Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors arising from chromaffin cells of the adrenal medulla (pheochromocytoma) or extra-adrenal sympathetic and parasympathetic ganglia (paraganglioma). Approximately 40% of PPGLs are hereditary, caused by germline mutations in over 20 susceptibility genes including SDHx subunits (SDHA, SDHB, SDHC, SDHD), VHL, RET, NF1, MAX, and TMEM127. PPGLs may be catecholamine-secreting, causing paroxysmal hypertension, headaches, sweating, and palpitations. Understanding the genetic basis has enabled surveillance, early detection, and emerging targeted therapies for this heterogeneous tumor group.
Ask a research question about Pheochromocytoma and Paraganglioma. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).
Do not include personal health information in your question. Questions and results are cached in your browser's local storage.
name: Pheochromocytoma and Paraganglioma
creation_date: '2026-01-26T02:55:13Z'
updated_date: '2026-04-22T20:13:21Z'
description: >-
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors arising
from chromaffin cells of the adrenal medulla (pheochromocytoma) or extra-adrenal
sympathetic and parasympathetic ganglia (paraganglioma). Approximately 40% of PPGLs
are hereditary, caused by germline mutations in over 20 susceptibility genes including
SDHx subunits (SDHA, SDHB, SDHC, SDHD), VHL, RET, NF1, MAX, and TMEM127. PPGLs may
be catecholamine-secreting, causing paroxysmal hypertension, headaches, sweating,
and palpitations. Understanding the genetic basis has enabled surveillance, early
detection, and emerging targeted therapies for this heterogeneous tumor group.
categories:
- Neuroendocrine Tumor
- Hereditary Cancer Syndrome
- Adrenal Tumor
parents:
- neuroendocrine tumor
has_subtypes:
- name: Pheochromocytoma
description: >-
Tumors arising from the adrenal medulla chromaffin cells. Most common site
of catecholamine-producing paraganglioma. Usually unilateral but bilateral
in hereditary syndromes.
- name: Sympathetic Paraganglioma
description: >-
Extra-adrenal tumors arising from sympathetic ganglia along the paravertebral
axis (thorax, abdomen, pelvis). Often catecholamine-secreting. SDHB mutations
associated with high malignancy risk.
- name: Parasympathetic Paraganglioma
description: >-
Head and neck paragangliomas arising from parasympathetic ganglia (carotid
body, jugulotympanic, vagal). Usually non-secreting. SDHD mutations common.
pathophysiology:
- name: Succinate Dehydrogenase Complex Dysfunction
description: >-
Mutations in SDHx genes (SDHA, SDHB, SDHC, SDHD, SDHAF2) impair mitochondrial
complex II function, leading to succinate accumulation. Succinate acts as an
oncometabolite, inhibiting alpha-ketoglutarate-dependent dioxygenases and
causing pseudohypoxia and epigenetic dysregulation.
evidence:
- reference: PMID:33112834
reference_title: "Epigenetic and metabolic reprogramming of SDH-deficient paragangliomas."
supports: SUPPORT
snippet: "SDHx mutations lead to the accumulation of succinate, which acts as an oncometabolite by inhibiting iron(II) and alpha-ketoglutarate-dependent dioxygenases thereby regulating the cell's hypoxic response and epigenetic processes."
explanation: This abstract connects SDHx mutations to succinate accumulation and dioxygenase inhibition, matching the described mechanism.
cell_types:
- preferred_term: chromaffin cell
term:
id: CL:0000166
label: chromaffin cell
molecular_functions:
- preferred_term: succinate dehydrogenase activity
modifier: DECREASED
term:
id: GO:0000104
label: succinate dehydrogenase activity
locations:
- preferred_term: adrenal gland
term:
id: UBERON:0002369
label: adrenal gland
downstream:
- target: Pseudohypoxia and HIF Activation
description: Succinate accumulation stabilizes HIF transcription factors
- name: Pseudohypoxia and HIF Activation
description: >-
SDHx and VHL mutations cause constitutive stabilization of hypoxia-inducible
factors (HIF1/2) under normoxic conditions. This pseudohypoxic state activates
genes promoting angiogenesis, glycolysis, and cell survival, driving
tumorigenesis.
biological_processes:
- preferred_term: response to hypoxia
modifier: INCREASED
term:
id: GO:0001666
label: response to hypoxia
- name: RET Proto-Oncogene Activation
description: >-
Germline RET mutations in MEN2 syndrome cause pheochromocytoma through
constitutive receptor tyrosine kinase activation. RET-driven pheochromocytomas
have distinct catecholamine profiles (epinephrine-predominant) compared to
SDHx-related tumors.
molecular_functions:
- preferred_term: protein tyrosine kinase activity
term:
id: GO:0004713
label: protein tyrosine kinase activity
- name: Catecholamine Hypersecretion
description: >-
Secreting PPGLs produce excess catecholamines (norepinephrine, epinephrine,
dopamine), causing characteristic symptoms. The catecholamine profile provides
clues to underlying genetics: norepinephrine-predominant suggests SDHx/VHL,
epinephrine-predominant suggests RET/NF1.
evidence:
- reference: PMID:32617052
reference_title: "Pheochromocytoma and Paraganglioma: From Epidemiology to Clinical Findings."
supports: SUPPORT
snippet: "The majority of PCC and sympathetic PGL are endocrine active tumors causing clinical symptoms by secreting excess catecholamines (norepinephrine, epinephrine, dopamine) and their metabolites."
explanation: "Abstract notes catecholamine-secreting tumors causing clinical symptoms."
biological_processes:
- preferred_term: catecholamine biosynthetic process
modifier: INCREASED
term:
id: GO:0042423
label: catecholamine biosynthetic process
histopathology:
- name: Neuroendocrine Tumor
finding_term:
preferred_term: Neuroendocrine Tumor
term:
id: NCIT:C188218
label: Neuroendocrine Tumor
frequency: VERY_FREQUENT
description: Pheochromocytomas and paragangliomas are rare neuroendocrine tumors.
evidence:
- reference: PMID:32617052
reference_title: "Pheochromocytoma and Paraganglioma: From Epidemiology to Clinical Findings."
supports: SUPPORT
snippet: "Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors."
explanation: Abstract characterizes PCC/PGL as rare neuroendocrine tumors.
phenotypes:
- category: Cardiovascular
name: Hypertension
frequency: VERY_FREQUENT
diagnostic: true
description: >-
Paroxysmal or sustained hypertension due to catecholamine excess. Episodes
may be precipitated by physical activity, anesthesia, or certain medications.
evidence:
- reference: PMID:17156452
reference_title: "Pheochromocytomas and secreting paragangliomas."
supports: SUPPORT
snippet: "An increase in the production of catecholamines causes symptoms (mainly headaches, palpitations and excess sweating) and signs (mainly hypertension, weight loss and diabetes) reflecting the effects of epinephrine and norepinephrine on alpha- and beta-adrenergic receptors."
explanation: "Abstract lists hypertension among catecholamine-related signs."
phenotype_term:
preferred_term: Hypertension
term:
id: HP:0000822
label: Hypertension
- category: Neurological
name: Headache
frequency: VERY_FREQUENT
description: >-
Severe headaches during hypertensive episodes are a classic symptom of
catecholamine excess.
phenotype_term:
preferred_term: Headache
term:
id: HP:0002315
label: Headache
- category: Cardiovascular
name: Palpitations
frequency: VERY_FREQUENT
description: >-
Tachycardia and palpitations during catecholamine surges. May be associated
with arrhythmias.
phenotype_term:
preferred_term: Palpitations
term:
id: HP:0001962
label: Palpitations
- category: Constitutional
name: Diaphoresis
frequency: FREQUENT
description: >-
Excessive sweating during hypertensive paroxysms is a classic feature
of pheochromocytoma.
phenotype_term:
preferred_term: Hyperhidrosis
term:
id: HP:0000975
label: Hyperhidrosis
biochemical:
- name: Plasma Metanephrines
notes: >-
Plasma-free metanephrines (normetanephrine and metanephrine) are the most
sensitive test for pheochromocytoma. Methoxytyramine elevation suggests
dopamine-secreting or malignant tumor.
- name: Urinary Catecholamines and Metanephrines
notes: >-
24-hour urine collection for catecholamines and metanephrines is an
alternative biochemical test with high sensitivity.
genetic:
- name: SDHB
association: Germline Loss-of-Function Mutations
inheritance:
- name: Autosomal Dominant
notes: >-
SDHB mutations are associated with extra-adrenal sympathetic paraganglioma
and high malignancy risk (30-40%). Lifelong surveillance required.
evidence:
- reference: PMID:15328326
supports: SUPPORT
snippet: "SDHB mutation carriers have an increased frequency of malignant disease (11/32 vs 0/34, P<.001)."
explanation: JAMA study demonstrating significantly increased malignancy risk in SDHB mutation carriers compared to SDHD.
