Gamze AKKUŞ, Baris KARAGÜN, Nuri Eralp ÇETİNALP, Arbil AÇIKALIN, Fulya ODABAŞ, Mehtap EVRAN OLGUN, Murat SERT, Suzan ZORLUDEMİR, Bekir Tamer TETİKER

Klinik olarak belirgin Cushing hastalığı olan hastalar ile sessiz kortikotrof hücreli adenomu olan hastaların klinik, hormonal, radyolojik ve morfolojik olarak karşılaştırılması

Amaç: Bu çalışmada retrospektif olarak kendi kliniğimizde takip edilen sessiz kortikotrof adenomu (SKA) olan hastalar ile belirgin kortizol sekrete eden adenomu (Cushing Hastalığı (CH)) olan hastaları klinik, radyolojik, immunohistokimyasal ve cerrahi sonuçlarına göre karşılaştırılması amaçlanmıştır. Gereç ve Yöntem: Retrospektif olarak takip edilmiş 17 hastanın 10 tanesi SKA; diğer 7 tanesi aşikar CH olan bireyleri klinik, biyokimyasal, nöroradyolojik ve patolojik verilerine göre toplayıp karşılaştırdık. Bulgular: CH olan hastalar ile SKA’sı olan hastaların preoperatif ACTH değerleri (60.4±29.5, 45.5±34.6 pg/mL) birbirine benzer olup, preoperatif kortizol değerleri (21.2±4.4 vs 11.5±4.0 mcg/dL) arasında anlamlı farklılık vardı. SKA’sı olan hastaların ortalama hipofiz adenom boyutları (20.4±4.5 mm), CH olan bireylerin ortalama adenom boyutlarından (8.8±4.0 mm) daha fazla idi. Aynı şekilde kavernöz sinüs invazyonu SKA’sı olan hastalarda daha fazla görülmekte idi. Her iki grupta immunohistokimyasal olarak seyrek granüllü boyanma paterni (SKA 7/10, CH 4/7) daha fazla görülmekte idi. Sonuç: Sessiz kortikotrof adenomlar klinik ve postoperatif sonuçları itibari ile aşikar CH olan bireylerden tamamı ile farklıdır. Bu yönü ile sessiz kortikotrof adenomları pituiter adenomların farklı bir sub-grubu gibi değerlendirmek daha doğru olacaktır.

Clinical, hormonal, radiological and morphological comparison of patients with clinically evident Cushing's disease and patients with silent corticotroph cell adenoma

Purpose: The aim of the study was to review our clinical 7 years experiences with silent corticotroph adenoma (SCA) and Cushing disease (CD) with regard to clinical, radiological features, immunohistochemical and surgical outcomes and compare the results between two groups. Material and Methods: We retrospectively reviewed a series of patients (n=17; SCA 10, CD 7) with corticotroph adenomas and collected biochemical, neuroradiological and pathological data of those during follow-up time. Results: Mean pre-operative ACTH values of the patients with CD and SCA were 60.4±29.5, 45.5±34.6 pg/mL, respectively. Mean preoperative cortisol of the patient with CD (21.2±4.4 vs 11.5±4.0 mcg/dL) was increased than the patients with SCA measurements’. Patients with SCA had larger pituitary mass (20.4±4.5 vs 8.8±4.0 mm) than the patients with CD. And cavernous sinus invasion also was determined in all patients with SCA. Sparsely granulation staining was more common in all patients with SCA (7/10) or CD (4/7). Conclusion: SCAs are totally different from functional CD adenomas related with clinical characteristics and postoperative outcomes. SCA can be thought of as a diverse group of pituitary adenomas.

Keywords:

