Clinical Presentations, Biochemical Phenotypes, and Genotype-Phenotype Correlations in Patients withSuccinate Dehydrogenase Subunit B-Associated Pheochromocytomas and Paragangliomas

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Abstract
Context: Mutations of the gene encoding succinate dehydrogenase subunit B (SDHB) predispose to malignant paraganglioma (PGL). Recognition of the SDHB phenotype in apparently sporadic PGL directs appropriate treatment and family screening. Objective: The objective of the study was to assess mutation-specific clinical and biochemical characteristics of SDHB-related PGL. Design: The study design was retrospective descriptive. Patients: Patients included 29 patients (16 males) with SDHB-related abdominal or thoracic PGL. Intervention: There was no intervention. Main Outcome Measures: Clinical presentations, plasma and urine concentrations of catecholamines and O-methylated metabolites, and genotype-phenotype correlations were measured. Results: Mean ± sd age at diagnosis was 33.7 ± 15.7 yr. Tumor-related pain was among the presenting symptoms in 54% of patients and was the sole symptom in 14%. Seventy-six percent had hypertension, and 90% lacked a family history of PGL. All primary tumors but one originated from extraadrenal locations. Mean ± sd tumor size was 7.8 ± 3.7 cm. In this referral-based study, 28% presented with metastatic disease and all but one eventually developed metastases after 2.7 ± 4.1 yr. Ten percent had additional head and neck PGLs. The biochemical phenotype was consistent with hypersecretion of both norepinephrine and dopamine in 46%, norepinephrine only in 41%, and dopamine only in 3%. Ten percent had normal catecholamine (metabolite) levels, consistent with biochemically silent PGL. No obvious genotype-phenotype correlations were identified. Conclusions:SDHB-related PGL often presents as apparently sporadic PGL with symptoms related to tumor mass effect rather than to catecholamine excess. The predominant biochemical phenotype consists of hypersecretion of norepinephrine and/or dopamine, whereas 10% of tumors are biochemically silent. The clinical expression of these tumors cannot be predicted by the genotype.