Gestational diastolic hypertension with gene mutation-related pheochromocytoma positive at (18)F-DOPA PET/CT: Diagnostic and therapeutic implications.

A 38-year-old woman referred to the hypertension centre of Rovigo Hospital in January 2012 for uncontrolled hypertension despite treatment with long-acting nefidipine (30mg once daily). She reported a history of gestational diastolic hypertension, arose during her three pregnancies, respectively in 2004, 2007 and 2008. In 2008, during the latter pregnancy, abdominal ultrasound performed for suspected cholelithiasis incidentally detected a right adrenal mass. The patient denied symptoms attributable to hyper- 17 tensive crisis. In 2009 a magnetic resonance imaging (MRI) was performed, showing a solid right adrenal lesion (Fig. 1a), with oval shape and sharp margins. Twenty-four-hour urinary catecholamines, 24-h cortisoluria, renin and aldosterone serum levels were normal. In 2012 a positron emission tomography (PET)with the radiolabelled amino acid-based radiopharmaceutical L-6-[18F]fluoro-3,4-25 dihydroxyphenylalanine (18F-DOPA), combined with computed tomography (CT),was performed. 18F-DOPAPET/CT images showed an oval area of increased pathological uptake of the tracer in the lodge of right adrenal gland,with axial diameter of 3.5 cmandwith maximal standardized uptake value of 40.0. Family medical history showed that the 65-year-old father of the patient was hypertensive and in 1993 underwent left adrenalectomy for a benign nodule. 33 Among the instrumental investigations carried out on the patient, 24-h ambulatory blood pressure measurement showed uncontrolled hypertension with systolic–diastolic average values of 137.2/93.6mmHg during 24 h, normal blood pressure variability, circadian rhythmwith non-dipper pattern and nocturnal hypertension, and mean heart rate of 90 bpm. No signs of cardiac, vascular or renal organ damage were detected. Among the urinary metabolites of catecholamines, a marked increase in nor-metanephrine levels was detected (5_mol/24-h, normal values 0.57–1.90). MRI and 18F-DOPA PET/CT findings enabled a diagnosis of pheochromocytoma. Further imaging studies, such as neck and pancreas ultrasonography, excluded multiple endocrine neoplasms. After anti-hypertensive treatment with amlodipine (5mg once 46 a day) and doxazosin (4mg once a day), the patient underwent right adreanalectomy via videolaparoscopy. Histological examination showed a typical pheochromocytoma of the adrenal medulla without necrosis or atypia, with compression of adjacent cortical and focal areas of recent haemorrhage. Genetic analysis showed a mutation of the associated factor X gene (MAX). MAX gene mutation, only recently identified in literature, is associated with family forms of pheochromocytoma; it is transmitted through the paternal way and appears to be associated with an increased risk of malignancy. In conclusion, pheochromocytoma is a rare catecholamine producing endocrine tumour. Even more it rarely occurs during pregnancy, but it deserves some special considerations in view of high rate of maternal and foetal mortality that in some surveys reached 40–50%.2 Early and timely diagnosis is required, as the neoplasm can be removed at any stage of pregnancy. It is there- 60 fore recommended to use evaluation of urinary metanephrines and particularly 18F-DOPA PET/CT, that allows to diagnose pheochromocytomas even when not detectable by other scintigraphic methods and with multiple spread.3 Furthermore, genetic analysis can identify some rare genetic mutations associated with family forms of pheochromocytoma, reaching early diagnosis also in the relatives, avoiding fatal complications.