Insulin like growth factor-I in acute subarachnoid hemorrhage: a prospective cohort study

Stepani Bendel, Timo Koivisto, Olli-Pekka Ryynänen, Esko Ruokonen, Jarkko Romppanen, Vesa Kiviniemi, Ari Uusaro, Stepani Bendel, Timo Koivisto, Olli-Pekka Ryynänen, Esko Ruokonen, Jarkko Romppanen, Vesa Kiviniemi, Ari Uusaro

Abstract

Introduction: Neuroendocrine deficiencies may affect recovery after aneurysmal subarachnoid hemorrhage (aSAH). Insulin like growth factor-I (IGF-I) regulates neuronal growth and apoptosis in ischemic stroke. Our study was designed to a) characterize the behavior of serum IGF-I and growth hormone (GH) in the acute and late phases after aSAH reflecting possible pituitary gland function and b) evaluate the association between IGF-I and morbidity assessed by Glasgow outcome scale (GOS) and health related quality of life (HRQoL) in patients with aSAH.

Methods: In this prospective cohort study, patients with aSAH (n = 30) were compared to patients who underwent elective aneurysm surgery (n = 16). Serum GH and IGF-I concentrations were measured daily for five (controls) or seven (aSAH) days and at three months. GOS and 15d HRQoL was measured at three months. A mixed models method was used for testing between the groups. For factors possibly affecting HRQoL in aSAH patients, we constructed a Bayesian predicting model using a P-course Bayesian classifier.

Results: The mean IGF-I concentrations for days one to five were 8.1 +/- 3.5 nmol/l in patients with aSAH and 11.2 +/- 3.1 in the control group (P = 0.01). No corresponding difference was found at three months. Serum GH concentrations were similar in both patient groups. Severity of the aSAH did not affect serum IGF-I concentrations. Patients with GOS <or= 4 had lower IGF-I concentrations and lower HRQoL than patients with GOS 5 (P = 0.02 and 0.003 respectively). The 15d HRQoL was 0.81 +/- 0.16 in patients with aSAH and 0.86 +/- 0.09 in control patients (P = 0.24). In the Bayesian model, the use of statins prior to aSAH, hyponatremia, high maximal sequential organ specific score (SOFAmax), and low cumulative IGF-I concentrations on days one to seven were associated with poor HRQoL (accuracy 89%, sensitivity 86%, and specificity 93%).

Conclusions: IGF-I concentrations are low during acute aSAH, which may have an impact on morbidity.

Trial registration: ClinicalTrials.gov Identifier NCT00614887.

Figures

Figure 1
Figure 1
Serum IGF-I concentrations in patients with aSAH and in the control group. P = 0.01 for the difference between groups on days one to five and P = 0.9 at three months. Data are presented as median, interquartile ranges, and outliers. For more detailed numbers see Table 2. aSAH, aneurysmal subarachnoid hemorrhage; IGF-I, insulin like growth factor-I.
Figure 2
Figure 2
Pooled IGF-I concentrations in patients with aSAH and in the control group. The line represents the cut-off level of 11 nmol/l. The insulin like growth factor-I (IGF-I) concentration was below 11 nmol/l on day one in 77% of aneurysmal subarachnoid hemorrhage (aSAH) patients and in 23% (P = 0.02) of control patients. The respective values were 74% and 27% (P = 0.05) on day two, 70% and 30% (P = 0.3) on day three, 72% and 28% (P = 0.22) on day four, and 74% and 27% (P = 0.05) on day five. In the aSAH group, 83% of patients on day six and 76% on day seven had IGF-concentrations below 11 nmol/l. At three months, no patient had IGF-concentrations lower than 11 nmol/l.

