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Ase Krogh Rasmussen, Karine Bech, Ulla Feldt-Rasmussen, Svenn Poulsen, Kaj Siersbæk-Nielsen, Thorkild Friis and K. Bendtzen

Cytokines are hormonal signals essential for cellular communication in immune responses. Interleukin 1 (IL-1) is a T- and B-lymphocyte-activating cytokine released primarily by antigen-presenting macrophages (Bendtzen 1983; Dinarello 1984). In addition to its lymphocyte-activating properties, IL-1 has a broad spectrum of other activities, including the ability to alter neuroendocrine and metabolic functions (Bendtzen 1983; Dinarello 1984).

Recently, supernatants of activated human blood mononuclear cells (MNC), and native and recombinant IL-1 (rIL-1) have been shown to directly affect the insulin secretion as well as the structure of beta-cells in pancreatic islets of Langerhans (Bendtzen et al. 1986).

The purpose of this study was to investigate the influence of rIL-1, on another endocrine target cell in order to elucidate a possible participation of IL-1 in the pathogenesis of autoimmune thyroid diseases. We found that IL-1 is a potent inhibitor of thyroglobulin (Tg) and cyclic AMP (cAMP) production and/or release from in vitro

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Torquil Watt, Mogens Groenvold, Åse Krogh Rasmussen, Steen Joop Bonnema, Laszlo Hegedüs, Jakob Bue Bjorner and Ulla Feldt-Rasmussen

The importance of patient-reported outcomes such as health-related quality of life (HRQL) in clinical research is increasingly acknowledged. In order to yield valid results, the measurement properties of HRQL questionnaires must be thoroughly investigated. One aspect of such a validation process is the demonstration of content validity, i.e. that the questionnaire covers all relevant aspects. We review studies reporting on consequences of thyroid disorders and present the frequency of identified aspects, both overall HRQL issues and classical thyroid symptoms, in order to evaluate which issues are relevant for patients with thyroid diseases. Furthermore, existing questionnaires for thyroid patients are reviewed. A systematic search was performed in the Medline, Cinahl and Psycinfo databases and the reference lists of the relevant articles were hand-searched. Seventy-five relevant studies were identified. According to these studies, patients with untreated thyroid disease suffer from a wide range of symptoms and have major impairment in most areas of HRQL. Furthermore, the studies indicate that impairments in HRQL are also frequent in the long term. Six HRQL questionnaires for thyroid patients were identified. Generally, data supporting the validity of these questionnaires were sparse. According to the available literature, the quality of life of thyroid patients is substantially impaired over a wide range of aspects of HRQL in the untreated phase and continues to be so in many patients also in the long term. Studies systematically exploring the relative importance of these various aspects to thyroid patients are lacking, as is a comprehensive, validated thyroid-specific HRQL questionnaire.

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Torquil Watt, Laszlo Hegedüs, Mogens Groenvold, Jakob Bue Bjorner, Åse Krogh Rasmussen, Steen Joop Bonnema and Ulla Feldt-Rasmussen


Appropriate scale validity and internal consistency reliability have recently been documented for the new thyroid-specific quality of life (QoL) patient-reported outcome (PRO) measure for benign thyroid disorders, the ThyPRO. However, before clinical use, clinical validity and test–retest reliability should be evaluated.


To investigate clinical (‘known-groups’) validity and test–retest reliability of the Danish version of the ThyPRO.


For each of the 13 ThyPRO scales, we defined groups expected to have high versus low scores (‘known-groups’). The clinical validity (known-groups validity) was evaluated by whether the ThyPRO scales could detect expected differences in a cross-sectional study of 907 thyroid patients. Test–retest reliability was evaluated by intra-class correlations of two responses to the ThyPRO 2 weeks apart in a subsample of 87 stable patients.


On all 13 ThyPRO scales, we found substantial and significant differences between the groups expected to have high versus low scores. Test–retest reliability was above 0.70 (range 0.77–0.89) for all scales, which is usually considered necessary for comparisons among patient groups, but below 0.90, which is the usual threshold for use in individual patients.


