Endocrine oncology (Bristol, England)最新文献

{"title":"Succinate dehydrogenase variants in paraganglioma: why are B subunit variants 'bad'?","authors":"Lucinda M Gruber,&nbsp;Steven N Hart,&nbsp;Louis James Maher Iii","doi":"10.1530/EO-22-0093","DOIUrl":"https://doi.org/10.1530/EO-22-0093","url":null,"abstract":"<p><p>Mutations that predispose to familial pheochromocytoma and paraganglioma include inherited variants in the four genes (<i>SDHA</i>, <i>SDHB</i>, <i>SDHC</i> and <i>SDHD</i>) encoding subunits of succinate dehydrogenase (SDH), an enzyme of the mitochondrial tricarboxylic acid cycle and complex II of the electron transport chain. In heterozygous variant carriers, somatic loss of heterozygosity is thought to result in tumorigenic accumulation of succinate and reactive oxygen species. Inexplicably, variants affecting the SDHB subunit predict worse clinical outcomes. Why? Here we consider two hypotheses. First, relative to SDH A, C and D subunits, the small SDHB subunit might be more intrinsically 'fragile' to missense mutations because of its relatively large fraction of amino acids contacting prosthetic groups and other SDH subunits. We show evidence that supports this hypothesis. Second, the natural pool of human SDHB variants might, by chance, be biased toward severe truncating variants and missense variants causing more disruptive amino acid substitutions. We tested this hypothesis by creating a database of known SDH variants and predicting their biochemical severities. Our data suggest that natural SDHB variants are more pathogenic. It is unclear if this bias is sufficient to explain clinical data. Other explanations include the possibility that SDH subcomplexes remaining after SDHB loss have unique tumorigenic gain-of-function characteristics, and/or that SDHB may have additional unknown tumor-suppressor functions.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"3 1","pages":"e220093"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/58/cb/EO-22-0093.PMC10305465.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10171996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lobectomy and completion thyroidectomy rates increase after the 2015 American Thyroid Association Differentiated Thyroid Cancer Guidelines update.","authors":"Benjamin J Worrall,&nbsp;Alexander Papachristos,&nbsp;Ahmad Aniss,&nbsp;Anthony Glover,&nbsp;Stan B Sidhu,&nbsp;Roderick J Clifton-Bligh,&nbsp;Diana Learoyd,&nbsp;Venessa H M Tsang,&nbsp;Matti Gild,&nbsp;Bruce G Robinson,&nbsp;Mark S Sywak","doi":"10.1530/EO-22-0095","DOIUrl":"https://doi.org/10.1530/EO-22-0095","url":null,"abstract":"<p><strong>Background: </strong>The 2015 American Thyroid Association (ATA) Guidelines permit thyroid lobectomy (TL) or total thyroidectomy in the management of low-risk papillary thyroid cancer (PTC). As definitive risk-stratification is only possible post-operatively, some patients may require completion thyroidectomy (CT) after final histopathological analysis.</p><p><strong>Methods: </strong>A retrospective cohort study of patients undergoing surgery for low-risk PTC in a tertiary referral centre was undertaken. Consecutive adult patients treated from January 2013 to March 2021 were divided into two groups (pre- and post-publication of ATA Guidelines on 01/01/2016). Only those eligible for lobectomy under rule 35(B) of the ATA Guidelines were included: Bethesda V/VI cytology, 1-4 cm post-operative size and without pre-operative evidence of extrathyroidal extension or nodal metastases. We examined rates of TL, CT, local recurrence and surgical complications.</p><p><strong>Results: </strong>There were 1488 primary surgical procedures performed for PTC on consecutive adult patients during the study period, of which 461 were eligible for TL. Mean tumour size (<i>P</i> = 0.20) and mean age (<i>P</i> = 0.78) were similar between time periods. The TL rate increased significantly from 4.5 to 18% in the post-publication period (<i>P</i> < 0.001). The proportion of TL patients requiring CT (43 vs 38%) was similar between groups (<i>P</i> = 1.0). There was no significant change in complications (<i>P</i> = 0.55) or local recurrence rates (<i>P</i> = 0.24).</p><p><strong>Conclusion: </strong>The introduction of the 2015 ATA Guidelines resulted in a modest but significant increase in the rate of lobectomy for eligible PTC patients. In the post-publication period, 38% of patients who underwent TL ultimately required CT after complete pathological analysis.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"3 1","pages":"e220095"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9f/ba/EO-22-0095.PMC10305631.