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Article ; Online: Imaging of Pheochromocytomas and Paragangliomas.

Timmers, Henri J L M / Taïeb, David / Pacak, Karel / Lenders, Jacques W M

2024

Abstract: 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 ... ...

Abstract	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 (e.g. 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 as well as 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 workup and course of the disease, including adrenal incidentaloma, established biochemical diagnosis, post-surgical follow-up, tumor screening in pathogenic variant carriers, staging and restaging of metastatic disease, theranostics and response monitoring.
Language	English
Publishing date	2024-01-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	603096-8
ISSN	1945-7189 ; 0163-769X
ISSN (online)	1945-7189
ISSN	0163-769X
DOI	10.1210/endrev/bnae001
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Article ; Online: Onverwachte spontane zwangerschap bij vrouwen met het syndroom van Turner.

Meijerink, Aukje M / Besselink, Dagmar E / Timmers, Henri J L M / Duijnhouwer, Anthonie L / van der Velden, Janiëlle A E M / Beerendonk, C C M

Nederlands tijdschrift voor geneeskunde

2024 Volume 168

Abstract: Most women with Turner syndrome have premature ovarian insufficiency from childhood. The chance of a spontaneous pregnancy is higher in women with a Turner mosaicism and in women who have had a spontaneous menarche. This chance is estimated at 5-8%. We ... ...

Title translation	Unexpected spontaneous pregnancy in women with Turner syndrome.
Abstract	Most women with Turner syndrome have premature ovarian insufficiency from childhood. The chance of a spontaneous pregnancy is higher in women with a Turner mosaicism and in women who have had a spontaneous menarche. This chance is estimated at 5-8%. We discuss 2 women with Turner mosaicism who were misinformed about their chances of a spontaneous pregnancy. In both cases, puberty induction was started because of suspected gonadal dysgenesis but in retrospect only puberty was delayed, while ovarian function was still good at that time. The cases presented show that in long-term follow-up there is a pitfall in adopting incorrect assumptions. Critical re-evaluation of medical data during childhood and adolescence is therefore essential. The impact of infertility is great in women with Turner syndrome. Because pregnancy has an increased risk of complications, an unplanned pregnancy should be prevented.
MeSH term(s)	Adolescent ; Pregnancy ; Female ; Humans ; Turner Syndrome/complications ; Pregnancy, Unplanned ; Infertility
Language	Dutch
Publishing date	2024-03-06
Publishing country	Netherlands
Document type	English Abstract ; Journal Article
ZDB-ID	82073-8
ISSN	1876-8784 ; 0028-2162
ISSN (online)	1876-8784
ISSN	0028-2162
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Article ; Online: MITOCHONDRIA: Succinate dehydrogenase subunit B-associated phaeochromocytoma and paraganglioma.

Dona, Margo / Neijman, Kim / Timmers, Henri J L M

The international journal of biochemistry & cell biology

2021 Volume 134, Page(s) 105949

Abstract: Phaeochromocytomas and paragangliomas are rare neuroendocrine tumours. So far, over 20 causative genes have been identified, of which the most frequent and strongest indicator for malignancies are mutations in succinate dehydrogenase subunit B. No ... ...

Abstract	Phaeochromocytomas and paragangliomas are rare neuroendocrine tumours. So far, over 20 causative genes have been identified, of which the most frequent and strongest indicator for malignancies are mutations in succinate dehydrogenase subunit B. No curative therapy is available for patients with metastases resulting in poor prognosis. Therapy development has been hindered by lack of suitable model systems. The succinate dehydrogenase complex is located in the inner membrane of the mitochondria and plays a crucial role in the oxidative phosphorylation chain and the tricarboxylic acid-cycle. Succinate dehydrogenase deficiency results in accumulation of the oncometabolite succinate inducing hypoxia inducible factor stabilization, deoxyribonucleic acid and histone methylation inhibition, and impaired production of adenosine triphosphate. It remains unknown which combination of pathways and/or triggers are decisive for metastases development. In this review, the role of mitochondria in malignant succinate dehydrogenase subunit B-associated phaeochromocytomas and paragangliomas and implications for mitochondria as therapeutic target are discussed.
MeSH term(s)	Adrenal Gland Neoplasms/enzymology ; Adrenal Gland Neoplasms/genetics ; Adrenal Gland Neoplasms/metabolism ; Adrenal Gland Neoplasms/pathology ; Animals ; Electron Transport Complex II/deficiency ; Electron Transport Complex II/genetics ; Electron Transport Complex II/metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Metabolism, Inborn Errors/enzymology ; Metabolism, Inborn Errors/genetics ; Metabolism, Inborn Errors/metabolism ; Metabolism, Inborn Errors/pathology ; Mitochondria/enzymology ; Mitochondria/genetics ; Mitochondria/metabolism ; Mitochondria/pathology ; Mitochondrial Diseases/enzymology ; Mitochondrial Diseases/genetics ; Mitochondrial Diseases/metabolism ; Mitochondrial Diseases/pathology ; Mutation ; Paraganglioma/enzymology ; Paraganglioma/genetics ; Paraganglioma/metabolism ; Paraganglioma/pathology ; Pheochromocytoma/enzymology ; Pheochromocytoma/genetics ; Pheochromocytoma/metabolism ; Pheochromocytoma/pathology ; Reactive Oxygen Species/metabolism ; Succinate Dehydrogenase/genetics ; Succinate Dehydrogenase/metabolism
Chemical Substances	HIF1A protein, human ; Hypoxia-Inducible Factor 1, alpha Subunit ; Reactive Oxygen Species ; Electron Transport Complex II (EC 1.3.5.1) ; SDHB protein, human (EC 1.3.5.1) ; Succinate Dehydrogenase (EC 1.3.99.1)
Language	English
Publishing date	2021-02-17
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1228429-4
ISSN	1878-5875 ; 1357-2725
ISSN (online)	1878-5875
ISSN	1357-2725
DOI	10.1016/j.biocel.2021.105949
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Zs.A 431: Show issues

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Article ; Online: Response to Letter to the Editor "CT Characteristics of Pheochromocytoma: Relevance for the Evaluation of Adrenal Incidentaloma".

Canu, Letizia / Timmers, Henri J L M

The Journal of clinical endocrinology and metabolism

2019 Volume 104, Issue 11, Page(s) 5114–5115

MeSH term(s)	Adrenal Gland Neoplasms/surgery ; Adrenalectomy ; Humans ; Pheochromocytoma/surgery ; Tomography, X-Ray Computed
Language	English
Publishing date	2019-05-21
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/jc.2019-00868
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Article: Targeting the Redox Balance Pathway Using Ascorbic Acid in

Dona, Margo / Lamers, Maaike / Rohde, Svenja / Gorissen, Marnix / Timmers, Henri J L M

Cancers

2021 Volume 13, Issue 20

Abstract: Patients with mutations in the β-subunit of the succinate dehydrogenase ( ...

Abstract	Patients with mutations in the β-subunit of the succinate dehydrogenase (
Language	English
Publishing date	2021-10-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13205124
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Article: Extensive patient-to-patient single nucleus transcriptome heterogeneity in pheochromocytomas and paragangliomas.

Brazda, Peter / Ruiz-Moreno, Cristian / Megchelenbrink, Wout L / Timmers, Henri J L M / Stunnenberg, Hendrik G

Frontiers in oncology

2022 Volume 12, Page(s) 965168

Abstract: Pheochromocytoma, neuroendocrine tumor, single cell RNA-sequencing, transcriptome, heterogeneity, SDHB, RET, paraganglinoma; Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors with varied genetic makeup and are associated with ... ...

Abstract	Pheochromocytoma, neuroendocrine tumor, single cell RNA-sequencing, transcriptome, heterogeneity, SDHB, RET, paraganglinoma; Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors with varied genetic makeup and are associated with high cardiovascular morbidity and a variable risk of malignancy. The source of the transcriptional heterogeneity of the disease and the underlying biological processes that determine the outcome of PCPG remain largely unclear. We focused on PCPG tumors with germline SDHB and RET mutations, which represent distinct prognostic groups with worse or better prognoses, respectively. We applied single-nuclei RNA sequencing (snRNA-seq) to tissue samples from 11 patients and found high patient-to-patient transcriptome heterogeneity in neuroendocrine tumor cells. The tumor microenvironment also showed heterogeneous profiles, mainly contributed by macrophages of the immune cell clusters and Schwann cells of the stroma. By performing non-negative matrix factorization, we identified common transcriptional programs active in RET and SDHB, as well as distinct modules, including neuronal development, hormone synthesis and secretion, and DNA replication. Similarities between the transcriptomes of the tumor cells and those of the chromaffin- and precursor cell types suggests different developmental stages at which PC and PG tumors appear to be arrested.
Language	English
Publishing date	2022-08-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.965168
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Article ; Online: A prospective case series to evaluate subcostal nerve injury with high-resolution ultrasound in posterior retroperitoneoscopic adrenalectomy.

van Uitert, Allon / Chaman-Baz, Hossein A / van der Wal, Selina E I / Zhu, Xiaoye / Wijntjes, Juerd / Timmers, Henri J L M / Witjes, J Alfred / van Alfen, Nens / Langenhuijsen, Johan F

Surgical endoscopy

2024

Abstract: Background: Posterior retroperitoneoscopic adrenalectomy has several advantages over transabdominal laparoscopic adrenalectomy regarding operating time, blood loss, postoperative pain, and recovery. However, postoperatively several patients report ... ...

Abstract	Background: Posterior retroperitoneoscopic adrenalectomy has several advantages over transabdominal laparoscopic adrenalectomy regarding operating time, blood loss, postoperative pain, and recovery. However, postoperatively several patients report chronic pain or hypoesthesia. We hypothesized that these symptoms may be the result of damage to the subcostal nerve, because it passes the surgical area. Methods: A prospective single-center case series was performed in adult patients without preoperative pain or numbness of the abdominal wall who underwent unilateral posterior retroperitoneoscopic adrenalectomy. Patients received pre- and postoperative questionnaires and a high-resolution ultrasound scan of the subcostal nerve and abdominal wall muscles was performed before and directly after surgery. Clinical evaluation at 6 weeks was performed with repeat questionnaires, physical examination, and high-resolution ultrasound. Long-term recovery was evaluated with questionnaires, and photographs from the patients were examined for abdominal wall asymmetry. Results: A total of 25 patients were included in the study. There were no surgical complications. Preoperative visualization of the subcostal nerve was possible in all patients. At 6 weeks, ultrasound showed nerve damage in 15 patients, with no significant association between nerve damage and postsurgical pain. However, there was a significant association between nerve damage and hypoesthesia (p = 0.01), sensory (p < 0.001), and motor (p < 0.001) dysfunction on physical examination. After a median follow-up of 18 months, 5 patients still experienced either numbness or muscle weakness, and one patient experienced chronic postsurgical pain. Conclusion: In this exporatory case series the incidence of postoperative damage to the subcostal nerve, both clinically and radiologically, was 60% after posterior retroperitoneoscopic adrenalectomy. There was no association with pain, and the spontaneous recovery rate was high.
Language	English
Publishing date	2024-04-16
Publishing country	Germany
Document type	Journal Article
ZDB-ID	639039-0
ISSN	1432-2218 ; 0930-2794
ISSN (online)	1432-2218
ISSN	0930-2794
DOI	10.1007/s00464-024-10836-5
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Zs.A 2214: Show issues

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Article ; Online: Response to Letter to the Editor: "Approach to the Patient: Perioperative Management of the Patient With Pheochromocytoma or Sympathetic Paraganglioma".

Berends, Annika M A / Kerstens, Michiel N / Lenders, Jacques W M / Timmers, Henri J L M

The Journal of clinical endocrinology and metabolism

2020 Volume 105, Issue 12

MeSH term(s)	Adrenal Gland Neoplasms/surgery ; Brain Neoplasms ; Humans ; Paraganglioma/surgery ; Pheochromocytoma/surgery
Language	English
Publishing date	2020-09-07
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgaa602
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Article: MITOCHONDRIA: Succinate dehydrogenase subunit B-associated phaeochromocytoma and paraganglioma

Dona, Margo / Neijman, Kim / Timmers, Henri J.L.M

international journal of biochemistry & cell biology. 2021 May, v. 134

2021

Abstract	Phaeochromocytomas and paragangliomas are rare neuroendocrine tumours. So far, over 20 causative genes have been identified, of which the most frequent and strongest indicator for malignancies are mutations in succinate dehydrogenase subunit B. No curative therapy is available for patients with metastases resulting in poor prognosis. Therapy development has been hindered by lack of suitable model systems. The succinate dehydrogenase complex is located in the inner membrane of the mitochondria and plays a crucial role in the oxidative phosphorylation chain and the tricarboxylic acid-cycle. Succinate dehydrogenase deficiency results in accumulation of the oncometabolite succinate inducing hypoxia inducible factor stabilization, deoxyribonucleic acid and histone methylation inhibition, and impaired production of adenosine triphosphate. It remains unknown which combination of pathways and/or triggers are decisive for metastases development. In this review, the role of mitochondria in malignant succinate dehydrogenase subunit B-associated phaeochromocytomas and paragangliomas and implications for mitochondria as therapeutic target are discussed.
Keywords	DNA ; adenosine triphosphate ; histones ; hypoxia ; methylation ; mitochondria ; oxidative phosphorylation ; prognosis ; succinate dehydrogenase (quinone) ; succinic acid ; therapeutics
Language	English
Dates of publication	2021-05
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	1228429-4
ISSN	1878-5875 ; 1357-2725
ISSN (online)	1878-5875
ISSN	1357-2725
DOI	10.1016/j.biocel.2021.105949
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 431: Show issues

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Article ; Online: Approach to the Patient: Perioperative Management of the Patient with Pheochromocytoma or Sympathetic Paraganglioma.

Berends, Annika M A / Kerstens, Michiel N / Lenders, Jacques W M / Timmers, Henri J L M

The Journal of clinical endocrinology and metabolism

2020 Volume 105, Issue 9

Abstract: Pheochromocytomas and sympathetic paraganglioma (PPGL) are rare chromaffin cell tumors originating in the adrenal medulla and sympathetic paraganglia, respectively, which share the capacity to synthesize and release catecholamines. The incidence of PPGL ... ...

Abstract	Pheochromocytomas and sympathetic paraganglioma (PPGL) are rare chromaffin cell tumors originating in the adrenal medulla and sympathetic paraganglia, respectively, which share the capacity to synthesize and release catecholamines. The incidence of PPGL has increased in recent years. Surgical resection is the only curative treatment for PPGL. Management of patients with PPGL is complex and should be done by a specialized multidisciplinary team in centers with broad expertise. Surgical resection of a PPGL is a high-risk procedure for which optimal pretreatment with antihypertensive drugs is required in combination with state-of-the-art surgical procedures and anesthesiological techniques. In this article we discuss the underlying evidence and the pros and cons of presurgical medical preparation. Finally, the areas of uncertainty and controversies in this field are addressed.
MeSH term(s)	Adrenal Gland Neoplasms/complications ; Adrenal Gland Neoplasms/diagnosis ; Adrenal Gland Neoplasms/drug therapy ; Adrenal Gland Neoplasms/surgery ; Antihypertensive Agents/administration & dosage ; Autonomic Nervous System Diseases/diagnosis ; Autonomic Nervous System Diseases/drug therapy ; Autonomic Nervous System Diseases/etiology ; Autonomic Nervous System Diseases/surgery ; Combined Modality Therapy ; Drug Administration Schedule ; Female ; Humans ; Paraganglia, Chromaffin/pathology ; Paraganglioma/complications ; Paraganglioma/diagnosis ; Paraganglioma/drug therapy ; Paraganglioma/surgery ; Patient-Centered Care/methods ; Patient-Centered Care/organization & administration ; Perioperative Care/methods ; Perioperative Care/standards ; Perioperative Period ; Pheochromocytoma/complications ; Pheochromocytoma/diagnosis ; Pheochromocytoma/drug therapy ; Pheochromocytoma/surgery ; Young Adult
Chemical Substances	Antihypertensive Agents
Keywords	covid19
Language	English
Publishing date	2020-07-28
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgaa441
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