Abstract
Introduction
Double adenomas in the pituitary gland are a rare occurrence. The ability to cure a hormone-producing adenoma with surgery is dependent on the ability to identify and completely remove the correct adenoma. The relative frequency of each subtype of hormone-secreting adenomas confirmed with magnetic resonance image (MRI), surgery and immunohistochemistry is not defined.
Methods
Following PRISMA guidelines, we performed a systematic review of PubMed Central, Google Scholar, Scopus Database, Cochrane database and Science Research, using the key-words: “double pituitary adenomas”, “multiple pituitary adenomas” and only papers where multiple or truly separate double pituitary adenomas were identified pre-surgically by MRI and/or confirmed by pathology/immunohistochemistry staining were included.
Results
We reviewed papers from 1975 to 2016 and found 17 cases with two pituitary adenomas and 1 with three pituitary adenomas. The ages ranged from 22 to 67 years old, and there were twelve females and five males. Immunohistochemical staining showed that the most common double pituitary adenomas were growth hormone (GH)- followed by adrenocorticotropic (ACTH)-secreting.
Conclusion
Double pituitary adenomas are rare but most commonly found with GH- or ACTH-producing tumors. It is critical to remove all identified possible adenomas to achieve biochemical cure and clinicians should have heightened sensitivity in patients with acromegaly or Cushing’s Disease.
Similar content being viewed by others
References
Andrioli M, Giraldi FP, Losa M, Terreni M, Invitti C, Cavagnini F (2010) Cushing’s disease due to double pituitary ACTH-secreting adenomas: the first case report. Endocr J 57(9):833–837
Bader LJ, Carter KD, Latchaw RE, Ellis WG, Wexler JA, Watson JC (2004) Simultaneous symptomatic Rathke’s cleft cyst and GH secreting pituitary adenoma: a case report. Pituitary 7(1):3–44
Budan RM, Georgescu CE (2016) Multiple pituitary adenomas: a systematic review. Front Endocrinol 7:1. doi:10.3389/fendo.2016.00001
Cannavò S, Curtò L, Lania A, Saccomanno K, Salpietro FM, Trimarchi F (1999) Unusual MRI finding of multiple adenomas in the pituitary gland: a case report and review of the literature. Magn Reson Imaging 17:633–636
Chohan MO, Levin AM, Singh R, Zhou Z, Green CL, Kazam JJ, Tsiouris AJ, Anand VK, Schwartz TH (2016) Two-dimensional planar measurements versus three-dimensional volumetric measurements in defining giant adenoma surgery outcomes. J Neurol Surg Part B 77(S 01):A121
Davis FG, Kupelian V, Freels S, McCarthy B, Surawicz T (2001) Prevalence estimates for primary brain tumors in the United States by behavior and major histology groups. Neuro-Oncology 3(3):152–158
de Oliveira Andrade LJ, Santos França L, Santos França L, Cordeiro de Almeida MA (2010) Double pituitary prolactinoma. J Clin Endocrinol Metab 95(11):4848–4849
Eytan S, Kim KY, Bleich D, Raghuwanshi M, Eloy JA, Liu JK (2015) Isolated double pituitary adenomas: a silent corticotroph adenoma and a microprolactinoma. J Clin Neurosci 22(10):1676–1678
Fliers E, Korbonits M, Romijn JA (2014) Nonfunctioning pituitary tumors. Clin Neuroendocrinol 28:167
Goldberg AS, Stein R, Merritt NH, Inculet R, Van Uum S (2014) A pediatric patient with Cushing syndrome caused by ectopic ACTH syndrome and concomitant pituitary incidentalomas. J Pediatr Endocrinol Metab 27(1–2):123–128
Hashimoto N, Handa H, Yamagami T, Kojima M, Aoki M, Okamoto S, Kato Y, Imura H (1984) Acromegaly with multiple secreting pituitary adenomas. Surg Neurol 22(6):556–558
Hofstetter C, Mannah RM, Mubita L, Anand VK, Dehdashti A, Schwartz TH (2010) Endoscopic endonasal approach for growth-hormone secreting pituitary adenomas. Neurosurg Focus 29(4):E6
