Volume 32, Issue 1

The goal of precise, accurate and specific measurement of bilirubin and its subfractions in serum has not yet been achieved, despite many different methods being available. In addition to the traditional photometric diazo procedures, drychemistry methods, direct spectrophotometry in serum and whole blood and for scientific purposes separations by HPLC were established. For point-of-care diagnostics several test procedures are available. This article reviews the most notable methods and describes advantages and disadvantages of the different bilirubin analyses.

The goal of precise, accurate and specific measurement of bilirubin and its subfractions in serum has not yet been achieved, despite many different methods being available. In addition to the traditional photometric diazo procedures, drychemistry methods, direct spectro-photometry in serum and whole blood and for scientific purposes separations by HPLC were established. For point-of-care diagnostics several test procedures are available. This article reviews the most notable methods and describes advantages and disadvantages of the different bilirubin analyses.

Insulin-like growth factor I (IGF-I) represents the key marker for the evaluation of growth hormone (GH) status. A large number of determinants, including age, gender, genetic factors, nutrition and disease states, influence IGF-I serum levels. Accurate normative data are essential to translate patient data into diagnostic meaning or even use IGF-I levels for adequate monitoring of patients with an over- or underactive GH axis. Even though reference ranges have been developed in large cohorts of healthy subjects, the dependency of these data on a given assay technology argues for assay specific normative data for IGF-I.

Clinical thyrotoxicosis in patients with Graves' disease is caused by stimulating thyrotropin receptor antibodies (TRAB). In this study, new methods to detect TRAB and their clinical use are addressed and discussed in detail. Highly sensitive TRAB assays are widely available and are cost efficient, and their routine clinical use allows a clear differentiation between immunogenic hyperthyroidism and other forms. Despite the increase of sensitivity and specificity for detection of TRAB, the new TRAB assays cannot be used for an individual outcome prediction in Graves' disease or endocrine orbitopathy.

Clinical thyrotoxicosis in Graves' disease patients is caused by stimulatory thyrotropin receptor antibodies (TRAbs). New methods of detecting these antibodies and their clinical use are addressed and discussed in detail. These highly sensitive assays are widely available and cost effective, and their routine clinical use allows a clear differentiation between immunogenic hyperthyroidism and other forms. Despite improved sensitivity and specificity, the new TRAb assays cannot lead to an individual prognosis for Graves' disease or endocrine orbitopathy.

Hyponatraemia is a common complication in patients with disorders of the central nervous system or undergoing neurosurgery. The differentiation between the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and the cerebral salt-wasting syndrome (CSW) is important, because both diseases have different prognosis and require different specific treatment. Although most physicians are familiar with SIADH, they are much less familiar with CSW. This review emphasizes the need for CSW to be included in the differential diagnosis of hyponatraemia. We review the aetiology, mechanisms, treatment and differential diagnosis, with a special focus on laboratory markers of CSW.

Hyponatraemia is one of the most common complications in patients with disorders of the central nervous system or those who have undergone cerebral neurosurgery. The differentiation between the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and the cerebral salt-wasting syndrome (CSWS) is important because the two diseases have different prognoses and require different specific treatment. Although most physicians are familiar with SIADH, they are much less familiar with CSW. This paper emphasizes the need for CSW to be included in the differential diagnosis of hyponatraemia; it reviews the aetiology, pathophysiology, treatment and differential diagnoses of CSW; particular attention is given to diagnostic laboratory markers, both those that are already established and those that are still under investigation.

Diagnosis of active Lyme borreliosis (LB) remains a challenge in clinically ambiguous, serologically indeterminant and polymerase chain reaction-negative patients. Lymphocyte transformation tests (LTT) have been applied to detect specific cellular immune reactivity, but their clinical application has been severely hampered by the poorly defined Borrelia antigens and non-standardized LTT formats used. In this study, we describe the development and clinical relevance of a novel LTT using a validated format (MELISA ® ) together with well-defined recombinant Borrelia-specific antigens. From an initial screening of 244 patients with suspected Borrelia infection or disease, four informative recombinant antigens were selected: OspC ( B. afzelii ), p41-int 1 ( B. garinii ), p41-int 2 ( B. afzelii ) and p100 ( B. afzelii ). Thereafter, 30 seronegative healthy controls were tested using the LTT-MELISA ® to determine specificity, 68 patients were tested in parallel to determine reproducibility, and 54 lymphocyte reactive, symptomatic patients were tested before and after antibiotic therapy to assess clinical relevance. Most (86.2%) of the 36.9% (90/244) LTT-MELISA ® -positive patients were seropositive and showed symptoms of active LB. Specificity was 96.7%, and reproducibility 92.6%. After therapy, most patients (90.7%) showed negative or markedly reduced lymphocyte reactivity correlating with clinical improvement. This novel LTT-MELISA ® assay appears to correlate with active LB and may have diagnostic relevance in confirming LB in clinically and serologically ambiguous cases.

The fungus Pneumocystis jirovecii ( P. jirovecii ) causes Pneumocystis Pneumonia (PCP) in immunosuppressed patients, most frequently in HIV patients. More recently, the number of PCP cases in transplant patients and patients with immunosuppressive disorders or therapy has markedly increased. P. jirovecii is routinely diagnosed using different staining methods, which are less sensitive than molecular approaches. Using PCR-based methods, the sensitivity exceeds 95%. Distinct PCR methods may also be used for resistance testing or the detection of transmission routes between patients.

Pneumocystis pneumonia (PCP), caused by the fungus Pneumocystis jirovecii ( P. jirovecii ), is known chiefly from its involvement of HIV patients. More recently, however, the number of PCP cases has increased after organ transplants and in other immunosuppressed patients. Laboratory diagnosis of PCP often employs traditional staining methods with low sensitivity. Molecular methods using the polymerase chain reaction can achieve a sensitivity of >95% and can – depending on the detected gene – also be used for resistance testing to trace chains of infection.