Growth hormone deficiency and human immunodeficiency virus.

Best practice & research. Clinical endocrinology & metabolism2017PMID: 28477736

View on PubMed DOI: 10.1016/j.beem.2017.02.006

Plain Language Summary

Review of GH/IGF-1 axis dysfunction in HIV infection—covering both GH deficiency from increased somatostatin tone and AIDS wasting—and the evidence for tesamorelin as a targeted GHRH analog that restores pulsatile GH secretion to reduce visceral fat without the supraphysiologic side effects of exogenous GH therapy. Provides endocrinological context for tesamorelin's mechanism. Establishes the endocrine rationale for tesamorelin's mechanism in HIV—explaining why GHRH analog therapy (physiologically stimulated GH pulses) is preferable to direct GH replacement (continuous supraphysiologic exposure) for treating HIV-associated GH deficiency and lipodystrophy.

Abstract

Treatment with highly active antiretroviral drugs (HAART) is associated with several endocrine and metabolic comorbidities. Pituitary growth hormone (GH) secretion seems to be altered in human immunodeficiency virus (HIV) infection, and about one-third of patients have biochemical GH deficiency (GHD). We undertake a historical review of the functioning of the GH/insulin-like growth factor-1 (IGF-1) axis in patients with acquired immunodeficiency syndrome, and provide an overview of the main changes of the GH/IGF-1 axis occurring today in patients with HIV. Both spontaneous GH secretion and GH response to provocative stimuli are reduced in patients with HIV infection, especially in those with HIV-related lipodystrophy. The role of fat accumulation on flattened GH secretion is discussed, together with all factors able to potentially interfere with the pituitary secretion of GH. Several factors contribute to the development of GHD, but the pathophysiologic mechanisms involved in the genesis of GHD are complex and not yet fully elucidated owing to the difficulty in separating the effects of HIV infection from those of HAART, comorbidities and body changes. An update on the putative mechanisms involved in the pathogenesis of altered GH secretion in these patients is provided, together with an overview on the therapeutic strategies targeting the GH/IGF-1 axis to counteract fat redistribution associated with HIV-related lipodystrophy. The clinical significance of GHD in the context of HIV infection is discussed. The administration of tesamorelin, a GH releasing hormone analogue, is effective in reducing visceral fat in HIV-infected patients with lipodystrophy. This treatment is promising and safer than treatment with high doses of recombinant human growth hormone, which has several side-effects.

Authors

Rochira, Vincenzo; Guaraldi, Giovanni

Keywords

GHGHDHIVIGF-1hypopituitarism