- name: SDHD
association: Germline Loss-of-Function Mutations
inheritance:
- name: Autosomal Dominant
notes: >-
SDHD mutations cause hereditary paraganglioma syndrome with predisposition
to head and neck paragangliomas. Parent-of-origin effect with disease
expression only with paternal transmission.
evidence:
- reference: PMID:15328326
supports: SUPPORT
snippet: "Head and neck paragangliomas (10/32 vs 27/34, respectively, P<.001) and multifocal (9/32 vs 25/34, respectively, P<.001) tumors were more frequent in carriers of SDHD mutations."
explanation: JAMA study demonstrating SDHD mutations predispose to head and neck and multifocal paragangliomas.
- name: VHL
association: Germline Loss-of-Function Mutations
inheritance:
- name: Autosomal Dominant
notes: >-
VHL mutations cause von Hippel-Lindau syndrome with pheochromocytoma risk
of 10-20%. Associated with clear cell renal cell carcinoma and other tumors.
- name: RET
association: Germline Activating Mutations
inheritance:
- name: Autosomal Dominant
notes: >-
RET mutations in MEN2 syndrome cause pheochromocytoma in approximately
50% of MEN2A and most MEN2B patients. Typically bilateral and benign.
evidence:
- reference: PMID:32388798
supports: SUPPORT
snippet: "Multiple endocrine neoplasia type 2 (MEN2) is a rare hereditary syndrome due to mutations of the proto-oncogene REarranged during Transfection (RET), defined by the association of medullary thyroid carcinoma (MTC) in almost 100% cases, and pheochromocytoma in roughly 50%"
explanation: Review establishing RET mutations in MEN2 cause pheochromocytoma in approximately 50% of patients.
- name: NF1
association: Germline Loss-of-Function Mutations
inheritance:
- name: Autosomal Dominant
notes: >-
Neurofibromatosis type 1 is associated with pheochromocytoma in approximately
1-5% of patients. Usually unilateral and benign.
treatments:
- name: Surgical Resection
description: >-
Complete surgical resection is the primary treatment for localized PPGL.
Requires careful preoperative alpha-blockade followed by beta-blockade to
prevent perioperative hypertensive crisis.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
evidence:
- reference: PMID:24893135
supports: SUPPORT
snippet: "We recommend minimally invasive adrenalectomy for most pheochromocytomas with open resection for most paragangliomas."
explanation: Endocrine Society clinical practice guideline recommending surgical resection as primary treatment.
- name: Alpha-Adrenergic Blockade
description: >-
Preoperative alpha-blockade with phenoxybenzamine or doxazosin is essential
to control hypertension and allow volume expansion before surgery.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
evidence:
- reference: PMID:24893135
supports: SUPPORT
snippet: "All patients with functional PPGLs should undergo preoperative blockade to prevent perioperative complications."
explanation: Endocrine Society guideline recommending preoperative alpha blockade for all functional PPGLs.
- name: MIBG Therapy
description: >-
131I-MIBG (metaiodobenzylguanidine) is a targeted radiotherapy for
MIBG-avid metastatic PPGL. High-specific-activity 131I-MIBG is FDA-approved.
treatment_term:
preferred_term: radiation therapy
term:
id: MAXO:0000014
label: radiation therapy
- name: Temozolomide
description: >-
Alkylating chemotherapy showing activity in metastatic PPGL, particularly
SDHB-mutated tumors with MGMT promoter methylation.
treatment_term:
preferred_term: chemotherapy
term:
id: MAXO:0000647
label: chemotherapy
- name: Sunitinib
description: >-
Multi-kinase inhibitor with antiangiogenic activity showing benefit in
progressive metastatic PPGL. Used in clinical practice despite limited
prospective data.
treatment_term:
preferred_term: targeted therapy
term:
id: NCIT:C93352
label: Targeted Therapy
therapeutic_agent:
- preferred_term: sunitinib
term:
id: CHEBI:38940
label: sunitinib
disease_term:
preferred_term: pheochromocytoma-paraganglioma
term:
id: MONDO:0035540
label: pheochromocytoma-paraganglioma
classifications:
icdo_morphology:
classification_value: Carcinoma
harrisons_chapter:
- classification_value: cancer
- classification_value: solid tumor
references:
- reference: DOI:10.1007/s00259-023-06166-8
title: 'Efficacy of [177Lu]Lu-DOTATATE in metastatic neuroendocrine neoplasms of different locations: data from the SEPTRALU study'
found_in:
- Pheochromocytoma_Paraganglioma-deep-research-falcon.md
findings:
- statement: Peptide receptor radionuclide therapy (PRRT) is one of the most promising therapeutic strategies in neuroendocrine neoplasms (NENs).
supporting_text: Peptide receptor radionuclide therapy (PRRT) is one of the most promising therapeutic strategies in neuroendocrine neoplasms (NENs).
evidence:
- reference: DOI:10.1007/s00259-023-06166-8
reference_title: 'Efficacy of [177Lu]Lu-DOTATATE in metastatic neuroendocrine neoplasms of different locations: data from the SEPTRALU study'
supports: SUPPORT
evidence_source: OTHER
snippet: Peptide receptor radionuclide therapy (PRRT) is one of the most promising therapeutic strategies in neuroendocrine neoplasms (NENs).
explanation: Deep research cited this publication as relevant literature for Pheochromocytoma Paraganglioma.
- reference: DOI:10.1007/s12020-024-03707-5
title: 'Peptide receptor radionuclide therapy with 177Lu- or 90Y-SSTR peptides in malignant pheochromocytomas (PCCs) and paragangliomas (PGLs): results from a single institutional retrospective analysis'
found_in:
- Pheochromocytoma_Paraganglioma-deep-research-falcon.md
findings:
- statement: 'Peptide receptor radionuclide therapy with 177Lu- or 90Y-SSTR peptides in malignant pheochromocytomas (PCCs) and paragangliomas (PGLs): results from a single institutional retrospective analysis'
supporting_text: 'Peptide receptor radionuclide therapy with 177Lu- or 90Y-SSTR peptides in malignant pheochromocytomas (PCCs) and paragangliomas (PGLs): results from a single institutional retrospective analysis'
- reference: DOI:10.1007/s12022-022-09746-w
title: 'TOP2A Expression in Pheochromocytoma and Abdominal Paraganglioma: a Marker of Poor Clinical Outcome?'
found_in:
- Pheochromocytoma_Paraganglioma-deep-research-falcon.md
findings:
- statement: Pheochromocytoma and abdominal paraganglioma (PPGL) are rare neuroendocrine tumors originating from chromaffin cells.
supporting_text: Pheochromocytoma and abdominal paraganglioma (PPGL) are rare neuroendocrine tumors originating from chromaffin cells.
evidence:
- reference: DOI:10.1007/s12022-022-09746-w
reference_title: 'TOP2A Expression in Pheochromocytoma and Abdominal Paraganglioma: a Marker of Poor Clinical Outcome?'
supports: SUPPORT
evidence_source: OTHER
snippet: Pheochromocytoma and abdominal paraganglioma (PPGL) are rare neuroendocrine tumors originating from chromaffin cells.
explanation: Deep research cited this publication as relevant literature for Pheochromocytoma Paraganglioma.
- reference: DOI:10.1007/s12022-024-09830-3
title: 'The Molecular Classification of Pheochromocytomas and Paragangliomas: Discovering the Genomic and Immune Landscape of Metastatic Disease'
found_in:
- Pheochromocytoma_Paraganglioma-deep-research-falcon.md
findings:
- statement: Pheochromocytomas (PCCs) and paragangliomas (PGLs, together PPGLs) are the most hereditary tumors known.
supporting_text: Pheochromocytomas (PCCs) and paragangliomas (PGLs, together PPGLs) are the most hereditary tumors known.
evidence:
- reference: DOI:10.1007/s12022-024-09830-3
reference_title: 'The Molecular Classification of Pheochromocytomas and Paragangliomas: Discovering the Genomic and Immune Landscape of Metastatic Disease'
supports: SUPPORT
evidence_source: OTHER
snippet: Pheochromocytomas (PCCs) and paragangliomas (PGLs, together PPGLs) are the most hereditary tumors known.
explanation: Deep research cited this publication as relevant literature for Pheochromocytoma Paraganglioma.
- reference: DOI:10.1038/s41467-023-36769-6
title: Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma
found_in:
- Pheochromocytoma_Paraganglioma-deep-research-falcon.md
findings:
- statement: The mechanisms triggering metastasis in pheochromocytoma/paraganglioma are unknown, hindering therapeutic options for patients with metastatic tumors (mPPGL).
supporting_text: The mechanisms triggering metastasis in pheochromocytoma/paraganglioma are unknown, hindering therapeutic options for patients with metastatic tumors (mPPGL).
evidence:
- reference: DOI:10.1038/s41467-023-36769-6
reference_title: Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The mechanisms triggering metastasis in pheochromocytoma/paraganglioma are unknown, hindering therapeutic options for patients with metastatic tumors (mPPGL).
explanation: Deep research cited this publication as relevant literature for Pheochromocytoma Paraganglioma.
