Cephalgic syndrome in patients with acromegaly
https://doi.org/10.14341/probl13423
Abstract
The aim of this review is to summarize the data available in the literature on the causes of headache in patients with acromegaly, as well as on the effect of various methods of acromegaly treatment on headache. Publications were searched in the PubMed database using the keywords «Headache in patients with acromegaly», «Headache in patients with pituitary adenomas», «Tension-type headache», «Migraine». Headache in patients with pituitary adenomas secreting somatotropic hormone (STH) is not uncommon: according to various authors, cephalgic syndrome occurs in 30–70% of patients with acromegaly and can worsen their quality of life, along with other factors, up to disability. By the nature of development, headache with acromegaly is classified into primary (migraine, tension headache, trigeminal autonomic cephalgia, for example, SUNCT syndrome and cluster headaches), and can also be caused by various causes directly related to the tumor. All this requires differential diagnosis. The factors causing headaches in somatotropinomas have not yet been well studied and require further research. These include the mass effect of the tumor, hormonal hypersecretion, pathology of the temporomandibular joint, sodium and fluid retention in the body, psychological factors, etc. The authors evaluated the effect on headache of various methods of acromegaly treatment: transnasal transsphenoidal adenomectomy, radiation therapy and drug therapy with somatostatin analogues, dopamine agonists and growth hormone receptor antagonist. However, even when normal levels of STH and insulin-like growth factor 1 (IGF-1) are reached, cephalgic syndrome may persist, therefore patients should be warned about this in advance and referred to a cephalgologist to select adequate headache therapy.
Supporting agencies: Работа выполнена по инициативе авторов без привлечения финансирования
About the Authors
G. N. Nurullina
The First Republican Clinical Hospital of Udmurt Republic
Russian Federation
Competing Interests:
Russian Federation
Guzel M. Nurullina - PhD.
57 Votkinskoe shosse street, 426039 Izhevsk
Competing Interests:
none
I. N. Pushkarev
Izhevsk State Medical Academy
Russian Federation
Competing Interests:
Russian Federation
Igor N. Pushkarev
Izhevsk
Competing Interests:
none
E. G. Przhiyalkovskaya
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Elena G. Przhiyalkovskaya - MD, PhD.
Moscow
Competing Interests:
none
References
1. Donovan LE, Welch MR. Headaches in Patients with Pituitary Tumors: a Clinical Conundrum. Curr Pain Headache Rep. 2018;22(8):57. doi: https://doi.org/10.1007/s11916-018-0709-1
2. Puledda F, Silva EM, Suwanlaong K, Goadsby PJ. Migraine: from pathophysiology to treatment. J Neurol. 2023;270(7):3654-3666. doi: https://doi.org/10.1007/s00415-023-11706-1
3. 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(4):348-355. doi: https://doi.org/10.1177/0333102416648347
4. Lake MG, Krook LS, Cruz SV. Pituitary adenomas: an overview. Am Fam Physician. 2013;88(5):319-327
5. Giustina A, Gola M, Colao A, et al. The management of the patient with acromegaly and headache: a still open clinical challenge. J Endocrinol Invest. 2008;31(10):919-924. doi: https://doi.org/10.1007/BF0334644
6. Nurullina GM, Akhmadullina GI, Maslova IS, Nikolaeva AR. Clinical characteristics and efficacy of acromegaly treatment in the Udmurt Republic. Almanac of Clinical Medicine. 2022;50(3):170-176. (in Russ.) doi: https://doi.org/10.18786/2072-0505-2022-50-037
7. Zhang Y, Pan Q, Jiang H, et al. A prospective study of headache and neuropeptides in patients with pituitary adenomas. Cephalalgia. 2019;39(8):1049-1057. doi: https://doi.org/10.1177/0333102419839963
