Establishment of Clinical and Lab Algorithms for the Identification of Carriers of Mutations in CYP21A2 - A Study of 365 Children and Adolescents.

BACKGROUND: Mutations of CYP21A2 encoding 21-hydroxylase are the most frequent cause of congenital adrenal hyperplasia (CAH) and are associated either with elevated basal or ACTH-stimulated levels of 17-hydroxyprogesterone (17OHP) in blood. OBJECTIVE: The study objective was to identify the most suitable of 12 different test algorithms and appropriate cut-off levels for that test to recognize patients with non-classical congenital adrenal hyperplasia (NCCAH) and carriers of clinically relevant mutations in CYP21A2. METHOD AND PATIENTS: Between July 2006 and July 2015 ACTH-tests were conducted in 365 children and adolescents (Age 1-20 y) suspected to have NCCAH. As a reference, results from subsequent gene sequencing of CYP21A2 was used. Inclusion criteria that were used were premature pubarche with accelerated bone age, hyperandrogenism, hirsutism, or menstrual irregularities. Receiver operating characteristics (ROC) were plotted. Evaluated test algorithms were composed around 17OHP measurements by radioimmunoassays. The most suitable test was identified by the greatest area under the curve (AUC). RESULTS: Among the 12 tested algorithms, the sum of 30 min and 60 min stimulated 17OHP values (sum17OHPstim) showed the highest AUC of 0.774 for identifying heterozygous and bi-allelic mutations. A cut-off of 10.1 µg/l was advisable. Bi-allelic mutations only were best identified calculating the difference between 30 min and basal 17OHP values (Δ17OHP30). A cut-off of 9.4 µg/l was most effective. CONCLUSION: Alternatively to the above mentioned cut-offs the difference of 60 min after stimulation to basal 17OHP (Δ17OHP60) can be used for the benefit of a combined test to identify both heterozygotes and bi-allelic patients. There are minimal decreases in sensitivity and specificity compared to an approach that applies two tests. However, it denotes a simpler approach in the clinical routine.

[Indomethacin in the prevention of para-articular ossification following total hip endoprosthesis]. / Indomethazin zur Prophylaxe paraartikulärer Ossifikationen (PAO) nach Hüft-Totalendoprothesen.

Indomethacin for prophylaxis of para-articular ossifications (PAO) after Total-Hip-Replacement We studied in a retrospective clinical trial the effect of indomethacin on the prevention of formation of heterotopic bone after total hip replacement. Compared were the grade lesions of ossification (described by Arcq) in the group of 63 patients that had received with the group of patients without indomethacin. Significantly fewer patients (p less than or equal to 0.001) who had received indomethacin had formation of heterotopic bone compared with the control group.

[Spontaneous and simultaneous rupture of the right patellar ligament and avulsion fracture of the left tibial tuberosity in osteomalacia]. / Spontane und simultane Ruptur des Ligamentum patellae rechts und Abrissfraktur der Tuberositas tibiae links bei Osteomalazie.

Bilateral simultaneous and spontaneous patellar tendon ruptures are exceedingly rare. The diagnosis is established by clinical examination. Early diagnosis and surgical repair is essential to provide a satisfactory functional result. A case of patella tendon rupture on the right side and a fracture of the tuberositas tibiae on the other one after minor trauma in an 31-year-old woman with osteomalacia is presented. In case of spontaneous and bilateral tendon ruptures other diseases, especially generalized bone diseases, systemic lupus erythematodes, metabolic diseases and rheumatoid arthritis should be excluded.