bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of 1-year treatment with interferon-beta1b on thyroid function and autoimmunity in patients with multiple sclerosis
Authors: Monzani F , Caraccio N , Meucci G , Lombardo F , Moscato G , Casolaro A , Ferdeghini M , Murri L , Ferrannini E
Published: January 2005

OBJECTIVE: Interferon-beta (IFN-beta) is a widely used therapy for multiple sclerosis (MS), a demyelinating disease of the central nervous system. This study has evaluated the effect on thyroid function and autoimmunity of a 1-year treatment with IFN-beta1b in patients with MS. PATIENTS: We studied 31 patients (age 34+/-7 years, 21 women) with relapsing-remitting MS during IFN-beta1b treatment of 1 year duration. Systematic thyroid assessment and measurements of serum interleukin-6 (IL-6) levels were performed at baseline and every 3 months during treatment. RESULTS: Sixteen percent of the patients had autoimmune thyroiditis before IFN-beta1b, all positive for anti-peroxidase antibodies. The overall incidence of thyroid dysfunction was 33% over 1 year (10% hyperthyroidism, 23% hypothyroidism). Thyroid autoimmunity developed in 5/26 patients (19%), in one case without dysfunction. In addition to autoantibody positivity at baseline, female gender and the presence of an ultrasound thyroid pattern suggestive of thyroiditis were identified by multiple logistic regression as additional risk predictors for the development of thyroid dysfunction. During IFN-beta1b treatment, serum IL-6 levels rose in a consistent biphasic pattern; there was, however, no difference between patients with or without incident thyroid abnormalities. CONCLUSIONS: We conclude that IFN-beta1b therapy can induce multiple alterations in thyroid function, some of which are unrelated to thyroid autoimmunity. IL-6 measurement is not useful to identify patients prone to develop thyroid abnormalities. Though thyroid dysfunction is generally subclinical and often transient, systematic thyroid assessment should be performed during IFN-beta1b treatment.
Standardized grey scale ultrasonography in Graves' disease: correlation to autoimmune activity
Authors: Schiemann U , Gellner R , Riemann B , Schierbaum G , Menzel J , Domschke W , Hengst K
Published: January 2005

OBJECTIVE: Graves' disease leads to thyroid enlargement and to reduction of tissue echogenicity. Our purpose was to correlate grey scale ultrasonography of the thyroid gland with clinical and laboratory findings in patients with Graves' disease. DESIGN: Fifty-three patients with Graves'disease were included in our study, 100 euthyroid volunteers served as control group. Free thyroxine (FT(4)), TSH and TRAb (TSH receptor antibodies) values were measured and correlated with sonographic echogenicity of the thyroid gland. METHODS: All patients and control persons underwent ultrasonographical histogram analyses under standardized conditions. Mean densities of the thyroid tissues were determined in grey scales (GWE). RESULTS: Compared with controls with homogeneous thyroid lobes of normal size (25.6 +/- 2.0GWE, mean +/- S.D.) echogenicity in patients with Graves' disease was significantly lower (21.3 +/- 3. 3GWE, mean +/- S.D., P < 0.0001). Among the patients with Graves' disease significant differences of thyroid echo levels were revealed for patients with suppressed (20.4 +/- 3.1 GWE, mean +/- S.D., n=34) and normalized TSH values (22.5 +/- 3.6GWE, mean +/- S.D., n=19, P < 0.02). Significantly lower echogenicities were also measured in cases of persistent elevated TRAb levels (19.9 +/- 2.9GWE, mean +/- S.D., n=31) in comparison with normal TRAb levels (22.9 +/- 3.5 GWE, mean +/- S.D., n=22, P < 0.0015). No correlation could be verified between echogenicity and either still elevated or already normalized FT(4) values or the thyroid volume. In coincidence of hyperthyroidism and Graves' ophthalmopathy (19.7 +/- 3.5GWE, mean +/- S.D., n=23) significantly lower echogenicity was measured than in the absence of ophthalmological symptoms (22.3 +/- 3.3GWE, mean +/- S.D., n=30, P < 0.016). Patients needing active antithyroid drug treatment revealed significantly lower thyroid echogenicity (20.3 +/- 3.1 GWE, mean +/- S.D., n=40) than patients in remission (23.7 +/- 3.4 GWE, mean +/- S.D., n=13, P < 0.001). Statistical evaluation was carried out using Student's t-test. CONCLUSIONS: Standardized grey scale histogram analysis allows for supplementary judgements of thyroid function and degree of autoimmune activity in Graves' disease. Whether these values help to estimate the risk of recurrence of hyperthyroidism after withdrawal of antithyroid medication should be evaluated in a prospective study.
Changes in metabolism of TRH in euthyroid sick syndrome
Authors: Duntas LH , Nguyen TT , Keck FS , Nelson DK , Iii JJ
Published: January 2005

