Update in mortality in GH-treated patients

Abstract

During GH therapy for 2.3-9.6 years, male adult-onset GH-deficient patients with a diagnosis of a nonfunctioning adenoma have no increased all-cause mortality. However, women with adult-onset GH deficiency (GHD) are still at slightly higher risk. This general improvement in mortality is due to a more contemporary regimen of cardiovascular drugs, a refinement of surgical procedures, besides the introduction of GH therapy improved hormone replacement regimens with lowered glucocorticoid replacement, updated approaches of sex steroids for women, and less use of cranial radiotherapy. The underlying disease is the most important predictor for mortality: eg, a craniopharyngioma, malignant causes of hypopituitarism, previous Cushing's disease, and the presence of diabetes insipidus/aggressive tumors. The main cause of increased mortality was cerebrovascular diseases and infectious/respiratory diseases in ACTH-deficient patients. Furthermore, there was a significant impact of young age at disease onset and of death from secondary brain tumors, with a higher risk after cranial radiotherapy. Reports on four cohorts of GH-treated childhood-onset GHD patients have been published. Two of them included only patients with idiopathic isolated GHD, neurosecretory dysfunction, idiopathic short stature, or being born short for gestational age. Increased mortality in circulatory disorders, ill-defined diseases, and bone cancer were recorded in one study, but not in the other smaller study, where suicide and accidents caused the majority of deaths. A third childhood-onset GHD cohort included patients with a background of malignant tumors, craniopharyngioma, pituitary adenomas, pituitary aplasia/hypoplasia, and trauma. An increase of all-cause mortality was recorded in both males and females. The fourth cohort included isolated GHD and idiopathic short stature (60%), but also diagnosis of chronic renal failure and Turner's syndrome. In these latter studies, an underlying serious condition was the most important factor for death, with central nervous system tumors (recurrent or new tumor) being the leading cause of mortality.