Targeted gene deletions, mutagenesis screens and a genome-scale RNA interference (RNAi) screen have identified approximately 300 gene inactivations that cause fat reduction and approximately 100 gene inactivations that cause fat accumulation without significant effects on growth and viability ( Ashrafi et al., 2003 ; Jia et al., 2004 ; Kniazeva et al., 2004 ; Kniazeva et al., 2003 ; Ludewig et al., 2004 ; Mak et al., 2006 ; McKay et al., 2003 ; Mukhopadhyay et al., 2005 ; Taubert et al., 2006 ; Van Gilst et al., 2005 ; Vellai et al., 2003 ; Watts and Browse, 2002 ; Yang et al., 2006 ). Another approximately 250 gene inactivations cause dramatic fat reductions concomitant with defects ranging from sterility to growth arrest and lethality. Because of these pleiotropies, it is difficult to assign specific fat regulatory functions to such genes although they include some well-known components of metabolism.
During minor illness (., flu or fever >38° C [° F]) the hydrocortisone dose should be doubled for 2 or 3 days. The inability to ingest hydrocortisone tablets warrants parenteral administration. Most patients can be educated to self administer hydrocortisone, 100 mg IM, and reduce the risk of an emergency room visit. Hydrocortisone, 75 mg/day, provides adequate glucocorticoid coverage for outpatient surgery. Parenteral hydrocortisone, 150 to 200 mg/day (in three or four divided doses), is needed for major surgery, with a rapid taper to normal replacement during the recovery. Patients taking more than 100 mg hydrocortisone/day do not need any additional mineralocorticoid replacement. All patients should wear some form of identification indicating their adrenal insufficiency status.