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Pituitary

Published in:

01-04-2018

Epidemiology, clinical presentation and diagnosis of non-functioning pituitary adenomas

Authors: Georgia Ntali, John A. Wass

Published in: Pituitary | Issue 2/2018

Abstract

Purpose

Non-functioning pituitary adenomas (NFPAs) are benign pituitary neoplasms that do not cause a hormonal hypersecretory syndrome. An improved understanding of their epidemiology, clinical presentation and diagnosis is needed.

Method

A literature review was performed using Pubmed to identify research reports and clinical case series on NFPAs.

Results

They account for 14–54% of pituitary adenomas and have a prevalence of 7–41.3/100,000 population. Their standardized incidence rate is 0.65–2.34/100,000 and the peak occurence is from the fourth to the eighth decade. The clinical spectrum of NFPAs varies from being completely asymptomatic to causing significant hypothalamic/pituitary dysfunction and visual field compromise due to their large size. Most patients present with symptoms of mass effect, such as headaches, visual field defects, ophthalmoplegias, and hypopituitarism but also hyperprolactinaemia due to pituitary stalk deviation and less frequently pituitary apoplexy. Non-functioning pituitary incidentalomas are found on brain imaging performed for an unrelated reason. Diagnostic approach includes magnetic resonance imaging of the sellar region, laboratory evaluations, screening for hormone hypersecretion and for hypopituitarism, and a visual field examination if the lesion abuts the optic nerves or chiasm.

Conclusion

This article reviews the epidemiology, clinical behaviour and diagnostic approach of non-functioning pituitary adenomas.

Daly AF, Rixhon M, Adam C et al (2006) High prevalence of pituitary adenomas: a cross-sectional study in the Province of Liege, Belgium. J Clin Endocrinol Metab 91:4769–4775CrossRefPubMed

Fernandez A, Karavitaki N, Wass JA (2010) Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol 72:377–382CrossRef

Fontana E, Gaillard R (2009) Epidemiology of pituitary adenoma: results of the first Swiss study. Rev Med Suisse 5:2172–2174PubMed

Gruppetta M, Merciera C, Vassallo J (2013) Prevalence and incidence of pituitary adenomas: a population based study in Malta. Pituitary 16:545–553CrossRefPubMed

Raappana A, Koivukangas J, Ebeling T et al (2010) Incidence of pituitary adenomas in Northern Finland in 1992–2007. J Clin Endocrinol Metab 95(9):4268–4275CrossRefPubMed

Agustsson TT, Baldvinsdottir T, Jonasson JG et al (2015) The epidemiology of pituitary adenomas in Iceland, 1955–2012: a nationwide population-based study. Eur J Endocrinol 173(5):655–664CrossRefPubMed

Tjörnstrand A, Gunnarsson K, Evert M et al (2014) The incidence rate of pituitary adenomas in western Sweden for the period 2001–2011. Eur J Endocrinol 171(4):519–526CrossRefPubMed

Al-Dahmani K, Mohammad S, Imran F et al (2016) Sellar masses: an epidemiological study. Can J Neurol Sci 43(2):291–297CrossRefPubMed

Day PF, Loto MG, Glerean M et al (2016) Incidence and prevalence of clinically relevant pituitary adenomas: retrospective cohort study in a Health Management Organization in Buenos Aires, Argentina. Arch Endocrinol Metab 60(6):554–561CrossRefPubMed

10.

Davis JR, Farrell WE, Clayton RN (2001) Pituitary tumors. Reproduction 121(3):363–371CrossRefPubMed

11.

Drange MR, Fram NR, Herman-Bonert V et al (2000) Pituitary tumor registry: a novel clinical resource. J Clin Endocrinol Metab 85(1):168–174PubMed

12.

Fernández-Balsells MM, Murad MH, Barwise A et al (2011) Natural history of nonfunctioning pituitary adenomas and incidentalomas: a systematic review and metaanalysis. J Clin Endocrinol Metab 96(4):905–912CrossRefPubMed

13.

Robenshtok E, Benbassat CA, Hirsch D et al (2014) Clinical course and outcome of nonfunctioning pituitary adenomas in the elderly compared with younger age groups. Endocr Pract 20(2):159–164CrossRefPubMed

14.

Freda PU, Beckers AM, Katznelson L et al (2011) Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 96(4):894–904CrossRefPubMedPubMedCentral

15.

Hall WA, Luciano MG, Doppman JL et al (1994) Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population. Ann Intern Med 120(10):817–820CrossRefPubMed

16.

