Pituitary-adrenal function in asthmatic patients treated with high dose of beclomethasone.

Ten asthmatic patients receiving long term treatment with high dose of inhaled beclomethasone dipropionate (BDP) (750 to 2,250 micrograms/die, average 1,400 +/- 474 micrograms) underwent evaluation of hypothalamic-pituitary-adrenal (HPA) axis under basal conditions (serum cortisol and ACTH levels at 8.00 AM and 8.00 PM, 24-hours free urinary cortisol) and by means of pharmacological tests (short tetracosactide and Corticotrophin Releasing Factor Tests). Basal ACTH serum levels at 8.00 PM were lower than the normal values in all patients: three patients had reduced 24-hr free urinary cortisol and six subjects showed lower cortisol serum levels at 8.00 PM. A normal response to the short tetracosactide test was observed in all patients, whilst Corticotrophin Releasing Factor (CRF) induced an increase in ACTH and cortisol levels (expressed as delta AUC) that was significantly lower in the BPD treated patients compared with a control group of five healthy subjects (p < 0.05). Thus BPD, in high doses, may cause a partial inhibition of HPA axis. Our results show that determination of basal ACTH level and CRF test are more sensitive than serum cortisol levels and short tetracosactide test to evaluate a suppression of HPA axis in patients receiving long term inhaled high doses of BD

T regulatory cells distinguish two types of primary hypophysitis

Numerous cases of primary hypophysitis have been described over the past 25 years with, however, little insight into the cause(s) of this disease. In order to guide treatment, a better understanding of the pathogenesis is needed. We studied the pathogenesis of primary hypophysitis by analysing systematically the immune response at the pituitary tissue level of consecutive cases of ‘lymphocytic’ hypophysitis who underwent pituitary biopsy. In order to investigate further the pathogenesis of their diseases we characterized two cases at clinical, cellular and molecular levels. We show here, for the first time, that lymphocytic hypophysitis probably encompasses at least two separate entities. One entity, in agreement with the classical description of lymphocytic hypophysitis, demonstrates an autoimmune process with T helper 17 cell dominance and lack of T regulatory cells. The other entity represents a process in which T regulatory cells seem to control the immune response, which may not be self- but foreign-targeted. Our data suggest that it may be necessary to biopsy suspected primary hypophysitis and to analyse pituitary tissue with immune markers to guide treatment. Based on our results, hypophysitis driven by an immune homeostatic process should not be treated with immunosuppression, while autoimmune-defined hypophysitis may benefit from it. We show here for the first time two different pathogenic processes classified under one disease type and how to distinguish them. Because of our findings, changes in current diagnostic and therapeutic approaches may need to be considered