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Clinical case
Metastatic pheochromocytoma: An unusual case and its multidisciplinary management
Feocromocitoma metastásico: un caso inusual y su manejo multidisciplinar
J.M. Ruiz-Cánovasa,
Corresponding author
jruizcanovas@salud.madrid.org

Corresponding authors.
, E.A. Achote-Reaa, T. Alonso-Gordoab, A. Martínez-Lorcac, M. Araujo-Castroa,d,
Corresponding author
marta.araujo@salud.madrid.org

Corresponding authors.
a Department of Endocrinology and Nutrition, Ramón y Cajal University Hospital, Madrid, Spain
b Department of Medical Oncology, Ramón y Cajal University Hospital, Madrid, Spain
c Department of Nuclear Medicine, Ramón y Cajal University Hospital, Madrid, Spain
d Ramón y Cajal Research Institute (IRYCIS), Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Metastatic pheochromocytomas are uncommon tumors&#46; Among all patients with pheochromocytoma&#44; approximately 10&#37; have metastatic disease and five-year overall survival ranges between 34&#37; and 60&#37;&#44; with some studies reporting 10-year overall survival rates of 25&#37;&#46; The unpredictable nature of pheochromocytomas&#44; particularly their potential for late metastasis&#44; poses ongoing challenges in patient management&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case presentation</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Chief complaints</span><p id="par0010" class="elsevierStylePara elsevierViewall">We describe the case of an 80-year-old man with sporadic right pheochromocytoma who developed metastatic disease 6 years after the initial diagnosis of pheochromocytoma&#46; The patient underwent total right adrenalectomy in June 2015 with biochemical cure criteria after surgery&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Past medical history</span><p id="par0015" class="elsevierStylePara elsevierViewall">He has type 2 diabetes mellitus&#44; dyslipidemia&#44; arterial hypertension&#44; permanent atrial fibrillation and autoimmune hypothyroidism&#46; The patient had proper blood pressure &#40;BP&#41; control with 32<span class="elsevierStyleHsp" style=""></span>mg daily of candesartan and 10<span class="elsevierStyleHsp" style=""></span>mg daily of amlodipine&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Physical and laboratory examinations</span><p id="par0020" class="elsevierStylePara elsevierViewall">In August 2021&#44; 74 months after the initial diagnosis of the pheochromocytoma&#44; an annual review detected elevated chromogranin A levels &#40;1212&#46;0<span class="elsevierStyleHsp" style=""></span>ng&#47;mL &#91;upper limit of normality &#40;ULN&#41;<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>84&#46;7&#93;&#41; with normal metanephrine levels&#46; This elevated value was initially suspected that might be related with the use of proton pump inhibitors &#40;Omeprazole&#41;&#46; The patient was asymptomatic&#44; without catecholaminergic paroxysms and with acceptable BP control&#46; Thus&#44; chromogranin A was repeated after cessation of omeprazole&#44; confirming pathological values &#40;1148&#46;0<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41;&#44; and the determination of metanephrines was found to be elevated in this second determination &#40;2496<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;24<span class="elsevierStyleHsp" style=""></span>h &#91;ULN<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>1000&#93;&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Imaging examinations</span><p id="par0025" class="elsevierStylePara elsevierViewall">Given these findings&#44; a contrast-enhanced thoraco-abdomin-pelvic CT scan was performed&#44; where new-onset hypervascular lesions were described&#44; consistent with metastatic lesions of hematogenous&#44; nodal and peritoneal dissemination&#58; bilateral pulmonary nodules &#40;the dominant one in right upper lobe of 13<span class="elsevierStyleHsp" style=""></span>mm&#41;&#44; hepatic of 11<span class="elsevierStyleHsp" style=""></span>mm in periphery of segment VI&#44; implant in right prostatic cell of 23<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>22<span class="elsevierStyleHsp" style=""></span>mm&#44; as well as adenopathies in right diaphragmatic crura of up to 27<span class="elsevierStyleHsp" style=""></span>mm&#44; low retrocrural station &#40;8<span class="elsevierStyleHsp" style=""></span>mm&#41;&#44; previous retroperitoneal lymphadenectomy bed at interaortocaval level &#40;40<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>37<span