Chong BW, Kucharczyk W, Singer W et al (1994) Pituitary gland MR: a comparative study of healthy volunteers and patients with microadenomas. Am J Neuroradiol 15(4):675–679PubMed

17.

Yue NC, Longstreth WT Jr, Elster AD et al (1997) Clinically serious abnormalities found incidentally at MR imaging of the brain: data from the Cardiovascular Health Study. Radiology 202(1):41–46CrossRefPubMed

18.

Vernooij MW, Ikram MA, Tanghe HL et al (2007) Incidental findings on brain MRI in the general population. N Engl J Med 357(18):1821–1828CrossRefPubMed

19.

Feldkamp J, Santen R, Harms E et al (1999) Incidentally discovered pituitary lesions: high frequency of macroadenomas and hormone-secreting adenomas—results of a prospective study. Clin Endocrinol (Oxf) 51(1):109–113CrossRef

20.

Arita K, Tominaga A, Sugiyama K et al (2006) Natural course of incidentally found nonfunctioning pituitary adenoma, with special reference to pituitary apoplexy during follow-up examination. J Neurosurg 104(6):884–891CrossRefPubMed

21.

Sanno N, Oyama K, Tahara S et al (2003) A survey of pituitary incidentaloma in Japan. Eur J Endocrinol 149(2):123–127CrossRefPubMed

22.

Day PF, Guitelman M, Artese R et al (2004) Retrospective multicentric study of pituitary incidentalomas. Pituitary 7(3):145–148CrossRefPubMed

23.

Anagnostis P, Adamidou F, Polyzos SA et al (2011) Pituitary incidentalomas: a single-centre experience. Int J Clin Pract 65(2):172–177CrossRefPubMed

24.

Imran SA, Yip CE, Papneja N et al (2016) Analysis and natural history of pituitary incidentalomas. Eur J Endocrinol 175(1):1–9CrossRefPubMed

25.

Famini P, Maya MM, Melmed S (2011) Pituitary magnetic resonance imaging for sellar and parasellar masses: ten-year experience in 2598 patients. J Endocrinol Metab 96(6):1633–1641CrossRef

26.

Molitch ME (2009) Pituitary tumors: pituitary incidentalomas. Best Pract Res Clin Endocrinol Metab 23(5):667–765CrossRefPubMed

27.

Buurman H, Saeger W (2006) Subclinical adenomas in postmortem pituitaries: classification and correlations to clinical data. Eur J Endocrinol 154(5):753–758CrossRefPubMed

28.

Greenman Y, Stern N (2009) Non-functioning pituitary adenomas. Best Pract Res Clin Endocrinol Metab 23(5):625–638CrossRefPubMed

29.

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 155(6):823–829CrossRefPubMed

30.

Brochier S, Galland F, Kujas M et al (2010) Factors predicting relapse of nonfunctioning pituitary macroadenomas after neurosurgery: a study of 142 patients. Eur J Endocrinol 163(2):193–200CrossRefPubMed

31.

Nomikos P, Ladar C, Fahlbusch R et al (2004) Impact of primary surgery on pituitary function in patients with non-functioning pituitary adenomas—a study on 721 patients. Acta Neurochir (Wien) 146(1):27–35CrossRef

32.

Losa M, Donofrio CA, Barzaghi R et al (2013) Presentation and surgical results of incidentally discovered nonfunctioning pituitary adenomas: evidence for a better outcome independently of other patients’ characteristics. Eur J Endocrinol 169(6):735–742CrossRefPubMed

33.

O’Sullivan EP, Woods C, Glynn N et al (2009) The natural history of surgically treated but radiotherapy-naïve nonfunctioning pituitary adenomas. Clin Endocrinol (Oxf) 71(5):709–714CrossRef

34.

Chang EF, Zada G, Kim S et al (2008) Long-term recurrence and mortality after surgery and adjuvant radiotherapy for nonfunctional pituitary adenomas. J Neurosurg 108(4):736–745CrossRefPubMed

35.

Vergès B, Boureille F, Goudet P et al (2002) Pituitary disease in MEN type 1 (MEN1): data from the France–Belgium MEN1 multicenter study. J Clin Endocrinol Metab 87(2):457–465CrossRefPubMed

36.

de Laat JM, Dekkers OM, Pieterman CR et al (2015) Long-term natural course of pituitary tumors in patients with MEN1: results from the Dutch MEN1 Study Group (DMSG). J Clin Endocrinol Metab 100(9):3288–3296CrossRefPubMed

37.

