Examining the relationship between vitamin D levels and Helicobacter pylori infection and its effect on the hypothalamic-pituitary-adrenal axis in dyspeptic patients

Abstract

 

The purpose of this study was to determine whether or not Helicobacter pylori (H. pylori) infection affects the hypothalamic-pituitary-adrenal (HPA) axis and to evaluate the association between vitamin D levels with H. pylori infected and eradicated patients. The glucagon stimulation test (GST) was used to assess the HPA gland axis. An H. pylori infection was diagnosed based on the rapid urease test and histology. All infected patients received triple eradication therapy. Three months after the treatment, 14C urea breath test was reinstituted, and GST was repeated in patients who were negative for H. pylori. Of the 43 patients, 20 (46%) were found to have a lower mean value of peak cortisol than normal responses to the GST in the H. pylori-infected subjects. In 29 subjects, H. pylori infection was successfully eradicated. Twelve (41%) out of 29 subjects were defined as having a blunted GST response and 17 (%59) subjects had normal HPA axis response to GST in the H. pylori-eradicated subjects. A significant correlation between low 25-hydroxyvitamin D3 (25(OH)D3) level and low peak cortisol response to GST was identified in the H. pylori-infected subjects. After H. pylori eradication, the positive correlation between 25(OH)D3 level and high peak cortisol response to GST was also identified. Mean 25(OH)D3 levels were lower in the H. pylori-infected subjects than in the H. pylori-eradicated subjects. Our results indicate an increased prevalence of blunted glucocorticoid response to GST in patients with infected H. pylori. Vitamin D deficiency is also common in the H. pylori-infected subjects and associated with blunted glucocorticoid response. These findings suggest that H. pylori eradication increases the cortisol response to GST. Vitamin D supports adrenal/cortisol production whereby a deficiency can result blunted glucocorticoid response to GST in patients with infected H. pylori.

Keywords

• Cortisol
• Dyspeptic patients
• Helicobacter pylori
• Hypothalamic-pituitary-adrenal axis
• Vitamin D

References

1. Ahmed, M.A., 2013. Impact of vitamin D3 on cardiovascular responses to glucocorticoid excess. J. Physiol Biochem. 69, 267-276. doi: 10.1007/ s13105-012-0209-4.
2. Alvarez-Arellano, L., Maldonado-Bernal, C., 2014. Helicobacter pylori and neurological diseases: Married by the laws of inflammation. World J. Gastrointest. Pathophysiol. 5, 400-404. doi: 10.4291/wjgp.v5.i4.400.
3. Ando, T., Goto, Y., Maeda, O., Watanabe, O., Ishiguro, K., Goto, H., 2006. Causal role of Helicobacter pylori infection in gastric cancer. World J. Gastroenterol. 12, 181-186.
4. Bilgir, O., Kebapcilar, L., Bilgir, F., Sari, I., Oner, P., Karaca, B., Alacacioglu, I., 2010. Is there any relationship between imatinib mesylate medication and hypothalamic-pituitary-adrenal axis dysfunction? Int. J. Clin. Pract. 64, 45-450. doi: 10.1111/j.1742-1241.2008.01856.x.
5. Dammann, H.G., Bethke, T., Burkhardt, F., Wolf, N., Khalil, H., Luehmann, R., 1994. Effects of pantoprazole on endocrine function in healthy male volunteers. Aliment. Pharmacol. Ther. 8, 549-554.
6. Dammann, H.G., Burkhardt, F., Wolf, N., 1999. The effects of oral rabeprazole on endocrine and gastric secretory function in healthy volunteers. Aliment. Pharmacol. Ther. 13, 1195-1203.
7. Dammann, H.G., Von Zur Mühlen, A., Balks, H.J., Damaschke, A., Steinhoff, J., Hennig, U., Schwarz, J.A., Fuchs, W., 1993. The effects of lansoprazole, 30 or 60 mg daily, on intragastric pH and on endocrine function in healthy volunteers. Aliment. Pharmacol. Ther. 7, 191-196.
8. Del Rey, A., Chrousos, G., Besedovsky, H., 2007. The hypothalamus-pituitary-adrenal axis. Amsterdam: Elsevier Science. 7, 1-416.

