Growth hormone deficiency and hypopituitarism in adults after complicated mild traumatic brain injury
- 566 Downloads
Traumatic brain injury is considered the main cause of hypopituitarism in adults, and GH deficiency appears to be the most frequent pituitary deficit. Most of the available studies have included all degrees of severity of trauma. We aimed to assess pituitary function and GH deficiency in adult patients at different time lengths after complicated mild TBI according to Glasgow Coma Scale. We also aimed to evaluate whether mild TBI patients with GH deficiency had developed alterations in the glycolipid profile.
Forty-eight patients (34 men and 14 women) with complicated mild TBI were included in the study. Twenty-three patients were evaluated at 1 year (Group A) and 25 patients at 5 years or longer after the injury (Group B). All patients underwent basal hormonal evaluation for pituitary function. GH deficiency was investigated by the combined test (GH releasing hormone + arginine). The glycolipid profile was also evaluated.
GH deficiency occurred in 8/23 patients (34.7 %) of Group A and in 12/25 patients (48 %) of Group B. In addition, two patients, one in each group, showed evidence of central hypothyroidism. Patients with GH deficiency, especially in Group A, presented a higher frequency of visceral adiposity and adverse metabolic profile as compared to no-GH deficiency patients.
Patients examined at 1 year or several years from complicated mild TBI had a similarly high occurrence of isolated GH deficiency, which was associated with visceral adiposity and metabolic alterations. Our findings suggest that patients undergone complicated mild TBI should be evaluated for GH deficiency even after several years from trauma.
KeywordsGrowth hormone deficiency in adults Hypopituitarism Complicated mild traumatic brain injury GHD Cardiovascular risk
This work was supported in part by grant IG 14066/2013 to AB from the Associazione Italiana per la Ricerca sul Cancro (AIRC). SG has received financial support for educational programs from Merck-Serono.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- 1.D.K. Menon, K. Schwab, D.W. Wright, A.I. Maas; Demographics, Clinical Assessment Working Group of the, I., Interagency Initiative toward Common Data Elements for Research on Traumatic Brain, I., Psychological, H., : Position statement: definition of traumatic brain injury. Arch. Phys. Med. Rehabil. 91(11), 1637–1640 (2010). doi: 10.1016/j.apmr.2010.05.017 CrossRefPubMedGoogle Scholar
- 4.V. Popovic, S. Pekic, D. Pavlovic, N. Maric, M. Jasovic-Gasic, B. Djurovic, M. Medic Stojanoska, V. Zivkovic, M. Stojanovic, M. Doknic, N. Milic, M. Djurovic, C. Dieguez, F.F. Casanueva, Hypopituitarism as a consequence of traumatic brain injury (TBI) and its possible relation with cognitive disabilities and mental distress. J. Endocrinol. Invest. 27(11), 1048–1054 (2004)CrossRefPubMedGoogle Scholar
- 6.G. Aimaretti, M.R. Ambrosio, C. Di Somma, M. Gasperi, S. Cannavo, C. Scaroni, A. Fusco, P. Del Monte, E. De Menis, M. Faustini-Fustini, F. Grimaldi, F. Logoluso, P. Razzore, S. Rovere, S. Benvenga, E.C. Degli Uberti, L. De Marinis, G. Lombardi, F. Mantero, E. Martino, G. Giordano, E. Ghigo, Residual pituitary function after brain injury-induced hypopituitarism: a prospective 12-month study. J. Clin. Endocrinol. Metab. 90(11), 6085–6092 (2005). doi: 10.1210/jc.2005-0504 CrossRefPubMedGoogle Scholar
- 8.F. Tanriverdi, H. Ulutabanca, K. Unluhizarci, A. Selcuklu, F.F. Casanueva, F. Kelestimur, Three years prospective investigation of anterior pituitary function after traumatic brain injury: a pilot study. Clin. Endocrinol. (Oxf). 68(4), 573–579 (2008). doi: 10.1111/j.1365-2265.2007.03070.x CrossRefPubMedGoogle Scholar
