Skip to main content

Advertisement

SpringerLink
Log in

Headaches in Patients with Pituitary Tumors: a Clinical Conundrum

  • Secondary Headache (M Robbins, Section Editor)
  • Published:
Current Pain and Headache Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Pituitary tumors account for approximately 17% of all intracranial neoplasms, with the majority being pituitary adenomas. Often, these are found incidentally during a workup for headache; however, the relationship between symptom and pathology remains unclear. The purpose of this article is to review the most recent literature on the epidemiology, pathophysiology, and management of headaches in patients with pituitary tumors.

Recent Findings

The current literature is limited, with few prospective trials focusing on this question. With the exception of pituitary apoplexy, the relationship between headaches and pituitary masses remains unclear. Intervention does not always improve headache and can lead to development of new headache syndromes.

Summary

Further research is needed to better elucidate the relationship between pituitary tumors and headaches. Headache alone is rarely an indication for surgical management of a pituitary adenoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Ostrom QT, Gittleman H, Liao P, Vecchione-Koval T, Wolinsky Y, Kruchko C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2010-2014. Neuro-Oncology. 2017;19:v1–v88.

    Article  PubMed  Google Scholar 

  2. Abe T, Matsumoto K, Kuwazawa J, Toyoda I, Sasaki K. Headache associated with pituitary adenomas. Headache. 1998;38:782–6.

    Article  PubMed  CAS  Google Scholar 

  3. • Jahangiri A, Wagner JR, Chin AT, Han SW, Tran MT, Miller LM, et al. Incidence of headache as a presenting complaint in over 1000 patients with sellar lesions and factors predicting postoperative improvement. Clin Neurol Neurosurg. 2015;132:16–20. This descriptive study represents the largest series of consecutively treated patients with pituitary pathology.

    Article  PubMed  Google Scholar 

  4. Larkin S, Ansorge O. In: De Groot LJ, Chrousos G, Dungan K, et al., editors. Pathology and pathogenesis of pituitary adenomas and other sellar lesions. South Dartmouth: Endotext; 2000.

    Google Scholar 

  5. Ragel BT, Couldwell WT. Pituitary carcinoma: a review of the literature. Neurosurg Focus. 2004;16:E7.

    Article  PubMed  Google Scholar 

  6. Louis DN, Ohgaki H, Wiestler OD, et al. WHO classification of tumours of the central nervous system. 4th ed. Lyon: International Agency for Research on Cancer (IARC); 2016.

    Google Scholar 

  7. Bresson D, Herman P, Polivka M, Froelich S. Sellar lesions/pathology. Otolaryngol Clin N Am. 2016;49:63–93.

    Article  Google Scholar 

  8. Dillard T, Yedinak CG, Alumkal J, Fleseriu M. Anti-CTLA-4 antibody therapy associated autoimmune hypophysitis: serious immune related adverse events across a spectrum of cancer subtypes. Pituitary. 2010;13:29–38.

    Article  PubMed  CAS  Google Scholar 

  9. Culver SA, Grober Y, Ornan DA, Patrie JT, Oldfield EH, Jane JA Jr, et al. A case for conservative management: characterizing the natural history of radiographically diagnosed Rathke cleft cysts. J Clin Endocrinol Metab. 2015;100:3943–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. De Sousa SM, Earls P, McCormack AI. Pituitary hyperplasia: case series and literature review of an under-recognised and heterogeneous condition. Endocrinol Diabetes Metab Case Rep. 2015;2015:150017.

    PubMed  PubMed Central  Google Scholar 

  11. Molitch ME. Diagnosis and treatment of pituitary adenomas: a review. JAMA. 2017;317:516–24.

    Article  PubMed  Google Scholar 

  12. Molitch ME. Nonfunctioning pituitary tumors. Handb Clin Neurol. 2014;124:167–84.

    Article  PubMed  Google Scholar 

  13. Hall WA, Luciano MG, Doppman JL, Patronas NJ, Oldfield EH. Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population. Ann Intern Med. 1994;120:817–20.

    Article  PubMed  CAS  Google Scholar 

  14. Lopes MBS. The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. Acta Neuropathol. 2017;134:521–35.

    Article  PubMed  CAS  Google Scholar 

  15. Al-Brahim NY, Asa SL. My approach to pathology of the pituitary gland. J Clin Pathol. 2006;59:1245–53.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Asa SL, Mete O. What’s new in pituitary pathology? Histopathology. 2018;72:133–41.

