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Biomedical subjects

T Zimmermann-Belsing

Publications and source records attributed to T Zimmermann-Belsing.

17 recordsLinked to original sources
PubMed2004

The insulin-like growth axis in patients with autoimmune thyrotoxicosis: effect of antithyroid drug treatment.

OBJECTIVE: Hyperthyroidism is associated with altered growth hormone (GH) secretion. Many patients with thyroid dysfunction experience several poorly described complications such as symptoms and signs also seen in patients with growth hormone deficiency (GHD). We have therefore prospectively evaluated a possible relationship between the thyroid function, body composition, leptin levels and insulin-like growth factor (IGF) related peptides in patients with Graves' disease. DESIGN, PATIENTS, AND MEASUREMENTS: In a prospective group of 24 fasting female patients with Graves' disease (mean age (CI 95%): 40 years (33-47)), we measured serum thyroxine, triiodothyronine, thyrotropine (TSH), TSH receptor antibodies, anti-thyroid peroxidase, leptin, body composition, body mass index (BMI) and IGF-related peptides at diagnosis and after 12 months of treatment with thiamazol (ATD). RESULTS: In thyrotoxic patients IGF-I plus IGF-II correlated positively with IGFBP-3 at baseline (r = 0.90, p < 0.1 x 10(16)) and after 12 months follow-up (r = 0.87, p < 0.1 x 10(-16)). In the thyrotoxic state total IGF-I, IGF-II, IGF binding protein 3 (IGFBP-3) and acid-labile subunit (ALS) but not free IGF-I decreased significantly from 223 microg/L (189-260) (mean (CI 95%), 877 microg/L (801-953), 4165 microg/L (3772-4577) and 22 mg/L (18-26)) to 198 microg/L (172-226), 788 microg/L (711-865), 3431 microg/L (3135-3741) and 19 mg/L (16-26) (p <0.006), respectively, after 12 months of ATD despite an increase in BMI from 22 (21-23) to 23 kg/m(2) (22-25) (p < 0.0004) but no significant changes in leptin. CONCLUSIONS: The complex IGF systems seemed intact in thyrotoxic patients but change in body composition and the regulation of leptin and insulin secretion during treatment of autoimmune thyroid disease influence IGF-related peptides leaving the patient in a state somewhat similar to partial GHD, but the mechanism behind these alterations remains unclear.

Adult↗
PubMed2002

The influence of alpha1-acid glycoprotein (orosomucoid) and its glycoforms on the function of human thyrocytes and CHO cells transfected with the human TSH receptor.

Local immunological reactions might influence the structure of alpha1-acid glycoprotein (AGP, orosomucoid) leading to a pathological condition in e.g. the thyroid. The aim of this study was to investigate whether the AGP molecule had a direct effect on thyroid cell function in vitro. The influence of AGP and its three glycoforms, TSH (1.0 U/l), serum samples and several sugars (methyl-mannose, methyl-glycoside, N-acetyl-D-galactose, N-acetyl-D-glycoside, neuramidase) were studied with respect to their influence on the function of the Chinese Hamster Ovary (CHO) cell line transfected with the human TSH receptor (hTSHr) and on human thyroid follicular epithelial cells (TFEC) in secondary cultures. We found that low concentrations of AGP (0.001-0.05 microg/l) stimulated while high concentrations of AGP (0.25-1.0 microg/l) inhibited cAMP accumulation in both cell systems (n=24, P<0.0002). In CHO cells (JP26) and TFEC glycoforms 1 (n=9), 2 (n=12) or 3 (n=11) significantly inhibited the TSH stimulated cAMP production, respectively, compared to controls (P<0.0001) and was partially reversed by mannose (P<0.0004). Control CHO cells (JP02) without the hTSHr showed no response. The specificity of the reaction was further confirmed by binding of biotinylated glycoforms and streptavidin conjugated FITC to both cell systems. This is the first report demonstrating that AGP and/or its glycoforms affects thyroid cell function in vitro and that it does so by influencing the second messenger cAMP probably by interacting directly with the TSH receptor.

Animals↗
PubMed2002

Long-term pathologic changes of alpha1-acid glycoprotein (orosomucoid) glycoforms in autoimmune thyroid disease.