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9869874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pituitary tumors and the risk of other malignancies: is the relationship coincidental or causal?","authors":"Sandra Pekic, Marko Stojanovic, Vera Popovic","doi":"10.1530/EO-21-0033","DOIUrl":"10.1530/EO-21-0033","url":null,"abstract":"<p><p>Pituitary adenomas are benign neoplasms of the pituitary. The most prevalent are prolactinomas and non-functioning pituitary adenomas, followed by growth hormone- and ACTH-secreting adenomas. Most pituitary adenomas seem to be sporadic and their persistent growth is very atypical. No molecular markers predict their behavior. The occurrence of pituitary adenomas and malignancies in the same patient can be either pure coincidence or caused by shared underlying genetic susceptibility involved in tumorigenesis. Detailed family history on cancers/tumors in the first, second and third generation of family members on each side of the family has been reported in a few studies. They found an association of pituitary tumors with positive family history for breast, lung and colorectal cancer. We have reported that in about 50% of patients with pituitary adenomas, an association with positive family history for cancer has been found independent of secretory phenotype (acromegaly, prolactinoma, Cushing's disease or non-functioning pituitary adenomas). We also found earlier onset of pituitary tumors (younger age at diagnosis of pituitary tumors) in patients with a strong family history of cancer. In our recent unpublished series of 1300 patients with pituitary adenomas, 6.8% of patients were diagnosed with malignancy. The latency period between the diagnosis of pituitary adenoma and cancer was variable, and in 33% of patients, it was longer than 5 years. Besides the inherited trophic mechanisms (shared underlying genetic variants), the potential influence of shared complex epigenetic influences (environmental and behavioral factors - obesity, smoking, alcohol intake and insulin resistance) is discussed. Further studies are needed to better understand if patients with pituitary adenomas are at increased risk for cancer.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"2 1","pages":"R1-R13"},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10191702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cabergoline-associated valvulopathy of the tricuspid valve in the treatment of prolactinoma.","authors":"Annabelle G Hayes, Masoumeh G Shirazi, Anand Thiyagarajah, David J Torpy, Sunita M C De Sousa","doi":"10.1530/EO-22-0086","DOIUrl":"10.1530/EO-22-0086","url":null,"abstract":"<p><p>Cabergoline-associated valvulopathy (CAV) is defined by the echocardiographic triad of moderate or severe regurgitation, valvular thickening and restricted valvular motion. While it is a well-described complication of dopamine agonist therapy in Parkinson's disease, only three convincing cases of CAV have previously been described in the treatment of prolactinoma, with none involving the tricuspid valve. We describe a case of CAV affecting the tricuspid valve, ultimately resulting in the patient's death. The novel finding of CAV affecting the tricuspid valve suggests a possible link between confirmed cases of CAV and the echocardiographic surveillance studies of cabergoline-treated prolactinoma patients which have mostly demonstrated subclinical tricuspid valve changes. The risk of CAV, although small, prompts a mindful prescription of dopamine agonist therapy for prolactinomas and consideration of measures to minimise cabergoline exposure. The cumulative cabergoline doses and duration of therapy associated with CAV in published cases exceed what has been evaluated in case series and surveillance studies, underscoring the importance of case reports in understanding CAV.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"3 1","pages":"e220086"},"PeriodicalIF":0.0,"publicationDate":"2022-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/84/89/EO-22-0086.PMC10305698.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9869875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential pitfalls in diagnosis of immunotherapy-induced hypothalamic-pituitary-adrenal axis suppression.","authors":"Darran Mc Donald, Rachel Katherine Crowley","doi":"10.1530/EO-22-0069","DOIUrl":"10.1530/EO-22-0069","url":null,"abstract":"","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"2 1","pages":"L1-L3"},"PeriodicalIF":0.0,"publicationDate":"2022-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10191707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pheochromocytoma and paraganglioma: germline genetics and hereditary syndromes.","authors":"Christie G Turin, Molly M Crenshaw, Lauren Fishbein","doi":"10.1530/EO-22-0044","DOIUrl":"10.1530/EO-22-0044","url":null,"abstract":"<p><p>Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors arising from the adrenal medulla and extra-adrenal ganglia, respectively. Approximately 15-25% of PCC/PGL can become metastatic. Up to 30-40% of patients with PCC/PGL have a germline pathogenic variant in a known susceptibility gene for PCC/PGL; therefore, all patients with PCC/PGL should undergo clinical genetic testing. Most of the susceptibility genes are associated with variable penetrance for PCC/PGL and are associated with different syndromes, which include susceptibility for other tumors and conditions. The objective of this review is to provide an overview of the germline susceptibility genes for PCC/PGL, the associated clinical syndromes, and recommended surveillance.