9. Dowie, L.J., Smith, J.E., MacGilchrist, A.J., Fraser, R., Honour, J.W., Reid, J.L., Kenyon, C.J., 1988 In vivo and in vitro studies of the site of inhibitory action of omeprazole on adrenocortical steroidogenesis. Eur. J. Clin. Pharmacol. 35, 625-629.
10. Erturk, E., Jaffe, C.A., Barkan, A.L., 1998. Evaluation of the integrity of the hypothalamic-pituitary-adrenal axis by insulin hypoglycemia test. J. Clin. Endocrinol. Metab. 83, 2350-2354.
11. Filaretova, L.P., Podvigina, T.T., Bagaeva, T.R.,Tanaka, A., Takeuchi, K., 2004. Mechanisms underlying the gastroprotective action of glucocorticoids released in response to ulcerogenic stress factors. Ann. N. Y. Acad. Sci. 1018, 288-292.
12. Gasbarrini, A., Franceschi, F., 1999. Autoimmune diseases and Helicobacter pylori infection. Biomed. Pharmacother. 56, 223-226.
13. Guo, L., Chen, W., Zhu, H., Chen, Y., Wan, X., Yang, N., Xu, S., Yu, C., Chen, L., 2014. Helicobacter pylori induces increased expression of the vitamin d receptor in immune responses. Helicobacter. 19, 37-47. doi: 10.1111/hel.12102.
14. Guran, T., Guran, O., Paketci, C., Kipoglu, O., Firat, I., Turan, S., Atay, Z., Haliloglu, B., Bereket, A., 2015. Effects of leukemia inhibitory receptor gene mutations on human hypothalamo-pituitary-adrenal function. Pituitary. 18, 456-460. doi: 10.1007/s11102-014-0594-5.
15. Hagg, E., Asplund, K., Lithner, F., 1987. Value of basal plasma cortisol assays in the assessment of pituitary-adrenal insufficiency. Clin. Endocrinol (Oxf). 26, 221-226.
16. Harvey, P.W., Sutcliffe, C., 2010. Adrenocortical hypertrophy: Establishing cause and toxicological significance. J. Appl. Toxicol. 30, 617-626. doi: 10.1002/jat.1569.
17. Holick, M.F., Binkley, N.C., Bischoff-Ferrari, H.A., Gordon, C.M., Hanley, D.A., Heaney, R.P., Murad, M.H., Weaver, C.M., Endocrine Society, 2011. Evaluation, treatment, and prevention of vitamin D deficiency: An endocrine society clinical practice guideline. J. Clin. Endocrinol Metab. 96, 1911-1930. doi: 10.1210/jc.2011-0385.
18. Inder, W.J., Hunt, P.J., 2002. Glucocorticoid replacement in pituitary surgery: Guidelines for perioperative assessment and management. J. Clin. Endocrinol. Metab. 87, 2745-2750.
19. Izquierdo, M.J., Cavia, M., Muñiz, de Francisco A.L., Arias, M., Santos, J. Abaigar, P., 2012. Paricalcitol reduces oxidative stress and inflammation in hemodialysis patients. BMC Nephrol. 13, 159. doi: 10.1186/1471-2369-13-159.
20. Kappy, M.S., Drake, A., Gao, D., Ratliff, R., 2006. Assessing adrenal function in primary care settings with a single sample subcutaneous glucagon test. J. Pediatr. 149, 682-686.
21. Karaca, Z., Lale, A., Tanriverdi, F., Kula, M., Unluhizarci, K., Kelestimur, F., 2011. The comparison of low and standard dose ACTH and glucagon stimulation tests in the evaluation of hypothalamo-pituitary-adrenal axis in healthy adults. Pituitary. 14, 134-140.
22. Katagiri, F., Inoue, S., Sato, Y., Itoh, H., Takeyama, M., 2006. Comparison of the effects of proton pump inhibitors on human plasma adrenocorticotropic hormone and cortisol levels under the starved condition. Biomed. Pharmacother. 60, 109-112.
