Preventive iodine administration and iodine excretion in the Vienna area and in the forest quarter

In order to reduce the still substantial iodine deficiency in the Austrian population, compulsory iodisation of salt was increased in 1990 from 10 mg potassium iodide/kg salt to 20 mg potassium iodide/kg. In this investigation we evaluated the adequacy of iodine supply in Vienna and the Waldviertel, a rural region northwest of Vienna. Daily iodine excretion (which reflects daily iodine intake) was investigated in 92 persons from the Waldviertel (all without thyroid gland pathology) and 110 persons from Vienna (54 with unremarkable thyroid glands, 56 with endemic goiter). Daily iodine excretion was higher in persons from the Waldviertel (161 +/- 90.7 micrograms/24 h, p < 0.05) than in those from Vienna (with healthy thyroid glands 126.4 +/- 42.9 micrograms/24 h and with goiter 117.2 +/- 60.5 micrograms/24 h, resp.). In both populations iodine supply as defined by the WHO (excretion of > 150 ug iodine/day) was inadequate. The recommended level was not achieved in 50% of the persons from the Waldviertel region and in 75% of persons from Vienna (healthy thyroid glands 76%, goiter: 75%). Iodine deficiency (intake < 100 micrograms/24 h) was present in 42% persons from the Waldviertel and in 31% and 24% persons, respectively, from Vienna with unremarkable thyroid glands and goiter. We conclude that although the iodine content of salt was increased, an iodine deficiency was present in a considerable portion of the population of an industrialized country (approximately 40% of persons from a rural region and 30% from the city of Vienna).     

Autoimmune hypothyroidism

Most of the acquired hypothyroidisms are related to chronic lymphocytic thyroiditis which reduce the functional thyroid parenchyma, determine acquired organification disorders or rarely generation of blocking anti-TSH receptor antibodies. In subjects with genetic predisposition, autoimmunization against the thyroid involves recognition of thyroid antigens, cooperation between B and T lymphocytes and production of cytokines. Biologic markers of antithyroid autoimmune disorders are now widely available. Nevertheless therapeutic approach of autoimmune hypothyroidisms is still symptomatic: thyroid hormone is able to correct hypothyroidism, to reduce the volume of goiter if present and also to lower the biological evidence of thyroid autoimmunity.     

Antibodies against thyroid gland peroxidase and thyroglobulin in various thyroid diseases

Autoantibodies to thyroperoxidase (anti-TPOAb) and thyroglobulin (anti-TgAb) were measured in 564 patients with various thyroid disorders and in 59 healthy subjects using chemiluminometric immunoassay. The frequency of elevated titers was 8.6% in healthy subjects, 76.2% in patients with untreated hyperthyroidism and diffuse goiter, 80.7% in patients with relapse of hyperthyroidism. 83.4% of patient with hyperfunction changed spontaneously to hypothyroidism and 71.5% of patients with hypothyroidism and goiter had antibodies above the normal range. Unexpectedly low prevalence of autoantibodies were detected in patients with primary myxoedema without goiter (48.2%) and in patients with endocrine ophthalmopathy and euthyroidism (33.2%). In the subgroup of patients with hyperthyroidism under methimazole treatment we found an incidence of positivity of 56% and the mean of positive values was lower compared with the untreated ones. In 42.8% of patients with hyperthyroidism and diffuse goiter treated successfully by methimazole, surgery or radioiodine elevated concentrations of antibodies could be detected, however they were in remission for more than five years. 197 (82.4%) of the patients with positive antibody titers showed higher concentrations to peroxidase compared with thyroglobulin. 57.9% of serum samples positive for anti-TPOAb were negative for anti-TgAb, whereas 9.4% of samples positive for anti-TgAb were anti-TPOAb negative. The diagnosis of thyroid autoimmunity could generally be based on measurement of anti-TPOAb with additional measurement of anti-TgAb in special cases.     

