J. Teuber

Subclinical hyperthyroidism: Physical and mental state of patients

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

SCREENING FOR THYROID DISORDERS IN A WORKING POPULATION

SummarySubclinical thyroid disorders have received increasing attention in recent years due to refined laboratory methods and a stronger emphasis on the role of preventive medicine. We performed a screening for thyroid-stimulating hormone (TSH) on 6884 persons in a working population. In cases in which TSH was not within the normal range we also measured the levels of triiodothyronine (T3), thyroxine (T4), and thyroxine-binding globulin (TBG). All persons who did not present with exclusion criteria or other nonthyroidal illnesses (n = 59) and the controls (n = 39) were submitted to thyrotropin-releasing hormone (TRH)-testing. Additionally, sonography of the thyroid was performed on 120 persons (59 subjects with abnormal hormone levels and 61 controls) to determine thyroid size and rule out morphological abnormalities. Based on the TRH test and T3, T4, and TBG measurements we found a prevalence of 0.03% (2/6884) for overt hyperthyroidism, 0.33% (23/6884) for subclinical hyperthyroidism, 0.09% (6/6884) for subclinical hypothyroidism, and 0.015% (1/6884) for overt hypothyroidism in the healthy population. In subjects with overt or subclinical hyperthyroidism the prevalence of goiters (thyroid volume > 18 ml in women, > 25 ml in men) was 28%. Of this group 48% had structural abnormalities. All persons with goiters and/or structural abnormalities were over 35 years of age. Among the euthyroid, 20% had thyroid enlargement, and the same proportion presented with structural abnormalities. There were no differences between the two age groups. In the group with overt/subclinical hypothyroidism 47% presented with structural abnormalities of the thyroid; however, none presented with thyroid enlargement. Thyroid nodules were found only in older persons (> > 35 years) with euthyroidism or hypothyroidism. These data confirm the relatively high prevalence of functional and morphological abnormalities of the thyroid. An early substitution with iodine is warranted to prevent functional and morphological disorders of the thyroid in older age. People with subclinical hyperthyroid disorders must avoid exposure to iodine, which can cause an exacerbation of the disease.

Hypothalamo-hypophysäre Schilddrüsen-Achse, Plasmaproteinkonzentrationen und die hypophysäre Gonaden-Achse im Low-T3-Syndrom nach akutem Myokardinfarkt (AMI)

SummaryIn patients with severely acute diseases, a special relationship of thyroidal hormones with decreased T3 and increased rT3 levels is known, the so-called low T3 syndrome. The aim of this study was to elucidate the involvement of the hypothalamo-pituitary thyroid axis, the pituitary-gonadal axis, the altered hepatic function, the plasma proteins in the low T3 syndrome, and the evaluation of these parameters for prognosis in patients with acute myocardial infarction. Thirty-one patients (29 male, 2 female) with AMI entered the study for the determination of hypothalamo-pituitary thyroid axis and the plasma proteins. Besides routine laboratory determinations, TRH, TSH, T4, T3, rT3, CHE, albumin, total protein, TBG, and estradiol concentrations in plasma were measured daily for 5 days after AMI using immunological and other methods. Twelve male patients with AMI entered the study for the determination of pituitary-gonadal axis; the T3, rT3, estradiol, testosterone, FSH, and LH concentrations in serum were determined using immunological methods. We found that T3 and T4 decreased significantly to a minimum on the first and the second day, respectively, after admission and increased in the course of the observation period. In contrast, rT3 was elevated significantly within the first 2 days and decreased later. TSH and TRH decreased in the first 2 days and increased in the following days. CHE, albumin, and total protein levels significantly showed a minimum on day 4 and TBG significantly showed a minimum on the second day after AMI and increased to day 4. The estradiol and testosterone levels were high on admission and decreased in the following days and increased again in the observation period. FSH decreased in the first 2 days and increased in the following course similar to estradiol and testosterone. Patients who died within 2 weaks after AMI showed a plasma hormonal pattern of hypothyroidism with low TSH levels and hypogonadotropic hypogonadism on the second day, whereas this pattern is persistent in the following days. These results show the involvement of the hypothalamo-pituitary axis in the low T3 syndrome and that characteristics for acute partial insufficiency of the anterior pituitary gland are signs of a bad prognosis. Whether Gn-RH and ACTH also decreased after AMI is unknown. The necessity for substitution is unclear and needs further investigationIn patients with severely acute diseases, a special relationship of thyroidal hormones with decreased T3 and increased rT3 levels is known, the so-called low T3 syndrome. The aim of this study was to elucidate the involvement of the hypothalamo-pituitary thyroid axis, the pituitary-gonadal axis, the altered hepatic function, the plasma proteins in the low T3 syndrome, and the evaluation of these parameters for prognosis in patients with acute myocardial infarction. Thirty-one patients (29 male, 2 female) with AMI entered the study for the determination of hypothalamo-pituitary thyroid axis and the plasma proteins. Besides routine laboratory determinations, TRH, TSH, T4, T3, rT3, CHE, albumin, total protein, TBG, and estradiol concentrations in plasma were measured daily for 5 days after AMI using immunological and other methods. Twelve male patients with AMI entered the study for the determination of pituitary-gonadal axis; the T3, rT3, estradiol, testosterone, FSH, and LH concentrations in serum were determined using immunological methods. We found that T3 and T4 decreased significantly to a minimum on the first and the second day, respectively, after admission and increased in the course of the observation period. In contrast, rT3 was elevated significantly within the first 2 days and decreased later. TSH and TRH decreased in the first 2 days and increased in the following days. CHE, albumin, and total protein levels significantly showed a minimum on day 4 and TBG significantly showed a minimum on the second day after AMI and increased to day 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Der Nachweis von HIV-1-Antigen — Bestimmung mit Hilfe von drei verschiedenen Testsystemen

