Abstract
Pituitary tumors may give rise to headache via numerous mechanisms. The traditional explanation for headache is dural stretch and cavernous sinus invasion, although this is not borne out by clinical studies. Certain functional pituitary tumors are associated with headache, notably growth hormone and prolactin-secreting tumors. The observation that somatostatin analogues can have a dramatic analgesic effect in acromegaly suggests that biochemical properties of the tumor may be important. The genetic predisposition of the patient to primary headache also determines whether headache occurs with pituitary tumors. This article attempts to outline the clinical features, management strategies, and key academic questions regarding the subject of pituitary tumors and headache.
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Ezzat S, Asa S, Couldwell WT, et al.: The prevalence of pituitary adenomas: a systematic review. Cancer. 2004, 101:613–19
Abe T, Matsumoto K, Kuwazawa J, et al.: Headache associated with pituitary adenomas. Headache 1998, 38:782–786.
Levy MJ, Jager HR, Powell M, et al.: Pituitary volume and headache: size is not everything. Arch Neurol 2005, 61:721–25
Levy MJ, Matharu MS, Meeran K, et al.: The clinical characteristics of headache in patients with pituitary tumours. Brain 2005, 128:1921–1930.
Levy MJ, Bejon P, Barakat M, et al.: Acromegaly: a unique human headache model. Headache 2003, 43:794–7.
Levy MJ, Matharu MS, Goadsby PJ: Prolactinomas, dopamine agonists and headache: two case reports. Eur.J.Neurol 2003, 10:169–173.
Milos P, Havelius U, Hindfelt B: Clusterlike headache in a patient with a pituitary adenoma. With a review of the literature. Headache 1996, 36:184–188.
Massiou H, Launay JM, Levy C, et al.: SUNCT syndrome in two patients with prolactinomas and bromocriptine-induced attacks. Neurology 2002, 58:1698–1699.
Matharu MS, Levy MJ, Merry RT, et al.: SUNCT syndrome secondary to prolactinoma. J Neurol Neurosurg Psychiatry. 2003, 74:1590–2.
Williams G, Ball JA, Lawson RA, et al.: Analgesic effect of somatostatin analogue (octreotide) in headache associated with pituitary tumours. Br Med J (Clin Res Ed) 1987, 295:247–8.
Tfelt-Hansen P, Paulson OB, Krabbe AA: Invasive adenoma of the pituitary gland and chronic migrainous neuralgia. A rare coincidence or a causal relationship? Cephalalgia 1982, 2:25–28.
Greve E, Mai J: Cluster headache-like headaches: a symptomatic feature? A report of three patients with intracranial pathologic findings. Cephalalgia 1988, 8:79–82.
Porta-Etessam J, Ramos-Carrasco A, Berbel-Garcia A, et al.: Clusterlike headache as first manifestation of a prolactinoma. Headache 2001, 41:723–725.
Friedman AH, Wilkins RH, Kenan PD, et al.: Pituitary adenoma presenting as facial pain: report of two cases and review of the literature. Neurosurgery 1982, 10:742–745.
Gelabert Gonzalez M, Bollar Zabala A, Garcia Allut A: Trigeminal neuralgia as the first manifestation of craniopharyngioma. An Med Interna 1990, 7:545.
Gazioglu N, Tanriover N, Tuzgen S: Pituitary tumour presenting with trigeminal neuralgia as an isolated symptom. Br J Neurosurg 2000, 14:579.
Millan-Guerrero RO, Isais-Cardenas MA: Headache associated with pituitary adenomas. Headache 1999, 39: 522–523.
Gabrielli M, Gasbarrini A, Fiore G, et al.: Resolution of migraine with aura after successful treatment of a pituitary microadenoma. Cephalalgia 2002, 22: 149–150.
Lee AH: Pituitary adenoma causing classical migraine. Br J Neurosurg 1990, 4: 347–348.
• Cittadini E, Matharu MS: Symptomatic trigeminal autonomic cephalalgias. Neurologist. 2009, 15:305–12. This is a review of TACs in a tertiary headache center showing a relatively high prevalence of pituitary tumors in patients with atypical and refractory presentations.
Sarov M, Valade D, Jublanc C, et al.: Chronic paroxysmal hemicrania in a patient with a macroprolactinoma. Cephalalgia 2006, 26: 738–41.
Ferrari MD, Haan J, van Seters AP: Bromocriptine-induced trigeminal neuralgia attacks in a patient with a pituitary tumor. Neurology 1988, 38: 1482–1484.
King JT, Jr., Justice AC, Aron DC: Management of incidental pituitary microadenomas: a cost-effectiveness analysis. J Clin Endocrinol Metab. 1997 82, 11:3625–32.
Karavitaki N, Thanabalasingham G, Shore HC, et al.: Do the limits of serum prolactin in disconnection hyperprolactinaemia need re-definition? A study of 226 patients with histologically verified non-functioning pituitary macroadenoma. Clinical Endocrinology 2006, 65:524–9
S Melmed, A Colao, A Barkan, et al.: Guidelines for acromegaly management: an update. J Clin Endo Metab 2009, 94:1509–17
Arafah BM, Prunty D, Ybarra J, et al.: 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.
