pp 1–10 | Cite as

Granulomatous hypophysitis causing compression of the internal carotid arteries reversible with azathioprine and rituximab treatment

  • Pauline Gendreitzig
  • Jürgen Honegger
  • Marcus QuinklerEmail author



Compression of the internal carotid artery (ICA) in the cavernous sinus area is a rare event and is mostly associated with pituitary adenomas and meningiomas. Other causes of ICA compression are less well known. We present a rare case of granulomatous hypophysitis causing compression of the ICA, which was treated successfully with immune-suppressive agents.


The electronic database MEDLINE (PubMed) was searched systematically and other cases with ICA compression were identified and analyzed.


A female patient with a history of two previous transsphenoidal operations for suspected pituitary adenoma and post-operative complete pituitary insufficiency presented with severe headaches, nausea, fatigue, and diplopia. Pituitary MRI scan suggested relapse of the pituitary lesion with atypical bilateral infiltration of cavernous sinuses and compression of ICAs. After histological reevaluation of her previous pituitary operations, granulomatous hypophysitis was diagnosed. Treatment was started with high doses of prednisolone. With decreasing doses of prednisolone, symptoms recurred, and azathioprine was started, followed by administration of rituximab resulting in clinical recovery and regression of ICA compression. Literature analysis disclosed 36 case reports with ICA compression in the cavernous sinus region (12 pituitary adenoma, 6 meningioma, 7 hypophysitis, 5 other tumors, and 4 other etiologies). Two cases of hypophysitis recovered completely; five cases improved only partly.


In the case of ICA compression, clinical signs, onset of symptoms, radiological findings and pituitary insufficiencies should be thoroughly evaluated, and hypophysitis should be considered as a possible cause. In our patient, treatment with azathioprine and, finally, rituximab was successful.


