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Perioperative hypothalamic pituitary adrenal function in patients with silent corticotroph adenomas



Silent corticotroph adenomas (SCAs) are characterized by strong ACTH immunostaining without clinical manifestations of hypercortisolism. Patients with SCAs often present with mechanical symptoms related to tumor growth. This study investigates the hypothalamic pituitary adrenal axis (HPA) characteristics after adenomectomy in patients with SCAs.


Biochemical parameters of HPA function were monitored frequently after surgical resection of non-functioning macroadenomas. Levels of ACTH, cortisol, DHEA and DHEA-S were measured frequently for 48 h after adenomectomy. HPA data of patients with SCAs (n = 38) were compared to others (Controls) with non-secreting, ACTH-negative immunostaining adenomas of similar age and gender distribution (n = 182) who had adenomectomy.


Plasma ACTH increased (P < 0.0001) equally in patients with SCA and controls reaching a peak at 3 h (238 ± 123 vs. 233 ± 96 ng/L, respectively) after extubation declining thereafter to baseline values 24–36 h. Similarly, serum cortisol levels increased (P < 0.0001) equally in both groups reaching a maximum at 7 h (36.8 ± 13.9 vs. 39.3 ± 13.3 ug/dL). Serum DHEA also increased (P < 0.001) equally in both groups in parallel to the rise in serum cortisol. Serum DHEA-S levels similarly increased (P < 0.001) from their respective baseline (105.9 ± 67.5 and 106.5 ± 58.7 ug/dL) reaching their peak (154.5 ± 69.5 and 153.5 ± 68.6 ug/dL; respectively) at 15 h after extubation. None of the patients acquired any hormone deficits.


Under the maximal stimulation of the peri-operative stress, HPA function in patients with SCA behaved in an identical manner to others with ACTH-negative macroadenomas. Thus, despite the strong ACTH-positive immunostaining of these tumors, SCAs are truly non- functional.

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  1. Zada G, Woodmansee WW, Ramkissoon S, Amadio J, Nose V, Laws ER Jr (2011) Atypical pituitary adenomas: incidence, clinical characteristics, and implications. J Neurosurg 114:336–344

    Article  PubMed  Google Scholar 

  2. Saeger W, Ludecke DK, Buchfelder M, Fahlbusch R, Quabbe HJ, Petersenn S (2007) Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Registry. Eur J Endocrinol 156:203–216

    CAS  Article  PubMed  Google Scholar 

  3. Di leva A, Rotondo F, Syro LV, Cusimano MD, Kovacs K (2014) Aggressive pituitary adenomas—diagnosis and emerging treatments. Nat Rev Endocrinol 10:423–435

    Article  Google Scholar 

  4. Hassoun J, Charpin C, Jaquet P, Oliver C, Lissitky JC, Grisoli F, Toga M (1987) Analogies immunocytochemiques des adenomes hypohysaires de la maladie de Cushing et des adenomes “non functionnels” (adenomes chromophobes) de l’hypohpyse. Ann Endocrinol (Paris) 40:559

  5. Horvath E, Kovacs K, Killinger DW, Smyth HS, Platts ME, Singer W (1980) Silent corticotropic adenomas of the human pituitary gland. a histological, immunocytologic and ultrastructural study. Am J Pathol 98:617–636

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Scheithauer, B, Jaap A, Horvath E, Kovacs K, Lloyd R, Meyer F, Laws E, Young W Jr (2000) Clinically silent corticotroph tumors of the pituitary gland. Neurosurgery 47:723–729

    CAS  PubMed  Google Scholar 

  7. Jahangiri A, Wagner J, Pekmezci M, Hiniker A, Chang E, Kunwar S, Blevins L, Aghi M (2013) A comprehensive long-term retrospective analysis of silent corticotrophic adenomas versus hormone-negative adenomas. Neurosurgery 73:8–17

    Article  PubMed  Google Scholar 

  8. Arafah BM, Kailani SH, Nekl KE, Gold RS, Selman WR (1994) Immediate recovery of pituitary function following transsphenoidal resection of pituitary macroadenoma. J Clin Endocrinol Metab 79:348–354