Prevalence of goiter, iodine deficiency and iodine prophylaxis in Poland. The results of a nationwide study

A nation-wide epidemiological survey was conducted on a random sample of 19,300 schoolchildren, 0.5% of the 6-13-years-old child population. The study included data on body mass, height, thyroid size according to the ICCIDD/WHO classification, and information on iodized salt intake. Thyroid volume was measured with a portable USG also, and iodine concentrations in casual urine specimens were measured. In 80% of the children, urine iodine concentrations were below 100 mu/l; about 5% of the children had enlarged thyroid glands in class II or III of the ICCIDD/WHO classification, and hypothyroidism was not observed during examination. These findings mean that Poland is an area of mild or moderate endemic goiter. The highest prevalence of goiter as determined by USG was observed in the Sudeten, Carpathian, and northeastern parts of Poland. In these areas, 40-80% of the children had urine iodine concentrations within 0-50 micrograms/l; this region was classified as a moderate endemia area. The lowest prevalence was in the northwestern part of the country; 60-90% of the children had iodine concentrations above 50 micrograms/l, and 23-35% above 100 micrograms/l. This area was classified as a mild endemic goiter area. Comparison of the thyroid size measures yields a very low (20%) coefficient of accuracy for class Ia. This class seems of questionable value for an epidemiological survey. Multifactorial analysis of variance of iodine concentrations shows the effects of some main factors: geographical area, iodine prophylaxis and urban/rural residence. The questionnaire results indicate that only about 20% of the total population uses iodized salt. The effectiveness of prophylaxis was very low; increases in urine iodine concentrations and decreases of goiter prevalence in the children using iodized salt did not exceed 10%. This points to the need to increase the KJ dose in table salt and to develop a new model for distribution of iodized salt in Poland.     

Kashin-Beck osteoarthropathy in rural Tibet in relation to selenium and iodine status

BACKGROUND AND METHODS: Kashin-Beck disease is a degenerative osteoarticular disorder that is endemic to certain areas of Tibet, where selenium deficiency is also endemic. Because selenium is involved in thyroid hormone metabolism, we studied the relation among the serum selenium concentration, thyroid function, and Kashin-Beck disease in 575 subjects 5 to 15 years of age in 12 villages around Lhasa, Tibet, including 1 control village in which no subject had Kashin-Beck disease. Clinical, radiologic, and biochemical data were collected. RESULTS: Among the 575 subjects, 280 (49 percent) had Kashin-Beck disease, 267 (46 percent) had goiter, and 7 (1 percent) had cretinism. Of the 557 subjects in whom urinary iodine was measured, 66 percent had a urinary iodine concentration of less than 2 microg per deciliter (157 nmol per liter; normal, 5 to 25 microg per deciliter [394 to 1968 nmol per liter]). The mean urinary iodine concentration was lower in subjects with Kashin-Beck disease than in control subjects (1.2 vs. 1.8 microg per deciliter [94 vs. 142 nmol per liter], P<0.001) and hypothyroidism was more frequent (23 percent vs. 4 percent, P=0.01). Severe selenium deficiency was documented in all villages; 38 percent of subjects had serum concentrations of less than 5 ng per milliliter (64 nmol per liter; normal, 60 to 105 ng per milliliter [762 to 1334 nmol per liter]). When age and sex were controlled for in a multivariate analysis, low urinary iodine, high serum thyrotropin, and low serum thyroxine-binding globulin values were associated with an increased risk of Kashin-Beck disease, but a low serum selenium concentration was not. CONCLUSIONS: In areas where severe selenium deficiency is endemic, iodine deficiency is a risk factor for Kashin-Beck disease.     

The instability of dietary iodine supply over time in an affluent society

In the Bernese region, where goiter was formerly endemic, alimentary salt has been supplemented by increasing amounts of potassium iodide (KI): 5, 10, 20 mg KI/kg in 1922, 1965 and 1980 respectively. Ioduria rose from < 30 micrograms I/g creatinine in 1920 to > 100 micrograms I/g creatinine in the 1980s. In 1992 ioduria was estimated in 55 healthy volunteers (group A and individual B) and 234 thyroid carcinoma patients after thyroidectomy: hypothyroid patients with (C) and without thyroid remnants (D) and euthyroid patients on T4 substitution (E). The arithmetic mean iodine excretion of the healthy volunteers in group A and individual B was found to be 87 +/- 40 micrograms I/g creatinine. This is insufficient according to the recommendations of the WHO. In all groups, the iodine excretion reached the recommended level only in some members: 24% (A, B), 19% (C), 38% (D) and 81% (E). It was thought in the 1980s that in a formerly iodine-deficient society, iodinated salt would continue to provide an adequate supply of iodine. However, iodine intake in this affluent society has proved to be unstable. This can be attributed to modifications of eating habits, which include a reduction of total salt consumption, combined with a growing consumption of manufactured food of cosmopolitan origin, prepared using salt containing little or no iodine.     

