TRH: Pathophysiologic and clinical implications

Thyrotropin releasing hormone is thought to be a tonic stimulator of the pituitary TSH secretion regulating the setpoint of the thyrotrophs to the suppressive effect of thyroid hormones. The peptide stimulates the release of normal and elevated prolactin. ACTH and GH may increase in response to exogenous TRH in pituitary ACTH and GH hypersecretion syndromes and in some extrapituitary diseases. The pathophysiological implications of extrahypothalamic TRH in humans are essentially unknown. The TSH response to TRH is nowadays widely used as a diganostic amplifier in thyroid diseases being suppressed in borderline and overt hyperthyroid states and increased in primary thyroid failure. In hypothyroid states of hypothalamic origin, TSH increases in response to exogenous TRH often with a delayed and/or exaggerated time course. But in patients with pituitary tumors and suprasellar extension TSH may also respond to TRH despite secondary hypothyroidism. This TSH increase may indicate a suprasellar cause for the secondary hypothyroidism, probably due to portal vessel occlusion. The TSH released in these cases is shown to be biologically inactive

Understanding the role of objects in cross-disciplinary collaboration

In this paper we make a case for the use of multiple theoretical perspectives – theory on boundary objects, epistemic objects, cultural historical activity theory and objects as infrastructure - to understand the role of objects in cross-disciplinary collaboration. A pluralist approach highlights that objects perform at least three types of work in this context: they motivate collaboration; they allow participants to work across different types of boundaries; and they constitute the fundamental infrastructure of the activity. Building on the results of an empirical study we illustrate the insights that each theoretical lens affords into practices of collaboration and develop a novel analytical framework that organizes objects according to the active work they perform. Our framework can help shed new light on the phenomenon, especially with regards the shifting status of objects and sources of conflict (and change) in collaboration. After discussing these novel insights, we outline directions for future research stemming from a pluralist approach. We conclude by noting the managerial implications of our finding

A Sensitive Tg Assay or rhTSH Stimulated Tg: What's the Best in the Long-Term Follow-Up of Patients with Differentiated Thyroid Carcinoma?

Sensitivity of thyroglobulin (Tg) measurement in the follow-up of differentiated thyroid carcinoma (DTC) can be optimized by using a sensitive Tg assay and rhTSH stimulation. We evaluated the diagnostic yield of a sensitive Tg assay and rhTSH stimulated Tg in the detection of recurrences in the follow-up of DTC. Additionally the value of imaging techniques for the localization of recurrences was evaluated. We included 121 disease free patients in long-term follow-up for DTC (median 10 years, range 1–34). Tg during thyroid hormone suppression therapy (Tg-on) and rhTSH stimulated Tg were measured with a sensitive Tg assay. Patients with rhTSH stimulated Tg ≥1.0 ng/ml underwent imaging with neck ultrasound, FDG-PET and post therapy 131I WBS. Sensitive Tg measurement resulted in 3 patients with Tg-on ≥1.0 ng/ml, recurrence could be localized in 2 of them. RhTSH stimulation resulted in Tg ≥1.0 ng/ml in another 17 of 118 patients. Recurrence could be localized in only 1 additional patient (1 out of 118 patients). Recurrence was localized by neck ultrasound in 1 of 3, by FDG-PET in 2 of 3 and by post therapy 131I WBS in 2 of 3 patients. In the detection of recurrences in DTC, rhTSH stimulation had very limited additional value in comparison to Tg-on measurement with a sensitive Tg assay. We consider this too low to justify rhTSH stimulation in all patients during long-term follow up. Neck ultrasound, FDG-PET and post therapy 131I WBS showed complementary value in localization of disease, but were only positive in a small fracture of all procedures

Dynamic coordination in brain and mind

Our goal here is to clarify the concept of 'dynamic coordination', and to note major issues that it raises for the cognitive neurosciences. In general, coordinating interactions are those that produce coherent and relevant overall patterns of activity, while preserving the essential individual identities and functions of the activities coordinated. 'Dynamic coordination' is the coordination that is created on a moment-by-moment basis so as to deal effectively with unpredictable aspects of the current situation. We distinguish different computational goals for dynamic coordination, and outline issues that arise concerning local cortical circuits, brain systems, cognition, and evolution. Our focus here is on dynamic coordination by widely distributed processes of self-organisation, but we also discuss the role of central executive processes

Relating circulating thyroid hormone concentrations to serum interleukins-6 and -10 in association with non-thyroidal illnesses including chronic renal insufficiency

<p>Abstract</p> <p>Background</p> <p>Because of the possible role of cytokines including interleukins (IL) in systemic non-thyroidal illnesses' (NTI) pathogenesis and consequently the frequently associated alterations in thyroid hormone (TH) concentrations constituting the euthyroid sick syndrome (ESS), we aimed in this research to elucidate the possible relation between IL-6 & IL-10 and any documented ESS in a cohort of patients with NTI.</p> <p>Methods</p> <p>Sixty patients and twenty healthy volunteers were recruited. The patients were subdivided into three subgroups depending on their underlying NTI and included 20 patients with chronic renal insufficiency (CRI), congestive heart failure (CHF), and ICU patients with myocardial infarction (MI). Determination of the circulating serum levels of IL-6 and IL-10, thyroid stimulating hormone (TSH), as well as total T4 and T3 was carried out.</p> <p>Results</p> <p>In the whole group of patients, we detected a significantly lower T3 and T4 levels compared to control subjects (0.938 ± 0.477 vs 1.345 ± 0.44 nmol/L, p = 0.001 and 47.9 ± 28.41 vs 108 ± 19.49 nmol/L, p < 0.0001 respectively) while the TSH level was normal (1.08+0.518 μIU/L). Further, IL-6 was substantially higher above controls' levels (105.18 ± 72.01 vs 3.35 ± 1.18 ng/L, p < 0.00001) and correlated negatively with both T3 and T4 (r = -0.620, p < 0.0001 & -0.267, p < 0.001, respectively). Similarly was IL-10 level (74.13 ± 52.99 vs 2.64 ± 0.92 ng/ml, p < 0.00001) that correlated negatively with T3 (r = -0.512, p < 0.0001) but not T4. Interestingly, both interleukins correlated positively (r = 0.770, p = <0.001). Moreover, IL-6 (R²= 0.338, p = 0.001) and not IL-10 was a predictor of low T3 levels with only a borderline significance for T4 (R²= 0.082, p = 0.071).</p> <p>By subgroup analysis, the proportion of patients with subnormal T3, T4, and TSH levels was highest in the MI patients (70%, 70%, and 72%, respectively) who displayed the greatest IL-6 and IL-10 concentrations (192.5 ± 45.1 ng/L & 122.95 ± 46.1 ng/L, respectively) compared with CHF (82.95 ± 28.9 ng/L & 69.05 ± 44.0 ng/L, respectively) and CRI patients (40.05 ± 28.9 ng/L & 30.4 ± 10.6 ng/L, respectively). Surprisingly, CRI patients showed the least disturbance in IL-6 and IL-10 despite the lower levels of T3, T4, and TSH in a higher proportion of them compared to CHF patients (40%, 45%, & 26% vs 35%, 25%, & 18%, respectively).</p> <p>Conclusion</p> <p>the high prevalence of ESS we detected in NTI including CRI may be linked to IL-6 and IL-10 alterations. Further, perturbation of IL-6 and not IL-10 might be involved in ESS pathogenesis although it is not the only key player as suggested by our findings in CRI.</p