pp 1–11 | Cite as

Pituitary tumors: epidemiology and clinical presentation spectrum

  • Marta Araujo-CastroEmail author
  • Víctor Rodríguez Berrocal
  • Eider Pascual-Corrales
Review Article


Pituitary tumors (PTs) are a heterogeneous group of lesions of the central nervous system that are usually benign. Most of them occur sporadically, but 5% can do so within family syndromes, usually at a young age. There are differences by sex, age, race, and genetic factors in the prevalence of different tumor cell types and clinical presentation. Functioning-PTs (FPTs) are usually diagnosed earlier than non-functioning PTs (NFPTs). However, this depends on the PT type. Headaches and visual disturbances are the most frequent mass-effect symptoms, but seizures or hydrocephalus may also occur. Pituitary apoplexy is another possible mode of presentation, and it requires special attention because of its potential severity. PTs in pregnancy, childhood, and old age present a series of clinical peculiarities that must be taken into account when evaluating these patients. Ectopic PTs (EPTs) are uncommon and share the same clinical-epidemiological data as eutopic PTs, but, depending on their location, other types of clinical manifestations may appear. Silent PTs are often detected as an incidentaloma or due to neurologic symptoms related to mass-effect. Aggressive PTs and pituitary carcinomas (PCs), which are very rare, are characterized by multiple local recurrences and metastases, respectively. This review addresses the epidemiology and clinical presentation of PTs, from the classical hormonal and mass-effect symptoms to the different rare presentations, such as pituitary apoplexy, hydrocephalus, or diabetes insipidus. Moreover, special situations of the presentation of PTs are discussed, namely, PTs in pregnancy, childhood, and the elderly, EPTs, silent and aggressive PTs, and PCs.


Pituitary tumors Non-functioning pituitary tumors Mass-effect symptoms Hormonal symptoms Pituitary apoplexy 


Compliance with ethical standards

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.