Incidence of thyroid autoantibodies in the endemic goiter

The aim of our study was to investigate the incidence of thyroid autoantibodies (TA) in the endemic region of the north-eastern Poland. The mean titres of ATMA and TGAb were measured in 1508 randomly chosen persons aged 3 to 68 yrs. ATMA or TGAb were positive in 17% of the population studied. Frequency and mean titres of TA were observed to increase with age. Autoantibodies were more frequently noted in persons with parenchymatous goiter. There was no correlation between the incidence of autoantibodies and goiter enlargement, however, the highest percentage of TGA was noted in people with large thyroid (III). TA were also found in 10% of the subjects without goitre. Our results do not confirm the hypothesis that thyroid autoantibodies play a key role in the pathogenesis of endemic goiter.     

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.     

Effect of long-term treatment with salmeterol on asthma control: a double blind, randomised crossover study

OBJECTIVES: To determine the effect of adding salmeterol 50 micrograms twice daily for six months to current treatment in subjects with asthma who control their inhaled corticosteroid dose according to a management plan. DESIGN: A double blind, randomised crossover study. SETTING: Nottingham. SUBJECTS: 101 subjects with mild or moderate asthma taking at least 200 micrograms twice daily of beclomethasone dipropionate or budesonide. INTERVENTIONS: Salmeterol 50 micrograms twice daily and placebo for six months each, with a one month washout. Subjects adjusted inhaled steroid dose according to guidelines. MAIN OUTCOME MEASURE: Reduction in inhaled steroid use, exacerbations of asthma, and use of oral steroids. RESULTS: Data were available for 87 subjects. When compared with placebo salmeterol treatment was associated with a 17% reduction in inhaled steroid use (95% confidence interval 12% to 22%) with no significant difference in the number of subjects who had an exacerbation (placebo 25%, salmeterol 16%) or use of oral steroids. For secondary end points salmeterol treatment was associated with higher morning and evening peak expiratory flow and forced expiratory volume in one second; a reduction in symptoms, bronchodilator use and airway responsiveness to methacholine; and no effect on serum potassium concentration, 24 hour heart rate, or the final forced expiratory volume in one second achieved during a salbutamol dose-response study. CONCLUSIONS: In subjects who adjusted their inhaled steroid treatment according to guidelines the addition of salmeterol 50 micrograms twice daily was associated with a reduction in inhaled steroid use and improved lung function and symptom control.     

Iodine induced thyroid disease

Although iodine prevents goiter, enlarged thyroid glands continue to be detected in subjects, especially children, in spite of adequate iodine ingestion. Iodine may cause goiter in susceptible individuals by inhibiting the organic binding of iodine as is seen in adult asthmatics, neonates born of iodine ingesting mothers and in subjects residing along the littoral of Japan. Myxedema, especially in treated Graves' disease and Hashimoto's disease, may also be precipitated by iodine. On the other hand, iodine given to euthyroid subjects in areas of endemic goiter and to subjects with nontoxic nodular goiter may induce thyrotoxicosis by disclosing diffuse autonomously functioning thyroid tissue. An indirect adverse effect of iodine upon the thyroid gland may be manifested by lymphocyte glandular infiltrates and chronic thyroiditis which were sparse or absent in thyroid glands removed from subjects living in iodine deficient areas before iodine prophylaxis and therapy. Not only has the incidence of thyroiditis increased, but the histologic and clinical distinctions between treated Graves' disease and chronic thyroiditis have become indistinct. Experimentally, chronic thyroiditis has been produced in animals following large doses of iodine. Accumulated evidence supports the concept that iodine contributes to the genesis of chronic thyroiditis.     

