Search PubMed⌕ Search

Biomedical subjects

G J Kahaly

Publications and source records attributed to G J Kahaly.

At least 19 recordsLinked to original sources
PubMed2000

Cardiovascular and atherogenic aspects of subclinical hypothyroidism.

Subclinical hypothyroidism (SH) is common, especially among elderly women. There is no clear evidence to date that SH causes clinical heart disease. However, mild thyroid gland failure, evidenced solely by elevation of the serum thyrotropin (TSH) concentration, may be associated with increased morbidity, particularly for cardiovascular disease, and subtly decreased myocardial contractility. In SH, both cardiac structures and function remain normal at rest, but impaired ventricular function as well as cardiovascular and respiratory adaptation to effort may become unmasked during exercise. These changes are reversible when euthyroidism is restored. Flow-mediated vasodilatation, a marker of endothelial function, is significantly impaired in SH, and decreased heart rate variability, a marker of autonomic activity, suggests hypofunctional abnormalities in the parasympathetic nervous system. SH does result in a small increase in low-density lipoprotein (LDL) cholesterol (C) and a decrease in high-density lipoprotein (HDL)-C, changes that enhance the risk for development of atherosclerosis and coronary artery disease (CAD). After coronary revascularization, a trend toward higher rates of chest pain, dissection, and reocclusion has been noted in SH subjects. Smoking may contribute to the high incidence of SH and may aggravate its metabolic effects. Subjects with SH with marked TSH elevation and high titers of thyroid autoantibodies are at higher risk of unnoticed progression to overt hypothyroidism. Especially women over 50 years with TSH levels greater than 10 mU/L and smoking habits have the highest risk for cardiovascular complications. The magnitude of the lipid changes and the subtle impairment of left ventricular function and cardiopulmonary exercise capacity in SH may justify use of hormone replacement. Early levothyroxine (LT4) treatment in SH may reduce the C level by an average of 8% and normalize all metabolic effects in smokers, nevertheless, in some patients, LT4 therapy may exacerbate angina pectoris or an underlying cardiac arrhythmia. Longitudinal follow-up to define the actual cardiovascular disease risk associated with SH is warranted.

Animals↗
PubMed2000

Somatostatin-receptor scintigraphy in Graves' disease: reproducibility and variance of orbital activity.

Somatostatin-receptor (SSTR) scintigraphy using the single photon emission computed tomography (SPECT) technique allows the assessment of orbital inflammation in patients with Graves' disease. Previous studies showed differences in orbital octreotide uptake already 4 hr after injection. In this study, analysis of inter-/intra-observer variance and reproducibility in the evaluation of orbital SPECT images was performed. First, SPECT data of one representative female patient with clinically active Graves' ophthalmopathy (GO), obtained 4 hr after intravenous injection of 110 MBq 111In-pentetreotide and processed by filtered backprojection, were analyzed. Transverse SPECT images were reconstructed, an optimal orbital image was selected and predetermined regions of interests (ROIs) for both orbits were positioned by three independent observers 15 to 19 times each. In a second step, SPECT data of 8 different patients with GO were evaluated in the same manner by four independent observers 3 to 4 times each. Variance component partitioning was used to compare the order of intra- and inter-observer variation. For the right and the left orbit, the inter-observer variance proportion was 90% and 79%, whereas intra-observer variance partition was 10% and 21%, respectively. The corresponding ratios 0.11 and 0.27 summarize the comparison of sources of variance. The overall reliability was 84%, representing the patients influence on the total variance. Intra-observer reliability for both orbits was 88%, 89%, 97% and 98% (mean over orbits), respectively for observers I to IV. Using the Spearman Brown prophecy formula it follows that two replications per patient are sufficient to ensure a minimum reproducibility of 90%, which is also confirmed by the low intra-observer variation. Furthermore, intra-class correlation as a measure of (multiple) observer reproducibility was 94%. In conclusion, due to the increased inter-observer variance proportion and the high variation in intra-observer reliability, evaluations of orbital SSTR scintigraphy have to be done by the same and experienced observer leading to comparable data. But an automatic and quantitative computerized technique for evaluation of these SPECT data should be exactly reproducible and probably lead to more accurate and representative results.

Adult↗
PubMed2000

Low- versus high-dose radiotherapy for Graves' ophthalmopathy: a randomized, single blind trial.