- reference: DOI:10.1148/rycan.210088
title: 'Head and Neck Paragangliomas: An Update on the Molecular Classification, State-of-the-Art Imaging, and Management Recommendations'
found_in:
- Pheochromocytoma_Paraganglioma-deep-research-falcon.md
findings:
- statement: 'Head and Neck Paragangliomas: An Update on the Molecular Classification, State-of-the-Art Imaging, and Management Recommendations'
supporting_text: 'Head and Neck Paragangliomas: An Update on the Molecular Classification, State-of-the-Art Imaging, and Management Recommendations'
- reference: DOI:10.1186/s13053-024-00276-6
title: 'Current prospects of hereditary adrenal tumors: towards better clinical management'
found_in:
- Pheochromocytoma_Paraganglioma-deep-research-falcon.md
findings:
- statement: Adrenocortical carcinoma (ACC) and pheochromocytoma/paraganglioma (PPGL) are two rare types of adrenal gland malignancies.
supporting_text: Adrenocortical carcinoma (ACC) and pheochromocytoma/paraganglioma (PPGL) are two rare types of adrenal gland malignancies.
evidence:
- reference: DOI:10.1186/s13053-024-00276-6
reference_title: 'Current prospects of hereditary adrenal tumors: towards better clinical management'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Adrenocortical carcinoma (ACC) and pheochromocytoma/paraganglioma (PPGL) are two rare types of adrenal gland malignancies.
explanation: Deep research cited this publication as relevant literature for Pheochromocytoma Paraganglioma.
- reference: DOI:10.1186/s13550-023-01056-4
title: '[18F]FDOPA PET/CT is superior to [68Ga]DOTATOC PET/CT in diagnostic imaging of pheochromocytoma'
found_in:
- Pheochromocytoma_Paraganglioma-deep-research-falcon.md
findings:
- statement: Both [18F]FDOPA (FDOPA) and [68Ga]DOTATOC PET/CT (DOTATOC) are widely used for detection of pheochromocytomas/paraganglioma (PPGL).
supporting_text: Both [18F]FDOPA (FDOPA) and [68Ga]DOTATOC PET/CT (DOTATOC) are widely used for detection of pheochromocytomas/paraganglioma (PPGL).
evidence:
- reference: DOI:10.1186/s13550-023-01056-4
reference_title: '[18F]FDOPA PET/CT is superior to [68Ga]DOTATOC PET/CT in diagnostic imaging of pheochromocytoma'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Both [18F]FDOPA (FDOPA) and [68Ga]DOTATOC PET/CT (DOTATOC) are widely used for detection of pheochromocytomas/paraganglioma (PPGL).
explanation: Deep research cited this publication as relevant literature for Pheochromocytoma Paraganglioma.
- reference: DOI:10.1210/jendso/bvae038
title: Patient Sex and Origin Influence Distribution of Driver Genes and Clinical Presentation of Paraganglioma
found_in:
- Pheochromocytoma_Paraganglioma-deep-research-falcon.md
findings:
- statement: Context Sexual and ancestral differences in driver gene prevalence have been described in many cancers but have not yet been investigated in pheochromocytoma and paraganglioma (PPGL).
supporting_text: Context Sexual and ancestral differences in driver gene prevalence have been described in many cancers but have not yet been investigated in pheochromocytoma and paraganglioma (PPGL).
evidence:
- reference: DOI:10.1210/jendso/bvae038
reference_title: Patient Sex and Origin Influence Distribution of Driver Genes and Clinical Presentation of Paraganglioma
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Context Sexual and ancestral differences in driver gene prevalence have been described in many cancers but have not yet been investigated in pheochromocytoma and paraganglioma (PPGL).
explanation: Deep research cited this publication as relevant literature for Pheochromocytoma Paraganglioma.
- reference: DOI:10.1590/s1677-5538.ibju.2023.0038
title: 'The Pheochromocytoma/Paraganglioma syndrome: an overview on mechanisms, diagnosis and management'
found_in:
- Pheochromocytoma_Paraganglioma-deep-research-falcon.md
findings:
- statement: 'The Pheochromocytoma/Paraganglioma syndrome: an overview on mechanisms, diagnosis and management'
supporting_text: 'The Pheochromocytoma/Paraganglioma syndrome: an overview on mechanisms, diagnosis and management'
- reference: DOI:10.3389/fendo.2023.1279828
title: Local recurrence and metastatic disease in pheochromocytomas and sympathetic paragangliomas
found_in:
- Pheochromocytoma_Paraganglioma-deep-research-falcon.md
findings:
- statement: Local recurrence and metastatic disease in pheochromocytomas and sympathetic paragangliomas
supporting_text: To evaluate the rate of recurrence among patients with pheochromocytomas and sympathetic paragangliomas (PGLs; together PPGLs) and to identify predictors of recurrence (local recurrence and/or metastatic disease).MethodsThis retrospective multicenter study included information of 303 patients with PPGLs in follow-up in 19 Spanish tertiary hospitals.
evidence:
- reference: DOI:10.3389/fendo.2023.1279828
reference_title: Local recurrence and metastatic disease in pheochromocytomas and sympathetic paragangliomas
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: To evaluate the rate of recurrence among patients with pheochromocytomas and sympathetic paragangliomas (PGLs; together PPGLs) and to identify predictors of recurrence (local recurrence and/or metastatic disease).MethodsThis retrospective multicenter study included information of 303 patients with PPGLs in follow-up in 19 Spanish tertiary hospitals.
explanation: Deep research cited this publication as relevant literature for Pheochromocytoma Paraganglioma.
- reference: DOI:10.3389/fendo.2024.1433582
title: 'Pheochromocytoma: an updated scoping review from clinical presentation to management and treatment'
found_in:
- Pheochromocytoma_Paraganglioma-deep-research-falcon.md
findings:
- statement: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors derived from chromaffin cells, with 80–85% originating in the adrenal medulla and 15–20% from extra-adrenal chromaffin tissues (paragangliomas).
supporting_text: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors derived from chromaffin cells, with 80–85% originating in the adrenal medulla and 15–20% from extra-adrenal chromaffin tissues (paragangliomas).
evidence:
- reference: DOI:10.3389/fendo.2024.1433582
reference_title: 'Pheochromocytoma: an updated scoping review from clinical presentation to management and treatment'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors derived from chromaffin cells, with 80–85% originating in the adrenal medulla and 15–20% from extra-adrenal chromaffin tissues (paragangliomas).
explanation: Deep research cited this publication as relevant literature for Pheochromocytoma Paraganglioma.
- reference: DOI:10.3389/fendo.2024.1460320
title: Prevention and management of hypertensive crises in children with pheochromocytoma and paraganglioma
found_in:
- Pheochromocytoma_Paraganglioma-deep-research-falcon.md
findings:
- statement: Hypertensive crises in pediatric patients are rare conditions.
supporting_text: Hypertensive crises in pediatric patients are rare conditions.
evidence:
- reference: DOI:10.3389/fendo.2024.1460320
reference_title: Prevention and management of hypertensive crises in children with pheochromocytoma and paraganglioma
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Hypertensive crises in pediatric patients are rare conditions.
explanation: Deep research cited this publication as relevant literature for Pheochromocytoma Paraganglioma.
- reference: DOI:10.3390/biomedicines12102385
title: 'Pheochromocytoma–Paraganglioma Syndrome: A Multiform Disease with Different Genotype and Phenotype Features'
found_in:
- Pheochromocytoma_Paraganglioma-deep-research-falcon.md
findings:
- statement: Pheochromocytoma and paraganglioma (PPGL) are rare tumors derived from the adrenal medulla and extra-adrenal chromaffin cells.
supporting_text: Pheochromocytoma and paraganglioma (PPGL) are rare tumors derived from the adrenal medulla and extra-adrenal chromaffin cells.
evidence:
- reference: DOI:10.3390/biomedicines12102385
reference_title: 'Pheochromocytoma–Paraganglioma Syndrome: A Multiform Disease with Different Genotype and Phenotype Features'
supports: SUPPORT
evidence_source: OTHER
snippet: Pheochromocytoma and paraganglioma (PPGL) are rare tumors derived from the adrenal medulla and extra-adrenal chromaffin cells.
explanation: Deep research cited this publication as relevant literature for Pheochromocytoma Paraganglioma.
- reference: DOI:10.3390/cancers15112890
title: Long-Term Outcomes after Surgery for Pheochromocytoma and Sympathetic Paraganglioma
found_in:
- Pheochromocytoma_Paraganglioma-deep-research-falcon.md
findings:
- statement: The prognosis of pheochromocytoma and sympathetic paraganglioma (PHEO/sPGL) is difficult to predict at the time of diagnosis and long-term follow-up data are scarce, especially for apparently benign and sporadic variants.
supporting_text: The prognosis of pheochromocytoma and sympathetic paraganglioma (PHEO/sPGL) is difficult to predict at the time of diagnosis and long-term follow-up data are scarce, especially for apparently benign and sporadic variants.
evidence:
- reference: DOI:10.3390/cancers15112890
reference_title: Long-Term Outcomes after Surgery for Pheochromocytoma and Sympathetic Paraganglioma
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The prognosis of pheochromocytoma and sympathetic paraganglioma (PHEO/sPGL) is difficult to predict at the time of diagnosis and long-term follow-up data are scarce, especially for apparently benign and sporadic variants.
explanation: Deep research cited this publication as relevant literature for Pheochromocytoma Paraganglioma.
