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Nobels FRE, de Herder WW, Kwekkeboom DJ, Coopmans W, Mulder A, Bouillon R, Lamberts SWJ. Serum chromogranin A in the differential diagnosis of Cushing's syndrome. Eur J Endocrinol 1994:131:589–93. ISSN 0804–4643
We evaluated whether measuring serum levels of chromogranin A, a marker of neuroendocrine tumours, could be useful in the differential diagnosis between pituitary, adrenal and ectopic causes of Cushing's syndrome. Thirty patients with Cushing's syndrome were studied. The localization of the tumours responsible was pituitary in 15, adrenal in 5 and ectopic in 10 patients. Serum concentrations of chromogranin A were measured in all patients. Petrosal sinus sampling for chromogranin A was performed in the cases with pituitary-dependent Cushing's syndrome. Immunohistochemical staining for chromogranin A was carried out on part of the tumour specimens. Slightly elevated serum levels of chromogranin A (range 223–262 µg/1) were detected in inferior petrosal sinus and peripheral venous samples from three patients with pituitary-dependent Cushing's syndrome. Serum chromogranin A showed no significant pituitary to peripheral gradient in these patients. Chromogranin A levels were not elevated in cases of adrenal Cushing's syndrome. Markedly elevated concentrations (range 270–13900 µg/1) were shown in seven of 10 patients with neuroendocrine tumours with ectopic adrenocorticotrophin (ACTH) and/or corticotrophin-releasing hormone (CRH) production. Widespread metastasis was present in all these cases. Subjects with "occult" carcinoid tumours, with limited spread, had normal chromogranin A levels Immunohistochemical staining for chromogranin A was positive in three out of five pituitary adenomas and in all neuroendocrine tumours with ectopic ACTH and/or CRH production, while it was negative in all adrenocortical tumour specimens. It is concluded that elevated serum levels of chromogranin A can serve as markers of neuroendocrine tumours with ectopic ACTH and/or CRH production. The circulating levels are dependent mainly on the size of the tumours. Serum chromogranin A is not useful in the diagnosis of so-called occult Cushing's syndrome, caused by ectopic ACTH and/or CRH secretion by small neuroendocrine tumours.
F Nobels, Department of Endocrinology, Onze Lieve Vrouw Hospital, 164 Moorselbaan, 9300 Aalst, Belgium
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