Summary51 human sera containing antibodies to human immunodeficiency virus 1 (=HIV-1) were examined for HIV-1-antigen by three different enzyme immunoassay procedures (=EIA) of Abbott, Organon and Dupont. Sensibilities, handling as well as the correlation with the clinical stages of HIV-infection were compared. The EIAs diagnosed in accordance 6 sera which contained HIV-1-antigen and 42 sera to be HIV-1-antigen negative. 3 sera showed differences: according to the EIA of Organon none of these sera contained HIV-1-antigen, the EIA of Abbott (but not of Dupont) analysed HIV-1-antigen in one of these sera, in the other two sera only the EIA of Dupont showed HIV-1-Antigen.It is concluded that the differences in these 3 serum samples may originate not only in the different types of EIA used (indirect/direct procedure) but also in the different capture antibodies provided (antibodies against p-24 antigen or polyvalent antibodies).51 human sera containing antibodies to human immunodeficiency virus 1 (= HIV-1) were examined for HIV-1-antigen by three different enzyme immunoassay procedures (= EIA) of Abbott, Organon and Dupont. Sensibilities, handling as well as the correlation with the clinical stages of HIV-infection were compared. The EIAs diagnosed in accordance 6 sera which contained HIV-1-antigen and 42 sera to be HIV-1-antigen negative. 3 sera showed differences: according to the EIA of Organon none of these sera contained HIV-1-antigen, the EIA of Abbott (but not of Dupont) analysed HIV-1-antigen in one of these sera, in the other two sera only the EIA of Dupont showed HIV-1-Antigen. It is concluded that the differences in these 3 serum samples may originate not only in the different types of EIA used (indirect/direct procedure) but also in the different capture antibodies provided (antibodies against p-24 antigen or polyvalent antibodies).

Die Rolle des TSH für Psychische VerÄnderungen und BefindlichkeitsverÄnderungen bei Schilddrüsenfunktionsstörungen