- reference: DOI:10.3390/cancers16071349
title: 'Effects of Peptide Receptor Radiotherapy in Patients with Advanced Paraganglioma and Pheochromocytoma: A Nation-Wide Cohort Study'
found_in:
- Pheochromocytoma_Paraganglioma-deep-research-falcon.md
findings:
- statement: Pheochromocytomas and paragangliomas are rare neuroendocrine tumours that originate from chromaffin cells within the adrenal medulla or extra-adrenal sympathetic ganglia.
supporting_text: Pheochromocytomas and paragangliomas are rare neuroendocrine tumours that originate from chromaffin cells within the adrenal medulla or extra-adrenal sympathetic ganglia.
evidence:
- reference: DOI:10.3390/cancers16071349
reference_title: 'Effects of Peptide Receptor Radiotherapy in Patients with Advanced Paraganglioma and Pheochromocytoma: A Nation-Wide Cohort Study'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Pheochromocytomas and paragangliomas are rare neuroendocrine tumours that originate from chromaffin cells within the adrenal medulla or extra-adrenal sympathetic ganglia.
explanation: Deep research cited this publication as relevant literature for Pheochromocytoma Paraganglioma.
- reference: DOI:10.3390/jcm12041494
title: 'Response to Peptide Receptor Radionuclide Therapy in Pheocromocytomas and Paragangliomas: A Systematic Review and Meta-Analysis'
found_in:
- Pheochromocytoma_Paraganglioma-deep-research-falcon.md
findings:
- statement: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE and 90Y-DOTATOC showed efficacy in the metastatic setting of pheocromocytomas (PCCs) and paragangliomas (PGLs) where no standard therapies have been established.
supporting_text: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE and 90Y-DOTATOC showed efficacy in the metastatic setting of pheocromocytomas (PCCs) and paragangliomas (PGLs) where no standard therapies have been established.
evidence:
- reference: DOI:10.3390/jcm12041494
reference_title: 'Response to Peptide Receptor Radionuclide Therapy in Pheocromocytomas and Paragangliomas: A Systematic Review and Meta-Analysis'
supports: SUPPORT
evidence_source: OTHER
snippet: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE and 90Y-DOTATOC showed efficacy in the metastatic setting of pheocromocytomas (PCCs) and paragangliomas (PGLs) where no standard therapies have been established.
explanation: Deep research cited this publication as relevant literature for Pheochromocytoma Paraganglioma.
- reference: DOI:10.37349/etat.2024.00222
title: 'Tumor metabolism in pheochromocytomas: clinical and therapeutic implications'
found_in:
- Pheochromocytoma_Paraganglioma-deep-research-falcon.md
findings:
- statement: Pheochromocytomas and paragangliomas (PPGLs) have emerged as one of the most common endocrine tumors.
supporting_text: Pheochromocytomas and paragangliomas (PPGLs) have emerged as one of the most common endocrine tumors.
evidence:
- reference: DOI:10.37349/etat.2024.00222
reference_title: 'Tumor metabolism in pheochromocytomas: clinical and therapeutic implications'
supports: SUPPORT
evidence_source: OTHER
snippet: Pheochromocytomas and paragangliomas (PPGLs) have emerged as one of the most common endocrine tumors.
explanation: Deep research cited this publication as relevant literature for Pheochromocytoma Paraganglioma.
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.
Please provide a comprehensive research report on Pheochromocytoma and Paraganglioma covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.
For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.
Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed
Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases
Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases
Search first: CTD, PubMed, PheGenI, GxE databases
Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC
For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities
For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype
Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser
Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases
Search first: CDC databases, WHO, PubMed, NHANES
Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON
Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc
Search first: Gene Ontology (GO), Reactome, KEGG, PubMed
Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold
Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA
Search first: ImmPort, Immunome Database, IEDB, Gene Ontology
Search first: PubMed, Gene Ontology, Reactome
Search first: BRENDA, UniProt, KEGG, OMIM, PubMed
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types
Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT
Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB
Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas
Search first: OMIM, Orphanet, HPO, PubMed
Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM
Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries
Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen
For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.
Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database
Search first: CDC, WHO, behavioral intervention databases, Cochrane Library
Search first: NSGC resources, ACMG guidelines, GeneReviews
Search first: Clinical guidelines, FDA approvals, PubMed
Search first: NCBI Taxonomy
Search first: VBO (Vertebrate Breed Ontology)
Search first: NCBI Gene
Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease
This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details
Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors of neural crest origin that arise from chromaffin/paraganglionic tissue distributed from the skull base to the pelvic floor. PCCs arise in the adrenal medulla, while PGLs arise from extra-adrenal sympathetic or parasympathetic paraganglia. Sympathetic tumors are more often catecholamine-secreting; parasympathetic head-and-neck PGLs are often nonfunctional or dopamine-predominant. Contemporary WHO framing treats all PPGLs as malignant neoplasms with variable metastatic potential, and histology alone cannot reliably predict metastasis. (bresser2024themolecularclassification pages 1-2, t.2024pheochromocytomaanupdated pages 1-2)
| Topic | Key PPGL fact | Key examples/details | Main recent source(s) with year and URL | Evidence citation |
|---|---|---|---|---|
| Definition and origin | PPGL comprises pheochromocytomas (adrenal medulla) and paragangliomas (extra-adrenal paraganglia), neuroendocrine tumors of neural crest/chromaffin origin. | PCC usually arises in adrenal medulla; PGL arises from sympathetic or parasympathetic paraganglia distributed from skull base to pelvic floor. | de Bresser & de Krijger, 2024, Endocrine Pathology, https://doi.org/10.1007/s12022-024-09830-3; Giacché et al., 2024, Biomedicines, https://doi.org/10.3390/biomedicines12102385; Saavedra T. et al., 2024, Frontiers in Endocrinology, https://doi.org/10.3389/fendo.2024.1433582 | (bresser2024themolecularclassification pages 1-2, t.2024pheochromocytomaanupdated pages 1-2, giacche2024pheochromocytoma–paragangliomasyndromea pages 1-2) |
| Major anatomic sites | Sympathetic and parasympathetic sites differ in location and behavior. | Sympathetic: adrenal medulla, retroperitoneum, organ of Zuckerkandl, bladder, mediastinum; parasympathetic: head and neck/carotid body, vagal, jugulotympanic, other skull-base to cervical sites. | de Bresser & de Krijger, 2024, https://doi.org/10.1007/s12022-024-09830-3; Giacché et al., 2024, https://doi.org/10.3390/biomedicines12102385 | (bresser2024themolecularclassification pages 1-2, giacche2024pheochromocytoma–paragangliomasyndromea pages 1-2) |
| Functional vs nonfunctional biology | Sympathetic PCC/PGL are more often catecholamine-secreting; parasympathetic head-and-neck PGLs are usually nonfunctional or dopamine-predominant. | Catecholamines/metabolites relevant to diagnosis include metanephrine, normetanephrine, and 3-methoxytyramine. | de Bresser & de Krijger, 2024, https://doi.org/10.1007/s12022-024-09830-3; Giacché et al., 2024, https://doi.org/10.3390/biomedicines12102385; Bima et al., 2024, Frontiers in Endocrinology, https://doi.org/10.3389/fendo.2024.1460320 | (bresser2024themolecularclassification pages 1-2, giacche2024pheochromocytoma–paragangliomasyndromea pages 1-2, bima2024preventionandmanagement pages 4-5) |
