A comparison of the insulin tolerance/glucagon test with the short ACTH stimulation test in the assessment of the hypothalamo‐pituitary‐adrenal axis in the early post‐operative period after hypophysectomy
Abstract
OBJECTIVE: The insulin tolerance test (ITT) is the established reference test for assessing the hypothalamo‐pituitary‐adrenal (HPA) axis. Various authorities, however, have suggested that the 250 μg short ACTH stimulation test may be used to assess the HPA axis in place of the ITT in suspected hypopituitarism, although a number of other studies have suggested that the test may be unreliable in this setting. In this study, the ITT (or glucagon test) has been compared with the 250 μg short ACTH stimulation test in patients with pituitary tumours pre‐operatively and within 2 weeks of trans‐sphenoidal hypophysectomy. DESIGN: An ITT, or a glucagon test when the ITT was contraindicated, and the 250 μg short ACTH stimulation test, were performed in all the patients before (an ITT in 18 and a glucagon test in three patients) and within 2 weeks after trans‐sphenoidal hypophysectomy (an ITT in 16 and a glucagon test in five patients). PATIENTS: Twenty‐one patients with pituitary disorders (15 with acromegaly, one with a prolactinoma and five with non‐functioning tumours) were studied; four had a microadenoma, two a mesoadenoma and 15 a macroadenoma. MEASUREMENTS: Serum cortisol was measured by radioimmunoassay. A normal response was defined as a rise in serum cortisol to 580 nmol/l or above for all the tests. RESULTS: Before surgery, three of 18 patients (17%) had a discrepancy between the ITT and the 30 minute short ACTH stimulation test and one of three between the glucagon test and the 30 minute short ACTH stimulation test. Combined together, pre‐operatively, four of 21 patients (19%) had discrepant results. In the early post‐operative period, the discrepancy between ITT and the 30 minute short ACTH stimulation test was higher with four of 16 patients (25%) showing discordant results; one of the five patients tested had a discrepancy between the glucagon test and the 30 minute short ACTH stimulation test. On combining the tests, the post‐operative discrepancy was five of 21 patients (24%). CONCLUSIONS: The 250 μg short ACTH stimulation test produces discordant results from the ITT in a clinically significant proportion of affected patients when assessing the HPA axis, although the rate of discordance varies according to the criteria used for normality for both the tests. We suggest that the ITT should remain the preferred test for assessing ACTH secretory capacity compared with the standard 250 μg short ACTH stimulation test, both in the pre‐operative and in the early post‐trans‐sphenoidal hypophysectomy period.
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It is not possible to be certain that the five patients who failed the GST but passed the SST have intact corticotrophic function because of well-reported false-pass results with the SST.
“However, it is not possible to be certain that the five patients who failed the GST but passed the SST have intact corticotrophic function because of well-reported falsepass results with the latter test (45)(46)(47)(48).”
From Anterior Pituitary Dysfunction in Survivors of Traumatic Brain Injury (2004) · cites this paper as [45]
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Nomikos, P. V., Ladar, C., Fahlbusch, R., & Buchfelder, M. (2004) · Acta Neurochirurgica · doi:10.1007/s00701-003-0174-3 · Cited by 268 · see citing works
Ospina, N. S., Al Nofal, A., Bancos, I., Javed, A., Benkhadra, K., Kapoor, E., Lteif, A. N., Natt, N., & Murad, M. H. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-1700 · Cited by 247 · see citing works
Hahner, S., Ross, R. J., Arlt, W., Bancos, I., Burger-Stritt, S., Torpy, D. J., Husebye, E. S., & Quinkler, M. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00252-7 · Cited by 223 · see citing works