    Article  PubMed  Google Scholar 

  17. Mete O, Lopes MB. Overview of the 2017 WHO classification of pituitary tumors. Endocr Pathol. 2017;28:228–43.

    Article  PubMed  CAS  Google Scholar 

  18. Chaidarun SS, Klibanski A. Gonadotropinomas. Semin Reprod Med. 2002;20:339–48.

    Article  PubMed  Google Scholar 

  19. Stovner LJ, Andree C. Prevalence of headache in Europe: a review for the Eurolight project. J Headache Pain. 2010;11:289–99.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kreitschmann-Andermahr I, Siegel S, Weber Carneiro R, Maubach JM, Harbeck B, Brabant G. Headache and pituitary disease: a systematic review. Clin Endocrinol. 2013;79:760–9.

    Article  CAS  Google Scholar 

  21. Rizzoli P, Iuliano S, Weizenbaum E, Laws E. Headache in patients with pituitary lesions: a longitudinal cohort study. Neurosurgery. 2016;78:316–23.

    Article  PubMed  Google Scholar 

  22. • Siegel S, Weber Carneiro R, Buchfelder M, Kleist B, Grzywotz A, Buslei R, et al. Presence of headache and headache types in patients with tumors of the sellar region-can surgery solve the problem? Results of a prospective single center study. Endocrine. 2017;56:325–35. One of the few prospective studies examining the relationship between pituitary lesions and headaches.

    Article  PubMed  CAS  Google Scholar 

  23. Yu B, Ji N, Ma Y, Yang B, Kang P, Luo F. Clinical characteristics and risk factors for headache associated with non-functioning pituitary adenomas. Cephalalgia. 2017;37:348–55.

    Article  PubMed  Google Scholar 

  24. Wolf A, Goncalves S, Salehi F, Bird J, Cooper P, van Uum S, et al. Quantitative evaluation of headache severity before and after endoscopic transsphenoidal surgery for pituitary adenoma. J Neurosurg. 2016;124:1627–33.

    Article  PubMed  Google Scholar 

  25. Gravdahl GB, Tronvik EA, Fougner SL, Solheim O. Pituitary adenoma and non-acute headache: is there an association, and does treatment help? World Neurosurg. 2016;92:284–91.

    Article  PubMed  Google Scholar 

  26. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38:1–211.

    Article  Google Scholar 

  27. Levy MJ, Matharu MS, Meeran K, Powell M, Goadsby PJ. The clinical characteristics of headache in patients with pituitary tumours. Brain. 2005;128:1921–30.

    Article  PubMed  CAS  Google Scholar 

  28. Favier I, van Vliet JA, Roon KI, Witteveen RJW, Verschuuren JJGM, Ferrari MD, et al. Trigeminal autonomic cephalgias due to structural lesions: a review of 31 cases. Arch Neurol. 2007;64:25–31.

    Article  PubMed  Google Scholar 

  29. Wilbrink LA, Ferrari MD, Kruit MC, Haan J. Neuroimaging in trigeminal autonomic cephalgias: when, how, and of what? Curr Opin Neurol. 2009;22:247–53.

    Article  PubMed  Google Scholar 

  30. Edvardsson B. Symptomatic cluster headache: a review of 63 cases. Springerplus. 2014;3:64.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Prakash S, Rathore C. Side-locked headaches: an algorithm-based approach. J Headache Pain. 2016;17:95.

    Article  PubMed  PubMed Central  Google Scholar 

  32. De Pue A, Lutin B, Paemeleire K. Chronic cluster headache and the pituitary gland. J Headache Pain. 2016;17:23.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Forsyth PA, Posner JB. Headaches in patients with brain tumors: a study of 111 patients. Neurology. 1993;43:1678–83.

    Article  PubMed  CAS  Google Scholar 

  34. Gondim JA, de Almeida JP, de Albuquerque LA, Schops M, Gomes E, Ferraz T. Headache associated with pituitary tumors. J Headache Pain. 2009;10:15–20.

    Article  PubMed  Google Scholar 

  35. Levy MJ, Classey JD, Maneesri S, Meeran K, Powell M, Goadsby PJ. The association between calcitonin gene-related peptide (CGRP), substance P and headache in pituitary tumours. Pituitary. 2004;7:67–71.

    Article  PubMed  CAS  Google Scholar 

  36. Nathoo S, Classey JD, Levy MJ, Meeran K, Powell M, Goadsby PJ. No relationship between vasoactive intestinal polypeptide expression and headache in pituitary tumours. Acta Neurol Scand. 2005;111:317–22.

    Article  PubMed  CAS  Google Scholar 

  37. Levy MJ, Classey JD, Maneesri S, Meeran K, Powell M, Goadsby PJ. The relationship between neuropeptide Y expression and headache in pituitary tumours. Eur J Neurol. 2006;13:125–9.

    Article  PubMed  CAS  Google Scholar 

  38. Arafah BM, Prunty D, Ybarra J, Hlavin ML, Selman WR. The dominant role of increased intrasellar pressure in the pathogenesis of hypopituitarism, hyperprolactinemia, and headaches in patients with pituitary adenomas. J Clin Endocrinol Metab. 2000;85:1789–93.

