Proteins secreted from adipocytes - so-called adipokines - influence metabolic and vascular function. Recent data suggest that various adipokines are dysregulated in gestational diabetes mellitus (GDM) and pre-eclampsia (PE) and might be of pathophysiological and prognostic significance in these complications of pregnancy. This review gives an overview on the regulation and pathophysiology of leptin and adiponectin in GDM and PE. Furthermore, data on novel adipokines including resistin, visfatin, retinol-binding protein 4 and vaspin are summarized.
Multiple endocrine neoplasia type 2 is characterized by germline mutations in RET. For exon 10, comprehensive molecular and corresponding phenotypic data are scarce. The International RET Exon 10 Consortium, comprising 27 centers from 15 countries, analyzed patients with RET exon 10 mutations for clinical-risk profiles. Presentation, age-dependent penetrance, and stage at presentation of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism were studied. A total of 340 subjects from 103 families, age 4-86, were registered. There were 21 distinct single nucleotide germline mutations located in codons 609 (45 subjects), 611 (50), 618 (94), and 620 (151). MTC was present in 263 registrants, pheochromocytoma in 54, and hyperparathyroidism in 8 subjects. Of the patients with MTC, 53% were detected when asymptomatic, and among those with pheochromocytoma, 54%. Penetrance for MTC was 4% by age 10, 25% by 25, and 80% by 50. Codon-associated penetrance by age 50 ranged from 60% (codon 611) to 86% (620). More advanced stage and increasing risk of metastases correlated with mutation in codon position (609→620) near the juxtamembrane domain. Our data provide rigorous bases for timing of premorbid diagnosis and personalized treatment/prophylactic procedure decisions depending on specific RET exon 10 codons affected.
High diagnostic sensitivity of plasma normetanephrine, metanephrine and methoxytyramine for the detection of PPGL can only be guaranteed using upper cut-offs of reference intervals established with blood sampling under supine fasting conditions. With such cut-offs, sampling under seated nonfasting conditions can lead to a 5·7-fold increase in false-positive results necessitating repeat sampling under supine fasting conditions.
Thyroid ultrasound is used in the routine clinical assessment and the follow-up of thyroid disorders. The follow- up of patients with thyroid nodules is mostly based on thyroid nodule volume determinations performed by different observers. However, for the judgment of treatment effects there is uncertainty about the interobserver variation of thyroid nodule volume measurements by ultrasound because there are no prospective blinded studies available comparing the interobserver variation in thyroid nodule volume measurement. The aim of our study was therefore to determine the variation of thyroid nodule volume determinations for different observers. We conducted a prospective blinded trial. Our study population consisted of 42 probands (8 men, 34 women) with an uniform distribution of thyroid nodule sizes (25 uninodular and 17 multinodular thyroid glands). We compared the results of 3 ultrasonographers with certified experience in thyroid ultrasound. The interobserver variation for the determination of thyroid nodule volume (n = 38) was 48.96% for the ellipsoid method and 48.64% for the planimetric method. The interobserver variation for determining thyroid volume (n = 40) was 23.69% for the ellipsoid method and 17.82% for the planimetric method. A regression analysis revealed that the probability for the identification of the same nodule in nodular thyroids by all sonographers is 90%, if the nodule is at least 15mm in greatest diameter. Future investigations should not describe changes in nodule volume less than 50% as therapy effects because only volume changes of at least 49% or more can be interpreted as nodule shrinkage or growth. Reporting of nodule volume modification 50% or more and lack of information for ultrasound procedures introduce a bias in studies evaluating the effects of nodule treatments. The clinical interpretation of a shrinking/growing thyroid nodule based on volume determinations by ultrasound is not well established because it is difficult to reproduce a two-dimensional image plane for follow-up studies.