Orbital radiotherapy (Rx) is a commonly used treatment for Graves' ophthalmopathy (GO), but controlled clinical trials evaluating different Rx doses and application forms have not been performed. In euthyroid patients with moderately severe GO, we randomly compared the efficacy and tolerability of three Rx protocols. Orbital Rx (telecobalt) was administered either in 20 divided fractions of 1 Gray (Gy) weekly over 20 weeks (group A) or in 10 fractions of 1 Gy (B) and 2 Gy (C) daily over 2 weeks. Before and 24 weeks after starting Rx, ophthalmic investigation and magnetic resonance imaging were performed. Response to therapy, defined as a significant amelioration of three objective parameters, was noted in 12 A (67%), 13 B (59%), and 12 C (55%) subjects (C vs. A, P = 0.007). Ophthalmic symptoms and signs regressed most in group A; changes in lid fissure width were -1.5, -0.5, and 0 mm in the A, B, and C groups, respectively (A vs. C, P = 0.005), whereas changes in intraocular pressure (upgaze) were -3, +1, and -1.5 mm Hg, respectively (A vs. B, P = 0.002). The median decreases in proptosis were -2 mm (A, P = 0.0001), -1.5 mm (B, P = 0.02), and -1 mm (C, P = 0.007; A vs. C, P = 0.0380. Visual acuity (+0.15; P = 0.02) and eye muscle motility (bulbar elevation, 30 degrees vs. 37 degrees, P = 0.03, A vs. C, P = 0.0020; abduction, 45 vs. 49 degrees, P = 0.02; A vs. C, P = 0.017) improved in group A only. A significant change in all rectus muscle areas was noted in 14 A (78%), 12 B (55%), and 9 C (41%) subjects (C vs. A, P = 0.002). A decrease in the NOSPECS classes was observed in 12 A (67%), 13 B (59%), and 13 C (59%) patients (A vs. B/C, P = 0.01). Rx-induced conjunctivitis was not observed in group A, but was seen in 4 B (18%) and 8 C (36%) subjects (C vs. A, P = 0.003). At 24 weeks, satisfaction rates were 67%, 59%, and 55% in the A, B, and C groups, respectively (C vs. A, P = 0.008). Thus, in patients with moderately severe GO, similar response rates were observed for low and high Rx doses, but the 1 Gy/week protocol was more effective and better tolerated than the short arm regimens.

Adult↗
PubMed1999

Neuroradiological diagnosis in thyroid-associated orbitopathy.

No renunciation can be made of modern imaging techniques in primary diagnosis as well as in the course of endocrine orbitopathy. Even in times of cost reduction of the public health and although expansive CT and MR play a constant role in the interdisciplinary challenge, concerning the treatment of these patients. Both methods show the actual objective morphological findings, MR giving additional information concerning the acuteness (T2 relaxation time) or chronicity (fatty degeneration), which is of great importance for the chosen therapy. CT and MR is mandatory for the control of the clinical course after conservative, surgical and/or radiotherapeutic therapy.

Graves Disease↗
PubMed1999

Increased sulfatation of orbital glycosaminoglycans in Graves' ophthalmopathy.

Accumulation of interstitial glycosaminoglycans (GAG) in orbital tissue of patients with Graves' ophthalmopathy (GO) leads to edema, increased orbital pressure, and proptosis. In this study, a new, highly sensitive, high performance liquid chromatography method was developed to determine the altered concentration and biochemical composition of different GAG polymers in orbital connective tissue of 27 GO patients and 18 controls. GAG were isolated by tissue homogenization and digestion, followed by sequential enzymatic GAG hydrolysis and high performance liquid chromatographic analysis of the resulting alpha,beta-unsaturated disaccharides. High recovery rates of 78 +/- 6% (mean +/- SE) and a detection limit of 4.0 microg/L (0.01 micromol/L) were obtained. Total tissue GAG amounted to 254 +/- 16 microg/g wet tissue wt in patients and 150 +/- 13 microg/g (P < 0.0001) in controls. Regarding the GAG polymers, marked differences were detected between patients and controls (chondroitin sulfate, 127 +/- 13 vs. 47 +/- 5 microg/g; hyaluronic acid, 56 +/- 5 vs. 34 +/- 4 microg/g; both P < 0.0001; dermatan sulfate, 77 +/- 6 vs. 69 +/- 6 microg/g; P < 0.05). In patients, chondroitin sulfate was the major GAG component (48 +/- 6 vs. 31 +/- 5% of total GAG in controls), whereas dermatan sulfate was dominant in controls (46 +/- 8% vs. 30 +/- 5%). The sulfated disaccharide digestion products were markedly increased (P < 0.0001) in patients, and the ratio of sulfated vs. total disaccharide content was 85 +/- 6% vs. 65 +/- 5% (P < 0.05) in patients and controls, respectively. As accumulation of negatively charged sulfate residues in GAG disaccharides results in enhanced water-binding capacity, beside inflammation and increased volume of the orbital adipose tissue, the altered structure and nature of sulfated GAG units in the orbit may be responsible for the pathogenic changes in Graves' ophthalmopathy.

