Endocrine oncology (Bristol, England)最新文献

{"title":"Low but not undetectable early postoperative nadir serum cortisol predicts sustained remission in Cushing's disease.","authors":"Anna Stroud,&nbsp;Pearl Dhaliwal,&nbsp;Richard J Harvey,&nbsp;Raquel Alvarado,&nbsp;Benjamin P Jonker,&nbsp;Mark J Winder,&nbsp;Jessica W Grayson,&nbsp;Ann McCormack","doi":"10.1530/EO-21-0026","DOIUrl":"https://doi.org/10.1530/EO-21-0026","url":null,"abstract":"<p><strong>Objective: </strong>Transsphenoidal surgery (TSS) is the first-line treatment for Cushing's disease. The objectives of the study were to determine remission and recurrence rates after TSS for Cushing's disease, identify factors that predict these outcomes, and define the threshold for postoperative morning serum cortisol (MSeC) that most accurately predicts sustained remission.</p><p><strong>Methods: </strong>Records were retrospectively reviewed for consecutive adults undergoing TSS for Cushing's disease at a tertiary centre (1990-2019). Remission was defined as MSeC <138 nmol/L by 6 weeks postoperatively. Recurrence was defined as elevated 24-h urine free cortisol, lack of suppression after dexamethasone or elevated midnight salivary cortisol.</p><p><strong>Results: </strong>In this study, 42 patients (age 47 ± 13 years, 83% female) were assessed with 55 ± 56 months of follow-up. Remission occurred after 77% of primary (<i>n</i> = 30) and 42% of revision operations (<i>n</i> = 12). After primary surgery, remission was associated with lower MSeC nadir (26 ± 36 nmol/L vs 347 ± 220 nmol/L, <i>P</i>  < 0.01) and lower adrenocorticotropin nadir (2 ± 3 pmol/L vs 6 ± 3 pmol/L, <i>P</i> = 0.01). Sustained remission 5 years after surgery was predicted by MSeC <92 nmol/L within 2 weeks postoperatively (sensitivity 100% and specificity 100%). After revision surgery, remission was predicted by lower MSeC nadir (70 ± 45 nmol/L vs 408 ± 305 nmol/L, <i>P</i> = 0.03), smaller tumour diameter (3 ± 2 mm vs 15 ± 13 mm, <i>P</i> = 0.05) and absence of cavernous sinus invasion (0% vs 71%, <i>P</i> = 0.03). Recurrence after primary and revision surgery occurred in 17% and 20% of patients respectively.</p><p><strong>Conclusions: </strong>Lower postoperative MSeC nadir strongly predicted remission after both primary and revision surgery. Following primary surgery, an MSeC <92 nmol/L within 2 weeks predicted sustained remission at 5 years. MSeC nadir was the most important prognostic marker following TSS for Cushing's disease.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"2 1","pages":"19-31"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9805302","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":"Diverse role of androgen action in human breast cancer.","authors":"Kiyoshi Takagi,&nbsp;Mio Yamaguchi,&nbsp;Minoru Miyashita,&nbsp;Hironobu Sasano,&nbsp;Takashi Suzuki","doi":"10.1530/EO-22-0048","DOIUrl":"https://doi.org/10.1530/EO-22-0048","url":null,"abstract":"<p><p>Breast cancer is a hormone-dependent cancer, and sex steroids play a pivotal role in breast cancer progression. Estrogens are strongly associated with breast cancers, and the estrogen receptor (estrogen receptor α; ERα) is expressed in 70-80% of human breast carcinoma tissues. Although antiestrogen therapies (endocrine therapies) have significantly improved clinical outcomes in ERα-positive breast cancer patients, some patients experience recurrence after treatment. In addition, patients with breast carcinoma lacking ERα expression do not benefit from endocrine therapy. The androgen receptor (AR) is also expressed in >70% of breast carcinoma tissues. Growing evidence supports this novel therapeutic target for the treatment of triple-negative breast cancers that lack ERα, progesterone receptor, and human EGF receptor 2, and ERα-positive breast cancers, which are resistant to conventional endocrine therapy. However, the clinical significance of AR expression is still controversial and the biological function of androgens in breast cancers is unclear. In this review, we focus on the recent findings concerning androgen action in breast cancers and the contributions of androgens to improved breast cancer therapy.