Nelson Syndrome Treatment & Management

  • Author: Thomas A Wilson, MD; Chief Editor: Stephen Kemp, MD, PhD   more...
 
Updated: Mar 5, 2012
 

Medical Care

Although Nelson syndrome was previously thought to be primarily due to a pituitary macroadenoma, and medical treatment alone was thought to be rarely curative, recent high-resolution MRI that allows detection of microadenomas and the use of a newer class of drugs have shown promising results for medical treatment alone to be possible in some cases.

  • Case reports have demonstrated successful remission of Nelson syndrome with cabergoline (dopamine receptor agonist), with decline and normalization of adrenocorticotropin (ACTH) levels and resolution of the pituitary macroadenoma or microadenoma.[9, 10, 11]
  • Various other drugs that have been used in an attempt to medically control tumor growth, with variable success, include octreotide (a parenterally administered somatostatin analog), cyproheptadine with and without bromocriptine, and sodium valproate. Octreotide or other analogue of somatostatin may be helpful to control ACTH levels, although it is only useful as a means of controlling levels until definitive treatment is undertaken because it does not result in appreciable tumor shrinkage. Because it suppresses other hormones, including insulin, it may result in other problems, such as carbohydrate intolerance. In addition, it may cause sludging within the gall bladder.
  • Radiotherapy is important in the treatment of patients with Nelson syndrome.[12]
    • Historically, the irradiated field needed to be large, which led to increased risk of damage to the surrounding brain.
    • The most serious long-term problems have included learning and memory difficulties, radiation-induced visual damage, and, most importantly, the risk of secondary tumors.
    • With the advent of newer means of reducing radiation scatter (eg, linear accelerator [LINAC], gamma radiosurgery[13, 14, 15] ), radiotherapy-associated morbidity has significantly decreased and may be helpful in tumors that are not amenable to surgery.
Next

Surgical Care

Surgery remains one of the best hopes of cure for patients with Nelson syndrome and is the treatment of choice for large tumors that are producing acute compression of the optic apparatus and other vital structures.

  • Transsphenoidal surgery by an experienced surgeon is optimal because it offers the lowest risk of hypothalamic injury.
  • Stereotactic radiosurgery, called gamma knife surgery (GKS), has recently been successfully performed in secretory pituitary tumors (including Nelson syndrome tumors) that are refractory to other surgical interventions.[13, 14, 15, 16]
  • Determinants of success include the degree of tumor invasion of brain parenchyma, optic apparatus, cavernous sinuses, dura, and bone and the skill of the surgeon.
  • The goal of surgery is to remove all macroscopic tumor tissue without compromising vital structures.
  • In cases of incomplete removal or where invasion is present, adjunctive irradiation reduces that rate of recurrence and improves the prognosis.
  • Incidence of treatment-associated hypopituitarism is high, particularly with large tumors.
Previous
Next

Consultations

  • Pediatric endocrinologist
  • Pediatric ophthalmologist
  • Pediatric neurosurgeon (with expertise in transsphenoidal and/or gamma knife surgery)
  • Radiation oncologist (stereotactic radiosurgical center)
Previous
Next

Diet

  • No restrictions on diet are necessary.
Previous
Next

Activity

Previous
Proceed to Medication
 
 
Contributor Information and Disclosures
Author

Thomas A Wilson, MD  Professor of Clinical Pediatrics, Chief and Program Director, Division of Pediatric Endocrinology, Department of Pediatrics, The School of Medicine at Stony Brook University Medical Center

Thomas A Wilson, MD is a member of the following medical societies: Endocrine Society, Pediatric Endocrine Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Coauthor(s)

Vardhini Desikan, MBBS, MPH  Pediatric Endocrinology Fellow, Department of Pediatrics, State University of New York at Stony Brook

Vardhini Desikan, MBBS, MPH is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London)  Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece; UNESCO Chair on Adolescent Health Care, University of Athens, Greece

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Antony Lafferty, MB ChB, FRACP  Senior Lecturer of Pediatric Endocrinology, Monash University Department of Pediatrics, National Institutes of Health, Bethesda, MD, and Princess Margaret Hospital for Children, Perth, Western Australia

Antony Lafferty, MB ChB, FRACP is a member of the following medical societies: Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Angelo P Giardino, MD, PhD, MPH  Associate Professor, Baylor College of Medicine; Chief Medical Officer, Texas Children's Health Plan; Chief Quality Officer, Medicine, Texas Children's Hospital

Angelo P Giardino, MD, PhD, MPH is a member of the following medical societies: Academic Pediatric Association, American Academy of Pediatrics, American Professional Society on the Abuse of Children, Harris County Medical Society, Helfer Society, and International Society for Prevention of Child Abuse and Neglect

Disclosure: Bayer Honoraria Review panel membership; Pfizer Grant/research funds Independent contractor; MedImmune Honoraria Review panel membership; Teva Pharmacutical travel & honoraria Managed Care Advisory Panel; CIGNA Honoraria Physician Advisory Council

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Lynne Lipton Levitsky, MD  Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor of Pediatrics, Harvard Medical School

Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Pfizer Grant/research funds P.I.; Tercica Grant/research funds Other; Eli Lily Grant/research funds PI; NovoNordisk Grant/research funds PI; NovoNordisk Consulting fee Consulting; Onyx Heart Valve Consulting fee Consulting

Merrily P M Poth, MD  Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences

Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD  Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

References

  1. Barber TM, Adams E, Ansorge O, Byrne JV, Karavitaki N, Wass JA. Nelson's syndrome. Eur J Endocrinol. Oct 2010;163(4):495-507. [Medline].