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Leong, K. S., Walker, A. B., Martin, I., Wile, D., Wilding, J., & MacFarlane, I. A. (2001) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2001.01169.x · Cited by 140 · see citing works
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Martin‐Grace, J., Dineen, R., Sherlock, M., & Thompson, C. J. (2020) · Clinica Chimica Acta · doi:10.1016/j.cca.2020.01.029 · Cited by 104 · see citing works
Courtney, C. H., McAllister, A. S., McCance, D. R., Bell, P. M., Hadden, D. R., Leslie, H., Sheridan, B., & Atkinson, A. B. (2000) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2000.01106.x · Cited by 94 · see citing works
Hamrahian, A. H., Yuen, K. C. J., Gordon, M. B., Pulaski-Liebert, K. J., Bena, J., & Biller, B. M. K. (2016) · Pituitary · doi:10.1007/s11102-016-0712-7 · Cited by 92 · see citing works
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Self-citationAmbrosi, B., Barbetta, L., Re, T., Passini, E., & Faglia, G. (1998) · European Journal of Endocrinology · doi:10.1530/eje.0.1390575 · Cited by 76 · see citing works
Gonzálbez, Villabona, Ramón, Navarro, Giménez, Ricart, & Soler (2000) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2000.01028.x · Cited by 72 · see citing works
Dökmetaş, H. S., Çolak, R., Keleştimur, F., Selçuklu, A., Ünlühızarcı, K., & Bayram, F. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.10.6879 · Cited by 75 · see citing works
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Christ‐Crain, M., Jutla, S., Suter‐Widmer, I., Couppis, O., König, C., Pargger, H., Puder, J. J., Edwards, R., Müller-Stich, B. P., & Grossman, A. B. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2361 · Cited by 68 · see citing works
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Wallace, I., Cunningham, S., & Lindsay, J. (2009) · Annals of Clinical Biochemistry · doi:10.1258/acb.2009.009101 · Cited by 43 · see citing works
Marko, N. F., Gonugunta, V. A., Hamrahian, A. H., Usmani, A., Mayberg, M. R., & Weil, R. J. (2009) · Journal of Neurosurgery · doi:10.3171/2008.12.jns081265 · Cited by 67 · see citing works
Woodmansee, W. W., Carmichael, J. D., Kelly, D. F., & Katznelson, L. J. (2015) · Endocrine Practice · doi:10.4158/ep14541.dscr · Cited by 63 · see citing works
Gleeson, H. K., Walker, B. R., Seckl, J. R., & Padfield, P. L. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020969 · Cited by 85 · see citing works
Bangar, V., & Clayton, R. (1998) · European Journal of Endocrinology · doi:10.1530/eje.0.1390580 · Cited by 52 · see citing works
Oelkers, W. (1998) · European Journal of Endocrinology · doi:10.1530/eje.0.1390567 · Cited by 54 · see citing works
Klose, M., Lange, M., Kostel-janetz, M., Poulsgaard, L., & Feldt-Rasmussen, U. (2005) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2005.02368.x · Cited by 56 · see citing works
Marko, N. F., Hamrahian, A. H., & Weil, R. J. (2010) · Pituitary · doi:10.1007/s11102-010-0227-6 · Cited by 49 · see citing works
Hoeck, H. C., Jakobsen, P. E., Vestergaard, P., Falhof, J., & Laurberg, P. (1999) · Growth Hormone & IGF Research · doi:10.1054/ghir.1998.0085 · Cited by 49 · see citing works
Courtney, C., McAllister, McCance, Hadden, Leslie, Sheridan, & Atkinson (2000) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2000.01093.x · Cited by 49 · see citing works
Orme, S. M., Price, A., Weetman, A. P., & Ross, R. J. M. (1998) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1998.00610.x · Cited by 48 · see citing works
Žarković, M., Ćirić, J., Stojanovic, M. M., Penezić, Z., Trbojević, B., Drezgić, M., & Nesović, M. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.9.5947 · Cited by 45 · see citing works
Böttner, A., Kratzsch, J., Liebermann, S., Keller, A., Pfäffle, R. W., Kiess, W., & Keller, E. A. (2005) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2005.18.5.433 · Cited by 42 · see citing works
Arvat, E., Maccagno, B., Ramunni, J., Maccario, M., Giordano, R., Broglio, F., Camanni, F., & Ghigo, E. (2000) · European Journal of Endocrinology · doi:10.1530/eje.0.1430099 · Cited by 35 · see citing works
