Stress hormone response to instrumented lumbar spine fusion surgery

20 The purpose of the present study was to investigate stress, anabolic and catabolic hormonal 21 levels and their association with interleukin 6 (IL-6) cytokine in patients undergoing lumbar 22 spine fusion (LSF) surgery. Blood samples were collected preoperatively, and at 1, 3, 42 and 90 23 days postoperatively (POD) from 49 LSF patients with a mean (SD) age of 62 (11) years. 24 Serum concentrations of adrenocorticotropic hormone (ACTH), cortisol, growth hormone 25 (GH), insulin-like growth factor 1 (IGF-1), testosterone, sex hormone-binding globulin 26 (SHBG) and IL-6 were analyzed. In women, cortisol concentration rose above baseline values 27 despite a fall in ACTH levels. GH showed a decrease on PODs 1 and 3 whereas IGF-1 levels 28 remained stable. In males, SHBG increased, and both testosterone and free testosterone showed 29 a decrease during PODs 1-3. The other hormone concentrations had returned to normal by 30 PODs 42 or 90, except for IGF-1, which remained above the baseline value on PODs 42 and 31 90. IL-6 correlated significantly with cortisol (p <0.001) level on POD 1. The results suggest 32 that hypercortisolism after operative stress is caused by cytokine-induced non-ACTH-driven 33 cortisol production or reduced cortisol breakdown suppressing the production of ACTH via 34 feedback inhibition. Furthermore, GH levels decrease rapidly.

spine fusion (LSF) surgery. Blood samples were collected preoperatively, and at 1, 3, 42 and 90 23 days postoperatively (POD) from 49 LSF patients with a mean (SD) age of 62 (11) years. 24 Serum concentrations of adrenocorticotropic hormone (ACTH), cortisol, growth hormone 25 (GH), insulin-like growth factor 1 (IGF-1), testosterone, sex hormone-binding globulin 26 (SHBG) and IL-6 were analyzed. In women, cortisol concentration rose above baseline values 27 despite a fall in ACTH levels. GH showed a decrease on PODs 1 and 3 whereas IGF-1 levels 28 remained stable. In males, SHBG increased, and both testosterone and free testosterone showed Low plasma ACTH in the presence of high plasma cortisol concentrations has been 50 interpreted as non-ACTH-driven cortisol production, a process in which cytokines could play a 51 role. 3 Alternatively, this phenomenon could be explained by reduced cortisol breakdown 52 suppressing the production of ACTH via feedback inhibition. A study by Boonen et al. showed 53 that cortisol production during a critical illness was only slightly higher than in healthy 54 subjects. 2 Cortisol breakdown was substantially reduced, probably explaining the increased 55 levels of plasma cortisol despite no increase in its production. Both ACTH and cortisol have 56 returned to their normal levels as early as 4-6 days after surgery in patients who have 57 undergone hepatectomy. 4 To our knowledge, no previous studies have investigated cortisol, 58 ACTH and cytokine responses after acute surgical stress.

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The main insulin counter-regulatory hormones are growth hormone, glucagon, Participants were asked to complete patient-reported outcome instruments and questionnaires 106 on sociodemographic variables, duration of preoperative symptoms, and back and radicular 107 pain at the time of admission. Information on patients' height, weight, medical conditions, 108 6 current medication, tobacco use, and received treatments was also elicited by questionnaire.  Table 1. No significant gender differences were found in baseline characteristics.

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Hormone levels 144 Serum cortisol concentrations had risen above the baseline level on POD 3 in women ( Figure   145 1) but had returned to their baseline values at 6 weeks after surgery. The total variance was 146 statistically significant (p = 0.04). However, a significant decrease in ACTH was noted already 147 on PODs 1 (p < 0.001) and 3 (p = 0.0001) but not on PODs 42 and 90.

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In both sexes, GH decreased during the first three PODs but had returned to its baseline value 149 by POD 42. IGF-1 decreased slightly during the first 3 PODs. IGF-1 had risen significantly 150 above the preoperative level at 6 weeks and 3 months after surgery.

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Furthermore, serum testosterone showed a decrease on PODs 1 and POD 3 but had returned to 153 normal by POD 42 (p < 0.001). SHBG had decreased to its baseline level by 6 weeks after  Lumbar spine surgery and remain elevated at one-hour post-surgery. 14 In the present study, 176 with the exception of IGF-1, which continued to show an increase at 3 months after surgery, 9 GH had returned to the preoperative level by 6 weeks after surgery. The increase in IGF-1 at 6 178 weeks and at 3 months could indicate a late anabolic effect after surgical trauma. Further 179 studies would be needed to unravel the effect of IGF-1 on anabolic metabolism. IGF-1 levels 180 are associated with age and gender, although to a lesser degree after age 40. In the present 181 study, no gender differences were observed in the baseline levels of IGF-1. The authors used 182 IGF-1, as all the patients were at an age where the IGF-1 reference values do not change 183 drastically by gender.

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The results of the present study suggest that acute surgical stress has a dramatic impact  reported in previous published studies. [9][10]16 The study contained more women than men 206 simply because the prospective unselective sample contained more women. A weakness of the 207 study was that the comparison of testosterone levels in older patients is difficult, as 208 testosterone levels are notably higher in men than in women. Furthermore, the study did not 209 test luteinizing hormone levels. In the same way as the present analysis provided information The results showed that ACTH, cortisol, IL-6, testosterone GH, and SHGB levels respond 217 rapidly to tissue trauma. Surgical stress after instrumented lumbar spine fusion induces tissue 218 trauma that elevates IL-6. Postoperative high cortisol was not associated with the elevation in 219 the level of ACTH. The late elevation of IGF-1 seems to be associated with late tissue repair 220 process. Further studies could investigate whether inter-individual differences exist in 221 hormonal responses to surgical stress and whether surgical stress affects surgical outcomes or 222 complications.

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Conflicts of Interests: None to declare.  Preoperative value has been set to zero (preoperative values are presented in Table 1).