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"2 1","pages":"R102-R111"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9812413","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":"Unusual presentation of lung carcinoma with pituitary metastasis: a challenging diagnosis and sodium management dilemmas.","authors":"Poh Shean Wong,&nbsp;Subashini Rajoo,&nbsp;Hairuddin Achmad Sankala,&nbsp;Mohamed Badrulnizam Long Bidin","doi":"10.1530/EO-22-0064","DOIUrl":"https://doi.org/10.1530/EO-22-0064","url":null,"abstract":"<p><strong>Summary: </strong>Pituitary metastasis (PM) is a rare complication of an advanced malignancy. Albeit rare, PM can be more detected and achieve a longer survival rate through frequent neuroimaging and newer oncology therapies. Lung cancer is the most frequent primary site, followed by breast and kidney cancers. Patients with lung cancer generally present with respiratory symptoms and are commonly diagnosed at an advanced stage already. Nevertheless, physicians should be mindful of other systemic manifestations as well as signs and symptoms related to metastatic spread and paraneoplastic syndromes. Herein, we report the case of a 53-year-old woman who presented with PM as the first sign of an undiagnosed lung cancer. Initially, her condition was a challenging diagnosis and was even complicated with diabetes insipidus (DI), which can present as severe hyponatremia when coexisting with adrenal insufficiency. This case also highlights that treating DI with antidiuretic hormone (ADH) replacement was complicated by extreme difficulties in attaining satisfactory sodium and water balance during the clinical course, with the possibility of coexistent DI and syndrome of inappropriate ADH secretion because of the underlying lung cancer.</p><p><strong>Learning points: </strong>When patients present with pituitary mass and diabetes insipidus (DI), pituitary metastasis should be considered as an initial differential diagnosis. DI caused by pituitary adenoma is rare and is typically a late finding.DI can present as severe hyponatremia when coexisting with adrenal insufficiency.Cortisol can directly inhibit endogenous antidiuretic hormone (ADH) secretion. Patients with adrenocorticotropic hormone deficiency will have increased tonic ADH activity and subsequently reduced capacity for free-water excretion. However, when on steroid therapy, patients should be monitored for possible DI because steroids can restore free-water excretion.A substantial change in serum sodium after desmopressin treatment should eliminate the possibility of desmopressin overdose or coexistence of DI and syndrome of inappropriate ADH secretion in patients with lung cancer. Therefore, frequent monitoring of serum sodium concentrations is crucial.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"2 1","pages":"K15-K20"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9815506","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":"SAKK 21/12: a phase II trial of transdermal CR1447 in breast cancer patients.","authors":"Marcus Vetter,&nbsp;Karin M Rothgiesser,&nbsp;Qiyu Li,&nbsp;Hanne Hawle,&nbsp;Wolfgang Schönfeld,&nbsp;Karin Ribi,&nbsp;Salome Riniker,&nbsp;Roger von Moos,&nbsp;Andreas Trojan,&nbsp;Elena Kralidis,&nbsp;Mathias Fehr,&nbsp;Andreas Müller,&nbsp;Beat Thürlimann","doi":"10.1530/EO-21-0009","DOIUrl":"https://doi.org/10.1530/EO-21-0009","url":null,"abstract":"<p><strong>Objective: </strong>CR1447, a novel transdermal formulation of 4-hydroxytestosterone, has aromatase-inhibiting and androgen receptor (AR)-modulating properties (IC₅₀4.4 nM) with antitumor effects against AR-positive tumor cells <i>in vitro.</i> This trial investigated the efficacy and safety of CR1447 for patients with metastatic estrogen receptor-positive (A) and AR-positive triple-negative breast cancers (B).</p><p><strong>Design and methods: </strong>(A) included patients with at most one prior endocrine therapy line without progression ≥6 months, whereas (B) included patients with ≤2 prior chemotherapy lines, all displaying advanced signs of disease. The primary endpoint was disease control at week 24 (DC24). The null hypothesis was DC24 ≤30% (A) and ≤15% (B). Thirty-seven patients were recruited (29 in (A) and 8 in (B)); accrual was stopped following an interim analysis demonstrating futility in (A) and slow accrual in (B).</p><p><strong>Results: </strong>DC24 was attained in 5/21 (95% CI: 8.2-47.2) patients in (A) and none in (B). The median progression-free survival was 5.1 months (95% CI: 2.5-5.6) in (A) and 2.5 months (95% CI: 0.7-2.6) in (B). The median overall survival was 24.6 months (95% CI: 22.9-not applicable) in (A) and 10.8 months (95% CI: 3.3-10.9) in (B). CR1447 had a favorable safety profile without treatment-related grade 3-5 toxicities in (A). Especially no side effects linked to androgenic effects were observed.