Copeptin under glucagon stimulation

Krzysztof C Lewandowski, Andrzej Lewiński, Elżbieta Skowrońska-Jóźwiak, Magdalena Stasiak, Wojciech Horzelski, Georg Brabant, Krzysztof C Lewandowski, Andrzej Lewiński, Elżbieta Skowrońska-Jóźwiak, Magdalena Stasiak, Wojciech Horzelski, Georg Brabant

Abstract

Stimulation of growth hormone (GH) and adrenocorticotropic hormone (ACTH) secretion by glucagon is a standard procedure to assess pituitary dysfunction but the pathomechanism of glucagon action remains unclear. As arginine vasopressin (AVP) may act on the release of both, GH and ACTH, we tested here the role of AVP in GST by measuring a stable precursor fragment, copeptin, which is stoichiometrically secreted with AVP in a 1:1 ratio. ACTH, cortisol, GH, and copeptin were measured at 0, 60, 90, 120, 150, and 180 min during GST in 79 subjects: healthy controls (Group 1, n = 32), subjects with pituitary disease, but with adequate cortisol and GH responses during GST (Group 2, n = 29), and those with overt hypopituitarism (Group 3, n = 18). Copeptin concentrations significantly increased over baseline 150 and 180 min following glucagon stimulation in controls and patients with intact pituitary function but not in hypopituitarism. Copeptin concentrations were stimulated over time and the maximal increment correlated with ACTH, while correlations between copeptin and GH were weaker. Interestingly, copeptin as well as GH secretion was significantly attenuated when comparing subjects within the highest to those in the lowest BMI quartile (p < 0.05). Copeptin is significantly released following glucagon stimulation. As this release is BMI-dependent, the time-dependent relation between copeptin and GH may be obscured, whereas the close relation to ACTH suggests that AVP/copeptin release might be linked to the activation of the adrenal axis.

Keywords: ACTH; Copeptin; Cortisol; GH; Glucagon stimulation test; Hypopituitarism.

Figures

Fig. 1
Fig. 1
ACTH, Copeptin, and Growth Hormone concentrations during a glucagon stimulation test (GST). Patients were subdivided into Group 1 (healthy controls, n = 32), Group 2 (history of pituitary disease, but passed GST, n = 29), and Group 3 (unsatisfactory response during GST for GH, cortisol, or both, n = 18). Vertical lines denote standard errors of the means (SEMs)