| WHO 2022 classification concept | Modern classification treats all PPGLs as neoplasms with variable metastatic potential rather than benign vs malignant categories. | Histology alone cannot reliably predict which tumors will metastasize; metastatic risk varies by genotype, site, size, and other factors. | de Bresser & de Krijger, 2024, https://doi.org/10.1007/s12022-024-09830-3; Saavedra T. et al., 2024, https://doi.org/10.3389/fendo.2024.1433582 | (bresser2024themolecularclassification pages 1-2, t.2024pheochromocytomaanupdated pages 1-2) |
| Hereditary fraction | PPGL is among the most heritable tumor types. | Germline predisposition is reported in ~30–40% overall; some recent reviews cite ~40–50%; pediatric hereditary proportion is higher (~70–80%). | Giacché et al., 2024, https://doi.org/10.3390/biomedicines12102385; Saavedra T. et al., 2024, https://doi.org/10.3389/fendo.2024.1433582; Bima et al., 2024, https://doi.org/10.3389/fendo.2024.1460320; Richter & Bechmann, 2024, Journal of the Endocrine Society, https://doi.org/10.1210/jendso/bvae038 | (giacche2024pheochromocytoma–paragangliomasyndromea pages 1-2, bima2024preventionandmanagement pages 4-5, richter2024patientsexand pages 1-2, t.2024pheochromocytomaanupdated pages 1-2) |
| Main molecular clusters | Three principal molecular/transcriptomic clusters are consistently recognized. | Cluster 1 pseudohypoxia; Cluster 2 kinase signaling/neural identity; Cluster 3 Wnt signaling. Cluster 1 is often extra-adrenal/noradrenergic and more aggressive; Cluster 2 more often adrenal/adrenergic; Cluster 3 is less common and includes Wnt-related drivers. | Giacché et al., 2024, https://doi.org/10.3390/biomedicines12102385; Bima et al., 2024, https://doi.org/10.3389/fendo.2024.1460320; Richter & Bechmann, 2024, https://doi.org/10.1210/jendso/bvae038; de Bresser & de Krijger, 2024, https://doi.org/10.1007/s12022-024-09830-3 | (giacche2024pheochromocytoma–paragangliomasyndromea pages 1-2, bima2024preventionandmanagement pages 4-5, giacche2024pheochromocytoma–paragangliomasyndromea pages 5-6, richter2024patientsexand pages 1-2) |
| Major susceptibility genes: Cluster 1 pseudohypoxia | Genes affecting Krebs cycle/hypoxia signaling dominate this cluster. | SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, FH, EPAS1/HIF2A, EGLN1/PHD, MDH2; some reviews also list IDH1, DLST, GOT2, SLC25A11. | Giacché et al., 2024, https://doi.org/10.3390/biomedicines12102385; Bima et al., 2024, https://doi.org/10.3389/fendo.2024.1460320; Richter & Bechmann, 2024, https://doi.org/10.1210/jendso/bvae038 | (bima2024preventionandmanagement pages 4-5, giacche2024pheochromocytoma–paragangliomasyndromea pages 5-6, richter2024patientsexand pages 1-2, giacche2024pheochromocytoma–paragangliomasyndromea pages 9-10) |
| Major susceptibility genes: Cluster 2 kinase signaling | Kinase/RAS/MAPK and neural-identity signaling genes define this cluster. | RET, NF1, TMEM127, MAX, HRAS; some reviews also include FGFR1, MET, MERTK, BRAF. | Giacché et al., 2024, https://doi.org/10.3390/biomedicines12102385; Bima et al., 2024, https://doi.org/10.3389/fendo.2024.1460320; Richter & Bechmann, 2024, https://doi.org/10.1210/jendso/bvae038 | (bima2024preventionandmanagement pages 4-5, giacche2024pheochromocytoma–paragangliomasyndromea pages 5-6, richter2024patientsexand pages 1-2) |
| Major susceptibility genes: Cluster 3 Wnt signaling | Wnt-altered tumors are less common and mainly defined by somatic drivers. | MAML3 fusions and CSDE1 alterations are the canonical examples in recent classification schemes. | Giacché et al., 2024, https://doi.org/10.3390/biomedicines12102385; Bima et al., 2024, https://doi.org/10.3389/fendo.2024.1460320 | (bima2024preventionandmanagement pages 4-5, giacche2024pheochromocytoma–paragangliomasyndromea pages 5-6) |
| Clinical stratification note | Sex and ancestry/origin may influence driver-gene distribution and presentation. | In one 2024 synthesis, males more often had hypoxia-pathway germline PVs, sympathetic PGL, and metastasis; European females more often had kinase-signaling drivers such as RET/TMEM127. | Richter & Bechmann, 2024, https://doi.org/10.1210/jendso/bvae038 | (richter2024patientsexand pages 1-2) |
Table: This table summarizes core disease-level facts for pheochromocytoma and paraganglioma, including definition, sites, functionality, WHO classification concept, heritability, and molecular genetics. It is structured for direct reuse in a knowledge base and includes citation-ready evidence IDs plus recent source URLs.
Commonly used terms include: - Pheochromocytoma (PCC), paraganglioma (PGL), PPGL - Head and neck paraganglioma (HNPGL) for parasympathetic PGLs in skull base/neck. (lin2022headandneck pages 1-2)
PPGL is among the most heritable human tumor types. - A 2024 review states: “germline mutation in susceptibility genes is detected in 40% of subjects,” and ~10–12% of clinically sporadic presentations still carry germline mutations. (giacche2024pheochromocytoma–paragangliomasyndromea pages 1-2) - A 2024 pediatric-focused review summarizes ~40–50% germline contribution overall and higher rates in children (reported 70–80% hereditary; one study ~80%). (bima2024preventionandmanagement pages 4-5) - A 2024 analysis of sex/ancestry effects notes that genetic drivers explain ~80% of PPGLs and that “half of which are caused by germline pathogenic variants (PVs) in… >20 susceptibility genes,” consistent with ~40% germline overall. (richter2024patientsexand pages 1-2)
Major susceptibility genes (examples repeatedly emphasized in recent reviews): - Cluster 1 (pseudohypoxia / Krebs cycle): SDHA/SDHB/SDHC/SDHD/SDHAF2, VHL, FH, EPAS1(HIF2A), plus additional metabolic/hypoxia genes (e.g., MDH2; and in some classifications IDH1, DLST, GOT2, SLC25A11). (giacche2024pheochromocytoma–paragangliomasyndromea pages 5-6, richter2024patientsexand pages 1-2) - Cluster 2 (kinase signaling): RET, NF1, TMEM127, MAX, HRAS (and sometimes FGFR1/MET etc. in expanded schemas). (giacche2024pheochromocytoma–paragangliomasyndromea pages 5-6, richter2024patientsexand pages 1-2) - Cluster 3 (Wnt-altered): MAML3 fusions, CSDE1 (somatic drivers). (giacche2024pheochromocytoma–paragangliomasyndromea pages 5-6)
Genotype–phenotype coupling (high-level): A 2024 review summarizes that pseudo-hypoxic (cluster‑1) tumors tend toward extra-adrenal location and noradrenergic/dopaminergic biochemical profiles with greater aggressiveness, whereas kinase (cluster‑2) tumors more often are adrenal/adrenergic. (giacche2024pheochromocytoma–paragangliomasyndromea pages 5-6)
Typical manifestations largely reflect catecholamine excess. - A 2023 review states systemic arterial hypertension occurs in ~90% of cases and highlights the classic paroxysmal triad of “headache, palpitations, and sweating.” (junior2023thepheochromocytomaparagangliomasyndrome pages 1-2) - A 2024 review provides pooled sensitivities: hypertension ~80.7%, palpitations ~59.3%, diaphoresis ~52.4%, and classic triad sensitivity ~58%. (giacche2024pheochromocytoma–paragangliomasyndromea pages 2-4) - Hypertension pattern differs: sustained hypertension more common than paroxysmal in some series; one 2024 scoping review summarizes sustained hypertension ~50–55% and paroxysmal ~30–45%. (t.2024pheochromocytomaanupdated pages 3-6)
Pediatric phenotype differences: sustained hypertension is especially common in children (reported ~60–90%), and the classic triad is reported in up to 54% of affected children. (bima2024preventionandmanagement pages 2-4)
Cardiovascular complications (high clinical importance): - Catecholamine-induced cardiomyopathy complicates ~8–10% of cases, and cardiovascular event rates in PPGL cohorts are reported at 19.3% and 28% in cited studies. (giacche2024pheochromocytoma–paragangliomasyndromea pages 4-5)
(These are ontology mapping suggestions for knowledge-base use; not claims about frequency unless stated above.) - Hypertension HP:0000822; Paroxysmal hypertension HP:0004921 - Headache HP:0002315 - Palpitations HP:0001962 - Diaphoresis HP:0000972 - Tachycardia HP:0001649; Arrhythmia HP:0011675 - Orthostatic hypotension HP:0001278 (often coded as HP:0001278 is incorrect; better: Orthostatic hypotension HP:0001278 may be mismatched—curators should verify; suggestion only) - Hyperglycemia HP:0003074; Diabetes mellitus HP:0000819 - Cardiomyopathy HP:0001638; Takotsubo cardiomyopathy (no single HPO term in this context; curate as appropriate)
A 2024 review lists major susceptibility genes including NF1, VHL, RET, SDHx (SDHA/SDHB/SDHC/SDHD/SDHAF2), TMEM127, MAX, FH. (giacche2024pheochromocytoma–paragangliomasyndromea pages 1-2)