Adult↗
PubMed1999

Stress echocardiography in hyperthyroidism.

Exertion symptoms occur frequently in subjects with hyperthyroidism. Using stress echocardiography, exercise capacity and global left ventricular function can be assessed noninvasively. To evaluate stress-induced changes in cardiovascular function, 42 patients with untreated thyrotoxicosis were examined using exercise echocardiography. Studies were performed during hyperthyroidism, after treatment with propranolol, and after restoration of euthyroidism. Twenty-two healthy subjects served as controls. Ergometry was performed with patients in a semisupine position using a continuous ramp protocol starting at 20 watts/min. In contrast to control and euthyroidism, the change in end-systolic volume index from rest to maximal exercise was lower in hyperthyroidism. At rest, the stroke volume index, ejection fraction, and cardiac index were significantly increased in hyperthyroidism, but exhibited a blunted response to exercise, which normalized after restoration of euthyroidism. Propranolol treatment also led to a significant increase of delta (delta) stroke volume index. Maximal work load and delta heart rate were markedly lower in hyper- vs. euthyroidism. Compared to the control value, systemic vascular resistance was lowered by 36% in hyperthyroidism at rest, but no further decline was noted at maximal exercise. The delta stroke volume index, delta ejection fraction, delta heart rate, and maximal work load were significantly reduced in severe hyperthyroidism. Negative correlations between free T3 and diastolic blood pressure, maximal work load, delta heart rate, and delta ejection fraction were noted. Thus, in hyperthyroidism, stress echocardiography revealed impaired chronotropic, contractile, and vasodilatatory cardiovascular reserves, which were reversible when euthyroidism was restored.

Adult↗
PubMed1999

The role of octreoscan in thyroid eye disease.

Until recently there was no imaging technique available which could demonstrate pathological changes in orbital tissues and could be regarded as a reliable measure of inflammation in thyroid eye disease (TED). Pentetreotide (a synthetic derivative of somatostatin) labelled with 111In has been used to localize tumours which possess surface or membrane receptors for somatostatin in vivo using a gamma camera (1). This technique visualizes somatostatin receptors in endocrine-related tumours in vivo and predicts the inhibitory effect of the somatostatin analogue octreotide on hormone secretion by the tumours (1). By applying 111In-DTPA-d-Phe octreotide scintigraphy (octreoscan), accumulation of the radionuclide was also detected in both the thyroid and orbit of patients with Graves' disease (2-4). If peak activity in the orbit 5h after injection of radiolabelled octreotide is set at 100%, a decrease to 40+/-4% is found at 24h, significantly different from the decrease in blood pool radioactivity, which is 15+/-4% at 24h. Accumulation of the radionuclide is most probably due to the presence in the orbital tissue of activated lymphocytes bearing somatostatin receptors (5). Alternative explanations are binding to receptors on other cell types (e.g. myoblasts, fibroblasts or endothelial cells) or local blood pooling due to venous stasis by the autoimmune orbital inflammation.

Graves Disease↗
PubMed1998

Cardiac risks of hyperthyroidism in the elderly.