</p><p><strong>Conclusions: </strong>Despite this trial being negative, the 24% DC24 rate in a second-line setting, and the prolonged partial response experienced by a patient, indicate activity. Further evaluation of CR1447 in endocrine-sensitive patients or combination trials appears warranted.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"2 1","pages":"9-18"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9870423","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":"Synchronous AML and pancreatic neuroendocrine neoplasm, both successfully treated with somatostatin analogs and decitabine.","authors":"Syed Ehsanullah,&nbsp;Nikolaos A Trikalinos","doi":"10.1530/EO-22-0052","DOIUrl":"https://doi.org/10.1530/EO-22-0052","url":null,"abstract":"<p><strong>Summary: </strong>Downregulation of tumor suppression genes by DNA hypermethylation has been proposed as a potential cause of neuroendocrine neoplasm (NEN) formation. In this report, we present a patient simultaneously diagnosed with acute myeloid leukemia (AML) and a metastatic nonfunctioning pancreatic NEN. Because of the two competing diagnoses, he was treated with lanreotide, venetoclax and a long course of the hypomethylating agent decitabine. The AML responded to venetoclax and decitabine treatment while the PanNEN stabilized on lanreotide. Over multiple months of treatment, the PanNEN showed gradual tumor response, consistent with decitabine treatment effect, and the patient remained without disease progression for both malignancies. We believe that some PanNENs can benefit from treatment with hypomethylating agents such as decitabine. To support this, we review the relevant literature and suggest a mechanism for the efficacy of decitabine in our case.</p><p><strong>Learning points: </strong>Neuroendocrine neoplasms are associated with an increased risk of second primary cancers.Epigenetic changes such as hypermethylation and inhibition of tumor suppressor genes might explain the development and behavior of certain NENs.The use of hypomethylating agents such as decitabine might have a role in the treatment of PanNENs. Future studies are needed to confirm that.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"2 1","pages":"K1-K4"},"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/0e/ee/EO-22-0052.PMC10259290.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10191704","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":"Characterization of hyperlipidemia secondary to mitotane in adrenocortical carcinoma.","authors":"Nadia Gagnon,&nbsp;Sophie Bernard,&nbsp;Martine Paquette,&nbsp;Catherine Alguire,&nbsp;André Lacroix,&nbsp;Pierre-Olivier Hétu,&nbsp;Harold J Olney,&nbsp;Isabelle Bourdeau","doi":"10.1530/EO-21-0021","DOIUrl":"https://doi.org/10.1530/EO-21-0021","url":null,"abstract":"<p><strong>Background: </strong>This study examined the magnitude of changes and the time required to observe maximal changes in LDL-c, HDL-c, triglycerides (Tg) and non-HDL-c after the introduction of mitotane.</p><p><strong>Methods: </strong>Retrospective study of 45 patients with adrenocortical carcinoma who were treated at the Centre hospitalier de l'Université de Montréal. Clinical and biochemical data were collected, including lipid profiles before and during the first year of treatment with mitotane.</p><p><strong>Results: </strong>Among the 45 studied patients, 26 (58%) had a complete lipid profile before the introduction of mitotane and at least 1 lipid profile during the first year of treatment, and 19 patients (42%) had a lipid profile following initiation of the treatment. Among the 26 patients who had lipid profiles before and after the introduction of mitotane, the increase of LDL-c was 2.19 mmol/L (76%) (<i>P</i>< 0.0001), HDL-c was 0.54 mmol/L (35%) (<i>P</i>= 0.0002), Tg was 1.80 mmol/L (129%) (<i>P</i>< 0.0001) and non-HDL-c was 2.73 mmol/L (79%) (<i>P</i>< 0.0001). Between the first and the sixth month of mitotane treatment, peak values (<i>n</i>  = 45) of LDL-c and non-HDL-c were reached in 42 patients (93%) and 37 patients (82%), respectively, whereas peak values of HDL-c were reached after 6 months of mitotane treatment in 29 patients (66%). The peak value of Tg was almost equal throughout the first year. The mean peak values of HDL-c, Tg and non-HDL-c showed significant associations with their respective mitotane concentrations (β = 0.352, <i>P</i>= 0.03; β = 0.406, <i>P</i>= 0.02 and β = 0.339, <i>P</i>= 0.05).