References

    1. Nieuwkamp DJ, Setz LE, Algra A, Linn FH, de Rooij NK, Rinkel GJ. Changes in case fatality of aneurysmal subarachnoid haemorrhage over time, according to age, sex, and region: a meta-analysis. Lancet Neurol. 2009;8:635–642. doi: 10.1016/S1474-4422(09)70126-7.
    1. Schneider HJ, Kreitschmann-Andermahr I, Ghigo E, Stalla GK, Agha A. Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review. JAMA. 2007;298:1429–1438. doi: 10.1001/jama.298.12.1429.
    1. Bendel S, Koivisto T, Ruokonen E, Rinne J, Romppanen J, Vauhkonen I, Kiviniemi V, Uusaro A. Pituitary-adrenal function in patients with acute subarachnoid haemorrhage: A prospective cohort study. Crit Care. 2008;12:R126. doi: 10.1186/cc7084.
    1. Aimaretti G, Ambrosio MR, Di Somma C, Fusco A, Cannavo S, Gasperi M, Scaroni C, De Marinis L, Benvenga S, Degli Uberti EC, Lombardi G, Mantero F, Martino E, Giordano G, Ghigo E. Traumatic brain injury and subarachnoid haemorrhage are conditions at high risk for hypopituitarism: Screening study at 3 months after the brain injury. Clin Endocrinol (Oxf) 2004;61:320–326. doi: 10.1111/j.1365-2265.2004.02094.x.
    1. Espiner EA, Leikis R, Ferch RD, MacFarlane MR, Bonkowski JA, Frampton CM, Richards AM. The neuro-cardio-endocrine response to acute subarachnoid haemorrhage. Clin Endocrinol (Oxf) 2002;56:629–635. doi: 10.1046/j.1365-2265.2002.01285.x.
    1. Kelly DF, Gonzalo IT, Cohan P, Berman N, Swerdloff R, Wang C. Hypopituitarism following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a preliminary report. J Neurosurg. 2000;93:743–752. doi: 10.3171/jns.2000.93.5.0743.
    1. Brandt L, Saveland H, Valdemarsson S, Sjoholma H, Reinsturp P. Fatigue after aneurysmal subarachnoid hemorrhage evaluated by pituitary function and 3D-CBF. Acta Neurol Scand. 2004;109:91–96. doi: 10.1046/j.0001-6314.2003.00189.x.
    1. Tanriverdi F, Dagli AT, Karaca Z, Unluhirzarci K, Selcuklu A, Casanueva FF, Kelestimur F. High risk of pituitary dysfunction due to aneurysmal subarachnoid haemorrhage: A prospective investigation of anterior pituitary function in the acute phase and 12 months after the event. Clin Endocrinol (Oxf) 2007;67:931–937. doi: 10.1111/j.1365-2265.2007.02989.x.
    1. Kreitschmann-Andermahr I, Poll E, Hutter BO, Reineke A, Kristes S, Gilsbach JM, Saller B. Quality of life and psychiatric sequelae following aneurysmal subarachnoid haemorrhage: Does neuroendocrine dysfunction play a role? Clin Endocrinol (Oxf) 2007;66:833–837. doi: 10.1111/j.1365-2265.2007.02821.x.
    1. Kooijman R. Regulation of apoptosis by insulin-like growth factor (IGF)-I. Cytokine Growth Factor Rev. 2006;17:305–323. doi: 10.1016/j.cytogfr.2006.02.002.
    1. Kooijman R, Sarre S, Michotte Y, De Keyser J. Insulin-like growth factor I. A potential neuroprotective compound for the treatment of acute ischemic stroke? Stroke. 2009;40:e83–88. doi: 10.1161/STROKEAHA.108.528356.
    1. Aleman A, Torres-Alemán I. Circulating insulin-like growth factor I and cognitive function: Neuromodulation throughout the lifespan. Prog Neurobiol. 2009;89:256–265. doi: 10.1016/j.pneurobio.2009.07.008.
    1. Cahill J, Calvert JW, Zhang JH. Mechanisms of early brain injury after subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2006;26:1341–1353. doi: 10.1038/sj.jcbfm.9600283.
    1. Baxter RC, Hawker FH, To C, Steward PM, Holman SR. Thirty-day monitoring of insulin-like growth factors and their binding proteins in intensive care unit patients. Growth Horm IGF Res. 1998;8:455–463. doi: 10.1016/S1096-6374(98)80298-0.
    1. Bondanelli M, Ambrosio MR, Onofri A, Bergonzoni A, Lavezzi S, Zatelli MC, Valle D, Basaglia N, Degli Uberti EC. Predictive value of circulating insulin-like growth factor I levels in ischemic stroke outcome. J Clin Endocrinol Metab. 2006;91:3928–3934. doi: 10.1210/jc.2006-1040.
    1. Denti L, Annoni V, Cattadori E, Salvagnini MA, Visioli S, Merli MF, Corradi F, Ceresini G, Valentini G, Hoffman AR, Ceda GP. Insulin-like growth factor 1 as a predictor of ischemic stroke outcome in the elderly. Am J Med. 2004;117:312–317. doi: 10.1016/j.amjmed.2004.02.049.
