Last updated:
11/21/2023
Years published: 1987, 1989, 1998, 2005, 2007, 2023
NORD gratefully acknowledges Kayla Nguyen and Zhaohan Zhu, NORD Editorial Interns from the University of Notre Dame and Niki Karavitaki, MBBS, MD, PhD, MSc, University of Birmingham, UK, for assistance in the preparation of this report.
Summary
Nelson syndrome is a rare endocrine disorder that can arise typically one to four years following the surgical removal of the adrenal glands (bilateral adrenalectomy) in individuals with Cushing disease. The adrenal glands are located at the top of the kidneys and play a key role in maintaining hormonal balance within the body. Patients most commonly have hyperpigmentation, in which the skin color becomes darker, high adrenocorticotropic hormone (ACTH) secretion and the development of large growths of the pituitary gland called adenomas. The chance of developing Nelson syndrome following bilateral adrenalectomy ranges from 8 to 47 percent in adults and 25 to 66 percent in children. Bilateral adrenalectomy is no longer routinely recommended for patients with Cushing disease, so fewer people are being diagnosed with Nelson syndrome. Treatment for Nelson syndrome involves the removal of the pituitary gland tumor, radiation of the tumor region and in difficult cases, medications.
Introduction
Cushing disease occurs when excess adrenocorticotropin hormone (ACTH) production from a benign pituitary tumor (adenoma) causes the adrenal glands to produce excessive amounts of cortisol. Approximately 70% of cases of Cushing syndrome are caused by Cushing disease. Cushing syndrome is a rare endocrine disorder, characterized by a variety of symptoms and physical abnormalities that occur as a result of excessive amounts of the hormone cortisol.
Major symptoms and signs of Nelson syndrome include the following:
Cushing disease is characterized by the presence of a non-cancerous tumor on the pituitary gland causing excessive production of ACTH. Nelson syndrome develops when the tumor in the pituitary gland grows after the removal of the adrenal glands (bilateral adrenalectomy). The adrenal glands normally produce cortisol. When no cortisol is produced, the hypothalamus signals the pituitary gland to produce adrenocorticotropic hormone (ACTH), which normally signals the adrenal glands to produce cortisol. Since the adrenal glands are removed, the pituitary gland continues to produce ACTH. This eventually leads to enlargement of the pituitary gland tumors or new growths.
Nelson syndrome is diagnosed more often in females than males (8:1), especially in middle-aged females who have Cushing disease. Of the small population (about 6 percent) of Cushing disease patients who have surgery to remove both adrenal glands, 15 to 25 percent develop Nelson syndrome one to four years after the procedure. However, the disorder can arise up to 24 years after the surgery. Current data indicates 21 percent of cases of Nelson syndrome occur within 5 years of a bilateral adrenalectomy.
Nelson disease may be suspected when hyperpigmentation occurs in a patient who has had a bilateral adrenalectomy.
The proposed criterion for diagnosis of Nelson disease is three consecutive readings of a 30 percent increase of adrenocorticotropic hormone (ACTH) from the initial reading, following a bilateral adrenalectomy. Brain magnetic resonance imaging (MRI) can also be used for diagnosis
The first recommended step in treating Nelson syndrome is the removal of the tumor using surgery through the nasal passages (transsphenoidal surgery). Radiation therapy might be used after surgery. For some patients, frequent medical imaging may be recommended to monitor tumors instead of offering surgery. Because patients with Nelson syndrome are not able to produce cortisol and aldosterone, hydrocortisone and mineralocorticoids are required supplements. Additional therapies can be used to treat individual symptoms and provide pain relief. Recent studies have shown mixed results with drug therapies.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov
Some current clinical trials are also posted on the following page on the NORD website: https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/
For information about clinical trials sponsored by private sources, contact: www.centerwatch.com
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Fountas A, Karavitaki N. Management of Nelson’s syndrome. Medicina.2022;58(11):1580. doi:10.3390/medicina58111580
Valassi E, Castinetti F, Ferriere A, et al. Corticotroph tumor progression after ilateral adrenalectomy: data from ERCUSYN. Endocrelat cancer. 2022;29(12). doi:10.1530/ERC-22-0074
Papakokkinou E, Piasecka M, Carlsen HK, et al. Prevalence of Nelson’s syndrome after bilateral adrenalectomy in patients with cushing’s disease: a systematic review and meta-analysis. Pituitary. 2021;24(5):797-809. doi:10.1007/s11102-021-01158-z
Fountas A, Karavitaki N. Nelson’s syndrome: An update. Endocrinol Metab Clin North Am. 2020;49(3). doi:10.1016/j.ecl.2020.05.004
Maccora D, Walls GV, Sadler GP, Mihai R. Bilateral adrenalectomy: a review of 10 years’ experience. Ann R Coll Surg Engl. 2017;99(2):119-122. doi:10.1308/rcsann.2016.0266
Patel J, Eloy JA, Liu JK. Nelson’s syndrome: a review of the clinical manifestations, pathophysiology, and treatment strategies. Neurosurgical Focus. 2015;38(2). doi:10.3171/2014.10.FOCUS14681
Sharma ST, Nieman LK, Feelders RA. Cushing’s syndrome: epidemiology and developments in disease management. Clinical Epidemiology. 2015;7. doi:10.2147/CLEP.S44336
Andreassen M, Kristensen LO: Rosiglitazone for prevention or adjuvant treatment of Nelson’s syndrome after bilateral adrenalectomy. Eur J Endocrinol. 2005 Oct;153(4):503-5
Hentschel SJ, McCutcheon IE. Stereotactic radiosurgery for Cushing disease. Neurosurg Focus. 2004;16:E5.
Munir A, Song F, Ince P, Ross R, Newell-Price J: A pilot study of prolonged high dose rosiglitazone therapy (12mg/day) in Nelson’s syndrome. Endocrine Abstracts. 2004; 8 OC24.
Jane JA Jr, Vance ML, Woodburn CJ, et al. Stereotactic radiosurgery for hypersecreting pituitary tumors: part of a multimodality approach. Neurosurg Focus.2003;14:e12.
Kobayashi T, Kida Y, Mori Y. Gamma knife radiosurgery in the treatment of Cushing disease: long-term results. J Neurosurg. 2002;97(5 Suppl):422-28.
Kelly PA, Samandouras G Grossman AB, et al. Neurosurgical treatment of Nelson’s syndrome. J Clin Endocrinol Metab. 2002;87:5465-69.
Pollock BE, Young WF Jr. Stereotactic radiosurgery for patients with ACTH-producing pituitary adenomas after prior adrenalectomy. Int J Radiat Oncol Biol Phys.2002;54:640-41.
Xing B, Ren Z, Su C, et al. Microsurgical treatment of Nelson’s syndrome. Chin Med J (English). 2002;115:1150-52.
Kasperlik-Zaluska AA, Jeske W. Management of Nelson’s syndrome: observations in fifteen patients. Clin Endocrinol (Oxf). 2001;55:819.
Arafah BM, Nasrallah MP. Pituitary tumors, pathophysiology, clinical manifestations and management. Endocr Relat Cancer. 2001;8:287-305.
Cushing H. The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism). 1932. Obes Res. 1994;2(5):486-508. doi:10.1002/j.1550-8528.1994.tb00097.x
INTERNET
Monserrate AE, De Jesus O. Nelson Syndrome. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560755/ Accessed Nov 15, 2023.
Wilson TA, Nelson Syndrome Medscape. Mar 25, 2021. https://emedicine.medscape.com/article/923425-overview Accessed Nov 15, 2023.
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