</p><p><strong>Conclusion: </strong>The introduction of mitotane produces a clinically significant elevation of lipid parameters (LDL-c, HDL-c, Tg and non-HDL-c) during the first year of treatment.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"2 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9815503","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":"Regulatory genes in the androgen production, uptake and conversion (APUC) pathway in advanced prostate cancer.","authors":"Sean McSweeney,&nbsp;Hannah E Bergom,&nbsp;Anna Prizment,&nbsp;Susan Halabi,&nbsp;Nima Sharifi,&nbsp;Charles Ryan,&nbsp;Justin Hwang","doi":"10.1530/EO-22-0058","DOIUrl":"https://doi.org/10.1530/EO-22-0058","url":null,"abstract":"<p><p>The androgen receptor (AR) signaling pathway regulates the progression of prostate cancer (PC). Metastatic castration-resistant prostate cancer (mCRPC) patients generally receive AR-targeted therapies (ART) or androgen-deprivation therapies (ADT) with the initial response; however, resistance is inevitably observed. Prior studies have shown activity and upregulation of a family of androgen production, uptake, and conversion - APUC genes - based on genomic analyses of patient germlines. Genetic variants of some APUC genes, such as the conversion gene, HSD3B1, predict response to second-generation androgen-targeted therapies. Studies have begun to elucidate the overall role of APUC genes, each with unique actionable enzymatic activity, in mCRPC patient outcomes. The current role and knowledge of the genetic and genomic features of APUC genes in advanced prostate cancer and beyond are discussed in this review. These studies inform of how interpreting behavior of APUC genes through genomic tools will impact the treatment of advanced prostate cancer.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"2 1","pages":"R51-R64"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10191700","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":"Visualization of the protein-protein interactions of hormone receptors in hormone-dependent cancer research.","authors":"Erina Iwabuchi,&nbsp;Yasuhiro Miki,&nbsp;Takashi Suzuki,&nbsp;Hironobu Sasano","doi":"10.1530/EO-22-0059","DOIUrl":"https://doi.org/10.1530/EO-22-0059","url":null,"abstract":"<p><p>In hormone-dependent cancers, the activation of hormone receptors promotes the progression of cancer cells. Many proteins exert their functions through protein-protein interactions (PPIs). Moreover, in such cancers, hormone-hormone receptor binding, receptor dimerization, and cofactor mobilization PPIs occur primarily in hormone receptors, including estrogen, progesterone, glucocorticoid, androgen, and mineralocorticoid receptors. The visualization of hormone signaling has been primarily reported by immunohistochemistry using specific antibodies; however, the visualization of PPIs is expected to improve our understanding of hormone signaling and disease pathogenesis. Visualization techniques for PPIs include Förster resonance energy transfer (FRET) and bimolecular fluorescence complementation analysis; however, these techniques require the insertion of probes in the cells for PPI detection. Proximity ligation assay (PLA) is a method that could be used for both formalin-fixed paraffin-embedded (FFPE) tissue as well as immunostaining. It can also visualize hormone receptor localization and post-translational modifications of hormone receptors. This review summarizes the results of recent studies on visualization techniques for PPIs with hormone receptors; these techniques include FRET and PLA. In addition, super-resolution microscopy has been recently reported to be applicable to their visualization in both FFPE tissues and living cells. Super-resolution microscopy in conjunction with PLA and FRET could also contribute to the visualization of PPIs and subsequently provide a better understanding of the pathogenesis of hormone-dependent cancers in the future.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"2 1","pages":"R132-R142"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10191701","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":"Tumour volume is a predictor of lymphovascular invasion in differentiated small thyroid cancer.","authors":"Krishna Vikneson,&nbsp;Tariq Haniff,&nbsp;May Thwin,&nbsp;Ahmad Aniss,&nbsp;Alex Papachristos,&nbsp;Mark Sywak,&nbsp;Anthony Glover","doi":"10.1530/EO-22-0066","DOIUrl":"https://doi.org/10.1530/EO-22-0066","url":null,"abstract":"<p><strong>Objectives: </strong>For small thyroid cancers (≤2 cm), tumour volume may better predict aggressive disease, defined by lymphovascular invasion (LVI) than a traditional single measurement of diameter. We aimed to investigate the relationship between tumour diameter, volume and associated LVI.