SummaryThe characteristic psychic and somatic features found in patients with overt hyper- or hypothyroidism are usually attributed to elevated or diminished levels, respectively, of thyroid hormones. This concept does not sufficiently explain our previous investigations in which the same symptoms, albeit attenuated, were also seen in patients suffering from so-called latent disturbances of thyroid function. This state of disorder, however, exhibits normal concentrations of peripheral thyroid hormones. Only the response of thyroid-stimulating hormone (TSH) to thyrotropin-releasing hormone (TRH) stimulation is in accordance with the behaviour of the overt thyroid dysfunction and enables its differentiation from the euthyroid state. In this context, we investigated the question as to whether pathologic signs in thyroid disorders are correlated to alterations of peripheral thyroid hormones or to changes in the hypothalamus pituitary axis. Therefore, we investigated two groups of ten patients each who suffered from latent hyper- or hypothyroidism, respectively, and ten euthyroid controls. All were matched from sex and age. Endocrine function was estimated by TRH testing, TT3, TT4 and thyroxine binding globuline (TBG). Psychologic testing was performed by questionnaires concerning subjective somatic symptoms, emotional disturbances, psychomotoric performance, cognitive impairment and personality. Patients with latent hyperthyroidism were more subject to somatic symptoms and affective complaints than were those who had latent hypothyroidism. As compared with controls, there were significant differences in exhaustion and pain in the limbs and heart. In terms of affective complaints, patients were more depressive, anxious, touchy and irritable; their personalities showed a higher degree of emotional lability, excitement and irritability. Many symptoms described in overt thyroid dysfunction could be found in latent metabolic disturbances. Therefore, we conclude that the alterations of health in thyroid disorders are more likely to be caused by hypothalamic pituitary impairment than by changes in peripheral hormone levels. The stronger symptoms occurring in overt thyroid dysfunction as compared with latent metabolic disturbances may reflect the degree of hypothalamic pituitary dysfunction.The characteristic psychic and somatic features found in patients with overt hyper- or hypothyroidism are usually attributed to elevated or diminished levels, respectively, of thyroid hormones. This concept does not sufficiently explain our previous investigations in which the same symptoms, albeit attenuated, were also seen in patients suffering from so-called latent disturbances of thyroid function. This state of disorder, however, exhibits normal concentrations of peripheral thyroid hormones. Only the response of thyroid-stimulating hormone (TSH) to thyrotropin-releasing hormone (TRH) stimulation is in accordance with the behaviour of the overt thyroid dysfunction and enables its differentiation from the euthyroid state. In this context, we investigated the question as to whether pathologic signs in thyroid disorders are correlated to alterations of peripheral thyroid hormones or to changes in the hypothalamus pituitary axis. Therefore, we investigated two groups of ten patients each who suffered from latent hyper- or hypothyroidism, respectively, and ten euthyroid controls. All were matched from sex and age. Endocrine function was estimated by TRH testing, TT3, TT4 and thyroxine binding globulin (TBG). Psychologic testing was performed by questionnaires concerning subjective somatic symptoms, emotional disturbances, psychomotoric performance, cognitive impairment and personality. Patients with latent hyperthyroidism were more subject to somatic symptoms and affective complaints than were those who had latent hypothyroidism. As compared with controls, there were significant differences in exhaustion and pain in the limbs and heart. In terms of affective complaints, patients were more depressive, anxious, touchy and irritable; their personalities showed a higher degree of emotional lability, excitement and irritability.(ABSTRACT TRUNCATED AT 250 WORDS)

Heterotransplantation of Autoimmune Human Thyroid to Nude Mice as a Tool for in Vivo Autoimmune Research

Various experimental transplantation models have been used in order to investigate the physiology, pathophysiology and treatment of grafted tissues under in vivo conditions(1). Since in homologous and especially in heterologous transplantation models severe immunological problems exist, the description of thymus aplastic nude(nu/nu)mice(2)and nude(rnu/ rnu)rats(3)has stimulated experimental transplantation research. The genes governing thymic agenesis and hairlessness proved to be linked and inherited as autosomal traits. This effect is linked with loss’ of immunocompetend T-lymphocytes, resulting in a lack of immune resistance. If nude mice or rats are used as recipients, hetero(xeno-)transplantation can be achieved without immunosuppressive therapy. Beside malignant and also various benign human tissue were successfully transplanted to nude mice.

