Low-dose growth hormone administration mobilizes endothelial progenitor cells in healthy adults.

OBJECTIVE: Endothelial progenitor cells (EPCs) mobilize from the bone marrow secondary to a stimulus and home to sites of injury, where they differentiate into endothelial cells and contribute to the repair of damaged vasculature. We hypothesized that growth hormone (GH) administration would increase the number of circulating EPCs in adults and thereby represent a mechanism to enhance vascular health. DESIGN: A prospective trial of low-dose GH (0.03mg/kg/week for 4 weeks followed by 0.06mg/kg/week for a maximum of four additional weeks) in 10 healthy adults (6 males and 4 females; mean age 37 years, range 26-65). Primary outcomes measured included the number of circulating EPCs as assessed by colony-forming unit (CFU) assay and flow cytometry. Secondary outcomes included plasma measurements of known mediators of EPC mobilization and indices of nitric oxide (NO). Outcomes were measured at baseline and at study completion. RESULTS: GH administration increased serum IGF-1 (143ng/mL [IQR 121-164] to 222 [IQR 194-244]; P=0.005). The increase in early-outgrowth EPCs (13 CFU per high-power field [IQR 6-24] to 19 [IQR 13-40]; P=0.005) correlated with the peak IGF-1 after adjustment for the baseline number of early-outgrowth EPCs (r=0.719 [95% CI 0.06, 0.93]; P=0.027). The number of late-outgrowth EPCs as well as CD34+, VEGFR2(KDR)+, and AC133+ cells did not significantly change. Other mediators of EPC mobilization were stable while plasma nitrite trended upwards (1.3micromol/L [IQR 0-2.5] to 3.7 [IQR 2.2-8.9]; P=0.052). CONCLUSIONS: GH administration selectively augments the early-outgrowth EPC population in healthy individuals. These findings both support GH replacement in the setting of GH deficiency to maintain vascular integrity and have implications for the use of GH in future regenerative cell-based therapies. Furthermore, the decrease in EPCs observed with aging may in part be explained by the declining somatotropic axis, and thereby contribute to cardiovascular senescence.

Markedly impaired fibrinolytic balance contributes to cardiovascular risk in adults with growth hormone deficiency.

CONTEXT: Adults with GH deficiency (GHD) have multiple cardiovascular risk factors, including an unfavorable lipid profile and body composition as well as impairments in endothelial function and cardiac performance. We hypothesized that GHD is associated with elevated levels of plasminogen activator inhibitor-1 (PAI-1), the major inhibitor of plasminogen activation in the circulation. OBJECTIVE: The objective of the study was to determine the fibrinolytic profile of adults with GHD in comparison with controls. STUDY DESIGN AND PARTICIPANTS: This was a prospective, observational study including 12 adults with GHD. Twelve gender-, age-, and body mass index-matched adults served as controls. MAIN OUTCOME MEASURES: The primary outcome measures were circadian plasma PAI-1 antigen with corresponding tissue-plasminogen activator (tPA) activity values. Endothelial function was assessed by flow-mediated vasodilation and fibrinolytic potential by venous occlusion test. RESULTS: Adults with GHD exhibited an unfavorable 24-h fibrinolytic profile characterized by a mean 62% elevation in PAI-1 antigen (2.77 ng/ml after adjustment for baseline PAI-1; P = 0.049) in the setting of a mean 24% reduction in tPA activity (-0.17 IU/ml after adjustment for baseline tPA; P = 0.003). Fibrinolytic response was defective in GHD, as demonstrated by a sustained elevation in PAI-1 activity greater than 4 IU/ml after venous occlusion [7.2 IU/ml (interquartile range 0.8-17.4); P = 0.018]. Endothelial function was impaired in GHD, as quantified by percent flow-mediated vasodilation over 120 sec [area under the curve 3.8 (interquartile range -2.4 to 7.9) vs. 12.8 (interquartile range 2.1-19.4); P = 0.043]. CONCLUSIONS: Adults with GHD demonstrate alterations in plasma fibrinolytic balance, including elevated levels of PAI-1 antigen with decreased tPA activity. These changes may contribute to the increased cardiovascular morbidity within this population.

Disorders of water metabolism following transsphenoidal pituitary surgery: a single institution's experience.

Disorders of water metabolism are a common complication of pituitary surgery. The primary purpose of this study was to determine the incidence and duration of post-surgical diabetes insipidus (DI) at our institution. Secondary objectives included characterizing the incidence of post-operative hyponatremia as well as delineating factors associated with the onset of these complications. Records of 319 patients who underwent transsphenoidal pituitary surgery at the authors' institution between 1998 and 2005 were reviewed for the presence of disorders of water metabolism using pre-specified criteria. DI was diagnosed in 59 (18.5%) of our patients at a mean time of 13.6 h following surgery. DI resolved in nearly half of our patients within one week. Approximately 80% of our patients enjoyed resolution of DI at a mean time of 2.9 months following surgery. Duration of DI was not significantly influenced by tumor size or location. Additionally, 28 (8.8%) of our patients exhibited a period of hyponatremia at a mean time of 4 days following surgery. One quarter of these patients carried a diagnosis of Cushing's disease. We herein report an incidence of DI as well as hyponatremia within our post-operative population comparable to that reported by other high-volume pituitary centers. Over half of our patients still exhibited DI at the time of discharge, therefore, patient education regarding the treatment of DI, signs of its resolution, and symptoms consistent with the onset of hyponatremia should be an integral part of every hospitalization.