OBJECTIVE: The aim of this study was to examine the metabolism of a simple dose, intravenously administered TRH bolus of 200 microg, in patients with euthyroid sick syndrome (ESS). PATIENTS AND METHODS: A TRH test was performed on ten ESS patients and ten controls upon admission (d1) and after recovery (d2). Blood samples were collected at 0, 10, 20 and 30min after TRH injection. We analyzed the volume of distribution (V(d)), the plasma clearance rate (PCR), the fractional clearance rate (FCR), the half-life (t(1/2)) and the TSH response to the injection of TRH. RESULTS: All patients had lower tri-iodothyronine (T(3)) levels compared with controls (0.9 +/- 0. 1nmol/l vs 1.9 +/- 0.1 nmol/l; P < 0.0001; mean +/- S.D.; paired t-test). In addition, the V(d) (16.7 +/- 5.9/l vs 30.6 +/- 0.6/l; P < 0.0005) and PCR (2.0 +/- 0.80 l/min vs 3.3 +/- 0.25 l/min; P <0. 0005) were found statistically lowered in patients than in controls, whereas FCR (0.119 +/- 0.01 permin vs 0.110 +/- 0.01 per min; P < 0. 025) was found increased in patients as opposed to controls. The t(1/2) of exogenously administered TRH was increased in ESS compared with controls (7.2 +/- 0.7 min vs 6.3 +/- 0.6 min; P <0.005). TSH response to TRH was found significantly repressed at 10, 20 and 30 min after TRH injection. On d2, these findings had reverted to normal and no changes regarding the kinetics of TRH and the response of TSH could be detected between patients and controls. CONCLUSIONS: The results demonstrate an impairment of TRH metabolism in ESS. The findings may suggest altered enzymatic activity, responsible for TRH degradation in states of acute ESS. These changes might be involved in the pathogenesis of ESS and represent part of an adaptive mechanism to this syndrome.
Effect of 6 months of GH treatment on myosin heavy chain composition in GH-deficient patients
Authors:   Daugaard, Bramnert M , Manhem P , Endre T , Groop LC , Lofman M , Richter EA
Published: January 2005

OBJECTIVE: To investigate the effect of GH on myosin heavy chain (MHC) isoform composition, physical fitness and body composition in GH-deficient (GHD) patients. DESIGN: Twenty-two GHD patients were randomized in a double blind manner and half were treated with recombinant human GH (rhGH) and half were treated with placebo for 6 months. Twelve age-matched controls were also included in the study. METHODS: MHC isoform composition in biopsies obtained from the vastus lateralis muscle was determined using SDS-PAGE. Physical fitness was determined on a bicycle ergometer and body composition was determined using bioelectrical impedance analysis. RESULTS: More MHC IIX (28.9 +/- 4.1% and 10.0 +/- 3.1% in GHD and controls respectively (means +/- S.E.M.)) and less MHC I (36.2 +/- 2.4% and 51.7 +/- 3.9% in GHD and controls respectively (means +/- S.E.M.)) were present in the GHD patients compared with the controls. No significant difference in the amount of MHC IIA was detected. Linear regression was used to determine the relationship between variables. There were no significant relationships between the concentration of insulin-like growth factor-I (IGF-I) or the body composition and the MHC composition. Maximal oxygen uptake (VO(2)max) per kg body weight (BW) (litres/min per kg) correlated significantly with the amount of MHC I (r=0.60) and MHC IIX (r=-0.72) but not with the amount of MHC IIA (r=0.35). Treatment of GHD patients with rhGH for 6 months increased the concentration of IGF-I, lean body mass and decreased fat mass but had no effect on MHC composition and physical fitness. CONCLUSIONS: We conclude that a major part of the differences in MHC composition between GHD patients and age-matched controls can be explained by variation in physical fitness. The severity of the GHD and the body composition does not seem to be important for the MHC composition. Furthermore, treatment with GH for 6 months does not affect MHC composition in GHD patients.
Serum reg protein level is not related to the beta cell destruction/regeneration process during early phases of diabetogenesis in type I diabetes
Authors: Christofilis MA , Carrere J , Atlan-Gepner C , Zevaco-Mattei C , Thivolet C , Baeza N , Figarella C , Vialettes B
Published: January 2005

OBJECTIVE: In type I diabetes mellitus, early markers of beta cell damage are needed in order to detect the infraclinical development of the disease. The reg protein may be a good candidate, as the reg gene has been proposed to play a role in the pancreatic beta cell destruction/regeneration process during diabetogenesis in animal models of autoimmune diabetes. The aim of this study was to test the hypothesis whether serum reg protein level could be representative of either the destructive or regenerative process at the beta cell level during the early phases of type I diabetes in humans. DESIGN AND METHODS: We used a highly specific immunoassay to measure serum reg protein level in controls and in three groups of either diabetes prone or diabetic subjects: recently diagnosed diabetic patients, long-standing diabetic patients and islet cell antibody-positive non-diabetic subjects. RESULTS: We found no significant difference between the values observed in these three groups in comparison with control group (90.7+/-18.1ng/ml, 83.1+/-5.6ng/ml, 98.7+/-24.5ng/ml vs 85.5+/- 5.6ng/ml respectively). Moreover, when the insulin reserve was evaluated at 6 months in the recently diagnosed group, serum reg protein levels were not different between patients with or without residual insulin secretion (at onset: 103+/-42 vs 70.3+/-8. 5ng/ml respectively; at 6 months: 79.7+/-25.8ng/ml vs 81.6+/-15ng/ml respectively). In contrast, trypsin levels were significantly lower in every group of diabetic patients. Results were expressed as means +/- S.E.M. and groups compared by Student's t-test (P<0.05). CONCLUSIONS: We conclude that serum reg protein level cannot be used as a marker for the progression of the diabetogenic process in type I diabetes.
Neonatal diabetes mellitus with hypergalactosemia
Authors: Kentrup H , Altmuller J , Pfaffle R , Heimann G
Published: January 2005

We report the case of a male, small-for-gestational-age newborn who presented with failure to thrive, severe fluctuation of blood glucose concentrations, and increased serum concentrations of galactose. The infant responded well to a lactose-free diet supplemented with fructose, inulin and corn starch. The metabolic disorder disappeared within 6 months. The transient course, and results of a molecular analysis of the glucose transporter 2 (Glut2) gene seem to rule out Fanconi-Bickel syndrome.
Dopamine agonists both stimulate and inhibit prolactin release in GH4ZR7 cells
Authors: Chang A , Shin SH
Published: January 2005