pituitary adenomas, silent corticotroph adenomas, clinical comparison,

PDF

___

1. Baldeweg SE, Pollock JR, Powell M, Ahlquist J. A spectrum of behaviour in silent corticotroph pituitary adenomas. Br J Neurosurg. 2005;19:38-42.
2. Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP,. Diagnosis and complications of Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab. 2003;88:5593– 5602
3. Cooper O, Ben-Shlomo A, Bonert V, Bannykh S, Mirocha J, Melmed S. Silent corticogonadotroph adenomas: clinical and cellular characteristics and long-term outcomes. Horm Cancer. 2010;1:80–92.
4. Scheithauer BW, Jaap AJ, Horvath E, Kovacs K, Lloyd RV, Meyer FB, et al. Clinically silent corticotroph tumors of the pituitary gland. Neurosurgery. 2000;47:723–29.
5. Kovacs K, Horvath E, Bayley TA, Hassaram ST, Ezrin C. Silent corticotroph cell adenoma with lysosomal accumulation and crinophagy. A distinct clinicopathologic entity. Am J Med. 1978;64:492–99.
6. Guttenberg K, Mayson S, Sawon C, Kharlip J. Prevalence of clinically silent corticotroph macroadenomas. Clin Endocrinol. 2016;85:874-80.
7. Kageyama K, Oki Y, Nigawara T. Pathophysiology and treatment of subclinical Cushing’s disease and pituitary silent corticotroph adenomas. Endocr. Journal. 2014;61:941-8.
8. Bradley KJ, Wass JA, Turner HE. Non-functioning pituitary adenomas with positive immunoreactivity for ACTH behave more aggressively than ACTH immunonegative tumours but do not recur more frequently. Clin Endocrinol (Oxf). 2003;58:59-64.
9. Nishioka H, Inoshita N, Mete O, Asa SL, Hayashi K, Takeshita A et al. The complementary role of transcription factors in the accurate diagnosis of clinically nonfunctioning pituitary adenomas. Endocr Pathol. 2015;26:349-55.
10. DeLellis RA, Lloyd RV, Heitz PU, Eng C. Pathology and Genetics of tumors of Endocrine Organs. In: PU K, LH S, editors. World Health Organization Classification of Tumours. IARC Press; City: 2004.
11. Jahangiri A, Wagner JR, Pekmezci M, Hiniker A, Chang EF, Kunwar S et al. A comprehensive longterm retrospective analysis of silent corticotrophic adenomas vs hormone-negative adenomas. Neurosurgery. 2013;73:8–17.
12. Tateno T, Kato M, Tani Y, Oyama K, Yamada S, Hirata Y. Differential expression of somatostatin and dopamine receptor subtype genes in adrenocorticotropin (ACTH)-secreting pituitary tumors and silent corticotroph adenomas. Endocr J. 2009;56:579–84.
13. Mete O, Lopes MB. Overview of the 2017 WHO classification of pituitary tumors. Endocr Pathol. 2017;28:228-243.
14. Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93:1526–40.
15. Knosp E, Steiner E, Kitz K, Matula C. Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery. 1993;33:610-17.
16. Hosoyama T, Nishijo K, Garcia MM, Schaffer BS, Ohshima-Hosoyama S, Prajapati SI et al. A postnatal Pax7 progenitor gives rise to pituitary adenomas. Genes Cancer. 2010;1:388–402.
17. Webb KM, Laurent JJ, Okonkwo DO, Lopes MB, Vance ML, Laws ER. Clinical characteristics of silent corticotrophic adenomas and creation of an internet- accessible database to facilitate their multi- institutional study. Neurosurgery. 2003;53:1076–85.
18. Bradley KJ, Wass JA, Turner HE. Non-functioning pituitary adenomas with positive immunoreactivity for ACTH behave more aggressively than ACTH immunonegative tumours but do not recur more frequently. Clin Endocrinol (Oxf). 2003;58:59-64
19. Horvath E, Kovacs K, Lloyd RV. Pars intermedia of the human pituitary revisited: morphologic aspects and frequency of hyperplasia of POMC-peptide immunoreactive cells. Endocr Pathol. 1999;10:55–64.
20. Kojima Y, Suzuki S, Yamamura K, Ohhashi G, Yamamoto I. Comparison of ACTH secretion in Cushing's adenoma and clinically silent corticotroph adenoma by cell immunoblot assay. Endocr J. 2002;49:285–92.
21. Shlomo A, Cooper O. Silent corticotroph adenomas. Pituitary. 2018;21:183-93.
22. Takumi I, Steiner DF, Sanno N, Teramoto A, Osamura RY. Localization of prohormone convertases 1/3 and 2 in the human pituitary gland and pituitary adenomas: analysis by immunohistochemistry, immunoelectron microscopy, and laser scanning microscopy. Mod Pathol. 1998;11:232–8.
23. Ohta S, Nishizawa S, Oki Y, Yokoyama T, Namba H. Significance of absent prohormone convertase 1/3 in inducing clinically silent corticotroph pituitary adenoma of subtype I–immunohistochemical study. Pituitary. 2002;5:221–3.
24. Ioachimescu, A.G., Eiland, L., Chhabra, V.S. Silent corticotroph adenomas: Emory University cohort and comparison with ACTH negative nonfunctioning pituitary adenomas. Neurosurgery. 2012;71:296–303.
25. Scheithauer, B.W., Jaap, A.J., Horvath, E. Clinically silent corticotroph tumors of the pituitary gland. Neurosurgery. 2000;47:723–9.
26. Kim D, Ku C, Park S, Moon Ju, Kim Eui. Clinical parameters to distinguish silent corticotroph adenomas from other nonfunctioning pituitary adenomas. World Neurosurg. 2018;115:64-71.
27. Cazabat L, Dupuy M, Boulin A, Bernier M. Silent,but not unseen: multimicrocystic aspect on T2-weighted MRI in silent corticotroph adenomas. Clin Endocrinol. 2014;81:566-72.
28. Fahlbusch R, , Buchfelder M, & Müller OA: Transsphenoidal surgery for Cushing's disease. J R Soc Med.1986;79:262–9.
29. Tindall GT, Herring CJ, Clark RV, Adams DA, & Watts NB: Cushing's disease: results of transsphenoidal microsurgery with emphasis on surgical failures. J Neurosurg. 1990;72:363–9.
30. Cho HY, Cho SW, Kim SW, Shin CS, Park KS, Kim SY. Silent corticotroph adenomas have unique recurrence characteristics compared with other nonfunctioning pituitary adenomas. Clin Endocrinol (Oxf). 2010;72:648-53.
31. Smith T, Hulou M, Huang K, Nery B. Complications after transsphenoidal surgery for patients with Cushing's disease and silent corticotroph adenomas. J Neurosurg. 2015;38:E12.
32. Yamakita, N., Murai, T., Kawamura, S. High molecular weight corticotropin measured with immunoradiometric assay in a patient with asymptomatic pituitary corticotropinoma. Endocr J. 1999;46:563–71.
33. Zoli M, Fustini M, Mazzatenta D, Marucci G, Carlo E. ACTH adenomas transforming their clinical expression: report of 5 cases. Neurosurg Focus. 2015;38:2015.