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Ach, T., Hasni, Y., Maatoug, J., Asma, B. A., Maha, K., Molka, C., Rouatbi, S., Monia, Z., & Ach, K. (2018) · Endocrine Journal · doi:10.1507/endocrj.ej18-0147 · Cited by 30 · see citing works
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Lee, P., Greenfield, J. R., & Ho, K. K. Y. (2009) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03466.x · Cited by 27 · see citing works
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Self-citationManaka, K., Sato, J., Takeuchi, M., Watanabe, K., Kage, H., Kawai, T., Sato, Y., Miyagawa, T., Yamada, D., Kume, H., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-91032-6 · Cited by 23 · see citing works
Carvalho, P., Lau, E., & Carvalho, D. M. (2015) · Pituitary · doi:10.1007/s11102-015-0661-6 · Cited by 23 · see citing works
Cegla, J., Jones, B. J., Seyani, L., Papadoulou, D., Wynne, K., Martin, N. M., Meeran, K. M., Chapman, R., Donaldson, M., Goldstone, A. P., et al. (2012) · Clinical Endocrinology · doi:10.1111/cen.12043 · Cited by 22 · see citing works
Zada, G., Tirosh, A., Huang, A. P., Laws, E. R., & Woodmansee, W. W. (2012) · Pituitary · doi:10.1007/s11102-012-0423-7 · Cited by 21 · see citing works
Kong, W. M., Alaghband-Zadeh, J., Jones, J., Carter, G. D., & O'Shea, D. (1999) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jcem.84.9.5998 · Cited by 23 · see citing works
Arvat, E., Maccagno, B., Ramunni, J., Giordano, R., DiVito, L., Broglio, F., Maccario, M., Camanni, F., & Ghigo, E. (2000) · Pituitary · doi:10.1023/a:1011451710004 · Cited by 19 · see citing works
Arvat, E., Maccagno, B., Ramunni, J., Giordano, R., Broglio, F., Gianotti, L., Maccario, M., Camanni, F., & Ghigo, E. (2000) · European Journal of Endocrinology · doi:10.1530/eje.0.1430601 · Cited by 17 · see citing works
Gibney, J., Healy, M., Smith, T. P., & McKenna, T. J. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0154 · Cited by 13 · see citing works
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Ajlan, A. M., Almufawez, K. A., Albakr, A. A., Katznelson, L. J., & Harsh, G. R. (2018) · World Neurosurgery · doi:10.1016/j.wneu.2018.01.182 · Cited by 11 · see citing works
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Caputo, M., Mele, C., Ferrero, A., Leone, I., Daffara, T., Marzullo, P., Prodam, F., & Aimaretti, G. (2021) · Neuroendocrinology · doi:10.1159/000514434 · Cited by 11 · see citing works
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Barthel, A., Willenberg, H., Gruber, M., & Bornstein, S. R. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-18907-1.00102-5 · Cited by 4 · see citing works
Marko, N. F., & Weil, R. J. (2011) · Neurosurgery · doi:10.1227/neu.0b013e31820cd45a · Cited by 10 · see citing works
Prencipe, N., Parasiliti‐Caprino, M., Gatti, F., Penner, F., Berton, A. M., Bona, C., Caputo, M., D’Angelo, V., Cappiello, V., Gasco, V., et al. (2020) · Neuroendocrinology · doi:10.1159/000509092 · Cited by 10 · see citing works
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Sarlos, S., & Inder, W. J. (2013) · Internal Medicine Journal · doi:10.1111/imj.12011 · Cited by 9 · see citing works
Lazarus, K., Hayes, A., Narula, K., Papadopolou, D., Tan, T., Meeran, K. M., & Choudhury, S. (2024) · Clinical Endocrinology · doi:10.1111/cen.15074 · Cited by 8 · see citing works
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McKenna, T. J. (2002) · Springer eBooks · doi:10.1007/978-1-4615-1103-8_12 · Cited by 8 · see citing works
Jackanich, A., Tavakol, S., Strickland, B. A., Rutkowski, M. J., Kamel, D., Carmichael, J. D., Weiss, M. H., & Zada, G. (2019) · Journal of neurosurgery · doi:10.3171/2018.11.jns182521 · Cited by 8 · see citing works
Yeoh, P., Dwyer, A. A., Anghel, E., Bouloux, P. M., Khoo, B. C. E., Chew, S., Wernig, F., Carroll, P., Aylwin, S. J. B., Baldeweg, S. E., et al. (2022) · International Journal of Endocrinology · doi:10.1155/2022/7360282 · Cited by 8 · see citing works
