LITERATURE UPDATE
phaeochromocytoma or paraganglioma (PPGL). Barriers to accessing genetics evaluation are incompletely understood, and therefore the objective of this study was to identify individual- and provider-level barriers to genetic testing.
The was a retrospective study of patients with PPGL who underwent resection at a tertiary academic centre. Study outcomes included referral rates for genetic counselling and completion of germline testing.
Of 224 patients who underwent
resection of PPGL, 75% were referred for genetic counselling, and 49% completed testing. Genetic testing was highest after 2019. More individuals 50 years or younger underwent testing compared to over 50 (65% vs. 37%, P<0.001). Medicare insurance was associated with lower rates of testing compared to commercial insurances (32% vs. 64%, P=0.006). Controlling for individual and temporal factors, head and neck paragangliomas were least likely to undergo genetic testing (odds ratio [OR] 0.13, 95% confidence interval [CI]: 0.05–0.31). Reasons for not undergoing testing included insurance denial, time constraints, and patient uncertainty. Twenty-two percent (14/68) of patients with phaeochromocytoma had a positive finding (FH, MSH3, MUTYH, NF1, RET, SDHD and VHL), while 46% (19/41) of patients with paraganglioma had a positive finding (MSH6, SDHA, SDHB, SDHD, TMEM127 and VHL). Germline testing was performed in less than half of patients with PPGL, and 30% who underwent testing carried a pathogenic mutation, reinforcing the importance of genetics evaluation. Older age, Medicare coverage, and head and neck paragangliomas were associated with lower rates of genetic testing, presenting opportunities to improve education and equity in the management of patients with PPGL.
A Laboratory Medicine Perspective on the Investigation of Phaeochromocytoma and Paraganglioma Boot CS. Diagnostics (Basel). 2023 Sep 13; 13 (18): 2940. doi: 10.3390/ diagnostics13182940.
Phaeochromocytomas (PC) and sympathetic paragangliomas (PGL) are potentially malignant tumours arising from the adrenal medulla (PC) or elsewhere in the sympathetic nervous system (PGL). These tumours usually secrete catecholamines and are
58 Superior surface of kidney Medulla
Depiction of location of adrenal glands, showing a cross section of gland cortex, including connective tissue capsule, zona glomerulosa, zona fasciculata, and zona reticularis, and central medulla.
associated with significant morbidity and mortality, so accurate and timely diagnosis is essential. The initial diagnosis of
phaeochromocytoma/paraganglioma (PPGL) is often dependent on biochemical testing. There is a range of pre-analytical, analytical and post- analytical factors influencing the analytical and diagnostic performance of biochemical tests for PPGL. Pre-analytical factors include patient preparation, sample handling and choice of test. Analytical factors include choice of methodology and the potential for analytical interference from medications and other compounds. Important factors in the post-analytical phase include provision of appropriate reference ranges, an understanding of the potential effects of various medications on metanephrine concentrations in urine and plasma, and a consideration of PPGL prevalence in the patient population being tested. This article reviews these pre-analytical, analytical and post-analytical factors that must be understood in order to provide effective laboratory services for biochemical testing in the diagnosis of PPGL.
Metastatic Pheochromocytomas and Abdominal Paragangliomas Granberg D, Juhlin CC, Falhammar H. J Clin Endocrinol Metab. 2021 Apr 23; 106 (5): e1937–e1952. doi: 10.1210/clinem/dgaa982.
Phaeochromocytomas and paragangliomas (PPGLs) are believed to harbour malignant potential; about 10% to 15% of phaeochromocytomas and up to 50% of abdominal paragangliomas will exhibit metastatic behaviour. Extensive searches in the PubMed database with various combinations of the key words pheochromocytoma,
paraganglioma, metastatic, malignant, diagnosis, pathology, genetic, and treatment were the basis for the present review. To pinpoint metastatic potential in PPGLs is difficult, but nevertheless crucial for the individual patient to receive tailor- made follow-up and adjuvant treatment following primary surgery. A combination of histological workup and molecular predictive markers can possibly aid the clinicians in this aspect.
Most patients with PPGLs have localised disease and may be cured by surgery. Plasma metanephrines are the main biochemical tests. Genetic testing is important, both for counselling and prognostic estimation. Apart from computed tomography and magnetic resonance imaging, molecular imaging using 68Ga-DOTATOC/DOTATATE should be performed. 123I-MIBG scintigraphy may be performed to determine whether 131I-MIBG therapy is a possible option. As first-line treatment in patients with metastatic disease, 177Lu- DOTATATE or 131I-MIBG is recommended, depending on which shows best expression. In patients with very low proliferative activity, watch-and-wait or primary treatment with long-acting somatostatin analogues may be considered. As second-line treatment, or first-line in patients with high proliferative rate, chemotherapy with temozolomide or cyclophosphamide + vincristine + dacarbazine is the therapy of choice. Other therapies, including sunitinib, cabozantinib, everolimus, and PD-1/PDL- 1 inhibitors, have shown modest effect. Metastatic PPGLs need individualised management and should always be discussed in specialised and interdisciplinary tumour boards. Further studies and newer treatment modalities are urgently needed.
DECEMBER 2025
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Connective tissue capsule
Zona Adrenal gland Cortex
glomerulosa Zona
fasciculata
Zona reticularis
EdgarasLe, CC BY-SA 4.0 / Wikimedia Commons
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