class="elsevierStyleHsp" style=""></span>mm&#41;&#44; retrocaval &#40;24<span class="elsevierStyleHsp" style=""></span>mm&#41; and right lateroconal space &#40;10<span class="elsevierStyleHsp" style=""></span>mm&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Subsequently&#44; in October 2021&#44; a thoracoabdominal SPECT-CT with metaiodobenzylguanidine-&#91;<span class="elsevierStyleSup">123</span>I&#93; MIBG was performed &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B and C&#41;&#44; displaying deposits in the surgical bed of right adrenalectomy in relation to recurrence of a chromaffin-like tumor with pulmonary and hepatic metastases and pathological retrocrural and retroperitoneal lymphadenopathies of the same nature&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Final diagnosis</span><p id="par0035" class="elsevierStylePara elsevierViewall">Finally&#44; after assessing functionality and initiating alpha-blocker treatment&#44; the diagnosis of metastatic pheochromocytoma was performed and systematic therapy was planning&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Treatment</span><p id="par0040" class="elsevierStylePara elsevierViewall">Alpha-blocker treatment was started with 4<span class="elsevierStyleHsp" style=""></span>mg of doxazosin daily&#44; achieving adequate target BP of less than 130&#47;80<span class="elsevierStyleHsp" style=""></span>mmHg and heart rate 60&#8211;70<span class="elsevierStyleHsp" style=""></span>bpm seated and 70&#8211;80<span class="elsevierStyleHsp" style=""></span>bpm standing&#46; High-sodium diet was established 2&#8211;3 days later to replenish intravascular volume&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In view of the diagnostic confirmation and distant extension&#44; unresectable and progressive&#44; systemic treatment with &#91;<span class="elsevierStyleSup">131</span>I&#93; MIBG was chosen since there was no contraindication due to excellent BP and heart rate control&#46; A single dose of 6216MBq-&#40;168<span class="elsevierStyleHsp" style=""></span>mCi&#41; was administered in December 2021&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Outcome and follow-up</span><p id="par0050" class="elsevierStylePara elsevierViewall">Regarding chromogranin A levels&#44; after this therapy&#44; there was a slight decrease to 1148 units in February 2022&#46; Subsequent measurements showed a decreasing trend&#58; 508&#46;5 units in May 2022&#44; 378&#46;8 in July 2022&#44; 197&#46;6 in January 2023&#44; 284 in August 2023&#44; and 252 units in October 2023&#46; However&#44; following treatment&#44; 24-h urine methanephrines levels increased to 3713 units in February 2022&#46; Thereafter&#44; the levels fluctuated&#58; 1470 units in May 2022&#44; 4814 in July 2022&#44; 2431 in January 2023&#44; 3345 in August 2023&#44; and 2399 units in October 2023&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Systemic therapy has meant for the patient&#58; maintenance of ability to carry out work of light or sedentary nature&#44; ambulatory but restricted in physically strenuous activities &#40;ECOG 1&#41;&#44; adequate BP control without paroxysms with 4<span class="elsevierStyleHsp" style=""></span>mg of doxazosin per day&#44; radiological stability in control CT scans &#40;last performed in August 2023&#41;&#44; without significant variations in the levels of metanephrines&#44; but a slightly reduction in chromogranin levels &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">This clinical case highlights the importance of long-term follow-up with biochemical monitoring as a vital tool for the early diagnosis of tumor recurrence of patients with pheochromocytomas&#44; having a positive impact on the prognosis of an entity with a median onset of metastasis after initial diagnosis of 5&#46;5 years &#40;range 0&#46;3&#8211;53&#46;4 years&#41; and a median age of onset of 39 years &#40;range 7&#8211;83 years&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The reported rates of recurrence &#40;local and metastatic together&#41; widely range between 6 and 22&#37;&#44; which have been independently associated with the presence of <span class="elsevierStyleItalic">succinate dehydrogenase B &#40;SDHB</span>&#41; pathogenic variant&#44; higher levels of urinary normetanephrine and a larger tumor size&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> Also&#44; this degree of extension seems to be associated with the elevation of 3-methoxytyramine and metanephrines&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Although risk