Onset and duration of action of single doses of formoterol inhaled via Turbuhaler

The aim of the study was to investigate the time of onset and the duration of the bronchodilating effect of different doses of formoterol administered via Turbuhaler in patients with moderate asthma. Thirty-one patients (five women) with a mean forced expiratory volume in 1 s (FEV1) of 1.97 +/- 0.54 1 and a mean reversibility of 31 +/- 14% of baseline were included in this double-blind, randomized, placebo-controlled and cross-over study. The patients inhaled single doses of placebo, i.e. 6, 12, 24, or 48 micrograms formoterol fumarate, on 5 separate days. Serial measurements of specific airways conductance (SGAW) and FEV1 were performed at regular time intervals for 12 h. The majority of the patients had at least a 50% increase in SGAW within 1-4 min after administration of all active treatments. The maximum increase in FEV1 over placebo was dose-dependent: 12% (6 micrograms), 18% (12 micrograms), 19% (24 micrograms), and 26% (48 micrograms) (P < 0.001). Twelve hours after administration of 6, 12, 24, and 48 micrograms formoterol, the mean increase in FEV1 was still 7%, 15%, 18%, and 27%, respectively, above the value following placebo. Headache was the most frequently reported adverse event in all treatments including placebo. After inhalation of 48 micrograms, three patients experienced mild tremor lasting for less than 1 h; likewise, one patient experienced the same event for 3 h after placebo. Formoterol administered via Turbuhaler10 gave a rapid and dose-related bronchodilating effect lasting for 12 h and was well tolerated.     

Free and total insulin-like growth factors and insulin-like growth factor binding proteins during 14 days of growth hormone administration in healthy adults

The objective was to investigate the effect of growth hormone (GH) administration on circulating levels of free insulin-like growth factors (IGFs) in healthy adults. Eight healthy male subjects were given placebo and two doses of GH (3 and 6 IU/m2 per day) for 14 days in a double-blind crossover study. Fasting blood samples were obtained every second day. Free IGF-I and IGF-II were determined by ultrafiltration of serum. Total IGF-I and IGF-II were measured after acid-ethanol extraction. In addition, GH, insulin, IGF binding protein 1 (IGFBP-1) and IGFBP-3 were measured. Serum-free and total IGF-I increased in a dose-dependent manner during the 14 days of GH administration. After 14 days, serum-free IGF-I values were 610 +/- 100 ng/l (mean +/- SEM) (placebo), 2760 +/- 190 ng/l (3 IU/ m2) and 3720 +/- 240 ng/l (6 IU/m2) (p = 0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.004 for 3 IU/m2 vs 6 IU/m2). Total IGF-I values were 190 +/- 10 micrograms/l (placebo), 525 +/- 10 (3 IU/m2), and 655 +/- 40 micrograms/l (6 IU/m2) (p < 0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.04 for 3 IU/m2). There were no differences in the levels of free or total IGF-II during the three study periods. Insulin-like growth factor binding protein 1 was decreased during GH administration (p = 0.04 for placebo vs 3 IU/m2; p = 0.006 for placebo vs 6 IU/m2). In conclusion, fasting serum free IGF-I increased dose dependently during GH administration and free IGF-I increased relatively more than total IGF-I. This may partly be due to the decrease in IGFBP-1.     

Management of hyperparathyroidism in an endemic goiter area

In an endemic goiter area patients with hyperparathyroidism (HPTH) frequently also have thyroid abnormalities. In a retrospective study of 95 patients with HPTH we assessed the diagnostic accuracy of imaging techniques (ultrasonography or radionuclide scanning) for preoperative localization of parathyroid adenomas. Altogether 86% of our patients had goiter, requiring thyroid resections in 37%. For 19 patients the parathyroid exploration was the second or third cervical operation, most of them due to goiter. We found that the overall rate of transient and permanent recurrent nerve paralysis is considerably increased in patients with previous neck surgery (26% vs. 7%). The combination of ultrasonography and radionuclide scanning can lead surgeons to the site of parathyroid lesions responsible for HPTH in 85% of cases, although frequent nodular goiters can produce pitfalls for correct imaging in iodine-deficient countries. In endemic goiter areas preoperative localization studies can be recommended in patients with primary HPTH--for evaluation of thyroid pathology possibly leading to resection or its accuracy in localizing parathyroid adenomas. These studies also seem justified in patients with previously unsuccessful neck explorations for HPTH.     