  1. 1.
    Villa C, Vasiljevic A, Jaffrain-Rea ML et al (2019) A standardised diagnostic approach to pituitary neuroendocrine tumours (PitNETs): a European Pituitary Pathology Group (EPPG) proposal. Virchows Arch. PubMedCrossRefGoogle Scholar
  2. 2.
    Ho KKY, Fleseriu M, Wass J et al (2019) A tale of pituitary adenomas: to NET or not to NET. Pituitary. PubMedCrossRefGoogle Scholar
  3. 3.
    Aflorei ED, Korbonits M (2014) Epidemiology and etiopathogenesis of pituitary adenomas. J Neuro-Oncol. PubMedCrossRefGoogle Scholar
  4. 4.
    Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, McCutcheon IE (2004) The prevalence of pituitary adenomas: a systematic review. Cancer 101(3):613–619CrossRefGoogle Scholar
  5. 5.
    Mindermann T, Wilson CB (1994) Age-related and gender-related occurrence of pituitary adenomas. Clin Endocrinol 41(3):359–364CrossRefGoogle Scholar
  6. 6.
    Beckers A, Daly AF (2007) The clinical, pathological, and genetic features of familial isolated pituitary adenomas. Eur J Endocrinol. PubMedCrossRefGoogle Scholar
  7. 7.
    Solari D, Pivonello R, Caggiano C, Guadagno E, Chiaramonte C, Miccoli G, Cavallo LM, Del Basso De Caro M, Colao A, Cappabianca P (2019) Pituitary adenomas: what are the key features? What are the current treatments? Where is the future taking us? World Neurosurg 127:695–709. CrossRefPubMedGoogle Scholar
  8. 8.
    Alrezk R, Hannah-Shmouni F, Stratakis CA (2017) MEN4 and CDKN1B mutations: the latest of the MEN syndromes. Endocr Relat Cancer. PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Vasilev V, Daly AF, Petrossians P, Zacharieva S, Beckers A (2011) Familial pituitary tumor syndromes. Endocr Pract 17(Suppl 3):41–46. CrossRefPubMedGoogle Scholar
  10. 10.
    Shaid M, Korbonits M (2017 May-Jun) Genetics of pituitary adenomas. Neurol India 65(3):577–587. CrossRefPubMedGoogle Scholar
  11. 11.
    Pepe S, Korbonits M, Iacovazzo D (2019) Germline and mosaic mutations causing pituitary tumours: genetic and molecular aspects. J Endocrinol.
  12. 12.
    Drange MR, Fram NR, Herman-Bonert V, Melmed S (2000) Pituitary tumor registry: a novel clinical resource. J Clin Endocrinol Metab. Google Scholar
  13. 13.
    Karaca Z, Yarman S, Ozbas I et al (2018) How does pregnancy affect the patients with pituitary adenomas: a study on 113 pregnancies from Turkey. J Endocrinol Investig. PubMedCrossRefGoogle Scholar
  14. 14.
    Perry A, Graffeo CS, Marcellino C, Pollock BE, Wetjen NM, Meyer FB (2018) Pediatric pituitary adenoma: case series, review of the literature, and a skull base treatment paradigm. J Neurol Surg Part B Skull Base. CrossRefGoogle Scholar
  15. 15.
    Minniti G, Esposito V, Piccirilli M, Fratticci A, Santoro A, Jaffrain-Rea ML (2005) Diagnosis and management of pituitary tumours in the elderly: a review based on personal experience and evidence of literature. Eur J Endocrinol. PubMedCrossRefGoogle Scholar
  16. 16.
    Agely A, Okromelidze L, Vilanilam GK, Chaichana KL, Middlebrooks EH, Gupta V (2019) Ectopic pituitary adenomas: common presentations of a rare entity. Pituitary. PubMedCrossRefGoogle Scholar
  17. 17.
    Mayson SE, Snyder PJ (2015) Silent pituitary adenomas. Endocrinol Metab Clin N Am. PubMedCrossRefGoogle Scholar
  18. 18.
    Raverot G, Trouillas J, Burman P, McCormack A, Heaney A, Petersenn S, Popovic V, Dekkers OM (2018 Jan) European society of endocrinology clinical practice guidelines for the management of aggressive pituitary tumours and carcinomas. Eur J Endocrinol 178(1):G1–G24. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Lloyd RV, Osamura YR, Kloppel G, Rosai J (2017) WHO classification of tumours of endocrine organs. WHO PressGoogle Scholar
  20. 20.
    Nilsson B, Gustavsson-Kadaka E, Bengtsson BÅ, Jonsson B (2000) Pituitary adenomas in Sweden between 1958 and 1991: incidence, survival, and mortality. J Clin Endocrinol Metab. Google Scholar
  21. 21.
