SHEEHAN’S SYNDROME: CURRENT INSIGHTS INTO PATHOPHYSIOLOGY, CLINICAL MANIFESTATIONS, DIAGNOSTIC CHALLENGES AND MANAGEMENT STRATEGIES
Abstract
Aims: Sheehan’s Syndrome (SS), also known as postpartum hypopituitarism, is a rare and potentially life-threatening endocrine disorder caused by ischemic necrosis of the pituitary gland due to massive postpartum hemorrhage and hypovolemic shock. The aim of this article is to present a comprehensive and up-to-date overview of the current understanding of Sheehan’s syndrome, including its pathophysiology, epidemiology, clinical presentation, diagnostic challenges, and therapeutic approaches.
Methods: A narrative review of the literature was conducted using the PubMed, Oxford Academic, Google Scholar, and Embase databases. The analysis included original research articles, systematic reviews, and clinical guidelines published in English over recent years.
Results: Sheehan’s syndrome remains an underdiagnosed condition due to its highly variable and often delayed clinical presentation. Symptoms may appear months to years after the inciting obstetric event, which hinders timely diagnosis. The most common manifestations include failure to lactate, amenorrhea, fatigue, hypotension, and features of secondary hypothyroidism or adrenal insufficiency. MRI typically reveals an empty sella or pituitary atrophy. Hormonal testing confirms multiple anterior pituitary hormone deficiencies. The condition is still most prevalent in regions with inadequate obstetric care.
Conclusions: Early recognition of Sheehan’s syndrome, based on detailed obstetric history and characteristic clinical and laboratory findings, is essential to prevent severe complications and reduce diagnostic delays. Increased awareness among primary care physicians and perinatal care providers is crucial. Timely initiation of appropriate hormone replacement therapy can significantly improve patient outcomes and quality of life.
References
Adil, M. L., Alvi, M., Khan, A., Qaiser, S. M. M., Osman, M., & Bashir, M. N. (2023). From acute abdomen to hormonal crisis: Case report on a long-delayed Sheehan's syndrome diagnosis. International Journal of Surgery Case Reports, 111, 108831. https://doi.org/10.1016/j.ijscr.2023.108831
Agarwal, P., Gomez, R., Bhatia, E., & Yadav, S. (2019). Decreased bone mineral density in women with Sheehan's syndrome and improvement following oestrogen replacement and nutritional supplementation. Journal of Bone and Mineral Metabolism, 37(1), 171–178. https://doi.org/10.1007/s00774-018-0911-6
Al-Chalabi, M., Bass, A. N., & Alsalman, I. (2023). Physiology, prolactin. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK507829/
Benson, J. C., Malyuk, D. F., Madhavan, A., Guerin, J. B., Krecke, K. N., Little, J. T., Passe, T. J., DeLone, D. R., Lindell, E. P., & Eckel, L. J. (2024). Pituitary volume changes in pregnancy and the post-partum period. Neuroradiology Journal, 37(1), 39–42. https://doi.org/10.1177/19714009231196470
Borlu, M., Tanriverdi, F., Koc, C. A., Unluhizarci, K., Utas, S., & Kelestimur, F. (2007). The effects of severe growth hormone deficiency on the skin of patients with Sheehan's syndrome. Journal of the European Academy of Dermatology and Venereology, 21(2), 199–204. https://doi.org/10.1111/j.1468-3083.2006.01898.x
