, Volume 63, Issue 3, pp 463–469 | Cite as

High prevalence of adrenal insufficiency at diagnosis and headache recovery in surgically resected Rathke’s cleft cysts—a large retrospective single center study

  • Fabienne Langlois
  • Anamaria Manea
  • Dawn Shao Ting Lim
  • Shirley McCartney
  • Christine G. Yedinak
  • Justin S. Cetas
  • Maria FleseriuEmail author
Endocrine Surgery



Rathke’s cleft cysts (RCC) are lesions that arise from Rathke’s pouch. Though frequently incidental, resulting symptoms in a minority of cases are indicators for surgical resection, which may prove beneficial.


To characterize a cohort of surgically-resected RCC cases at Oregon Health & Science University; tabulate associated hormonal imbalances and symptoms, possible symptom reversal with surgery, determine recurrence risk; identify predictors of recurrence and headache improvement.


Electronic records of all RCC resected cases (from 2006–2016; 11 years) were retrospectively reviewed. Patients had been evaluated by one neuroendocrinologist using a uniform protocol.


A pathological RCC diagnosis was established in 73 of 814 (9%) surgical pituitary cases. The RCC cohort was 77% (n = 56/73) female, mean age was 39.5 ± 14.9 years at first surgery, and at presentation headache was reported in 88% and visual defects/diplopia in 18% of patients. Initial RCC maximum diameter was 1.3 ± 0.7 cm. The most frequent hormonal deficit was cortisol; 24% of patients had a new adrenal insufficiency (AI) diagnosis, however, 36% also had AI at 3 months post-operatively. Mean follow up was 4.0 ± 4.5 years. Two-thirds of patients (41/62) had headache improvement 3 months post-operatively. Post-operative imaging revealed no residual cyst in 58% (38/65). In those patients with no residual RCC, 29% had recurrence and 71% had long lasting cure. From the 42% (27/65) of patients with residual cyst on post-operative imaging; 59% (16/27) remained stable, 26% (7/27) progressed and 15% (4/27) regressed.


Symptomatic RCC present mostly in women, with a high proportion reporting headaches. Prevalence of AI at diagnosis is high. Surgery may not achieve adrenal axis recovery, but renders a high percentage of headache improvement. Approximately 25% of RCC will recur by 4 years postoperatively. Clinicians should cautiously screen patients with symptomatic RCC, regardless of lesion size for AI.


Rathke’s cleft cysts Pituitary cyst Pituitary lesions Adrenal insufficiency Transsphenoidal surgery Headache 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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 and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was waived in this institutional approved retrospective study.


