Abstract. We studied the blocking type TSH receptor antibodies in 28 patients with primary myxedema and 21 patients with goitrous Hashimoto's thyroiditis by measuring the ability of their IgGs to inhibit TSH binding to its receptor, and to inhibit TSH-stimulated cAMP increase and [3H] thymidine incorporation in a rat thyroid cell line, FRTL-5. The incidences of TSH binding inhibitor immunoglobulin, thyroid stimulation inhibiting immunoglobulin and thyroid growth inhibiting immunoglobulin in patients with primary myxedema were 54.6, 75 and 65.2%, respectively, against 14.3,0 and 17.7%, respectively, in goitrous Hashimoto's thyroiditis. The antibodies inhibited dose-dependently not only TSH stimulated but also Graves' IgG-stimulated cAMP increase and [3H] thymidine incorporation. The TSH binding inhibitor immunoglobulin activities in patients with primary myxedema were significantly correlated with both the thyroid stimulation inhibiting immunoglobulin (r = 0.665; P<0.01) and the thyroid growth inhibiting immunoglobulin (r = 0.618; P<0.01) activity. Thirteen patients whose TSH binding inhibitor immunoglobulin activities were more than 50% had both strong thyroid stimulation inhibiting immunoglobulin (75.1–100%) and thyroid growth inhibiting immunoglobulin (57.4–100%) activities. These data suggest that the vast majority of patients with primary myxedema have potent blocking type TSH receptor antibodies. These might play a role in primary myxedema causing hypothyroidism and thyroid atrophy through inhibiting TSH-stimulated cAMP generation.
B. Y. Cho, Y. K. Shong, H. K. Lee, C.-S. Koh and H. K. Min
Abstract. A 40-year-old male who developed Graves' hyperthyroidism following primary hypothyroidism is reported. He presented with clinical signs of hypothyroidism and concomitant myasthenia gravis. The thyroid was not palpable. He was treated with T4, pyridostigmine and prednisolone. One year later he developed hyperthyroidism and goitre. His initial serum IgG had no intrinsic thyroid stimulating activity, but showed almost complete inhibition of TSH-stimulated cAMP generation (99.4%, normal <38%) and [3H]thymidine incorporation (99.5%, normal<40%) into rat thyroid cells, FRTL-5 cells, with very high activity (80.2%, normal <15%) of TSH binding inhibitor immunoglobulin. When he developed hyperthyroidism and goitre, his IgG showed a strong thyroid stimulation, both cAMP production (27-fold increase) and [3H]thymidine incorporation (5.5-fold increase). No inhibitory activities were noted. These findings suggest that clinical states of autoimmune thyroid diseases can be changed in accordance with changes of functional properties of TSH receptor antibodies.
Byung J Lee, Jin H Kim, Chae K Lee, Hae M Kang, Hyun C Kim and Sung G Kang
Lee BJ, Kim JH, Lee CK, Kang HM, Kim HC, Kang SG. Changes in mRNA levels of a pituitary-specific trans-acting factor, Pit-1, and prolactin during the rat estrous cycle. Eur J Endocrinol 1995;132:771–6. ISSN 0804–4643
The present study examined the changes in mRNA levels of a pituitary-specific trans-acting factor, Pit-1, and prolactin during the rat estrous cycle. Total cytoplasmic RNA was analyzed by Northern blot and slot-blot hybridization to examine the prolactin mRNA level. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to examine the Pit-1 mRNA level. Proestrous and estrous prolactin mRNA levels were significantly higher than the metestrous and diestrous levels, whereas Pit-1 mRNA levels of the estrous and metestrous stages were about two- to threefold higher than those of the proestrous and diestrous stages. Proestrous Pit-1 mRNA levels increased gradually from 10.00 h to 20.00 h, while prolactin mRNA levels slightly decreased until 14.00 h but increased later until 20.00 h. During the rat estrous cycle, especially in the afternoon of the proestrous day, changes of prolactin mRNA levels seem to follow a prior increase of Pit-1 mRNA. Therefore, Pit-1 may be partly involved in the regulation of prolactin gene expression according to the rat estrous cycle. Estradiol administration to ovariectomized rats significantly increased both the mRNA levels of prolactin and Pit-1, which suggests that the gene expression of Pit-1 is regulated by estrogen through indirect extracellular pathways.