23. Klose, M., Lange, M., Kosteljanetz, M., Poulsgaard, L., Feldt-Rasmussen, U., 2005. Adrenocortical insufficiency after pituitary surgery: An audit of the reliability of the conventional short synacthen test. Clin. Endocrinology. 63, 499-505.
24. Korf, H., Decallonne, B., Mathieu, C., 2014. Vitamin D for infections. Curr. Opin. Endocrinol. Diabetes Obes. 21, 431-436. doi: 10.1097/ MED.0000000000000108.
25. Koşan, B., Yüksel, O., Ustün, I., Köklü, S., Topal, F., Yilmaz, M., Ergül, B., Karaahmetoğlu, S., Eskioğlu, E., Altiparmak, E., 2008. Role of endogenous cortisol on Helicobacter pylori colonization. Clin. Biochem. 41, 917-919.
26. Kunz-Ebrecht, S.R., Mohamed-Ali, V., Feldman, P.J., Kirschbaum, C., Steptoe, A., 2003. Cortisol responses to mild psychological stress are inversely associated with proinflammatory cytokines. Brain Behav. Immun. 17, 373-383.
27. Montecucco, C., Rappuoli, R. 2001. Living dangerously: How Helicobacter pylori survives in the human stomach. Nat. Rev. Mol. Cell Biol. 2, 457-466.
28. Morris, K.L., Zemel, M.B. 2005. 1,25-dihydroxyvitamin D3 modulation of adipocyte glucocorticoid function. Obes. Res. 13, 670-677.
29. Murison, R., Milde, A.M. 2007. Ulceration, gastric. In: Encyclopedia of Stress (vol. 3). Fink G, ed, 2nd edn. Victoria: Elsevier, pp. 787-791.
30. Obradovic, D., Gronemeyer, H., Lutz, B.R. Rein, T., 2006. Cross-talk of vitamin D and glucocorticoids in hippocampal cells. J. Neurochem. 96, 500-509.
31. Oelkers, W., 1996. Adrenal insufficiency. N. Engl. J. Med. 335, 1206-1212.
32. Pani, M.A., Seissler, J., Usadel, K.H., Badenhoop, K., 2002. Vitamin D receptor genotype is associated with Addison’s disease. Eur. J. Endocrinol. 147, 635-640.
33. Peek, R.M., Fiske, C., Wilson, K.T., 2010. Role of innate immunity in Helicobacter pylori-induced gastric malignancy. Physiol. Rev. 90, 831- 858. doi: 10.1152/physrev.00039.2009.
34. Pereira, O., Bevan, J.S., 2008. Preoperative assessment for pituitary surgery. Pituitary. 11, 347-351. doi: 10.1007/s11102-008-0093-7.
35. Rao, R.H., Spathis, G.S., 1987. Intramuscular glucagon as a provocative stimulus for the assessment of pituitary function: Growth hormone and cortisol responses. Metabolism. 36, 658-663.
36. Simsek, Y., Karaca, Z., Tanriverdi, F.,Unluhizarci, K., Selcuklu, A., Kelestimur, F., 2015. A comparison of low-dose ACTH, glucagon stimulation and insulin tolerance test in patients with pituitary disorders. Clin. Endocrinol (Oxf). 82, 45-52. doi: 10.1111/cen.12528.
37. Tenenbaum, A., Phillip, M., Vries, L., 2014. The intramuscular glucagon stimulation test does not provide good discrimination between normal and inadequate ACTH reserve when used in the investigation of short healthy children. Horm. Res. Paediatr. 82, 194-200.
38. Wang, T.T., Nestel, F.P., Bourdeau, V., Nagai, Y., Wang, Q., Liao, J., Tavera-Mendoza, L., Lin, R., Hanrahan, J.W., Mader, S., White, J.H., 2004. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J. Immunol. 173, 2909-2912.
39. World Gastroenterology Organisation, 2011. World Gastroenterology Organisation Global Guideline: Helicobacter pylori in developing countries. J. Clin. Gastroenterol. 45, 383-388.