ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P694 | DOI: 10.1530/endoabs.63.P694

New markers of systemic inflammation and oxidative macromolecular damage in partial and total Adult Growth Hormone Deficiency

Carmine Bruno, Edoardo Vergani, Alessandro Brunetti, Francesco Guidi, Flavia Angelini, Elisabetta Meucci, Andrea Silvestrini, Umberto Basile & Antonio Mancini

Fondazione Policlinico Universitario A Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

It is known that adult growth hormone deficiency (GHD) is associated with oxidative stress (OS): both GH and IGF-1 exert antioxidant functions. OS is in turn related to systemic inflammation and cardiovascular/oncological risk. Discordant data concerning GH effects on antioxidants are reported. Moreover, no data are available in partial GHD, which can induce cardiovascular alterations. To evaluate oxidative damage on macromolecules and systemic inflammation, 80 patients, studied by GHRH+arginine test were enrolled. On the basis of GH peak, they were classified as: 26 total-GHD (t-GHD) (39–70 years, BMI 31.1±2.6 Kg/m2 with peak GH<9 ug/l or <4 ug/l when BMI≥30 kg/m2), 25 partial-GHD (p-GHD) (24–73 years; BMI 26.9±1.5, with GH peak 9–16 ug/l). Finally, 29 subjects (aged 20–73 years, BMI 25.5±1.1) with GH peak>16 ug/ml were classified as controls (ctrl). A blood sample was collected for Total Antioxidant Capacity (TAC) evaluation, by spectroscopical method, expressed as latency time of appearance of radical species using the Metmyoglobin-H2O2-ABTS system. In t-GHD and ctrl we also evaluated k and λ free light chains (FLCs), produced by plasmacells and related to chronic inflammation, by turbidimetric method. A morning urine sample was collected for determination, by ELISA, of: Hexanoyl-Lysine (HEL) adduct, biomarker of lipid peroxidation; dityrosine (DT), biomarker of protein oxidation; 8-OH-2-deoxy-guanosine (8–OHdG), parameter of DNA damage. Concerning urine parameters, a trend to increase in HEL in t-GHD vs p-GHD and ctrl was observed, although not significant. 8-OHdG did not significantly differ among the three groups. On the contrary, significantly lower levels of DT in p-GHD vs t-GHD and ctrl were found (mean±S.E.M, 0.41±0.10, 1.07±0.19 and 0.83±0.24 umol/l, respectively, P<0.05). The most important results were observed in TAC, which was significantly increased in p-GHD vs controls, with further significant increment in t-GHD (52.3±2.9, 43.39±2.2 and 67.7±3.0 sec, respectively, P<0.05). Concerning FLCs, t-GHD showed levels significantly higher than ctrl (k 37.21±6.97 and 12.34±0.85 mg/l; λ 19.44±2.61 and 11.67±0.77 mg/l, respectively). Our data show an increase in antioxidants, related to GHD severity; while in p-GHD such compensation is sufficient to counteract oxidative damage, leading to low DT levels, in t-GHD, oxidative and inflammatory parameters again augmented, despite further increase of antioxidants. These data suggest a condition of antioxidant reactivity also in p-GHD, hypothesizing a condition of OS, magnified in t-GHD. If partial and total-GHD represent different phases in the natural history of this condition requires further investigations.