Prednisolone Azathioprine Rituximab Pituitary adenoma Meningioma 



No funding.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Berliner Ärztekammer) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Hunn BH, Martin WG, Simpson S Jr, McLean CA (2014) Idiopathic granulomatous hypophysitis: a systematic review of 82 cases in the literature. Pituitary 17:357–365PubMedCrossRefGoogle Scholar
  2. 2.
    Joshi MN, Whitelaw BC, Carroll PV (2018) Mechanisms in endocrinology: hypophysitis: diagnosis and treatment. Eur J Endocrinol 179:R151–R163PubMedCrossRefGoogle Scholar
  3. 3.
    Karaca Z, Kelestimur F (2016) The management of hypophysitis. Minerva Endocrinol 41:390–399PubMedGoogle Scholar
  4. 4.
    Carmichael JD (2012) Update on the diagnosis and management of hypophysitis. Curr Opin Endocrinol Diabetes Obes 19:314–321PubMedCrossRefGoogle Scholar
  5. 5.
    Leung GK, Lopes MB, Thorner MO, Vance ML, Laws ER Jr (2004) Primary hypophysitis: a single-center experience in 16 cases. J Neurosurg 101:262–271PubMedCrossRefGoogle Scholar
  6. 6.
    Honegger J et al (2015) Diagnosis of primary hypophysitis in Germany. J Clin Endocrinol Metab 100:3841–3849PubMedCrossRefGoogle Scholar
  7. 7.
    Caturegli P et al (2005) Autoimmune hypophysitis. Endocr Rev 26:599–614PubMedCrossRefGoogle Scholar
  8. 8.
    Chiloiro S et al (2018) Hypophysitis outcome and factors predicting responsiveness to glucocorticoid therapy: a prospective and double-arm study. J Clin Endocrinol Metab 103:3877–3889PubMedCrossRefGoogle Scholar
  9. 9.
    Feigin VL et al (2018) Global, regional, and country-specific lifetime risks of stroke, 1990 and 2016. N Engl J Med 379:2429–2437PubMedCrossRefGoogle Scholar
  10. 10.
    Benjamin EJ et al (2017) Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation 135:e146–e603PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Molitch ME et al (2012) Tumors invading the cavernous sinus that cause internal carotid artery compression are rarely pituitary adenomas. Pituitary 15:598–600PubMedCrossRefGoogle Scholar
  12. 12.
    De Jong T, Matricali B (1990) Asymptomatic occlusion of the internal carotid artery at the skull base. J Neurosurg Sci 34:21–27PubMedGoogle Scholar
  13. 13.
    Oppido PA, Delfini R, Santoro A, Missori P (1989) Intra-extracranial thrombosis of the internal carotid artery associated with meningioma. Neurochirurgia 32:195–199PubMedGoogle Scholar
  14. 14.
    Alzhrani G, Derrico N, Abou-Al-Shaar H, Couldwell WT (2019) Management of cavernous sinus meningioma presenting with cerebrovascular insufficiency secondary to cavernous carotid artery occlusion: report of 2 cases. Op. Neurosurg. Hagerstown, Md.) 16:503–513Google Scholar
  15. 15.
    Nagure PV, Nikam VR, Garud AS (2018) Pituitary apoplexy producing internal carotid and basilar artery compression: a rare case report. Asian J Neurosurg 13:1264–1268PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    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 21:541–546PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Asaithambi G (2015) Carotid artery compression from pituitary apoplexy. QJM 108:159PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Yang SH, Lee KS, Lee KY, Lee SW, Hong YK (2008) Pituitary apoplexy producing internal carotid artery compression: a case report. J Korean Med Sci 23:1113–1117PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Rosenbaum TJ, Houser OW, Laws ER (1977) Pituitary apoplexy producing internal carotid artery occlusion. Case report. J Neurosurg 47:599–604PubMedCrossRefGoogle Scholar
  20. 20.
    Schnur S, Clar HE (1989) Occlusion of the intracranial segment of the carotid artery by a hypophyseal tumor. Neurochirurgia 32:58–60PubMedGoogle Scholar
  21. 21.
    Yaghmai R, Olan WJ, O’Malley S, Bank WO (1996) Nonhemorrhagic pituitary macroadenoma producing reversible internal carotid artery occlusion: case report. Neurosurgery 38:1245–1248PubMedGoogle Scholar
  22. 22.
    Chokyu I et al (2011) Pituitary apoplexy causing internal carotid artery occlusion—case report. Neurol Med Chir 51:48–51CrossRefGoogle Scholar
  23. 23.
    Kasl RA, Hughes J, Burrows AM, Meyer FB (2015) Pediatric ischemic stroke from an apoplectic prolactinoma. Child's Nervous System 31:1387–1392PubMedCrossRefGoogle Scholar
  24. 24.
    Ahmed SK, Semple PL (2008) Cerebral ischaemia in pituitary apoplexy. Acta Neurochir 150:1193–1196 (discussion 1196)PubMedCrossRefGoogle Scholar
  25. 25.
    Matsuo R, Kamouchi M, Inoue T, Okada Y, Ibayashi S (2002) Cerebral infarction due to carotid occlusion caused by cervical vagal neurilemmoma: report of a case. Stroke 33:1428–1431PubMedCrossRefGoogle Scholar
  26. 26.
    Boia ER et al (2013) Non-keratinizing undifferentiated carcinoma of the nasopharynx. Roman J Morphol Embryol = Revue roumaine de morphologie et embryologie 54:839–843Google Scholar
  27. 27.
    Shi T, Farrell MA (1984) Kaufmann JC (1984) Fibrosarcoma complicating irradiated pituitary adenoma. Surg Neurol 22:277–284PubMedCrossRefGoogle Scholar
  28. 28.
    Kojima T, Waga S (1982) Stenosis of the intracranial internal carotid artery by a craniopharyngioma: report of a case: No shinkei geka. Neurol Surg 10:777–782Google Scholar
  29. 29.
    Salame K, Ouaknine GE, Yossipov J, Rochkind S (2001) Paraganglioma of the pituitary fossa: diagnosis and management. J Neuro-Oncol 54:49–52CrossRefGoogle Scholar
  30. 30.
    Ozdemir S et al (2013) A case of extramedullary plasmacytoma in the sphenoid sinus with unilateral loss of vision. J Cranio-Maxillo-Facial Surg 41:140–143CrossRefGoogle Scholar
  31. 31.
    Smolock CJ, Blackmon S, Garami Z, Hassoun HT (2012) Endovascular management of carotid artery stenosis secondary to sclerosing mediastinitis. J Vasc Surg 56:492–495PubMedCrossRefGoogle Scholar
  32. 32.
    Nishi T, Saito Y, Watanabe K, Uozumi T (1992) Intracranial extension of an orbital pseudotumor accompanied by internal carotid artery occlusion–case report. Neurol Med Chir 32:758–761CrossRefGoogle Scholar
  33. 33.
    Gutenberg A, Larsen J, Lupi I, Rohde V, Caturegli P (2009) A radiologic score to distinguish autoimmune hypophysitis from nonsecreting pituitary adenoma preoperatively. AJNR Am J Neuroradiol 30:1766–1772PubMedCrossRefGoogle Scholar
  34. 34.
    Bellastella G et al (2016) Revisitation of autoimmune hypophysitis: knowledge and uncertainties on pathophysiological and clinical aspects. Pituitary 19:625–642PubMedCrossRefGoogle Scholar
  35. 35.
    Famini P, Maya MM, Melmed S (2011) Pituitary magnetic resonance imaging for sellar and parasellar masses: ten-year experience in 2598 patients. J Clin Endocrinol Metab 96:1633–1641PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Honegger J et al (2015) Treatment of primary hypophysitis in Germany. J Clin Endocrinol Metab 100:3460–3469PubMedCrossRefGoogle Scholar
  37. 37.
    Gutenberg A et al (2006) Primary hypophysitis: clinical-pathological correlations. Eur J Endocrinol 155:101PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Lupi I et al (2017) Diabetes insipidus is an unfavorable prognostic factor for response to glucocorticoids in patients with autoimmune hypophysitis. Eur J Endocrinol 177:127–135PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Katsiveli P et al (2016) A complicated case of primary hypophysitis with bilateral intracavernous carotid artery occlusion. Hormones (Athens, Greece) 15:291–296Google Scholar
  40. 40.
    Lecube A et al (2003) Lymphocytic hypophysitis successfully treated with azathioprine: first case report. J Neurol Neurosurg Psychiatry 74:1581–1583PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Yang GQ et al (2011) Recurrent autoimmune hypophysitis successfully treated with glucocorticoids plus azathioprine: a report of three cases. Endocr J 58:675–683PubMedCrossRefGoogle Scholar
  42. 42.
    Xu C, Ricciuti A, Caturegli P, Keene CD, Kargi AY (2015) Autoimmune lymphocytic hypophysitis in association with autoimmune eye disease and sequential treatment with infliximab and rituximab. Pituitary 18:441–447PubMedCrossRefGoogle Scholar
  43. 43.
    Schreckinger M et al (2012) Novel strategy to treat a case of recurrent lymphocytic hypophysitis using rituximab. J Neurosurg 116:1318–1323PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Endocrinology in CharlottenburgBerlinGermany
  2. 2.Department for NeurosurgeryUniversity Hospital TübingenTübingenGermany

Personalised recommendations