  1. 1.
    C.J. Aho, C. Liu, V. Zelman, W.T. Couldwell, M.H. Weiss, Surgical outcomes in 118 patients with Rathke cleft cysts. J. Neurosurg. 102, 189–193 (2005)CrossRefPubMedGoogle Scholar
  2. 2.
    R. Trifanescu, V. Stavrinides, P. Plaha, S. Cudlip, J.V. Byrne, O. Ansorge, J.A. Wass, N. Karavitaki, Outcome in surgically treated Rathke’s cleft cysts: long-term monitoring needed. Eur. J. Endocrinol. 165, 33–37 (2011)CrossRefPubMedGoogle Scholar
  3. 3.
    G. Childs, Pituitary Gland (Cell Types, Mediators, Development), in Squire L (ed): Encyclopedia of Neuroscience. California: Academic Press 2009, Vol 7, pp 719–726Google Scholar
  4. 4.
    E. Kim, Symptomatic Rathke cleft cyst: clinical features and surgical outcomes. World Neurosurg. 78, 527–534 (2012)CrossRefPubMedGoogle Scholar
  5. 5.
    S.A. Culver, Y. Grober, D.A. Ornan, J.T. Patrie, E.H. Oldfield, J.A. Jane Jr., M.O. Thorner, A case for conservative management: characterizing the natural history of radiographically diagnosed Rathke cleft cysts. J. Clin. Endocrinol. Metab. 100, 3943–3948 (2015)CrossRefPubMedGoogle Scholar
  6. 6.
    V. Vasilev, L. Rostomyan, A.F. Daly, I. Potorac, S. Zacharieva, J.F. Bonneville, A. Beckers, Management of endocrine disease: pituitary “incidentaloma”: neuroradiological assessment and differential diagnosis. Eur. J. Endocrinol. 175, R171–184 (2016)CrossRefPubMedGoogle Scholar
  7. 7.
    P.U. Freda, A.M. Beckers, L. Katznelson, M.E. Molitch, V.M. Montori, K.D. Post, M.L. Vance, S. Endocrine, Pituitary incidentaloma: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 96, 894–904 (2011)CrossRefPubMedGoogle Scholar
  8. 8.
    R. Trifanescu, O. Ansorge, J.A. Wass, A.B. Grossman, N. Karavitaki, Rathke’s cleft cysts. Clin. Endocrinol. (Oxf.) 76, 151–160 (2012)CrossRefGoogle Scholar
  9. 9.
    J.L. Shin, S.L. Asa, L.J. Woodhouse, H.S. Smyth, S. Ezzat, Cystic lesions of the pituitary: clinicopathological features distinguishing craniopharyngioma, Rathke’s cleft cyst, and arachnoid cyst. J. Clin. Endocrinol. Metab. 84, 3972–3982 (1999)PubMedGoogle Scholar
  10. 10.
    M.E. Molitch, D.R. Clemmons, S. Malozowski, G.R. Merriam, M.L. Vance, S. Endocrine, Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 96, 1587–1609 (2011)CrossRefPubMedGoogle Scholar
  11. 11.
    M. Fleseriu, I.A. Hashim, N. Karavitaki, S. Melmed, M.H. Murad, R. Salvatori, M.H. Samuels, Hormonal replacement in hypopituitarism in adults: an Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 101, 3888–3921 (2016)CrossRefPubMedGoogle Scholar
  12. 12.
    L. Wen, L.B. Hu, X.Y. Feng, G. Desai, L.G. Zou, W.X. Wang, D. Zhang, Rathke’s cleft cyst: clinicopathological and MRI findings in 22 patients. Clin. Radiol. 65, 47–55 (2010)CrossRefPubMedGoogle Scholar
  13. 13.
    E. Sala, J.M. Moore, A. Amorin, G. Carosi, H. Martinez Jr., G.R. Harsh, M. Arosio, G.Mantovani, L. Katznelson, Natural history of Rathke's cleft cysts: a retrospective analysis of a two centers experience. Clin. Endocrinol. 89, 178–186 (2018).CrossRefGoogle Scholar
  14. 14.
    R.J. Benveniste, W.A. King, J. Walsh, J.S. Lee, T.P. Naidich, K.D. Post, Surgery for Rathke cleft cysts: technical considerations and outcomes. J. Neurosurg. 101, 577–584 (2004)CrossRefPubMedGoogle Scholar
  15. 15.
    P. Cohan, A. Foulad, F. Esposito, N.A. Martin, D.F. Kelly, Symptomatic Rathke’s cleft cysts: a report of 24 cases. J. Endocrinol. Invest. 27, 943–948 (2004)CrossRefPubMedGoogle Scholar
  16. 16.
    H. Nishioka, J. Haraoka, H. Izawa, Y. Ikeda, Headaches associated with Rathke’s cleft cyst. Headache 46, 1580–1586 (2006)CrossRefPubMedGoogle Scholar
