Final Diagnosis -- Nelsonís Syndrome


DIAGNOSIS AND DISCUSSION

DIAGNOSIS

Nelson's Syndrome

DISCUSSION

Cushing's Disease is caused by an adrenocorticotropin hormone (ACTH)-secreting pituitary adenoma. Refractory Cushing's Disease may be treated by bilateral adrenalectomy, which is a definitive treatment, but 20-30% of these cases will develop Nelson's syndrome in which the adenoma continues to grow and secrete ACTH (1, 3). Hyperpigmentation is often seen and when the adenoma grows large enough there may be visual field defects or cranial nerve symptoms.

Crooke's hyaline change was first described in 1935 in the normal anterior pituitary surrounding an ACTH-secreting adenoma. The non-neoplastic corticotrophs have increased eosinophilic cytoplasm filled with perinuclear cytokeratin while the adenoma itself does not. The cause of Crooke's hyaline change is uncertain, but it is related to increased glucocorticoid or cortisol levels. Crooke's cells are found in pituitaries of Cushing's Disease, but not in the pituitary surrounding the adenomas of Nelson's syndrome (4).

In very rare cases the ACTH-secreting adenoma is itself composed of cells with Crooke's hyaline change (Fig 11). Because of the perinuclear accumulation of cytokeratin, the ACTH stains show ring-like areas of negative staining (Fig 12). Although pituitary adenomas are positive for CAM5.2, Crooke's cells (whether in the surrounding pituitary or in the adenoma) will show very strong perinuclear and ring-like accumulations of positive staining (Fig 13). These tumors are called Crooke's Cell Adenomas and they are an aggressive variant of ACTH-secreting adenomas. In 2003, 36 cases of Crooke's Cell Adenomas were examined and compared to the 7 cases previously published (2). None of these adenomas were in cases of Nelson's Syndrome.

REFERENCES

  1. Barber TM, Adams E, Ansorge O, Byrne JV, Karavitaki N, Wass JAH (2010) Nelson's Syndrome. Eur J Endocrinol 163:495-507.
  2. George DH, Scheithauer BW, Kovacs K, Horvath E, Young Jr. WF, Lloyd RV, Meyer FB (2003) Crooke's Cell Adenoma of the pituitary: an aggressive variant of corticotroph adenoma. Am J Surg Pathol 27:1330-1336.
  3. Hornyak M, Weiss MH, Nelson DH, Couldwell WT (2007) Nelson syndrome: historical perspectives and current concepts. Neurosurg Focus 2007: 23 (E12): 1-9,
  4. Martin R, Cetin Y, Fehm HL, Fahlbusch R, Voigt KH (1982) Multiple cellular forms of corticotrophs in surgically removed pituitary adenomas and periadenomatous tissue in Cushing's Disease. Am J Pathol 106:332-341.

Acknowledgments: Figures 11, 12 and 13 courtesy of Dr. Arie Perry.

Contributed by David M Atkinson, MD1, Ronald L Hamilton, MD2




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