Circadian and pulsatile levels of human thyroid-stimulating hormone (TSH) in various stages of hyperthyroidism

We investigated the influence of various degrees of hyperthyroidism to thyrotropin circadian and pulsatile pattern for 24 h. Furthermore, we investigated the influence of sex and of sleep deprivation on the circadian and pulsatile pattern of TSH in euthyroid female and male volunteers. In euthyroidism the circadian rhythym is well known [1, 3]. With regard to circadian rhythm of TSH in hyperthyroidism only very preliminary data have been described [2]. We observed a total of 10 euthyroid healthy volunteers (age range 23-26 years, 4 men, 6 women); from 5 of them we collected blood from sleep on, and from the rest we collected blood during sleep deprivation tbr 24 h. Furthermore, blood was collected in 4 patients (age range 60-74 years, 3 women, 1 man), 2 presenting latent and 2 manifest hyperthyroidism. Informed consent was obtained from each subject. The subjects were classified into euthyroid and hyperthyroid status according to known biochemical criteria. In M1 subjects blood was collected at 10-min intervals for 24 h from an indwelling cubital vein canule kept patent with a slow infusion of saline. All subjects were hospitalized for the study period; regular hospital meals and only standard activities were allowed during the study period. All premenopausat female sujects were in the luteal phase of the menstrual cycle. TSH was measured using a very sensitive enhanced luminescence method (Amerlite TSH Assay, monoclonal) [7]. Statistical analysis was performed by spectrum analysis [4] and spline techniques [5]. In euthyroid volunteers we found intraindividually three overlapped patterns of TSH, which are different in amplitude and frequency and can be found interindividually, too. The first pattern is equivalent to the circadian rhythm with a nocturnal acrophase. The last pattern is equivalent to the methodic rustle, with a TSIt amplitude of 0.07 gU/ml (TSH mean level 1.2 gU/ml) or 0.02 gU/ml in lower TSH range, and a variable frequency. The second pattern is equivalent to the putsatile secretion with a frequency of 12.0_+ 1.9 pulses/24 h and TSH mean amplitude of 0.19 _+ 0.04 gU/mt. We did not find that the TSH pulsatile pattern depended on sex. During sleep deprivation for 24 h, TSH levels remain on a high plateau for the night period until approximately 8.00 h. Sleep deprivation prevents TSH decrease after the midnight TSH peak. The mean TSH level for 24 h in latent hyperthyroidism (2 = 0.09 gU/ml) is higher than in manifest hyperthyroidism (£=0.015 gU/ml). In both cases the circadian pattern is nonexistent. Whereas the pulsatile secretion in latent hyperthyroidism is existent, in manifest hyperthyroidism the TSH pulses are abolished. In manifest hyperthyroidism depressive symptoms are well known. Until now the latent hyperthyroidism as already defined was not regarded as illness. However, in our own open pilot study latent hyperthyroidism altered psychometric parameters [6], and few clinical symptoms improved after carbimazole treatment. Prospective trials in this respect are ongoing. Our data suggest that the 24 h TSH pattern is dependent on the degree of the hyperthyroidism and that the latent and manifest hyperthyroidism, as defined until now, might be revised and updated as degrees of hyperthyroidism. As proposed we would recommend the following classification of hyperthyroidism: stage I, tosts of circadian TSH rhythm, existence of TSH pulses, normal T3, T4, TBG levels, and little clinical symptoms; stage II, T3 and T4 elevated, TSH as stage I but no pulses existent, little or typical clinical symptoms; and stage III, thyroidal storm with coma (thyrotoxic crisis).

Metastasierungsverhalten des Schilddrüsenkarzinoms in Abhängigkeit zur Membranexpression von MHC-Klasse-I- und -II-Proteinen auf den Tumorzellen

Insbesondere tierexperimentelle Untersuchungen zeigen eine inverse Korrelation der MHC-I-Antigen(Ag)-Expression zur Metastasierungspotenz bei malignen Primartumorzellen. Andererseits scheint die aberrierende MHC-II-Ag-Expression eine Signalfunktion fur autozytotoxische Reaktionen des Immunsystems zu besitzen. In diesem Zusammenhang interessierte uns die prospektive Bedeutung des Vorkommens von MHC-I- und -II-Ag fur das Auftreten von Organmetastasen beim Schilddrusenkarzinom.

Antiidiotypic Blocking of Graves′ Disease Biologic Activity with Autologous Sera But Not Consistently with Homologous Sera: Evidence for Polyclonality of Thyroid Receptor Antibodies (Trab)

Although there is multiple evidence for the functional heterogeneity and polyclonality of TRAb (1 - 3) both statements are questioned by some investigators (4, 5). Furthermore there is growing evidence for an idiotypic-antiidiotypic regulation of Graves disease and other autoimmune diseases (6, 7).