The importance of cardiovascular system involvement in hyperthyroidism has been recognized for many years. In the elderly patient, often with mild but prolonged elevation of plasma thyroid hormones, symptoms and signs of heart failure and complicating atrial fibrillation (AF) may dominate the clinical picture and mask the more classic endocrine manifestations of the disease. Impaired cardiopulmonary function and exercise capacity, significantly more marked in older patients, is observed in hyperthyroidism. Thyrotoxicosis can aggravate pre-existing heart disease and can also lead to AF, congestive heart failure, or worsening of angina pectoris. Regarding the high incidence of AF in older patients with hyperthyroidism, it is also important to detect subclinical hyperthyroidism in older patients with AF, thus warranting the measurement of the serum thyrotropin (TSH) concentration for early recognition and treatment. Most cardiac abnormalities return to normal once a euthyroid state has been achieved, although AF may persist in a minority. Optimal treatment requires rapid and definitive antithyroid therapy. Furthermore, anticoagulation is recommended for thyrotoxic patients with AF older than 50 years, those who have histories of previous emboli, hypertension, or with echocardiographic evidence of left atrial enlargement and/or myxomatous valves.

Aged↗
PubMed1998

Somatostatin receptor scintigraphy in thyroid eye disease.

Orbital lymphocytic infiltration in thyroid eye disease (TED), as well as identification of somatostatin (SMS) receptors on activated lymphocytes, has provided a rationale for receptor imaging with the radiolabeled SMS analog Pentetreotide. In 80 patients with TED, single-photon emission computed tomography (SPECT) images of the orbit were performed 4 and 24 hours after injection of Pentetreotide. Semiquantitative evaluation was performed using the SPECT slices with irregular regions of interests placed over the orbits and both hemispheres. In contrast to controls (median 5 counts per voxel per millibecquerel (cts/vox/MBq) injected activity), TED patients showed threefold increased orbital accumulation of Pentetreotide (15 cts/vox/MBq, p = 0.003). When considering patients with active TED only, even higher uptake was registered (23 cts/vox/MBq, p = 0.0006 vs. controls, sensitivity for active TED 61/68, 90%; specificity 12/12, 100%). In 40 patients with active TED, the radionuclide accumulation decreased sharply after completion of immunosuppressive therapy. A high pretreatment Pentetreotide orbit-to-brain ratio correlated with a response to therapy (positive and negative predictive values 28/32, 88%, and 8/8, 100%, respectively). In conclusion, SMS receptor scintigraphy may be regarded as a semiobjective tool in the evaluation of TED, both at initial stages as well as during treatment.

Adult↗
PubMed1998

Ineffective cardiorespiratory function in hyperthyroidism.

Dyspnea on exertion is a common complaint in hyperthyroidism, and this thyroid dysfunction has been implicated as a primary cause of impaired effort tolerance. Using spirometry and spiroergometry, 42 patients with untreated hyperthyroidism were examined, and the condition was controlled 7 days later under propranolol monotherapy, as well as after 6 months in euthyroidism. While hyperthyroid, reduced forced vital capacity and tidal volume at the anaerobic threshold (AT) were observed in comparison to euthyroidism. Decreased oxygen (O2) pulse at AT (7 +/- 0.4 vs. 9.1 +/- 0.4 mL/beat, P = 0.0012) and at maximal exercise was noted in hyperthyroidism and was enhanced under propranolol (8.9 +/- 0.4 mL/beat, P = 0.0001). During exercise, the increment of minute ventilation (16.1 +/- 0.7 vs. 20.2 +/- 1.0 L/min, P = 0.0015), O2 uptake (9 +/- 0.5 vs. 11.4 +/- 0.5 mL/min/kg, P = 0.0022), O2 pulse (4.0 +/- 0.3 vs. 5.6 +/- 0.3 mL/beat, P = 0.0001), and heart rate (53 +/- 2 vs. 65 +/- 3 beat/min, P = 0.0004) was markedly lower in hyper- vs. euthyroidism. Work rate at AT and at maximum was reduced in hyper- vs. euthyroidism (107.4 +/- 3 vs. 141.1 +/- 4 watt, P = 0.0001). Negative correlations between free T3 and O2 pulse at AT (r = -0.59, P = 0.0005), delta O2 uptake (r = -0.54, P = 0.0007), delta minute ventilation (r = -0.48, P = 0.0007), and maximal work rate (r = -0.62, P = 0.0001) were noted. In hyperthyroidism, analysis of respiratory gas exchange showed low efficiency of cardiopulmonary function, respiratory muscle weakness, and impaired exercise capacity, which were reversible in euthyroidism.

Adult↗
PubMed1998

Iodide induces thyroid autoimmunity in patients with endemic goitre: a randomised, double-blind, placebo-controlled trial.