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"2 1","pages":"R65-R77"},"PeriodicalIF":0.0,"publicationDate":"2022-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10191706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dopamine agonist therapy for prolactinomas: do we need to rethink the place of surgery in prolactinoma management?","authors":"Sunita M C De Sousa","doi":"10.1530/EO-21-0038","DOIUrl":"10.1530/EO-21-0038","url":null,"abstract":"<p><p>The current treatment paradigm for prolactinomas involves dopamine agonist (DA) therapy as the first-line treatment, with surgical resection reserved for cases where there is DA failure due to resistance or intolerance. This review highlights how DA therapy can be optimised to overcome its increasingly recognised pitfalls, whilst also addressing the potential for expanding the use of surgery in the management of prolactinomas. The first part of the review discusses the limitations of DA therapy, namely: DA resistance; common DA side effects; and the rare but serious DA-induced risks of cardiac valvulopathy, impulse control disorders, psychosis, CSF rhinorrhoea and tumour fibrosis. The second part of the review explores the role of surgery in prolactinoma management with reference to its current second-line position and recent calls for surgery to be considered as an alternative first-line treatment alongside DA therapy. Randomised trials comparing medical vs surgical therapy for prolactinomas are currently underway. Pending these results, a low surgical threshold approach is herein proposed, whereby DA therapy remains the default treatment for prolactinomas unless there are specific triggers to consider surgery, including concern regarding DA side effects or risks in vulnerable patients, persistent and bothersome DA side effects, emergence of any serious risks of DA therapy, expected need for long-term DA therapy, as well as the traditional indications for surgery. This approach should optimise the use of DA therapy for those who will most benefit from it, whilst instituting surgery early in others in order to minimise the cumulative burden of prolonged DA therapy.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"2 1","pages":"R31-R50"},"PeriodicalIF":0.0,"publicationDate":"2022-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/82/fb/EO-21-0038.PMC10259306.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10191708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pituitary carcinoma: reclassification and implications in the NET schema.","authors":"Sylvia L Asa, Shereen Ezzat","doi":"10.1530/EO-22-0041","DOIUrl":"10.1530/EO-22-0041","url":null,"abstract":"<p><p>The entity known as pituitary carcinoma has been traditionally defined as a tumor of adenohypophysial cells that metastasizes systemically or craniospinally independent of the histological appearance of the lesion. Reported cases of pituitary carcinoma have clinically and histologically resembled their non-metastatic counterparts that were classified as adenomas; the majority of cases were initially diagnosed as adenomas, and with tumor progression and spread, the diagnosis was changed to carcinoma. This classification has been challenged since the definition of malignancy in most organs is not based only on metastatic spread. The extent of local invasion resulting in an inability to completely resect an adenohypophysial tumor can have serious consequences that can cause harm and are therefore not benign. To address this dilemma, it was proposed that pituitary tumors be classified as neuroendocrine tumors. This change in nomenclature is totally appropriate since these tumors are composed of classical neuroendocrine cells; as with other neuroendocrine tumors, they have variable behavior that can be indolent but can involve metastasis. With the new nomenclature, there is no requirement for a distinction between adenomas and carcinomas. Moreover, the WHO/IARC has provided an overarching classification for neuroendocrine neoplasms at all body sites; in this new classification, the term 'neuroendocrine carcinoma' is reserved for poorly differentiated high-grade malignancies that are clinically, morphologically and genetically distinct from well-differentiated neuroendocrine tumors. It remains to be determined if there are true pituitary neuroendocrine carcinomas.