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Nelson Syndrome Workup

  • Author: Thomas A Wilson, MD; Chief Editor: Stephen Kemp, MD, PhD  more...
 
Updated: Dec 11, 2015
 

Laboratory Studies

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, Phi Beta Kappa

Disclosure: Nothing to disclose.

Coauthor(s)

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 Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, American College of Endocrinology

Disclosure: Nothing to disclose.

Antony Lafferty, MB, BCh 

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

Disclosure: Nothing to disclose.

Specialty Editor Board

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, Society for Pediatric Research

Disclosure: Received grant/research funds from Eli Lilly for pi; Received grant/research funds from NovoNordisk for pi; Received consulting fee from NovoNordisk for consulting; Partner received consulting fee from Onyx Heart Valve for consulting.

Chief Editor

Stephen Kemp, MD, PhD Former 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, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Angelo P Giardino, MD, MPH, PhD Professor and Section Head, Academic General Pediatrics, Baylor College of Medicine; Senior Vice President and Chief Quality Officer, Texas Children’s Hospital

Angelo P Giardino, MD, MPH, PhD 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, International Society for the Prevention of Child Abuse and Neglect, Ray E Helfer Society

Disclosure: Received grant/research funds from Health Resources and Services Administration (HRSA) Integrated Community Systems for CSHCN Grant for other; Received advisory board from Baxter Healthcare Corporation for board membership.

Acknowledgements

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.

References
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