Skip to main content
Log in

Sheehan's Syndrome

  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

Sheehan's syndrome occurs as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage. It may be rarely seen without massive bleeding or after normal delivery. Improvement in obstetric care and availability of rapid blood transfusion coincided with a remarkable reduction in the frequency of Sheehan's syndrome particularly in western society. But it has recently been reported more often from well-developed countries. It is one of the most common causes of hypopituitarism in underdeveloped or developing countries. Enlargement of pituitary gland, small sella size, disseminated intravascular coagulation and autoimmunity have been suggested to play a role in the pathogenesis of Sheehan's syndrome in women who suffer from severe postpartum hemorrhage. The patients may seek medical advice because of various presentations ranging from non-specific symptoms to coma and the clinical manifestation may change from one patient to another. Failure of postpartum lactation and failure to resume menses after delivery are the most common presenting symptoms. Although a small percentage of patients with Sheehan's syndrome may cause abrupt onset severe hypopituitarism immediately after delivery, most patients have a mild disease and go undiagnosed and untreated for a long time. It may result in partial or panhypopituitarism and GH is one of the hormones lost earliest. The great majority of the patients has empty sella on CT or MRI. Lymphocytic hypophysitis should be kept in mind in differential diagnosis. In this review, the old and recent data regarding Sheehan's syndrome are presented.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Züleyha Karaca, Bashir A. Laway, … Fahrettin Kelestimur

References

  1. Sheehan HL. Postpartum necrosis of the anterior pituitary. J Pathol Bact 1937;45:189–214.

    Google Scholar 

  2. Glinski LK. Z. Kazuistyki zmian anatomo-patologicznych w przysada mozgowej. Przogl Lek 1913;52:13–14.

    Google Scholar 

  3. Simmonds M. Uber hypophysisschwund mit todlichem ausgang. Dtsch Med Wschr 1914;40:322–323.

    Google Scholar 

  4. Sheehan HL. Simmonds disease due to postpartum necrosis of the anterior pituitary following postpartum haemorrhage. Q J Med 1939;32:277–309.

    Google Scholar 

  5. Sheehan HL. The frequency of post-partum hypopituitarism. Obstet Gynaecol Br Commonw 1965;72:103–111.

    Google Scholar 

  6. Abs R, Bengtsson B-A, Hernberg-Stahl E, Monson JP, Tauber J-P, Wilton P, Wüster C. GH replacement in 1034 growth hormone deficient hypopituitary adults: Demographic and clinical characteristics, dosing and safety. Clin Endocrinol 1999;50:703–713.

    Google Scholar 

  7. Kovacs K. Sheehan syndrome. Lancet 2003;361:520–522.

    Google Scholar 

  8. Comte L. Contribution a l'etude de l'hypophse humaine. Doctoral thesis, Lausanne, Switzerland, 1898.

  9. Erdheim J, Stumme E. Ñber die schwangerschaftsveranderung der hypophuse. Beitr Z Pathol Anat Allg Pathol 1909;46:1–132.

    Google Scholar 

  10. Goluboff LG, Ezrin C. Effect of pregnancy on the somatotroph and the prolactin cell of the human adenohypophysis. J Clin Endocrinol Metab 1969;29:1533–1538.

    Google Scholar 

  11. Molitch ME. Pituitary diseases in pregnancy. Semin Perinatol 1998;22:457–470.

    Google Scholar 

  12. Scheithauer BW, Sano T, Kovacs KT, Young WF, Ryan N, Randall RV. The pituitary gland in pregnancy: A clinicopathologic and immunohistochemical study of 69 cases. Mayo Clin Proc 1990;65:461–474.

    Google Scholar 

  13. Bergland RM, Ray BS, Torack RM. Anatomical variations in the pituitary gland and adjacent structures in 225 human autopsy cases. J Neurosurg 1968;28:93–99.

    Google Scholar 

  14. Gonzalez JG, Elizondo G, Saldivar D, Nanez H, Todd LE, Villarreal JZ. Pituitary gland growth during normal pregnancy: An in vivo study using magnetic rezonance imaging. Am J Med 1988;85:217–220.