Cluster 1: Pseudohypoxia / Krebs cycle dysregulation (SDHx, FH, VHL/EPAS1 axis) - Mechanistic chain (conceptual): SDHx/FH dysfunction → accumulation of oncometabolites (succinate, fumarate) → inhibition of α‑ketoglutarate–dependent dioxygenases → epigenetic dysregulation (hypermethylation) and stabilization of hypoxia-inducible signaling → pro-angiogenic and pro-proliferative transcriptional programs contributing to tumorigenesis and aggressiveness. (jeeyavudeen2024tumormetabolismin pages 1-3, bresser2024themolecularclassification pages 6-7)
Cluster 2: Kinase signaling (RET/NF1/TMEM127/MAX/HRAS) - Mechanistic chain (conceptual): kinase/RAS pathway activation → altered growth signaling and adrenal-predominant, adrenergic biochemical phenotypes in many cases. (giacche2024pheochromocytoma–paragangliomasyndromea pages 5-6, richter2024patientsexand pages 1-2)
Cluster 3: Wnt-altered (MAML3/CSDE1) - Wnt-altered tumors (e.g., MAML3 fusions) are highlighted in modern classifiers and may show higher metastatic propensity and distinct immune features (including PD‑L1 expression in MAML3-related tumors in metastatic cohorts). (bresser2024themolecularclassification pages 7-9, calsina2023genomicandimmune pages 1-2)
A large Nature Communications 2023 study profiled metastatic PPGL and identified genomic instability and immune features relevant to prognostication: - High TMB, MSI, and SCNA burden associated with ATRX/TERT alterations were proposed as prognostic markers; transcriptomics highlighted CDK1 as an additional marker. (calsina2023genomicandimmune pages 1-2, calsina2023genomicandimmune pages 4-5) - The tumor microenvironment in metastatic PPGL was described as generally immunosuppressive, with an exception for PD‑L1–expressing MAML3-related tumors, suggesting a subset potentially more amenable to immune checkpoint approaches. (calsina2023genomicandimmune pages 1-2)
Functional imaging tracer selection is genotype- and site-informed in modern practice. (giacche2024pheochromocytoma–paragangliomasyndromea pages 10-12)
Direct head-to-head diagnostic performance (recent, quantitative): - In a 2023 retrospective comparison (n=113), 18F‑FDOPA PET/CT detected and correctly localized all 55 PCC lesions vs 25 by 68Ga‑DOTATOC, with sensitivity 100% vs 49%, accuracy 98% vs 70%, and NPV 100% vs 63%. (iversen2023[18f]fdopapetctis pages 1-2)
PRRT (177Lu‑DOTATATE / 90Y‑DOTATATE) for SSTR-positive advanced/metastatic PPGL - Nationwide cohort (Denmark, 2024; n=28): median OS 72 months, 5‑year survival 65%, median PFS 30 months, with low toxicity; germline mutation carriers had better survival (p=0.041). (kornerup2024effectsofpeptide pages 1-2) - Large multicenter PRRT cohort including PPGL (SEPTRALU, 2023): PPGL subgroup median PFS 30.6 months under standard 4-cycle 7.4 GBq q8wk regimen. (mitjavila2023efficacyof[177lu]ludotatate pages 1-2) - Meta-analysis (2023; 213 patients): pooled disease control rate (DCR) 0.81 overall; 177Lu DCR 0.83, 90Y DCR 0.76. (marretta2023responsetopeptide pages 1-2) - Single-institution long follow-up cohort (2024; n=30 PCC/PGL): partial response 23% and stable disease 63%; 5- and 10-year OS 75% and 59%, respectively; grade 3–4 acute hematologic toxicity in 10%. (rubino2024peptidereceptorradionuclide pages 1-3)
131I‑MIBG therapy - A 2022 phase II single-dose 131I‑mIBG trial (n=16 treated) reported biochemical response rate 23.5% (≥50% decrease in urinary catecholamines), RECIST response rate 5.9%, and common hematologic AEs up to grade 3 in 14/16. (inaki2022; not converted to pqac evidence id in this run, so not cited further.)
Primary prevention is not established for genetically driven PPGL; prevention focuses on: - Secondary prevention: cascade genetic testing and structured surveillance of mutation carriers; early biochemical testing and imaging when indicated. High heritability and guideline emphasis on genetic testing support this approach. (lin2022headandneck pages 1-2, ohmoto2024currentprospectsof pages 1-2) - Tertiary prevention: lifelong follow-up to prevent late metastatic recurrence and manage cardiovascular complications. (torresan2023longtermoutcomesafter pages 1-2, araujocastro2023localrecurrenceand pages 1-2)
Naturally occurring PPGL occurs in companion animals and can serve as comparative biology. - A 2024 prospective metabolomics study of canine pheochromocytomas (21 dogs vs 10 controls) found PCC tissue had markedly higher norepinephrine fraction (median 88% vs 14%) and identified a dog with an aberrant succinate:fumarate ratio (~25-fold higher) suggesting SDHx mutation; supporting metabolomics for genetic inference in dogs. (berg2024metabolomicprofilingof; not assigned a pqac evidence id in this run, so not cited further.)
A recurring translational gap is the scarcity of faithful PPGL models, especially for SDHB-deficient metastatic biology. - A zebrafish CRISPR model introducing truncating sdhb lesions showed reduced complex II activity and “significant succinate accumulation,” mimicking SDHB-associated metabolic effects and enabling in vivo screening. (dona2021lossofsdhb) - A 2024 conditional SDHC loss study in early Sox10+ neural crest cells produced developmental phenotypes but “not paraganglioma tumorigenesis,” underscoring difficulty modeling human SDHx-driven tumorigenesis in mice. (lewis2024mousedevelopmentaldefects)
(These model-system sources were retrieved as paper metadata in this run but not extracted into pqac evidence IDs; therefore, they are described qualitatively here without pqac citation IDs.)
References
(bresser2024themolecularclassification pages 1-2): Carolijn J. M. de Bresser and Ronald R. de Krijger. The molecular classification of pheochromocytomas and paragangliomas: discovering the genomic and immune landscape of metastatic disease. Endocrine Pathology, 35:279-292, Oct 2024. URL: https://doi.org/10.1007/s12022-024-09830-3, doi:10.1007/s12022-024-09830-3. This article has 13 citations and is from a peer-reviewed journal.
(t.2024pheochromocytomaanupdated pages 1-2): J. S. Saavedra T., Humberto Alejandro Nati-Castillo, L. A. Valderrama Cometa, Wilfredo A. Rivera-Martínez, Josué Asprilla, C. M. Castaño-Giraldo, Leonardo Sánchez S., Mishell Heredia-Espín, Marlon Arias-Intriago, and Juan S. Izquierdo-Condoy. Pheochromocytoma: an updated scoping review from clinical presentation to management and treatment. Frontiers in Endocrinology, Dec 2024. URL: https://doi.org/10.3389/fendo.2024.1433582, doi:10.3389/fendo.2024.1433582. This article has 32 citations.
(giacche2024pheochromocytoma–paragangliomasyndromea pages 1-2): Mara Giacché, Maria Chiara Tacchetti, Claudia Agabiti-Rosei, Francesco Torlone, Francesco Bandera, Claudia Izzi, and Enrico Agabiti-Rosei. Pheochromocytoma–paraganglioma syndrome: a multiform disease with different genotype and phenotype features. Biomedicines, 12:2385, Oct 2024. URL: https://doi.org/10.3390/biomedicines12102385, doi:10.3390/biomedicines12102385. This article has 7 citations.
(bima2024preventionandmanagement pages 4-5): Chiara Bima, Chiara Lopez, Gerdi Tuli, Jessica Munarin, Stefano Arata, Matteo Procopio, Martina Bollati, Mauro Maccario, Luisa De Sanctis, and Mirko Parasiliti-Caprino. Prevention and management of hypertensive crises in children with pheochromocytoma and paraganglioma. Frontiers in Endocrinology, Aug 2024. URL: https://doi.org/10.3389/fendo.2024.1460320, doi:10.3389/fendo.2024.1460320. This article has 13 citations.
(richter2024patientsexand pages 1-2): Susan Richter and Nicole Bechmann. Patient sex and origin influence distribution of driver genes and clinical presentation of paraganglioma. Journal of the Endocrine Society, Feb 2024. URL: https://doi.org/10.1210/jendso/bvae038, doi:10.1210/jendso/bvae038. This article has 11 citations and is from a peer-reviewed journal.
(giacche2024pheochromocytoma–paragangliomasyndromea pages 5-6): Mara Giacché, Maria Chiara Tacchetti, Claudia Agabiti-Rosei, Francesco Torlone, Francesco Bandera, Claudia Izzi, and Enrico Agabiti-Rosei. Pheochromocytoma–paraganglioma syndrome: a multiform disease with different genotype and phenotype features. Biomedicines, 12:2385, Oct 2024. URL: https://doi.org/10.3390/biomedicines12102385, doi:10.3390/biomedicines12102385. This article has 7 citations.
(giacche2024pheochromocytoma–paragangliomasyndromea pages 9-10): Mara Giacché, Maria Chiara Tacchetti, Claudia Agabiti-Rosei, Francesco Torlone, Francesco Bandera, Claudia Izzi, and Enrico Agabiti-Rosei. Pheochromocytoma–paraganglioma syndrome: a multiform disease with different genotype and phenotype features. Biomedicines, 12:2385, Oct 2024. URL: https://doi.org/10.3390/biomedicines12102385, doi:10.3390/biomedicines12102385. This article has 7 citations.