Prolactin secretion from the anterior pituitary gland is regulated by multiple factors including prolactin-release inhibiting factors (PIFs) and prolactin releasing factors. PIFs, however, usually dominate to exert a tonic inhibition in the biological system, and the physiological PIF is believed to be dopamine. However, there is accumulating evidence that dopamine can not only inhibit but also stimulate prolactin release. Many investigators believe that this is achieved by activating inhibitory and stimulatory subtypes of dopamine receptors. We tried to demonstrate that one subtype of dopamine receptors is capable of both inhibiting or stimulating prolactin release using GH(4)ZR(7) cells. GH(4)ZR(7) cells express only a short form of dopamine D(2) receptors (D(2s)). Low concentrations of three well-established D(2) receptor agonists (dopamine, apomorphine and bromocriptine) stimulated prolactin release from GH(4)ZR(7) cells while high concentrations inhibited the release. Haloperidol, a D(2) receptor antagonist, blocked the inhibitory action, but was unable to block the dopamine-induced stimulatory action. Pretreatment of cells with phenoxybenzamine, a receptor alkylating agent, abolished both the dopamine-induced stimulatory and inhibitory actions. Our results support the thesis that the stimulation of prolactin release induced by dopamine is mediated through dopamine D(2s) receptors since the GH(4)ZR(7) cells have only D(2s) receptors among dopamine receptors. We have concluded that the D(2s) receptor is capable of both stimulating and inhibiting prolactin release, probably via the activation of a G(s) protein by low concentrations and a G(i) protein by high concentrations of dopaminergic agents.
Somatostatin and its analog lanreotide inhibit the proliferation of dispersed human non-functioning pituitary adenoma cells in vitro
Authors: Florio T , Thellung S , Arena S , Corsaro A , Spaziante R , Gussoni G , Acuto G , Giusti M , Giordano G , Schettini G
Published: January 2005

OBJECTIVE: Somatostatin is a powerful inhibitor of hormone secretion and cell proliferation. Treatment with somatostatin analogs in humans causes a reduction in size and secretory activity of some endocrine tumors, including somatotropic pituitary adenomas. Less studied are the effects of somatostatin agonists on non-functioning pituitary adenomas (NFPAs). In this study we characterized the effects of somatostatin and its analog lanreotide on the proliferation of NFPAs in vitro and the intracellular mechanisms involved. DESIGN: Twenty-three NFPA post-surgical specimens were analyzed for somatostatin receptor (SSTR) expression and 12 of them were cultured in vitro to study somatostatin's effects on cell proliferation, assessed by means of [(3)H]thymidine uptake, and the intracellular signaling. RESULTS: One or more SSTR subtypes were expressed in 90% of the adenomas tested. Somatostatin and lanreotide treatment inhibited phorbol myristate acetate (PMA)-induced cell proliferation. Vanadate pretreatment reversed somatostatin and lanreotide inhibition of PMA-induced DNA synthesis suggesting an involvement of tyrosine phosphatase in this effect. In the only adenoma tested, somatostatin directly induced a tyrosine phosphatase activity. Somatostatin and lanreotide caused also a significant inhibition of voltage-sensitive calcium channel activity induced by 40mmol/l K(+) depolarization in microfluorimetric analysis. CONCLUSIONS: These data show that somatostatin and lanreotide inhibit human NFPA cell proliferation in vitro, and suggest that activation of tyrosine phosphatases and inhibition of the activity of voltage-dependent calcium channels may represent intracellular signals mediating this effect.
Human lymphocytes express hGH-N gene transcripts of 22kDa, 20kDa and minor forms of GH, but not hGH-V gene
Authors: Hattori N , Kitagawa K , Inagaki C
Published: January 2005

Expression of human growth hormone (hGH) in lymphocytes was examined by reverse transcription polymerase chain reaction (RT-PCR) in five normal subjects. Transcripts of hGH-N gene, but not hGH-V gene, were detected. Sequence analysis revealed four kinds of transcripts: 22kDa GH, 20kDa GH and two other forms of variant GH. The 20kDa GH transcript was generated by alternative splicing within exon 3, resulting in a 45bp deletion. One of the variant GH transcripts was also generated by alternative splicing within exon 3, but at a different site, resulting in a 73bp deletion. Because of a frameshift, this variant GH transcript may encode a 6.6kDa protein (truncated GH) that structurally differs from that of 22kDa GH after residue 31. In the other variant GH mRNA, exons 3 and 4 were completely skipped. The proportions of expression of 22kDa GH, 20kDa GH and the truncated GH were 60.9+/-13.6 (+/-S.D.)%, 32.7+/-14.1% and 6.4+/-1.1% (n=5), respectively, by comparative RT-PCR.We conclude that human lymphocytes, like the pituitary gland, express hGH-N gene transcripts of mainly 22kDa GH, but also 20kDa GH and minor variant forms of GH.
Adaptation of pancreatic islet B-cells during the last third of pregnancy: regulation of B-cell function and proliferation by lactogenic hormones in rats
Authors: Kawai M , Kishi K
Published: January 2005

