The role of intrа- and postoperative ACTH and cortisol levels measurement in patients with Cushing’s disease as an early predictors of remission

Objectives. The aim of this research was to study the dynamic changes of intra- and early postoperative hormonal parameters (ACTH and cortisol) as predictors of hypercorticism remission.

Material and methods. 50 patients with confirmed Cushing`s disease (CD) were sampled for this research. The patients were divided into 3 groups depending on the outcome of the operation. The first group – patients with secondary adrenal insufficiency confirmed by clinical picture and the level of cortisol less than 50 nmol/l; the second group – with normalization of levels of ACTH and cortisol; the third – with the persistence of the CD. The results of intraoperative studies during the transnasal adenomectomy were then studied. The group sample consisted of 38 women and 12 men, aged 15–66 years. To assess the levels of ACTH and cortisol blood sampling was performed from a peripheral vein. The first sample was taken during the incision of the Dura mater, the second – immediately after removal of the tumor and the last – 20 minutes after the removal of the adenoma. Then, 1 day after the surgery the hormones mentioned above were studied in all patients. The levels of ACTH and cortisol were measured by immunochemiluminescent analysis on the automated system Cobas 6000 (Roche, France). Reference intervals ACTH 0–30 ng/ml, cortisol123–626 nmol/l.

Results. The analysis of the obtained data did not suggest a relationship between the changes of intraoperative indicators of hormonal status and the likelihood of disease remission (p > 0.125). In the postoperative period, of the 50 patients, 41 (82%) developed adrenal insufficiency, 5 (10%) showed normalization and in 4 patients (8%) adrenal insufficiency was not observed. The results of the hormonal research after 1 day had a correlation with the frequency of postoperative remission (p < 0.125).

Conclusion. Intraoperative measurement of levels of ACTH and cortisol is not appropriate and cannot serve as guidance for further tactics of the surgeon to define the totality of tumor removal.

the treatment of Cushing`s disease, endoscopic adenomectomy, ACTH secreting pituitary adenoma, cortisol

1. Мельниченко Г.А., Дедов И.И., Белая Ж.Е., и др. Болезнь Иценко–Кушинга: клиника, диагностика, дифференциальная диагностика, методы лечения. // Проблемы эндокринологии. – 2015. – Т. 61. – №2. – С. 55–77. [Melnichenko GA, Dedov II, Belaya ZE, et al. Cushing’s disease: the clinical features, diagnostics, differential diagnostics, and methods of treatment. Problems of Endocrinology. 2015;61(2):55-77. (in Russ.)] doi: 10.14341/probl201561255-77.

2. Марова Е.И., Арапова С.Д., Белая Ж.Е., и др. Практическое руководство для врачей: Болезнь Иценко–Кушинга: клиника, диагностика, лечение. / под ред. И.И. Дедова, Г.А. Мельниченко. – М., 2012. – С. 22–32. [Marova EI, Arapova SD, Belaya JE, et al. The Itsenko-Cushing’s Disease: clinic, diagnostics, treatment. Ed. by Dedov II, Melnichenko GA. Moscow; 2012. p. 22-32. (in Russ.)]

3. Арапова С.Д., Григорьев А.Ю. Результаты нейрохирургического лечения. В кн.: Болезнь Иценко–Кушинга / под ред. И.И. Дедова, Г.А. Мельниченко. – М., 2011. – С. 215–235. [Arapova SD, Grigorjev AU. The results of neurosurgical treatment. In: Dedov II, Melnichenko GA, editors. The Itsenko-Cushing’s Disease. Moscow; 2011. p. 215-235 (in Russ.)]

4. Czirják S, Bezzegh A, Gál A, Rácz K. Intra- and postoperative plasma ACTH concentrations in patients with Cushing&apos;s disease cured by transsphenoidal pituitary surgery. Acta Neurochir (Wien). 2002;144(10):971-977. doi: 10.1007/s00701-002-0984-8.

5. Марова Е.И. Болезнь Иценко–Кушинга. В кн.: Клиническая нейроэндокринология / под ред. академика РАН и РАМН И.И. Дедова. – М., 2011. [Marova EI. Cushing’s disease. In: Dedov II, editor. Clinical neuroendocrinology. Moscow; 2011. (in Russ.)]

6. Patil CG, Prevedello DM, Lad SP, et al. Late recurrences of Cushing’s disease after initial successful transsphenoidal surgery. J Clin Endocr Metab. 2008;93(2):358-362. doi: 10.1210/jc.2007-2013.

7. Knappe UJ, Lüdecke DK. Persistent and recurrent hypercortisolism after transsphenoidal surgery for Cushing’s disease. In: Fahlbusch R, Bock WJ, Brock M, et al., editors. Modern neurosurgery of meningiomas and pituitary adenomas. Vienna: Springer Vienna; 1996. p. 31-34. doi: 10.1007/978-3-7091-9450-8_10.

8. Friedman RB, Oldfield EH, Nieman LK, et al. Repeat transsphenoidal surgery for Cushing&apos;s disease. J Neurosurg. 1989;71(4):520-527. doi: 10.3171/jns.1989.71.4.0520.

9. Petersenn S, Beckers A, Ferone D, et al. Therapy of endocrine disease: outcomes in patients with Cushing&apos;s disease undergoing transsphenoidal surgery: systematic review assessing criteria used to define remission and recurrence. Eur J Endocrinol. 2015;172(6):R227-239. doi: 10.1530/EJE-14-0883.

10. Дедов И.И., Ситкин И.И., Белая Ж.Е., и др. Первый опыт использования селективного забора крови из нижних каменистых синусов в России (клиническое наблюдение). // Проблемы эндокринологии. – 2009. – Т. 55. – №6. – С. 11–16. [Dedov II, Sitkin II, Belaya ZE, et al. The first experience with selective blood collection from the inferior petrosal sinuses in Russia (case reports). Problems of Endocrinology. 2009;55(6):11-16. (in Russ.)] doi: 10.14341/probl200955611-16.