Byung Ju Lee, Department of Biology, College of Natural Sciences, University of Ulsan 680-749, Ulsan, South Korea
S G Kim, H Y Kim, J A Seo, K W Lee, J H Oh, N H Kim, K M Choi, S H Baik and D S Choi
Objectives: We aimed to investigate the relationship between nonalcoholic fatty liver disease (NAFLD), serum adiponectin concentration and brachial-ankle pulse wave velocity (baPWV) as a risk marker for atherosclerosis.
Methods: A total of 213 nonalcoholic subjects (67 males, 146 females) participated in this study. Division of subjects into the NAFLD group or the normal group was based on the existence of fatty liver detected by sonography.
Results: Serum adiponectin levels in the NAFLD group were significantly lower than those in the normal group. After adjusting for age, body-mass index (BMI) and the homeostasis model of assessment (HOMA), there was a significant negative correlation between NAFLD and serum adiponectin level only in females (r = −0.22, P = 0.008). Multiple logistic regression analysis showed a tendency of inverse correlation between NAFLD and serum adiponectin level in females (P = 0.055). After adjustment for age, BMI and HOMA value, serum adiponectin levels were inversely correlated with serum alanine aminotransferase (ALT) and gamma-glutamyltranspeptidase (GGT) levels (r = −0.199 (P = 0.004) and r = −0.282 (P < 0.001)). On the other hand, baPWV in the NAFLD group was also significantly higher than that in the normal group in females (P = 0.005). Individual levels of serum ALT, aspatate aminotransferase (AST), alkaline phosphatase (ALP) and GGT were positively correlated with baPWV after adjusting for age, sex, BMI, HOMA and systolic blood pressure (P < 0.05).
Conclusion: Serum adiponectin level and baPWV were significantly associated with NAFLD and various liver enzymes, especially in females.
K M Choi, J S Lee, E J Kim, S H Baik, H S Seo, D S Choi, D J Oh and C G Park
Visfatin and lipocalin-2 are novel adipokines associated with insulin resistance (IR) and obesity-related metabolic disorders. We compared lipocalin-2 and visfatin concentrations between patients with coronary heart disease (CHD) and control subjects and evaluated their association with cardiovascular risk factors.
We examined serum visfatin, lipocalin-2 levels, and cardiovascular risk factors in 91 subjects (49 patients with angiographically confirmed CHD versus 42 age- and gender-matched control participants).
Circulating lipocalin-2 levels were significantly higher in patients with CHD compared with the control subjects (82.6±38.7 ng/ml versus 43.8±27.8 ng/ml; P<0.001). However, visfatin levels were not significantly different between patients with CHD and control subjects. Serum lipocalin-2 levels were positively associated with weight (r=0.26; P=0.036), fasting insulin (r=0.36; P=0.003), and IR (r=0.33; P=0.007), whereas these levels showed a negative correlation with high-density lipoprotein (HDL) cholesterol (r=−0.30; P=0.016) after adjustment for gender and body mass index. However, visfatin levels were not associated with any variables of the metabolic syndrome. The multiple regression analysis showed that lipocalin-2 levels were independently associated with HDL cholesterol and IR (R 2=0.199). Furthermore, the multiple logistic regression analysis showed that systolic blood pressure, IR, and lipocalin-2 levels were independently associated with CHD.
Serum lipocalin-2 levels were significantly elevated in patients with CHD and were independently associated with CHD. The present findings suggest that the measurement of serum lipocalin-2 levels may be useful for assessing CHD risk.
D B Allen, P Backeljauw, M Bidlingmaier, B M K Biller, M Boguszewski, P Burman, G Butler, K Chihara, J Christiansen, S Cianfarani, P Clayton, D Clemmons, P Cohen, F Darendeliler, C Deal, D Dunger, E M Erfurth, J S Fuqua, A Grimberg, M Haymond, C Higham, K Ho, A R Hoffman, A Hokken-Koelega, G Johannsson, A Juul, J Kopchick, P Lee, M Pollak, S Radovick, L Robison, R Rosenfeld, R J Ross, L Savendahl, P Saenger, H Toft Sorensen, K Stochholm, C Strasburger, A Swerdlow and M Thorner
Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that ‘for approved indications, GH is safe’; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.