    PubMed  CAS  Google Scholar 

  39. Hayashi Y, Kita D, Iwato M, Fukui I, Oishi M, Tsutsui T, et al. Significant improvement of intractable headache after transsphenoidal surgery in patients with pituitary adenomas; preoperative neuroradiological evaluation and intraoperative intrasellar pressure measurement. Pituitary. 2016;19:175–82.

    Article  PubMed  Google Scholar 

  40. Pereira-Neto A, Borba AM, Mello PA, Naves LA, Araujo AS Jr, Casulari LA. Mean intrasellar pressure, visual field, headache intensity and quality of life of patients with pituitary adenoma. Arq Neuropsiquiatr. 2010;68:350–4.

    Article  PubMed  Google Scholar 

  41. Buture A, Gooriah R, Nimeri R, Ahmed F. Current understanding on pain mechanism in migraine and cluster headache. Anesth Pain Med. 2016;6:e35190.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Milos P, Havelius U, Hindfelt B. Clusterlike headache in a patient with a pituitary adenoma. With a review of the literature. Headache. 1996;36:184–8.

    Article  PubMed  CAS  Google Scholar 

  43. Chong BW, Kucharczyk W, Singer W, George S. Pituitary gland MR: a comparative study of healthy volunteers and patients with microadenomas. AJNR Am J Neuroradiol. 1994;15:675–9.

    PubMed  CAS  Google Scholar 

  44. Freda PU, Beckers AM, Katznelson L, Molitch ME, Montori VM, Post KD, et al. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:894–904.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. King JT Jr, Justice AC, Aron DC. Management of incidental pituitary microadenomas: a cost-effectiveness analysis. J Clin Endocrinol Metab. 1997;82:3625–32.

    PubMed  CAS  Google Scholar 

  46. Musolino NR, Marino Junior R, Bronstein MD. Headache in acromegaly: dramatic improvement with the somatostatin analogue SMS 201-995. Clin J Pain. 1990;6:243–5.

    Article  PubMed  CAS  Google Scholar 

  47. • Lucas JW, Bodach ME, Tumialan LM, Oyesiku NM, Patil CG, Litvack Z, et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on primary management of patients with nonfunctioning pituitary adenomas. Neurosurgery. 2016;79:E533–5. Provides a summary of the current evidence and recommended guidelines for intervention in patients with non-functioning pituitary adenomas.

    Article  PubMed  Google Scholar 

  48. Penn DL, Burke WT, Laws ER. Management of non-functioning pituitary adenomas: surgery. Pituitary. 2018;21:145–53.

    Article  PubMed  Google Scholar 

  49. Solari D, Cavallo LM, Somma T, Chiaramonte C, Esposito F, del Basso de Caro M, et al. Endoscopic endonasal approach in the management of Rathke’s cleft cysts. PLoS One. 2015;10:e0139609.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Patel PN, Stafford AM, Patrinely JR, et al. Risk factors for intraoperative and postoperative cerebrospinal fluid leaks in endoscopic transsphenoidal sellar surgery. Otolaryngol Head Neck Surg. 2018;158:952–60.

    Article  PubMed  Google Scholar 

  51. Ivan ME, Iorgulescu JB, El-Sayed I, et al. Risk factors for postoperative cerebrospinal fluid leak and meningitis after expanded endoscopic endonasal surgery. J Clin Neurosci. 2015;22:48–54.

    Article  PubMed  Google Scholar 

  52. • Briet C, Salenave S, Bonneville JF, Laws ER, Chanson P. Pituitary apoplexy. Endocr Rev. 2015;36:622–45. A good review on pituitary apoplexy with summary of the literature.

    Article  PubMed  Google Scholar 

  53. Glezer A, Bronstein MD. Pituitary apoplexy: pathophysiology, diagnosis and management. Arch Endocrinol Metab. 2015;59:259–64.

    Article  PubMed  Google Scholar 

  54. Ishii M. Endocrine emergencies with neurologic manifestations. Continuum (Minneapolis, Minn). 2017;23:778–801.

    Google Scholar 

  55. Wildemberg LE, Glezer A, Bronstein MD, Gadelha MR. Apoplexy in nonfunctioning pituitary adenomas. Pituitary. 2018;21:138–44.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Neurological Institute of New York, 710 West 168th St, New York, NY, 10032, USA

    Laura E. Donovan & Mary R. Welch

Authors
  1. Laura E. Donovan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mary R. Welch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mary R. Welch.

Ethics declarations

Conflict of Interest

Laura E. Donovan and Mary R. Welch declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Secondary Headache

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Donovan, L.E., Welch, M.R. Headaches in Patients with Pituitary Tumors: a Clinical Conundrum. Curr Pain Headache Rep 22, 57 (2018). https://doi.org/10.1007/s11916-018-0709-1

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11916-018-0709-1

Keywords

Search

Navigation