8. Levy MJ, Matharu MS, Meeran K, Powell M, Goadsby PJ. The clinical characteristics of headache in patients with pituitary tumours. Brain. 2005;128(Pt8):1921-1930. doi: https://doi.org/10.1093/brain/awh525
9. Schankin CJ, Reifferscheid AK, Krumbholz M, et al. Headache in patients with pituitary adenoma: clinical and paraclinical findings. Cephalalgia. 2012;32(16):1198-1207. doi: https://doi.org/10.1177/033310241246263
10. Dallel S, Devoize L, Tauveron I, et al. Characteristics of pain in patients with pituitary adenomas: A cross-sectional study. Eur J Pain. 2021;25(4):913-923. doi: https://doi.org/10.1002/ejp.1721
11. Kreitschmann-Andermahr I, Siegel S, Weber Carneiro R, Maubach JM, Harbeck B, Brabant G. Headache and pituitary disease: a systematic review. Clin Endocrinol (Oxf). 2013;79(6):760-769. doi: https://doi.org/10.1111/cen.12314
12. Darendeliler F, Karagiannis G, Wilton P. Headache, idiopathic intracranial hypertension and slipped capital femoral epiphysis during growth hormone treatment: a safety update from the KIGS database. Horm Res. 2007;68(Suppl 5):41-47. doi: https://doi.org/10.1159/000110474
13. Graff-Radford SB. Temporomandibular disorders and headache. Dent Clin North Am. 2007;51(1):129-vii. doi: https://doi.org/10.1016/j.cden.2006.09.005
14. Gondim JA, de Almeida JP, de Albuquerque LA, Schops M, Gomes E, Ferraz T. Headache associated with pituitary tumors. J Headache Pain. 2009;10(1):15-20. doi: https://doi.org/10.1007/s10194-008-0084-0
15. Suri H, Dougherty C. Clinical Presentation and Management of Headache in Pituitary Tumors. Curr Pain Headache Rep. 2018;22(8):55. doi: https://doi.org/10.1007/s11916-018-0710-8
16. 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(5):1789-1793. doi: https://doi.org/10.1210/jcem.85.5.6611
17. Hayashi Y, Sasagawa Y, Oishi M, et al. Contribution of Intrasellar Pressure Elevation to Headache Manifestation in Pituitary Adenoma Evaluated With Intraoperative Pressure Measurement. Neurosurgery. 2019;84(3):599-606. doi: https://doi.org/10.1093/neuros/nyy087
18. Levy MJ. The association of pituitary tumors and headache. Curr Neurol Neurosci Rep. 2011;11(2):164-170. doi: https://doi.org/10.1007/s11910-010-0166-7
19. Kaiser EA, Russo AF. CGRP and migraine: could PACAP play a role too? Neuropeptides. 2013;47(6):451-461. doi: https://doi.org/10.1016/j.npep.2013.10.010
20. King HJ, Luther E, Morell AA, Ivan M, Komotar RJ. Management of a Growth Hormone-Secreting Pituitary Macroadenoma Associated With Idiopathic Intracranial Hypertension and an Empty Sella. Cureus. 2023;15(1):e34471. doi: https://doi.org/10.7759/cureus.34471
21. Olson SL, Wallace JD, Atkinson L, Cuneo RC: Benign intracranial hypertension associated with acromegaly. Endocrinologist. 2005;15:4. doi: https://doi.org/10.1097/01.ten.0000162371.75025.59
22. Malozowski S, Tanner LA, Wysowski DK, Fleming GA, Stadel BV. Benign intracranial hypertension in children with growth hormone deficiency treated with growth hormone. J Pediatr. 1995;126(6):996-999. doi: https://doi.org/10.1016/s0022-3476(95)70232-6
23. Lampit M, Nave T, Hochberg Z. Water and sodium retention during short-term administration of growth hormone to short normal children. Horm Res. 1998;50(2):83-88. doi: https://doi.org/10.1159/000023239
24. Maione L, Chanson P. National acromegaly registries. Best Pract Res Clin Endocrinol Metab. 2019;33(2):101264. doi: https://doi.org/10.1016/j.beem.2019.02.001
25. Puglisi S, Terzolo M. Hypertension and Acromegaly. Endocrinol Metab Clin North Am. 2019;48(4):779-793. doi: https://doi.org/10.1016/j.ecl.2019.08.008
26. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1-211. doi: https://doi.org/10.1177/0333102417738202
27. Finocchi C, Sassos D. Headache and arterial hypertension. Neurol Sci. 2017;38(Suppl 1):67-72. doi: https://doi.org/10.1007/s10072-017-2893-x