Low dose linomide in Type I juvenile diabetes of recent onset: a randomised placebo-controlled double blind trial

The quinoline-3-carboxamide, linomide, protects non-obese diabetic mice from diabetes. The effects of linomide on insulin needs and beta cell function were studied in recent juvenile Type I diabetes in a double-blind trial. Patients with recent onset diabetes were randomly assigned to treatment with a fixed dose of 2.5 mg linomide (42 patients) or placebo (21 patients) for 1 year, in addition to insulin and diet. Glycated haemoglobin was 10-15% lower at 9 months (p = 0.003) and 12 months (p < 0.05) in the linomide group. The insulin dose was 32-40% smaller in the linomide group at 3 (p < 0.03), 6 (p < 0.02), 9 (p < 0.001) and 12 months (p = 0.01). Insulin doses correlated negatively with C peptide values (p = 0.001-0.002). The trend for higher C peptide values in the linomide group did not reach significance. In a post hoc subgroup analysis performed in 40 patients (25 from the linomide group and 15 from the placebo group) who still had detectable residual beta cell function at entry, linomide was associated with 45-59% higher C peptide value at 6 months (p < 0.05), 9 months (p < 0.05) and 12 months (p < 0.05). The main adverse effects of linomide were mild transitory anaemia (45 vs 10% in the linomide and placebo groups), thrombocytopenia (24 vs 10%), and mild joint discomfort (45 vs 5%) with no clinical signs. In conclusion, low-dose linomide reduced the insulin needs in patients with juvenile Type I diabetes of recent onset and improved beta cell function in patients who still had detectable beta cell function at entry. These results support further clinical and experimental studies to define the effects of linomide in Type I diabetes provided the safety of linomide is reliably established.     

Long-term effect of 131I therapy of multinodular non-toxic goiter

The aim of this study was to investigate the long term effect of 131I treatment on thyroid function and size in patients with non-toxic multinodular goitre. The subjects were 69 consecutive patients with multinodular non-toxic goitre selected for 131I treatment and followed for a minimum of 12 months. Outcome measures were standard thyroid function variables and ultrasonically determined thyroid volume before and after treatment. Fifty-nine patients were treated with a single dose of 131I, 12 with two doses, and one with four doses. In 45 patients treated with one dose who remained euthyroid the median thyroid volume was reduced from 73 (interquartile range 50-106) ml to 29 (interquartile range 23-48) ml at 24 months. The median reduction was 40 (22-48) ml, half of which occurred within three months. Patients treated with two doses as well as those developing hypo- or hyper-thyroidism also had a significant reduction in thyroid volume. Eleven patients developed hypothyroidism (cumulative five year risk 22%). Side effects were few. In conclusion we find that 131I treatment of multinodular non-toxic goitre is an attractive alternative to surgery.     

The disorders induced by iodine deficiency

This paper reviews present knowledge on the etiology, pathophysiology, complications, prevention, and therapy of the disorders induced by iodine deficiency. The recommended dietary allowances of iodine are 100 micrograms/day for adults and adolescents, 60-100 micrograms/day for children aged 1 to 10 years, and 35-40 micrograms/day in infants aged less than 1 year. When the physiological requirements of iodine are not met in a given population, a series of functional and developmental abnormalities occur including thyroid function abnormalities and, when iodine deficiency is severe, endemic goiter and cretinism, endemic mental retardation, decreased fertility rate, increased perinatal death, and infant mortality. These complications, which constitute a hindrance to the development of the affected populations, are grouped under the general heading of iodine deficiency disorders (IDD). At least one billion people are at risk of IDD. Iodine deficiency, therefore, constitutes one of the most common preventable causes of mental deficiency in the world today. Most of the affected populations live in mountainous areas in preindustrialized countries, but 50 to 100 million people are still at risk in Europe. The most important target groups to the effects of iodine deficiency from a public health point of view are pregnant mothers, fetuses, neonates, and young infants because the main complication of IDD, i.e., brain damage resulting in irreversible mental retardation, is the consequence of thyroid failure occurring during pregnancy, fetal, and early postnatal life. The main cause of endemic goiter and cretinism is an insufficient dietary supply of iodine. The additional role of naturally occurring goitrogens has been documented in the case of certain foods (milk, cassava, millet, nuts) and bacterial and chemical water pollutants. The mechanism by which the thyroid gland adapts to an insufficient iodine supply is to increase the trapping of iodide as well as the subsequent steps of the intrathyroidal metabolism of iodine leading to preferential synthesis and secretion of triiodotyronine (T3). They are triggered and maintained by increased secretion of TSH, which is ultimately responsible for the development of goiter. The acceleration of the main steps of iodine kinetics and the degree of hyperstimulation by TSH are much more marked in the pediatric age groups, including neonates, than in adults, and the development of goiter appears as an unfavorable side effect in the process of adaptation to iodine deficiency during growth. The most serious complication of iodine deficiency is endemic cretinism, a syndrome characterized by irreversible mental retardation together with either a predominant neurological syndrome or predominant hypothyroidism, or a combination of both syndromes.(ABSTRACT TRUNCATED AT 400 WORDS)     

