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G Kahaly

Publications and source records attributed to G Kahaly.

At least 19 recordsLinked to original sources

Radionuclide-labeled somatostatin analogues for diagnostic and therapeutic purposes in nonmedullary thyroid cancer.

Despite the fact that several recent studies report an expression of somatostatin receptors in nonmedullary thyroid cancer (non-MTC), there is still no consensus concerning the diagnostic and therapeutic usefulness of radionuclide-labeled somatostatin analogues in non-MTC. We present the results of 50 scintigraphic studies with (111)In-Pentetreotide ((111)In-P) in 48 patients with metastasizing non-MTC (n = 9 papillary, n = 9 follicular, n = 29 Hurthle cell, n = 1 insular carcinoma). The findings were compared with histology and with other imaging modalities. (111)In-P provided unequivocally positive results in 37 of 50 (74%) of the patients (27% in the 11 patients with current thyroglobulin levels <10 ng/mL and 85% in the patients with thyroglobulin >10 ng/mL). Histopathology demonstrated that maximal uptake was observed in Hurthle cell carcinoma (95% positive examinations if thyroglobulin exceeds 10 ng/mL). We also describe for the first time dosimetric and clinical data from the courses of 90Y-DOTATOC therapy in three patients with progressive, somatostatin-receptor-positive non-MTC (up to 9.3 GBq per 4 cycles). Tumor progression could not be stopped in any of the patients treated with 90Y-DOTATOC. We conclude that (111)In-P is a promising tool for whole-body diagnosis in nonradioiodine-accumulating non-MTC, especially in Hürthle cell cancer, and if 2-[18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) is not available. Although the number of patients treated with 90Y-DOTATOC is still limited, our applied treatment protocol appears to be ineffective in metastasizing non-MTC.

Adult↗

[Polyglandular autoimmune syndrome type II: epidemiology and forms of manifestation].

BACKGROUND AND OBJECTIVE: Polyglandular autoimmune syndrome (PAS), is characterized by the coexistence of several autoimmune diseases, affecting predominantly the endocrine glands. The juvenile form (PAS type I) is distinguished from the adult type II in which autoimmune thyroiditis, adrenal cortical insufficiency and diabetes mellitus type I predominate. The connections between epidemiological, clinical and immunological aspects were analysed and described in this study of patients with PAS type II. PATIENTS AND METHODS: Among a total patient population of over 15,000 seen in our endocrinological university policlinic from 1992 through 1996, the clinical data of all 151 patients with PAS type II were analysed retrospectively. RESULTS: Of the 151 patients with PAS 37 were male (aged 16-74 years, median 42 years) and 114 female (aged 16-84 years; median 46 years), a prevalence of 1:100, 92 patients (61%) had diabetes mellitus type I (78% males, 55% females; p = 0.013), 50 (33%) had hyperthyroidism (32% and 33%; difference not significant), 49 had Hashimoto's thyroiditis (14% and 39%; p = 0.005) and 28 (18.5% had Addison's disease (14% males, 20% females; n.s.). Vitiligo was less common, occurring in 30 (20%), alopecia in 9 (6%), pernicious anaemia in 5 (5%) and hypogonadism in 8 (5%). The most common combination was diabetes type I with thyroiditis (33%), the time between manifestations of each disease being highly variable, diabetes was the first manifestation in half the cases. Partial cell antibodies were present in 62 patients (54%), and 52% had positive thyroid-associated antibodies without manifest signs of thyroid disease. CONCLUSION: PAS occurs relatively often among patients of an endocrinological centre, with a 3:1 female to male ratio. Because there is usually a long interval between the onset of the various endocrine diseases, regular monitoring of patients with an endocrine autoimmune disease is indicated, specific tests to be performed if additional immune diseases are suspected.

Addison Disease↗

[Cardiopulmonary parameters in hyperthyroidism].