Hofstetter C, Nanszko M, Mubita L, Tsiousris J, Anand V, Schwartz T (2011) Volumetric classification for giant pituitary macroadenomas predicts outcome and morbidity of endoscopic endonasal transsphenoidal surgery. Skull Base 21(S 01):A122
Hofstetter CP, Shin BJ, Mubita L, Huang C, Anand VK, Boockvar JA, Schwartz TH (2011) Endoscopic endonasal transsphenoidal surgery for functional pituitary adenomas. Neurosurg Focus 30(4):E10
Jastania RA, Alsaad KO, Al-Shraim M, Kovacs K, Asa SL (2005) Double adenomas of the pituitary: transcription factors Pit-1, T-pit, and SF-1 identify cytogenesis and differentiation. Endocr Pathol 16(3):187–194
Kannan S, Staugaitis SM, Weil RJ, Hatipoglu B (2012) A rare corticotroph-secreting tumor with coexisting prolactin and growth hormone staining cells. Case Rep Endocrinol 2012. doi:10.1155/2012/529730
Karavitaki N, Scheithauer BW, Watt J, Ansorge O, Moschopoulos M, Llaguno AV et al (2008) Collision lesions of the sella: co-existence of craniopharyngioma with gonadotroph adenoma and of Rathke’s cleft cyst with corticotroph adenoma. Pituitary 11(3):317–323
Kim K, Yamada S, Usui M, Sano T (2004) Preoperative identification of clearly separated double pituitary adenomas. Clin Endocrinol 61(1):26–30
Kobayashi Y, Takei M, Ohkubo Y, Kakizawa Y, Matoba H, Kumagai M, Takeda T, Suzuki S, Komatsu M (2014) A somatotropin-producing pituitary adenoma with an isolated adrenocorticotropin-producing pituitary adenoma in a female patient with acromegaly, subclinical Cushing’s disease and a left adrenal tumor. Endocr J 61(6):589–595
Komotar RJ, Starke RM, Raper DM, Anand VK, Schwartz TH (2012) Endoscopic endonasal compared with microscopic transsphenoidal and open transcranial resection of giant pituitary adenomas. Pituitary 15(2):150–159
Kontogeorgos G, Scheithauer BW, Kovacs K, Lloyd RV, Smyth HS, Rologis D (1992) Double adenomas of the pituitary: a clinicopathological study of 11 tumors. Neurosurgery 31(5):840–853
Koutourousiou M, Kontogeorgos G, Wesseling P, Grotenhuis AJ, Seretis A (2010) Collision sellar lesions: experience with eight cases and review of the literature. Pituitary 13(1):8–17
Kumar KH, Prusty P (2013) Resistant prolactinoma: is it monoclonal or polyclonal?. Indian J Endocrinol Metab 17(Suppl1):S139
Magri F, Villa C, Locatelli D, Scagnelli P, Lagonigro MS, Morbini P, Castellano M, Gabellieri E, Rotondi M, Solcia E, Daly AF (2010) Prevalence of double pituitary adenomas in a surgical series: clinical, histological and genetic features. J Endocrinol Investig 33(5):325–331
McKelvie PA, McNeill P (2002) Double pituitary adenomas: a series of three patients. Pathology 34(1):57–60
Mehta GU, Montgomery BK, Raghavan P, Sharma S, Nieman LK, Patronas N, Oldfield EH, Chittiboina P (2015) Different imaging characteristics of concurrent pituitary adenomas in a patient with Cushing’s disease. J Clin Neurosci 22(5):891–894
Meij BP, Lopes MB, Vance ML, Thorner MO, Laws ER (2000) Double pituitary lesions in three patients with Cushing’s disease. Pituitary 3(3):159–168
Molitch ME (2008) Nonfunctioning pituitary tumors and pituitary incidentalomas. Endocrinol Metab Clin North Am 37(1):151–171
Molitch ME (2009) Pituitary tumors: pituitary incidentalomas. Best Pract Res Clin Endocrinol Metab 23(5):667–675
Negm HM, Al-Mahfoudh R, Pai M, Singh H, Cohen S, Dhandapani S, Anand VK, Schwartz TH (2016) Reoperative endoscopic endonasal surgery for residual or recurrent pituitary adenomas. J Neurosurg. doi:10.3171/2016.8.JNS152709
Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, Stroup NE, Kruchko C, Barnholtz-Sloan JS (2013) CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neuro-Oncology. 15(suppl_2):ii1–56
