Background: Monitoring of treatment for patients diagnosed with congenital adrenal hyperplasia (CAH) can be performed by measuring the concentration of 17a-hydroxyprogesterone (17OHP) in bloodspots collected on filter papers. A method is described here for measuring 17OHP by liquid chromatography tandem mass spectrometry (LCMSMS). Methods: 17OHP was extracted by liquid-liquid extraction and analysed by LCMSMS. The method was validated for sensitivity, specificity, linearity, recovery, ion suppression, precision and bias. Results: The standard curve was linear from 0 to 400 nmol/L. Intra-assay %CVs were <10 and inter-assay %CVs were <15 over the range 10-200 nmol/L. Limit of quantitation was 6 nmol/L. No ion suppression was detected. The only interfering compound detected was deoxycorticosterone, an intermediate steroid with the same molecular weight as 17a-hydroxyprogesterone. The method was more accurate and precise than an existing radioimmunoassay. There was poor correlation between the two assays. Conclusions: We have developed a sensitive and specific assay suitable for quantitation of 17OHP in bloodspots. This method performs better than radioimmunoassay and allows smaller samples to be used.

Both FLC assays show good correlation in detecting the abnormal light chain subtype with discordance in absolute values and thus are not interchangeable.

Cryoglobulinaemia is characterised by immunoglobulins which precipitate at temperatures be-low 37°C and redissolve on warming. Monoclonal IgM immunoglobulin may be associated with type I and II cryoglobulinaemia with underlying Waldenström macroglobulinemia, monoclonal gammopathy of undetermined significance or other non-Hodgkin lymphoma. We review the clinical characteristics, laboratory testing and suggest a management approach for monoclonal IgM associated cryoglobulinaemia. Laboratory testing is critical as even a minimal amount of measurable cryoglobulin may result in symptoms. Accurate detection of cryoglobulins may be challenging and care must be taken with preanalytical variables and repeat testing of monoclo-nal protein and cryoglobulins is indicated if clinical suspicion is high. Presentations range from asymptomatic disease to multisystem involvement so careful evaluation of the features and thorough interrogation of organ systems and the underlying clone is critical. Immediate man-agement is required for clinical red flag features. Due to their rarity, data to inform treatment decisions are scant and collaborative research is imperative to aid defining optimal treatment strategies.

Cryoglobulinaemia is characterised by serum immunoglobulins that precipitate at temperatures below 37 °C and redissolve on warming. Monoclonal IgM immunoglobulin can be associated with type I and II cryoglobulinaemia with underlying Waldenström macroglobulinemia, monoclonal gammopathy of undetermined significance, or another non-Hodgkin lymphoma. In this research, we review the clinical characteristics of monoclonal IgM-associated cryoglobulinaemia and suggest a management approach for addressing them. Laboratory testing is critical as even a minimal amount of measurable cryoglobulin may result in symptoms. Accurate detection of cryoglobulins may be challenging, care must be taken with preanalytical variables, and repeated testing of monoclonal protein and cryoglobulins is indicated if clinical suspicion is high. Presentations range from asymptomatic to showing multisystem involvement, meaning that careful evaluation of the features and a thorough interrogation of organ systems and the underlying clone are critical. Immediate management is required for clinical red-flag features. Due to their rarity, data to inform treatment decisions are scant and collaborative research is imperative must be conducted to aid researchers in efforts to define optimal treatment strategies.