David NJ: Pituitary apoplexy goes to the bar: litigation for delayed diagnosis, deficient vision, and death. J Neuroophthalmol 2006, 26:128–33.
Elster AD, Chen MY, Williams DW 3rd, Key LL: Pituitary gland: MR imaging of physiologic hypertrophy in adolescence. Radiology1990, 174: 681–5.
Bahurel-Barrera H, Assie G, Silvera S, et al.: Inter- and intra-observer variability in detection and progression assessment with MRI of microadenoma in Cushing’s disease patients followed up after bilateral adrenalectomy. Pituitary 2008, 11:263–9.
• Levy MJ, Matharu M, Goadsby PJ: Chronic headache and pituitary tumors. Curr Pain Headache Rep 2008, 12:74–8. This is a review article outlining the management of patients with pituitary tumor–associated headache when there is no specific indication for hypophysectomy.
Nammour GM, Ybarra J, Naheedy MH, et al.: Incidental pituitary macroadenoma: a population-based study. Am J Med Sci. 1997, 314:287–91.
Yue NC, Longstreth WT, Jr., Elster AD, et al.: Clinically serious abnormalities found incidentally at MR imaging of the brain: data from the Cardiovascular Health Study. Radiology 1997, 202:41–6.
•• Sprenger T, Goadsby PJ: What has functional neuroimaging done for primary headache ... and for the clinical neurologist? J Clin Neurosci. 2010, 17: 547–53. This is a review of the functional imaging abnormalities observed in primary headache. This is important because it may relate to some of the headache syndromes observed in pituitary tumor–associated headache
Ezzat S, Snyder PJ, Young WF, et al.: Octreotide treatment of acromegaly. A randomized, multicenter study. Ann Intern Med 1992, 117:711–718.
Newman CB, Melmed S, Snyder PJ, et al.: Safety and efficacy of long-term octreotide therapy of acromegaly: results of a multicenter trial in 103 patients--a clinical research center study. J Clin Endocrinol Metab. 1995, 80:2768–2775.
Newman CB, Melmed S, George A, et al.: Octreotide as primary therapy for acromegaly. J Clin Endocrinol Metab. 1998, 83:3034–3040.
Lancranjan I, Atkinson AB: Results of a European multicentre study with Sandostatin LAR in acromegalic patients. Sandostatin LAR Group. Pituitary 1999, 1:105–114.
Cannavo S, Squadrito S, Curto L, et al.: Results of a two-year treatment with slow release lanreotide in acromegaly. Horm Metab Res 2000, 32:224–229.
Cannavo S, Squadrito S, Curto L, et al.: Effectiveness of slow-release lanreotide in previously operated and untreated patients with GH-secreting pituitary macroadenoma. Horm Metab Res 2001, 33:618–624.
Patel YC, Srikant CB: Subtype selectivity of peptide analogs for all five cloned human somatostatin receptors. Endocrinology 1994, 135:2814–2817.
Schaer JC, Waser B, Mengod G, et al.: Somatostatin receptor subtypes sst1, sst2, sst3 and sst5 expression in human pituitary, gastroentero-pancreatic and mammary tumors: comparison of mRNA analysis with receptor autoradiography. Int J Cancer 1997, 70:530–537.
Shimon I, Melmed S: Structure and function of somatostatin receptors in growth hormone control. J Endocrinol 1997, 155 Suppl 1:S3–6 discussion S7–8.
Shimon I, Yan X, Taylor JE, et al.: Somatostatin receptor (SSTR) subtype-selective analogues differentially suppress in vitro growth hormone and prolactin in human pituitary adenomas. Novel potential therapy for functional pituitary tumors. J Clin Invest 1997, 100:2386–2392.
Turpin G, Foubert L, Noel-Wekstein S, et al.: Analgesic effect on headaches of octreotide, a somatostatin analogue, in a case of non-functioning pituitary adenoma. Presse Med 1991, 20:2219–2220.
Yoenem A, Cakyr B, Azal O, et al.: Effect of octreotide acetate on thyrotropin-secreting adenoma: report of two cases and review of the literature. Endocr Regul 1999, 33:169–174.
May A, Lederbogen S, Diener HC: Octreotide dependency and headache: a case report. Cephalalgia 1994, 14:303–304.
Schindler M, Sellers LA, Humphrey PP, et al.: Immunohistochemical localization of the somatostatin SST2(A) receptor in the rat brain and spinal cord. Neuroscience 1997, 76:225–240.
Matharu MS, Levy MJ, Meeran K, Goadsby PJ: Subcutaneous octreotide in cluster headache: randomized placebo-controlled double-blind crossover study. Ann Neurol. 2004 56(4):488–94.
Kapicioglu S, Gokce E, Kapicioglu Z, et al.: Treatment of migraine attacks with a long-acting somatostatin analogue (octreotide, SMS 201-995). Cephalalgia 1997, 17:27–30.
Levy MJ, Classey J, Maneesi S, et al.: The association between CGRP, Substance P and headache in pituitary adenomas. Pituitary 2004, 7: 67–71.
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