- 12.F. Tanriverdi, H. Senyurek, K. Unluhizarci, A. Selcuklu, F.F. Casanueva, F. Kelestimur, High risk of hypopituitarism after traumatic brain injury: a prospective investigation of anterior pituitary function in the acute phase and 12 months after trauma. J. Clin. Endocrinol. Metab. 91(6), 2105–2111 (2006). doi: 10.1210/jc.2005-2476 CrossRefPubMedGoogle Scholar
- 20.D.F. Kelly, C. Chaloner, D. Evans, A. Mathews, P. Cohan, C. Wang, R. Swerdloff, M.S. Sim, J. Lee, M.J. Wright, C. Kernan, G. Barkhoudarian, K.C. Yuen, K. Guskiewicz, Prevalence of pituitary hormone dysfunction, metabolic syndrome, and impaired quality of life in retired professional football players: a prospective study. J. Neurotrauma 31(13), 1161–1171 (2014). doi: 10.1089/neu.2013.3212 CrossRefPubMedPubMedCentralGoogle Scholar
- 21.M. Klose, T. Watt, J. Brennum, U. Feldt-Rasmussen, Posttraumatic hypopituitarism is associated with an unfavorable body composition and lipid profile, and decreased quality of life 12 months after injury. J. Clin. Endocrinol. Metab. 92(10), 3861–3868 (2007). doi: 10.1210/jc.2007-0901 CrossRefPubMedGoogle Scholar
- 22.F. Prodam, V. Gasco, M. Caputo, M. Zavattaro, L. Pagano, P. Marzullo, S. Belcastro, A. Busti, C. Perino, S. Grottoli, E. Ghigo, G. Aimaretti, Metabolic alterations in patients who develop traumatic brain injury (TBI)-induced hypopituitarism. Growth Horm. IGF Res. 23(4), 109–113 (2013). doi: 10.1016/j.ghir.2013.04.001 CrossRefPubMedGoogle Scholar
- 23.F. Tanriverdi, A. De Bellis, H. Ulutabanca, A. Bizzarro, A.A. Sinisi, G. Bellastella, V. Amoresano Paglionico, L. Dalla Mora, A. Selcuklu, K. Unluhizarci, F.F. Casanueva, F. Kelestimur, A five year prospective investigation of anterior pituitary function after traumatic brain injury: is hypopituitarism long-term after head trauma associated with autoimmunity?. J. Neurotrauma 30(16), 1426–1433 (2013). doi: 10.1089/neu.2012.2752 CrossRefPubMedGoogle Scholar
- 27.B.M. Biller, M.H. Samuels, A. Zagar, D.M. Cook, B.M. Arafah, V. Bonert, S. Stavrou, D.L. Kleinberg, J.J. Chipman, M.L. Hartman, Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency. J. Clin. Endocrinol. Metab. 87(5), 2067–2079 (2002). doi: 10.1210/jcem.87.5.8509 CrossRefPubMedGoogle Scholar
- 28.K.K. Ho, G.H.D.C.W. Participants, Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European society for pediatric endocrinology, Lawson Wilkins society, European society of Endocrinology, Japan Endocrine Society, and Endocrine society of Australia. Eur. J. Endocrinol. 157(6), 695–700 (2007). doi: 10.1530/EJE-07-0631 CrossRefPubMedGoogle Scholar
- 29.G. Corneli, C. Di Somma, F. Prodam, J. Bellone, S. Bellone, V. Gasco, R. Baldelli, S. Rovere, H.J. Schneider, L. Gargantini, R. Gastaldi, L. Ghizzoni, D. Valle, M. Salerno, A. Colao, G. Bona, E. Ghigo, M. Maghnie, G. Aimaretti, Cut-off limits of the GH response to GHRH plus arginine test and IGF-I levels for the diagnosis of GH deficiency in late adolescents and young adults. Eur. J. Endocrinol. 157(6), 701–708 (2007). doi: 10.1530/EJE-07-0384 CrossRefPubMedGoogle Scholar
- 30.N.E. Kokshoorn, M.J. Wassenaar, N.R. Biermasz, F. Roelfsema, J.W. Smit, J.A. Romijn, A.M. Pereira, Hypopituitarism following traumatic brain injury: prevalence is affected by the use of different dynamic tests and different normal values. Eur. J. Endocrinol. 162(1), 11–18 (2010). doi: 10.1530/EJE-09-0601 CrossRefPubMedGoogle Scholar
- 36.L.A. Kreber, G.S. Griesbach, M.J. Ashley, Detection of growth hormone deficiency in adults with chronic traumatic brain injury. J. Neurotrauma (2015). 10.1089/neu.2015.4127.