Daly AF, Jaffrain-Rea ML, Ciccarelli A et al (2006) Clinical characterization of familial isolated pituitary adenomas. J Clin Endocrinol Metab 91(9):3316–3323CrossRefPubMed

38.

Dwight T, Mann K, Benn DE et al (2013) Familial SDHA mutation associated with pituitary adenoma and pheochromocytoma/paraganglioma. J Clin Endocrinol Metab 98(6):E1103–E1108CrossRefPubMed

39.

Vargas G, Gonzalez B, Ramirez C et al (2015) Clinical characteristics and treatment outcome of 485 patients with nonfunctioning pituitary macroadenomas. Int J Endocrinol. https://doi.org/10.1155/2015/756069

40.

Ntali G, Capatina C, Fazal-Sanderson V et al (2016) Mortality in patients with non-functioning pituitary adenoma is increased: systematic analysis of 546 cases with long follow-up. Eur J Endocrinol 174(2):137–145CrossRefPubMed

41.

Rizzoli P, Iuliano S, Weizenbaum E et al (2016) Headache in patients with pituitary lesions: a longitudinal cohort study. Neurosurgery 78(3):316–323CrossRefPubMed

42.

Jahangiri A, Wagner JR, Chin AT et al (2015) Incidence of headache as a presenting complaint in over 1000 patients with sellar lesions and factors predicting postoperative improvement. Clin Neurol Neurosurg 132:16–20CrossRefPubMed

43.

Greenman Y, Melmed S (1996) Diagnosis and management of nonfunctioning pituitary tumors. Annu Rev Med 47:95–106CrossRefPubMed

44.

Lee IH, Miller NR, Zan E et al (2015) Visual defects in patients with pituitary adenomas: the myth of bitemporal hemianopsia. Am J Roentgenol 205(5):W512–W518CrossRef

45.

Ogra S, Nichols AD, Stylli S et al (2014) Visual acuity and pattern of visual field loss at presentation in pituitary adenoma. J Clin Neurosci 21(5):735–740CrossRefPubMed

46.

Jahangiri A, Lamborn KR, Blevins L et al (2012) Factors associated with delay to pituitary adenoma diagnosis in patients with visual loss. J Neurosurg 116(2):283–289CrossRefPubMed

47.

Kim SH, Lee KC, Kim SH (2007) Cranial nerve palsies accompanying pituitary tumor. J Clin Neurosci 14(12):1158–1162CrossRefPubMed

48.

Verhelst J, Berwaerts J, Abs R (1998) Obstructive hydrocephalus as complication of a giant nonfunctioning pituitary adenoma: therapeutical approach. Acta Clin Belg 53(1):47–52CrossRefPubMed

49.

Baumann F, Schmid C, Bernays RL (2010) Intraoperative magnetic resonance imaging-guided transsphenoidal surgery for giant pituitary adenomas. Neurosurg Rev 33(1):83–90CrossRefPubMed

50.

Landeiro JA, Fonseca EO, Monnerat AL et al (2015) Nonfunctioning giant pituitary adenomas: invasiveness and recurrence. Surg Neurol Int 6:179CrossRefPubMedPubMedCentral

51.

Rey-Dios R, Payner TD, Cohen-Gadol AA (2014) Pituitary macroadenoma causing symptomatic internal carotid artery compression: surgical treatment through transsphenoidal tumor resection. J Clin Neurosci 21(4):541–546CrossRefPubMed

52.

Beckers A, Aaltonen LA, Daly AF et al (2013) Familial isolated pituitary adenomas (FIPA) and the pituitary adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. Endocr Rev 34(2):239–277CrossRefPubMedPubMedCentral

53.

Bujawansa S, Thondam SK, Steele C et al (2014) Presentation, management and outcomes in acute pituitary apoplexy: a large single-centre experience from the United Kingdom. Clin Endocrinol (Oxf) 80(3):419–424CrossRef

54.

Möller-Goede DL, Brändle M, Landau K et al (2011) Pituitary apoplexy: re-evaluation of risk factors for bleeding into pituitary adenomas and impact on outcome. Eur J Endocrinol 164(1):37–43CrossRefPubMed

55.

Randeva HS, Schoebel J, Byrne J et al (1999) Classical pituitary apoplexy: clinical features, management and outcome. Clin Endocrinol (Oxf) 51(2):181–188CrossRef

56.

Lubina A, Olchovsky D, Berezin M et al (2005) Management of pituitary apoplexy: clinical experience with 40 patients. Acta Neurochir (Wien) 147(2):151–157; discussion 157

57.

da Motta LA, de Mello PA, de Lacerda CM et al (1999) Pituitary apoplexy. Clinical course, endocrine evaluations and treatment analysis. J Neurosurg Sci 43(1):25–36PubMed

58.

