Exp Clin Endocrinol Diabetes 2014; 122 - P111
DOI: 10.1055/s-0034-1372128

SDHB mutation testing in metastatic pheochromocytoma and paraganglioma: Is this required in patients with adrenaline-producing tumors?

M Sue 1, V Martucci 2, F Frey 3, JWM Lenders 4, H Timmers 4, M Pęczkowska 5, M Robledo 6, K Pacak 2, G Eisenhofer 1, 3
  • 1University of Dresden, Department of Medicine III, Dresden, Germany
  • 2National Institutes of Health, Bethesda, United States
  • 3University of Dresden, Institute of Clinical Chemistry and Laboratory Medicine, Dresden, Germany
  • 4Radboud University Nijmegen Medical Center, Department of Internal Medicine, Nijmegen, Netherlands
  • 5Institute of Cardiology, Department of Hypertention, Warsaw, Poland
  • 6Spanish National Cancer Research Centre Medicine, Hereditary Endocrine Cancer Group, Madrid, Spain

Background: Testing for SDHB mutations is recommended in all patients presenting with metastatic pheochromocytomas or paragangliomas (PPGLs). However, PPGLs among patients with SDHB mutations do not produce adrenaline (Adr), suggesting testing for SDHB mutations may not be required when metastatic disease is accompanied by Adr production.

Methods: Presence of SDHB mutations or deletions was tested for by Sanger sequencing and multiplex ligand probe amplification in 186 patients (101 males) aged 41 ± 16 yr at diagnosis of metastatic PPGLs (age range, 9 to 86 yr). Plasma concentrations of normetanephrine (NMN) and metanephrine (MN) were measured in all patients at presentation of metastatic disease. Adr-producing tumors were defined by increased plasma concentrations of MN above the upper cut-offs (88 pg/mL) and with increases larger than 5% of the combined increases of both plasma NMN and MN.

Results: Twenty-two of the 186 patients (12%) with metastatic PPGLs had disease characterized by production of Adr, none of which had SDHB mutations. Of the other 165 patients with no tumoral Adr production, a much higher (P < 0.0001) proportion of 90 patients (55%) had SDHB mutations. Among all patients, 140 (75%) had metastases in bone, 74 (40%) in liver and 66 (35%) in lungs. Bone metastases were more prevalent among patients with than without SDHB mutations (85% vs. 66%, p < 0.005), and liver metastases were more prevalent among patients with adrenal than extra-adrenal primary tumors (57% vs. 31%, p = 0.0045).

Conclusions: Lack of findings of SDHB mutations in patients with Adr-producing metastatic PPGLs indicates that it is unnecessary to test for SDHB mutations among such patients. In contrast, the high prevalence of SDHB mutations in other patients with metastatic PPGLs supports recommendations that these patients should all receive SDHB mutation testing. Our data also indicate associations of patterns of metastatic spread with primary tumor location and presence of SDHB mutations.