Abstract
Biological markers (biomarkers) play a key role in drug development, regulatory approval
and clinical care of patients and are linked to clinical and surrogate outcomes.
Both acromegaly and Growth Hormone Deficiency (GHD) are pathological conditions related to
important comorbidities that, in addition to having stringent diagnostic criteria, require valid markers
for the definition of treatment, treatment monitoring and follow-up. GH and insulin-like growth
factor-I (IGF-I) are the main biomarkers of GH action in children and adults while, in acromegaly,
both GH and IGF-I are established biomarkers of disease activity.
However, although GH and IGF-I are widely validated biomarkers of GHD and acromegaly, their
role is not completely exhaustive or suitable for clinical classification and follow-up. Therefore,
new biological markers for acromegaly and GH replacement therapy are strongly needed.
The aim of this paper is to review and summarize the current state in the field pointing out new
potential biomarkers for acromegaly and GH use/abuse.
Keywords:
Growth hormone, miRNA, acromegaly, GH deficit, biomarkers, insulin-like growth factor-I.
Graphical Abstract
[29]
Cook, DM.; Yuen, KC.; Biller, BM.; Kemp, SF.; Vance, ML. American Association of Clinical Endocrinologists, American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in growth hormone-deficient adults and transition patients - 2009 update Endocr Pract, 2009, 15(Suppl 2), 1-29.
[48]
Rostomyan, L.; Daly, A.F.; Petrossians, P.; Nachev, E.; Lila, A.R.; Lecoq, A.L.; Lecumberri, B.; Trivellin, G.; Salvatori, R.; Moraitis, A.G.; Holdaway, I.; Kranenburg-van Klaveren, D.J.; Chiara Zatelli, M.; Palacios, N.; Nozieres, C.; Zacharin, M.; Ebeling, T.; Ojaniemi, M.; Rozhinskaya, L.; Verrua, E.; Jaffrain-Rea, M.L.; Filipponi, S.; Gusakova, D.; Pronin, V.; Bertherat, J.; Belaya, Z.; Ilovayskaya, I.; Sahnoun-Fathallah, M.; Sievers, C.; Stalla, G.K.; Castermans, E.; Caberg, J.H.; Sorkina, E.; Auriemma, R.S.; Mittal, S.; Kareva, M.; Lysy, P.A.; Emy, P.; De Menis, E.; Choong, C.S.; Mantovani, G.; Bours, V.; De Herder, W.; Brue, T.; Barlier, A.; Neggers, S.J.; Zacharieva, S.; Chanson, P.; Shah, N.S.; Stratakis, C.A.; Naves, L.A.; Beckers, A. Clinical and genetic characterization of pituitary gigantism: An international collaborative study in 208 patients.
Endocr. Relat. Cancer, 2015,
22(5), 745-757.
[
http://dx.doi.org/10.1530/ERC-15-0320] [PMID:
26187128]
[49]
Trivellin, G.; Daly, A.F.; Faucz, F.R.; Yuan, B.; Rostomyan, L.; Larco, D.O.; Schernthaner-Reiter, M.H.; Szarek, E.; Leal, L.F.; Caberg, J.H.; Castermans, E.; Villa, C.; Dimopoulos, A.; Chittiboina, P.; Xekouki, P.; Shah, N.; Metzger, D.; Lysy, P.A.; Ferrante, E.; Strebkova, N.; Mazerkina, N.; Zatelli, M.C.; Lodish, M.; Horvath, A.; de Alexandre, R.B.; Manning, A.D.; Levy, I.; Keil, M.F.; Sierra, Mde.L.; Palmeira, L.; Coppieters, W.; Georges, M.; Naves, L.A.; Jamar, M.; Bours, V.; Wu, T.J.; Choong, C.S.; Bertherat, J.; Chanson, P.; Kamenický, P.; Farrell, W.E.; Barlier, A.; Quezado, M.; Bjelobaba, I.; Stojilkovic, S.S.; Wess, J.; Costanzi, S.; Liu, P.; Lupski, J.R.; Beckers, A.; Stratakis, C.A. Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation.
N. Engl. J. Med., 2014,
371(25), 2363-2374.
[
http://dx.doi.org/10.1056/NEJMoa1408028] [PMID:
25470569]
[50]
Beckers, A.; Lodish, M.B.; Trivellin, G.; Rostomyan, L.; Lee, M.; Faucz, F.R.; Yuan, B.; Choong, C.S.; Caberg, J.H.; Verrua, E.; Naves, L.A.; Cheetham, T.D.; Young, J.; Lysy, P.A.; Petrossians, P.; Cotterill, A.; Shah, N.S.; Metzger, D.; Castermans, E.; Ambrosio, M.R.; Villa, C.; Strebkova, N.; Mazerkina, N.; Gaillard, S.; Barra, G.B.; Casulari, L.A.; Neggers, S.J.; Salvatori, R.; Jaffrain-Rea, M.L.; Zacharin, M.; Santamaria, B.L.; Zacharieva, S.; Lim, E.M.; Mantovani, G.; Zatelli, M.C.; Collins, M.T.; Bonneville, J.F.; Quezado, M.; Chittiboina, P.; Oldfield, E.H.; Bours, V.; Liu, P.; W de Herder, W.; Pellegata, N.; Lupski, J.R.; Daly, A.F.; Stratakis, C.A. X-linked acrogigantism syndrome: Clinical profile and therapeutic responses.
Endocr. Relat. Cancer, 2015,
22(3), 353-367.
[
http://dx.doi.org/10.1530/ERC-15-0038] [PMID:
25712922]
[74]
Schweizer, J.; Haenelt, M.; Schilbach, K.; Giannetti, A.; Bizzi, M.; Rocha, B.; Schopohl, J.; Ribeiro-Oliveira, A.; Bidlingmaier, M. Alpha Klotho as a marker of disease activity in acromegaly. J. Endocrinol. Soc., 2019, 3(suppl. 1), OR32-OR2.
[85]
Mao, ZG.; He, DS.; Zhou, J.; Yao, B.; Xiao, WW.; Chen, CH.; Zhu, YH.; Wang, HJ. Differential expression of microRNAs in GH-secreting pituitary adenomas Diagn Pathol, 2010, 7(5), 79.
[100]
Frystyk, J. Free insulin-like growth factors - measurements and relationships to growth hormone secretion and glucose homeostasis. Growth Horm IGF Res., 2004, 14(5), 337-375.
[109]
WADA technical document TD2015GH. 2015. Available from: https://www.wada-ama.org/sites/default/files/resources/files/wada-td2015-index-v2.0.pdf
[110]
World Anti-Doping Program. Human growth hormone (hGH) biomarkers test for doping control analysis , 2016, (version 2)
,
Teresa Porcelli
Download PDF Flyer