Rare Bilateral Adrenal Haemorrhage with Addisonian Crisis: When Risk Factors Come in Droves.

Addisonian crisis is the life-threatening acute manifestation of adrenal insufficiency due to absolute or relative glucocorticoid deficiency. Adrenal haemorrhage is a rare condition of unknown incidence with the risk of adrenal insufficiency and death, not uncommonly first being diagnosed on the pathologists table. We report the case of a 68-year-old female patient with respiratory tract infection suffering acute life-threatening adrenal insufficiency caused by bilateral adrenal haemorrhages following orthopedic surgery while taking anticoagulation therapy. The patient rapidly deteriorated with hypotension, showing how important it is to consider a possible Addisonian crisis when this scenario occurs, especially with precipitating factors such as anticoagulant therapy, sepsis, or surgery.

Molecular requirements for the combined effects of TRAIL and ionising radiation.

BACKGROUND AND PURPOSE: Previously it was shown that combination of death ligand TRAIL and irradiation strongly increases cell kill in several human tumour cell lines. Since Bcl-2 overexpression did not strongly interfere with the efficacy, components of the mitochondrial death pathway are not required for an effective combined treatment. In the present study the minimal molecular prerequisites for the efficacy of a combined treatment were determined. MATERIALS AND METHODS: Apoptosis induction in control, caspase-8 and FADD negative Jurkat cells, BJAB control and FADD-DN cells was analysed by FACS. Activation of caspase-8, -10 and -3 and cleavage of PARP was determined by immunoblotting. TRAIL receptors were activated using recombinant human TRAIL. Surface expression of TRAIL receptors DR4 and DR5 was analysed by FACS. RESULTS: Jurkat T-cells express the agonistic DR5 receptor but not DR4. Presence of FADD was found to be essential for TRAIL induced apoptosis. Caspase-8 negative cells show very low rates of apoptosis after prolonged stimulation with TRAIL. No combined effects of TRAIL with irradiation could be found in FADD-DN overexpressing and FADD deficient cells. However, the combination of TRAIL and irradiation clearly lead to a combined effect in caspase-8 negative Jurkat cells, albeit with reduced death rates. In these cells activation of the alternative initiator caspase-10 could be detected after combined treatment. CONCLUSION: Our data show that a combined therapy with TRAIL and irradiation will only be effective in cells expressing at least one agonistic TRAIL receptor, FADD and caspase-8 or caspase-10.