GH Supplementation Effects on Cardiovascular Risk in GH Deficient Adult Patients: A Systematic Review and Meta-analysis

Abstract

Background and Objective: The current meta-analysis aims at evaluating whether the existing clinical evidence may ascertain the effects of growth hormone (GH) replacement therapy on cardiovascular risk, both in isolated GH deficien-cy (GHD) and in compensated panhypopituitarism including GH deficit.Methods: Original articles published from 1991 to 2015 were searched on Medline (Pubmed). Among an overall number of 181 potentially suitable studies, 24 fulfilled the selection criteria and were included in the analysis. Data aggregation was car-ried out through the calculation of the absolute risk reduction. The meta-analysis was then conducted by means of a fixed-effects model, according to the heteroge-neity test (Chi-square statistic).Results: Fat-free mass (FFM) increase and fat mass (FM) reduction were found, together with a C-LDL reduction, a wide variation in glycaemia and a neutral effect on glycated haemoglobin (HbA1c) and blood pressure. These effects were valid both for isolated GHD patients and for those with compensated panhypopituitarism. The global out-come D showed a nonsignificant reduction of the overall cardiovascular risk (0.53; 95% C.I. -1.23, 2.85).Conclusion: Our meta-analysis shows no signnificatly positive trend in cardiovascular risk after both short and long-term GH supplementation therapy in adult GHD patients. However, a reduction of LDL cholesterol levels has been found. No differences were found between isolated GHD participants and those affected by panhypopituitarism well compensated since at least 3 months.

Follow-Up Study of Growth Hormone Therapy in Children with Kabuki Syndrome: Two-Year Treatment Results

“…Since ApoB100 concen- trations were also lowered, it can be suggested that not only LDL cholesterol concentrations but also the number of LDL particles was reduced. A recent meta-analysis by Giagulli et al [38] revealed an overall reduction in LDL levels in GHD patients, which echoes the findings in our study. This finding points to a preventative intervention against cardiovascular problems later in life.…”

IGF-1 and cardiovascular disease

“…On the other hand, a small-scale study indicated a lack of evidence of premature atherosclerosis in untreated severe GH deficiency due to a GH-releasing hormone receptor mutation [66], and also a study reported a lack of evidence of elevated mortality due to cardiovascular diseases in Laron syndrome subjects [67]. Of note, a recent meta-analysis failed to confirm a significant positive trend in cardiovascular risk after short and long-term GH supplementation therapy in adult GHD patients [68]. Potentially consistent with these clinical reports, twice-daily sc injection of GH releasing peptide-2 (20 μg/injection, a dose that significantly increases GH and IGF-1 levels [69]) failed to decrease atherosclerosis in Apoe-null mice, even though it successfully elevated serum IGF-1 levels, contradicting atheroprotective effects of IGF-1 [70].…”

Radiotherapy as a tool for the treatment of Cushing’s disease

“…Last but not least, secondary adrenal insufficiency (45,67,68), as well as untreated gonadotropin-deficiency (67,69), are associated with increased mortality. Also, central hypothyroidism (70) and growth hormone deficiency (71) are associated with adverse cardiometabolic profiles. Furthermore, at least half of all patients diagnosed with CD are young adults (72).…”