Caputo Marina, Pigni Stella, Mele Chiara, Pitino Rosa, Marzullo Paolo, Prodam Flavia, Aimaretti Gianluca
Department of Health Sciences, University of Piemonte Orientale, Novara, Italy.
Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.
Rev Endocr Metab Disord. 2024 Dec 17. doi: 10.1007/s11154-024-09938-1.
Growth hormone (GH) secretion is pulsatile, entropic, and nycthemeral and is mainly controlled by the hypothalamus through two neurohormones, the stimulating growth hormone releasing hormone (GHRH) and the inhibiting somatostatin. Shortly after its discovery and synthesis, GHRH was intensely investigated diagnostically to define GH secretion. The nascent enthusiasm for using GHRH as a single diagnostic tool to investigate GH deficiency (GHD) dropped down quickly due to a flawed reproducibility. The subsequent combinatory use of molecules implicated in GH secretion through inhibition of the somatostatinergic tone, such as arginine (ARG), or the synthesis of receptor-orphan pharmaceutical compounds capable of stimulating pituitary somatotrophs to release GH, such as the GH secretagogues (GHSs), improved the reproducibility of GH response to GHRH alone, thus gaining access into the clinical practice by means of different diagnostic approaches. This review will focus on the history of the GHRH test, with main emphasis on GHRH plus ARG as a dynamic testing for the diagnosis of GHD. Our attention will extend crosswise from studies aimed at validating GHRH-based tests for the clinical practice, to address main pitfall conditions capable of affecting per se GH secretion, such as obesity, hypothalamic damage, and ageing. The history of GHRH test has been progressively dismantled due to the cease of its production for business reasons, opening a gap in the diagnostic workup of patients with GHD. In the urgency to seek further robust, safe, and validated diagnostic tests or tools, we hope to stimulate attention on a so important peptide for the health of our patients suffering from pituitary diseases.
生长激素（GH）的分泌是脉冲式、有节律且昼夜性的，主要由下丘脑通过两种神经激素进行调控，即刺激生长激素释放激素（GHRH）和抑制性生长抑素。在GHRH被发现和合成后不久，就对其进行了深入的诊断研究以明确GH的分泌情况。由于其可重复性存在缺陷，最初将GHRH作为单一诊断工具来研究生长激素缺乏症（GHD）的热情很快就消退了。随后，通过抑制生长抑素能张力来影响GH分泌的分子（如精氨酸（ARG））的联合使用，或能够刺激垂体生长激素细胞释放GH的孤儿受体药物化合物（如生长激素促分泌素（GHSs））的合成，提高了单独使用GHRH时GH反应的可重复性，从而通过不同的诊断方法进入了临床实践。本综述将聚焦于GHRH试验的历史，主要强调GHRH加ARG作为诊断GHD的动态试验。我们的关注将从旨在验证基于GHRH的试验用于临床实践的研究横向扩展，以探讨能够影响GH分泌本身的主要陷阱情况，如肥胖、下丘脑损伤和衰老。由于商业原因停止生产，GHRH试验的历史已逐渐被拆解，这在GHD患者的诊断检查中留下了空白。在迫切需要寻求更可靠、安全且经过验证的诊断试验或工具的情况下，我们希望引起人们对这种对垂体疾病患者健康如此重要的肽的关注。