References

    1. Land H, Schutz G, Schmale H, Richter D. Nucleotide sequence of cloned cDNA encoding bovine arginine vasopressin-neurophysin II precursor. Nature. 1982;295:299–303. doi: 10.1038/295299a0.
    1. Morgenthaler NG, Struck J, Alonso C, Bergmann A. Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clin. Chem. 2006;52:112–119. doi: 10.1373/clinchem.2005.060038.
    1. Roussel R, Fezeu L, Marre M, et al. Comparison between copeptin and vasopressin in a population from the community and in people with chronic kidney disease. J. Clin. Endocrinol. Metab. 2014;99:4656–4663. doi: 10.1210/jc.2014-2295.
    1. Katan M, Morgenthaler NG, Dixit KCS, Rutishauser J, Brabant GE, Müller B, Christ-Crain M. Anterior and posterior pituitary function testing with simultaneous insulin tolerance test and a novel copeptin assay. J. Clin. Endocrinol. Metab. 2007;92:2640–2643. doi: 10.1210/jc.2006-2046.
    1. Gillies GE, Linton EA, Lowry PJ. Corticotropin releasing activity of the new CRF is potentiated several times by vasopressin. Nature. 1982;299:355–357. doi: 10.1038/299355a0.
    1. Rivier C, Vale W. Modulation of stress-induced ACTH release by corticotropin-releasing factor, catecholamines and vasopressin. Nature. 1983;305:325–327. doi: 10.1038/305325a0.
    1. Nickel CH, Bingisser R, Morgenthaler NG. The role of copeptin as a diagnostic and prognostic biomarker for risk stratification in the emergency department. BMC Med. 2012;10:7–13. doi: 10.1186/1741-7015-10-7.
    1. Dobsa L, Edozien KC. Copeptin and its potential role in diagnosis and prognosis of various diseases. Biochem. Med. 2013;23:172–190. doi: 10.11613/BM.2013.021.
    1. Gómez JM, Espadero RM, Escobar-Jiménez F, Hawkins F, Antonio P, Jos Luis H-P, Enric V, Alejandra D, Jordi M, Eduardo F, Anna S. Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults. Clin. Endocrinol. 2002;56:329–334. doi: 10.1046/j.1365-2265.2002.01472.x.
    1. Böttner A, Kratzsch J, Liebermann S, Alexandra K, Roland WP, Wieland K, Eberhard K. Comparison of adrenal function tests in children—the glucagon stimulation test allows the simultaneous assessment of adrenal function and growth hormone response in children. J. Pediatr. Endocrinol. Metab. 2005;18:433–442. doi: 10.1515/JPEM.2005.18.5.433.
    1. Orme SM, Peacey SR, Bath JH, Belchetz PE. Comparison of tests of stress-released cortisol secretion in pituitary disease. Clin. Endocrinol. (Oxford) 1996;45:135–140. doi: 10.1046/j.1365-2265.1996.d01-1562.x.
    1. Struck J, Morgenthaler NG, Bergmann A. Copeptin, a stable peptide derived from the vasopressin precursor, is elevated in serum of sepsis patients. Peptides. 2005;26:2500–2504. doi: 10.1016/j.peptides.2005.04.019.
    1. Toogood A, Brabant G, Maiter D, Jonsson B, Feldt-Rasmussen U, Koltowska-Haggstrom M, Rasmussen AK, Buchfelder M, Saller B, Biller BM. Similar clinical features among patients with severe adult growth hormone deficiency diagnosed with insulin tolerance test or arginine or glucagon stimulation test. Endocr. Pract. 2012;18:325–334. doi: 10.4158/EP11146.OR.
    1. Berg C, Meinel T, Lahner H, Yuece A, Mann K, Petersenn S. Diagnostic utility of the glucagon stimulation test in comparison with the insulin tolerance test in patients following pituitary surgery. Eur. J. Endocrinol. 2010;162:477–482. doi: 10.1530/EJE-09-0824.
    1. Cho HY, Kim JH, Kim SW, Shin CS, Park KS, Kim SW, Jang HC, Kim SY. Different cut-off values of the insulin tolerance test, the high-dose short Synacthen test (250 µg) and the low-dose short Synacthen test (1 µg) in assessing central adrenal insufficiency. Clin. Endocrinol. (Oxford) 2014;81:77–84. doi: 10.1111/cen.12397.
    1. Simsek Y, Karaca Z, Tanriverdi F, Unluhizarci K, Selcuklu A, Kelestimur F. A comparison of low-dose ACTH, glucagon stimulation and insulin tolerance test in patients with pituitary disorders. Clin. Endocrinol. (Oxford) 2015;82:45–52. doi: 10.1111/cen.12528.
    1. Kacheva S, Kolk K, Morgenthaler NG, Brabant G, Karges W. Gender-specific co-activation of arginine vasopressin and the hypothalamic-pituitary-adrenal axis during stress. Clin. Endocrinol. (Oxford) 2015;82:570–576. doi: 10.1111/cen.12608.
