Measurement of anti-TSH receptor antibodies: what is the correct cut-off value?

BACKGROUND: Autoantibodies against the thyroid stimulating hormone receptor, thyrotropin receptor autoantibodies (TRAb) are diagnostic for Graves' disease and can be measured by different methods. As antibody concentrations are not comparable between methods, appropriate cut-off values need to be established for every single method. For a third-generation TRAb assay (Phadia, Thermofisher), the manufacturer determined the cut-off value in a study population consisting of Graves' disease (both newly diagnosed and patients under treatment) and non-Graves' disease patients. The aim of this study was to verify whether this cut-off value holds true in our population. METHODS: Retrospective analysis was performed on TRAb measurements collected over a period of six months from all patients referred for TRAb testing. For our study, we included patients that were newly diagnosed with hyperthyroidism including Graves' disease, multinodular goitre, toxic adenoma, and thyroiditis. Furthermore, we included Graves' patients that were under treatment at the time of TRAb measurement. RESULTS: Whereas all patients with Graves' disease had positive TRAb, few patients with multinodular goitre, toxic adenoma, and thyroiditis scored positive for TRAb. ROC curve analysis revealed a cut-off value of 4.5 IU/l (compared to 3.3 IU/l established by the manufacturer). Newly diagnosed Graves' patients had higher TRAb concentrations compared to patients under treatment. CONCLUSION: The cut-off value of this immunoassay should probably be set higher in untreated Graves' patients than proposed by the manufacturer as the cut-off value should be determined in a study population excluding Graves' patients under treatment. The overall clinical picture remains crucial in the diagnosis of Graves' disease.

Thyrotoxic periodic paralysis: an unusual presentation of hyperthyroidism.

Thyrotoxic periodic paralysis (TPP) is a complication of hyperthyroidism among Asians, characterised by sudden onset of hypokalaemia and muscle paralysis. Several factors may contribute to a delay in diagnosis, including the subtlety of hyperthyroidism, the transient nature of the events and the rarity of this disease in the West. As life-threatening arrhythmias may occur during an attack, awareness among physicians is necessary for early recognition and treatment. Advances have been made in understanding the pathophysiological mechanism leading to hypokalaemia, which include recently identified mutations of the inwardly rectifying potassium channel Kir2.6. Treatment includes the supplementation of potassium, a nonselective beta-blocker, and ultimately treatment of the underlying hyperthyroidism. Here we report three cases of TPP in the Netherlands, and review the literature on clinical features, pathophysiological hypothesis and treatment.

Type-specific risk factors and outcome in an outbreak with 2 different Clostridium difficile types simultaneously in 1 hospital.

BACKGROUND: Clostridium difficile infection (CDI) due to polymerase chain reaction (PCR) ribotype 027 (type 027) has been described worldwide. In some countries, an increase was reported of toxin A-negative PCR ribotype 017 (type 017). We encountered an outbreak due to these 2 types occurring simultaneously in a 980-bed teaching hospital in the Netherlands. METHODS: In a case-control study from May 2005 through January 2007, we investigated general and type-specific risk factors as well as outcome parameters for CDI due to type 027 or 017. Clonal dissemination was investigated by multilocus variable number of tandem repeat analysis (MLVA). RESULTS: We identified 168 CDI patients: 57 (34%) with type 017, 46 (27%) with type 027, and 65 (39%) with 1 of 36 different other types. As controls, we included 77 non-CDI diarrheal patients and 162 patients without diarrhea. Risk factors for CDI were nasogastric intubation, recent hospitalization, and use of cephalosporins and clindamycin. Type-specific risk factors were older age for both types 017 and 027, use of clindamycin and immunosuppressive agents for type 017, and use of fluoroquinolones for type 027. At day 30 of follow-up, the overall mortality among patients with types 017, 027, other types, non-CDI diarrheal patients, and nondiarrheal patients was 23%, 26%, 3%, 2%, and 6%, respectively. MLVA showed persistent clonal dissemination of types 017 and 027, despite appropriate infection control measures. CONCLUSIONS: Patients with CDI have type-specific risk factors and mortality rates, with prolonged clonal spread of type 027 or 017.

Clostridium difficile infection in an endemic setting in the Netherlands.

The purpose of this investigation was to study risk factors for Clostridium difficile infection (CDI) in an endemic setting. In a 34-month prospective case-control study, we compared the risk factors and clinical characteristics of all consecutively diagnosed hospitalised CDI patients (n = 93) with those of patients without diarrhoea (n = 76) and patients with non-CDI diarrhoea (n = 64). The incidence of CDI was 17.5 per 10,000 hospital admissions. C. difficile polymerase chain reaction (PCR) ribotype 014 was the most frequently found type (15.9%), followed by types 078 (12.7%) and 015 (7.9%). Independent risk factors for endemic CDI were the use of second-generation cephalosporins, previous hospital admission and previous stay at the intensive care unit (ICU). The use of third-generation cephalosporins was a risk factor for diarrhoea in general. We found no association of CDI with the use of fluoroquinolones or proton pump inhibitors (PPIs). The overall 30-day mortality among CDI patients, patients without diarrhoea and patients with non-CDI diarrhoea was 7.5%, 0% and 1.6%, respectively. In this endemic setting, risk factors for CDI differed from those in outbreak situations. Some risk factors that have been ascribed to CDI earlier were, in this study, not specific for CDI, but for diarrhoea in general. The 30-day mortality among CDI patients was relatively high.