factors related to recurrence have been described&#44; patients with a low probability of metastatic disease&#44; as in this case &#40;sporadic pheochromocytoma in an 80-year-old male with no other risk factors&#41; may eventually develop the disease&#46; Hence&#44; the current recommendation is a lifelong follow-up in all patients with pheochromocytomas&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">It also emphasizes the value of chromogranin A as a sensitive parameter of recurrence&#44; which can precede the increase of metanephrines in an asymptomatic patient and underlines the importance of the coordination of the different departments involved in the management of these patients&#44;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">4&#44;5</span></a> ensuring individualized therapeutic adaptation for each patient according to scientific evidence and their preferences&#44; prioritizing their quality of life and continuous care&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The focus should be placed on the evaluation from the outset on the rate of evolution of the malignant disease&#44; tumor aggressiveness&#44; control of catecholamine-dependent symptoms&#44; those associated with the mass effect of the tumor itself and the overall tumor burden&#46; Given the absence of painful bone metastases or metastases that threatened structural function&#44; local treatment with external radiotherapy or thermoablation was not offered&#44; nor was a surgical approach to reduce tumor burden&#46; Radiofrequency ablation was not considered for the 11<span class="elsevierStyleHsp" style=""></span>mm hypervascular hepatic nodule&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Following this multimodal approach&#44; attending tumor extension and unresectability&#44; systemic therapy with &#91;<span class="elsevierStyleSup">131</span>I&#93; MIBG was chosen&#44; as an option for only approximately 60&#37; of cases&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> documenting median overall and metastatic pheochromocytoma-specific survival rates of 24&#46;6 and 33&#46;7 years&#44; respectively&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">The rates of complete response&#44; partial response&#44; stable disease&#44; and progressive disease achieved by &#91;<span class="elsevierStyleSup">131</span>I&#93; MIBG are 3&#37;&#44; 27&#37;&#44; 52&#37;&#44; 18&#37;&#44; respectively&#44; and the overall effectiveness is 82&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conclusion</span><p id="par0095" class="elsevierStylePara elsevierViewall">This case serves as a poignant reminder of the unpredictable nature of pheochromocytomas and the importance of ongoing&#44; individualized monitoring&#46; The success of systemic therapy in this instance highlights the potential for improved survival rates and quality of life when tailored treatments are employed&#46; The lessons learned from this case contribute valuable insights for future patient management strategies and emphasize the need for a holistic and interdisciplinary approach to care&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflict of interests</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors state that they have no conflict of interests&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">We describe the case of an 80-year-old man with sporadic right pheochromocytoma who developed metastatic disease six years after initial diagnosis&#46; Despite adequate blood pressure control and initial biochemical cure criteria after surgery&#44; elevated chromogranin A levels were detected during routine screening&#44; which anticipated elevated 24-h urine metanephrines&#46; Subsequent imaging tests revealed metastatic lesions in the lungs&#44; liver&#44; prostate and lymph nodes&#46; The patient underwent systemic treatment with &#91;131I&#93; MIBG&#44; which resulted in a decrease in chromogranin A levels&#44; achieving radiological and clinical stability&#46; This case highlights the importance of long-term follow-up and biochemical monitoring for early detection of tumor recurrence in patients with pheochromocytoma&#44; emphasizing the need for individualized treatment strategies and interdisciplinary care&#46;</p></span>"
      ]