We found support for the clinical validity of the new thyroid-specific QoL questionnaire, ThyPRO, and evidence of good test–retest reliability. The questionnaire is now ready for use in clinical studies of patients with thyroid diseases.

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Stina Willemoes Borresen, Marianne Klose, Bo Baslund, Åse Krogh Rasmussen, Linda Hilsted, Lennart Friis-Hansen, Henning Locht, Annette Hansen, Merete Lund Hetland, Magnus Christian Lydolph and Ulla Feldt-Rasmussen


Patients receiving long-term glucocorticoid treatment are at risk of developing adrenal insufficiency during treatment. We investigated the prevalence of prednisolone-induced adrenal insufficiency in the particular clinical situation where patients receive ongoing low-dose (5 mg/day) prednisolone treatment, a dose by itself too low to cover glucocorticoid needs during stress.

Design and methods

Cross-sectional study in 42 patients with rheumatoid arthritis (29 women, aged 36–86 years) treated with 5 mg prednisolone/day, who had received prednisolone for ≥6 months (median: 66, range: 6–444 months). Adrenal function was evaluated by a 250 μg Synacthen test performed after mean 48.7 h prednisolone pause. Local assay-specific cut-off for normal adrenal function was P-cortisol ≥420 nmol/L 30 min after Synacthen injection.


Overall, 20 of the 42 patients (48%, 95% CI: 33–62%) had an insufficient adrenal response to the Synacthen test. Including only patients who had not received concomitant treatment with any other glucocorticoid formulas within the last 3 months, 13 of 33 patients (39%, 95% CI: 25–56%) had an insufficient response. Adrenocorticotrophic hormone (ACTH) concentrations were generally low and anti-adrenal antibodies were negative indicating secondary adrenal insufficiency as the most likely diagnosis. There was no correlation between duration of treatment and 30 min P-cortisol (P = 0.62). Adrenal function did not depend on sex or seropositivity of rheumatoid arthritis.


We demonstrate a high prevalence of adrenal insufficiency during ongoing low-dose prednisolone treatment. The results urge to increase focus on the condition to ensure identification and correct management of insufficient patients during stress and withdrawal. Strategies for adrenal function evaluation during ongoing low-dose glucocorticoid treatment need to be established.

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Claudio Marcocci, Torquil Watt, Maria Antonietta Altea, Ase Krogh Rasmussen, Ulla Feldt-Rasmussen, Jacques Orgiazzi, Luigi Bartalena and for the European Group of Graves' Orbitopathy (EUGOGO)


The objective of this study was to investigate the side effects of glucocorticoid (GC) therapy observed by European thyroidologists during the treatment of Graves' orbitopathy (GO).


A questionnaire-based survey among members of the European Thyroid Association (ETA) who treat GO.


A response was obtained from 128 ETA members of which 115 used GC therapy for GO. The majority of respondents (83/115, 72%) used intravenous (i.v.) GC, with a relatively wide variety of therapeutic regimens. The cumulative dose of methylprednisolone ranged between 0.5 and 12 g (median 4.5 g) for i.v.GC and between 1.0 and 4.9 g (median 2.4 g) for oral GC. Adverse events were often reported during oral GCs (26/32, 81%); most side effects were non-severe, but ten respondents reported severe adverse events (hepatic, cardiovascular, and cerebrovascular complications), including two fatal cases, both receiving a total of 2.3 g prednisone. Adverse events were less common in i.v.GC (32/83 respondents, 39%), but mostly consisted of severe events, including seven fatal cases. All but one fatal event occurred in cumulative i.v.GC doses (>8 g) higher than those currently recommended.


GCs are preferentially administered i.v. for the treatment of GO in Europe. Both oral and i.v.GC may be associated with severe adverse effects, including fatal cases, which are more frequently reported in daily or alternate day i.v.GC. IvGC therapy should be undertaken in centers with appropriate expertise. Patients should be carefully examined for risk factors before treatment and monitored for side effects, which may be asymptomatic, both during and after treatment.