Self-citationChung, T., Grossman, A. B., & Clark, A. J. L. (2010) · Elsevier eBooks · doi:10.1016/b978-1-4160-5583-9.00101-5 · Cited by 7 · see citing works
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Martínez, F. J., & Lash, R. W. (1999) · Clinics in Chest Medicine · doi:10.1016/s0272-5231(05)70149-0 · Cited by 7 · see citing works
Perry, L., & Medbak, S. (2013) · Elsevier eBooks · doi:10.1016/b978-0-08-097037-0.00057-9 · Cited by 6 · see citing works
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Abucham, J., Vieira, T. C., Barbosa, E. R., Ribeiro, R. S., & Martins, M. R. A. (2003) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302003000400021 · Cited by 6 · see citing works
Moosig, F., Reinhold‐Keller, E., Holl‐Ulrich, K., Feller, A. C., Bley, T. A., Holle, J. U., Zwerina, J., Lamprecht, P., Dalhoff, K., Venhoff, N., et al. (2012) · Zeitschrift für Rheumatologie · doi:10.1007/s00393-012-0988-6 · Cited by 5 · see citing works
Glucagon administration elicits blunted GH but exaggerated ACTH response in obesity
Tassone, F., Grottoli, S., Rossetto, R., Maccagno, B., Gauna, C., Giordano, R., Ghigo, E., & Maccario, M. (2002) · Journal of Endocrinological Investigation · doi:10.1007/bf03345499 · Cited by 5 · see citing works
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Stewart, P. M., Clark, P. M. S., & Sheppard, M. C. (1998) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1998.0429d.x · Cited by 5 · see citing works
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Grossman, A. B. (2015) · Endocrine · doi:10.1007/s12020-015-0728-1 · Cited by 5 · see citing works
Self-citationThe low dose (1 μg) ACTH test ‐ when and how to use it.
Dickstein, G. (1998) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1998.00526.x · Cited by 5 · see citing works
Suppression of the HPA Axis in Pediatric Patients With Atopic Dermatitis
Ishay, A. (2007) · Archives of Dermatology · doi:10.1001/archderm.143.11.1449-b · Cited by 4 · see citing works
Nomikos, P. V., Ladar, C., Fahlbusch, R., & Buchfelder, M. (2004) · Cited by 3 · see citing works
Belien-Pallet, V., Cabrol, S., Fasola, S., Petit, A., Landman‐Parker, J., Auvrignon, A., & Leverger, G. (2010) · Archives de Pédiatrie · doi:10.1016/j.arcped.2010.09.001 · Cited by 1 · see citing works
Interpretation of biochemical investigations
Butler, J. (2002) · CRC Press eBooks · doi:10.1201/b15291-2 · Cited by 1 · see citing works
Blythe, R., Elkashif, I., & Malik, M. (2013) · Endocrine Abstracts · doi:10.1530/endoabs.32.p920
Luboshitzky, R., Ishai, A., Shen-Or, Z., Herer, P., & Luboshitzky, R. (2003)
(2009) · CRC Press eBooks · doi:10.1201/9781420079364.ch3
atualização Terapia de Reposição Hormonal no Hipopituitarismo
Abucham, J., Vieira, T. C., Barbosa, E. R., Ribeiro, R. S., & Martins, M. R. A. (2003)
- Authors
- Mukherjee, J. J., Jacome de Castro, J., Kaltsas, G., Afshar, F., Grossman, A. B., Wass, J. A. H., & Besser, G. M.
- Affiliations
- St Bartholomew's Hospital (GB)
- Corresponding author
- Besser, G. M.
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 1997-07
- Volume
- 47
- Issue
- 1
- Pages
- 51-60
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W2011962936
- Cited by
- 74
- References
- 0
- Citations by year
- 2024: 2 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 2 · 2016: 2 · 2015: 5 · 2013: 3 · 2012: 3
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- insulin tolerance test, glucagon stimulation test, hypothalamic-pituitary-adrenal axis, hypopituitarism, transsphenoidal hypophysectomy, pituitary tumors, acromegaly, serum cortisol, postoperative evaluation, test agreement, pituitary macroadenoma, pituitary microadenoma, prolactinoma
- MeSH terms
- Adenoma, Adrenocorticotropic Hormone, Female, Glucagon, Humans, Hypophysectomy, Hypothalamo-Hypophyseal System, Insulin, Male, Middle Aged, Pituitary Neoplasms, Pituitary-Adrenal System, Postoperative Period, Predictive Value of Tests
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