    Google Scholar 

  15. Dejager S, Gerber S, Foubert L, Turpin G. Sheehan's syndrome: Differential diagnosis in the acute phase. J Intern Med 1998;244:261–266.

    Google Scholar 

  16. Daughaday WH. The anterior pituitary. In:Wilson JD, Foster DW, eds. Textbook of Endocrinology. Philadelphia: W.B. Saunders, 1985:568–613.

    Google Scholar 

  17. Roberts DM. Sheehan's syndrome. Am Fam Physician 1998;37:223–227.

    Google Scholar 

  18. Gupta D, Gaiha M, Mahajan R, Daga MK. Atypical presentation of Sheehan's syndrome without postpartum haemorrahage. J Assoc Physicians India 2001;49:386–387.

    Google Scholar 

  19. Sheehan HL, Davis JC. Pituitary necrosis. Br Med Bull 1968;24:59–70.

    Google Scholar 

  20. Goswami R, Kochupillai N, Crock PA, Jaleel A, Gupta N, Pituitary autoimmunity in patients with Sheehan's syndrome. J Clin Endocrinol Metab 2002;87:4137–4141.

    Google Scholar 

  21. Engelberth O, Jezkova Z. Autoantibodies in Sheehan' syndrome. Lancet 1965;i:1075 (Letter).

    Google Scholar 

  22. Nishiyama S, Takano T, Hidaka Y et al. Acase of postpartum hypopituitarism associated with empty sella: Possible relation to postpartum autoimmune hypophysitis. Endocr J 1993;40:431–438.

    Google Scholar 

  23. Patel MC, Guneratne N, Hag N et al. Peripartum hypopituitarism and lymphocytic hypophysitis. Q J Med 1995;88:571–580.

    Google Scholar 

  24. Otsuka F, Kageyama J, Ogura T, Hattori T, Makino H. Sheehan's syndrome of more than 30 years' duration: An endocrine and MRI studies of 6 cases. Endocr J 1998;45:451–458.

    Google Scholar 

  25. Sherif IH, Vanderley CM, Beshyah S, Bosain S. Sella size and contents in Sheehan's syndrome. Clin Endocrinol 1989;30:613–618.

    Google Scholar 

  26. Meador CK, Worrell JL. The sella turcicca in postpartum pituitary necrosis (Sheehan's syndrome). Ann Intern Med 1966;65:259–264.

    Google Scholar 

  27. Bakiri F, Bendib S-E, Maoui R, Bendib A, Benmiloud M. The sella turcica in Sheehan's syndrome: Computerized tomograpic study in 54 patients. J Endocrinol Invest 1991;14:193–196.

    Google Scholar 

  28. Fleckman AM, Schubart UK, Danziger A, Fleicher N. Empty sella of normal size in Sheehan's syndrome. Am J Med 1983;75:585–591.

    Google Scholar 

  29. Lust K, McIntyre HD, Morton A. Sheehan's syndrome-acute presentation with hyponatremia and headache. Aust N Z J Obstet Gynaecol 2001;41:348–351.

    Google Scholar 

  30. Yamauchi T, Yoshio N, Mizuguchi T, Negoro E, Kamitani N, Ueda T. Acute fatty liver of pregnancy complicated with anterior pituitary insufficiency. Intern Med 2001;40:1227–1231.

    Google Scholar 

  31. Piech JJ, Thieblot P, Haberer JP, Delatour M, Moinade S, Gaillard G. Twin pregnancy with hepatic steatosis followed by hypopituitarism and diabetes insipidus. Press Med 1985;14:1421–1423.

    Google Scholar 

  32. Lavallee G, Morcos R, Palardy J, Aube M, Gilbert D. MR of nonhemorrhagic postpartum pituitary apoplexy. Am J Neuroradiol 1995;16:1939–1941.

    Google Scholar 

  33. Vaphiades MS, Simmons D, Archer RL, Stringer W. Sheehan's syndrome: A splinter of the mind. Surv Ophtalmol 2003;48:230–233.

    Google Scholar 

  34. Huang Y.-Y, Ting M-K, Hsu BRS, Tsar J-S. Demonstration of reserved anterior pituitary function among patients with amenorrhea after postpartum hemorrhage. Gynecol Endocrinol 2000; 14:99–104.