Lipodystrophy (LD) is a rare disease with a paucity of subcutaneous adipocytes and leptin deficiency. Patients often develop severe diabetes and, additionally, show a disturbed eating behavior with reduced satiety. The disturbed eating behavior can be restored by substitution with the leptin analog metreleptin. Long-term effects of metreleptin on resting state brain connectivity in treatmentnaive patients with LD have not been assessed. In this study, resting state functional MRI scans and extensive behavioral testing assessing changes in hunger/satiety regulation were performed during the first 52 weeks of metreleptin treatment in nine patients with LD. Resting state connectivity significantly increased over the course of metreleptin treatment in three brain areas (i.e., hypothalamus, insula/superior temporal gyrus, medial prefrontal cortex). Behavioral tests demonstrated that perceived hunger, importance of eating, eating frequencies, and liking ratings of food pictures significantly decreased during metreleptin therapy. Taken together, leptin substitution was accompanied by longterm changes of hedonic and homeostatic central nervous networks regulating eating behavior as well as decreased hunger feelings and diminished incentive value of food. Future studies need to assess whether metreleptin treatment in LD restores physiological processes important for the development of satiety.Lipodystrophy (LD) is a rare disease with a paucity of subcutaneous adipocytes and reduced blood concentrations of leptin. Several genetic mutations are known to cause partial or generalized forms of the disease. Also, cases of acquired LD have occurred (1). LD is frequently accompanied by type 2 diabetes and dyslipidemia. Leptin substitution in the form of the analog metreleptin has shown beneficial metabolic effects. In the biggest clinical trial on metreleptin treatment in LD so far, hemoglobin A 1c (HbA 1c ) on average decreased by 1.5% and serum triglycerides (TGs) fell by .50% after 1 year of treatment (2). Additionally, a disturbed eating behavior often develops in patients with LD, with reduced satiety after food consumption, leading to an increase in meal frequency (3). Impaired eating behavior can be improved by leptin substitution, too (4). Humoral leptin crosses the blood-brain barrier by active transport in the proximity of the mediobasal hypothalamus where the blood-brain barrier is well permeable for peripheral hormones (3,5). Through receptors in the arcuate nucleus, leptin inhibits food intake by direct activation of anorexigenic cocaine-and amphetamine-regulated transcript and proopiomelanocortin neurons (6,7) as well as by inhibition of orexigenic neuropeptide Y neurons (8). In a widely accepted model of the control of eating behavior, the hypothalamus is considered to govern the homeostatic component of human eating regulation, that is, the drive to eat to meet the bodily demands for energy (9,10).In addition, the leptin receptor is also expressed in neurons of the mesolimbic dopamine system, which is involved in...
Constitutively activating thyrotropin receptor (TSHR) germline mutations have been identified as a molecular cause of congenital hyperthyroidism. Patients with relapsing hyperthyroidism were previously treated with surgery and radioiodine. We report on a 22-year-old male patient who was treated for his multiple relapses of hyperthyroidism by repeated subtotal thyroidectomies (STE). During the 22 years of follow-up, the patient developed several relapses of hyperthyroidism, four of them after thyroid surgeries. Sequencing of the TSHR gene revealed a gain-of-function mutation with an amino acid exchange of aspartate to tyrosine in codon 633 which is located in the sixth transmembrane domain of the TSH receptor. The absence of the mutation in all other family members identifies the patient's TSHR mutation as a sporadic germline mutation. In this patient, thyroid tissue growth and hyperthyroidism could repeatedly be controlled only for limited periods by near total thyroidectomy. Therefore, this case confirms that early combined treatment with near-total thyroidectomy plus radioiodine therapy seems to be the treatment of choice for patients with sporadic non-autoimmune hyperthyroidism.
Distinguishing Graves' disease (GD) from a toxic multinodular goiter (TMG) subgroup with a diffuse but uneven Tc-distribution depends on the diagnostic power of the TSH-receptor antibody (TRAb) determination. Bioassays using CHO cell lines expressing the hTSH-receptor or a new TBII assay, which uses the hTSH-receptor as an antigen (DYNOTEST TRAK human, Brahms, Germany), showed a higher sensitivity for the detection of TRAbs in patients with GD than assays using solubilized porcine epithelial cell membranes. The aim of this study was to investigate whether the new Dynotest TRAK human assay has an increased sensitivity to distinguish GD from non-autoimmune hyperthyroidism. Therefore, we examined 21 consecutive patients with the initial diagnosis of TMG for thyroid-stimulating antibodies (TSAbs, JP26 cell assay) and TBII with the new highly sensitive Dynotest TRAK human (Brahms, Germany). The initial diagnosis of TMG was based on suppressed TSH and a patchy Tc-uptake of more than 1 % and less than 7 % or TSH of more than 0.3 mIE/l with a patchy Tc-uptake of more than 1.5 % and less than 7 % and negative TBII values in a displacement assay using solubilized porcine epithelial cell membranes (TRAK, Brahms, Germany). 11 sera from these 21 patients showed TSAb activity. Furthermore, 10 of these 11 TSAb-positive sera were also positive in the Dynotest TRAK human assay, whereas one serum sample was borderline positive. TSAb activity and inhibition of (125)I-bTSH binding in the Dynotest TRAK human assay correlated well (r = 0.7). Therefore, 11 of the 21 investigated patients initially classified as TMG actually had GD, which was undetectable using the porcine TBII assay. In conclusion, TSAbs or TRAbs detected with the Dynotest TRAK human have the highest diagnostic power to differentiate GD from TMG. Because of the less cumbersome assay technique, the Dynotest TRAK human measurements should be obtained for all patients with non-typical TMG to differentiate GD from non-autoimmune hyperthyroidism in order to select the appropriate therapy for these patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.