Nawar RN, AbdelMannan D, Selman WR et al (2008) Pituitary tumor apoplexy: a review. J Intensive Care Med 23(2):75–90CrossRefPubMed

59.

Bills DC, Meyer FB, Laws ER Jr et al (1993) A retrospective analysis of pituitary apoplexy. Neurosurgery 33(4):602–608; discussion 608–609

60.

Nishizawa S, Ohta S, Yokoyama T et al (1998) Therapeutic strategy for incidentally found pituitary tumors (“pituitary incidentalomas”). Neurosurgery 43(6):1344–1348; discussion 1348–1350

61.

Karavitaki N, Collison K, Halliday J et al (2007) What is the natural history of nonoperated nonfunctioning pituitary adenomas? Clin Endocrinol (Oxf) 67(6):938–943CrossRef

62.

Yamada S, Ohyama K, Taguchi M et al (2007) A study of the correlation between morphological findings and biological activities in clinically nonfunctioning pituitary adenomas. Neurosurgery 61(3):580–584; discussion 584–585

63.

Karavitaki N, Thanabalasingham G, Shore HC et al (2006) Do the limits of serum prolactin in disconnection hyperprolactinaemia need re-definition? A study of 226 patients with histologically verified non-functioning pituitary macroadenoma. Clin Endocrinol (Oxf) 65(4):524–529CrossRef

64.

Fatemi N, Dusick JR, Mattozo C et al (2008) Pituitary hormonal loss and recovery after transsphenoidal adenoma removal. Neurosurgery 63(4):709–718; discussion 718–719

65.

Berkmann S, Fandino J, Müller B et al (2012) Intraoperative MRI and endocrinological outcome of transsphenoidal surgery for non-functioning pituitary adenoma. Acta Neurochir (Wien) 154(4):639–647CrossRef

66.

Webb SM, Rigla M, Wägner A et al (1999) Recovery of hypopituitarism after neurosurgical treatment of pituitary adenomas. J Clin Endocrinol Metab 84(10):3696–3700CrossRefPubMed

67.

Dekkers OM, Pereira AM, Romijn JA (2008) Treatment and follow-up of clinically nonfunctioning pituitary macroadenomas. J Clin Endocrinol Metab 93(10):3717–3726CrossRefPubMed

68.

Del Monte P, Foppiani L, Ruelle A et al (2007) Clinically non-functioning pituitary macroadenomas in the elderly. Aging Clin Exp Res 19(1):34–40CrossRefPubMed

69.

Marazuela M, Astigarraga B, Vicente A et al (1994) Recovery of visual and endocrine function following transsphenoidal surgery of large nonfunctioning pituitary adenomas. J Endocrinol Investig 17(9):703–707CrossRef

70.

Dekkers OM, Pereira AM, Roelfsema F et al (2006) Observation alone after transsphenoidal surgery for nonfunctioning pituitary macroadenoma. J Clin Endocrinol Metab 91(5):1796–1801CrossRefPubMed

71.

Arafah BM (1986) Reversible hypopituitarism in patients with large nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 62(6):1173–1179CrossRefPubMed

72.

Cury ML, Fernandes JC, Machado HR et al (2009) Non-functioning pituitary adenomas: clinical feature, laboratorial and imaging assessment, therapeutic management and outcome. Arq Bras Endocrinol Metabol 53(1):31–39CrossRefPubMed

73.

Tjeerdsma G, Sluiter WJ, Hew JM et al (1996) Hyperprolactinaemia is associated with a higher prevalence of pituitary–adrenal dysfunction in non-functioning pituitary macroadenoma. Eur J Endocrinol 135(3):299–308CrossRefPubMed

74.

Chen L, White WL, Spetzler RF et al (2011) A prospective study of nonfunctioning pituitary adenomas: presentation, management, and clinical outcome. J Neurooncol 102(1):129–138CrossRefPubMed

75.

Wichers-Rother M, Hoven S, Kristof RA et al (2004) Non-functioning pituitary adenomas: endocrinological and clinical outcome after transsphenoidal and transcranial surgery. Exp Clin Endocrinol Diabetes 112(6):323–327CrossRefPubMed

76.

Comtois R, Beauregard H, Somma M et al (1991) The clinical and endocrine outcome to trans-sphenoidal microsurgery of nonsecreting pituitary adenomas. Cancer 68(4):860–866CrossRefPubMed

77.