28. Zhang J, Mao Y, Li Y, et al. Association between migraine or severe headache and hypertension among US adults: A cross-sectional study. Nutr Metab Cardiovasc Dis. 2023;33(2):350-358. doi: https://doi.org/10.1016/j.numecd.2022.11.014
29. Wechsler S. Facial Pain and Temporomandibular Joint Dysfunction Secondary to Acromegaly: Treatment with Manual Therapy, Neuromuscular Re-education - A Case Report. Rehabil Oncol. 2020;38(3):127-133. doi: https://doi.org/10.1097/01.reo.0000000000000190
30. Gauer RL, Semidey MJ. Diagnosis and treatment of temporomandibular disorders. Am Fam Physician. 2015;91(6):378-386
31. Thomas DC, Khan J, Manfredini D, Ailani J. Temporomandibular Joint Disorder Comorbidities. Dent Clin North Am. 2023;67(2):379-392. doi: https://doi.org/10.1016/j.cden.2022.10.005
32. Donegan D, Erickson D. Revisiting Pituitary Apoplexy. J Endocr Soc. 2022;6(9):bvac113. doi: https://doi.org/10.1210/jendso/bvac113
33. Nurullina GM, Pushkarev IN, Pigarova EA, Latkina NV, Akhmadullina GI. Hemorrhage into a somatotropinoma аs a first reason for examination of a patient with previously undiagnosed acromegaly and papillary thyroid cancer. Almanac of Clinical Medicine. 2023;51(2):126–133 (In Russ.). doi: https://doi.org/10.18786/2072-0505-2023-51-011
34. Suri H, Dougherty C. Presentation and Management of Headache in Pituitary Apoplexy. Curr Pain Headache Rep. 2019;23(9):61. doi: https://doi.org/10.1007/s11916-019-0798-5
35. Gadelha MR, Kasuki L, Lim DST, Fleseriu M. Systemic Complications of Acromegaly and the Impact of the Current Treatment Landscape: An Update. Endocr Rev. 2019;40(1):268-332. doi: https://doi.org/10.1210/er.2018-00115
36. Moon S, Hong S, Han K, Park CY. Risk of depression in patients with acromegaly in Korea (2006-2016): a nationwide population-based study. Eur J Endocrinol. 2023;189(3):363-371. doi: https://doi.org/10.1093/ejendo/lvad120
37. Lampl C, Thomas H, Tassorelli C, et al. Headache, depression and anxiety: associations in the Eurolight project. J Headache Pain. 2016;17:59. doi: https://doi.org/10.1186/s10194-016-0649-2
38. Cho SJ, Song TJ, Chu MK. Sleep and Tension-Type Headache. Curr Neurol Neurosci Rep. 2019;19(7):44. doi: https://doi.org/10.1007/s11910-019-0953-8
39. Andersson A, Hallén T, Olsson DS, et al. Headache Before and After Endoscopic Transsphenoidal Pituitary Tumor Surgery: A Prospective Study. J Neurol Surg B Skull Base. 2021;83(Suppl 2):e360-e366. doi: https://doi.org/10.1055/s-0041-1729180
40. Wang SJ, Hung CW, Fuh JL, Lirng JF, Hwu CM. Cranial autonomic symptoms in patients with pituitary adenoma presenting with headaches. Acta Neurol Taiwan. 2009;18(2):104-112
41. Fleseriu M, Biller BMK, Freda PU, et al. A Pituitary Society update to acromegaly management guidelines. Pituitary. 2021;24(1):1-13. doi: https://doi.org/10.1007/s11102-020-01091-7
42. Rocha Filho PA, Galvão AC, Teixeira MJ, et al. SUNCT syndrome associated with pituitary tumor: case report. Arq Neuropsiquiatr. 2006;64(2B):507-510. doi: https://doi.org/10.1590/s0004-282x2006000300029
43. Kaniuka-Jakubowska S, Levy MJ, Pal A, et al. A study of acromegaly-associated headache with somatostatin analgesia. Endocr Relat Cancer. 2023;30(3):e220138. doi: https://doi.org/10.1530/ERC-22-0138
44. Lovato CM, Kapsner PL. Analgesic effect of long-acting somatostatin receptor agonist pasireotide in a patient with acromegaly and intractable headaches. BMJ Case Rep. 2018;2018:bcr2017219686. doi: https://doi.org/10.1136/bcr-2017-219686
45. Curtis SB, Hewitt J, Yakubovitz S, Anzarut A, Hsiang YN, Buchan AM. Somatostatin receptor subtype expression and function in human vascular tissue. Am J Physiol Heart Circ Physiol. 2000;278(6):H1815-H1822. doi: https://doi.org/10.1152/ajpheart.2000.278.6.H1815
46. Marina D, Burman P, Klose M, et al. Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues — Observations in two patients with acromegaly and severe headache. Growth Horm IGF Res. 2015;25(5):262-267. doi: https://doi.org/10.1016/j.ghir.2015.07.003