    Daly AF, Tichomirowa MA, Beckers A (2009) The epidemiology and genetics of pituitary adenomas. Best Pract Res Clin Endocrinol Metab. CrossRefGoogle Scholar
  22. 22.
    Nammour GM, Ybarra J, Naheedy MH, Romeo JH, Aron DC (1997) Incidental pituitary macroadenoma: a population-based study. Am J Med Sci 314(5):287–291PubMedGoogle Scholar
  23. 23.
    Yue NC, Longstreth WT, Elster AD, Jungreis CA, O’Leary DH, Poirier VC (1997) Clinically serious abnormalities found incidentally at MR imaging of the brain: data from the Cardiovascular Health Study. Radiology. PubMedCrossRefGoogle Scholar
  24. 24.
    McDowell BD, Wallace RB, Carnahan RM, Chrischilles EA, Lynch CF, Schlechte JA (2011) Demographic differences in incidence for pituitary adenoma. Pituitary. CrossRefGoogle Scholar
  25. 25.
    Agustsson TT, Baldvinsdottir T, Jonasson JG, Olafsdottir E, Steinthorsdottir V, Sigurdsson G, Thorsson AV, Carroll PV, Korbonits M, Benediktsson R (2015) The epidemiology of pituitary adenomas in Iceland, 1955-2012: a nationwide population-based study. Eur J Endocrinol. PubMedCrossRefGoogle Scholar
  26. 26.
    Fernandez A, Karavitaki N, Wass JAH (2010) Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol. PubMedCrossRefGoogle Scholar
  27. 27.
    Richard N (1999) Clayton. Sporadic pituitary tumours: from epidemiology to use of databases. Baillieres Best Pract Res Clin Endocrinol Metab 13(3):451–460CrossRefGoogle Scholar
  28. 28.
    Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A (2006) High prevalence of pituitary adenomas: a cross-sectional study in the province of Liège. Belgium J Clin Endocrinol Metab doi. CrossRefGoogle Scholar
  29. 29.
    Heshmat MY, Kovi J, Simpson C, Kennedy J, Fan KJ (1976) Neoplasms of the central nervous system. Incidence and population selectivity in the Washington DC, metropolitan area. Cancer.<2135::AID-CNCR2820380543>3.0.CO;2-T
  30. 30.
    Gittleman H, Ostrom QT, Farah PD et al (2014) Descriptive epidemiology of pituitary tumors in the United States, 2004-2009: clinical article. J Neurosurg. PubMedCrossRefGoogle Scholar
  31. 31.
    Tjörnstrand A, Gunnarsson K, Evert M, et al. The incidence rate of pituitary adenomas in western Sweden for the period 2001-2011. Eur J Endocrinol. 2014;171(4):519–526PubMedCrossRefGoogle Scholar
  32. 32.
    Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, Wass JAH (2011) Diagnosis and treatment of hyperprolactinemia: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. CrossRefGoogle Scholar
  33. 33.
    Nieman LK, Biller BMK, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM (2008) The diagnosis of Cushing’s syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. CrossRefGoogle Scholar
  34. 34.
    Katznelson L, Laws ER, Melmed S, Molitch ME, Murad MH, Utz A, Wass JAH (2014) Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. CrossRefGoogle Scholar
  35. 35.
    Ntali G, Capatina C, Grossman A, Karavitaki N (2014) Functioning gonadotroph adenomas. J Clin Endocrinol Metab. CrossRefGoogle Scholar
  36. 36.
    Beck-Peccoz P, Persani L, Mannavola D, Campi I (2009) TSH-secreting adenomas. Best Pract Res Clin Endocrinol Metab. CrossRefGoogle Scholar
  37. 37.
    Penn DL, Burke WT, Laws ER (2018) Management of non-functioning pituitary adenomas: surgery. Pituitary. CrossRefGoogle Scholar
  38. 38.
    Lithgow K, Batra R, Matthews T (2019) Karavitaki N. Management of endocrine disease: visual morbidity in patients with pituitary adenoma. Eur J Endocrinol 181(5):R185–R197. CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Vié AL, Raverot G (2019) Modern neuro-ophthalmological evaluation of patients with pituitary disorders. Best Pract Res Clin Endocrinol Metab. CrossRefGoogle Scholar
  40. 40.
    Thomas R, Shenoy K, Seshadri MS, Muliyil J, Rao A, Paul P (2002) Visual field defects in non-functioning pituitary adenomas. Indian J Ophthalmol 50(2):127–130PubMedGoogle Scholar
  41. 41.