  2. Nelson DH, Meakin JW, Dealy JB, et al. ACTH-producing tumor of the pituitary gland. N Engl J Med. Jul 24 1958;259(4):161-4. [Medline].

  3. van Aken MO, Pereira AM, van den Berg G, Romijn JA, Veldhuis JD, Roelfsema F. Profound amplification of secretory-burst mass and anomalous regularity of ACTH secretory process in patients with Nelson's syndrome compared with Cushing's disease. Clin Endocrinol (Oxf). Jun 2004;60(6):765-72. [Medline].

  4. Chapuis Y, Pitre J, Conti F, et al. Role and operative risk of bilateral adrenalectomy in hypercortisolism. World J Surg. Sep 1996;20(7):775-9; discussion 779-80. [Medline].

  5. Tiyadatah BN, Kalavampara SV, Sukumar S, Mathew G, Pooleri GK, Prasanna AT, et al. Bilateral Simultaneous Laparoscopic Adrenalectomy in Cushing's Syndrome: Safe, Effective, and Curative. J Endourol. Feb 2012;26(2):157-63. [Medline].

  6. Rizk A, Honegger J, Milian M, Psaras T. Treatment Options in Cushing's Disease. Clin Med Insights Oncol. 2012;6:75-84. [Medline]. [Full Text].

  7. Biller BM, Grossman AB, Stewart PM, et al. Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab. Jul 2008;93(7):2454-62. [Medline].

  8. Barabash R, Moreno-Suárez FG, Rodríguez L, Molina AM, Conejo-Mir J. [Nelson syndrome: a rare cause of generalized hyperpigmentation of the skin]. Actas Dermosifiliogr. Jan-Feb 2010;101(1):76-80. [Medline].

  9. Casulari LA, Naves LA, Mello PA, Pereira Neto A, Papadia C. Nelson's syndrome: complete remission with cabergoline but not with bromocriptine or cyproheptadine treatment. Horm Res. 2004;62(6):300-5. [Medline].

  10. Pivonello R, Faggiano A, Di Salle F, Filippella M, Lombardi G, Colao A. Complete remission of Nelson's syndrome after 1-year treatment with cabergoline. J Endocrinol Invest. Dec 1999;22(11):860-5. [Medline].

  11. Shraga-Slutzky I, Shimon I, Weinshtein R. Clinical and biochemical stabilization of Nelson's syndrome with long-term low-dose cabergoline treatment. Pituitary. 2006;9(2):151-4. [Medline].

  12. Petit JH, Biller BM, Yock TI, et al. Proton stereotactic radiotherapy for persistent adrenocorticotropin-producing adenomas. J Clin Endocrinol Metab. Feb 2008;93(2):393-9. [Medline].

  13. Kobayashi T, Kida Y, Mori Y. Gamma knife radiosurgery in the treatment of Cushing disease: long-term results. J Neurosurg. Dec 2002;97(5 Suppl):422-8. [Medline].

  14. Wolffenbuttel BH, Kitz K, Beuls EM. Beneficial gamma-knife radiosurgery in a patient with Nelson's syndrome. Clin Neurol Neurosurg. Mar 1998;100(1):60-3. [Medline].

  15. Mauermann WJ, Sheehan JP, Chernavvsky DR, Laws ER, Steiner L, Vance ML. Gamma Knife surgery for adrenocorticotropic hormone-producing pituitary adenomas after bilateral adrenalectomy. J Neurosurg. Jun 2007;106(6):988-93. [Medline].

  16. Vik-Mo EO, Oksnes M, Pedersen PH, et al. Gamma knife stereotactic radiosurgery of Nelson syndrome. Eur J Endocrinol. Feb 2009;160(2):143-8. [Medline].

  17. Assie G, Bahurel H, Coste J, et al. Corticotroph tumor progression after adrenalectomy in Cushing's Disease: A reappraisal of Nelson's Syndrome. J Clin Endocrinol Metab. Jan 2007;92(1):172-9. [Medline].

  18. De Tommasi C, Vance ML, Okonkwo DO, Diallo A, Laws ER Jr. Surgical management of adrenocorticotropic hormone-secreting macroadenomas: outcome and challenges in patients with Cushing's disease or Nelson's syndrome. J Neurosurg. Nov 2005;103(5):825-30. [Medline].