In rodents, placental lactogen (PL)-I is considered to be the first trigger to enhance pancreatic islet B-cell function, and after its secretion is diminished at mid-pregnancy, PL-II takes over this role. However, little information is available on the regulation of islet B-cell function and proliferation by lactogenic hormones during the last third of pregnancy. This was the focus of the present study using rats in which pregnancy was forcibly prolonged. This rat possesses unique characteristics in that PL-I is re-secreted during the prolonged period of pregnancy and the peak concentrations in maternal circulation are comparable with those observed during mid-pregnancy in normal-pregnancy rats. Pregnancy was prolonged by successive administration of pregnant mare's serum gonadotropin (30IU/rat, s.c. on day 12) and human chorionic gonadotropin (10IU/rat, i.v. on day 14). When the insulin secretory responses to 10mmol/l glucose in islets obtained from normal-pregnancy and prolonged-pregnancy rats were tested, each insulin secretory response correlated well with the values of plasma lactogenic activity throughout the period of pregnancy and lactation. Examination of B-cell proliferation in normal-pregnancy rats showed that 5-bromo-2'-deoxyuridine (BrdU) incorporation into dividing B-cells reached a maximum on day 15 and then decreased markedly towards term. No increase in B-cell proliferation was observed on day 19 when plasma lactogenic activity reached the maximum. In prolonged-pregnancy rats, BrdU incorporation also continued to decrease as observed in normal-pregnancy rats after day 15, and then no enhancement in B-cell proliferation was observed even when the plasma lactogenic activity, including re-secreted PL-I, reached maximum. These results suggest that, in the last third of pregnancy, B-cell proliferation is no longer stimulated by lactogenic hormones in contrast to the insulin secretory response which is sustained.
Changes in uterine ornithine decarboxylase activity and steroid receptor levels during decidualization in the rat induced by CDRI-85/287
Authors: Dwivedi A , Gupta G , Keshri G , Dhar JD
Published: January 2005

CDRI-85/287 is an anti-estrogen and interferes with decidualization in the rat uterus. In this study, uterine estrogen receptor (ER) and progesterone receptor (PR) levels were determined during the inhibition of decidualization. The effect of 85/287 on uterine ornithine decarboxylate (ODC) activity (a marker enzyme for decidualization) was also studied, using immature ovariectomized rats divided into four different groups: control, 2.5mg/kg 85/287 only; 1 microg estradiol only; and 85/287 + estradiol. Pseudopregnant rats were administered 85/287 (2.5mg/kg p.o.) on day 3 post-coitum. Deciduoma was induced in one of the uterine horns on day 4 and animals were autopsied 18h post-traumatization. Both ERs and PRs showed an increase in traumatized horns compared with non-traumatized. In the 85/287-treated uterus, there was a reduction in cytosolic ERs in both traumatized horns. However, nuclear ER and PR levels increased in both horns under the influence of 85/287. Similarly, in a tamoxifen (0.03mg/kg)-treated group a decline was noticed in cytosolic ER with a mild increase in nuclear PR. Total ER content, expressed per 100 microg DNA, showed a decline in 85/287- or tamoxifen-treated rats. However, no significant alterations were observed in total PR levels in non-traumatized horns. In an immature rat model, 85/287 caused a significant (>50%) reduction in estradiol-induced ODC activity. These findings suggest that the decidualization inhibitory activity of 85/287 may be attributed to inhibition of certain timed biochemical events and genomic/non-genomic actions of estrogens in the rat uterus.
Regulation of neuropeptide Y mRNA expression in cultured human pheochromocytoma cells
Authors: Liu J , Kahri AI , Heikkila P , Voutilainen R
Published: January 2005

The expression of the neuropeptide Y (NPY) gene varies considerably in human pheochromocytomas, but the mechanisms for this variation have not been clarified. To investigate the regulation pattern of the NPY gene in human pheochromocytomas, we screened 16 pheochromocytomas and 9 normal adrenal tissues with Northern blots. The expression level of NPY mRNA in normal adrenal medulla was low and relatively constant, while the pheochromocytomas showed a very wide variation in NPY mRNA levels in both malignant and benign tumors. This indicates that NPY gene expression is not correlated with malignancy in pheochromocytomas. In primary cultures of human pheochromocytoma cells, nerve growth factor treatment (causing neuronal differentiation) increased NPY mRNA accumulation 2- to 5-fold (P < 0.05). NPY mRNA levels were also induced by protein kinase modulators (Bu)(2)cAMP and staurosporine in the cultures (P < 0.05). In contrast, treatment with dexamethasone and IGF-II (causing or linked with chromaffin differentiation) reduced NPY mRNA accumulation (P < 0.05). These data show that the regulation pattern of NPY mRNA expression in cultured human pheochromocytoma cells is different from that previously described in rat pheochromocytoma PC12 cells. Regulation of NPY mRNA expression in primary cultures by these differentiating factors suggests that the expression of NPY mRNA in pheochromocytoma tissues may be associated with the neuronal differentiation of the tumor cells affected by multiple factors.
Sodium/iodide symporter: a key transport system in thyroid cancer cell metabolism
Authors: Filetti S , Bidart JM , Arturi F , Caillou B , Russo D , Schlumberger M
Published: January 2005