    1. van Rijn MJ, Slooter AJ, Bos MJ, Catarino CF, Koudstaal PJ, Hofman A, Breteler MM, van Duijn CM. Insulin-like growth factor I promoter polymorphism, risk of stroke, and survival after stroke: The rotterdam study. J Neurol Neurosurg Psychiatry. 2006;77:24–27. doi: 10.1136/jnnp.2005.067447.
    1. Sintonen H. The 15D instrument of health-related quality of life: properties and applications. Ann Med. 2001;33:328–336. doi: 10.3109/07853890109002086.
    1. Hartman ML, Crowe BJ, Biller BM, Ho KK, Clemmons DR, Chipman JJ. Hypos CCS Advisory Board, U.S.HypoCCS Study Group. Which patients do not require a GH stimulation test for the diagnosis of adult GH deficiency? J Clin Endocrinol Metab. 2002;87:477–485. doi: 10.1210/jc.87.2.477.
    1. 15d-instrument.
    1. Mattila AK, Saarni SI, Salminen JK, Huhtala H, Sintonen H, Joukamaa M. Alexithymia and health-related quality of life in a general population. Psychosomatics. 2009;50:59–68. doi: 10.1176/appi.psy.50.1.59.
    1. Soini E, Rissanen T, Tiihonen J, Hodgins S, Eronen M, Ryynänen O-P. Predicting forensic admission among the mentally ill in a multinational setting: a Bayesian modelling approach. Vol. 68. Data & Knowledge Engineering; 2009. pp. 1427–1440.
    1. Ng AY, Jordan MI. In: On discriminative vs. generative classifiers: a comparison of logistic regression and naive bayes. Dietterich T, Becker S, Ghahramani Z, editor. Cambridge, MIT press; 2002.
    1. Visser-Meily JM, Rhebergen ML, Rinkel GJ, van Zandvoort MJ, Post MW. Long-term health-related quality of life after aneurysmal subarachnoid hemorrhage: relationship with psychological symptoms and personality characteristics. Stroke. 2009;40:1526–1529. doi: 10.1161/STROKEAHA.108.531277.
    1. Juul A, Scheike T, Davidsen M, Gyllenborg J, Jorgensen T. Low serum insulin-like growth factor I is associated with increased risk of ischemic heart disease: a population-based case-control study. Circulation. 2002;106:939–944. doi: 10.1161/.
    1. de Groof F, Joosten KF, Janssen JA, de Kleijn ED, Hazelnet JA, Hop WC, Uitterlinden P, van Doorn J, Hokken-Koelega AC. Acute stress response in children with meningococcal sepsis: Important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors. J Clin Endocrinol Metab. 2002;87:3118–3124. doi: 10.1210/jc.87.7.3118.
    1. Brabant G, Wallaschofski H. Normal levels of serum IGF-I: Determinants and validity of current reference ranges. Pituitary. 2007;10:129–133. doi: 10.1007/s11102-007-0035-9.
    1. Aimaretti G, Ambrosio MR, Di Somma C, Gasperi M, Cannavo S, Scaroni C, Fusco A, Del Monte P, De Menis E, Faustini-Fustini M, Grimaldi F, Logoluso F, Razzore P, Rovere S, Benvenga S, Degli Uberti EC, De Marinis L, Lombardi G, Mantero F, Martino F, Martino E, Giordano G, Ghigo E. Residual pituitary function after brain injury-induced hypopituitarism: a prospective 12-month study. J Clin Endocrinol Metab. 2005;90:6085–6092. doi: 10.1210/jc.2005-0504.
    1. Popovic V. GH deficiency as the most common pituitary defect after TBI: clinical implications. Pituitary. 2005;8:239–243. doi: 10.1007/s11102-006-6047-z.
    1. Gasco V, Corneli G, Rovere S, Croce C, Beccuti G, Mainolfi A, Grottoli S, Aimaretti G, Ghigo E. Diagnosis of adult GH deficiency. Pituitary. 2008;11:121–128. doi: 10.1007/s11102-008-0110-x.
    1. Biller BM, Samuels MH, Zagar A, Cook DM, Arafah BM, Bonert V, Stavrou S, Kleinberg DL, Chipman JJ, Hartman ML. Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency. J Clin Endocrinol Metab. 2002;87:2067–2079. doi: 10.1210/jc.87.5.2067.
    1. Ghigo E, Masel B, Aimaretti G, Leon-Carrion J, Casanueva FF, Dominguez-Morales MR, Elovic E, Perrone K, Stalla G, Thompson C, Urban R. Consensus guidelines on screening for hypopituitarism following traumatic brain injury. Brain Inj. 2005;19:711–724. doi: 10.1080/02699050400025315.
    1. Koivisto T, Vanninen R, Hurskainen H, Saari T, Hernesniemi J, Vapalahti M. Outcomes of early endovascular versus surgical treatment of ruptured cerebral aneurysms. A prospective randomized study. Stroke. 2000;31:2369–2377.
    1. O'Kelly CJ, Kulkarni AV, Austin PC, Wallace MC, Urbach D. The impact of therapeutic modality on outcomes following repair of ruptured intracranial aneurysms: an administrative data analysis. J Neurosurg. 2009. in press .

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren