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Medicina Clinica Jun 2024Pheochromocytomas are rare neuroendocrine tumors that derive from the chromaffin cells of the adrenal medulla and secrete catecholamines. The measurement of plasma or... (Review)
Review
Pheochromocytomas are rare neuroendocrine tumors that derive from the chromaffin cells of the adrenal medulla and secrete catecholamines. The measurement of plasma or fractionated urine metanephrines is the hormonal determination of choice for the biochemical diagnosis. Once the biochemical diagnosis is confirmed, the next step is the localization study. It is recommended to request a genetic study in all patients with pheochromocytomas since 40% of cases are hereditary. Once the diagnostic study is completed, preoperative treatment with alpha blockers should be instituted at least 7-14 days before adrenalectomy. However, in low-risk patients, the omission of presurgical treatment could be considered if the surgery is performed in centers with experience and a strict monitoring of the patient is carried out during the perioperative period. This document offers a practical guide on the diagnosis and perioperative approach in patients with pheochromocytomas.
PubMed: 38849272
DOI: 10.1016/j.medcli.2024.03.025 -
Endocrine Reviews May 2024Pheochromocytomas/paragangliomas are unique in their highly variable molecular landscape driven by genetic alterations, either germline or somatic. These mutations... (Review)
Review
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. This also warrants selection of the most appropriate and locally available imaging modalities tailored to an individual patient based on consideration of many relevant factors including age, (anticipated) tumor location(s), size, and multifocality, underlying genotype, biochemical phenotype, chance of metastases, as well as the patient's personal preference and treatment goals. Anatomical imaging using computed tomography and magnetic resonance imaging and functional imaging using positron emission tomography and single photon emission computed tomography are currently a cornerstone in the evaluation of patients with pheochromocytomas/paragangliomas. In modern nuclear medicine practice, a multitude of radionuclides with relevance to diagnostic work-up and treatment planning (theranostics) is available, including radiolabeled metaiodobenzylguanidine, fluorodeoxyglucose, fluorodihydroxyphenylalanine, and somatostatin analogues. This review amalgamates up-to-date imaging guidelines, expert opinions, and recent discoveries. Based on the rich toolbox for anatomical and functional imaging that is currently available, we aim to define a customized approach in patients with (suspected) pheochromocytomas/paragangliomas from a practical clinical perspective. We provide imaging algorithms for different starting points for initial diagnostic work-up and course of the disease, including adrenal incidentaloma, established biochemical diagnosis, postsurgical follow-up, tumor screening in pathogenic variant carriers, staging and restaging of metastatic disease, theranostics, and response monitoring.
Topics: Humans; Pheochromocytoma; Adrenal Gland Neoplasms; Paraganglioma; Magnetic Resonance Imaging; Positron-Emission Tomography
PubMed: 38206185
DOI: 10.1210/endrev/bnae001 -
The Journal of Clinical Endocrinology... Sep 2023Pheochromocytomas and paragangliomas (PPGLs) with pathogenic mutations in the succinate dehydrogenase subunit B (SDHB) are associated with a high metastatic risk....
CONTEXT
Pheochromocytomas and paragangliomas (PPGLs) with pathogenic mutations in the succinate dehydrogenase subunit B (SDHB) are associated with a high metastatic risk. Somatostatin receptor 2 (SSTR2)-dependent imaging is the most sensitive imaging modality for SDHB-related PPGLs, suggesting that SSTR2 expression is a significant cell surface therapeutic biomarker of such tumors.
OBJECTIVE
Exploration of the relationship between SSTR2 immunoreactivity and SDHB immunoreactivity, mutational status, and clinical behavior of PPGLs. Evaluation of SSTR-based therapies in metastatic PPGLs.
METHODS
Retrospective analysis of a multicenter cohort of PPGLs at 6 specialized Endocrine Tumor Centers in Germany, The Netherlands, and Switzerland. Patients with PPGLs participating in the ENSAT registry were included. Clinical data were extracted from medical records, and immunohistochemistry (IHC) for SDHB and SSTR2 was performed in patients with available tumor tissue. Immunoreactivity of SSTR2 was investigated using Volante scores. The main outcome measure was the association of SSTR2 IHC positivity with genetic and clinical-pathological features of PPGLs.
RESULTS
Of 202 patients with PPGLs, 50% were SSTR2 positive. SSTR2 positivity was significantly associated with SDHB- and SDHx-related PPGLs, with the strongest SSTR2 staining intensity in SDHB-related PPGLs (P = .01). Moreover, SSTR2 expression was significantly associated with metastatic disease independent of SDHB/SDHx mutation status (P < .001). In metastatic PPGLs, the disease control rate with first-line SSTR-based radionuclide therapy was 67% (n = 22, n = 11 SDHx), and with first-line "cold" somatostatin analogs 100% (n = 6, n = 3 SDHx).
CONCLUSION
SSTR2 expression was independently associated with SDHB/SDHx mutations and metastatic disease. We confirm a high disease control rate of somatostatin receptor-based therapies in metastatic PPGLs.
Topics: Humans; Adrenal Gland Neoplasms; Neoplasms, Second Primary; Paraganglioma; Pheochromocytoma; Receptors, Somatostatin; Retrospective Studies; Succinate Dehydrogenase
PubMed: 36946182
DOI: 10.1210/clinem/dgad166 -
Oxford Medical Case Reports Jul 2023
PubMed: 37484550
DOI: 10.1093/omcr/omad070 -
Endocrine-related Cancer Aug 2024In 2012, somatic EPAS1 pathogenic variants were found to cause a triad of pheochromocytoma/paragangliomas (PPGLs), polycythemia, and somatostatinoma. Since then, a... (Review)
Review
In 2012, somatic EPAS1 pathogenic variants were found to cause a triad of pheochromocytoma/paragangliomas (PPGLs), polycythemia, and somatostatinoma. Since then, a limited number of studies on this subject have been reported, and data on the long-term outcome of metastatic disease are not available on this rare syndrome. We comprehensively reviewed EPAS1-related PPGL and describe an unusual patient who has been living with an EPAS1-related metastatic PPGL for 47 years. The results of this work show that EPAS1 pathogenic variants are rare, more in females and patients without pathogenic variants in other PPGL susceptibility genes. PPGLs are the most common manifestation followed by polycythemia and somatostatinoma. The EPAS1 pathogenic variants are often postzygotic, and the timing of their acquirement during embryonic development seems to correlate with the number and timing of development of the disease manifestations. Although recurrent and multifocal disease is common in EPAS1-related PPGL, distant metastases are uncommon and usually indolent. This is illustrated by a case of a man who was diagnosed at the age of 9 years and is currently 56 years old, alive, and well for 47 years with these metastases. He was found to have a somatic EPAS1 pathogenic variant (c.1592C>A, p.Pro531His) in bilateral pheochomocytoma and a pancreatic NET (somatostatinoma) but not in genomic DNA isolated from peripheral leukocytes. This and previous reports suggest that distant metastases are uncommon and less aggressive in EPAS1-related PPGLs compared to those found in other hereditary PPGLs.
Topics: Humans; Male; Middle Aged; Adrenal Gland Neoplasms; Basic Helix-Loop-Helix Transcription Factors; Paraganglioma; Pheochromocytoma
PubMed: 38767322
DOI: 10.1530/ERC-23-0303 -
Acta Chirurgica Belgica Oct 2023Pheochromocytoma is a rare catecholamine-secreting tumor of neuroendocrine origin. It has a prevalence of <1% in adults with hypertension. In some cases, hypertension is...
BACKGROUND
Pheochromocytoma is a rare catecholamine-secreting tumor of neuroendocrine origin. It has a prevalence of <1% in adults with hypertension. In some cases, hypertension is associated with the classical triad of headache, sweating, and tachycardia. Cardiogenic shock due to stress-induced cardiomyopathy caused by catecholamine excess may rarely be the initial symptom of pheochromocytoma, mimicking Takotsubo Syndrome.
METHODS
We report the case of a 58-year-old female patient with pheochromocytoma-induced cardiogenic shock (PICS) in the early postoperative period after thyroidectomy.
RESULTS
PICS is caused by a catecholamine storm, which induces myocardial stress and cardiac dysfunction. In such cases, early management with mechanical circulatory assistance may be promptly considered, given the increased risk of mortality.
CONCLUSION
PICS is a rare and serious condition. Prompt diagnosis and adequate resuscitation measures are necessary to avoid high mortality.
Topics: Adult; Female; Humans; Middle Aged; Pheochromocytoma; Shock, Cardiogenic; Catecholamines; Adrenal Gland Neoplasms; Hypertension
PubMed: 35583372
DOI: 10.1080/00015458.2022.2079822 -
Abdominal Radiology (New York) May 2024
PubMed: 38761273
DOI: 10.1007/s00261-024-04289-6 -
Clinical Endocrinology Jul 2023Paediatric phaeochromocytomas and paragangliomas (PPGLs), though rare tumours, are associated with significant disability and death in the most vulnerable of patients... (Review)
Review
Paediatric phaeochromocytomas and paragangliomas (PPGLs), though rare tumours, are associated with significant disability and death in the most vulnerable of patients early in their lives. However, unlike cryptogenic and insidious disease states, the clinical presentation of paediatric patients with PPGLs can be rather overt, allowing early diagnosis, granted that salient findings are recognized. Additionally, with prompt and effective intervention, prognosis is favourable if timely intervention is implemented. For this reason, this review focuses on four exemplary paediatric cases, succinctly emphasizing the now state-of-the-art concepts in paediatric PPGL management.
PubMed: 37515400
DOI: 10.1111/cen.14955 -
Trends in Endocrinology and Metabolism:... Apr 2024Cushing's syndrome (CS) refers to the clinical features of prolonged pathological glucocorticoid excess. About 10-20% of individuals with CS have ectopic CS (ECS), that... (Review)
Review
Cushing's syndrome (CS) refers to the clinical features of prolonged pathological glucocorticoid excess. About 10-20% of individuals with CS have ectopic CS (ECS), that is, an adrenocorticotropin (ACTH)-producing tumour outside the pituitary gland. ACTH-secreting neuroendocrine neoplasia (NENs) can arise from many organs, although bronchial NEN, small cell lung cancer (SCLC), pancreatic NEN, thymic NEN, medullary thyroid cancer (MTC), and pheochromocytoma are the most common. Patients with ECS frequently present with severe hypercortisolism. The risk of life-threatening complications is high in severe cases, unless the hypercortisolism is effectively treated. A good outcome in ECS requires a methodical approach, incorporating prompt diagnosis, tumour localization, control of cortisol excess, and resection of the primary tumour when possible.
Topics: Humans; Cushing Syndrome; Adrenocorticotropic Hormone; Neuroendocrine Tumors; Pituitary Gland; Adrenal Gland Neoplasms
PubMed: 38143211
DOI: 10.1016/j.tem.2023.12.003