SHDB mutant functional metastatic paraganglioma: The efficacy of Lutetium-177 DOTATE
Authors: Erturk Banu , Tuncel Murat , Orhan Diclehan , Turer Ozlem Bozbeyi , Dizdar Omer , Sendur Suleyman Nahit 
Published: January 2023

Abstract

Introduction
Therapeutic options for metastatic paraganglioma (PGL) are limited, especially in the presence of uncontrolled secondary hypertension (HTN). Early findings from Lutetium-177 (Lu-177) DOTATE show promise for efficacy, although data on HTN control and survival are uncertain. Herein, we presented the successful treatment of a patient with metastatic PGL and uncontrolled HTN with Lu-177 DOTATE.

Clinical Case
A 16-year-old woman was admitted to the emergency department with severe headache, nausea and vomiting. She also reported stomach and low back pain for three months. The patient's blood pressure was 220/140 mmHg and a sodium nitroprusside infusion was started to treat the hypertensive crisis. On physical examination she had abdominal tenderness. A computer tomography (CT) examination revealed 6 cm mass, multiple metastatic nodular lesions in the lung and liver, as well as lytic lesions in all bones, and metastatic lymph nodes in thorax and abdomen. She is referred to our department for further evaluation HTN. Laboratory examinations revealed that plasma norepinephrine 24926 ng/L (70–480), 24-hour urine norepinephrine 1335 µg/day (20–81), metanephrine 534 µg/day (52–341), 3-metoksitiramine 771 µg/day (0–451), normetanephrine 20456 µg/day (88–444). Other laboratory findings were normal range. MIBG I131 scan which showed pathological uptake of MIBG was demonstrated in the regions described on CT. Genetic panel by next-generation sequencing (NGS) identify germline mutation and she had heterozygous mutations in SHDB (c.725 G&gt;A) and BUB1B (c.1378 C&gt;T). Surgical treatment was performed, and pathological finding reported 6cm mass, Ki-67 labeling index: %2, chromogranin A diffuse positive and there was vascular invasion. It was confirmed to be malignant PGL. 131I-MIBG therapy couldn't be given because of drugs interaction that used by patient. She received 13 cycles chemotherapy (cyclophosphamide, vincristine, dacarbazine) and palliative radiotherapy to metastatic bone lesions. She continued, however, to suffer from low back pain and HTN. Rising plasma and urine catecholamine levels. Therefore, conventional chemotherapy had been discontinued and he was commenced on Lu-DOTATATE therapy. Up to now, she has received 2 cycles at intervals of three months. Her clinical response was excellent with gradual improvement of symptoms and quality of life. Blood pressure is now within normal values without medication. There was significant reduction in the size of overall metastatic disease on Ga-68 DOTATE scanning.

Conclusion
Lu-177 DOTATE has potential advantages (drug interaction, radiation-safety) compared with 131I-MIBG therapy and chemotherapy. Our case demonstrates significant clinical and biochemical success in patients with metastatic PGL in addition to excellent disease management with low toxicity from PRRT. Lu-177 DOTATATE therapy is an effective and safe modality of treatment for patients with metastatic PGL.