The glucagon test in diagnosis of secondary adrenal insufficiency after craniospinal irradiation: the feasibility of application, the features of performing the test, and its diagnostic informativity

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  • Authors: Yudina A.E.1, Pavlova M.G.1, Sotnikov V.M.2, Tselovalnikova T.Y.1, Mazerkina N.A.3, Zheludkova O.G.4, Gerasimov A.N.1, Teryaeva N.B.3, Martynova E.1, Kim E.I.1
  • Affiliations:
    1. I.M. Sechenov First Moscow State Medical University
    2. Russian Scientific Center of Roentgeno-Radiology
    3. N.N. Burdenko National Scientific and Practical Center for Neurosurgery
    4. Russian Scientific Center of Roentgenoradiology
  • Issue: Vol 65, No 4 (2019)
  • Pages: 227-235
  • Section: Original Studies
  • URL: https://probl-endojournals.ru/probl/article/view/10219
  • DOI: https://doi.org/10.14341/probl10219
  • Cite item
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Abstract


BACKGROUND: The glucagon test (GT) is a promising alternative to the insulin hypoglycemia test (IHT) in diagnosis of secondary adrenal insufficiency (SAI).

AIM: To study the feasibility of using the GT in patients after craniospinal irradiation and to determine the cut-off value to rule out SAI.

METHODS: A total of 28 patients (14 males and 14 females) with the median age of 19 years (17; 23) who had undergone combination treatment (surgery, craniospinal irradiation (35 Gy) with boost to the tumor bed, and polychemotherapy) of extrapituitary brain tumors no later than 2 years before study initiation and 10 healthy volunteers of matching sex and age were examined. All the subjects underwent the GT and IHT with an interval of at least 5–7 days. The cortisol, ACTH, and glucose levels were measured.

RESULTS: Twelve out of 28 patients were diagnosed with SAI according to the IHT results. ROC analysis revealed that cortisol release during the GT >499 nmol/L ruled out SAI [100% sensitivity (Se); 62% specificity (Sp)], while the absence of a rise >340 nmol/l verified SAI (Sp 100%; 55% Se). For GT, the area under a curve (AUC) was 93.6%, which corresponds to a very good diagnostic informativity. In 19 patients, the IHT and GT results were concordant (in ten patients, the release of cortisol occurred above the cut-off value in both tests; no release was detected in nine patients). In nine cases, the results were discordant: the maximum cortisol level detected in the GT was ≤500 nmol/l, but the IHT results ruled out SAI (the GT yielded a false positive outcome). Contrariwise, in three (10.7%) patients the release of cortisol detected in the GT was adequate, while being insufficient in the IHT test. Adverse events (nausea) were reported during the GT test in 9 (25%) subjects; one patient had hypoglycemia (1.8 mmol/l).

CONCLUSION: GT is highly informative and can be used as a first-level stimulation test for ruling out SAI in patients exposed to craniospinal irradiation performed to manage brain tumors. The cortisol level of 500 nmol/L is the best cut-off value for ruling out SAI according to the GT results. The insulin hypoglycemia test is used as the second-level supporting test in patients with positive GT results.


Alla E. Yudina

I.M. Sechenov First Moscow State Medical University

Author for correspondence.
Email: alla1301@yandex.ru
ORCID iD: 0000-0002-4704-8453
SPIN-code: 9307-7889

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

Postgraduate student, M.D. Chair of endocrinology

Maria G. Pavlova

I.M. Sechenov First Moscow State Medical University

Email: mgpavlova68@rambler.ru
ORCID iD: 0000-0001-6073-328X
SPIN-code: 2205-1288

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

Ph.D., M.D.endocrinologist, Chair of endocrinology

Vladimir M. Sotnikov

Russian Scientific Center of Roentgeno-Radiology

Email: vmsotnikov@mail.ru
ORCID iD: 0000-0003-0498-314X
SPIN-code: 3845-0154

Russian Federation, 86, Profsoyuznaya street, Moscow, 117997

MD, PhD, Professor, Leading Researcher, Head of the X-ray and combined therapy methods department

Tatyana Y. Tselovalnikova

I.M. Sechenov First Moscow State Medical University

Email: t.tselovalnikova@gmail.com
ORCID iD: 0000-0003-4262-2724
SPIN-code: 2688-6494

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

M.D.endocrinologist, Chair of endocrinology

Nadezhda A. Mazerkina

N.N. Burdenko National Scientific and Practical Center for Neurosurgery

Email: nmazer@nsi.ru
ORCID iD: 0000-0002-0428-0498
SPIN-code: 1012-2923

Russian Federation, 16, 4-ya Tverskaya-Yamskaya street, Moscow, 125047

P.h.d., M.D.endocrinologist

Olga G. Zheludkova

Russian Scientific Center of Roentgenoradiology

Email: clelud@mail.ru
ORCID iD: 0000-0002-8607-3635
SPIN-code: 4850-7788

Russian Federation, 86, Profsoyuznaya street, Moscow, 117997

PhD, MD, oncologist

Andrey N. Gerasimov

I.M. Sechenov First Moscow State Medical University

Email: andr-gerasim@yandex.ru
ORCID iD: 0000-0003-4549-7172
SPIN-code: 4742-1459

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

PhD, DSc., Head of the department of Medical Statistics and Informatics

Nadezhda B. Teryaeva

N.N. Burdenko National Scientific and Practical Center for Neurosurgery

Email: nteryaeva@nsi.ru
ORCID iD: 0000-0001-8535-8535
SPIN-code: 2822-3279

Russian Federation, 16, 4-ya Tverskaya-Yamskaya street, Moscow, 125047

Phd

Evgeniya Martynova

I.M. Sechenov First Moscow State Medical University

Email: doctor.martynova@gmail.com
ORCID iD: 0000-0002-0681-4772
SPIN-code: 4992-0837

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

MD

Ekaterina I. Kim

I.M. Sechenov First Moscow State Medical University

Email: kat-alex2007@mail.ru
ORCID iD: 0000-0001-7879-8495
SPIN-code: 1628-2139

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

medical student

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Supplementary files

Supplementary Files Action
1. Fig. 1. Error curve for the maximum concentration of cortisol during the glucagon test. View (39KB) Indexing metadata
2. Fig. 2. The dynamics of the concentration of cortisol (median and interquartile range) in the study groups during the test with glucagon. View (87KB) Indexing metadata
3. Fig. 3. Dynamics of glucose concentration (median and interquartile range) during the glucagon test in patients with truly positive and truly negative results. View (61KB) Indexing metadata

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Copyright (c) 2019 Yudina A.E., Pavlova M.G., Sotnikov V.M., Tselovalnikova T.Y., Mazerkina N.A., Zheludkova O.G., Gerasimov A.N., Teryaeva N.B., Martynova E., Kim E.I.

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