Cironi, K. A., Decater, T., Iwanaga, J., Dumont, A. S., & Tubbs, R. S. (2020). Arterial supply to the pituitary gland: A comprehensive review. World Neurosurgery, 142, 206–211. https://doi.org/10.1016/j.wneu.2020.06.221
Diri, H., Karaca, Z., Tanriverdi, F., Unluhizarci, K., & Kelestimur, F. (2016). Sheehan's syndrome: New insights into an old disease. Endocrine, 51(1), 22–31. https://doi.org/10.1007/s12020-015-0726-3
Diri, H., Sener, E. F., Bayram, F., Dundar, M., Simsek, Y., Baspinar, O., & Zararsiz, G. (2016). Genetic disorders of pituitary development in patients with Sheehan's syndrome. Acta Endocrinologica (Bucharest), 12(4), 413–417. https://doi.org/10.4183/aeb.2016.413
Diri, H., Tanriverdi, F., Karaca, Z., Senol, S., Unluhizarci, K., Durak, A. C., Atmaca, H., & Kelestimur, F. (2014). Extensive investigation of 114 patients with Sheehan's syndrome: A continuing disorder. European Journal of Endocrinology, 171(3), 311–318. https://doi.org/10.1530/EJE-14-0244
Das, L., Sahoo, J., Dahiya, N., Taneja, S., Bhadada, S. K., Bhat, M. H., Singh, P., Suri, V., Laway, B. A., & Dutta, P. (2022). Long-term hepatic and cardiac health in patients diagnosed with Sheehan's syndrome. Pituitary, 25(6), 971–981. https://doi.org/10.1007/s11102-022-01282-4
De Bellis, A., Kelestimur, F., Sinisi, A. A., Ruocco, G., Tirelli, G., Battaglia, M., Bellastella, G., Conzo, G., Tanriverdi, F., Unluhizarci, K., Bizzarro, A., & Bellastella, A. (2008). Anti-hypothalamus and anti-pituitary antibodies may contribute to perpetuate the hypopituitarism in patients with Sheehan's syndrome. European Journal of Endocrinology, 158(2), 147–152. https://doi.org/10.1530/EJE-07-0647
Donald, D. M., McDonnell, T., O’Reilly, M. W., et al. (2024). Replacement with sex steroids in hypopituitary men and women: Implications for gender differences in morbidities and mortality. Reviews in Endocrine and Metabolic Disorders, 25, 839–854. https://doi.org/10.1007/s11154-024-09897-7
Gaspar, B. (2018). Diagnosis and treatment challenges of Sheehan's syndrome. Frontiers in Women's Health, 3. https://doi.org/10.15761/FWH.100015
Gokalp, D., Tuzcu, A., Bahceci, M., Ayyildiz, O., Yurt, M., Celik, Y., & Alpagat, G. (2011). Analysis of thrombophilic genetic mutations in patients with Sheehan's syndrome: Is thrombophilia responsible for the pathogenesis of Sheehan's syndrome? Pituitary, 14(2), 168–173. https://doi.org/10.1007/s11102-010-0276-x
Goswami, R., Kochupillai, N., Crock, P. A., Jaleel, A., & Gupta, N. (2002). Pituitary autoimmunity in patients with Sheehan's syndrome. Journal of Clinical Endocrinology & Metabolism, 87(9), 4137–4141. https://doi.org/10.1210/jc.2001-020242
Govorov, I., Löfgren, S., Chaireti, R., Holmström, M., Bremme, K., & Mints, M. (2016). Postpartum hemorrhage in women with von Willebrand disease – A retrospective observational study. PLoS ONE, 11(10), e0164683. https://doi.org/10.1371/journal.pone.0164683
Gupta, V., & Lee, M. (2011). Central hypothyroidism. Indian Journal of Endocrinology and Metabolism, 15(Suppl 2), S99–S106. https://doi.org/10.4103/2230-8210.83337
Iglesias, P. (2024). An update on advances in hypopituitarism: Etiology, diagnosis, and current management. Journal of Clinical Medicine, 13(20), 6161. https://doi.org/10.3390/jcm13206161
