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

Reproductive Biology and Medicine Branch (H.J.L.M.T., A.K., K.T.A., D.S., K.P.), National Institute of Child Health and Human Development, Clinical Neurocardiology Section (G.E.), National Institute of Neurological Disorders and Stroke, and Laboratory of Clinical Genetics (M.R.), National Institutes of Health, Bethesda, Maryland 20892-1109; and Department of Internal Medicine (J.W.M.L.), Division of General Internal Medicine, and Department of Endocrinology (H.J.L.M.T.), Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands

Address all correspondence and requests for reprints to: Karel Pacak, M.D., Ph.D., D.Sc., Head, Section on Medical Neuroendocrinology, Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, 10 Center Drive, Building 10, CRC, Room 1-E 3140, MSC 1109, Bethesda, Maryland 20892-1109. E-mail: karel{at}mail.nih.gov.

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.

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