OBJECTIVE: We measured alpha1-acid-glycoprotein (AGP) in patients with autoimmune thyroid disease to study a possible relationship between microheterogeneity of the naturally occurring glycoforms of AGP and autoimmune thyroid disease. DESIGN, PATIENTS, MEASUREMENTS: In a group of 12 fasting thyrotoxic patients (11 females, mean age: 43 years) with newly diagnosed Graves' disease (subgroup 1), we measured serum concentrations of total AGP and its 3 glycoforms (micromol/l, crossed affinity immunoelectrophoresis with con A in the first dimension gel) as well as total thyroxine, total triiodothyronine, thyrotropine, thyroid peroxidase antibodies (anti-TPO), antibodies against the TSH receptor (TRAb, TRAK), at baseline and after 12 months of antithyroid drug therapy (ATD). For comparison, 4 subgroups of thyroid patients (patients with Graves' disease and thyroid associated ophthalmopathy (TAO) (subgroup 2, n = 10), radioiodine treated Graves' patients (subgroup 3, n = 7), Graves' patients without TAO (subgroup 4, n = 13), patients with Hashimoto's thyroiditis (subgroup 5, n = 8)) and 25 normal controls (17 females, mean age: 38 years) were studied. RESULTS: In subgroups of TRAb positive Graves patients' serum levels of glycoform 1, 2 or 3 increased significantly (p < 0.005) after 12 months of ATD as compared to both baseline of that person or normal controls. No significant changes were found in the TRAb negative Hashimoto subgroup. CONCLUSION: Patients with autoimmune Graves' disease changed their relationship to AGP, and thus a role of AGP and its 3 glycoforms is suggested in the pathogenesis of Graves' disease.

Blood Proteins↗
PubMed2002

Use of the 2nd generation TRAK human assay did not improve prediction of relapse after antithyroid medical therapy of Graves' disease.

OBJECTIVE: Antithyroid drug treatment (ATD) is used world-wide in the treatment of thyrotoxicosis in patients with Graves' disease (GD). The main problem is a relapse rate of 30 to 50% within 2 years after the treatment has stopped. The measurement of thyrotropin receptor antibodies (TRAb) in serum has been used to confirm the diagnosis of GD in selected patients with a diagnostic specificity of 70 to 90%. However, in predicting the recurrence of thyrotoxicosis after discontinuing ATD it has been of little value. The aim of this study was to evaluate the ability of TRAb measured by the more sensitive recombinant human TSH receptor method to predict risk of recurrence of GD after discontinuing ATD. MATERIALS, PATIENTS AND METHODS: One hundred and twenty nine patients with newly diagnosed GD were included. Of these, 58 had relapse of hyperthyroidism in a follow-up of at least 11 months (median 18 months, range 11-49) after discontinuing ATD. In 122 Graves' patients TRAb were measured at the time of diagnosis and in all patients when discontinuing ATD by a competitive radioreceptor assay using recombinant human TSH receptors (TRAK human assay). RESULTS: We found an increased diagnostic specificity (99%) compared with the old TRAK porcine assay. The predictive values of a positive and negative test in relation to the prediction of a relapse of GD were found to be only 55% and 62% respectively when using a cut-off level of 1.5 IU/l, and the predictive value of a positive test decreased to 49% and of a negative test to 60% at a lower cut-off limit (1 IU/l). CONCLUSION: Our study confirms that the new TRAK human assay had a superior diagnostic sensitivity in comparison with the old TRAK porcine assay. Despite the higher diagnostic sensitivity of the TRAK human method, we could not find any improvement of predictive values for relapse of hyperthyroidism in the measurement of TRAb at the end of ATD.

Adult↗
PubMed2000

Free and protein bound leptin are distinct and independently controlled factors in energy regulation.

AIMS/HYPOTHESIS: Leptin exerts important regulating effects on energy homeostasis and could have a central role in our understanding of obesity, diabetes mellitus and the metabolic syndrome. Leptin circulates in a free and protein bound form. The aim of the present study was to test whether both fractions of the leptin system can be selectively regulated and thus serve independent physiological roles. METHODS: Using specific radioimmunoassays we measured both leptin components in relation to BMI in healthy subjects before and after weight reduction and in hyperthyroid patients during correction of thyrotoxicosis. In the latter group body composition and resting energy expenditure was monitored. In addition, we measured serum and cerebrospinal fluid concentrations of free and bound leptin in patients with neurological disorders. RESULTS: Under all conditions free leptin concentrations reflected body fat mass. Bound leptin concentrations decreased during weight reduction but also after treatment of hyperthyroidism despite an increase in fat mass. Direct measurement of resting energy expenditure and bound leptin in hyperthyroid patients and under thyrostatic treatment showed a significant positive correlation of both variables. In contrast to free leptin whose transport into the cerebrospinal fluid appears to be saturated at low physiological concentrations of serum free leptin, bound leptin concentrations in the cerebrospinal fluid increased in parallel to serum concentrations over the whole physiologically relevant range. CONCLUSION/INTERPRETATION: Our data indicate a distinct role of free and bound leptin in the feedback regulating energy intake and expenditure and could have important implications for our understanding of the physiology and pathophysiology of leptin-dependent signalling.