    1. Enhorning S, Wang TJ, Nilsson PM, Almgren P, Hedblad B, Berglund G, Struck J, Morgenthaler NG, Bergmann A, Lindholm E, Groop L, Lyssenko V, Orho-Melander M, Newton-Cheh C, Melander O. Plasma copeptin and the risk of diabetes mellitus. Circulation. 2010;121:2102–2108. doi: 10.1161/CIRCULATIONAHA.109.909663.
    1. Tanoue A, Ito S, Honda K, Oshikawa S, Kitagawa Y, Koshimizu T, Mori T, Tsujimoto G. The vasopressin V1b receptor critically regulates hypothalamic-pituitary-adrenal axis activity under both stress and resting conditions. J. Clin. Investig. 2004;113:302–309. doi: 10.1172/JCI200419656.
    1. Aguilera G, Subburaju S, Young S, Chen J. The parvocellular vasopressinergic system and responsiveness of the hypothalamic pituitary axis adrenal axis during chronic stress. Prog. Brain Res. 2008;170:29–39. doi: 10.1016/S0079-6123(08)00403-2.
    1. Katan M, Morgenthaler N, Widmer I, Puder JJ, Koning C, Muller B, Christ-Crain M, et al. Copeptin, a stable peptide derived from the vasopressin precursor, correlates with the individual stress level. Neuroendocrinol. Lett. 2008;29:341–346.
    1. Arvat E, Maccagno B, Ramunni J, Maccario M, Giordano R, Broglio F, Cammanni F, Ghigo E. Interaction between glucagon and human corticotropin-releasing hormone or vasopressin on ACTH and cortisol secretion in humans. Eur. J. Endocrinol. 2000;143:99–104. doi: 10.1530/eje.0.1430099.
    1. Kreitschmann-Andermahr I, Suarez P, Jennings R, Evers N, Brabant G. GH/IGF-I regulation in obesity–mechanisms and practical consequences in children and adults. Hormon. Res. Paediatr. 2010;73:153–160. doi: 10.1159/000284355.
    1. Savastano S, Di Somma C, Barrea L, et al. The complex relationship between obesity and the somatropic axis: the long and winding road. Growth Hormon. IGF Res. 2014;24:221–226. doi: 10.1016/j.ghir.2014.09.002.
    1. Dichtel LE, Yuen KC, Bredella MA, Gerweck AV, Russell BM, Riccio AD, Gurel MH, Sluss PM, Biller BM, Miller KK. Overweight/obese adults with pituitary disorders require lower peak growth hormone cutoff values on glucagon stimulation testing to avoid overdiagnosis of growth hormone deficiency. J. Clin. Endocrinol. Metab. 2014;99:4712–4719. doi: 10.1210/jc.2014-2830.
    1. Schöfl C, Schleth A, Berger D, Terkamp C, von zur Mühlen A, Brabant G. Sympathoadrenal counterregulation in patients with hypothalamic craniopharyngioma. J. Clin. Endocrinol. Metab. 2002;87:624–629. doi: 10.1210/jcem.87.2.8193.
    1. Arvat E, Maccagno B, Ramunni J, Giordano R, Broglio F, Gianotti L, Maccario M, Camanni F, Ghigo E. Interaction between glucagon and hexarelin, a peptidyl GH secretagogue, on somatotroph and corticotroph secretion in humans. Eur. J. Endocrinol. 2000;143:601–606. doi: 10.1530/eje.0.1430601.
    1. Leong KS, Walker AB, Martin I, Wile D, Wilding J, MacFarlane IA. An audit of 500 subcutaneous glucagon stimulation tests to assess growth hormone and ACTH secretion in patients with hypothalamo-pituitary disease. Clin. Endocrinol. (Oxford) 2001;54:463–468. doi: 10.1046/j.1365-2265.2001.01169.x.
    1. Urwyler SA, Schuetz P, Sailer C, Christ-Crain M. Copeptin as a stress marker prior and after a written examination—the CoEXAM study. Stress. 2015;18(1):134–137. doi: 10.3109/10253890.2014.993966.
    1. Siegenthaler J, Walti C, Urwyler SA, Schuetz P, Christ-Crain M. Copeptin concentrations during psychological stress: the PsyCo study. Eur. J. Endocrinol. 2014;171:737–742. doi: 10.1530/EJE-14-0405.
    1. Geisel O, Panneck P, Hellweg R, Wiedermann K, Müller CA. Hypothalamic-pituitary-adrenal axis activity in patients with pathological gambling and internet use disorder. Psychiatry Res. 2015;226:97–102. doi: 10.1016/j.psychres.2014.11.078.
    1. Allolio B. Extensive expertise in endocrinology. Adrenal crisis. Eur. J. Endocrinol. 2015;172:R115–R2434. doi: 10.1530/EJE-14-0824.
    1. Wuttke A, Dixit KC, Szinnai G, Werth SC, Haagen U, Christ-Crain M, Morgenthaler N, Brabant G. Copeptin as a marker for arginine-vasopressin/antidiuretic hormone secretion in the diagnosis of paraneoplastic syndrome of inappropriate ADH secretion. Endocrine. 2013;44:744–749. doi: 10.1007/s12020-013-9919-9.

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