Recombinant human TSH-aided radioiodine treatment of advanced differentiated thyroid carcinoma: a single-centre study of 54 patients

We sought to evaluate the efficacy, biochemical effects, safety and outcome of recombinant human thyroid-stimulating hormone (rhTSH) as an adjunct to radioiodine treatment of advanced differentiated thyroid carcinoma (DTC). We also sought to determine whether rhTSH is useful as an adjunct to radioiodine treatment following isotretinoin re-differentiation therapy of DTC metastases that have lost function. Therefore, in 54 consecutive patients who had retained bulky metastatic and/or locoregional lesions of DTC despite the exhaustion of other therapeutic options, we gave one to four courses of two consecutive daily intramuscular injections of rhTSH, 0.9 mg, followed by a therapeutic activity of (131)I per os on day 3. Fifty patients had received prior radioiodine treatment aided by l-thyroxine (T(4)) withdrawal. We included in the study 23 patients who had received a trial of isotretinoin therapy for re-differentiation of confirmed de-differentiated metastases. In a blinded, within-patient comparison of post-therapy whole-body scans after the first rhTSH-aided and latest withdrawal-aided treatments in patients with functional metastases at baseline, 18 of 27 (67%) scan pairs were concordant, four (15%) were discordant in favour of the rhTSH-aided scan and five (19%) were discordant in favour of the withdrawal-aided scan. In total, 37 (74%) of 50 paired scans were concordant, eight (16%) favoured rhTSH and five (10%) favoured withdrawal. All differences appeared to be attributable to clinical causes, not to any difference between endogenous and exogenous TSH stimulation. Reflecting the biochemical activity of rhTSH and the release of thyroglobulin (Tg) due to tumour destruction, median serum Tg concentration rose approximately fourfold between baseline and day 6 of the rhTSH-aided treatment course. rhTSH was well tolerated, with mostly minor, transient toxicity, except for neck oedema in three patients with neck infiltrates and pathological spine fracture in one patient with a large vertebral metastasis. At 6 months, complete response occurred in one (2%), partial response in 12 (26%) and disease stabilisation in 19 (40%) of 47 evaluable patients. The rate of complete + partial response was 41% and that of disease stabilisation, 30%, in the 27 evaluable patients with functional metastases at baseline; the corresponding rates were 10% and 55% in the 20 evaluable patients with non-functional metastases at baseline. Although within-patient comparison of early outcome after both modalities is limited by a significantly greater median number of courses and a greater median cumulative activity of radioiodine given under withdrawal, response to rhTSH-aided and withdrawal-aided treatment was similar in 23 (52%) of 44 evaluable patients, superior with rhTSH in 12 (27%) and superior with withdrawal in seven (16%). In two patients, a superior response was obtained after isotretinoin pretreatment and rhTSH and attributed to re-differentiation therapy. In conclusion, our study provides preliminary evidence that rhTSH safely and effectively aids radioiodine treatment of advanced DTC, and does so to an at least equivalent degree as does T(4) withdrawal.     

CFTR and FOXO1 gene expression are reduced and high mobility group box 1 (HMGB1) is increased in the ovaries and serum of women with polycystic ovarian syndrome

Abstract

We previously described increased HMGB1 and reduced FOXO1 dependent on CFTR loss of function in cystic fibrosis (CF) and we showed in vitro that HMGB1 was lowered by insulin. Reduced CFTR gene expression has been described in granulosa cells (GC) from PCOS-induced rats. We aimed at studying CFTR and FOXO1 gene expression in GC, HMGB1 concentrations in serum and follicular fluids (FF), and insulin and IL-6 in FF in PCOS women. Thirty PCOS and 36 non-PCOS women (CTRL) undergoing in vitro fertilization were enrolled. CFTR and FOXO1 gene expression were downregulated in PCOS (p?≤?.05). HMGB1 was higher in PCOS both in FF (p?≤?.05) and in serum (p?<?.005) whereas insulin was lower, and IL-6 was unchanged with respect to controls. 17-β estradiol was higher in PCOS than in CTRL (p?≤?.005). HMGB1 correlated negatively with insulin in FF (p?≤?.005). The increase in HMGB1 both in FF and in serum, likely reflects both low grade inflammation and insulin sensitivity. IL-6 was unchanged possibly reflecting functions other than inflammation.     

Psychometric properties of a German version of the neck pain and disability scale

The aim of this study is to evaluate the validity and the psychometric properties of a German version of the 20-item neck pain and disability scale (NPAD) for use in primary care settings. Four hundred and forty-eight participants from 15 general practices in the area of Göttingen Germany completed a multidimensional questionnaire including a newly developed German version of the NPAD (NPAD-d) and self-reported demographic and clinical information. Reliability was tested using Cronbach’s alpha. Item-to-total score correlations were analysed. Factor structure was explored by using unrestricted principal factor analysis. Construct validity of the NPAD-d was evaluated by simple correlation analyses (Pearson’s rho) with social and clinical characteristics. The discriminative abilities of the NPAD-d were examined by comparing differences between subgroups stratified on non-NPAD-d pain related characteristics using t tests for mean scores. Cronbach’s alpha of NPAD-d was 0.94. Item-to-total scale correlations ranged between 0.414 and 0.829. Exploratory principal factor analysis indicated that the NPAD-d covers one factor with an explained variance of 48%. Correlation analysis showed high correlations with criterion variables. The NAPD-d scores of subgroups of patients were significantly different showing good discriminative validity of the scale. The NPAD-d demonstrated good validity and reliability in this general practice setting. The NPAD-d may be useful in the clinical assessment process and the management of neck pain.