Abstract
In a seminal paper from 1990, Rosen and Bengtsson suggested that hypopituitary patients with a presumed growth hormone (GH) deficiency (GHD) have an excess mortality. Later studies have confirmed this finding but have also shown that the cause of the increased risk of death in these patients is multifactorial, including unreplaced GHD as well as non-physiological replacement therapy of other deficiencies, the etiology of hypopituitarism, and the side effects of tumor treatment. Only a few studies have investigated mortality in hypopituitary patients with GHD receiving GH replacement therapy (GHRT): these studies are retrospective observational studies with a wide range of underlying diseases but most of them show a mortality that is not different from the general population. Even though the research field of survival in GHD patients with and without GHRT is lacking prospective randomized trials, the evidence suggests that GHD in hypopituitary patients contributes to an excess mortality and modern replacement therapy including GHRT will result in a mortality that is approaching normal. Herein, we review the literature in the field of survival in GHD patients with and without GHRT. In addition, we outline the most important issues when evaluating studies in this area.
Highlights
Growth hormone (GH) deficiency (GHD) in adults is a wellknown entity for several decades
The first study that demonstrated an excess mortality in adults with hypopituitarism and presumed GHD was published by Rosen and Bengtsson in 1990 [5]
The sponsored prospective safety surveillance database, the Hypopituitary Control and Complication Study (HypoCCS), published their mortality data in 2013 [22]. They found a lower mortality in patients with GH replacement therapy (GHRT) compared to an untreated control group and an standardized mortality ratio (SMR) of 0.86 compared to the US general population, the mean follow-up period was limited to 2.3 years
Summary
Growth hormone (GH) deficiency (GHD) in adults is a wellknown entity for several decades. Hypopituitarism and its underlying causes are complex and, today, it is believed that the reason for the excess mortality is multifactorial including, for example, the etiology of hypopituitarism, GHD, non-physiological (glucocorticoid) replacement therapies, and tumor treatment and its side effects [8–10]. This role for factors other than GHD has been confirmed by the West Midlands Prospective Hypopituitary Study, since it did not find an association between the degree of hypopituitarism and mortality but did find an association with the risk factors mentioned above [10]. The aim of this paper is to review the effect of severe GHD and daily GHRT on survival in adult patients
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