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Review Series - Recent Advances in the Management of Secondary Hypertension

Recent advances in the management of pheochromocytoma and paraganglioma

Hypertension Research volume 43, pages 1141–1151 (2020)Cite this article

Abstract

Pheochromocytomas and paragangliomas (PPGLs) are rare tumors that cause refractory hypertension and hypertensive crisis. Although metastatic disease accounts for 30% of PPGLs, the diagnosis of malignancy is difficult without the presence of metastatic lesions. Here, we review several advancements in the diagnosis and treatment of PPGL. A nationwide epidemiological survey in Japan revealed that the annual number of patients with PPGL was 3000, which was higher than that reported previously. While plasma and urine fractionated metanephrines are recommended for use in specific biochemical testing for diagnosis, creatinine-corrected fractionated metanephrines in spot urine samples that had been widely used in Japan as a convenient screening test were shown to be as useful as 24-h urine fractionated metanephrines. Regarding imaging studies, a more specific functional imaging for PPGLs, 68Ga DOTATATE, was newly developed. 68Ga DOTATATE provides a clear image with high sensitivity and specificity. Currently, PASS or GAPP histological scores and SDHB immunostaining are clinically used to attempt to discriminate benign from malignant tumors. However, since this distinguishing process remains difficult, all cases were classified as malignant with the possibility of metastasis in the WHO classification of endocrine tumors updated in 2017. Approximately 60% of PPGLs have germline mutations in PPGL-related genes. Currently, the genes are classified into two clusters based on their mechanism for the etiology of tumorigenesis. Based on the possible mechanisms of tumor development associated with gene mutations, several molecular target drugs are under evaluation to explore more promising treatments for malignant PPGL.

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Acknowledgements

We thank the PHEO-J study members and ACPA-J study members for their collaboration. We also thank Keiko Umegaki for supporting our study as a member of the secretariat. This study was supported in part by grants-in-aid from the National Center for Global Health and Medicine, Japan (27-1402 and 30-1008); the Japan Rare Adrenal Diseases Study (JRAS) of the Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development (AMED) (JP17ek0109122 and JP20ek0109352); and Pheochromocytoma (PHEO-J) of the Research on Measures for Intractable Diseases from the Ministry of Health, Labour and Welfare, Japan and Health and Labor Sciences Research Grants (H29-046).

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  1. Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan

    Akiyo Tanabe

  2. Clinical Research Institute of Endocrinology and Metabolism, NHO Kyoto Medical Center, Kyoto, Japan

    Mitsuhide Naruse

  3. Endocrine Center, Ijinkai Takeda General Hospital, Kyoto, Japan

    Mitsuhide Naruse

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Tanabe, A., Naruse, M. Recent advances in the management of pheochromocytoma and paraganglioma. Hypertens Res 43, 1141–1151 (2020). https://doi.org/10.1038/s41440-020-0531-0

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