    Rizzoli P, Iuliano S, Weizenbaum E, Laws E (2016) Headache in patients with pituitary lesions: a longitudinal cohort study. Neurosurgery. CrossRefGoogle Scholar
  42. 42.
    Arafah BM, Prunty D, Ybarra J, Hlavin ML, Selman WR (2000) The dominant role of increased intrasellar pressure in the pathogenesis of hypopituitarism, hyperprolactinemia, and headaches in patients with pituitary adenomas. J Clin Endocrinol Metab. Google Scholar
  43. 43.
    Levy MJ (2011) The association of pituitary tumors and headache. Curr Neurol Neurosci Rep. CrossRefGoogle Scholar
  44. 44.
    Turcu AF, Erickson BJ, Lin E, Guadalix S, Schwartz K, Scheithauer BW, Atkinson JLD, Young WF (2013) Pituitary stalk lesions: the mayo clinic experience. J Clin Endocrinol Metab. CrossRefGoogle Scholar
  45. 45.
    Iglesias P, Rodríguez Berrocal V, Díez JJ (2018) Giant pituitary adenoma: histological types, clinical features and therapeutic approaches. Endocrine. PubMedCrossRefGoogle Scholar
  46. 46.
    Chentli F, Akkache L, Daffeur K, Azzoug S (2014) General seizures revealing macro-adenomas secreting prolactin or prolactin and growth hormone in men. Indian J Endocrinol Metab. PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Brisman MH, Fetell MR, Post KD (1993) Reversible dementia due to macroprolactinoma. Case Rep J Neurosurg. PubMedCrossRefGoogle Scholar
  48. 48.
    Freda PU, Beckers AM, Katznelson L, Molitch ME, Montori VM, Post KD, Lee Vance M (2011) Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. CrossRefGoogle Scholar
  49. 49.
    Molitch ME (2009) Pituitary tumours: pituitary incidentalomas. Best Pract Res Clin Endocrinol Metab. CrossRefGoogle Scholar
  50. 50.
    Bills DC, Meyer FB, Laws ER, Davis DH, Ebersold MJ, Scheithauer BW, Ilstrup DM, Abboud CF (1993) A retrospective analysis of pituitary apoplexy. Neurosurgery 33(4):602–608PubMedGoogle Scholar
  51. 51.
    Randeva HS, Schoebel J, Byrne J, Esiri M, Adams CBT, Wass JAH (1999) Classical pituitary apoplexy: clinical features, management and outcome. Clin Endocrinol. PubMedCrossRefGoogle Scholar
  52. 52.
    Möller-Goede DL, Brändle M, Landau K, Bernays RL, Schmid C (2011) Pituitary apoplexy: re-evaluation of risk factors for bleeding into pituitary adenomas and impact on outcome. Eur J Endocrinol. PubMedCrossRefGoogle Scholar
  53. 53.
    Barkhoudarian G, Kelly DF (2019) Pituitary apoplexy. Neurosurg Clin N Am 30(4):457–463. CrossRefPubMedGoogle Scholar
  54. 54.
    Glezer A, Bronstein MD (2015) Pituitary apoplexy: pathophysiology, diagnosis and management. Arch Endocrinol Metab 59(3):259–264. CrossRefPubMedGoogle Scholar
  55. 55.
    Hannon AM, O’Shea T, Thompson CA, Hannon MJ, Dineen R, Khattak A et al (2019) Pregnancy in acromegaly is safe and is associated with improvements in IGF-1 concentrations. Eur J Endocrinol 180(4):K21–K29. CrossRefPubMedGoogle Scholar
  56. 56.
    Brue T, Amodru V, Castinetti F (2018) Management of Cushing’s syndrome during pregnancy: solved and unsolved questions. Eur J Endocrinol. PubMedCrossRefGoogle Scholar
  57. 57.
    Hannah-Shmouni F, Stratakis CA (2018) An update on the genetics of benign pituitary adenomas in children and adolescents. Curr Opin Endocr Metab Res. PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Fideleff HL, Boquete HR, Sequera A, Suárez M, Sobrado P, Giaccio A (2000) Peripubertal prolactinomas: clinical presentation and long-term outcome with different therapeutic approaches. J Pediatr Endocrinol Metab.
  59. 59.
    Stratakis CA (2018) An update on Cushing syndrome in pediatrics. Ann Endocrinol (Paris). PubMedCrossRefGoogle Scholar
  60. 60.
    Joshi SM, Hewitt RJD, Storr HL, Rezajooi K, Ellamushi H, Grossman AB, Savage MO, Afshar F (2005) Cushing’s disease in children and adolescents: 20 years of experience in a single neurosurgical center. Neurosurgery. PubMedCrossRefGoogle Scholar
  61. 61.
    Abe T, Tara LA, Ludecke DK (1999) Growth hormone-secreting pituitary adenomas in childhood and adolescence: features and results of transnasal surgery. Neurosurgery 45(1):1–10PubMedCrossRefGoogle Scholar
