Search

Up to 20% of individuals with primary hypothyroidism treated with L-thyroxine still suffer from severe symptoms. These are supposedly brain derived and involve both cognitive and emotional domains. Previously, no consistent relationship has been found between thyroid hormones (TH) or TSH levels in blood and quality of life (QoL). Recently, we reported an association between cerebrospinal fluid (CSF)/serum free-thyroxine (f-T4) ratio and QoL, in juvenile hypothyroid patients. Here, we investigated if CSF/serum f-T4 ratio and QoL estimates correlate also during L-thyroxine treatment. Moreover, the CSF biomarker neurogranin (Ng) was used as a biomarker for synaptic function and integrity in clinical research. Ng is partially controlled by TH and therefore we investigated the relationship between QoL parameters and Ng levels. Patients diagnosed with primary hypothyroidism were investigated using vital parameters, serum and CSF analyses of TH, TSH, Ng and QoL questionnaires. Similar procedures were performed after 6 months of treatment. The most marked associations with QoL were found for CSF/serum f-T4 ratio, which was strongly related to several QoL parameters such as the mental subscore of SF-36 (r = 0.83, p < .0005). Ng, which did not differ from that in our healthy controls, was lower in some patients during treatment and higher in others. However, the change in Ng during treatment was significantly correlated with QoL parameters including the mental subscore of SF-36 (r = -0.86, p < .0001). In addition, the CSF/serum f-T4 ratio correlated with the change in Ng (r = -0.75, p = .001). Our results suggest that the ratio between CSF and serum f-T4 is an important biomarker for QoL during treatment of patients with primary hypothyroidism, so far in research, but in the future maybe also in clinical settings. Moreover, this ratio also correlates with the changes in Ng levels during L-thyroxine treatment, further supporting the impact of the TH balance between serum

Background & Objective: Patients with mild hypothyroidism often are depressed and have impaired quality of life despite serum free-T4 and T3 within reference values. Therefore, we investigated whether their symptoms were dependent on the concentrations of free -T4 and T3 in the circulation and cerebrospinal fluid (CSF). Methods: Twenty-five newly diagnosed, untreated hypothyroid subjects and as many age- and sex-matched healthy controls were investigated. Blood and CSF sampling was performed in the morning after an overnight fast. Quality of life (QoL) was assessed by a Likert scale. In the hypothyroid subjects, the MADRS rating scale was also used to evaluate symptoms of depression. Furthermore, the results obtained by the questionnaires were related to serum and CSF levels of free- T4 and T3 as well as the ratios between them in CSF and in serum. Results: Self-reported health was considerably lower in hypothyroid subjects. MADRS was considerably higher than the normal range for healthy individuals. Low CSF/serum free-T4 ratio was correlated with an increased depressed state according to MADRS (p < 0.01), and in addition, CSF/serum free-T4 ratio correlated positively with the self-reported general health Likert scale (p < 0.05). Concentrations of TSH, or free-T3 in serum or CSF, were not associated with an increased depressed state or self-reported general health. Conclusions: Low CSF/serum ratio of free-T4 was correlated with impaired general health and mood, in contrast to serum measurements not showing any correlations. These findings might partly explain why some patients with hypothyroidism suffer from mental symptoms, despite adequate serum levels of free-T4. However, the findings need to be confirmed in further and larger studies., Funding Agency:Sodra Sjukvardsregionen and Region Hallands forskningsfond

Background: Commercially available fibrin is routinely being used as both a matrix in certain cartilage repair techniques and a method for scaffold fixation. Chondrocytes from non-digested particulated cartilage fragments are proposed as a possible source for new cartilage tissue formation in some operative techniques. The goal of this study was to test that chondrocytes from particulated articular cartilage embedded in fibrin have an active role in the process of cartilage repair, as well as if commercially available fibrin should be used as a suitable matrix. Methods: Articular cartilage was obtained from patients undergoing total knee replacement surgery. The biopsies were particulated in small, 1-2-mm(3) pieces and embedded in fibrin. Two groups were compared in our study, particulated articular cartilage with and without collagenase treatment. The specimens were analyzed by optical microscopy after 2-5 weeks of cultivation in a special construct embedded in a cell culture medium containing particulated cartilage embedded in fibrin in the upper phase and cancellous bone in the lower phase under the perforated nylon membrane. Results: None of the biopsies taken from four different patients showed the outgrowth of chondrocytes or bone marrow-originated cells into the fibrin matrix in our experimental model. Conclusions: It has been shown in our experimental model in vitro little to support the theory that articular chondrocytes from particulated articular cartilage embedded in fibrin have an active role in cartilage repair in its early stage.

