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
[http://dx.doi.org/10.1210/er.2008-0027] [PMID: 19240267]
[http://dx.doi.org/10.1515/jpem-2000-s604] [PMID: 11202205]
[http://dx.doi.org/10.1016/j.endonu.2012.09.010] [PMID: 23246411]
[http://dx.doi.org/10.1530/EJE-07-0358] [PMID: 17893253]
[http://dx.doi.org/10.1055/s-2006-948313] [PMID: 17115347]
[http://dx.doi.org/10.1530/EJE-12-0084] [PMID: 22596288]
[http://dx.doi.org/10.1111/j.1365-2265.2009.03667.x] [PMID: 19650784]
[http://dx.doi.org/10.1007/s11102-015-0655-4] [PMID: 25893613]
[http://dx.doi.org/10.1530/eje.0.1510439] [PMID: 15476442]
[http://dx.doi.org/10.1007/s11102-016-0754-x] [PMID: 27743174]
[http://dx.doi.org/10.1530/EJE-14-0144] [PMID: 25084775]
[http://dx.doi.org/10.1007/s11102-015-0701-2] [PMID: 26792654]
[http://dx.doi.org/10.1007/s11102-012-0420-x] [PMID: 22903574]
[http://dx.doi.org/10.1056/NEJMra062453] [PMID: 17167139]
[http://dx.doi.org/10.1016/S0889-8529(18)30204-4] [PMID: 1521514]
[http://dx.doi.org/10.2147/PPA.S102302] [PMID: 27471378]
[http://dx.doi.org/10.1210/jc.2014-2700] [PMID: 25356808]
[http://dx.doi.org/10.1210/jc.2007-2104] [PMID: 18230660]
[http://dx.doi.org/10.1210/jc.83.11.3808] [PMID: 9814451]
[http://dx.doi.org/10.1210/jcem.87.7.8631] [PMID: 12107214]
[http://dx.doi.org/10.1210/jc.2007-2084] [PMID: 18171702]
[http://dx.doi.org/10.1210/jc.85.2.526] [PMID: 10690849]
[http://dx.doi.org/10.1530/eje.1.02036]
[http://dx.doi.org/10.1210/jc.2008-2421] [PMID: 19208732]
[http://dx.doi.org/10.1038/s41574-018-0058-5] [PMID: 30050156]
[http://dx.doi.org/10.1016/j.ghir.2009.09.005] [PMID: 19818659]
[http://dx.doi.org/10.1016/j.ghir.2009.09.004] [PMID: 19818658]
[PMID: 23143695]
[http://dx.doi.org/10.1097/MED.0b013e32834ec952] [PMID: 22157400]
[http://dx.doi.org/10.5604/17322693.1218181] [PMID: 27668645]
[http://dx.doi.org/10.1530/EJE-09-0258] [PMID: 19684058]
[http://dx.doi.org/10.3390/ijms18071447] [PMID: 28678199]
[http://dx.doi.org/10.4158/EP.17.S4.1] [PMID: 21846616]
[http://dx.doi.org/10.3171/2010.7.FOCUS10168] [PMID: 20887124]
[http://dx.doi.org/10.1038/nrendo.2014.21] [PMID: 24566817]
[http://dx.doi.org/10.1210/er.2010-0002] [PMID: 21123741]
[http://dx.doi.org/10.1530/EJE-07-0562] [PMID: 18299461]
[http://dx.doi.org/10.1210/jc.85.2.781] [PMID: 10690891]
[http://dx.doi.org/10.1007/s11102-009-0175-1] [PMID: 19330452]
[http://dx.doi.org/10.1210/jcem-68-4-844] [PMID: 2537844]
[http://dx.doi.org/10.1210/jc.2007-1986] [PMID: 18198230]
[http://dx.doi.org/10.1159/000080741] [PMID: 15477717]
[http://dx.doi.org/10.1530/EJE-15-0391] [PMID: 26888629]
[http://dx.doi.org/10.1111/jcmm.13427] [PMID: 29377493]
[PMID: 9589663]
[http://dx.doi.org/10.1210/jcem-71-6-1421] [PMID: 1977758]
[http://dx.doi.org/10.1530/ERC-15-0320] [PMID: 26187128]
[http://dx.doi.org/10.1056/NEJMoa1408028] [PMID: 25470569]
[http://dx.doi.org/10.1530/ERC-15-0038] [PMID: 25712922]
[http://dx.doi.org/10.1530/ERC-16-0082] [PMID: 26935837]
[http://dx.doi.org/10.1016/j.tem.2012.11.007] [PMID: 23270713]
[http://dx.doi.org/10.1210/jc.2012-1111] [PMID: 22659247]
[http://dx.doi.org/10.1002/ijc.24602] [PMID: 19637311]
[http://dx.doi.org/10.1530/ERC-12-0020] [PMID: 22420004]
[http://dx.doi.org/10.1530/ERC-12-0322] [PMID: 23940012]
[http://dx.doi.org/10.1038/onc.2014.50] [PMID: 24662816]
[http://dx.doi.org/10.1210/jc.2009-2197] [PMID: 20335450]
[PMID: 11156236]
[http://dx.doi.org/10.1111/his.12869] [PMID: 26768029]
[http://dx.doi.org/10.1210/jc.2008-2075] [PMID: 19158195]