Growth hormone versus placebo treatment for one year in growth hormone deficient adults: increase in exercise capacity and normalization of body composition

OBJECTIVE: Studies with GH substitution in GH-deficient (GHD) adults lasting more than 6 months have so far been uncontrolled. End-points such as physical fitness and body composition may be subject to a considerable placebo effect which weakens the validity of open studies. We therefore tested GH (2 IU/m2 per day) versus placebo treatment for 12 months. DESIGN: Twenty-nine patients (mean age 45.5 +/- 2.0 years) with adult-onset GHD were studied in a double-blind, parallel design. Measurements of body composition by means of conventional anthropometry, bioelectrical impedance (BIA), CT scan and DEXA scan, exercise capacity, and isometric muscle strength were performed at baseline and after 12 months treatment. For body composition measurements a control group of 39 healthy, age and sex-matched subjects was included. RESULTS: Sum of skinfolds (SKF) at 4 sites decreased significantly after GH treatment. Total body fat (TBF) as assessed by DEXA and BIA was elevated at baseline but normalized after GH. TBF assessed by SKF revealed significantly higher levels compared to DEXA and BIA, although all estimates intercorrelated closely. Visceral and subcutaneous abdominal fat decreased by 25 and 17%, respectively after GH (P < 0.01) to levels no longer different from the control group. CT of the mid thigh revealed a significant reduction in fat tissue and a significant increase in muscle volume after GH treatment, both of which resulted in a normalization of the muscle: fat ratio (%) (placebo: 58:42 (baseline) vs 58:42 (12 months); GH: 66:34 (baseline) vs 72:28 (12 months) (P = 0.002); normal subjects: 67:33 (P < 0.05 when compared to 12 months placebo data)). Total body resistance and resistance relative to muscle volume decreased significantly after GH treatment suggesting over-hydration as compared to normal subjects. Exercise capacity (kJ) increased significantly after GH treatment (placebo: 54.7 +/- 9.8 (baseline) vs 51.6 +/- 8.2 (12 months); GH: 64.9 +/- 13.3 (baseline) vs 73.5 +/- 13.6 (12 months) (P < 0.05)). Isometric quadriceps strength increased after GH but no treatment effect could be detected owing to a small increase in the placebo group. Serum IGF-I levels (microgram/l) were low baseline and increased markedly after GH treatment to a level exceeding that of normal subjects (270 +/- 31 (12 months GH) vs 156 +/- 8 (normal subjects (P < 0.01)). The levels of serum electrolytes and HbA1c remained unchanged. The number of adverse effects were higher in the GH group after 3 months, but not after 6 and 12 months. CONCLUSIONS: (1) The reduction in excess visceral fat during GH substitution is pronounced and sustained; (2) beneficial effects on total body fat, muscle volume and physical fitness can be reproduced during prolonged placebo-controlled conditions; (3) uncontrolled data on muscle strength must be interpreted with caution; (4) a daily GH substitution dose of 2 IU/m2 seems too high in many adult patients.     

Bromocriptine in systemic lupus erythematosus: a double-blind, randomized, placebo-controlled study

The objective of this study was to investigate the efficacy and safety of bromocriptine (BRC) as an adjunct to conventional treatment in systemic lupus erythematosus (SLE). A prospective, double-blind, randomized, placebo-controlled study compared BRC at a fixed daily dosage of 2.5 mg with placebo. Patients were followed for 2-17 months (mean 12.5 months). Disease activity was assessed using the SLE Disease Activity Index (SLEDAI), numbers of flares were recorded, and serum prolactin (PRL) levels were obtained at intervals during the study. Patients were allowed to take prednisone and immunosuppressive drugs. Sixty-six patients with SLE entered the study. Thirty-six were treated with BRC, and 30 controls received placebo. Sixteen patients were removed from the study during the treatment period: five in each group left the study because of adverse effects, five became pregnant, and one patient who took placebo died with central nervous system lupus. Four patients in the BRC treatment group and three patients in the placebo group moved away or stopped coming for study visits for unknown reasons, and were lost to follow-up during the course. At entry, serum PRL was (mean+/-s.d.) 24.8 ng/ml+/-18.4 in the BRC treatment group. This value fell to 5.8+/-9.0 after 12 months of treatment. Corresponding PRL values in controls were 23.7+/-22.1 pretreatment and 20.3+/-14 after 12 months. PRL levels in BRC-treated subjects were significantly lower than levels in control subjects after 3, 6, 9, and 12 months of treatment. The SLEDAI score on the fifth protocol visit was decreased significantly in the BRC group vs controls: 0.9+/-1.4 vs 2.6+/-4.5 (P < 0.05). Although the absolute number of flares in each group was similar, the mean number of flares/patient/month was decreased significantly in the BRC group compared to the control group (0.08+/-0.1 vs 0.18+/-0.2, P = 0.03). Long term treatment with a low dose of BRC appears to be a safe and effective means of decreasing SLE flares in SLE patients.     