Adolescent↗
PubMed2000

A case of sarcoidosis and sarcoid granuloma, papillary carcinoma, and Graves' disease in the thyroid gland.

Sarcoidosis is a systemic chronic granulomatous disease of unknown etiology most commonly affecting young females. The disease was first described in the thyroid gland in 1938. Our patient, a 27-year-old male with known sarcoidosis, was referred to the National University Hospital for acute symptoms of thyrotoxicosis (weight loss of 6 kg, tremor, thyroid enlargement, and tachycardia). Laboratory findings showed suppressed serum thyrotropin (TSH, <0.03 mU/L [0.5-4.20]), increased total thyroxine (T4) (223 nmol/L, [60-140]), and triiodothyronine (T3) (8.5 nmol/L, [1.5-2.7]). Furthermore, Tc-99m pertechnetate scintigraphy disclosed diffuse accumulation of the isotope confirming the diagnosis of Graves' disease. During the next 18 months of antithyroid treatment (thiamazole, Thycapzol) hyperthyroidism was difficult to control, the thyroid gland gradually enlarged, and surgery was recommended. Initially, the patient declined surgery but after an additional 18 months, he accepted surgery. During the 36-month period of antithyroid drug treatment TSH was suppressed (<0.01 mU/L) and T3 often elevated despite high doses of thiamazole. Total thyroidectomy was performed, and histologic examination of the removed thyroid tissue confirmed the diagnosis of Graves' disease and also the presence of sarcoid granuloma and metastatic papillary adenocarcinoma with spread to neck lymph nodes. Four months later, a modified radical neck dissection was performed with removal of neck lymph nodes followed by external radiation therapy (2 Gy x 32 fractions to the neck). The concomitant presence of sarcoidosis, papillary carcinoma, and Graves' disease in a thyroid gland, to our knowledge, has not previously been described in the literature.

Adult↗
PubMed1998

The relationship between the serum leptin concentrations of thyrotoxic patients during treatment and their total fat mass is different from that of normal subjects.

OBJECTIVE: Previous studies of leptin in thyrotoxic human subjects have been short-term and cross-sectional. We have measured serum leptin concentrations in thyrotoxic patients in order to study the influence of endogenous thyroid hormones on the relationship between serum leptin and fat mass. DESIGN PATIENTS, MEASUREMENTS: In 10 fasting thyrotoxic patients (8 females, 2 males, mean age: 51 years) we measured serum leptin (microgram/l), total thyroxine (TT4), total triiodothyronine (TT3), thyrotropin (TSH) and by Dual Energy X-ray Absorptiometry (DEXA) total fat mass (TFM, kg) at time of diagnosis (0 months, baseline) and during 12 months treatment with thiamazole. For comparison 16 fasting thiamazole-treated euthyroid patients (14 females, 2 males, mean age: 38 years) were studied after one year follow-up (26 months (15-48)) and 18 normal controls (12 females, 6 males, mean age: 39 years). RESULTS: The serum leptin concentration was 9.1 (1.3 micrograms/l (mean (SEM) in the thyrotoxic patients and increased significantly to 16.0 (1.3 micrograms/l (P < 0.0005) after 12 months treatment compared to both normal subjects and their own baseline. There was a significant correlation between serum leptin concentration and TFM in the normal control group (r = 0.79, P < 0.00009), in the thiamazole-treated euthyroid group (r = 0.85, P < 0.00003) and in the baseline thyrotoxic group (r = 0.84, P < 0.002) but the serum leptin/TFM ratio increased significantly during 12 months of antithyroid drug treatment from 0.34 (1.2 micrograms/l/kg to 0.53 (1.2 micrograms/l/kg (P < 0.03). CONCLUSION: The thiamazole-treated thyrotoxic patients increased their serum leptin concentrations during 12 months antithyroid drug treatment without a significant corresponding degree of changes in TFM as expected from normal controls. It is suggested that the metabolic state in thyrotoxic patients can influence the regulation of serum leptin concentrations without any associated changes in TFM.

