Nelson Syndrome Workup

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

Laboratory Studies

The following laboratory studies are indicated in Nelson syndrome:

  • Adrenocorticotropin (ACTH) measurement
    • ACTH levels are markedly elevated in Nelson syndrome, usually in the thousands of picograms per milliliter.
    • Levels of other derivatives of the precursor peptide, proopiomelanocortin (POMC), are also elevated, although their measurement is not required for diagnosis.
    • Patients with Nelson syndrome often have an exaggerated ACTH response to corticotropin-releasing hormone (CRH). This test is not required for diagnostic purposes.
  • Thyroid function tests
    • Central hypothyroidism, which is not always clinically detectable, may be present.
    • Free thyroxine (T4) levels are commonly just below the lower limit of the reference range, and thyroid-stimulating hormone (TSH) levels may be low, normal, or even mildly elevated.
  • Prolactin measurement
    • Any lesion that disrupts the pituitary stalk or hypothalamic-pituitary portal system results in mild hyperprolactinemia (< 100 ng/dL) because of loss of dopaminergic inhibition.
    • Patients with prolactin-secreting pituitary adenomas typically have levels that exceed 150-200 ng/dL, with levels being many times greater in patients with macroadenomas.
  • Growth hormone measurement
    • Insulinlike growth factor–1 (IGF-1) and insulinlike growth factor–binding protein-3 (IGF-BP3) measurement is a useful means of screening for growth hormone deficiency in children older than 3 years.
    • These results must be interpreted according to age-appropriate, sex-appropriate, and pubertal stage–appropriate reference range values. If these are low, more formal testing should be performed (see Short Stature).
  • Gonadotropin measurement
    • Measure gonadotropin levels in adolescents in whom pubertal arrest or delay is suggested.
    • Hyperprolactinemia causes hypogonadotropic hypogonadism.
    • If androgenization with testicular enlargement, symptoms of pituitary or visual disturbance, and suppressed gonadotropins are present, human chorionic gonadotropin (HCG) should be measured to exclude a germ cell tumor.
  • Urine osmolality or specific gravity tests
    • Central diabetes insipidus occurs if the tumor has destroyed the posterior pituitary gland or disrupted the stalk. This is a rare occurrence because vasopressin secretion can occur more proximally if impingement on the neurohypophysis is gradual.
    • If an history of polyuria and polydipsia is noted, an early morning urine specimen should be collected. In healthy children, the urine osmolality should be greater than 600-700 mOsm/kg or the specific gravity should be greater than 1.010 in the morning. If the early morning urine is dilute, a water deprivation test should be performed.
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Imaging Studies

  • MRI of the pituitary and parasellar region
    • A gadolinium-enhanced MRI of the pituitary and parasellar region with 3-mm cuts through the pituitary adequately demonstrates the tumor and provides evidence of compression or invasion of surrounding structures.
    • In young children and patients with claustrophobia, sedation or anesthesia is required to obtain good quality images.
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Other Tests

  • Visual field assessment
    • All children with large masses in the region of the pituitary or optic nerves should be referred for formal visual field assessment by a pediatric ophthalmologist.
    • Patients, especially children, do not always report visual symptoms.
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Histologic Findings

  • Tumors immunostain positive for ACTH.
  • Crooke hyaline change, observed in Cushing disease, is not usually present because patients with Nelson syndrome are not hypercortisolemic.
  • Little histologic difference is observed between the ACTH-secreting adenoma observed in Cushing disease and that of Nelson syndrome, except that the latter is usually much larger and more likely to exhibit aggressive behavior.
  • Nelson syndrome tumors may have cytological features that include increased cellular proliferation, with mitoses and cellular and nuclear pleomorphism. At the molecular level, this aggressive behavior may reflect the development of genetic mutations in oncogenes and genes regulating pituitary growth and differentiation, although this has not been investigated.
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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].

 
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