Uncertainties in endocrine substitution therapy for central endocrine insufficiencies: growth hormone deficiency.

The growth hormone deficiency (GHD) syndrome is associated with several metabolic abnormalities and it has been postulated that the increased cardiovascular disease (CVD) morbidity and mortality in GHD patients may be related to the missing metabolic effects of GH. Many CVD risk factors show improvements after GH therapy. Reduced bone mineral density (BMD) has been recorded both in patients with isolated GHD and in those with multiple pituitary deficiencies, indicating that GHD per se is responsible for the low BMD in both types of patients. These matters are, however, more complicated, as hypopituitary patients with GHD may have different phenotypes due to differences in underlying diagnoses. These phenotypes may not be clear-cut in individual patients. Moreover, patients may transit between different phenotypes over time due to extension of the pathology in the pituitary and/or the consequences of the treatment (surgery and/or radiotherapy). Three different phenotypes of hypopituitary patients will be discussed, with a focus on CVD risk and bone health: (1) patients with isolated GHD, e.g. due to prophylactic cranial radiotherapy for lymphoblastic leukaemia in childhood; (2) patients with GHD and multiple hormone deficiencies due to pituitary macroadenomas treated by surgery; (3) patients with GHD caused by craniopharyngiomas with multiple hormone deficiencies and hypothalamic involvement, where hypothalamic damage frequently dominates the positive metabolic effects of GH therapy. These phenotypes illustrate the differential impact of various pituitary pathologies on the phenotype of patients with GHD.