Adult↗
PubMed1998

Lack of thyroglobulin synthesis as an indicator of early random dedifferentiation of the Fischer rat thyroid cell line FRTL-5.

Fischer rat thyroid cells (FRTL-5) are widely used for the study of thyroid cell function. With age or transformation the characteristics of FRTL-5 cells change, leading to poor differentiation and accelerated growth. Thyroglobulin production from FRTL-5 cells indicates differentiation to a higher extent than does the cyclic adenosine-3',5'-monophosphate (cAMP) response to thyrotropin (TSH) and growth. This study investigated the release of the differentiation marker thyroglobulin from FRTL-5 cells into the medium during various early subcultures compared with cAMP response and cell growth. Growth was measured by 3H-thymidine incorporation into DNA and by the amount of DNA in each well. Cell differentiation was measured by release of cAMP and thyroglobulin from the cells. TSH (1 U/l) stimulated 3H-thymidine incorporation (p<0.001), release of cAMP (p<0.1x10(-6)) and thyroglobulin (p<0.1x10(-6)). However, five passages showed an unexpected lack of thyroglobulin production (less than 15 ng/microg DNA, i.e. below the limit of detection). These results were reproduced from two different cell stocks. The passages which had lost their ability to produce thyroglobulin demonstrated a significant increase in DNA content (p<0.001), and a highly significant decrease in cAMP response to TSH (p<0.00001) compared with the passages that continued to produce thyroglobulin. This study shows that FRTL-5 cells randomly change their biological properties, which is consistent with dedifferentiation of cells in early passages. Lack of thyroglobulin production is a marker of this dedifferentiation.

Animals↗
PubMed1996

[Preoperative scintigraphic localization of hyperfunctioning parathyroid glands].

Preoperative identification of hyperfunctioning parathyroid glands was performed by 99m-Tc-sestamibi scintigrams in 29 patients with hyperparathyroidism. Out of 30 histopathologically proven diseased parathyroid glands 21 were identified by scintigraphy. The diagnostic specificity (PVpos) was 88%. All diseased glands weighing more than 1200 mg were identified by scintigraphy including four glands in the mediastinum. 99m-Tc-sestamibi scintigraphy can identify the larger hyperfunctioning parathyroid glands with high reliability. The method was of great value in situations with ectopic abnormal parathyroid glands.

Adult↗
PubMed1994

Riedel's thyroiditis: an autoimmune or primary fibrotic disease?

Riedel's thyroiditis is a rare condition with an unknown aetiology. The condition was discovered by Riedel in 1883. In 1904, Hashimoto described another condition of invasive fibrous thyroiditis. Since then it has been discussed whether Hashimoto's thyroiditis and Riedel's thyroiditis are one disease in different states or whether they are two different diseases. Hashimoto's thyroiditis is known to have an autoimmune aetiology and can be seen in conjunction with other autoimmune diseases such as pernicious anaemia. The co-existence of Riedel's thyroiditis and pernicious anaemia is reported for the first time in this case story. Our patient was initially treated with a high dose of steroids and today is well on low-dose steroids and without relapse. The co-existence mentioned, the good effect of steroid treatment, the frequent presence of thyroid autoantibodies and lymphoid infiltration of the thyroid gland resembling that of Hashimoto's thyroiditis might indicate an autoimmune aetiology. It may be that the action on fibroblasts of cytokines known to be released by infiltrating lymphocytes constitutes a possible fibrogenic mechanism, but the primary lesion is still unknown.

Diagnosis, Differential↗
PubMed1993

[Invasive fibrous thyroiditis--Riedel's goiter. A review of the literature and a case report].

Invasive fibrous thyroiditis (Riedel's goitre) is a rare condition of an unknown aetiology. The condition was first described by Riedel in 1883. In 1904 Hashimoto described another condition of invasive fibrous thyroiditis. Since then it has been discussed if Hashimoto's thyroiditis and Riedel's goitre were one disease in different states or two different diseases. Hashimoto's thyroiditis is known to have an autoimmune aetiology and it can be seen together with pernicious anaemia. Co-existence of Riedel's goitre and pernicious anaemia has never been reported. The patient mentioned had both Riedel's goitre and pernicious anaemia, and was first treated with subtotal thyroidectomy, relapsed after one year and consequently received steroids. Such coexistence and the very good effect of steroids could be explained on the basis of Hashimoto's and Riedel's thyroiditis being one condition in different states and with an autoimmune aetiology. It is recommended that patients with Riedel's goitre are postoperatively treated with steroids.