Jain, D. (2013). A ray of hope for a woman with Sheehan's syndrome. BMJ Case Reports, 2013, bcr2012008445. https://doi.org/10.1136/bcr-2012-008445
Jayte, M., Dubad, F., Ali, H., Ahmed, A., Karshe, A., Nor, F., Hussein, Z., Guled, A., Sandeyl, A., Saria, D., Nor, A., Ibrahim, A., & Athanus, L. (2025). Successful diagnosis and management of Sheehan’s syndrome without MRI: A case report. Medical Reports, 13, 100242. https://doi.org/10.1016/j.hmedic.2025.100242
Karaca, Z., & Kelestimur, F. (2025). Sheehan syndrome: A current approach to a dormant disease. Pituitary, 28, 20. https://doi.org/10.1007/s11102-024-01481-1
Kaplun, J., Fratila, C., Ferenczi, A., Yang, W. C., Lantos, G., Fleckman, A. M., & Schubart, U. K. (2008). Sequential pituitary MR imaging in Sheehan syndrome: Report of 2 cases. American Journal of Neuroradiology, 29(5), 941–943. https://doi.org/10.3174/ajnr.A1016
Keleştimur, F. (2003). Sheehan's syndrome. Pituitary, 6(4), 181–188. https://doi.org/10.1023/b:pitu.0000023425.20854.8e
Kristjansdottir, H. L., Bodvarsdottir, S. P., & Sigurjonsdottir, H. A. (2011). Sheehan’s syndrome in modern times: A nationwide retrospective study in Iceland. European Journal of Endocrinology, 164(3), 349–354. https://doi.org/10.1530/EJE-10-1004
Laway, B. A., & Baba, M. S. (2023). Sheehan syndrome: Cardiovascular and metabolic comorbidities. Frontiers in Endocrinology, 14, 1086731. https://doi.org/10.3389/fendo.2023.1086731
Liang, L., Liu, J. B., Chen, F. Q., Zhao, J., & Zhang, X. L. (2017). Refractory hypotension induced by Sheehan syndrome with pituitary crisis: A case report. Experimental and Therapeutic Medicine, 13(5), 2097–2101. https://doi.org/10.3892/etm.2017.4188
Mandal, S., Mukhopadhyay, P., & Ghosh, S. (2021). Sexual dysfunction in Sheehan syndrome. Endocrine Practice, 27(12), 1212–1215. https://doi.org/10.1016/j.eprac.2021.07.013
Mandal, S., Mukhopadhyay, P., & Ghosh, S. (2022). DHEA on sexual function in Sheehan syndrome: A randomized double-blind placebo-controlled crossover trial. The Journal of Clinical Endocrinology & Metabolism, 107(8), e3395–e3402. https://doi.org/10.1210/clinem/dgac260
Matsuwaki, T., Khan, K. N., Inoue, T., Yoshida, A., & Masuzaki, H. (2014). Evaluation of obstetrical factors related to Sheehan syndrome. Journal of Obstetrics and Gynaecology Research, 40(1), 46–52. https://doi.org/10.1111/jog.12119
Matsuzaki, S., Endo, M., Ueda, Y., et al. (2017). A case of acute Sheehan’s syndrome and literature review: A rare but life-threatening complication of postpartum hemorrhage. BMC Pregnancy and Childbirth, 17, 188. https://doi.org/10.1186/s12884-017-1380-y
Mesbah, O., Messaoud, O., Kabila, B., El Aoufir, O., Jroundi, L., & Houssaini, Z. I. (2025). Unmasking the pituitary shadow 11 years postpartum: A case report of late-stage Sheehan's syndrome. Radiology Case Reports, 20(7), 3267–3270. https://doi.org/10.1016/j.radcr.2025.03.027
Miljic, D., Pekic, S., & Popovic, V. (2024). Empty sella. In K. R. Feingold, S. F. Ahmed, B. Anawalt, M. R. Blackman, A. Boyce, G. Chrousos, E. Corpas, W. W. de Herder, K. Dhatariya, K. Dungan, J. Hofland, S. Kalra, G. Kaltsas, N. Kapoor, C. Koch, P. Kopp, M. Korbonits, C. S. Kovacs, W. Kuohung, B. Laferrère, M. Levy, E. A. McGee, R. McLachlan, R. Muzumdar, J. Purnell, R. Rey, R. Sahay, A. S. Shah, F. Singer, M. A. Sperling, C. A. Stratakis, D. L. Trence, & D. P. Wilson (Eds.), Endotext [Internet]. MDText.com, Inc. https://www.ncbi.nlm.nih.gov/books/NBK532084/