</p><p><strong>Methods: </strong>Differentiated thyroid cancers (DTC) ≤ 2 cm surgically resected between 2007 and 2016 were analysed. Volume was calculated using the formula for an ellipsoid shape from pathological dimensions. A 'larger volume' cut-off was established by receiver operating characteristic (ROC) analysis using the presence of lateral cervical lymph node metastasis (N1b). Logistic regression was performed to compare the 'larger volume' cut-off to traditional measurements of diameter in the prediction.</p><p><strong>Results: </strong>During the study period, 2405 DTCs were surgically treated and 523 met the inclusion criteria. The variance of tumour volume relative to diameter increased exponentially with increasing tumour size; the interquartile ranges for the volumes of 10, 15 and 20 mm diameter tumours were 126, 491 and 1225 mm^3, respectively. ROC analysis using volume to predict N1b disease established an optimal volume cut-off of 350 mm³ (area under curve = 0.59, <i>P</i> = 0.02) as 'larger volume'. 'Larger volume' DTC was an independent predictor for LVI in multivariate analysis (odds ratio (OR) = 1.7, <i>P</i> = 0.02), whereas tumour diameter > 1 cm was not (OR = 1.5, <i>P</i> = 0.13). Both the volume > 350 mm³ and dimension > 1 cm were associated with greater than five lymph node metastasis and extrathyroidal extension.</p><p><strong>Conclusion: </strong>In this study for small DTCs ≤ 2 cm, the volume of >350 mm³ was a better predictor of LVI than greatest dimension > 1 cm.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"2 1","pages":"42-49"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10173153","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 abnormalities: a clinical case.","authors":"Yixi Bi,&nbsp;Safwaan Adam,&nbsp;Viktoria Chatzimavridou,&nbsp;Paul Lorigan,&nbsp;Yinglai Huang","doi":"10.1530/EO-21-0023","DOIUrl":"https://doi.org/10.1530/EO-21-0023","url":null,"abstract":"<p><strong>Summary: </strong>Short synacthen tests (SST) are frequently used for assessing adrenocorticotropin hormone (ACTH) deficiency. In this study, we present the case of a 53-year-old man receiving immunotherapy for metastatic melanoma, who subsequently developed immune checkpoint inhibitor (ICI)-induced hypothyroidism and was investigated for the presence of ICI-induced hypocortisolaemia on different occasions. Despite two reassuring SSTs, he subsequently developed clinical and biochemical evidence of ACTH deficiency. The ACTH on local measurement was not conclusive in keeping with ICI-related ACTH deficiency but when repeated using an alternative assay confirmed the diagnosis. The case illustrates the evolution of ACTH deficiency and exposes the potential pitfalls of screening strategies. Two important lessons may be gleaned from this case: (i) SSTs can be normal in early cases of secondary adrenal insufficiency, for example, hypophysitis due to adrenal reserve and (ii) when there is mismatch between the clinical and biochemical presentation, the ACTH should be repeated using a different assay.</p><p><strong>Learning points: </strong>Short synacthen tests, useful for ruling out adrenalitis and primary adrenal failure, may be normal in early adrenocorticotrophic hormone deficiency and secondary adrenal failure due to residual adrenal reserve.If clinical suspicion of adrenal insufficiency persists despite an initial satisfactory SST, it is important to recognise the need for re-assessment of cortisol levels.Insulin tolerance test remains a useful tool in the investigation of secondary adrenal insufficiency.Levothyroxine replacement may accelerate the metabolism of cortisol in cases of concurrent hypothyroidism and hypoadrenalism, and therefore, glucocorticoid replacement must precede levothyroxine treatment, to avoid adrenal crisis.The prevalence of immunotherapy-related endocrinopathies is likely to increase with increasing use of ICI and it is crucial that clinicians are alert to their subtle symptoms.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"2 1","pages":"K5-K9"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10173154","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}