Heart failure as a multiple hormonal deficiency syndrome

Abstract

The MHD model extends the classic neurohormonal theory and its application by focusing on restoring HF-related metabolic or hormonal deficiencies. Each component of MHD is associated with impaired functional capacity and poor clinical outcome. However, the replacement approaches so far attempted have provided additional benefits on top of standard therapy (Table 2). There are no data regarding the crucial question of whether life expectancy is also improved. Each component of MHD may interact negatively with the deficiency of other hormones. This is not a minor issue because the number of deficiencies has a profound impact on the progression of HF and outcome. In HF patients with concurrent deficiency of testosterone, dehydroepiandrosterone, and IGF-1, the 3-year survival rate was as low as 27% versus 75% when only 1 anabolic hormone was defective.3 Another important issue is the definition of hormonal or metabolic deficiency. Whereas IR is diagnosed by the HOMA-IR and the insulin clamp tests, and GH deficiency is easily identified by the GHRH plus arginine test, a standardized procedure for GH resistance has not yet been officially recommended. The low-T3 syndrome is currently diagnosed by an arbitrarily low-T3 value in the presence of near-normal T4 and TSH. With regard to testosterone and dehydroepiandrosterone, the Endocrine Society has recently issued guidelines for the diagnosis of androgen deficiency in adult men.84 A final, but fundamental, question relates to the meaning of the MHD syndrome. MHD may be one outcome of HF as a complex multiorgan disease. In this scenario, the pituitary gland might be a particular target of HF, with consequent dysfunction of cell lines that control the production of some of the hormones involved in the MHD syndrome. In this case, MHD must be searched for and rectified by adequate hormonal supplementation. If MHD is an ensemble of biomarkers that are not mechanistically linked to HF, MHD may be useful only for staging and monitoring purposes. Finally, if MHD represents the body's attempt to limit energy dissipation, we must acknowledge such an adaptive response and leave the status quo. The evidence presented in this review strongly suggests that MHD is not a simple disease marker or a compensatory response. Even assuming that it originates as an adaptive reaction, ultimately, each hormonal deficiency is associated with reduced functional capacity and, more importantly, is a powerful and independent predictor of poor clinical outcome.3,6,43,48,58,60 This finding in itself justifies the implementation of robust clinical trials to determine whether either single or multiple hormone replacement is a workable strategy to adopt in HF patients in addition to current pharmacotherapy. © 2009 American Heart Association, Inc.