[http://dx.doi.org/10.1385/EP:13:4:341] [PMID: 12665652]
[http://dx.doi.org/10.1023/A:1005709014239] [PMID: 9210056]
[http://dx.doi.org/10.1111/jne.12352] [PMID: 26686489]
[http://dx.doi.org/10.1111/j.1365-2265.2011.04163.x] [PMID: 21722151]
[http://dx.doi.org/10.1016/j.mce.2015.09.016] [PMID: 26391562]
[http://dx.doi.org/10.1007/s12022-008-9029-z] [PMID: 18629656]
[http://dx.doi.org/10.1530/EJE-10-0586] [PMID: 20688896]
[http://dx.doi.org/10.1046/j.1365-2265.2003.01921.x] [PMID: 14974920]
[http://dx.doi.org/10.1111/jcmm.13851] [PMID: 30843342]
[http://dx.doi.org/10.1530/JOE-13-0285] [PMID: 24096965]
[http://dx.doi.org/10.1530/EJE-12-1045] [PMID: 23360820]
[http://dx.doi.org/10.1016/j.ygcen.2013.04.024] [PMID: 23648743]
[http://dx.doi.org/10.1007/BF01420300] [PMID: 8738388]
[http://dx.doi.org/10.2152/jmi.52.151] [PMID: 16167532]
[http://dx.doi.org/10.1007/s00401-003-0747-5]
[http://dx.doi.org/10.1007/s12020-017-1283-8] [PMID: 28332074]
[http://dx.doi.org/10.1038/nrm2347]
[http://dx.doi.org/10.1038/nrc1840] [PMID: 16557279]
[http://dx.doi.org/10.1158/0008-5472.CAN-07-1083] [PMID: 17699775]
[http://dx.doi.org/10.1016/j.semcancer.2008.01.008] [PMID: 18295504]
[http://dx.doi.org/10.1158/0008-5472.CAN-06-0800] [PMID: 16885332]
[http://dx.doi.org/10.1002/jcp.20282] [PMID: 15648093]
[http://dx.doi.org/10.1002/jcp.20832] [PMID: 17111382]
[http://dx.doi.org/10.1210/jc.2008-1451] [PMID: 18840638]
[http://dx.doi.org/10.1210/jc.2011-3482] [PMID: 22564666]
[http://dx.doi.org/10.1038/onc.2012.190] [PMID: 22614013]
[http://dx.doi.org/10.1186/s12014-017-9160-2] [PMID: 28670222]
[http://dx.doi.org/10.1530/eje.0.148s003] [PMID: 12670294]
[http://dx.doi.org/10.1093/geronj/40.1.2] [PMID: 4038409]
[http://dx.doi.org/10.1210/jcem-67-1-69]
[http://dx.doi.org/10.1210/jcem-64-1-51] [PMID: 3782436]
[PMID: 7684744]
[http://dx.doi.org/10.1373/clinchem.2010.150631] [PMID: 21285256]
[http://dx.doi.org/10.1172/JCI110757] [PMID: 6681614]
[http://dx.doi.org/10.1530/EJE-07-0631] [PMID: 18057375]
[http://dx.doi.org/10.1210/jc.2009-2139] [PMID: 20207829]
[http://dx.doi.org/10.1007/s11102-007-0032-z] [PMID: 17429590]
[http://dx.doi.org/10.1210/jc.2011-0051] [PMID: 21565786]
[http://dx.doi.org/10.1152/ajpendo.00410.2002] [PMID: 12604504]
[http://dx.doi.org/10.1016/S0140-6736(04)16413-1] [PMID: 15194259]
[PMID: 8432773]
[http://dx.doi.org/10.1038/nrendo.2013.77] [PMID: 23629539]
[http://dx.doi.org/10.1210/jc.2011-0197] [PMID: 21543428]
[http://dx.doi.org/10.7326/0003-4819-152-9-201005040-00007] [PMID: 20439575]
[http://dx.doi.org/10.1373/clinchem.2005.047845] [PMID: 16020502]
[http://dx.doi.org/10.1111/j.1745-7262.2008.00395.x] [PMID: 18385903]
[http://dx.doi.org/10.1210/jc.2008-0402] [PMID: 18381573]
[http://dx.doi.org/10.1016/j.ghir.2007.01.011] [PMID: 17339122]
[PMID: 10523001]
[http://dx.doi.org/10.1210/jc.2002-020037] [PMID: 12519882]
[http://dx.doi.org/10.1038/s41598-017-09968-7] [PMID: 28855568]
[http://dx.doi.org/10.1161/01.ATV.13.2.296] [PMID: 8427864]
[http://dx.doi.org/10.1161/01.ATV.19.10.2439] [PMID: 10521374]
[http://dx.doi.org/10.1007/BF00268015] [PMID: 7682208]
[http://dx.doi.org/10.1016/j.cellsig.2012.12.011] [PMID: 23314177]
[http://dx.doi.org/10.1530/EC-14-0021] [PMID: 24692509]
[http://dx.doi.org/10.1007/s12020-015-0789-1] [PMID: 26547217]
[http://dx.doi.org/10.1530/acta.0.1270331] [PMID: 1449044]
[http://dx.doi.org/10.1002/dta.1469] [PMID: 23495241]
[http://dx.doi.org/10.1261/rna.965408] [PMID: 18426918]