The history of an effective, specific and sensitive diagnostic test: the GHRH test in clinical practice

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.