Greenman Y, Tordjman K, Kisch E et al (1995) Relative sparing of anterior pituitary function in patients with growth hormone-secreting macroadenomas: comparison with nonfunctioning macroadenomas. J Clin Endocrinol Metab 80(5):1577–1583PubMed

78.

Ebersold MJ, Quast LM, Laws ER Jr et al (1986) Long-term results in transsphenoidal removal of nonfunctioning pituitary adenomas. J Neurosurg 64(5):713–719CrossRefPubMed

79.

Reincke M, Allolio B, SaegerW et al (1990) The ‘incidentaloma’ of the pituitary gland. Is neurosurgery required? JAMA 263:2772–2776CrossRefPubMed

80.

Sam AH, Shah S, Saleh K et al (2015) Clinical outcomes in patients with nonfunctioning pituitary adenomas managed conservatively. Clin Endocrinol (Oxf) 83(6):861–865CrossRef

81.

Carosi G, Malchiodi E, Ferrante E et al (2015) Hypothalamic–pituitary axis in non-functioning pituitary adenomas: focus on the prevalence of isolated central hypoadrenalism. Neuroendocrinology 102(4):267–273CrossRefPubMed

82.

Yuen KC, Cook DM, Sahasranam P et al (2008) Prevalence of GH and other anterior pituitary hormone deficiencies in adults with nonsecreting pituitary microadenomas and normal serum IGF-1 levels. Clin Endocrinol (Oxf) 69(2):292–298CrossRef

83.

Cannavò S, Venturino M, Curtò L et al (2003) Clinical presentation and outcome of pituitary adenomas in teenagers. Clin Endocrinol (Oxf) 58(4):519–527CrossRef

84.

Lopes MBS (2017) The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. Acta Neuropathol 134(4):521–535CrossRefPubMed

85.

Mayson SE, Snyder PJ (2014) Silent (clinically nonfunctioning) pituitary adenomas. J Neurooncol 117(3):429–436CrossRefPubMed

86.

Vézina JL, Hardy J, Yamashita M (1975) Microadenomas and hypersecreting pituitary adenomas. Arq Neuropsiquiatr 33(2):119–127CrossRefPubMed

87.

Knosp E, Steiner E, Kitz K et al (1993) Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery 33(4):610–617; discussion 617–618

88.

Bonneville JF (2016) Magnetic resonance imaging of pituitary tumors. Front Horm Res 45:97–120CrossRefPubMed

89.

Nishioka H, Inoshita N, Sano T et al (2012) Correlation between histological subtypes and MRI findings in clinically nonfunctioning pituitary adenomas. Endocr Pathol 23(3):151–156CrossRefPubMed

90.

Newman SA, Turbin RE, Bodach ME et al (2016) Congress of neurological surgeons systematic review and evidence-based guideline on pretreatment ophthalmology evaluation in patients with suspected nonfunctioning pituitary adenomas. Neurosurgery 79(4):E530–E532CrossRefPubMed

91.

Fleseriu M, Bodach ME, Tumialan LM et al (2016) Congress of neurological surgeons systematic review and evidence-based guideline for pretreatment endocrine evaluation of patients with nonfunctioning pituitary adenomas. Neurosurgery 79(4):E527–E529CrossRefPubMed

92.

Nieman LK, Biller BM, Findling JW et al (2008) The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 93(5):1526–1540CrossRefPubMedPubMedCentral

93.

Manetti L, Rossi G, Grasso L et al (2013) Usefulness of salivary cortisol in the diagnosis of hypercortisolism: comparison with serum and urinary cortisol. Eur J Endocrinol 168(3):315–321CrossRefPubMed

94.

Vasilev V, Rostomyan L, Daly AF et al (2016) Management of endocrine disease: pituitary ‘incidentaloma’: neuroradiological assessment and differential diagnosis. Eur J Endocrinol (4):R171–R184

95.

Zhang F, Huang Y, Ding C et al (2015) The prevalence of hyperprolactinemia in non-functioning pituitary macroadenomas. Int J Clin Exp Med 8(10):18990–18997PubMedPubMedCentral

Title: Epidemiology, clinical presentation and diagnosis of non-functioning pituitary adenomas
Authors: Georgia Ntali
John A. Wass
Publication date: 01-04-2018
Publisher: Springer US
Published in: Pituitary / Issue 2/2018
Print ISSN: 1386-341X
Electronic ISSN: 1573-7403
DOI: https://doi.org/10.1007/s11102-018-0869-3

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