Nelson Syndrome Workup
- Author: Thomas A Wilson, MD; Chief Editor: Stephen Kemp, MD, PhD more...
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.
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).
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.
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.
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.
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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