BACKGROUND: Hyperthyroid patients often suffer from impaired exercise capacity with dyspnoea. Two well established, non-invasive methods were used to evaluate the influence of hyperthyroidism on cardiopulmonary function. PATIENTS AND METHODS: In 42 patients with hyperthyroidism we performed spirometry and cardiopulmonary exercise testing before and after 7 days of propranolol therapy as well as in euthyroidism. RESULTS: In hyperthyroidism reduced vital capacity and 1-second capacity were observed (95.5 +/- 2.4% vs 102.6 +/- 1.5%; p = 0.0087; 89.4 +/- 2.3% vs 95.2 +/- 2.2%; p = 0.0179). No changes showed during beta-blockade. At the anaerobic threshold reduced tidal volume and enhanced respiratory frequency were noted (1119.8 +/- 48.9 ml vs 1289.3 +/- 62.7 ml; p = 0.0227; 28.3 +/- 0.8 vs 25.4 +/- 0.9; p = 0.0012). A significant tachycardia could be shown. Impaired response to exercise in pulse and respiratory frequency were observed. Work at the anaerobic threshold was impaired in hyperthyroidism (70 +/- 5 watts vs 86.9 +/- 5.7 watts; p = 0.016) and did not change during propranolol therapy. Oxygen pulse at the anaeorbic threshold was reduced in hyperthyroidism (7.7 +/- 0.4 ml O2/beat vs 9.1 +/- 0.4 ml O2/beat; p = 0.0012) and increased with propranolol (8.9 +/- 0.4 ml O2/beat; p = 0.0001). CONCLUSION: In hyperthyroidism significant changes in cardiopulmonary function were noted at rest and exercise. High resting function and impaired response to exercise suggest a cardiopulmonary work with low efficiency. Propranolol leads to economization and lowers patients complaints.

Adrenergic beta-Antagonists↗

[Somatostatin receptor status in non-medullary thyroid carcinoma].

AIM: Recent in-vitro and in-vivo studies demonstrated a somatostatin receptor expression in some non-medullary thyroid carcinomas. In this study we investigated the somatostatin receptor status for this particular tumor entity in a larger patient group. SUBJECT AND METHODS: We compared 131-iodine with 111-In-pentetreotide scans in 24 patients with metastasizing, non-medullary thyroid cancer. The findings were correlated with other imaging modalities. Additionally, we performed receptor autoradiography in one patient, octreotide therapy in another patient and administration of 90-Y- and 111-In-DOTATOC in 2 consecutive patients. RESULTS: In the 15 patients with papillary or follicular carcinoma, 111-In-pentetreotide was inferior to 131-I in 8/15, equal in 1/15, and superior in 6/15 patients. In 8/9 of the patients with Hürthle cell carcinoma, metastases showed a 111-In-pentetreotide accumulation of various intensity, while 131-iodine scans were negative except for one patient. 111-In-pentetreotide was equal or superior compared to 201-Tl or 99m-Tc-sestamibi, but for the most part inferior in comparison with 18-F-FDG-PET. The findings of 111-In-pentetreotide scintigraphy correlated well with the receptor autoradiography and the accumulation of DOTATOC, but not with the therapeutic effect of "cold" octreotide on the thyroid cancer metastases. CONCLUSIONS: Several metastases of papillary and follicular carcinoma, and the majority of Hürthle cell cancer metastases can express somatostatin receptors. 111-In-pentetreotide scintigraphy is a promising tool for localization of metastases especially in Hürthle cell cancer or if PET is not available, and may be useful for selection of possible candidates, if therapeutic effective beta-emitting somatostatin analogues will be available for routine application.

Adenocarcinoma, Follicular↗

[Bioequivalence of a combination of levothyroxine and iodine in comparison with levothyroxine only. A controlled double-blind study of bioavailability].

BACKGROUND: Iodine deficiency is the main cause of endemic goitre. Iodine supplementation and decrease of pituitary TSH are the therapeutical aims. In this study, bioavailability of levothyroxine combined with iodide and the same dose of levothyroxine alone were compared. PATIENTS AND METHODS: Fourty-eight subjects aged 18 to 40 years were randomly assigned for 6 days either 150 micrograms levothyroxine and 150 micrograms iodide (group A, n = 25) or 150 micrograms levothyroxine (group B, n = 23). Baseline TSH and thyroid hormones were measured 2 days before starting therapy as well as daily till day 6. TRH-test (delta TSH) and thyroid sonography were performed at day -2 and 6. RESULTS: During therapy baseline TSH decreased markedly from 1.26 to 0.35 mU/ml (median) in group A and from 1.37 to 0.39 to 0.39 mU/ml in group B (both p < 0.001), as well as delta TSH (A from 5.66 to 2.61 mU/ml; B from 6.3 to 2.95 mU/ml; p < 0.001). Difference of delta TSH (day -2 versus day 6) was negatively correlated to body surface (r = -0.307; p < 0.05). TT4 levels increased in both groups (A from 7.1 to 9.1 microU/dl; B from 7.2 to 9.4 microU/dl; p < 0.005). No significant differences were noted between both groups for thyroid-related parameters. In both groups, confidence intervals for baseline TSH and TT4 were in the expected range. CONCLUSION: In this study, similar bioavailability and bioequivalence for levothyroxine and the combination of levothyroxine with iodide were demonstrated.