Pantelia E, Kontogeorgos G, Piaditis G, Rologis D (1998) Triple pituitary adenoma in Cushing’s disease: case report. Acta Neurochir 140(2):190–193
Ratliff JK, Oldfield EH (2000) Multiple pituitary adenomas in Cushing’s disease. J Neurosurg 93(5):753–761
Roberts S, Borges MT, Lillehei KO, Kleinschmidt-DeMasters BK (2016) Double separate versus contiguous pituitary adenomas: MRI features and endocrinological follow up. Pituitary 19(5):472–481
Salpietro FM, Alafaci C, Grasso G, Lucerna S, Passalacqua M, Tomasello F (1999) Transsphenoidal microsurgical selective removal of multiple (triple) adenomas of the pituitary gland. Acta Neurochir 141(4):425–428
Sano T, Horiguchi H, Xu B, Li C, Hino A, Sakaki M, Kannuki S, Yamada S (1999) Double pituitary adenomas: six surgical cases. Pituitary 1(3):243–250
Shimizu C, Koike T, Sawamura Y (2004) Double pituitary adenomas with distinct histological features and immunophenotypes. J Neurol Neurosurg Psychiatry 75(1):140
Singh H, Essayed WI, Cohen-Gadol A, Zada G, Schwartz TH (2016) Resection of pituitary tumors: endoscopic versus microscopic. J Neuro-Oncol 130(2):309–317
Stobo DB, Lindsay RS, Connell JM, Dunn L, Forbes KP (2011) Initial experience of 3 T versus conventional field strength magnetic resonance imaging of small functioning pituitary tumours. Clin Endocrinol 75(5):673–677
Tabaee A, Anand VK, Barrón Y, Hiltzik DH, Brown SM, Kacker A, Mazumdar M, Schwartz TH (2009) Endoscopic pituitary surgery: a systematic review and meta-analysis. J Neurosurg 111(3):545–554
Tabaee A, Anand VK, Barrón Y, Hiltzik DH, Brown SM, Kacker A, Mazumdar M, Schwartz TH (2009) Predictors of short-term outcomes following endoscopic pituitary surgery. Clin Neurol Neurosurg 111(2):119–122
Tabarin A, Laurent F, Catargi B, Olivier-Puel F, Lescene R, Berge J, San Galli F, Drouillard J, Roger P, Guerin J (1998) Comparative evaluation of conventional and dynamic magnetic resonance imaging of the pituitary gland for the diagnosis of Cushing’s disease. Clin Endocrinol 49(3):293–300
Tosaka M, Kohga H, Kobayashi S, Zama A, Tamura M, Murakami M, Sasaki T (2000) Double pituitary adenomas detected on preoperative magnetic resonance images: case illustration. J Neurosurg 92(2):361
Vidal S, Syro L, Horvath E, Uribe H, Kovacs K (1999) Ultrastructural and immunoelectron microscopic study of three unusual plurihormonal pituitary adenomas. Ultrastruct Pathol 23(3):141–148
Woosley RE (1983) Multiple secreting microadenomas as a possible cause of selective transsphenoidal adenomectomy failure: case report. J Neurosurg 58(2):267–269
Zieliński G, Maksymowicz M, Podgórski J, Olszewski WT (2013) Double, synchronous pituitary adenomas causing acromegaly and Cushing’s disease. A case report and review of literature. Endocr Pathol 24(2):92–99
Melmed S (2003) Mechanisms for pituitary tumorigenesis: the plastic pituitary. J Clin Investig 112(11):1603
Bates AS, Farrell WE, Bicknell EJ, McNicol AM, Talbot AJ, Broome JC, Perrett CW, Thakker RV, Clayton RN (1997) Allelic deletion in pituitary adenomas reflects aggressive biological activity and has potential value as a prognostic marker. J Clin Endocrinol Metab 82(3):818–824
Oyama K, Yamada S, Hukuhara N, Hiramatsu R, Taguchi M, Yazawa M, Matsuda A, Ohmura E, Imai Y (2006) FSH-producing macroadenoma associated in a patient with Cushing’s disease. Neuro Endocrinol Lett 27(6):733–736
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Rights and permissions
About this article
Cite this article
Ogando-Rivas, E., Alalade, A.F., Boatey, J. et al. Double pituitary adenomas are most commonly associated with GH- and ACTH-secreting tumors: systematic review of the literature. Pituitary 20, 702–708 (2017). https://doi.org/10.1007/s11102-017-0826-6
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11102-017-0826-6