The recent cloning of the gene encoding the sodium/iodide symporter (NIS) has enabled better characterization of the molecular mechanisms underlying iodide transport, thus opening the way to clarifying its role in thyroid diseases. Several studies, at both the mRNA and the protein expression levels, have demonstrated that TSH, the primary regulator of iodide uptake, upregulates NIS gene expression and NIS protein abundance, both in vitro and in vivo. However, other factors, including iodide, retinoic acid, transforming growth factor-beta, interleukin-1alpha and tumour necrosis factor alpha, may participate in the regulation of NIS expression. Investigation of NIS mRNA expression in different thyroid tissues has revealed increased levels of expression in Graves' disease and toxic adenomas, whereas a reduction or loss of NIS transcript was detected in differentiated thyroid carcinomas, despite the expression of other specific thyroid markers. NIS mRNA was also detected in non-thyroid tissues able to concentrate radioiodine, including salivary glands, stomach, thymus and breast. The production of specific antibodies against the NIS has facilitated study of the expression of the symporter protein. Despite of the presence of high levels of human (h)NIS mRNA, normal thyroid glands exhibit a heterogeneous expression of NIS protein, limited to the basolateral membrane of the thyrocytes. By immunohistochemistry, staining of hNIS protein was stronger in Graves' and toxic adenomas and reduced in thyroid carcinomas. Measurement of iodide uptake by thyroid cancer cells is the cornerstone of the follow-up and treatment of patients with thyroid cancer. However, radioiodide uptake is found only in about 67% of patients with persistent or recurrent disease. Several studies have demonstrated a decrease in or a loss of NIS expression in primary human thyroid carcinomas, and immunohistochemical studies have confirmed this considerably decreased expression of the NIS protein in thyroid cancer tissues, suggesting that the low expression of NIS may represent an early abnormality in the pathway of thyroid cell transformation, rather than being a consequence of cancer progression. The relationship between radioiodine uptake and NIS expression by thyroid cancer cells require further study. New strategies, based on manipulation of NIS expression, to obtain NIS gene reactivation or for use as NIS gene therapy in the treatment of radiosensitive cancer, are also being investigated.
Non-suppressed thyrotropin and elevated thyroglobulin are independent predictors of recurrence in differentiated thyroid carcinoma
Authors: Bohm J , Kosma VM , Eskelinen M , Hollmen S , Niskanen M , Tulla H , Alhava E , Niskanen L
Published: January 2005

OBJECTIVE: Although in most cases differentiated thyroid carcinoma (DTC) responds to surgery and radioiodine (RaI) therapy, some patients will have recurrence and eventually cancer-related death. However, although various prognostic factors of DTC have been identified (e.g. staging, suppressed thyrotropin), none of the previous studies have assessed simultaneously their role in multivariate analysis. DESIGN AND METHODS: In this retrospective population-based study, we reviewed the clinicopathological data of 254 DTC patients treated in eastern Finland during the years 1976-1995, for clinical characteristics, primary treatment, follow-up and cancer recurrence. Tumor stage was based on pathological tumor-node-metastasis (pTNM) classification, and histopathological specimens were re-evaluated. RESULTS: DTC recurrence occurred in 33 patients (13%). In univariate analyses, the predictors of recurrence were older age (>60 years, P<0.05), follicular tumor type (P<0.01), pTNM classification system (P<0.05) and post-ablative radioiodine uptake outside the neck (P<0.05). Non-suppressed serum thyrotropin (TSH) and elevated serum thyroglobulin (>3 microg/l) measured one year after operation were both related to tumor recurrence (P<0.05 and P<0.001 respectively). In multivariate analysis the independent predictors for recurrence were both elevated thyroglobulin (P<0.001) and non-suppressed TSH (P<0.05) independent of histology, pTNM stage and RaI uptake. Adjusted risk ratio for recurrence of DTC for unsuppressed thyrotropin was 2.3, for elevated thyroglobulin 14.0 and, if both conditions were present, the risk ratio increased to 45.1. CONCLUSION: Our results suggest that both non-suppressed serum TSH and elevated serum thyroglobulin are related to an increased risk of DTC recurrence independent of tumor type and pTNM stage.
Observational study in adult hypopituitary patients with untreated growth hormone deficiency (ODA study). Socio-economic impact and health status. Collaborative ODA (Observational GH Deficiency in Adults) Group
Authors: Sanmarti A , Lucas A , Hawkins F , Webb SM , Ulied A
Published: January 2005

OBJECTIVE: The aim of the present study was to assess the socio-economic impact at baseline and after one year of follow-up of clinical and health status characteristics and laboratory tests of adult-onset GH deficiency (AGHD), a well-known clinical entity, in a large group of Spanish hypopituitary patients with untreated AGHD. DESIGN AND METHODS: A total of 926 eligible patients with GHD (GH </= 5 ng/ml after stimulation) and at least one further pituitary hormone deficiency were retrospectively studied; 356 of these were followed for one year. Complete physical examination, IGF-I, lipid and routine biochemistry measurements and health-related quality of life (HRQoL) with the specific QoL-Assessment of Growth Hormone Deficiency in Adults (AGHDA) questionnaire were assessed at baseline and at 12 months in the prospective study. Health status and health-economic evaluation were measured by a specific questionnaire and a patient diary and compared with Spanish population study results. RESULTS: Clinical characteristics and laboratory tests of AGHD showed a higher incidence of cardiovascular risk factors and mortality compared with the general population (hypercholesterolaemia in 29% vs 18% and hypertension in 22.1% vs 14. 9%). QoL-AGHDA scores for patients were significantly worse (P<0.01) and direct health costs were higher than in the general population. CONCLUSIONS: Hypopituitary GHD adults had more cardiovascular risk factors, higher mortality, worse HRQoL and higher absolute health costs than the general population in Spain.
Amino acid variants of the vitamin D-binding protein and risk of diabetes in white Americans of European origin
Authors: Klupa T , Malecki M , Hanna L , Sieradzka J , Frey J , Warram JH , Sieradzki J , Krolewski AS
Published: January 2005