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se describe el caso de un hombre de 80 a&#241;os con feocromocitoma derecho espor&#225;dico que desarroll&#243; enfermedad metast&#225;sica seis a&#241;os despu&#233;s del diagn&#243;stico inicial&#46; A pesar de un adecuado control de la presi&#243;n arterial y de los criterios iniciales de curaci&#243;n bioqu&#237;mica tras la cirug&#237;a&#44; se detectaron niveles elevados de cromogranina A durante una revisi&#243;n rutinaria&#44; que anticiparon la elevaci&#243;n de metanefrinas en orina de 24 horas&#46; Las pruebas de imagen posteriores revelaron lesiones metast&#225;sicas en los pulmones&#44; el h&#237;gado&#44; la pr&#243;stata y los ganglios linf&#225;ticos&#46; El paciente fue sometido a tratamiento sist&#233;mico con &#91;<span class="elsevierStyleSup">131</span>I&#93; MIBG&#44; lo que produjo una disminuci&#243;n de los niveles de cromogranina A&#44; logrando&#44; asimsimo&#44; estabilidad cl&#237;nica y radiol&#243;gica&#46; Este caso subraya la importancia del seguimiento a largo plazo y la monitorizaci&#243;n bioqu&#237;mica para la detecci&#243;n precoz de la recurrencia tumoral en pacientes con feocromocitoma&#44; enfatizando la necesidad de estrategias de tratamiento individualizadas y atenci&#243;n interdisciplinaria&#46;</p></span>"
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                  "referenciaCompleta" => "Young WF&#46; Paraganglioma and pheochromocytoma&#58; management of malignant disease &#91;Internet&#93;&#46; In&#58; Wen PY&#44; Shah SM&#44; editors&#46; UpToDate&#59; 2023&#46; Available from&#58; <a target="_blank" href="https://www.uptodate.com/contents/paraganglioma-and-pheochromocytoma-management-of-malignant-disease?search=feocromocitoma%20metastasico%26source=search_result%26selectedTitle=1~150%26usage_type=default%26display_rank=1">https&#58;&#47;&#47;www&#46;uptodate&#46;com&#47;contents&#47;paraganglioma-and-pheochromocytoma-management-of-malignant-disease&#63;search&#61;feocromocitoma&#37;20metastasico&#38;source&#61;search&#95;result&#38;selectedTitle&#61;1&#8764;150&#38;usage&#95;type&#61;default&#38;display&#95;rank&#61;1</a> &#91;accessed 15&#46;9&#46;23&#93;&#46;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Local recurrence and metastatic disease in pheochromocytomas and sympathetic paragangliomas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Araujo-Castro"
                            1 => "I&#46; Garc&#237;a Sanz"
                            2 => "C&#46; M&#237;nguez Ojeda"
                            3 => "F&#46; Hanzu"
                            4 => "M&#46; Mora"
                            5 => "A&#46; Vicente"
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                    0 => array:2 [
                      "doi" => "10.3389/fendo.2023.1279828"
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                        "tituloSerie" => "Front Endocrinol"
                        "fecha" => "2023"
                        "volumen" => "14"
                      ]
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                    0 => array:2 [
                      "titulo" => "Prediction of metastatic pheochromocytoma and paraganglioma&#58; a machine learning modelling study using data from a cross-sectional cohort"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Pamporaki"
                            1 => "A&#46;M&#46;A&#46; Berends"
                            2 => "A&#46; Filippatos"
                            3 => "T&#46; Prodanov"
                            4 => "L&#46; Meuter"
                            5 => "A&#46; Prejbisz"
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                        "tituloSerie" => "Lancet Dig Health"
                        "fecha" => "2023"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Protocol for presurgical and anesthetic management of pheochromocytomas and sympathetic paragangliomas&#58; a multidisciplinary approach"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            2 => "L&#46; Nattero Chavez"
                            3 => "A&#46; Mart&#237;nez Lorca"
                            4 => "T&#46; Alonso-Gordoa"
                            5 => "J&#46; Molina-Cerrillo"
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                      "doi" => "10.1007/s40618-021-01649-7"
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                        "tituloSerie" => "J Endocrinol Invest"
                        "fecha" => "2021"
                        "volumen" => "44"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Surgical and postsurgical management of abdominal paragangliomas and pheochromocytomas"
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Article information
ISSN: 18891837
Original language: English
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