Adolescent↗

[Endocrine orbitopathy 1998].

BACKGROUND: Ophthalmopathy is the most common extrathyroidal manifestation of Graves' disease, also called thyroid-associated ophthalmopathy. CLINICS: This autoimmune disorder is characterized by a lymphocyte infiltration of the retrobulbar space. Activated T cells react with the target organ and secrete cytokines, leading to accumulation of glycosaminoglycans, interstitial edema of the peri- and retrobulbar tissue and enlargement of the extraocular muscles. During the inflammatory stage, the increased orbital pressure results in the clinical manifestation of the eye disease. DIAGNOSIS AND TREATMENT: Thus, therapeutic immunosuppression is often used initially, and by suppressing inflammatory changes, it can result in subjective and objective improvement of the thyroid eye disease. In recent years, new pathogenetic aspects and clinical randomized trials led to modified therapy concepts. CONCLUSION: Interdisciplinary management is recommended for rapid diagnosis and effective therapy of patients with thyroid-associated ophthalmopathy.

Cytokines↗

[Individually dosed levothyroxine with 150 micrograms iodide versus 100 micrograms levothyroxine combined with 100 micrograms iodide. A randomized double-blind trial].

BASIC PROBLEM AND OBJECTIVE: Intrathyroid deficiency and the influence of thyroid stimulating hormone (TSH) are the main pathogenetic factors in the development of endemic euthyroid goitre. Goitre reduction is achieved with either administration of levothyroxine, which diminishes hypophyseal TSG production, or of iodide. Aim of this study was to compare the efficacy of treatment with a dose-fixed combination of levothyroxine plus iodide with that of an individualized dosage of levothyroxine plus iodide. PATIENTS AND METHODS: After randomization 49 patients with euthyroid goitre (24 women, 25 men, aged 20-43 years) were treated for 12 weeks in a double-blind trial. Patients in group A received levothyroxine in a weight-adapted dosage (75,100 or 150 micrograms) plus 150 micrograms iodide, while those in group B were given a fixed dosage of 100 micrograms levothyroxine plus 100 micrograms iodide. Basal TSH, thyroid hormones, iodide excretion, hyperthyroid score and sonographic volume of the thyroid were determined before treatment and after 12 weeks. RESULTS: Basal TSH levels were reduced in both groups (P < 0.0001), without significant difference between the two groups (median relative change: group A 78.1%, group B 52.8%). Thyroid volume was decreased independently of the form of treatment (P < 0.0001) (median relative reduction: group A 37.6%, group B 30.9%; difference not significant). Iodide excretion rose in both groups, without significant difference (group A 107%, group B 49%). There was hardly any change of the hyperthyroid score in both groups. There were no side effects. CONCLUSION: Both forms of medication were equally efficacious and well tolerated in the treatment of euthyroid goitre.