  17. 17.
    M. Lin, M.A. Wedemeyer, D. Bradley, D.A. Donoho, V.L. Fredrickson, M.H. Weiss, J.D. Carmichael, G. Zada, Long-term surgical outcomes following transsphenoidal surgery in patients with Rathke’s cleft cysts. J. Neurosurg. 1–7, (2018)
  18. 18.
    V. Ratha, S. Patil, V.S. Karmarkar, N.J. Shah, C.E. Deopujari, Surgical management of Rathke cleft cysts. World Neurosurg. 107, 276–284 (2017)CrossRefPubMedGoogle Scholar
  19. 19.
    E. Kim, Surgical treatment of symptomatic Rathke cleft cysts clinical features and results with special attention to recurrence. J. Neurosurg. 100, 33–40 (2004)CrossRefPubMedGoogle Scholar
  20. 20.
    W. Zhong, C. You, S. Jiang, S. Huang, H. Chen, J. Liu, P. Zhou, Y. Liu, B. Cai, Symptomatic Rathke cleft cyst. J. Clin. Neurosci. 19, 501–508 (2012)CrossRefPubMedGoogle Scholar
  21. 21.
    S. Chotai, Y. Liu, J. Pan, S. Qi, Characteristics of Rathke’s cleft cyst based on cyst location with a primary focus on recurrence after resection. J. Neurosurg. 122, 1380–1389 (2015)CrossRefPubMedGoogle Scholar
  22. 22.
    F. Langlois, D.S.T. Lim, C.G. Yedinak, I. Cetas, S. McCartney, J. Cetas, A. Dogan, M. Fleseriu, Predictors of silent corticotroph adenoma recurrence; a large retrospective single center study and systematic literature review. Pituitary 21, 32–40 (2018)CrossRefPubMedGoogle Scholar
  23. 23.
    K. Tanigawa, S. Yamashita, H. Namba, M.C. Villadolid, H. Kimura, T. Tominaga, M. Tsuruta, N. Yokoyama, M. Izumi, S. Nagataki, Acute adrenal insufficiency due to symptomatic Rathke’s cleft cyst. Intern. Med. 31, 467–469 (1992)CrossRefPubMedGoogle Scholar
  24. 24.
    Y. Hirayama, T. Kudo, N. Kasai, Acute adrenal insufficiency associated with Rathke’s cleft cyst. Intern. Med. 55, 639–642 (2016)CrossRefPubMedGoogle Scholar
  25. 25.
    C. Janeczko, J. McHugh, D. Rawluk, M. Farrell, P. Brennan, N. Delanty, Hypophysitis secondary to ruptured Rathke’s cyst mimicking neurosarcoidosis. J. Clin. Neurosci. 16, 599–600 (2009)CrossRefPubMedGoogle Scholar
  26. 26.
    Y. Hayashi, M. Oishi, D. Kita, T. Watanabe, O. Tachibana, J. Hamada, Pure lymphocytic infundibuloneurohypophysitis caused by the rupture of Rathke’s cleft cyst: report of 2 cases and review of the literature. Turk. Neurosurg. 25, 332–336 (2015)PubMedGoogle Scholar
  27. 27.
    M. Asakawa, R. Chin, Y. Niitsu, T. Sekine, A. Niwa, A. Miyake, N. Inoshita, M. Kawamura, Y. Ogawa, Y. Hirata, A case of Rathke’s cleft cyst associated with transient central adrenal insufficiency and masked diabetes insipidus. Case Rep. Endocrinol. 2014, 693294 (2014)PubMedGoogle Scholar
  28. 28.
    F. Komatsu, H. Tsugu, M. Komatsu, S. Sakamoto, S. Oshiro, T. Fukushima, K. Nabeshima, T. Inoue, Clinicopathological characteristics in patients presenting with acute onset of symptoms caused by Rathke’s cleft cysts. Acta Neurochir. 152, 1673–1678 (2010)CrossRefPubMedGoogle Scholar
  29. 29.
    K. Duan, S.L. Asa, D. Winer, Z. Gelareh, F. Gentili, O. Mete, Xanthomatous hypophysitis is associated with ruptured Rathke’s cleft cyst. Endocr. Pathol. 28, 83–90 (2017)CrossRefPubMedGoogle Scholar
  30. 30.
    J. Schittenhelm, R. Beschorner, T. Psaras, D. Capper, T. Nagele, R. Meyermann, W. Saeger, J. Honegger, M. Mittelbronn, Rathke’s cleft cyst rupture as potential initial event of a secondary perifocal lymphocytic hypophysitis: proposal of an unusual pathogenetic event and review of the literature. Neurosurg. Rev. 31, 157–163 (2008)CrossRefPubMedGoogle Scholar
  31. 31.
