Vol.:(0123456789) 1 3 Journal of Endocrinological Investigation https://doi.org/10.1007/s40618-019-01051-4 RAPID COMMUNICATION Impact of CFTR‑modulating drugs on GH‑IGF‑1 axis impairment in adult patients with cystic fbrosis C. Pascucci 1  · R. V. De Biase 2  · D. Savi 2,3  · S. Quattrucci 4  · L. Gnessi 1  · C. Lubrano 1  · A. Lenzi 1 Received: 27 November 2018 / Accepted: 10 April 2019 © Italian Society of Endocrinology (SIE) 2019 Abstract Introduction A new class of drugs in the treatment of cystic fbrosis (CF) includes two agents: lumacaftor, which corrects CFTR channel protein, and ivacaftor, which increases CFTR channel activity. In our previous study we recruited 50 stable adults with CF and 16 of them showed growth hormone defcit (GHD): 7 patients severe and 9 patients partial GHD. Material and methods We decided to re-evaluate ten patients with the GHRH + arginine test of whom only fve were treated with lumacaftor/ivacaftor. Results All CF patients in therapy with lumacaftor/ivacaftor showed a marked improvement in GHD. Two patients moved from a severe GHD to a normal response to the GH/IGF-1 axis test, and three patients who had partial GHD moved to normal response. Conclusion The pituitary gland may be damaged by CF disease and could beneft of the action of correcting drugs. Keywords Growth hormone · Insulin-like growth factor-1 · Cystic fbrosis · Lumacaftor · Ivacaftor · Adult patients Introduction In previous study, using the GHRH + arginine stimulus test, we diagnosed an alteration of the GH-IGF-1 axis (GHD, growth hormone defciency) in 16 of 50 adult CF patients (32%, based on the cut ofs established for BMI): seven patients with severe GHD (14%) and nine with partial GHD (16%). Initial hypothesis of the etiological mechanism of this late onset GHD was based on the belief that chronic tissue hypoxia of the pituitary gland leads to an alteration in the production and secretion of GH growth hormone. In fact, this mechanism of action has already been documented in the literature for other chronic diseases [1–3]. Pulmo- nary function data showed no signifcant diference between patients with GHD compared to those with normal GH/ IGF-1 function. We then looked for any other causes of the onset of the defciency, and in the course of previous work a correlation emerged between the presence of the homozy- gous F508del mutation and the GH deficiency in adult patients with CF leading to the hypothesis that there was a genetic predisposition in these patients to develop the GHD [4]. The most innovative therapy in treating CF consists of a new class of drugs called modulators of the CFTR protein channel (cystic fbrosis transmembrane conductance regula- tor). Lumacaftor (LUM), is a CFTR corrector that has been shown to correct F508del CFTR misprocessing and increase the amount of cell surface-localized protein. Ivacaftor (IVA) is an approved potentiator that increases CFTR chan- nel activity [5, 6]. The combination of the corrector LUM with the potentiator IVA has been approved for treatment of CF patients homozygous for F508del CFTR mutation [7]. F508del CFTR belongs to the II class of CFTR mutations and is by far the most widespread, serious mutation in the world. To date, longer-term efect of LUM/IVA treatment on GHD has not been investigated. * C. Pascucci chiarapascucci@libero.it 1 Section of Medical Pathophysiology, Endocrinology, Department Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy 2 Cystic Fibrosis Unit, Bambino Gesù Children’s Hospital, Rome, Italy 3 Department of Public Health and Infectious Diseases, Adult Cystic Fibrosis Center, Sapienza University of Rome, 00185 Rome, Italy 4 Pediatrics Department, Cystic Fibrosis Regional Center, Sapienza University of Rome, Rome, Italy