Adult↗

Analysis of orbital T cells in thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) has a major effect on the two compartments of the retro-orbital (RO) space, leading to enlargement of the extraocular muscles and other RO tissues. T lymphocyte infiltration of RO tissue is a characteristic feature of TAO and there is current interest in whether these T cells are specifically and selectively reactive to RO tissue itself. We recently established 18 T cell lines (TCL) from RO adipose/connective tissue of six patients with severe TAO by using IL-2, anti-CD3 antibodies and irradiated autologous peripheral blood mononuclear cells (PBMC) to maintain the growth of T cells reactive to autologous RO tissue protein fractions. Here we report on the phenotype characteristics and cytokine gene expression profiles of these orbital TCL and on their immunoreactivity to the organ-specific thyroid antigens thyrotropin receptor (TSH-R), thyroidal peroxidase (TPO) and thyroglobulin (TG). Flow cytometry revealed that 10 TCL were predominantly of CD4+ phenotype, three being mostly CD8+ and five neither CD4+ nor CD8+. Analysis with reverse transcriptase-polymerase chain reaction (RT-PCR) of cytokine gene expression revealed both Th1- and Th2-like products in all TCL: IL-2 product (in 17 TCL), interferon-gamma (IFN-gamma) (n = 10), tumour necrosis factor-beta (TNF-beta) (n = 15), IL-4 (n = 12), IL-5 (n = 17), IL-6 (n = 13), TNF-alpha (n = 12) and IL-10 (n = 4). Reactivity to thyroid antigens was observed only in two TCL, the other 16 being uniformly unreactive. Although 10 out of 18 RO tissue-reactive TCL were predominantly CD4+ there were no significant relationships between TCL phenotype, cytokine gene profile, magnitude of reactivity to RO tissue protein or the (rare) occurrence of thyroid reactivity. The findings of both Th1- and Th2-like cytokine gene expression in all RO tissue-reactive TCL support the concept that TAO is a tissue-specific autoimmune disease, distinct immunologically from the thyroid, and involving both T cell and B cell autoimmune mechanisms in disease pathogenesis.

Adult↗

Is there a methimazole dose effect on remission rate in Graves' disease? Results from a long-term prospective study. The European Multicentre Trial Group of the Treatment of Hyperthyroidism with Antithyroid Drugs.

OBJECTIVE: The optimal antithyroid drug regimen for Graves' disease remains a matter of controversy. The European Multicentre Trial Group has investigated the effects of methimazole drug dose on the long-term outcome of Graves' disease. DESIGN: Extended follow-up of patients from a prospective multicentre trial, designed to study methimazole dose effects on the outcome of Graves' disease. We have reported previously that the relapse rates did not differ after a medication-free observation period of 12 months; the relapse rates were 37% and 38%, respectively. In this paper, we describe the outcome in these patients after a mean observation period of 4.3 +/- 1.3 years and have looked for potential predictors of this outcome. PATIENTS: Three hundred and thirteen patients with Graves' disease were randomized to treatment with a constant dose of 10 or 40 mg of methimazole for 1 year, with levothyroxine supplementation as required. MEASUREMENTS: At the time of inclusion into the trial: thyroid size, T4, T3, TSH-binding inhibiting immunoglobulins, urinary iodide excretion, thyroid uptake, Crook's therapeutic index of hyperthyroidism (a measure of clinical disease severity). At the time of follow-up examination: TSH, T4, T3, thyroid size, thyroid ultrasound, THS-binding inhibiting immunoglobulins. RESULTS: The overall relapse rate was 58%. There was no difference in relapse rates between patients treated with either 10 or 40 mg of methimazole (58.3 vs. 57.8%). Five patients had become spontaneously hypothyroid, without obvious relationship to antithyroid drug dose. Patients who relapsed and patients who remained in remission did not differ with respect to: age, goitre size, ophthalmopathy, median iodine excretion, serum T4 or serum T3, Crook's therapeutic index and thyroid uptake at the time of study entry. Thus, none of these variables was potentially suitable for predicting outcome. This finding was confirmed by Cox's proportional hazard regression. Thyroid volume, measured by ultrasound, did not differ between patients in remission and patients with relapse. There was no difference in the course of endocrine eye signs, in the requirement for steroid and radiotherapy for eye signs, or in thyroid echostructure between patients in the 10 and in the 40 mg group, nor was serum TSH different in patients who had remained in remission (0.8 +/- 0.6 mU/l in the 10 mg group, 1.0 +/- 0.8 mU/l in the 40 mg group). CONCLUSIONS: The dose of methimazole in Graves' disease therapy can safely be kept to the minimal required dose. This will provide the same chance of remission as higher doses, and provide the best balance of risk and benefit.

Adult↗

Glycosaminoglycans in thyroid eye disease.