BACKGROUND: Genetic variants of vitamin D-binding protein (DBP) have been reported to be associated, not only with diabetes, but also with prediabetic traits, in several populations. There are two known polymorphisms in exon 11 of the DBP gene that result in amino acid variants: at codons 416 GAT-->GAG (Asp-->Glu) and 420 ACG-->AAG (Thr-->Lys). OBJECTIVE: To examine the association of these polymorphisms with diabetes in white Americans of European origin. METHODS: We studied unrelated individuals: 181 with type 1 diabetes, 215 with type 2 diabetes, and 163 healthy controls. Exon 11 was amplified using polymerase chain reaction and the two alleles were determined by digestion with specific endonucleases: HaeIII and StyI, respectively. RESULTS: At codon 416, Asp/Glu allele frequencies were 45%/55% in patients with type 1 diabetes, 43%/57% in patients with type 2 diabetes, and 46%/54% in controls (chi(2)=0.69, 2 d.f., P<0.71). At codon 420, corresponding Lys/Thr frequencies were 27%/73%, 30%/70%, and 30%/70% (chi(2)=1.25, 2 d.f., P=0.53). Distributions of genotypes at both loci, and the haplotypes defined by the two loci, were also very similar in all groups. CONCLUSION: DNA polymorphisms in the DBP gene are not associated with diabetes in white Americans of European origin.
Acquired lipoprotein lipase deficiency associated with chronic urticaria. A new etiology for type I hyperlipoproteinemia
Authors: Garcia-Otin AL , Civeira F , Peinado-Onsurbe J , Gonzalvo C , Llobera M , Pocovi M
Published: January 2005

Type I hyperlipoproteinemia (type I HLP) is a rare disorder of lipid metabolism characterized by fasting chylomicronemia and reduced postheparin plasma lipoprotein lipase (LPL) activity. Most cases of type I HLP are due to genetic defects in the LPL gene or in its activator, the apolipoprotein CII gene. Several cases of acquired type I HLP have also been described in the course of autoimmune diseases due to the presence of circulating inhibitors of LPL. Here we report a case of type I HLP due to a transient defect of LPL activity during puberty associated with chronic idiopathic urticaria (CIU). The absence of any circulating LPL inhibitor in plasma during the disease was demonstrated. The LPL genotype showed that the patient was heterozygous for the D9N variant. This mutation, previously described, can explain only minor defects in the LPL activity. The presence of HLP just after the onset of CIU, and the elevation of the LPL activity with remission of the HLP when the patient recovered from CIU, indicate that type I HLP was caused by CIU. In summary, we report a new etiology for type I HLP - a transient decrease in LPL activity associated with CIU and with absence of circulating inhibitors. This is the first description of this association, which suggests a new mechanism for type I HLP.
In vitro basal and GnRH-stimulated secretion of gonadotrophins reflects long-lasting modulatory effects, and peripheral levels are not predicted by pituitary responsiveness to GnRH
Authors: Evans JJ , Janmohamed S
Published: January 2005

OBJECTIVE: Production of the appropriate pattern of gonadotrophin levels is crucial to proper functioning of the female reproductive system. We aimed to establish whether the pituitary has invariant secretory characteristics when isolated from in vivo controls. We aimed to obtain information during both the rising and declining phases of the gonadotrophin surge. DESIGN: This study investigated factors that are directed at the pituitary by isolating it from the acute influences of the in vivo environment and studying gonadotrophin secretion in vitro. METHODS: Pituitaries of adult female rats were collected at selected times during the day of pro-oestrus and incubated in vitro, and at the same time blood was collected. Peripheral levels of LH and FSH were measured over the whole day of pro-oestrus, basal in vitro secretions of LH and FSH from pituitaries were measured, GnRH-stimulated LH and FSH secretion were assessed, and the responsiveness of LH and FSH secretion to GnRH were calculated. RESULTS: Peripheral levels of LH peaked at 1800 h (P<0.02) followed by a subsequent decline. In contrast, although FSH had a peak at 1800 h (P<0.01), serum levels were also high at the end pro-oestrus. The profile of basal LH and FSH secretion from the pituitary in vitro, in the absence of added secretagogue, resembled that of the peripheral blood levels of each gonadotrophin. Pituitaries collected at 1800 h secreted most LH (P<0. 02). FSH secretion was low early on the day of pro-oestrus and then increased to and was maintained at high levels in the last quarter of the day (P<0.01).When the pituitaries were stimulated with GnRH the patterns of LH release and FSH release approximated those observed for basal release. Responsiveness of the pituitaries to GnRH was calculated by determining the ratio of GnRH-stimulated release to basal release. However, low levels of gonadotrophin were secreted even from pituitaries which were highly responsive as determined from consideration of percentage increase in secretion induced by GnRH. CONCLUSIONS: The secretory activity was dependent on the time of day the pituitaries were collected. Since the secretion occurred after the tissue had been removed from the direct influence of the in vivo environment, the variations in secretion must reflect long-lasting components of the mechanism that regulate gonadotrophin concentrations. There were changes in both LH and FSH responsiveness to GnRH stimulation over the day of pro-oestrus. Delineation of the time courses and changing predominance of multiple processes is needed to assist understanding the mechanisms underlying the female reproductive cycle.
Effects of basic fibroblast growth factor and nerve growth factor on lactate production, gamma-glutamyl transpeptidase and aromatase activities in cultured Sertoli cells
Authors: Schteingart HF , Meroni SB , Canepa DF , Pellizzari EH , Cigorraga SB
Published: January 2005

