DIPEPTIDYLE PEPTIDASE 4 INHIBITOR ADMINISTRATION UNVEILS UNDERLYING PHEOCHROMOCYTOMA

Objective: Studies indicate that there is a correlation between dipeptidyle peptidase 4 (DPP4) inhibition and elevation of catecholamine and neuropeptide Y (NPY) 1-36 serum levels. Especially in patients treated with angiotensin-1 (AT1) or angiotensin converting enzyme inhibitors, a substance P receptor-dependent mechanism has been proposed for that. The following case report aims to showcase how this observation applied to a patient with an underlying pheochromocytoma, a tumor characterized by excessively producing and secreting cateholamines. Design and method: 53-year-old female patient with vomiting symptoms is admitted to hospital due to metabolic acidosis of elevated anion gap (pH 7,31) and acute kidney injury. Clinically, systolic blood pressure (SBP) between 140 and 180 mmHg despite treatment with AT1 inhibitor, as well as bilateral erythrodermia of the upper extremities was noticed. Arterial hypertension, an unilateral right-sided adrenal nodule with normal hormonal control 3 months before admission, and diabetes mellitus (DM) first diagnosed only 3 days before admission, under sitagliptin and metformin are referred from the patient’s medical record. Given the objective described above, it was suspected that a marginal pheochromocytoma might have got boosted by the administration of sitagliptin in this specific patient. Therefore, patient’s treatment was modified, with discontinuation of both AT1-inhibitor and metformin – sitagliptin combination, and initiation of calcium antagonist and insulin administration as well as intravenous hydration. As a result, both clinical and laboratory findings were corrected and the patient was dismissed. Reintroduction of sitagliptin led to a relapse of the patient’s symptoms, and therefore it was completely interrupted. A new hormonal control of the adrenal nodule was conducted. Results: Elevated blood and urine catecholamine values in this new test led to the nodule being confirmed as a malignant pheochromocytoma through a 18-fluorodexyglucose pozitrone emission/computer tomography (18-FDG PET/CT). Excision of the pheochromocytoma led to total remission of both arterial hypertension, and diabetes mellitus. Conclusions: It is indicated that catecholamine secretion increase induced by DPP-4 inhibitors can stimulate underlying marginal pheochromocytomas and their clinical manifestation, with further concerns raised about heart failure risk increase, even if DPP-4 inhibitors seem beneficial in terms of post-prandial blood pressure.