Equalis och Svensk Förening för Klinisk Kemi (SFKK) rekommenderar att de kliniska laboratorierna i Sverige använder enhetliga måttenheter vid hormonbestämningar för ökad jämförbarhet och patientsäkerhet. Vid analys i serum eller plasma med nuvarande metoder rekommenderas följande enheter: • Adrenokortikotropt hormon (ACTH): pmol/L • Insulin: mIE/L • Parathormon (PTH): pmol/L • Prolaktin: mIE/L • Tillväxthormon (GH): μg/L • Östradiol: pmol/L • Aldosteron: pmol/L • Reninkoncentration: mIE/L

The association between cerebrospinal fluid (CSF) and serum concentration of thyroid hormones and pituitary thyrotropin stimulating hormone (TSH) was studied in nine hypothyroid patients (HT) before and in seven after L-thyroxine treatment. With L-thyroxine, median free T4 increased 4-fold in serum (3.5 pmol/L vs 17.5 pmol/L) and 3-fold in CSF, (3.9pmol/L vs 11.5 pmol/L). Correspondingly, total T3 in serum increased two-fold (0.9 nmol/L vs 2.2 nmol/L). Unexpectedly, free T3 concentration in CSF was similar (1.5 pmol/L vs.1.5 pmol/L) before and during treatment. In HT, TSH in serum correlated with TSH in CSF as did free T4 in serum and in CSF. During L-thyroxine, the correlation with TSH in serum and CSF remained. Likewise, the free T4 concentration in serum correlated with that in CSF. However, no correlation was found between T3 in serum and free T3 in CSF. It seems evident that free T4 in serum equilibrates with that in the CSF both in the HT and during L-thyroxine. Despite a two-fold increase in total serum T3, free T3 in CSF remained unchanged, which agrees with previous results in rats showing that T3 is less exchangeable between serum and CSF. Alternatively, an accelerated conversion of T4 to T3 might have maintained the concentration of T3, due to strongly increased levels of TSH found in the hypothyroid state. The notion that free T4 in serum reflects the CSF concentration of free T4 is consistent with previous reports from studies in animals.

Cadmium and high vitamin A intake are both proposed risk factors for low bone mineral density (BMD), but potential interactions have not been studied. Within the Women's Health in the Lund Area, a population-based study in southern Sweden, we measured retinol in serum among 606 women aged 54-64 y. Data on BMD were measured by DXA at the distal forearm. Parathyroid hormone (PTH), bone alkaline phosphatase (bALP), and osteocalcin in serum and deoxypyridinoline (DPD) and cadmium in urine were available. Associations were evaluated using multivariable-adjusted linear regression analysis. Serum retinol concentrations (median, 1.9; range, 0.97-4.3 μmol/L) were inversely associated with the bone formation markers bALP and osteocalcin (P ≤ 0.04) and with PTH (P = 0.07) and tended to be positively associated with BMD (P = 0.08) but not with the bone resorption marker DPD, indicating different effects on bone compared to urinary cadmium (median, 0.66; range, 0.12-3.6 nmol/mmol creatinine). Women with serum retinol less than the median and cadmium greater than the median had lower BMD than those with retinol greater than the median and cadmium less than the median (P = 0.016 among all women and P = 0.010 among never-smokers). Our findings suggest that adequate vitamin A status may counteract the adverse association between cadmium and BMD.

Neuropeptides influence cellular events involved in tumour growth and differentiation. Neuroblastoma, a malignant childhood tumour of neural crest origin, synthesises and releases monoamines and neuropeptides. The concentrations of some of these neuropeptides in plasma are correlated to clinical stage and outcome. The neuropeptides exist in various molecular forms in plasma and tumour tissue but their biochemical structure in vivo are poorly investigated. The aim of the present work was to combine radioimmunoassays (RIA), different forms of liquid chromatography, amino acid sequence analysis and mass spectrometry to identify and characterise molecular forms of neuropeptides present in neuroblastoma tumour tissue, and to identify correlations to clinical parameters. The hypothesis tested was that the processing of neuropeptide Y (NPY) and other peptides in neuroblastoma generates molecular forms that may have clinical significance. Vasoactive intestinal peptide-like immunoreactivity (VIP-LI) and somatostatin-like immunoreactivity (SOM-LI) in neuroblastoma and benign ganglioneuroma tumour tissue were found in the form of the intact, biologically active peptides VIP-28, SOM-14 and SOM-28. However, the results for SOM-LI may be influenced by presence of the recently identified somatostatin homologoue cortistatin, that was shown to have similar affinity as somatostatin for the antiserum used. Pancreastatin-like immunoreactivity (PST-LI) showed molecular heterogeneity in neuroblastoma. The concentration of PST-LI in tumour tissue and plasma was higher in favourable neuroblastomas whereas low concentrations in both plasma and tumour tissue were correlated to poor outcome. NPY-like immunoreactivity (NPY-LI) in both neuroblastoma and ganglioneuroma tumour tissue showed considerable heterogeneity in general, as demonstrated by using two antisera specific for different epitopes of the NPY molecule. However, no clinical correlation was identified related to this heterogeneity.