(lin2022headandneck pages 1-2): Edward P. Lin, Bennett B. Chin, Lauren Fishbein, Toshio Moritani, Simone P. Montoya, Shehanaz Ellika, and Shawn Newlands. Head and neck paragangliomas: an update on the molecular classification, state-of-the-art imaging, and management recommendations. Radiology. Imaging cancer, 4 3:e210088, May 2022. URL: https://doi.org/10.1148/rycan.210088, doi:10.1148/rycan.210088. This article has 111 citations.
(araujocastro2023localrecurrenceand pages 1-2): Marta Araujo-Castro, Iñigo García Sanz, César Mínguez Ojeda, Felicia Hanzu, Mireia Mora, Almudena Vicente, Concepción Blanco Carrera, Paz de Miguel Novoa, María del Carmen López García, Cristina Lamas, Laura Manjón-Miguélez, María del Castillo Tous, Pablo Rodríguez de Vera, Rebeca Barahona San Millán, Mónica Recasens, Mariana Tomé Fernández-Ladreda, Nuria Valdés, Paola Gracia Gimeno, Cristina Robles Lazaro, Theodora Michalopoulou, Cristina Álvarez Escolá, Rogelio García Centeno, Verónica Barca-Tierno, Aura D. Herrera-Martínez, and María Calatayud. Local recurrence and metastatic disease in pheochromocytomas and sympathetic paragangliomas. Frontiers in Endocrinology, Dec 2023. URL: https://doi.org/10.3389/fendo.2023.1279828, doi:10.3389/fendo.2023.1279828. This article has 13 citations.
(giacche2024pheochromocytoma–paragangliomasyndromea pages 12-14): Mara Giacché, Maria Chiara Tacchetti, Claudia Agabiti-Rosei, Francesco Torlone, Francesco Bandera, Claudia Izzi, and Enrico Agabiti-Rosei. Pheochromocytoma–paraganglioma syndrome: a multiform disease with different genotype and phenotype features. Biomedicines, 12:2385, Oct 2024. URL: https://doi.org/10.3390/biomedicines12102385, doi:10.3390/biomedicines12102385. This article has 7 citations.
(junior2023thepheochromocytomaparagangliomasyndrome pages 1-2): José Viana Lima Junior and Claudio Elias Kater. The pheochromocytoma/paraganglioma syndrome: an overview on mechanisms, diagnosis and management. International braz j urol, 49:307-319, Jun 2023. URL: https://doi.org/10.1590/s1677-5538.ibju.2023.0038, doi:10.1590/s1677-5538.ibju.2023.0038. This article has 59 citations.
(giacche2024pheochromocytoma–paragangliomasyndromea pages 2-4): Mara Giacché, Maria Chiara Tacchetti, Claudia Agabiti-Rosei, Francesco Torlone, Francesco Bandera, Claudia Izzi, and Enrico Agabiti-Rosei. Pheochromocytoma–paraganglioma syndrome: a multiform disease with different genotype and phenotype features. Biomedicines, 12:2385, Oct 2024. URL: https://doi.org/10.3390/biomedicines12102385, doi:10.3390/biomedicines12102385. This article has 7 citations.
(t.2024pheochromocytomaanupdated pages 3-6): J. S. Saavedra T., Humberto Alejandro Nati-Castillo, L. A. Valderrama Cometa, Wilfredo A. Rivera-Martínez, Josué Asprilla, C. M. Castaño-Giraldo, Leonardo Sánchez S., Mishell Heredia-Espín, Marlon Arias-Intriago, and Juan S. Izquierdo-Condoy. Pheochromocytoma: an updated scoping review from clinical presentation to management and treatment. Frontiers in Endocrinology, Dec 2024. URL: https://doi.org/10.3389/fendo.2024.1433582, doi:10.3389/fendo.2024.1433582. This article has 32 citations.
(bima2024preventionandmanagement pages 2-4): Chiara Bima, Chiara Lopez, Gerdi Tuli, Jessica Munarin, Stefano Arata, Matteo Procopio, Martina Bollati, Mauro Maccario, Luisa De Sanctis, and Mirko Parasiliti-Caprino. Prevention and management of hypertensive crises in children with pheochromocytoma and paraganglioma. Frontiers in Endocrinology, Aug 2024. URL: https://doi.org/10.3389/fendo.2024.1460320, doi:10.3389/fendo.2024.1460320. This article has 13 citations.
(giacche2024pheochromocytoma–paragangliomasyndromea pages 4-5): Mara Giacché, Maria Chiara Tacchetti, Claudia Agabiti-Rosei, Francesco Torlone, Francesco Bandera, Claudia Izzi, and Enrico Agabiti-Rosei. Pheochromocytoma–paraganglioma syndrome: a multiform disease with different genotype and phenotype features. Biomedicines, 12:2385, Oct 2024. URL: https://doi.org/10.3390/biomedicines12102385, doi:10.3390/biomedicines12102385. This article has 7 citations.
(jeeyavudeen2024tumormetabolismin pages 1-3): Mohammad Sadiq Jeeyavudeen, Navin Mathiyalagan, Cornelius Fernandez James, and Joseph M. Pappachan. Tumor metabolism in pheochromocytomas: clinical and therapeutic implications. Exploration of Targeted Anti-tumor Therapy, 5:349-373, Apr 2024. URL: https://doi.org/10.37349/etat.2024.00222, doi:10.37349/etat.2024.00222. This article has 3 citations.
(bresser2024themolecularclassification pages 6-7): Carolijn J. M. de Bresser and Ronald R. de Krijger. The molecular classification of pheochromocytomas and paragangliomas: discovering the genomic and immune landscape of metastatic disease. Endocrine Pathology, 35:279-292, Oct 2024. URL: https://doi.org/10.1007/s12022-024-09830-3, doi:10.1007/s12022-024-09830-3. This article has 13 citations and is from a peer-reviewed journal.
(bresser2024themolecularclassification pages 7-9): Carolijn J. M. de Bresser and Ronald R. de Krijger. The molecular classification of pheochromocytomas and paragangliomas: discovering the genomic and immune landscape of metastatic disease. Endocrine Pathology, 35:279-292, Oct 2024. URL: https://doi.org/10.1007/s12022-024-09830-3, doi:10.1007/s12022-024-09830-3. This article has 13 citations and is from a peer-reviewed journal.
(calsina2023genomicandimmune pages 1-2): Bruna Calsina, Elena Piñeiro-Yáñez, Ángel M. Martínez-Montes, Eduardo Caleiras, Ángel Fernández-Sanromán, María Monteagudo, Rafael Torres-Pérez, Coral Fustero-Torre, Marta Pulgarín-Alfaro, Eduardo Gil, Rocío Letón, Scherezade Jiménez, Santiago García-Martín, Maria Carmen Martin, Juan María Roldán-Romero, Javier Lanillos, Sara Mellid, María Santos, Alberto Díaz-Talavera, Ángeles Rubio, Patricia González, Barbara Hernando, Nicole Bechmann, Margo Dona, María Calatayud, Sonsoles Guadalix, Cristina Álvarez-Escolá, Rita M. Regojo, Javier Aller, Maria Isabel Del Olmo-Garcia, Adrià López-Fernández, Stephanie M. J. Fliedner, Elena Rapizzi, Martin Fassnacht, Felix Beuschlein, Marcus Quinkler, Rodrigo A. Toledo, Massimo Mannelli, Henri J. Timmers, Graeme Eisenhofer, Sandra Rodríguez-Perales, Orlando Domínguez, Geoffrey Macintyre, Maria Currás-Freixes, Cristina Rodríguez-Antona, Alberto Cascón, Luis J. Leandro-García, Cristina Montero-Conde, Giovanna Roncador, Juan Fernando García-García, Karel Pacak, Fátima Al-Shahrour, and Mercedes Robledo. Genomic and immune landscape of metastatic pheochromocytoma and paraganglioma. Nature Communications, Feb 2023. URL: https://doi.org/10.1038/s41467-023-36769-6, doi:10.1038/s41467-023-36769-6. This article has 85 citations and is from a highest quality peer-reviewed journal.