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"2 1","pages":"R14-R23"},"PeriodicalIF":0.0,"publicationDate":"2022-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fd/c3/EO-22-0041.PMC10259303.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9815507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant therapy in adrenocortical carcinoma: prognostic factors and treatment options.","authors":"Ruaa Al-Ward,&nbsp;Celeste Zsembery,&nbsp;Mouhammed Amir Habra","doi":"10.1530/EO-22-0050","DOIUrl":"https://doi.org/10.1530/EO-22-0050","url":null,"abstract":"<p><p>Adrenocortical carcinoma (ACC) is a rare cancer with high recurrence rates and heterogeneous clinical behavior. The role of adjuvant therapy remains unclear because of the challenges in collecting high-quality data for a rare cancer. The current treatment recommendations and guidelines for adjuvant therapy are mostly derived retrospectively from national databases and the treatment outcomes of patients seen in referral centers. To better select patients for adjuvant therapy, multiple factors need to be considered including staging, markers of cellular proliferation (such as Ki67%), resection margins, hormonal function, and possibly genetic alterations of the tumor as well as patient-related factors such as age and performance status. Adjuvant mitotane remains the most commonly used adjuvant therapy in ACC based on clinical practice guidelines, though emerging data from ADIUVO trial (mitotane vs observation in low-risk ACC) suggest that mitotane use in low-risk patients may not be needed. An ongoing clinical trial (ADIUVO-2) is evaluating the role of mitotane vs mitotane combined with chemotherapy in high-risk ACC. The use of adjuvant therapy has been controversial but can be justified in select patients with positive resection margins or after the resection of localized recurrence. A prospective study is needed to study the role of adjuvant radiation in ACC as radiation is expected to help only with local control without impact on distant microscopic metastases. There are no recommendations or published data about using adjuvant immunotherapy in ACC, but this may be a future study after establishing the efficacy and safety profile of immunotherapy in metastatic ACC.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"2 1","pages":"R90-R101"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b5/cf/EO-22-0050.PMC10259337.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9805304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient remission of hyperparathyroidism after fine-needle aspiration biopsy.","authors":"Ana Rita Elvas,&nbsp;Andreia Martins Fernandes,&nbsp;Sara Reis,&nbsp;Joana Couto,&nbsp;Raquel G Martins,&nbsp;Jacinta Santos,&nbsp;Teresa Martins,&nbsp;Bernardo Marques,&nbsp;Joana Guimarães,&nbsp;Fernando J C Rodrigues","doi":"10.1530/EO-22-0060","DOIUrl":"https://doi.org/10.1530/EO-22-0060","url":null,"abstract":"<p><p>Primary hyperparathyroidism (PHPT) is the unregulated overproduction of parathyroid hormone (PTH), resulting in abnormal calcium homeostasis. PHPT is most commonly caused by a single adenoma of the parathyroid gland, which can have an intrathyroid location in rare cases. The measurement of intact PTH in the washout fluid obtained by ultrasound (US)-guided fineneedle aspiration (FNA) can be useful in clarifying the aetiology of these lesions. This study presented a 48-year-old man with a background history of symptomatic renal stone disease who was diagnosed with PHPT and referred to our Endocrinology department. A neck US revealed a thyroid nodule with a size of 21 mm in the right lobe. The patient underwent US-guided FNA of the lesion. The measurement of PTH in the washout fluid was significantly elevated. Following the procedure, he reported neck pain and noticed distal paraesthesias in the upper limbs. Blood test results showed significant hypocalcaemia and supplementation with calcium and calcitriol was started. The patient was closely monitored. Recurrence of hypercalcaemia was later observed, and the patient was submitted to surgery. We present a case of FNAinduced transitory remission of PHPT in a patient with an intrathyroid parathyroid adenoma. We conjecture that intra-nodular haemorrhage might have occurred, which temporarily affected the viability of the autonomous parathyroid tissue. A few similar cases of spontaneous or induced remission of PHPT after FNA have been previously described in the literature. This remission can be transitory or permanent, depending on the degree of cellular damage thus follow-up of these patients is recommended.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"2 1","pages":"K10-K14"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9815504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}