Monitoring for pheochromocytoma and paraganglioma in asymptomatic individuals with a predisposing genotype

Genes involved	Blood pressure, symptoms	Biochemical testing (plasma fractionated metanephrines)	MRI (skull base and neck, chest, abdomen, and pelvis)	MRI or CT of the abdomen	PET/CT or PET/MRI
SDHB^[1]	Annually	Annually, starting at age 5 years	Every 2 to 3 years, starting at age 6 years		Consider every 5 years
VHL^*[2]	Annually	Annually, starting at age 5 years		If plasma fractionated metanephrines are abnormal, and in women who are planning for pregnancy
SDHA^¶, SDHAF2^Δ, SDHC, or SDHD^Δ[1]	Annually	Annually, starting at age 10 years	Every 2 to 3 years, starting at age 10 years		Consider every 5 years
TMEM127 and MAX	Annually	Annually, starting at age 10 years		If plasma fractionated metanephrines are abnormal, and in women who are planning for pregnancy
MEN2 A and B due to RET variants^*[3]	Annually	Annually, starting at age 11 to 16 years depending on RET variant and the risk it confers for pheochromocytoma		If plasma fractionated metanephrines are abnormal, and in women who are planning for pregnancy
NF1^*[4]	Annually	Not recommended for asymptomatic patients^◊

This table summarizes monitoring of asymptomatic individuals with a pathogenic variant in SDH subunit genes (SDHA, SDHAF2, SDHB, SDHC, and SDHD, collectively known as SDHx), TMEM127, MAX, VHL disease, and MEN2 A or B due to pathogenic variants in the RET protooncogene and negative initial tumor screening. Biochemical testing and imaging may be appropriate at any age for patients with symptoms including severe hypertension.

CT: computed tomography; MEN2: multiple endocrine neoplasia type 2; MRI: magnetic resonance imaging; NF1: neurofibromatosis 1; PET: positron emission tomography; RET: rearranged during transfection; SDH: succinate dehydrogenase; VHL: von Hippel Lindau.

* Listed here are the screening studies for pheochromocytoma and paraganglioma. Screening studies for the other components of VHL disease and MEN2 are discussed elsewhere.

¶ Due to the low penetrance (approximately 10%)^[5], surveillance may not be needed^[6] or the frequency decreased in individuals with incidentally discovered SDHA pathogenic variants and no personal or family history of pheochromocytoma or paraganglioma or other SDHA-related tumors (eg, renal cell carcinoma).

Δ Due to maternal imprinting, surveillance is only indicated in individuals with paternally inherited pathogenic variants in SDHD and SDHAF2.

◊ Biochemical testing is recommended in hypertensive adults with NF1 who are >30 years of age or pregnant or have paroxysmal hypertension, hypertension-associated headache, palpitations, or sweating. Renal artery stenosis is another cause of severe hypertension in patients with NF1.

References:

Amar L, Pacak K, Steichen O, et al. International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers. Nat Rev Endocrinol 2021; 17:435
VHL Alliance. Professional Resources: VHL Surveillance Guidelines. https://www.vhl.org/healthcare-professionals/professional-resources/ (Accessed on March 18, 2024).
Stewart DR, Korf BR, Nathanson KL, et al. Care of adults with neurofibromatosis type 1: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med 2018; 20:671.
Wells SA Jr, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 2015; 25:567.
van der Tuin K, Mensenkamp AR, Tops CMJ, et al. Clinical aspects of SDHA-related pheochromocytoma and paraganglioma: A nationwide study. J Clin Endocrinol Metab. 2018; 103:438.
Hanson H, Durkie M, Lalloo F, et al. UK recommendations for SDHA germline genetic testing and surveillance in clinical practice. J Med Genet 2023; 60:107.

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Monitoring for pheochromocytoma and paraganglioma in asymptomatic individuals with a predisposing genotype