Pralmorelin Hydrochloride

To explore the potential of growth hormone–releasing peptide 2 (GHRP‐2) for tendon‐bone healing in a rat rotator cuff tear (RCT) model.

The impact of GHRP‐2 on M1 macrophage polarization in vitro was determined using real‐time polymerase chain reaction, Western blot, and immunofluorescence staining. GHRP‐2 was then applied in a rat RCT model, and the healing of the tendon‐bone interface was systemically evaluated by histologic staining, radiologic assessments, gait analysis, and biomechanical tests. M1 macrophage polarization at the tendon‐bone interface was assessed by immunofluorescence staining.

GHRP‐2 was found to reduce the expression of Cd86 , Nos2 , and tnfa (all P < .01), suggesting inhibited M1 macrophage polarization in vitro. The in vivo experiments showed that the proportion of M1 macrophages was reduced both 2 and 4 weeks after surgery ( P < .01), and the number of M1 was reduced 4 weeks after surgery ( P < .01) at the tendon‐bone interface. The in vivo experiments also showed that histologic scores and bone mineral density were increased by GHRP‐2 at 8 weeks postsurgery ( P < .01), suggesting improved healing of the tendon‐bone interface. Furthermore, the GHRP‐2 group showed a better biomechanical property at both 4 and 8 weeks postsurgery, including maximal failure load, stiffness, and tension (all P < .01), and better gait parameters at 8 weeks postsurgery, including mean area of the left front foot and mean intensity of the right front foot (all P < .05).

GHRP‐2 may be associated with decreased M1 macrophage production and increased histologic and biomechanical tendon‐bone healing properties in a rat RCT model.

The present study might be a transitional study to show the efficacy of GHRP‐2 in enhancing bone‐tendon healing and reduce retear rate after rotator cuff repair.

Growth hormone deficiency (GHD) develops early in patients with hypothalamic-pituitary disorder and is frequently accompanied by other anterior pituitary hormone deficiencies, including secondary adrenal insufficiency (AI). A growth hormone–releasing peptide-2 (GHRP2) test, which is widely used for the diagnosis of patients with GHD, is thought to induce release of not only growth hormone (GH) but also ACTH. However, its clinical usefulness in hypothalamic-pituitary disorder is unclear.

We aimed to determine the clinical utility of the GHRP2 test in patients with hypothalamic-pituitary disorders, particularly for AI concomitant with GHD.

The GHRP2 test, a cosyntropin stimulation test, corticotropin-releasing hormone (CRH) tests, and/or insulin tolerance tests (ITTs) were performed on 36 patients with hypothalamic-pituitary disorder.

Twenty-two (61%) had severe GHD, and 3 (8%) had moderate GHD by GHRP2. There was no difference in baseline ACTH and cortisol between non-GHD, moderate GHD, and severe GHD participants. However, a cosyntropin stimulation test and subsequent CRH tests and/or ITTs revealed that 17 (47%) had secondary AI and 16/17 (94%) cases of secondary AI were concomitant with severe GHD. ROC curve analysis demonstrated that the ACTH response in the GHRP2 test was useful for screening pituitary-AI, with a cutoff value of 1.55-fold (83% sensitivity and 88% specificity). Notably, the combination of ACTH response and the peak cortisol level in the GHRP2 test using each cutoff value (1.55-fold and 10 µg/dL, respectively) showed high specificity (100%) with high accuracy (0.94) for diagnosis of pituitary-AI.

We recommend measuring ACTH as well as GH during the GHRP2 test to avoid overlooking or delaying diagnosis of secondary AI that frequently accompanies GHD.