    CAS  PubMed  Google Scholar 

  9. Hamrahian A, El-Malawany NK, Arafah BM (1999) Evaluation and management of pituitary-adrenal function after pituitary surgery. Endocrinologist 9:16–24

    Article  Google Scholar 

  10. Abdelmannan D, Selman WR, Arafah BM (2010) Peri-operative management of cushing’s disease. Rev Endocr Metab Disord 11:127–134

    Article  PubMed  Google Scholar 

  11. Abdelmannan D, Selman WR, Arafah BM (2013) Recurrences of ACTH-secreting adenomas after pituitary adenomectomy can be accurately predicted by peri-operative measurements of plasma ACTH levels. J Clin Endocrinol Metab 98:1458–1465

    CAS  Article  PubMed  Google Scholar 

  12. El-Asmar, El-Sibai K, Al-Aridi R, Selman WR, Arafah BM (2016) Post operatively sellar hematoma after pituitary surgery: clinical and biochemical characteristics. Eur J Endocrinol 174:573–582

    Article  PubMed  Google Scholar 

  13. Bansal V, El Asmar N, Selman WR, Arafah BM (2015) Pitfalls in the diagnosis and management of Cushing’s syndrome. Neurosurg Focus 38:1–11

    Article  Google Scholar 

  14. Al-Aridi R, Abdelmannan D, Arafah BM (2011) Biochemical diagnosis of adrenal insufficiency: the added value of DHEA-S measurements. Endocr Pract 17:261–270

    Article  PubMed  Google Scholar 

  15. Sayyed Kassem L, El Sibai K, Chaiban J Abdelmannan D, Arafah BM (2012) Measurements of serum DHEA and DHEA-S levels improve the accuracy of low dose cosyntropin test in the diagnosis of central adrenal insufficiency. J Clin Endocrinol Metab 97:3655–3663

    Article  PubMed  PubMed Central  Google Scholar 

  16. Ioachimescu A, Eiland L, Chhabra V, Mastrogianakis G, Schniederjan M, Brat B, Pileggi A, Oyesiku N (2012) Silent corticotroph adenomas: emory university cohort and comparison with ACTH-negative nonfunctioning pituitary adenomas. Neurosurgery 71:296–303

    Article  PubMed  Google Scholar 

  17. Bradley KJ, Wass JA, Turner HE (2003) Non functioning pituitary adenomas with positive immunoreactivity for ACTH behave more aggressively than ACTH immunonegative tumours but do not recur more frequently. Clin Endocrinol 58:59–64

    CAS  Article  Google Scholar 

  18. Baldeweg SE, Pollock JR, Powell M, Ahlquist J (2005) A spectrum of behavior in silent corticotroph pituitary adenomas. Br J Neurosurg 19(1):38–42

    CAS  Article  PubMed  Google Scholar 

  19. Gibson S, Ray DW, Crosby SR, Dornan TL, Jennings AM, Bevan JS, Davis JR, White A (1996) Impaired processing of proopiomelanocortin in cotricotroph macroadenomas. J Clin Endocrinol Metab 81(2):497–502

    CAS  PubMed  Google Scholar 

  20. Ohta S, Nishizawa S, Oki Y, Yokoyama T, Namba H (2002) Significance of absent prohormone convertase 1/3 in inducing clinically silent corticotroph pituitary adenoma of subtype I—immunohistochemical study. Pituitary 5(4):221–223

    CAS  Article  PubMed  Google Scholar 

  21. Tateno T, Izumiyama H, Doi M, Akashi T, Ohno K, Hirata Y (2007) Defective expression of prohormone convertase 1/3 in silent corticotroph adenoma. Endocr J 54(5):777–782

    CAS  Article  PubMed  Google Scholar 

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This work was funded by local/departmental grant.

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Correspondence to Baha M. Arafah.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Cheres, A.F., ElAsmar, N., Rajpal, A. et al. Perioperative hypothalamic pituitary adrenal function in patients with silent corticotroph adenomas. Pituitary 20, 471–476 (2017).

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  • HPA function
  • Silent corticotroph adenomas
  • Non-secreting adenomas
  • Pituitary surgery