As a general guideline, one could consider a mean change of at least 6 points on one or both subscales an important change in daily functioning for patients. For more invasive therapies, a change of at least 10 points is recommended as a minimal clinically important difference.

A lack of clarity exists about the definition and adequate approach for evaluating responsiveness. An overview is presented of different categories of definitions and methods used for calculating responsiveness identified through a literature search. Twenty-five definitions and 31 measures were found. When applied to a general and a disease-specific quality of life questionnaire large variation in results was observed, partly explained by different goals of existing methods. Four major issues are considered to claim the usefulness of an evaluative health-related quality of life (HRQL) instrument. Their relation with responsiveness is discussed. The confusion about responsiveness arises mostly from a lack of distinction between cross-sectional and longitudinal validity and from a lack of distinction between responsiveness defined as the effect of treatment and responsiveness defined as the correlation of changes in the instrument with changes in other measures. All measures of what is currently called responsiveness can be looked at as measures of longitudinal validity or as measures of treatment effect. The latter ones tell us little about how well the instrument serves its purpose and are only of use in interpreting score changes. We therefore argue that the concept of responsiveness can be rejected as a separate measurement property of an evaluative instrument.

Smoking is associated with Graves' disease, and it especially increases the risk for the development of more severe ophthalmopathy. Thus, smoking appears to be one of the multiple factors inducing Graves' disease in genetically predisposed individuals.

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Thyrotropin secretion from the anterior pituitary is regulated mainly through TRH and thyroid hormones. Recent findings of a TSH receptor (TSHR) on folliculo-stellate (FS) cells in the human anterior pituitary indicate that TSH secretion might, in addition, be regulated in a paracrine manner via FS cells. In order to elucidate the physiological relevance of TSHR expression in FS cells we evaluated the effects of TSH on a murine FS cell line, TtT/GF. First, Western blot analysis confirmed the expression of TSHR protein in these cells. Second, three potential second messenger pathways were studied. Last, cDNA array hybridization was used to evaluate the effect of TSH on gene expression levels. TSH failed to induce either the adenylate cyclase/cAMP pathway, the phosphatidylinositol/calcium pathway, or the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) 3 pathway. Most of the genes regulated by TSH were related to cell proliferation, cell differentiation, and apoptosis. Moreover, TSH induced STAT5a and TGFbeta2 expression. We report that TtT/GF cells express a functional TSHR that is not coupled to cAMP nor IP (3) but probably signals through the JAK/STAT5a pathway. Functional TSHR expression in this cell line offers an in vitro model to study the role of TSHR in FS cells.

To clarify the rise in plasma creatinine concentration previously observed during prednisone treatment, we studied changes in renal function in Graves’ ophthalmopathy patients before and after 2 weeks of either prednisone 60 mg/day or retrobulbar radiotherapy (controls). Compared to retrobulbar radiotherapy, prednisone treatment was associated with an increase in: (a) plasma creatinine concentration (from 68 ± 4 to 76 ± 4 μmol/l), (b) glomerular filtration rate (GFR, from 93 ± 4 to 102 ± 5 ml/min/1.73 m²), and (c) urinary creatinine excretion rate (from 510 ± 40 to 570 ± 40 μmol/h). We conclude that GFR rises during 2 weeks of high-dose prednisone administration, a rise that is not reflected by a decrease in plasma creatinine concentration. On the contrary, both plasma creatinine concentration and urinary creatinine excretion increase, probably as a result of the catabolic effect of prednisone. As established by the present study, prednisone 60 mg/day is associated with protein wasting, also after 14 days of treatment.