substituted for at least 2 years as additional antiresorptive therapy.

• CYCLIC PLASMA IL-6 LEVELS DURING NORMAL MENSTRUAL CYCLE

  Authors: Matthias W.A. Angstwurm, Roland Gärtner, H.W.Löms Ziegler-Heitbrock

  Cytokine.

  Steroid hormones including sex hormones are known to influence cytokine production by cells in vitro. We investigated whether there are differences in cytokine production in vivo and ex vivo duringSteroid hormones including sex hormones are known to influence cytokine production by cells in vitro. We investigated whether there are differences in cytokine production in vivo and ex vivo during the menstrual cycle in five ovulating women compared with five pregnant women and nine males. Interleukin 6 (IL-6) in plasma changed periodically during 12 of 13 cycles in five women. The IL-6 levels were lowest in the luteal phase when progesterone levels were elevated and highest preovulatory when progesterone levels were low (P<0.009). The phenomenon was unrelated to changes in haematocrit or albumin and independent of cortisone, growth hormone, luteinizing or follicle stimulating hormone and testosterone. In contrast to IL-6, the soluble IL-6 receptor did not vary significantly during the menstrual cycle. In comparison, nine males and five pregnant women had low plasma IL-6 levels comparable with women during the luteal phase. In addition, levels of IL-6, IL-10 and TNF were determined after whole blood stimulation with lipopolysaccharide ex vivo during a menstrual cycle. Neither the number of CD-14++or CD14/CD16+cells nor the amounts of IL-6, IL-10 and TNF after stimulation showed cyclic changes.We suggest that sex hormones, especially oestrogen and progesterone, may influence immune responses by decreasing basal IL-6 levels in vivo.

• The role of iodine and delta-iodolactone in growth and apoptosis of malignant thyroid epithelial cells and breast cancer cells.

  Authors: Roland Gärtner, Petra Rank, Birgit Ander

  Hormones (Athens, Greece). 9(1):60-6.

  As we previously demonstrated, the inhibitory effect of iodine on thyroid cell growth is mediated by iodolactones, especially 6-iodo-5-hydroxy-eicosatrienoic acid (delta-iodolactone). In thisAs we previously demonstrated, the inhibitory effect of iodine on thyroid cell growth is mediated by iodolactones, especially 6-iodo-5-hydroxy-eicosatrienoic acid (delta-iodolactone). In this communication we compare the effect of iodide, molecular iodine and delta-iodolactone on growth inhibition and apoptosis on three human thyroid carcinoma cell lines (B-CPAP cells, FTC-133 cells and 8505C cells) as well as on human breast cancer cells (MCF 7). Thyroid carcinoma cells were cultured in Dulbecco's modified Eagle's medium (DMEM) and MCF 7 cells in Rowswell Park Memorial Institute (RPMI) culture medium, both containing 10% (v/v) Fetal Calf Serum (FCS), until they were confluent. Around 2000 cells were then distributed in 12-well plates and grown for 48 h in either DMEM (thyroid cancer cells) or in RPMI medium (MCF 7 cells) both containing 5% FCS. Thereafter, different concentrations of iodide, iodine or delta-iodolactone were added for 24 h. Growth rate was estimated by cell counting in a Coulter Counter adapted for epithelial cells. Apoptosis was determined by a mitochondrial potential assay. The growth rate of B-CPAP cells was unaffected by iodide, but was reduced by high concentreations of molecular iodine (100 and 500 microM). However, delta-iodolactone significantly reduced cell proliferation already with low concentrations (5 microM and 10 microM) and further in a dose-dependent manner up to 82%. FTC-133 and 8505C cells were unaffected by iodide, iodine or delta-iodolactone. In contrast, in MCF 7 cells, molecular iodine (100 microM) inhibited growth from 100% to 83% but delta-iodolactone (1, 5 and 10 microM) dose-dependently decreased growth rate from 100% to 82% and 62%, respectively. The inhibition of growth was through apoptosis, and not necrosis, as the amount of apoptotic cells corresponded to the growth inhibition. delta-Iotaodolactone seems to be the main iodocompound which can inhibit growth and induce apoptosis in B-CPAP cells as well as in MCF 7 breast cancer cells.