Occurrence of thyroid autoimmunity and dysfunction throughout a nine-month follow-up in patients undergoing interferon-beta therapy for multiple sclerosis

Thyroid autoimmunity and dysfunction are a well known side effect of IFN alpha therapy for viral hepatitis and tumors, while the IFN beta effects on the thyroid gland in neurological patients have not been studied. The aim of this longitudinal study was to look for the appearance of thyroid autoimmunity as well as for the occurrence of overt thyroid disease in the patients affected by multiple sclerosis (MS) treated with IFN beta 1b. Eight patients (4 males, 4 females) undergoing r-IFN beta 1b treatment (8 M.U. every other day for 9 months) for relapsing remitting multiple sclerosis entered the study. We have analyzed thyroid function parameters and auto antibody levels before and after 1, 2, 3, 6 and 9 months of therapy. None of them referred to familiar thyroid pathology or presented clinically overt thyroid disease except for one patient (case 4) who showed TPO-Ab pretreatment positivity and another (case 8) who was in therapy with Levothyroxine 100 microg/die for multinodular goiter. The number of patients with appearance of thyroid antibodies has slowly increased, until the third month of therapy with 3 patients out of 7 positive for TPO-Ab. The only case of overt thyroid dysfunction reported by us appeared after nine months of therapy and consisted of a hypothyroidism. Our data suggest that short-term interferon beta treatment is able to induce thyroid autoimmunity (42.8%) and dysfunction (12.5%).     

Treatment with the oral growth hormone secretagogue MK-677 increases markers of bone formation and bone resorption in obese young males

The effect of 2 months of treatment with the oral growth hormone (GH) secretagogue MK-677 on markers of bone metabolism was determined in healthy obese male subjects. This was a randomized, double-blind, parallel, placebo-controlled study. Twenty-four healthy obese males, 19-49 years of age, with body mass index > 30 kg/m2 were treated with MK-677 (25 mg/day; n = 12) or placebo (n = 12) for 8 weeks. MK-677 increased markers of bone formation; a 23% increase in the carboxy-terminal propeptide of type I procollagen levels and a 28% increase in procollagen III peptide levels were seen with as little as 2 weeks of MK-677 treatment (p < 0.01 and p = 0.001 vs. placebo, respectively) while a 15% increase in serum levels of osteocalcin was not detected until 8 weeks of treatment (p < 0.01 vs. placebo). Markers of bone resorption were induced within 2 weeks of treatment with MK-677; serum levels of the carboxy-terminal cross-linked telopeptide of type I collagen were increased 26% at 8 weeks (p = 0.001 vs. placebo), and urine hydroxyproline/creatinine and calcium/creatinine ratios at 8 weeks were increased by 23% (p < 0.05 vs. placebo) and 46% (p < 0.05 vs placebo), respectively, MK-677 increased serum insulin-like growth factor binding protein-5 (IGFBP-5) by 43-44% after 2-8 weeks of treatment (p < 0.01 vs. placebo). Serum IGFBP-4 was increased by 25% after 2 weeks of treatment (p < 0.001 vs. placebo) but no significant change from baseline was observed after 8 weeks of treatment. Plasma interleukin-6 was not significantly changed by active treatment. In conclusion, short-term treatment of healthy obese male volunteers with the GH secretagogue MK-677 increases markers of both bone resorption and formation. Large increases in serum levels of IGF-1 and IGFBP-5 and a transient increase in serum IGFBP-4 were found. Future long-term studies are needed to investigate if prolonged treatment with MK-677 increases bone mass.