International consensus statement on the diagnosis and management of phaeochromocytoma and paraganglioma in children and adolescents.

Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours that arise not only in adulthood but also in childhood and adolescence. Up to 70-80% of childhood PPGL are hereditary, accounting for a higher incidence of metastatic and/or multifocal PPGL in paediatric patients than in adult patients. Key differences in the tumour biology and management, together with rare disease incidence and therapeutic challenges in paediatric compared with adult patients, mandate close expert cross-disciplinary teamwork.

Steroidomics-Based Screening for Primary Aldosteronism: Impact of antihypertensive Drugs.

Background: Diagnosis of primary aldosteronism (PA) is complicated by the need to withdraw antihypertensive medications that interfere with test results, particularly renin. This study examined whether machine learning-based steroid-probability scores offer a renin measurement-independent approach for testing less prone to interference than the aldosterone-to-renin ratio (ARR).

Methods: This prospective multicenter cohort study involved the use of plasma steroidomics and the ARR in 839 patients tested for PA, including 190 with and 578 without PA (71 indeterminate).

Patient-reported burden associated with pheochromocytoma/paraganglioma diagnosis.

Pheochromocytoma and paragangliomas (PPGLs) originate from the chromaffin cells of the adrenal medulla or neural crest progenitors outside the adrenal gland, respectively. The estimated annual incidence of PPGL is between 2.0 and 8.

Screening for Primary Aldosteronism by Mass Spectrometry Versus Immunoassay Measurements of Aldosterone: A Prospective Within-Patient Study.

Background: Measurements of aldosterone by mass spectrometry are more accurate and less prone to interferences than immunoassay measurements, and may produce a more accurate aldosterone:renin ratio (ARR) when screening for primary aldosteronism (PA).

Methods: Differences in diagnostic performance of the ARR using mass spectrometry vs immunoassay measurements of aldosterone were examined in 710 patients screened for PA. PA was confirmed in 153 patients and excluded in 451 others.

Imaging of Pheochromocytomas and Paragangliomas.

Pheochromocytomas/paragangliomas are unique in their highly variable molecular landscape driven by genetic alterations, either germline or somatic. These mutations translate into different clusters with distinct tumor locations, biochemical/metabolomic features, tumor cell characteristics (eg, receptors, transporters), and disease course. Such tumor heterogeneity calls for different imaging strategies in order to provide proper diagnosis and follow-up.

Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement.

Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time.

Catecholamine-induced hypertensive crises: current insights and management.

Phaeochromocytomas and paragangliomas (PPGLs) release catecholamines leading to catecholamine-induced hypertensive (CIH) crises, with blood pressure greater than or equal to 180/120 mm Hg. CIH crises can be complicated by tachyarrhythmias, hypotension, or life-threatening target organ damage while treatment remains undefined, often requiring co-management between endocrinologists and cardiologists. Furthermore, biochemical diagnosis of a PPGL as a cause of a CIH crisis can be difficult to identify or confounded by comorbid conditions, potentially resulting in misdiagnosis.

Plasma Metanephrines Yield Fewer False-Positive Results Than Urine Metanephrines in Patients With Obstructive Sleep Apnea.

Context: Obstructive sleep apnea (OSA) is associated with increased nocturnal sympathetic activity. In OSA patients, elevations in metanephrines may lead to false-positive tests when evaluating for pheochromocytoma or paraganglioma (PPGL).

Objective: To evaluate whether morning plasma metanephrines would lead to fewer false-positive results than 24-hour urinary metanephrines in OSA patients.

Prediction of metastatic pheochromocytoma and paraganglioma: a machine learning modelling study using data from a cross-sectional cohort.

Background: Pheochromocytomas and paragangliomas have up to a 20% rate of metastatic disease that cannot be reliably predicted. This study prospectively assessed whether the dopamine metabolite, methoxytyramine, might predict metastatic disease, whether predictions might be improved using machine learning models that incorporate other features, and how machine learning-based predictions compare with predictions made by specialists in the field.

Methods: In this machine learning modelling study, we used cross-sectional cohort data from the PMT trial, based in Germany, Poland, and the Netherlands, to prospectively examine the utility of methoxytyramine to predict metastatic disease in 267 patients with pheochromocytoma or paraganglioma and positive biochemical test results at initial screening.

Clinical consensus guideline on the management of phaeochromocytoma and paraganglioma in patients harbouring germline SDHD pathogenic variants.

