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Marked chromogranin A elevation in a patient with bilateral adrenal incidentalomas, and its rapid normalization after discontinuation of proton pump inhibitor therapy

Chromogranin A (CgA) is a well-recognized tumour marker for various neuroendocrine tumours. 1 In their recent article Grossrubatscher et al. demonstrate the utility of CgA in the diagnosis and follow-up of phaeochromocytoma. 2 As the secretory activity of these tumours can be episodic, CgA measurement is of great value in cases where urinary catecholamines are negative. False-positive elevated CgA, however, can be related to various conditions, 1 including proton pump inhibitor (PPI) and steroid therapy, or be associated with impaired renal function and type A gastritis, and can lead to serious differential diagnostic problems in patients with adrenal tumours. Here, we report a case of highly elevated serum CgA level in a patient with bilateral adrenal adenomas, that was clearly associated with proton pump inhibitor therapy. As the patient also suffered from hypertension, the possibility of phaeochromocytoma had to be excluded. Discontinuation of PPI intake for 5 days normalized serum CgA, indicating that even a short interruption of PPI therapy can solve the differential diagnostic dilemma. A 73-year-old woman with a history of hypertension and gastrooesophageal reflux disease was examined for bilateral adrenal incidentalomas revealed by ultrasonography and subsequent computed tomography (CT). Although the clinical picture did not clearly suggest endocrine disease, routine endocrinological examination was undertaken. Hypercortisolism and primary aldosteronism were excluded. Serum CgA determined by radioimmunoassay (CISBio International, Gil-Sur-Yvette, France), however, was highly elevated (728 ng/ml, normal range 18–98·1 ng/ml). By contrast, urinary catecholamine metabolites (vanillylmandelic acid, normetanephrine, metanephrine, homovanillic acid) were normal, and 131 I-metaiodobenzylguanidine (MIBG) scintigraphy was also negative. Abdominal MRI showed that the signal intensities of bilateral adrenal tumours were different from those seen in phaeochromocytomas. 3 Serum creatinine and blood urea nitrogen were normal. As the patient had been treated with PPI for at least 8 years (omeprazole, and presently lansoprazole in a daily dose of 2 × 30 mg), iatrogenic elevation of CgA was suspected. To solve the serious differential diagnostic problem, we decided to suspend PPI therapy and replace it with sucralphate (4 × 1 g/day). Serum CgA returned to normal within 5 days (Fig. 1), and after a single dose (30 mg) of lansoprazole it increased again above the upper normal limit (132·4 ng/ml). Immunohistochemical analysis for CgA in mucosal biopsy samples from the gastric corpus indicated mild, simple (diffuse), enterochromaffin cell-like (ECL) hyperplasia. Although our patient did not present symptoms characteristic of phaeochromocytoma, suspicion was raised because of the highly elevated CgA together with the history of hypertension. As all other diagnostic examinations characteristic of phaeochromocytoma were negative, the possibility of PPI-related CgA elevation was raised. Short-, mediumand long-term PPI therapy has been shown to raise serum CgA. 4,5 Giusti et al . described the elevation of CgA in response to short-term (5–90 days) PPI therapy. 4 Our observation showing that a single dose of PPI may raise CgA above normal also supports a high sensitivity of serum CgA to PPI therapy. Elevation of CgA, however, was unusually high in the case presented. Available literature describes CgA levels up to 400 ng/ml (approx. 8 n m ), even after long-term PPI therapy. 5