NELSON SYNDROME
Nelson syndrome is progressive pituitary corticotroph tumor enlargement after bilateral adrenalectomy is performed for the treatment of pituitary-dependent Cushing syndrome. Although the treatment of choice for a corticotroph adenoma is selective adenectomy at the time of transsphenoidal surgery (see Plate 1-22), bilateral laparoscopic adrenalectomy is indicated when pituitary surgery is not successful. When bilateral adrenalectomy cures hypercortisolism, there is less negative feedback on the corticotroph tumor cells with physiologic glucocorticoid replacement, and the adenoma may grow. Nelson syndrome occurs in a minority of patients who follow the treatment sequence of failed transsphenoidal surgery and bilateral adrenalectomy. Most corticotroph microadenomas do not enlarge over time in this setting. However, when pituitary-dependent Cushing syndrome is caused by a corticotroph macroadenoma (10 mm in largest diameter), the risk of tumor enlargement after bilateral adrenalectomy is high.
The clinical features of Nelson
syndrome are skin hyperpigmentation related to the markedly increased blood
levels of pro-opiomelanocortin and corticotropin (adrenocorticotropic hormone
[ACTH]) and symptoms related to mass effects of an enlarging pituitary tumor
(e.g., visual field defects, oculomotor nerve palsies, hypopituitarism, and
headaches). As in Addison disease (see Plate 3-22), generalized
hyperpigmentation is caused by ACTH-driven increased melanin production in the
epidermal melanocytes. The extensor surfaces (e.g., knees, knuckles, elbows)
and other friction areas (e.g., belt line, bra straps) tend to be even more
hyper- pigmented. Other sites of prominent hyperpigmentation include the inner
surface of the lips, buccal mucosa, gums, hard palate, recent surgical scars,
areolae, freckles, and palmar creases (the latter may be a normal finding in
darker-skinned individuals). The fingernails may show linear bands of darkening
arising from the nail beds. Suspected Nelson syndrome can be confirmed by
magnetic resonance imaging (MRI) of the sella that demonstrates an enlarging
sellar mass. In addition, blood ACTH concentrations are markedly increased in
this setting (e.g., 1000 pg/mL; reference range, 10–60 pg/mL).
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| Plate 1-23 |
Patients with pituitary-dependent
Cushing syndrome who are treated with bilateral adrenalectomy should be monitored annually with pituitary MRI for
approximately 10 years. Tumor-directed radiation therapy should be considered
if tumor growth is documented on serial MRI. If feasible, gamma knife
radiosurgery is the treatment of choice for Nelson corticotroph tumors. However,
unlike most pituitary adenomas, these neoplasms may demonstrate aggressive
growth despite radiotherapy. Extensive cavernous sinus involvement may result
in multiple cranial nerve palsies. No effective pharmacologic options are
available to treat this locally aggressive
neoplasm. Temozolomide is being investigated as a potential treatment option
for aggressive pituitary tumors or carcinoma.
Despite the concern about potential
development of Nelson syndrome, clinicians should never hesitate to cure Cushing
syndrome with bilateral laparoscopic adrenalectomy when transsphenoidal surgery
has not been curative. Untreated Cushing syndrome can be fatal, but Nelson syndrome is usually
manageable.