Patients with germline SDHD pathogenic variants (encoding succinate dehydrogenase subunit D; ie, paraganglioma 1 syndrome) are predominantly affected by head and neck paragangliomas, which, in almost 20% of patients, might coexist with paragangliomas arising from other locations (eg, adrenal medulla, para-aortic, cardiac or thoracic, and pelvic). Given the higher risk of tumour multifocality and bilaterality for phaeochromocytomas and paragangliomas (PPGLs) because of SDHD pathogenic variants than for their sporadic and other genotypic counterparts, the management of patients with SDHD PPGLs is clinically complex in terms of imaging, treatment, and management options. Furthermore, locally aggressive disease can be discovered at a young age or late in the disease course, which presents challenges in balancing surgical intervention with various medical and radiotherapeutic approaches.

Biochemical Assessment of Pheochromocytoma and Paraganglioma.

Pheochromocytoma and paraganglioma (PPGL) require prompt consideration and efficient diagnosis and treatment to minimize associated morbidity and mortality. Once considered, appropriate biochemical testing is key to diagnosis. Advances in understanding catecholamine metabolism have clarified why measurements of the O-methylated catecholamine metabolites rather than the catecholamines themselves are important for effective diagnosis.

Silent pheochromocytoma and paraganglioma: Systematic review and proposed definitions for standardized terminology.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with heterogeneous clinical presentations and potential lethal outcomes. The diagnosis is based on clinical suspicion, biochemical testing, imaging and histopathological confirmation. Increasingly widespread use of imaging studies and surveillance of patients at risk of PPGL due to a hereditary background or a previous tumor is leading to the diagnosis of these tumors at an early stage.

Cardiac Phenotypes in Secondary Hypertension: JACC State-of-the-Art Review.

Several forms of secondary hypertension carry a high risk of cardiac morbidity and mortality. Evaluation of cardiac phenotypes in secondary hypertension provides a unique opportunity to study underlying hormonal and biochemical mechanisms affecting the heart. We review the characteristics of cardiac dysfunction in different forms of secondary hypertension and clarify the mechanisms behind the higher prevalence of heart damage in these patients than in those with primary hypertension.

Recurrent Disease in Patients With Sporadic Pheochromocytoma and Paraganglioma.

Context: Long-term follow-up has been recommended for patients with pheochromocytoma or paraganglioma (PPGL) due to potential for recurrent disease. However, the need to follow patients with sporadic PPGL has recently become controversial.

Objective: To investigate the prevalence of recurrence among patients with sporadic compared with hereditary PPGL and to identify predictors of recurrence for sporadic disease.

Integration of artificial intelligence and plasma steroidomics with laboratory information management systems: application to primary aldosteronism.

Objectives: Mass spectrometry-based steroidomics combined with machine learning (ML) provides a potentially powerful approach in endocrine diagnostics, but is hampered by limitations in the conveyance of results and interpretations to clinicians. We address this shortcoming by integration of the two technologies with a laboratory information management systems (LIMS) model.

Methods: The approach involves integration of ML algorithm-derived models with commercially available mathematical programming software and a web-based LIMS prototype.

Metastatic pheochromocytoma and paraganglioma: signs and symptoms related to catecholamine secretion.

Background: The presence or future development of metastatic pheochromocytomas or paragangliomas (mPPGLs) can be difficult to diagnose or predict at initial presentation. Since production of catecholamines from mPPGLs is different from non-metastatic tumors (non-mPPGLs), this study aimed to clarify whether presenting catecholamine-related signs and symptoms (cSS) might also differ.

Methods: The study included 249 patients, 43 with mPPGL and 206 with non-mPPGL.

The Saline Infusion Test for Primary Aldosteronism: Implications of Immunoassay Inaccuracy.

Context: Diagnosis of primary aldosteronism (PA) for many patients depends on positive results for the saline infusion test (SIT). Plasma aldosterone is often measured by immunoassays, which can return inaccurate results.

Objective: This study aimed to establish whether differences in aldosterone measurements by immunoassay versus mass spectrometry (MS) might impact confirmatory testing for PA.

Plasma Steroid Profiling in Patients With Adrenal Incidentaloma.

Context: Most patients with adrenal incidentaloma have nonfunctional lesions that do not require treatment, while others have functional or malignant tumors that require intervention. The plasma steroid metabolome may be useful to assess therapeutic need.

Objective: This work aimed to establish the utility of plasma steroid profiling combined with metanephrines and adrenal tumor size for the differential diagnosis of patients with adrenal incidentaloma.

Circulating adrenomedullin and B-type natriuretic peptide do not predict blood pressure fluctuations during pheochromocytoma resection: a cross-sectional study.

Background: Despite adequate presurgical management, blood pressure fluctuations are common during resection of pheochromocytoma or sympathetic paraganglioma (PPGL). To a large extent, the variability in blood pressure control during PPGL resection remains unexplained. Adrenomedullin and B-type natriuretic peptide, measured as MR-proADM and NT-proBNP, respectively, are circulating biomarkers of cardiovascular dysfunction.