Sertoli cells are under the control of FSH and androgens and also respond to polypeptidic factors locally produced. Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) have been proposed to belong to the large set of intratesticular regulators. The aim of the present investigation was to analyze the effects of bFGF and NGF on lactate production, gamma-glutamyl transpeptidase (gamma-GTP) and aromatase activities. Cultured Sertoli cells dose-dependently responded to bFGF by increasing lactate production and gamma-GTP activity under basal conditions. In FSH-stimulated cultures, a synergistic effect of FSH with bFGF for lactate production was observed. NGF did not produce changes in lactate production or gamma-GTP activity at any dose tested. Both peptides decreased FSH-stimulated aromatase activity. These results provide additional evidence for the participation of bFGF and NGF in the complex network of intratesticular regulators. bFGF has pleiotropic effects on Sertoli cell function while the actions of NGF seem to be more limited.
Does the use of mean or median Z-score of the thyroid volume indices provide a more precise description of the iodine deficiency disorder status of a population?
Authors: Foo LC , Mafauzy M
Published: January 2005

Endemic iodine deficiency is largely an environmental problem affecting whole populations. Currently, thyroid volume data from a population are analyzed with the sole objective of obtaining an estimate of goitre prevalence using +97th percentile or +2 standard deviations of an appropriate reference as cut-off. This paper proposes an alternative approach to the analysis and presentation of thyroid volume data using Z-scores (standard deviation scores) of the thyroid volume indices such as thyroid volume-for-age or thyroid volume-for-body surface area. The calculation of the summary statistics of the Z-scores, such as mean or median, provides an alternative to the prevalence-based approach for expressing severity of iodine deficiency disorders (IDD). An advantage of the mean or median Z-score is that it describes the thyroid volume profile (and therefore the IDD status) of the entire population directly, unlike goitre prevalence which gives information only about the extremes of distribution. The frequency curve or histogram of the Z-scores provides a complete picture of the whole distribution. Although qualitatively similar conclusions on IDD severity can be drawn from both analytical approaches, only the Z-score system is able to capture adequately the trends or changes in thyroid size over time, and to establish whether a previously iodine-deficient community's thyroid volume profile has returned to 'normal' (as indicated by a distribution that is not significantly different from that of the reference) following intervention. As a continuous variable, Z-scores are particularly useful for the analysis of data from populations where the sample size is relatively small, or where many individuals lie outside the extreme percentiles of the reference population. In view of its advantages in the context of activities based on single and multiple measurements, the Z-score system is to be preferred for the reporting and use of thyroid volume indices. A desirable consequence of this preference is that national goals will be oriented towards an improvement of the overall thyroid volume profile of the population, rather than just a reduction of the number of individuals at the extremes.
Multicenter study on TGPO autoantibody prevalence in various thyroid and non-thyroid diseases; relationships with thyroglobulin and thyroperoxidase autoantibody parameters
Authors: Estienne V , Duthoit C , Costanzo VD , Lejeune PJ , Rotondi M , Kornfeld S , Finke R , Lazarus JH , Feldt-Rasmussen U , Franke WG , Smyth P , D'Herbomez M , Conte-Devolx B , Persani L , Carella C ,   Jourdain, Izembart M , Toubert ME , Pinchera A , Weetman A , Sapin R , Carayon P , Ruf J
Published: January 2005

OBJECTIVE: TGPO autoantibodies (aAbs) that bind simultaneously to thyroglobulin (Tg) and thyroperoxidase (TPO) are present in the serum of patients with autoimmune thyroid diseases (AITD) and have been found to differ from monospecific Tg and TPO aAbs. To obtain further insights on the prevalence defined as the rate of occurrence and significance of TGPO aAbs in a large population, we carried out a collaborative study involving 15 European teams. METHODS: Serum samples from 3122 patients with various thyroid and non-thyroid diseases and normal subjects were assayed using a novel TGPO aAb detection kit. This test was designed so that TGPO aAbs are trapped between the Tg-coated solid phase and the soluble TPO labeled with a radioiodinated monoclonal antibody. RESULTS: Only three out of the 220 normal subjects (prevalence of 1.4%) were found to have positive TGPO aAb levels, which were mainly observed in the patients with AITD: the group of patients suffering from Hashimoto's thyroiditis had a TGPO aAb prevalence of 40.5% (n=437 patients), those with Graves' disease, a prevalence of 34.6% (n=645) and those with post-partum thyroiditis, 16.0% (n=243). Among the non-AITD patients with positive TGPO aAb levels, the TGPO aAb prevalence ranged from 20.7% among those with thyroid cancer (n=246) to 0% among those with toxic thyroid nodules (n=47). Among the patients with non-thyroid diseases, the TGPO aAb prevalence ranged from 9.8% in the case of Biermer's pernicious anemia (n=78) to 0% in that of premature ovarian failure (n=44). It is worth noting that the groups showing the highest TGPO aAb prevalence also contained the patients with the highest TGPO aAb titers. Statistical comparisons between the TGPO aAb prevalences in the various groups showed that TGPO aAb could be used as a parameter to distinguish between the groups of Hashimoto's and Graves' patients and between the women with post-partum thyroiditis and the post-partum women with only Tg and/or TPO aAb established during early pregnancy. Unexpectedly, the correlations between TGPO aAbs and Tg and TPO aAbs were found to depend mainly on the assay kit used. CONCLUSION: High TGPO aAb titers are consistently associated with AITD but the reverse was not found to be true. TGPO aAbs are a potentially useful tool, however, for establishing Hashimoto's diagnosis, and would be worth testing in this respect with a view to using them for routine AITD investigations.
Maternal compound W serial measurements for the management of fetal hypothyroidsm
Authors: Cortelazzi D , Morpurgo PS , Zamperini P , Fisher DA , Beck-Peccoz P , Wu SY
Published: January 2005