Diagnosis, Differential↗
PubMed1989

[Incest. A descriptive study of incest registered at the department of social medicine in Copenhagen during the period Jan. 1, 1987-Dec. 31, 1987].

The object of this investigation was to describe the cases of suspected incest registered in the Department of Social Medicine in the Municipality of Copenhagen in the course of the year 1987. A total of 19 cases were registered. In these, 22 children and adolescents were involved in incestuous relationships; 15 girl and 7 boys. The cases were complicated and far from uniformly illustrated. The differences between the results of the cases where the social authorities were concerned and where the legal prosecuting authorities and the police are described. This difference is expressed by the fact that 13 out of the 22 victims of incest were taken into care outside the home. In addition, 12 out of 22 victims of incest received psychological help. Ten out of 19 cases were reported to the police but a sentence was passed in one case only. Increased training is required for the professional persons involved, and a broad selection of therapeutic proposals should be offered to all of the families concerned, harmonizing with various instances particularly social and health authorities and the police and legal authorities.

Adolescent↗
PubMedDate not supplied

Co-existence of osteogenesis imperfecta and hyperparathyroidism.

Osteogenesis imperfecta (OI) and hyperparathyroidism (HTP) are disorders affecting the skeletal system and calcium metabolism not evidently related to one another. We report a case in which both OI and HPT were present. Our female patient presented with hypercalcaemia (S-Ca2+ 1.59 mmol/l; normal range 1.15-1.30) and 4-gland parathyroid hyperplasia at 30 years of age. Since her first year she had fractures, blue sclera, hypermobile joints, short stature (height 1.51 m, weight 49.5 kg) but normal hearing, and dentiogenesis imperfecta (tooth disease caused by defective formation of dentin) was absent. This patient bears many similarities with the 5 patients reported previously but it is the only patient, to our knowledge, with OI and early onset of HPT (30 year old female). We have found the OI to be type 1. A minor improvement of the rate of bone turnover 10 months after parathyroidectomy indicates the HPT to be primary and suggests the OI type 1 and pHPT to be two different calcium metabolic diseases incidentally occurring in the same patient.

Adult↗
PubMedDate not supplied

Ultrasound measurement of the horizontal external eye muscles in patients with thyroid disease. Is orbital involvement associated with thyroid autoantibodies?

PURPOSE: To describe ophthalmic findings with emphasis on exophthalmometry and ultrasonic assessment of extraocular eye muscle diameter in a consecutive group of females with Graves' disease (GD), compared with healthy controls and patients with other thyroid diseases. We also investigated the relationship with biochemical markers of thyroid autoimmunity such as TSH receptor antibodies (TRAb) and anti-thyroid peroxidase antibodies (anti-TPO). METHODS: Seventy adult women (age 26-74 years) with various types of thyroid disease consecutively entered the study at a tertiary referral center for thyroid-associated ophthalmopathy (TAO). Twenty-three had long-standing GD with TAO. Clinically, TAO was mainly absent in 22 with newly diagnosed GD and in seven with relapse of GD. Nine with Hashimoto's thyrolditis and nine with multinodular goiter were included for comparison and 18 healthy females served as controls. A full ophthalmic status included B-scan ultrasonic assessment of the four horizontal rectus muscle thicknesses, and a clinical NOSPECS score was attempted for each. RESULTS AND CONCLUSIONS: Besides higher NOSPECS scores, the TAO subgroup had higher exophthalmometry and muscle thickness. The GD groups without significant TAO also scored higher in these ratings compared to controls. Hertel recordings, NOSPECS and muscle thicknesses were all correlated in GD but showed no correlation to thyroid antibodies (TRAb and anti-TPO). Thus, the muscle thickness did not correlate with thyroid autoimmune activity. Nevertheless, we found extraocular muscle assessment useful since a) thicker muscles were usually found in patients with GD, with or without evidence of TAO, and b) other space-occupying orbital lesions could be excluded, thereby reducing the need for the more elaborate imaging techniques (CT, MRI, etc.).

Adult↗