Orbital accumulation of hydrophilic, interstitial glycosaminoglycans (GAG) and subsequent expansion of retrobulbar tissue lead to the clinical manifestation of exophthalmos in patients with thyroid eye disease (TED). In order to analyze whether the alteration of distribution pattern and biochemical composition of GAG and proteoglycans play a role in the development of the disease, a highly specific high-pressure liquid chromatography (HPLC) method was developed. The concentration of total GAG, chondroitin sulfate A (CA), dermatan sulfate (DS), and hyaluronic acid (HA) was determined in patients and controls, revealing marked differences in urinary concentration of total GAG and HA, as well as an elevation of CA in patients versus controls. Method sensitivity was 0.86 for patients with active disease, and 0.87 for patients with untreated ophthalmopathy, whereas specificity was 1.0 for patients with inactive disease. Patients with increased GAG concentration responded well to steroids and/or orbital irradiation. Furthermore, distribution pattern of orbital extracellular matrix GAG exhibited a significant increase in the tissue fractions of CA and HA in patients with TED in comparison to controls. In conclusion, GAG polysaccharides not only play a major role in the pathogenesis of TED but have been successfully introduced as an activity marker of the disease.

Chondroitin Sulfates↗

Indium-111-pentetreotide in Graves' disease.

UNLABELLED: Thyroidal and orbital lymphocytic infiltration in Graves' disease, as well as identification of somatostatin receptors on lymphocytes, has provided a rationale for receptor imaging with the radiolabeled somatostatin analog pentetreotide. Recently, we demonstrated that in contrast to controls, Graves' patients showed markedly increased orbital accumulation of pentetreotide. Longitudinal and follow-up data are presented here. METHODS: In 20 (16 hyperthyroid) Graves' patients with active eye disease, planar (thyroid) and SPECT (orbit) images were performed 4 and 24 hr after injection of 111In-pentetreotide (222 MBq) before and 3 mo after starting antithyroid and combined steroid and orbital radiotherapy. RESULTS: Thyroidal uptake decreased during methimazole treatment (4 hr postinjection, median: hyperthyroid 989 counts/pixel/MBq injected activity, euthyroid 253 counts, p = 0.001; 24 hr, 437 versus 95 counts/pixel/MBq, p = 0.005). Fourteen patients (70%) responded to steroid and radiotherapy. The pentetreotide orbit-to-brain ratio decreased markedly after completion of therapy (4 hr: 25 before versus 6.2 after therapy, p = 0.0003; 24 hr: 9.6 versus 2.7, p = 0.003). A high pretreatment ratio correlated with a response to therapy (p = 0.001: in 14 of 16 patients with a ratio > 10, 4 hr postinjection, ophthalmopathy improved; positive predictive value: 90%; median activity score before 6 versus 2 after therapy, p = 0.0001) in contrast to none of the four cases with a ratio less than 10 (score 5 versus 4, p = 0.08). CONCLUSION: Pentetreotide scans may be regarded as a semiobjective tool in the evaluation of Graves' disease, both at initial stages as well as during treatment.

Anti-Inflammatory Agents↗

[Combination therapy of endemic goiter with two different thyroxine/iodine combinations].

AIM: Of this study was to investigate the extent of thyrotropin (TSH) suppression and volume reduction in combination therapy of endemic goitre. We compared an individually adapted dose of thyroxine with a fixed dose. METHODS: 105 patients of a multicenter study (randomised, single blinded, controlled) received daily a weight-adjusted LT4-dose in combination with 150 micrograms iodide (group A) or a fixed combination of 100 micrograms LT4 plus 100 micrograms iodide (group B), respectively. At the beginning and after 12 weeks TSH-levels and goitre volume were examined. RESULTS: Although the amount of thyrotropin suppression showed no differences in both groups, there were more patients in the weight-adjusted treatment group with completely suppressed thyrotropin serum concentrations (p < 0.05). Both groups showed a reduction of goitre volume of 24% CONCLUSION: A weight-adjusted LT4-dose of 1.4 micrograms/kg body weight often leads to subclinical hyperthyroidism. To obtain low TSH-levels without complete suppression LT4-doses of 1.0 microgram/kg body weight plus 150 micrograms iodide are probably sufficient.

Adolescent↗

HPLC glycosaminoglycan analysis in patients with Graves' disease.

