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Clinical Predictors of Pseudohypoxia-Type Pheochromocytomas

  • Endocrine Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Introduction

Pheochromocytomas (PCCs) are rare tumors of neural crest origin with divergent transcriptional and metabolic profiles associated with mutational cluster types. Pseudohypoxia-type (PHT) PCCs have a poor prognosis; however diagnostic genetic testing is not always available. We aimed to investigate clinical parameters predictive of PHT PCCs.

Methods

Patients who underwent resection and genetic testing for PCC at two academic centers from 2006–2020 were retrospectively studied. Patients with PHT mutations (SDH-AF2/B/C/D, VHL) were compared to non-pseudohypoxia-type (nonPHT) PCCs to identify widely available clinical parameters predictive of PHT PCCs. Demographic, clinical, and pathologic characteristics were compared using student’s T and ANOVA tests. Operative hemodynamic instability was defined as systolic blood pressure (SBP) >  200 mmHg, SBP increase of >  30% relative to baseline, and/or heart rate (HR) > 110 bpm. Mann–Whitney U test was used to assess area under the curve (AUC), sensitivity, and specificity. Recursive partitioning was used to model predictive thresholds for PHT PCC and develop a predictive score.

Results

Of the 79 patients included in the cohort, 17 (22%) had PHT and 62 (78%) had nonPHT PCCs. PCC patients with >  2 of the examined predictive clinical parameters (preoperative weight loss [> 10% body weight], elevated preoperative hematocrit [>  50%], normal baseline heart rate [< 100 bpm], and normal plasma metanephrines [< 0.60 nmol/L]) were more likely to have PHT PCCs (AUC = 0.831, sensitivity = 0.882, specificity = 0.694, all p < 0.001).

Conclusions

Widely available preoperative clinical parameters including indicators of erythropoiesis (hemoglobin, hematocrit, and red blood cell count), baseline heart rate, plasma metanephrines, and weight loss may be useful predictors of PHT PCCs and may help guide management of PCCs when genetic testing is unavailable/delayed.

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Funding

NIH F32 CA236309, Burroughs Wellcome Fund Physician-Scientist Institutional Award #1018894 (to P.M.S.).

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Authors and Affiliations

  1. School of Medicine, Meharry Medical College, Nashville, TN, USA

    J. J. Baechle MD

  2. Division of Surgical Oncology and Endocrine Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

    P. Marincola Smith MD, PhD, C. C. Solórzano MD & C. M. Kiernan MD, MPH

  3. School of Medicine, Vanderbilt University, Nashville, TN, USA

    C. A. Ortega BS

  4. Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA

    T. S. Wang MD, MPH

Authors
  1. J. J. Baechle MD
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  2. P. Marincola Smith MD, PhD
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  4. T. S. Wang MD, MPH
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  5. C. C. Solórzano MD
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  6. C. M. Kiernan MD, MPH
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Correspondence to C. M. Kiernan MD, MPH.

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Previous meetings: These data were presented as a poster at American Association of Endocrine Surgeons 2021 Annual Meeting.

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Baechle, J.J., Smith, P.M., Ortega, C.A. et al. Clinical Predictors of Pseudohypoxia-Type Pheochromocytomas. Ann Surg Oncol 29, 3536–3546 (2022). https://doi.org/10.1245/s10434-022-11419-1

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