- 37.C.A. Lissett, P. Jonsson, J.P. Monson, S.M. Shalet, K.I. Board, Determinants of IGF-I status in a large cohort of growth hormone-deficient (GHD) subjects: the role of timing of onset of GHD. Clin. Endocrinol. (Oxf). 59(6), 773–778 (2003). doi: 10.1046/j.1365-2265.2003.01884.x CrossRefPubMedGoogle Scholar
- 38.K.C. Yuen, N.A. Tritos, S.L. Samson, A.R. Hoffman, L. Katznelson, American association of clinical endocrinologists and American college of endocrinology disease state clinical review: update on growth hormone stimulation testing and proposed revised cut-point for the glucagon stimulation test in the diagnosis of adult growth hormone deficiency. Endocr. Pract. 22(10), 1235–1244 (2016). doi: 10.4158/EP161407.DSCR CrossRefPubMedGoogle Scholar
- 42.M. Rizzo, R. Trepp, K. Berneis, E.R. Christ, Atherogenic lipoprotein phenotype and low-density lipoprotein size and subclasses in patients with growth hormone deficiency before and after short-term replacement therapy. Eur. J. Endocrinol. 156(3), 361–367 (2007). doi: 10.1530/EJE-06-0652 CrossRefPubMedGoogle Scholar
- 43.R. Abs, A.F. Mattsson, M. Thunander, J. Verhelst, M.I. Goth, P. Wilton, M. Koltowska-Haggstrom, A. Luger, Prevalence of diabetes mellitus in 6050 hypopituitary patients with adult-onset GH deficiency before GH replacement: a KIMS analysis. Eur. J. Endocrinol. 168(3), 297–305 (2013). doi: 10.1530/EJE-12-0807 CrossRefPubMedGoogle Scholar
- 44.C. Di Somma, R. Pivonello, G. Pizza, A. De Rosa, G. Lombardi, A. Colao, S. Savastano, Prevalence of the metabolic syndrome in moderately-severely obese subjects with and without growth hormone deficiency. J. Endocrinol. Invest. 33(3), 171–177 (2010). doi: 10.3275/651910.1007/BF03346577 CrossRefPubMedGoogle Scholar
- 45.M. Bondanelli, M.R. Ambrosio, A. Carli, A. Bergonzoni, A. Bertocchi, M.C. Zatelli, S. Ceruti, D. Valle, N. Basaglia, E.C. degli Uberti, Predictors of pituitary dysfunction in patients surviving ischemic stroke. J. Clin. Endocrinol. Metab. 95(10), 4660–4668 (2010). doi: 10.1210/jc.2010-0611 CrossRefPubMedGoogle Scholar
- 46.M. Bondanelli, M.R. Ambrosio, L. Cavazzini, A. Bertocchi, M.C. Zatelli, A. Carli, D. Valle, N. Basaglia, E.C. Uberti, Anterior pituitary function may predict functional and cognitive outcome in patients with traumatic brain injury undergoing rehabilitation. J. Neurotrauma 24(11), 1687–1697 (2007). doi: 10.1089/neu.2007.0343 CrossRefPubMedGoogle Scholar
- 47.A. Colao, C. di Somma, R. Pivonello, A. Cuocolo, L. Spinelli, D. Bonaduce, M. Salvatore, G. Lombardi, The cardiovascular risk of adult GH deficiency (GHD) improved after GH replacement and worsened in untreated GHD: a 12-month prospective study. J. Clin. Endocrinol. Metab. 87(3), 1088–1093 (2002). doi: 10.1210/jcem.87.3.8336 CrossRefPubMedGoogle Scholar
- 49.A.A. van der Klaauw, N.R. Biermasz, E.J. Feskens, M.B. Bos, J.W. Smit, F. Roelfsema, E.P. Corssmit, H. Pijl, J.A. Romijn, A.M. Pereira, The prevalence of the metabolic syndrome is increased in patients with GH deficiency, irrespective of long-term substitution with recombinant human GH. Eur. J. Endocrinol. 156(4), 455–462 (2007). doi: 10.1530/EJE-06-0699 CrossRefPubMedGoogle Scholar
- 50.W.M. High Jr., M. Briones-Galang, J.A. Clark, C. Gilkison, K.A. Mossberg, D.J. Zgaljardic, B.E. Masel, R.J. Urban, Effect of growth hormone replacement therapy on cognition after traumatic brain injury. J. Neurotrauma 27(9), 1565–1575 (2010). doi: 10.1089/neu.2009.1253 CrossRefPubMedPubMedCentralGoogle Scholar
- 51.P. Reimunde, A. Quintana, B. Castanon, N. Casteleiro, Z. Vilarnovo, A. Otero, A. Devesa, X.L. Otero-Cepeda, J. Devesa, Effects of growth hormone (GH) replacement and cognitive rehabilitation in patients with cognitive disorders after traumatic brain injury. Brain Inj. 25(1), 65–73 (2011). doi: 10.3109/02699052.2010.536196 CrossRefPubMedGoogle Scholar