Pahadiya, H. R., Lakhotia, M., Gandhi, R., Yadav, R. S., & Madan, S. (2016). Fasting intolerance and recurrent hypoglycemia: Ponder for Sheehan's. Indian Journal of Endocrinology and Metabolism, 20(5), 739–740. https://doi.org/10.4103/2230-8210.190593
Pineyro, M. M., Diaz, L., Guzzetti, M., Risso, M., & Pereda, J. (2022). Acute Sheehan's syndrome presenting with hyponatremia followed by a spontaneous pregnancy. Case Reports in Endocrinology, 2022, Article 9181365. https://doi.org/10.1155/2022/9181365
Qadri, M. I., Mushtaq, M. B., Qazi, I., Yousuf, S., & Rashid, A. (2015). Sheehan's syndrome presenting as major depressive disorder. Iranian Journal of Medical Sciences, 40(1), 73–76. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300485/
Rodríguez Piña, M., Vidal, N., García, B., Robles, P., & Mendieta Zerón, H. (2022). Expected prevalence of Sheehan's syndrome in Mexico by extrapolation of screenings in other countries. Revista Angolana de Ciências da Saúde, 3(1), 10–16. https://doi.org/10.54283/RACSaude.v3i1.2022.p10-16
Schury, M. P., & Adigun, R. (2023). Sheehan syndrome. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK459166/
Sethuram, R., Guilfoil, D. S., Amori, R., Kharlip, J., & Berkowitz, K. M. (2020). Sheehan syndrome: An unusual presentation without inciting factors. Women's Health Reports (New Rochelle), 1(1), 287–292. https://doi.org/10.1089/whr.2019.0028
Shivaprasad, C. (2011). Sheehan's syndrome: Newer advances. Indian Journal of Endocrinology and Metabolism, 15(Suppl 3), S203–S207. https://doi.org/10.4103/2230-8210.84869
Shoib, S., Dar, M. M., Arif, T., Bashir, H., Bhat, M. H., & Ahmed, J. (2013). Sheehan's syndrome presenting as psychosis: A rare clinical presentation. Medical Journal of the Islamic Republic of Iran, 27(1), 35–37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3592941/
Soares, D. V., Spina, L. D., de Lima Oliveira Brasil, R. R., Lobo, P. M., Salles, E., Coeli, C. M., Conceição, F. L., & Vaisman, M. (2006). Two years of growth hormone replacement therapy in a group of patients with Sheehan's syndrome. Pituitary, 9(2), 127–135. https://doi.org/10.1007/s11102-006-9990-9
Tanriverdi, F., Unluhizarci, K., Kula, M., Guven, M., Bayram, F., & Kelestimur, F. (2005). Effects of 18-month of growth hormone (GH) replacement therapy in patients with Sheehan's syndrome. Growth Hormone & IGF Research, 15(3), 231–237. https://doi.org/10.1016/j.ghir.2005.03.005
Thau, L., Gandhi, J., & Sharma, S. (2023). Physiology, cortisol. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK538239/
Vasconcelos, A. L., Pinto Ribeiro, R., Claúdio Ferreira, P., Maciel, J., & Araújo, R. (2024). A case report of Sheehan syndrome: A rare cause of hypopituitarism. Cureus, 16(2), e53544. https://doi.org/10.7759/cureus.53544
Copyright (c) 2025 Natalia Musialik, Maciej Magiera, Barbara Starosta, Monika Pelczar, Bartosz Brzychcy, Karolina Brzychcy, Karolina Paks, Zuzanna Gajda, Ewa Jench
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.