  62. 62.
    Webb C, Prayson RA (2008) Pediatric pituitary adenomas. Arch Pathol Lab Med 132(1):77–80.[77:PPA]2.0.CO;2 CrossRefPubMedGoogle Scholar
  63. 63.
    Benbow SJ, Foy P, Jones B, Shaw D, MacFarlane IA (1997) Pituitary tumours presenting in the elderly: management and outcome. Clin Endocrinol. PubMedCrossRefGoogle Scholar
  64. 64.
    Yang BT, Chong VFH, Wang ZC, Xian JF, Chen QH (2010) Sphenoid sinus ectopic pituitary adenomas: CT and MRI findings. Br J Radiol 83(987):218–224. CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Hou L, Harshbarger T, Herrick MK, Tse V, Ciric IS, Maartens NF, Laws ER, Marino R (2002) Suprasellar adrenocorticotropic hormone-secreting ectopic pituitary adenoma: case report and literature review. Neurosurgery. PubMedGoogle Scholar
  66. 66.
    Thompson LDR, Seethala RR, Müller S (2012) Ectopic sphenoid sinus pituitary adenoma (ESSPA) with normal anterior pituitary gland: a clinicopathologic and Immunophenotypic study of 32 cases with a comprehensive review of the English literature. Head Neck Pathol. PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Raappana A, Koivukangas J, Ebeling T, Pirilä T (2010) Incidence of pituitary adenomas in Northern Finland in 1992-2007. J Clin Endocrinol Metab. CrossRefGoogle Scholar
  68. 68.
    Park SH, Jang JH, Lee YM, Kim JS, Kim KH, Kim YZ (2017) Function of cell-cycle regulators in predicting silent pituitary adenoma progression following surgical resection. Oncol Lett.
  69. 69.
    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 Tumor Registry. Eur J Endocrinol 156(2):203–216PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Ferrante E, Ferraroni M, Castrignanò T et al (2006) Non-functioning pituitary adenoma database: a useful resource to improve the clinical management of pituitary tumors. Eur J Endocrinol. PubMedCrossRefGoogle Scholar
  71. 71.
    Baldeweg SE, Pollock JR, Powell M, Ahlquist J (2005) A spectrum of behaviour in silent corticotroph pituitary adenomas. Br J Neurosurg. PubMedCrossRefGoogle Scholar
  72. 72.
    Scheithauer BW, Jaap AJ, Horvath E, Kovacs K, Lloyd RV, Meyer FB, Laws ER, Young WF (2000) Clinically silent corticotroph tumors of the pituitary gland. Neurosurgery. PubMedGoogle Scholar
  73. 73.
    Langlois F, Woltjer R, Cetas JS, Fleseriu M (2018) Silent somatotroph pituitary adenomas: an update. Pituitary. PubMedCrossRefGoogle Scholar
  74. 74.
    Kim JS, Lee YS, Jung MJ, Hong YK (2016) The predictive value of pathologic features in pituitary adenoma and correlation with pituitary adenoma recurrence. J Pathol Transl Med. PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Pernicone PJ, Scheithauer BW, Sebo TJ, Kovacs KT, Horvath E, Young WF, Lloyd RV, Davis DH, Guthrie BL, Schoene WC (1997) Pituitary carcinoma: a clinicopathologic study of 15 cases. Cancer.<804::AID-CNCR18>3.0.CO;2-3
  76. 76.
    McCormack A, Dekkers OM, Petersenn S et al (2018) Treatment of aggressive pituitary tumours and carcinomas: results of a European Society of Endocrinology (ESE) survey 2016. Eur J Endocrinol.
  77. 77.
    Lenders N, McCormack A (2018) Malignant transformation in non-functioning pituitary adenomas (pituitary carcinoma). Pituitary. PubMedCrossRefGoogle Scholar
  78. 78.
    Yang Z, Zhang T, Gao H (2016) Genetic aspects of pituitary carcinoma: a systematic review. Med (United States). PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Dworakowska D, Grossman AB (2018) Aggressive and malignant pituitary tumours: state-of-the-art. Endocr Relat Cancer. PubMedCrossRefGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2020

Authors and Affiliations

  1. 1.Neuroendocrinology Unit, Endocrinology DepartmentRamón y Cajal University HospitalMadridSpain
  2. 2.Pituitary Surgery Unit, Neurosurgery DepartmentRamón y Cajal University HospitalMadridSpain

Personalised recommendations