1. Orbital accumulation of hydrophilic, interstitial glycosaminoglycans (GAGs) and subsequent expansion of retrobulbar tissue lead to the clinical manifestation of exophthalmos in patients with Graves' eye disease. 2. A highly specific method to determine the concentration and biochemical composition of different GAGs was developed in order to obtain a sensitive test system for the activity of the disease. By means of this method, GAG excretion in 24 h urine collections of 56 patients and 21 controls was analysed by precipitation with cetylpyridinium chloride and potassium acetate in ethanol, followed by sequential enzymic hydrolysis with chondroitin AC lyase, chondroitin ABC lyase and hyaluronate lyase, with HPLC analysis of the resulting alpha, beta-unsaturated disaccharides by anion-exchange chromatography. 3. Concentrations of GAG, chondroitin sulphate A (CA), dermatan sulphate (DS) and hyaluronic acid (HA) were determined in patients and controls, with high recovery rates [72.2 +/- 5.3%, mean +/- SEM; detection limit, 4.2 micrograms/l (0.01 mumol/l)], revealing marked differences in urinary concentrations of total GAG and HA, as well as an elevation of CA in patients compared with controls. 4. Method sensitivity was 0.86 for patients with active Graves' eye disease, and 0.87 for patients with untreated ophthalmopathy, whereas specificity was 1.0 for patients with inactive disease. Patients with increased GAG concentration responded well to steroids and/or orbital irradiation (before therapy: GAG, 111.49 +/- 40.32; CA, 59.58 +/- 21.34; DS, 25.05 +/- 8.12; HA, 26.88 +/- 11.63 mg/24 h; during therapy: GAG, 54.22 +/- 10.94; CA, 20.52 +/- 4.58; DS, 17.65 +/- 3.46; HA, 16.05 +/- 3.69 mg/24 h), whereas GAG excretion increased markedly 2-3 months after stopping prednisone therapy in patients with still active eye disease (GAG, 109.9 +/- 10.51; CA, 63.8 +/- 7.34; DS, 24.1 +/- 5.07; HA, 22.0 +/- 6.28 mg/24 h). 5. This sensitive method determines the nature of renally excreted GAGs, reflecting the aberrant synthesis pattern of fibroblasts in patients with Graves' disease.

Acute Disease↗

Diabetic microangiopathy and urinary glycosaminoglycans.

Alterations in the metabolism of glycosaminoglycans (GAG) may play a role in the pathogenesis of diabetic-associated microangiopathy. Consequently, the relationship between diabetic nephropathy and retinopathy and urinary GAG distribution was assessed in 96 IDDM patients in comparison to 103 healthy controls. GAG concentration in 24h urine samples was determined by precipitation with cetylpyridinium chloride and potassium acetate in ethanol followed by a colorimetric test with carbazole. A marked difference (P = 0.0008) in urinary GAG excretion between patients (24.3 +/- 1.5 mg/24 h, mean +/- SEM) and controls (16.2 +/- 0.75 mg/24 h) could be detected. In patients with IDDM of longer duration, GAG excretion was increased (< or = 10 yr: 20.8 +/- 2.1 vs > 10 yr: 27.4 +/- 2.1 mg/24 h; P = 0.03). Furthermore, IDDM patients with class 4 nephropathy and retinopathy exhibited a markedly higher GAG excretion compared to those without nephropathy (33.1 +/- 3.0 vs 22.6 +/- 1.7 mg/24 h, P = 0.005) or retinopathy (29.7 +/- 2.8 vs 21.2 +/- 1.7 mg/24 h, P = 0.009). An increased urinary GAG concentration was detected in IDDM patients with albuminuria (> 300 mg/24 h: 29.9 +/- 3.3 vs < 30 mg/24 h: 23.0 +/- 1.7 mg/24 h; P = 0.048), proteinuria (> 0.5 g/24 h: 30.3 +/- 3.7 vs < 0.05 g/24 h: 22.7 +/- 1.6 mg/24 h) and in patients with augmented serum creatinine in comparison to those with normal values (> 0.12 mg/L: 34.9 +/- 2.3 vs < 0.12 mg/L: 22.4 +/- 1.6 mg/24 h; P = 0.01). The results demonstrate a close relationship renal GAG excretion and the presence of microangiopathy in IDDM patients.

Adolescent↗

Randomized, double blind, placebo-controlled trial of low dose iodide in endemic goiter.