    F. Bonneville, F. Cattin, K. Marsot-Dupuch, D. Dormont, J.F. Bonneville, J. Chiras, T1 signal hyperintensity in the sellar region: spectrum of findings. Radiographics 26, 93–113 (2006)CrossRefPubMedGoogle Scholar
  32. 32.
    M. Fleseriu, C. Yedinak, C. Campbell, J.B. Delashaw, Significant headache improvement after transsphenoidal surgery in patients with small sellar lesions. J. Neurosurg. 110, 354–358 (2009)CrossRefPubMedGoogle Scholar
  33. 33.
    S.D. Wait, M.P. Garrett, A.S. Little, B.D. Killory, W.L. White, Endocrinopathy, vision, headache, and recurrence after transsphenoidal surgery for Rathke cleft cysts. Neurosurgery 67, 837–843 (2010)CrossRefPubMedGoogle Scholar
  34. 34.
    D.J. Cote, B.D. Besasie, M.M. Hulou, S.C. Yan, T.R. Smith, E.R. Laws, Transsphenoidal surgery for Rathke’s cleft cyst can reduce headache severity and frequency. Pituitary 19, 57–64 (2016)CrossRefPubMedGoogle Scholar
  35. 35.
    N. Altuwaijri, D.J. Cote, N. Lamba, W. Albenayan, S.P. Ren, I. Zaghloul, J. Doucette, H.A. Zaidi, R.A. Mekary, T.R. Smith, Headache resolution after Rathke cleft cyst resection: a meta-analysis. World Neurosurg. 111, e764–e772 (2018)CrossRefPubMedGoogle Scholar
  36. 36.
    I. Fukui, Y. Hayashi, D. Kita, Y. Sasagawa, M. Oishi, O. Tachibana, M. Nakada, Significant improvement in chronic persistent headaches caused by small Rathke cleft cysts after transsphenoidal surgery. World Neurosurg. 99, 362–368 (2017)CrossRefPubMedGoogle Scholar
  37. 37.
    M.B. Potts, A. Jahangiri, K.R. Lamborn, L.S. Blevins, S. Kunwar, M.K. Aghi, Suprasellar Rathke cleft cysts: clinical presentation and treatment outcomes. Neurosurgery 69, 1058–1068 (2011)PubMedGoogle Scholar
  38. 38.
    K.O. Lillehei, L. Widdel, C.A. Astete, M.E. Wierman, B.K. Kleinschmidt-DeMasters, J.M. Kerr, Transsphenoidal resection of 82 Rathke cleft cysts: limited value of alcohol cauterization in reducing recurrence rates. J. Neurosurg. 114, 310–317 (2011)CrossRefPubMedGoogle Scholar
  39. 39.
    D.M. Higgins, J.J. Van Gompel, T.B. Nippoldt, F.B. Meyer, Symptomatic Rathke cleft cysts: extent of resection and surgical complications. Neurosurg. Focus 31, E2 (2011)CrossRefPubMedGoogle Scholar
  40. 40.
    Y. Ogawa, M. Watanabe, T. Tominaga, Prognostic factors of operated Rathke’s cleft cysts with special reference to re-accumulation and recommended surgical strategy. Acta Neurochir. 153, 2427–2433 (2011)CrossRefPubMedGoogle Scholar
  41. 41.
    J.K. Park, E.J. Lee, S.H. Kim, Optimal surgical approaches for Rathke cleft cyst with consideration of endocrine function. Neurosurgery 70, 250–256 (2012). discussion 256-257PubMedGoogle Scholar
  42. 42.
    Y. Kinoshita, A. Tominaga, S. Usui, K. Arita, T. Sakoguchi, K. Sugiyama, K. Kurisu, The long-term recurrence of Rathke’s cleft cysts as predicted by histology but not by surgical procedure. J. Neurosurg. 125, 1002–1007 (2016)CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Fabienne Langlois
    • 1
  • Anamaria Manea
    • 2
  • Dawn Shao Ting Lim
    • 3
  • Shirley McCartney
    • 4
  • Christine G. Yedinak
    • 4
  • Justin S. Cetas
    • 4
  • Maria Fleseriu
    • 4
    • 5
    Email author
  1. 1.Department of Endocrinology, Centre hospitalier universitaire de SherbrookeFleurimontCanada
  2. 2.Pediatric EndocrinologyOregon Health & Science UniversityPortlandUSA
  3. 3.Department of Endocrinology, Singapore General HospitalSingaporeSingapore
  4. 4.Neurological SurgeryOregon Health & Science UniversityPortlandUSA
  5. 5.Pituitary Center, Medicine and Neurological SurgeryOregon Health & Science UniversityPortlandUSA

Personalised recommendations