  19. Forni C, Giovanelli MA. Nelson's syndrome in the paediatric age. Childs Brain. 1977;3(5):309-14. [Medline].

  20. Gil-Cardenas A, Herrera MF, Diaz-Polanco A, Rios JM, Pantoja JP. Nelson's syndrome after bilateral adrenalectomy for Cushing's disease. Surgery. Feb 2007;141(2):147-51; discussion 151-2. [Medline].

  21. Hopwood NJ, Forsman PJ, Kenny FM, Drash AL. Hypoglycemia in hypopituitary children. Am J Dis Child. Aug 1975;129(8):918-26. [Medline].

  22. Hornyak M, Weiss MH, Nelson DH, Couldwell WT. Nelson syndrome: historical perspectives and current concepts. Neurosurg Focus. 2007;23(3):E12. [Medline].

  23. Imai T, Funahashi H, Tanaka Y, et al. Adrenalectomy for treatment of Cushing syndrome: results in 122 patients and long-term follow-up studies. World J Surg. 1996;20(7):781-786. [Medline].

  24. Jane JA, Vance ML, Woodburn CJ, Laws ER Jr. Stereotactic radiosurgery for hypersecreting pituitary tumors: part of a multimodality approach. Neurosurg Focus. May 15 2003;14(5):e12. [Medline].

  25. Karl M, Von Wichert G, Kempter E, et al. Nelson's syndrome associated with a somatic frame shift mutation in the glucocorticoid receptor gene. J Clin Endocrinol Metab. Jan 1996;81(1):124-9. [Medline].

  26. Kasperlik-Zaluska AA, Bonicki W, Jeske W, Janik J, Zgliczynski W, Czernicki Z. Nelson's syndrome -- 46 years later: clinical experience with 37 patients. Zentralbl Neurochir. Feb 2006;67(1):14-20. [Medline].

  27. Kasperlik-Zaluska AA, Zgliczynski W, Jeske W, Zdunowski P. ACTH responses to somatostatin, valproic acid and dexamethasone in Nelson's syndrome. Neuro Endocrinol Lett. Dec 2005;26(6):709-12. [Medline].

  28. Kelly DF. Transsphenoidal surgery for Cushing's disease: a review of success rates, remission predictors, management of failed surgery, and Nelson's Syndrome. Neurosurg Focus. 2007;23(3):E5. [Medline].

  29. Kovacs K, Horvath E, Coire C, et al. Pituitary corticotroph hyperplasia preceding adenoma in a patient with Nelson's syndrome. Clin Neuropathol. Mar-Apr 2006;25(2):74-80. [Medline].

  30. Lafferty AR, Chrousos GP. Pituitary tumors in children and adolescents. J Clin Endocrinol Metab. Dec 1999;84(12):4317-23. [Medline].

  31. Mercado-Asis LB, Yanovski JA, Tracer HL, Chik CL, Cutler GB Jr. Acute effects of bromocriptine, cyproheptadine, and valproic acid on plasma adrenocorticotropin secretion in Nelson's syndrome. J Clin Endocrinol Metab. Feb 1997;82(2):514-7. [Medline].

  32. Mullan KR, Leslie H, McCance DR, Sheridan B, Atkinson AB. The PPAR-gamma activator rosiglitazone fails to lower plasma ACTH levels in patients with Nelson's syndrome. Clin Endocrinol (Oxf). May 2006;64(5):519-22. [Medline].

  33. Munir A, Song F, Ince P, Walters SJ, Ross R, Newell-Price J. Ineffectiveness of rosiglitazone therapy in Nelson's syndrome. J Clin Endocrinol Metab. May 2007;92(5):1758-63. [Medline].

  34. Munir A, Song F, Ince P, Walters SJ, Ross R, Newell-Price J. Ineffectiveness of rosiglitazone therapy in Nelson's syndrome. J Clin Endocrinol Metab. May 2007;92(5):1758-63. [Medline].

  35. Oldfield EH, Schulte HM, Chrousos GP, et al. Corticotropin-releasing hormone (CRH) stimulation in Nelson's syndrome: response of adrenocorticotropin secretion to pulse injection and continuous infusion of CRH. J Clin Endocrinol Metab. May 1986;62(5):1020-6. [Medline].

  36. Pereira MA, Halpern A, Salgado LR, et al. A study of patients with Nelson's syndrome. Clin Endocrinol (Oxf). Oct 1998;49(4):533-9. [Medline].

  37. Reuss WA, Saeger W, Ludecke DK. Electron microscopical morphometry of well-differentiated and undifferentiated ACTH secreting adenomas in Cushing's disease and Nelson's syndrome. Virchows Arch A Pathol Anat Histopathol. 1991;419(5):395-401. [Medline].

  38. Thomas CG Jr, Smith AT, Benson M, Griffith J. Nelson's syndrome after Cushing's disease in childhood: a continuing problem. Surgery. Dec 1984;96(6):1067-77. [Medline].

 
Previous
Next
 
Physical findings in Cushing syndrome.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.