Iodine (I) is essential for normal thyroid function, and the majority of subjects tolerate a wide range of dietary levels. However, a subset of individuals upon exposure to normal or elevated levels of I develop thyroid dysfunction and autoimmunity. In this double blind trial, we evaluated efficacy and tolerability of low dose I in adults with euthyroid, diffuse, endemic goiter. Sixty-two subjects were randomly assigned I (0.2 mg/day) or placebo for 12 months. After termination of therapy, both groups were followed for a further 6 months. Thyroid sonography and determinations of thyroid-related hormones, urinary I excretion per 24 h, and thyroid antibodies were carried out at baseline and at 3, 6, 9, 12, 15, and 18 months. Markedly elevated urinary I values were found during therapy in subjects receiving I (32 at baseline vs. 213 micrograms/24 h at 12 months; P = 0.0001) compared to placebo (34 and 33 micrograms/24 h, respectively; P < 0.0001 vs. I). I substantially reduced thyroid volume (29 vs. 18 mL at 12 months; -38%; P = 0.0001), and at 18 months, the therapeutic effect was sustained. In the placebo group, no significant changes were observed. High microsomal and thyroglobulin autoantibody titers were present in 3 of 31 (9.7%) subjects receiving I, and I-induced hypo- and hyperthyroidism developed in 2 and 1, respectively. Fine needle biopsy revealed marked lymphocytic infiltration in all 3 cases. After withdrawal of I, thyroid dysfunctions spontaneously remitted, and antibody titers as well as lymphocytic infiltration decreased markedly. Follow-up of these 3 subjects for an additional 2 yr showed normalization of antibody titers in 2. Thus, among subjects with endemic goiter, low dose I successfully normalized thyroid volume and body I supplementation; nevertheless, reversible I-induced thyroid dysfunctions and autoimmunity were observed in nearly 10% of the subjects.

Adult↗

[Premedication in pheochromocytoma].

Pheochromocytomas are active, catecholamine-producing tumours derived from chromaffine tissue, causing arterial hypertension. The therapeutical aim is the surgical removal of the tumour. Blockade of the alpha-adrenergic receptors during the preoperative phase is necessary to prevent cardiovascular complications. Phenoxybenzamine is the commonly used alpha-adrenergic blocking agent. Therapy begins with low doses and is increased stepwise up to 250 mg daily. The optimal duration of preoperative therapy is 10 to 14 days. Efficiency of therapy should be judged by reduction of symptoms, a stabilisation of arterial blood pressure, and the presence of light orthostatic hypotension. Swelling of nasal mucosa indicates a successful blockade of the alpha-adrenergic receptors. Persistent tachyarrhythmia is an indication to apply beta-adrenal receptor blockers, but only after alpha-blockade. Reexpansion of blood volume has to be adjusted according to hemodynamic monitoring data. With an adequate preoperative management, mortality of patients with pheochromocytomas has been reduced to less than 1 percent. Postoperatively, most patients become normotensive and other symptoms of excessive catecholamine-production disappear. In cases of long persisting and fixed hypertension paroxysmal crises of high blood pressure can be avoided.

Adrenal Gland Neoplasms↗

Randomized trial of intravenous immunoglobulins versus prednisolone in Graves' ophthalmopathy.

Glucocorticoids are usually given for management of Graves' ophthalmopathy (GO), but they may cause side effects. By comparison, intravenous administration of immunoglobulins resulted in clinical improvement and decreased antibody titres in a large number of autoimmune diseases. Therefore, a randomized trial was done, in which 19 patients with active GO were treated with a 20-week course of oral prednisolone (P, starting dose 100 mg/day), and 21 received 1 g immunoglobulin/kg body weight for 2 consecutive days every 3 weeks. The immunoglobulin course was repeated six times. Before and at the end (20 weeks) of immunomodulating therapy, ophthalmological investigation and quantitative magnetic resonance (MR) imaging were performed. A successful outcome was observed in 12 (63%) P- and in 13 (62%) immunoglobulin-treated patients. Overall, there were no marked differences in degree of improvement between the two groups. Responders to treatment in both groups showed improvements in proptosis (median from 24.5 to 21.5 mm; P < 0.005), visual acuity (from 0.6 to 0.85; P < 0.001), intraocular pressure (from 25 to 20 mmHg; P < 0.0001), lid aperture (from 14 to 12 mm: P < 0.01) and a decrease in eye muscle area (inferior, from 44 to 33 mm2; medial, from 43 to 34 mm2; both P < 0.0005). Among the immunoglobulin-treated patients, there was a marked decrease of thyroid antibody titres. Side effects were more frequent and severe during P than during immunoglobulin therapy. Thus, with respect to the above mentioned objective parameters, P and immunoglobulin appeared to be equally effective in treatment of active GO.

Administration, Oral↗