47. Matharu MS, Levy MJ, Meeran K, Goadsby PJ. Subcutaneous octreotide in cluster headache: randomized placebo-controlled double-blind crossover study [published correction appears in Ann Neurol. 2004 Nov;56(5):751]. Ann Neurol. 2004;56(4):488-494. doi: https://doi.org/10.1002/ana.20210
48. Otsuka F, Mizobuchi S, Ogura T, Sato K, Yokoyama M, Makino H. Long-term effects of octreotide on pituitary gigantism: its analgesic action on cluster headache. Endocr J. 2004;51(5):449-452. doi: https://doi.org/10.1507/endocrj.51.449
49. Giustina A, Arnaldi G, Bogazzi F, et al. Pegvisomant in acromegaly: an update [published correction appears in J Endocrinol Invest. 2017 Dec 28]. J Endocrinol Invest. 2017;40(6):577-589. doi: https://doi.org/10.1007/s40618-017-0614-1
50. Ershadinia N, Tritos NA. Diagnosis and Treatment of Acromegaly: An Update. Mayo Clin Proc. 2022;97(2):333-346. doi: https://doi.org/10.1016/j.mayocp.2021.11.007
51. Pulido Fontes L, Mayor Gómez S. SUNCT (Short-lasting unilateral neuralgiform headache attack with conjunctival injection and tearing) associated with pituitary lesion. Neurologia. 2015;30(7):458-459. doi: https://doi.org/10.1016/j.nrl.2013.09.00
52. De Pue A, Lutin B, Paemeleire K. Chronic cluster headache and the pituitary gland. J Headache Pain. 2016;17:23. doi: https://doi.org/10.1186/s10194-016-0614-0
53. Инструкция по применению препарата Пэгвисомант. Доступно по: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=b6b29f41-ae8b-4e36-95ae-dfb77bb91dce
54. Losa M, Gioia L, Picozzi P, et al. The role of stereotactic radiotherapy in patients with growth hormone-secreting pituitary adenoma. J Clin Endocrinol Metab. 2008;93(7):2546-2552. doi: https://doi.org/10.1210/jc.2008-0135
55. Vserossijskoe obshchestvo nevrologov, mezhregionalnaya obshchestvennaya organizaciya «Rossijskoe obshchestvo po izucheniyu golovnoj boli». Klinicheskie rekomendacii po golovnoj boli napryazheniya u vzroslyh, 2021 (In Russ.)
56. Vserossijskoe obshchestvo nevrologov, mezhregional’naya obshchestvennaya organizaciya «Rossijskoe obshchestvo po izucheniyu golovnoj boli». Klinicheskie rekomendacii po migreni u vzroslyh, 2021(In Russ.).
57. Zobdeh F, Ben Kraiem A, Attwood MM, et al. Pharmacological treatment of migraine: Drug classes, mechanisms of action, clinical trials and new treatments. Br J Pharmacol. 2021;178(23):4588-4607. doi: https://doi.org/10.1111/bph.15657
58. American Headache Society. The American Headache Society Position Statement On Integrating New Migraine Treatments Into Clinical Practice [published correction appears in Headache. 2019;59(4):650-651]. Headache. 2019;59(1):1-18. doi: https://doi.org/10.1111/head.13456
59. Sacco S, Amin FM, Ashina M, et al. European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention - 2022 update. J Headache Pain. 2022;23(1):67. doi: https://doi.org/10.1186/s10194-022-01431-x
60. Diener HC, May A. Drug Treatment of Cluster Headache. Drugs. 2022;82(1):33-42. doi: https://doi.org/10.1007/s40265-021-01658-z
61. Cheema S, Matharu M. Cluster Headache: What’s New? Neurol India. 2021;69(Supplement):S124-S134. doi: https://doi.org/10.4103/0028-3886.315983
62. Quist TS, Wall M. Growth hormone-related intracranial hypertension. EyeRounds.org. 2019. Available from: http://EyeRounds.org/cases/288-gh-related-iih.htm
63. Goyal A, Zarroli K. Should topiramate be initial therapy in the management of idiopathic intracranial hypertension?: A literature review. Medicine (Baltimore). 2023;102(42):e35545. doi: https://doi.org/10.1097/MD.0000000000035545
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Nurullina G.N., Pushkarev I.N., Przhiyalkovskaya E.G. Cephalgic syndrome in patients with acromegaly. Problems of Endocrinology. 2024;70(5):14-22. (In Russ.) https://doi.org/10.14341/probl13423
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