A bioluminescence assay for thyrotropin receptor antibodies predicts serum thyroid hormone levels in patients with de novo Graves' disease.

BACKGROUND: TSH receptor antibodies (TBII) in Graves' disease (GD) may be TSH receptor stimulating (TSAb) and blocking (TBAb) antibodies. In commercially available assays however, only total TBII titres can be measured, without discriminating between TSAb and TBAb. OBJECTIVE: To design a TBII bioassay to detect of TSAb and to correlate TSAb activity with severity of hyperthyroidism in de novo GD patients. PATIENTS: Thirty-five patients with de novo GD and 27 controls. METHODS: The JP-26-26 cell line, which constitutively expresses the TSH receptor (TSHR), was stably transfected with a cyclic adenosine monophosphate responsive element--luciferase construct. The clone B1 exhibited a near linear increase in luminescence from 0.2 mU/l to 50 mU/l bovine TSH and was used as a TBII bioassay. TBII, free T4 and TSH were measured in the sera of all patients and controls. RESULTS: In the sera of 35 GD patients, TBII titres did not correlate with serum free T4 concentrations. In contrast, a strong and highly significant correlation was found between TSHR stimulating activity (luminescence) as measured with the TBII bioassay and serum free T4 levels (R = 0.80, P < 0.001). Interestingly, the luminescence/TBII ratio had a wide range at low TBII titres, whereas high TBII titres were associated with a low degree of TSHR activation. The TBII bioassay also detected TBAb in GD patients who spontaneously developed hypothyroidism. CONCLUSIONS: The B1-TBII-bioassay as developed in our laboratory has a high sensitivity for the detection of TSAb in GD and predicts the severity of hyperthyroidism in untreated GD patients. In addition, we found that high TBII titres are associated with weak TSHR activation.

[The practice guideline 'Blood transfusion' (third integral revision)]. / Richtlijn 'Bloedtransfusie' (3e algehele herziening).

The revised and expanded practice guideline 'Blood transfusion' describes the whole transfusion chain within the hospital for the first time. Despite compatibility tests before transfusion (determination of the ABO and Rhesus blood groups and detection of clinically relevant antibodies (C, c, D, E, e, Fy(a), Fy(b), Jk(a), Jk(b), M, S and s)), transfusion reactions can occur. So that a transfusion reaction can be recognised in time, the patient must be observed intensively for the first 5-10 minutes after the start of any new transfusion and the vital functions must be recorded. In patients with a Hb level of 4-6 mmol/l, the decision whether or not to transfuse should be made dependent on the patient's other characteristics. Thrombocyte transfusion is not indicated in case of thrombopenia due to increased breakdown or pooling. If leukaemia, tumour infiltration or drug toxicity is the underlying cause of thrombopenia, then a platelet count of 10 x 10(9)/l or 20 x 10(9)/l should be the transfusion trigger. Reduction of the number of blood transfusions can be achieved by the administration of epoetin in case of renal insufficiency: transfusion can thus be avoided in more than 70% of the patients concerned. Autotransfusion during surgery with severe blood loss also results in a reduction of the number of allogenic blood transfusions.

[The CBO professional guideline 'monoclonal gammopathy' (paraproteinemia) (revision)]. / CBO-richtlijn 'Monoklonale gammopathie (paraproteïnemie)' (herziening).

The revised guideline 'Monoclonal gammopathy (paraproteinaemia)' of the Dutch Institute for Health Care Improvement (CBO) describes the most recent clinically relevant developments in the field of monoclonal proteins (M-proteins). Criteria with both prognostic and therapeutic significance are established for 'monoclonal gammopathy of undetermined significance' (MGUS) and (smouldering) multiple myeloma. If an M-protein is found incidentally, the therapeutic consequences will be determined mainly by the probability that the M-protein fits in with the diagnosis or the clinical findings in the patient in question, as well as with the type and extent of the monoclonal gammopathy. A myeloma risk score enables the treating physician to judge whether a bone marrow examination and determination of the skeletal status are required. The revised guideline contains specific clinical questions and indications that can be used on the laboratory order forms and which facilitate the interpretation of the test results. The investigation of skeletal abnormalities must fulfill established criteria in order to be able to discriminate between MGUS and multiple myeloma, and for the staging of multiple myeloma. There is no indication for routine MRI, but MRI must be performed urgently in patients with radicular symptoms or a (threatened) transverse lesion. Both cytology and histology of the bone marrow are an essential part of the initial diagnosis and classification of multiple myeloma. Cytogenetic studies of the bone marrow are recommended as well. In the case of unexplained polyneuropathy, an M-protein should be looked for.