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Gestational diastolic hypertension with gene mutation-related pheochromocytoma positive at 18F-DOPA PET/CT: Diagnostic and therapeutic implications
Hipertensión diastólica gestacional con feocromocitoma relacionado a mutación genética y PET/TC con 18F-DOPA positiva: implicaciones diagnósticas y terapéuticas
A. Mazzaa, M. Armigliatoa, A. Ferrettib,c, L. Schiavona, S. Zorzana, E. Casigliad, M.C. Marzolab, S. Tadayyonb, S. Chondrogiannisb, D. Rubellob,
Corresponding author
a Department of Internal Medicine, Santa Maria della Misericodia Hospital, Rovigo, Italy
b Department of Nuclear Medicine, Santa Maria della Misericodia Hospital, Rovigo, Italy
c Medical Physics Unit, Santa Maria della Misericodia Hospital, Rovigo, Italy
d Department of Medicine, Padova University, Padova, Italy
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"apellidos" => "Rubello" "email" => array:1 [ 0 => "domenico.rubello@libero.it" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Department of Internal Medicine, Santa Maria della Misericodia Hospital, Rovigo, Italy" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Nuclear Medicine, Santa Maria della Misericodia Hospital, Rovigo, Italy" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Medical Physics Unit, Santa Maria della Misericodia Hospital, Rovigo, Italy" "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Department of Medicine, Padova University, Padova, Italy" "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hipertensión diastólica gestacional con feocromocitoma relacionado a mutación genética y PET/TC con <span class="elsevierStyleSup">18</span>F-DOPA positiva: implicaciones diagnósticas y terapéuticas" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1277 "Ancho" => 3000 "Tamanyo" => 292863 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(a) Coronal T2-weighted magnetic resonance image, showing a right adrenal mass. (b) <span class="elsevierStyleSup">18</span>F-DOPA PET/CT images showing high, pathologic radiotracer uptake in a large area corresponding to the right adrenal and consistent with a pheochromocytoma. From left to right: coronal fused PET/CT image, sagittal fused PET/CT image, axial fused PET/CT image and MIP (maximum intense projection) image.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">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 (30<span class="elsevierStyleHsp" style=""></span>mg once daily). She reported a history of gestational diastolic hypertension, arose during her three pregnancies, respectively in 2004, 2007 and 2008.</p><p id="par0010" class="elsevierStylePara elsevierViewall">In 2008, during the latter pregnancy, abdominal ultrasound performed for suspected cholelithiasis incidentally detected a right adrenal mass. The patient denied symptoms attributable to hypertensive crisis.</p><p id="par0015" class="elsevierStylePara elsevierViewall">In 2009 a magnetic resonance imaging (MRI) was performed, showing a solid right adrenal lesion (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a), with oval shape and sharp margins. Twenty-four-hour urinary catecholamines, 24-h cortisoluria, renin and aldosterone serum levels were normal.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">In 2012 a positron emission tomography (PET) with the radiolabelled amino acid-based radiopharmaceutical L-6-[<span class="elsevierStyleSup">18</span>F]fluoro-3,4-dihydroxyphenylalanine (<span class="elsevierStyleSup">18</span>F-DOPA), combined with computed tomography (CT), was performed. <span class="elsevierStyleSup">18</span>F-DOPA PET/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<span class="elsevierStyleHsp" style=""></span>cm and with maximal standardized uptake value of 40.0 (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>b).</p><p id="par0025" class="elsevierStylePara elsevierViewall">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.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Among the instrumental investigations carried out on the patient, 24-h ambulatory blood pressure measurement showed uncontrolled hypertension with systolic–diastolic average values of 137.2/93.6<span class="elsevierStyleHsp" style=""></span>mmHg during 24<span class="elsevierStyleHsp" style=""></span>h, normal blood pressure variability, circadian rhythm with non-dipper pattern and nocturnal hypertension, and mean heart rate of 90<span class="elsevierStyleHsp" style=""></span>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<span class="elsevierStyleHsp" style=""></span>μmol/24-h, normal values 0.57–1.90). MRI and <span class="elsevierStyleSup">18</span>F-DOPA PET/CT findings enabled a diagnosis of pheochromocytoma. Further imaging studies, such as neck and pancreas ultrasonography, excluded multiple endocrine neoplasms.</p><p id="par0035" class="elsevierStylePara elsevierViewall">After anti-hypertensive treatment with amlodipine (5<span class="elsevierStyleHsp" style=""></span>mg once a day), doxazosin (4<span class="elsevierStyleHsp" style=""></span>mg once a day) and propranolol (40<span class="elsevierStyleHsp" style=""></span>mg three times 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.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">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%.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Early and timely diagnosis is required, as the neoplasm can be removed at any stage of pregnancy. It is therefore recommended to use evaluation of urinary metanephrines and particularly <span class="elsevierStyleSup">18</span>F-DOPA PET/CT, that allows to diagnose pheochromocytomas even when not detectable by other scintigraphic methods and with multiple spread.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> 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.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-09-07" "fechaAceptado" => "2012-09-27" "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1277 "Ancho" => 3000 "Tamanyo" => 292863 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(a) Coronal T2-weighted magnetic resonance image, showing a right adrenal mass. (b) <span class="elsevierStyleSup">18</span>F-DOPA PET/CT images showing high, pathologic radiotracer uptake in a large area corresponding to the right adrenal and consistent with a pheochromocytoma. From left to right: coronal fused PET/CT image, sagittal fused PET/CT image, axial fused PET/CT image and MIP (maximum intense projection) image.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:3 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I. Comino-Méndez" 1 => "F.J. Gracia-Aznarez" 2 => "F. Schiavi" 3 => "I. Landa" 4 => "L.J. Leandro-Garcia" 5 => "R. 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Walz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00259-012-2215-8" "Revista" => array:2 [ "tituloSerie" => "Eur J Nucl Med Mol Imaging" "fecha" => "2012" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/22538089/0000003200000002/v1_201305061041/S225380891300030X/v1_201305061041/en/main.assets" "Apartado" => array:4 [ "identificador" => "7927" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Interesting images" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/22538089/0000003200000002/v1_201305061041/S225380891300030X/v1_201305061041/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S225380891300030X?idApp=UINPBA00004N" ]
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