OBJECTIVE: Iodine is essential for normal thyroid function and the majority of individuals tolerate a wide range of dietary levels. However, a subset of individuals, on exposure to iodine, develop thyroid dysfunction. In this double-blind trial, we evaluated the efficacy and tolerability of low-dose iodine compared with those of levo-thyroxine (T4) in patients with endemic goitre. METHODS: Sixty-two patients were assigned randomly to groups to receive iodine (0.5 mg/day) or T4 (0.125 mg/day) for 6 months. Subsequently, both groups were subject to placebo for another 6 months. Thyroid sonography, determination of thyroid-related hormones and antibodies, and urinary excretion of iodine were carried out at baseline and at 1, 6 and 12 months. RESULTS: At 6 months, markedly increased urinary values of iodine were found in patients receiving iodine (36 microg/24 h at baseline, 415 microg/24 h at 6 months) compared with those receiving T4 (47 microg/ 24 h at baseline, 165 microg/24 h at 6 months; P < 0.0001 compared with iodine group). T4 administration engendered a greater (P < 0.01) decrease in thyroid volume (from 32 ml to 17 ml, P < 0.0001) than did intake of iodine (3 3 ml to 21 ml. P < 0.005). High microsomal and thyroglobulin autoantibody titres were present in six of 31 patients (19%) receiving iodine, and iodine-induced hypo- and hyperthyroidism developed in four and two of them, respectively. Fine-needle biopsy revealed marked lymphocyte infiltration in all six. After withdrawal of iodine thyroid dysfunction remitted spontaneously and antibody titres and lymphocyte infiltration decreased markedly. Follow-up of these six patients for an additional 3 years showed normalisation of antibody titres in four of them. CONCLUSION: Although nearly comparable results were obtained with both treatment regimens regarding thyroid size, partly reversible iodine-induced thyroid dysfunction and autoimmunity were observed among patients with endemic goitre.

Adult↗
PubMed1996

Orbital tissue-derived T lymphocytes from patients with Graves' ophthalmopathy recognize autologous orbital antigens.

Lymphocytic and other mononuclear cell infiltration of the retro-bulbar space is observed in Graves' ophthalmopathy (GO). We investigated the antigenic character of orbital adipose/connective tissue and muscle from 21 euthyroid patients with severe GO after orbital surgery. Orbital tissue proteins were separated and recovered in soluble form by means of an electroelution technique. Twenty-two protein fractions, identified according to their molecular mass ranges, were used as antigens for orbital tissue-derived and peripheral blood T lymphocytes. Seventeen T cell lines from 6 patients were established from in vivo activated orbital T cells using interleukin-2 and anti-CD3 antibodies. T cell proliferation was measured as [3H] thymidine uptake. When screened for their reactivity to autologous adipose/connective tissue proteins, all T cell lines responded significantly to protein fractions 6-10 kDa [stimulation index (SI) = 32.9 +/- 9.8 (mean +/- SE)] and 19-26 kDa (17 +/- 5), but not to tuberculin, which was used as a control. Phenotypic analysis analysis of 10 orbital T cell lines indicated that 6 lines consisted predominantly of CD4+ cells. Incubation of a representative T cell line with allogeneic orbital protein fraction induced a very low response to protein fraction 19-26 kDa, but not to other fractions. Thyroid protein fraction 6-10 kDa also induced the proliferation of orbital T cell lines. Incubation of peripheral blood mononuclear cells with autologous orbital protein fractions gave similar results; positive responses to 6-10 and 19-26 kDa fractions were observed with orbital tissue from 12 of 14 patients (mean SI = 22 +/- 5.9 and 6.3 +/- 1.7, respectively), and positive responses were observed with orbital tissue from 3 of 4 patients to eye muscle fractions 6-10 and 19-26 kDa (13.8 +/- 6.9 and 6 +/- 2, respectively). When proteins from cultured orbital fibroblasts were used as antigens, autologous peripheral blood mononuclear cells from the 7 of the 9 patients tested responded to these 2 fractions (15.2 +/- 6.9 and 6.8 +/- 2.4, respectively), whereas a response to cultured orbital myoblasts was observed with the 19-26 kDa fraction only (SI = 8). Positive responses to abdominal adipose or muscle proteins, as controls, were not found. The demonstration of sensitized, orbital tissue-specific, T lymphocytes in the peripheral blood and orbit from patients with GO provides evidence for a role of cellular immunity in the pathogenesis of this eye disorder.

Adult↗