OBJECTIVE: The diagnosis of fetal hypothyroidism is based at present on measurements of TSH and free thyroxine (FT4) in fetal blood samples obtained by cordocentesis. The measurement of maternal serum and urinary concentrations of compound W, immunologically similar to but chromatographically distinct from diiodothyronine sulfate (T2S), has been advocated as a new possible marker for fetal hypothyroidism. DESIGN: In this paper, we measured serum compound W levels in 84 pregnant women, 20 with and 64 without thyroid disorders before and during specific treatment. Compound W was also assessed in fetal blood obtained by cordocentesis from 49 normal fetuses and 4 fetuses with suspected hypothyroidism due to transplacental passage of propylthiouracil (PTU). Compound W levels were measured by T2S RIA in maternal and fetal serum. To assess the possible usefulness of 3, 5,3'-triiodothyroacetic acid (TRIAC) for therapy of fetal hypothyroidism we evaluated the transplacental passage of TRIAC by administering the drug to four pregnant women before therapeutic abortion. RESULTS: In normal pregnancies, both maternal and fetal compound W levels increased progressively during gestation with a significant direct correlation (P<0.001, in both mothers and fetuses). Moreover, a significant positive correlation was observed between fetal compound W and fetal FT4 values (P<0.005), whereas no correlation was observed between maternal serum compound W and maternal FT4 in either euthyroid or hyperthyroid women, suggesting the fetal origin of compound W. The hypothyroid fetuses of PTU-treated mothers showed low compound W levels, and maternal compound W values were in the low normal range and did not show the typical increase during progression of gestation. A significant increase of maternal compound W was observed when the PTU dose was reduced. TRIAC was documented to cross the placental barrier and the treatment of a hyperthyroid pregnant woman on PTU caused the high fetal TSH levels and goiter to normalize. CONCLUSIONS: Serial measurements of 3,3'-T2S crossreactive materials (compound W and 3, 3'-diiodothyroacetic acid sulfate) in maternal blood and the administration of TRIAC to the mother may represent a useful and safe alternative to invasive techniques for the diagnosis and therapy of fetal hypothyroidism.
Hormonal changes during the first year of oestrogen treatment in constitutionally tall girls
Authors: Wajs-Kuto E , De Beeck LO , Rooman RP , Caju MV
Published: January 2005

OBJECTIVE: Oestrogens are used to inhibit growth in girls with constitutionally tall stature. We studied the changes in different hormones that accompany such therapy. SUBJECTS AND METHODS: In this longitudinal study we examined the levels of total insulin-like growth factor-I (IGF-I), free thyroxine (FT(4)), thyrotrophin (TSH), testosterone, dehydroepiandrosterone sulphate (DHEA-S), cortisol and prolactin in two groups of girls receiving ethinyloestradiol at a dose of either 0.1mg daily (group A, n=22) or 0.2mg daily (group B, n=36). Hormonal measurements were performed at start of therapy and after 3, 6 and 12 months. RESULTS: In both groups the levels of IGF-I, testosterone and DHEA-S were reduced while the concentrations of cortisol and prolactin were increased. The pituitary-thyroid axis was not significantly affected by this therapy. The girls receiving 0.2mg ethinyloestradiol daily had lower IGF-I levels after 12 months of therapy and had higher serum prolactin concentrations than the girls treated with 0.1mg daily. The reduction in predicted height and the advancement in bone age were similar in both groups. CONCLUSIONS: Therapy with pharmacological doses of ethinyloestradiol changes the levels of several hormones including IGF-I, testosterone, DHEA-S, prolactin and cortisol but the role of the respective changes in the inhibition of growth is not clear. The suppression of DHEA-S levels by 40% suggests that the ovaries contribute significantly to the production of this hormone in pubertal girls.
The phosphorylation status of insulin-like growth factor-binding protein-1 in prepubertal obese children
Authors: Kamoda T , Saitoh H , Nakahara S , Inudoh M , Hirano T , Matsui A
Published: January 2005

OBJECTIVE: We measured the total and nonphosphorylated insulin-like growth factor-binding protein (IGFBP)-1 concentrations in obese children to determine the effect of obesity on the status of IGFBP-1 phosphorylation. We also measured the serum levels of insulin, total and free IGF-I, and IGFBP-3 to investigate their relationships to the IGFBP-1 phosphorylation status in obese subjects. SUBJECTS AND METHODS: Nineteen prepubertal obese and 15 age-matched control children were included in the study. The serum levels of total and nonphosphorylated IGFBP-1 were determined by noncompetitive RIAs. RESULTS: The serum levels of total and nonphosphorylated IGFBP-1 were significantly lower in the obese group (48.7+/-5.6 microgram/l, P<0.001 and 11.1+/-1.9 microgram/l, P<0.01 respectively) than in the controls (86.7+/-9.0 microgram/l and 28.8+/-6.2 microgram/l respectively). However, the ratio of nonphosphorylated IGFBP-1 to total IGFBP-1 did not differ significantly between the obese and control groups. The circulating free IGF-I level was significantly higher in the obese children than in the controls (P<0.05), while the serum levels of insulin, total IGF-I and IGFBP-3 were not significantly different between the two groups. A stepwise regression analysis of the combined group revealed that only the total IGFBP-1 level was an independent predictor of the free IGF-I concentration (P<0.001). CONCLUSION: The present study shows that both total and nonphosphorylated IGFBP-1 concentrations are decreased in obese children and the increased free IGF-I level in obese children is related to the reduced total IGFBP-1 level, but unrelated to the change in the IGFBP-1 phosphorylation status.