    Google Scholar 

  35. Haddock L, Vega LA, Aguiló F, Rodriguez O. Adrenocortical, thyroidal and human growth hormone reserve in Sheehan's syndrome. Johns Hopkins Med Bull 1972;131:80–99.

    Google Scholar 

  36. Kelestimur F. GH deficiency and the degree of hypopituitarism. Clin Endocrinol 1995;42:443–444 (letter).

    Google Scholar 

  37. Jialal I, Naidee C, Norman RJ, Rajput MJ, Omar MA, Joubert SM. Pituitary function in Sheehan's syndrome. Obstet Gynecol 1984;63:15–19.

    Google Scholar 

  38. Shahmanesh M, Ali Z, Pourmand M, Nourmand I. Pituitary function tests in Sheehan's syndrome. Clin Endocrinol 1980;12:3003–311.

    Google Scholar 

  39. Kelestimur F, Auernhammer C, Colak R, Gomez JM, Molvahlar S, Goth MI. Clinical characteristics and response to GH replacement in Sheehan's syndrome and non-functioning pituitary adenoma-similarities and differences. 6th European Congress of Endocrinology. 26–30 April, 2003. Lyon, France. P1090 (Abstract).

  40. Sheehan HL. Atypical hypopituitarism. Proc Royal Soc Med 1961;54:43–48.

  41. Kelestimur F. Hyperprolactinemia in a patient with Sheehan's syndrome. Southern Med J 1992;85:1008–1010.

    Google Scholar 

  42. Stacpoole PW, Kandell TW, Fisher WR. Primary empty sella, hyperprolactinemia, and isolated ACTH deficiency after postpartum hemorrhage. Am J Med 1983;74:905–908.

    Google Scholar 

  43. Grimes HG, Brooks MH. Pregnancy in Sheehan's syndrome. Report of a case and review. Obstet Gynecol Surv 1980;35:481–488.

    Google Scholar 

  44. Sheehan HL, Murdoch R. Postpartum necrosis of the anterior pituitary. Effect of subsequent pregnancy. Lancet 1939;1:818–820.

    Google Scholar 

  45. ÇolakoGlu M, Erçal T, KarslioGlu I. Am J Med 1987;82:578 (letter).

    Google Scholar 

  46. Keleştimur F, Utaş C, Özbakir Ö. Pituitary-adrenocortical axis in panhypopituitarism due to Sheehan's syndrome. Turk J Med Biol Res 1994;4:1–5.

    Google Scholar 

  47. DiZerega G, Kletzky OA, Mishell DR. Diagnosis of Sheehan's syndrome using a sequential pituitary stimulation test. Am J Obstet Gynecol 1978;132:348–353.

    Google Scholar 

  48. Sheehan HL, Whithead R. The neurohypophysis in postpartum hypopituitarism. J Pathol Bacteriol 1963;85:145–169.

    Google Scholar 

  49. Whitehead R. The hypothalamus in postpartum hypopituitarism. J Pathol Bacteriol 1963;86:55–67.

    Google Scholar 

  50. Kan AKS, Calligerous D. A case report of Sheehan's syndrome presenting with diabetes insipidus. Aust NZ J Obstet Gynaecol 1998;38:224–226.

    Google Scholar 

  51. Arnaout MA, Ajlouni K. Plasma vasopressin responses in postpartum hypopituitarism: Impaired response to osmotic stimuli. Acta Endocrinol 1992;127:494–498.

    Google Scholar 

  52. Güven M, Bayram F, Güven K, Kelestimur F. Evaluation of patients admitted with hypoglycaemia to a teaching hospital in Central Anatolia. Postgrad Med J 2000;76:150–152.

    Google Scholar 

  53. Bunch TJ, Dunn WF, Basu A, Gosman RI. Hyponatremia and hypoglycemia in acute Sheehan's syndrome. Gynecol Endocrinol 2002;16:419–423.

    Google Scholar 

  54. Aono T, Minagawa J, Kinugasa T, Tanizawa O, Kurachi K. Response of pituitary LH and FSH to synthetic LH-releasing hormone in normal subjects and patients with Sheehan's syndrome. Am J Obstet Gynecol 1973;117:1046–1052.

