Adult growth hormone deficiency (GHD) must be considered in the context of hypopituitarism, as the growth hormone (GH) axis is usually the first hormonal axis to be affected in patients with hypothalamic-pituitary disorders or as a consequence of their surgical or radio-oncological treatments [1], [2]. The clinical phenotype of hypopituitarism is highly variable and strongly dependent on the number of affected pituitary hormone deficiencies involved. Accurate epidemiological data on GHD in hypopituitarism are scarce. This is mainly due to the fact that the diagnosis of GHD requires dynamic testing, which is not routinely performed in all patients with hypopituitarism. Therefore, epidemiological data on patients with GHD can be approximated by epidemiological data on hypopituitarism. Cross-sectional studies from Spain have documented an overall prevalence of about 30-45 affected individuals per 100,000 persons [3], while the incidence of hypopituitarism has been reported to be around 4-5 per 100,000 persons per year [3].

Childhood-onset GHD is most often idiopathic and isolated. Other causes such as genetic, pituitary and brain tumours and their treatment (surgery and radiotherapy) do, however, exist but are rare [4]. Current guidelines suggest that all patients transitioning to adult care should be reassessed for GH deficiency, as most of these patients will regain normal GH secretion by adulthood [5], [6]. However, children with structural lesions of the hypothalamic-pituitary region or genetic causes are more likely to have persistent GHD requiring continued GHRT into adulthood [5]. In childhood, the clinical phenotype is primarily characterised by impaired growth. Growth per se is an extreme form of anabolism and GH has been shown to have important anabolic effects on protein and bone metabolism [7], [8].

Over the last few decades, the interest in GH and GH replacement therapy (GHRT) in adults has increased significantly due to two main events: First, the availability of recombinant GH as treatment option since the late 1980s and second, the publications of two landmark studies reporting poor outcomes of patients with GHD who did not receive GHRT [9], [10], with standard mortality rates (SMR) twice as high when compared to individuals under replacement therapy. The poorer outcome was mainly driven by a higher susceptibility of patients with GH deficiency towards cardiovascular events and associated mortality.

Adults with GHD present with a clinical phenotype that is characterized by increased fat mass − predominantly visceral fat – and reduced lean body mass [11]. This phenotype mimics features of the metabolic syndrome with signs of insulin resistance [12] and it is therefore not surprising that dyslipidaemia is a common finding in affected individuals. The dyslipidaemia documented in people with GH deficiency is mainly characterised by elevated total cholesterol and low-density lipoprotein (LDL) levels, both of which are established risk factors for the development of atherosclerotic cardiovascular disease (ASCVD) [13] and may be the underlying cause of the increased mortality observed in hypopituitary patients [14]. Studies have shown that these changes in lipid profiles can be reversed with GHRT [15]. In particular, observational data suggest that patients with hypopituitarism who receive GHRT have a lower mortality rate compared to individuals with those who not receive GHRT [1]. It is therefore tempting to speculate that the adverse lipid profile of GHD may be the causal factor for the increased mortality rate in hypopituitarism patients and that GHRT may have the ability to reduce this increased mortality rate to normal levels. However, whether there is a causal relationship between GHRT and these observations is still unclear because of the lack of prospective, placebo-controlled trials with hard clinical endpoints, i.e. major adverse cardiovascular (CV) events or CV-mortality.

This review aims at summarizing the current knowledge of altered lipid metabolism in GHD and the effect of GHRT on lipid profiles in children and adults. We will discuss possible underlying mechanisms and their clinical implications and highlight hot topics with unanswered questions.