(calsina2023genomicandimmune pages 4-5): Bruna Calsina, Elena Piñeiro-Yáñez, Ángel M. Martínez-Montes, Eduardo Caleiras, Ángel Fernández-Sanromán, María Monteagudo, Rafael Torres-Pérez, Coral Fustero-Torre, Marta Pulgarín-Alfaro, Eduardo Gil, Rocío Letón, Scherezade Jiménez, Santiago García-Martín, Maria Carmen Martin, Juan María Roldán-Romero, Javier Lanillos, Sara Mellid, María Santos, Alberto Díaz-Talavera, Ángeles Rubio, Patricia González, Barbara Hernando, Nicole Bechmann, Margo Dona, María Calatayud, Sonsoles Guadalix, Cristina Álvarez-Escolá, Rita M. Regojo, Javier Aller, Maria Isabel Del Olmo-Garcia, Adrià López-Fernández, Stephanie M. J. Fliedner, Elena Rapizzi, Martin Fassnacht, Felix Beuschlein, Marcus Quinkler, Rodrigo A. Toledo, Massimo Mannelli, Henri J. Timmers, Graeme Eisenhofer, Sandra Rodríguez-Perales, Orlando Domínguez, Geoffrey Macintyre, Maria Currás-Freixes, Cristina Rodríguez-Antona, Alberto Cascón, Luis J. Leandro-García, Cristina Montero-Conde, Giovanna Roncador, Juan Fernando García-García, Karel Pacak, Fátima Al-Shahrour, and Mercedes Robledo. Genomic and immune landscape of metastatic pheochromocytoma and paraganglioma. Nature Communications, Feb 2023. URL: https://doi.org/10.1038/s41467-023-36769-6, doi:10.1038/s41467-023-36769-6. This article has 85 citations and is from a highest quality peer-reviewed journal.
(torresan2023longtermoutcomesafter pages 1-2): Francesca Torresan, Arianna Beber, Donatella Schiavone, Stefania Zovato, Francesca Galuppini, Filippo Crimì, Filippo Ceccato, and Maurizio Iacobone. Long-term outcomes after surgery for pheochromocytoma and sympathetic paraganglioma. Cancers, 15:2890, May 2023. URL: https://doi.org/10.3390/cancers15112890, doi:10.3390/cancers15112890. This article has 19 citations.
(hose2023top2aexpressionin pages 1-2): Karolina Solhusløkk Höse, Adam Stenman, Fredrika Svahn, Catharina Larsson, and C. Christofer Juhlin. Top2a expression in pheochromocytoma and abdominal paraganglioma: a marker of poor clinical outcome? Endocrine Pathology, 34:129-141, Jan 2023. URL: https://doi.org/10.1007/s12022-022-09746-w, doi:10.1007/s12022-022-09746-w. This article has 10 citations and is from a peer-reviewed journal.
(junior2023thepheochromocytomaparagangliomasyndrome pages 5-7): José Viana Lima Junior and Claudio Elias Kater. The pheochromocytoma/paraganglioma syndrome: an overview on mechanisms, diagnosis and management. International braz j urol, 49:307-319, Jun 2023. URL: https://doi.org/10.1590/s1677-5538.ibju.2023.0038, doi:10.1590/s1677-5538.ibju.2023.0038. This article has 59 citations.
(giacche2024pheochromocytoma–paragangliomasyndromea pages 10-12): Mara Giacché, Maria Chiara Tacchetti, Claudia Agabiti-Rosei, Francesco Torlone, Francesco Bandera, Claudia Izzi, and Enrico Agabiti-Rosei. Pheochromocytoma–paraganglioma syndrome: a multiform disease with different genotype and phenotype features. Biomedicines, 12:2385, Oct 2024. URL: https://doi.org/10.3390/biomedicines12102385, doi:10.3390/biomedicines12102385. This article has 7 citations.
(iversen2023[18f]fdopapetctis pages 1-2): Peter Iversen, Stine Kramer, Andreas Ebbehoj, Esben Søndergaard, Kirstine Stochholm, Per Løgstrup Poulsen, and Karin Hjorthaug. [18f]fdopa pet/ct is superior to [68ga]dotatoc pet/ct in diagnostic imaging of pheochromocytoma. EJNMMI Research, Dec 2023. URL: https://doi.org/10.1186/s13550-023-01056-4, doi:10.1186/s13550-023-01056-4. This article has 9 citations and is from a peer-reviewed journal.
(ohmoto2024currentprospectsof pages 1-2): Akihiro Ohmoto, Naomi Hayashi, Shunji Takahashi, and Arisa Ueki. Current prospects of hereditary adrenal tumors: towards better clinical management. Hereditary Cancer in Clinical Practice, Mar 2024. URL: https://doi.org/10.1186/s13053-024-00276-6, doi:10.1186/s13053-024-00276-6. This article has 5 citations and is from a peer-reviewed journal.
(lin2022headandneck pages 2-3): Edward P. Lin, Bennett B. Chin, Lauren Fishbein, Toshio Moritani, Simone P. Montoya, Shehanaz Ellika, and Shawn Newlands. Head and neck paragangliomas: an update on the molecular classification, state-of-the-art imaging, and management recommendations. Radiology. Imaging cancer, 4 3:e210088, May 2022. URL: https://doi.org/10.1148/rycan.210088, doi:10.1148/rycan.210088. This article has 111 citations.
(kornerup2024effectsofpeptide pages 1-2): Linda Skibsted Kornerup, Mikkel Andreassen, Ulrich Knigge, Anne Kirstine Arveschoug, Per Løgstup Poulsen, Andreas Kjær, Peter Sandor Oturai, Henning Grønbæk, and Gitte Dam. Effects of peptide receptor radiotherapy in patients with advanced paraganglioma and pheochromocytoma: a nation-wide cohort study. Cancers, 16:1349, Mar 2024. URL: https://doi.org/10.3390/cancers16071349, doi:10.3390/cancers16071349. This article has 6 citations.
(mitjavila2023efficacyof[177lu]ludotatate pages 1-2): Mercedes Mitjavila, Paula Jimenez-Fonseca, Pilar Belló, Virginia Pubul, Juan Carlos Percovich, Amparo Garcia-Burillo, Jorge Hernando, Javier Arbizu, Emilia Rodeño, Montserrat Estorch, Belén Llana, Maribel Castellón, Lina García-Cañamaque, Pablo Gajate, Maria Carmen Riesco, Maria Begoña Miguel, David Balaguer-Muñoz, Ana Custodio, Juana María Cano, Alexandra Repetto, Pilar Garcia-Alonso, Maria Angustias Muros, Jose Luis Vercher-Conejero, and Alberto Carmona-Bayonas. Efficacy of [177lu]lu-dotatate in metastatic neuroendocrine neoplasms of different locations: data from the septralu study. European Journal of Nuclear Medicine and Molecular Imaging, 50:2486-2500, Mar 2023. URL: https://doi.org/10.1007/s00259-023-06166-8, doi:10.1007/s00259-023-06166-8. This article has 57 citations and is from a highest quality peer-reviewed journal.
(marretta2023responsetopeptide pages 1-2): Antonella Lucia Marretta, Alessandro Ottaiano, Domenico Iervolino, Alessandra Bracigliano, Ottavia Clemente, Francesca Di Gennaro, Roberto Tafuto, Mariachiara Santorsola, Secondo Lastoria, and Salvatore Tafuto. Response to peptide receptor radionuclide therapy in pheocromocytomas and paragangliomas: a systematic review and meta-analysis. Journal of Clinical Medicine, 12:1494, Feb 2023. URL: https://doi.org/10.3390/jcm12041494, doi:10.3390/jcm12041494. This article has 20 citations.
(rubino2024peptidereceptorradionuclide pages 1-3): Manila Rubino, Giuseppe Danilo Di Stasio, Lisa Bodei, Stefano Papi, Paola Anna Rocca, Mahila Esmeralda Ferrari, Cristiana Iuliana Fodor, Vincenzo Bagnardi, Samuele Frassoni, Riccardo Mei, Nicola Fazio, Francesco Ceci, and Chiara Maria Grana. Peptide receptor radionuclide therapy with 177lu- or 90y-sstr peptides in malignant pheochromocytomas (pccs) and paragangliomas (pgls): results from a single institutional retrospective analysis. Endocrine, 84:704-710, Feb 2024. URL: https://doi.org/10.1007/s12020-024-03707-5, doi:10.1007/s12020-024-03707-5. This article has 6 citations and is from a peer-reviewed journal.
(NCT03206060 chunk 1): Lu-177-DOTATATE (Lutathera) in Therapy of Inoperable Pheochromocytoma/ Paraganglioma. National Cancer Institute (NCI). 2017. ClinicalTrials.gov Identifier: NCT03206060
(NCT03206060 chunk 2): Lu-177-DOTATATE (Lutathera) in Therapy of Inoperable Pheochromocytoma/ Paraganglioma. National Cancer Institute (NCI). 2017. ClinicalTrials.gov Identifier: NCT03206060
(NCT02186678 chunk 1): Comparison of Diagnostic Performances of 68Ga-DOTATATE PET-CT and 18F-FDOPA PET-CT in Paragangliomas and Pheochromocytomas Evaluation. Assistance Publique Hopitaux De Marseille. 2014. ClinicalTrials.gov Identifier: NCT02186678
(NCT05948137 chunk 1): Jin-Sook Ryu. F-18 FDOPA PET/CT Versus I-123 MIBG Scintigraphy With SPECT/CT for the Diagnosis of Pheochromocytoma and Paraganglioma. Asan Medical Center. 2017. ClinicalTrials.gov Identifier: NCT05948137