    Google Scholar 

  55. Maccagnan P, Oliveira JHA, Castro V, Abucham J. Abnormal circadian rhythm and increased non-pulsatile secretion of thyrotrophin in Sheehan's syndrome. Clin Endocrinol 1999;51:439–447.

    Google Scholar 

  56. Abucham J, Castro V, Maccagnan P, Vieira JGH. Increased thyrotropin levels and loss of the nocturnal thyrotropin surge in Sheehan's syndrome. Clin Endocrinol 1997;47:515–522.

    Google Scholar 

  57. Oliveira JHA, Persani L, Beck-Peccoz P, Abucham J. Investigating the paradox of hypothyroidism and increased serum thyrotropin (TSH) levels in Sheehan's syndrome: Characterization of TSH carbohydrate content and bioactivity. J Clin Endocrinol Metab 2001;86:1694–1699.

    Google Scholar 

  58. Özbey N, Inanç S, Aral F, Azezli A, Orhan Y, Sencer E, Molvalilar S. Clinical and laboratory evaluation of 40 patients with Sheehan's syndrome. Isr J Med Sci 1994;30:826–829.

    Google Scholar 

  59. Haughton VM, Rosenbaum AE, Williams AL, Drayer B. Recognazing the empty sella by CT: The infundibulum sign. Am J Roentgenol 1981;136:293–295.

    Google Scholar 

  60. Dash RJ, Gupta V, Suri S. Sheehan's syndrome: Clinical profile, pituitary hormone responses and computed sellar tomography. Aust NZ J Med 1993;23:26–31.

    Google Scholar 

  61. Seager W. Tumor like lesions of the sellar region. In: Thapar K, Kovacs K, Scheithauer BW, Lloyd RV, eds. Diagnosis and Management of Pituitary Tumors. Totowa, New Jersey: Humana Press, 2001:449–460.

    Google Scholar 

  62. Hashimoto K, Takao T, Makino S. lymphocytic adenohypophysitis and lymphocytic infundibuloneurohypophysitis. Endocr J 1997;44:1–10.

    Google Scholar 

  63. Ishihara T, Hino M, Kurahachi H, Kobayashi H, Kajikawa M, Moridera K, Ikekubo K, Hattori N. Long-term clinical course of two cases of lymphocytic adenohypophysitis. Endocr J 1996;43:433–440.

    Google Scholar 

  64. Kelestimur F. Lymphocytic hypophysitis and autoimmune thyroid disease. J Endocrinol Invest 2000;23:339–340.

    Google Scholar 

  65. Ñnlühizarci K, Bayram F, Çolak R, Öztürk F, Selçuklu A, Durak AC, Kelestimur F. Distinc radiological and clinical appearance of lymphocytic hpophysitis. J Clin Endocrinol Metab 2001;86:1861–1864.

    Google Scholar 

  66. Kristof RA, Roost DV, Klingmüller D, Springer W, Schramm J. Lymphocytic hypophysitis: Non-invasive diagnosis and treatment by high dose methylprednisolone pulse therapy. J Neurol Neurosurg Psychiatry 1999;67:398–402.

    Google Scholar 

  67. Bayram F, Kelestimur F, Öztürk F, Selcüklu A, Patiroglu TE, Beyhan Z. Lymphocytic hypophysitis in a patient with Graves' disease. J Endocrinol Invest 1998;21:193–197.

    Google Scholar 

  68. Kelestimur F, Auernhammer C, Colak R, Gomez JM, Molvalilar S, Koltowska-Haggstrom M, Jonsson PJ, Goth MI. The baseline characteristics and the effects of GH replacement therapy in patients with Sheehan's syndrome as compared to non-functioning pituitary adenoma. The Endocrine Society's 85th Annual Meeting, Philadelphia, U.S.A. 2003. (Abstract).

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Keleştimur, F. Sheehan's Syndrome. Pituitary 6, 181–188 (2003). https://doi.org/10.1023/B:PITU.0000023425.20854.8e

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:PITU.0000023425.20854.8e

Navigation