BackgroundSince 2011 six immune checkpoint inhibitors (ICI) have been approved to treat patients with many advanced solid tumor and hematological malignancies to improve their prognosis. Case reports of their endocrine immune-related adverse events [irAEs]) are increasingly published as more real-world patients with these malignancies are treated with these drugs. They alert physicians of a drug’s AEs (which may change during a drug’s life cycle) and contribute to post-marketing safety surveillance. Using a modified framework of Arksey and O’Malley, we conducted a scoping review of the spectrum and characteristics of ICI-induced endocrinopathies case reports before and after ICIs are marketed.MethodsIn July 2017, we searched, without date and language restrictions, 4 citation databases for ICI-induced endocrinopathies. We also hand-searched articles’ references, contents of relevant journals, and ran supplemental searches to capture recent reports through January 2018. For this study, a case should have information on type of cancer, type of ICI, clinical presentation, biochemical tests, treatment plus temporal association of ICI initiation with endocrinopathies. Two endocrinologists independently extracted the data which were then summarized and categorized.ResultsOne hundred seventy nine articles reported 451 cases of ICI-induced endocrinopathies - 222 hypopituitarism, 152 thyroid disorders, 66 diabetes mellitus, 6 primary adrenal insufficiencies, 1 ACTH-dependent Cushing’s syndrome, 1 hypoparathyroidism and 3 diabetes insipidus cases. Their clinical presentations reflect hormone excess or deficiency. Some were asymptomatic and others life-threatening. One or more endocrine glands could be affected. Polyglandular endocrinopathies could present simultaneously or in sequence. Many occur within 5 months of therapy initiation; a few occurred after ICI was stopped. Mostly irreversible, they required long-term hormone replacement. High dose steroids were used when non-endocrine AEs coexisted or as therapy in adrenal insufficiency. There was variability of information in the case reports but all met the study criteria to make a diagnosis.ConclusionsThe spectrum of ICI-induced endocrinopathies is wide (5 glands affected) and their presentation varied (12 endocrinopathies). Clinical reasoning integrating clinical, biochemical and treatment information is needed to properly diagnose and manage them. Physicians should be vigilant for their occurrence and be able to diagnose, investigate and manage them appropriately at onset and follow-up.Electronic supplementary materialThe online version of this article (10.1186/s40842-018-0073-4) contains supplementary material, which is available to authorized users.
BackgroundTransgender medicine is an emergent subfield with clearly identified educational gaps.AimsThis manuscript evaluates a gender-affirming healthcare curriculum for second-year medical (M2) students.MethodsStudents received a survey assessing Gender Identity Competency in terms of skills, knowledge and attitudes regarding transgender and gender non-conforming (TGNC) issues. The authors administered the survey before and after the delivery of the curriculum. The curriculum included five online modules, a quiz, a 3-hour case-based workshop and a 2-hour interactive patient-provider panel.ResultsApproximately 60% of M2 students (n=77) completed both preassessments and postassessments. The following showed a statistically significant improvement from preassessment to postassessment: student Gender Identity Competency, t(76) = −11.07, p<0.001; skills, t(76) = −15.22, p<0.001; and self-reported knowledge, t(76) = −4.36, p<0.001. Negative attitudes did not differ (p=0.378). Interest in TGNC issues beyond healthcare settings did not change (p=0.334). M2 students reported a significant change in experience role-playing chosen pronouns in a clinical setting, t(76) = −8.95, p<0.001.ConclusionsThe curriculum improved students’ gender-affirming medical competency, knowledge and skills. The development of a sustained, longitudinal curriculum is recommended in addition to the continuing education of faculty to reinforce this expanding knowledge and skills base and to address discomfort working with this population.
Background: Only one case of uterine cancer in a trans man on testosterone is noted in literature prior to this case. No clinical evidence nor guidelines exist regarding testosterone therapy for this subset of patients. Clinical Case: A 41-year-old trans man was seen by Gynecology for vaginal bleeding, with work-up revealing thickened endometrium and biopsy with endometrial adenocarcinoma. Testosterone therapy was held, and patient underwent total hysterectomy with BSO and bilateral pelvic/aortic lymph node dissection. Pathology demonstrated stage IIIA invasive adenocarcinoma, endometrium type with focal squamous differentiation, low grade. The tumor extended into the endocervical stroma with small metastasis to one ovary. He received adjunct pelvic radiation and sandwich chemotherapy with carboplatin and taxol. Concurrently, he was referred to Endocrinology for management of hormone replacement therapy (HRT). He originally started weekly testosterone injections and anastrozole at an outside facility in 2016 and underwent bilateral mastectomy in 2017. Testosterone was held perioperatively and during chemoradiation, for a total duration of 9 months. The patient experienced worsening gender dysphoria during this time. Discussion was held on goal to restart HRT in the setting of a theoretical risk of testosterone conversion to estradiol with increased risk of cancer recurrence; thus, patient initially chose to delay re-initiation of HRT. Following the completion of chemotherapy, he started on low-dose (30mg) weekly IM testosterone with plans for continued monitoring of testosterone and estradiol levels. Conclusion: Research is needed in monitoring the effects of testosterone therapy on reproductive organs in patients assigned female at birth, and whether anastrozole therapy has protective effects for estrogen-driven cancers. Further, guidance is needed on monitoring of uterine lining in trans men and whether this should be standard of practice.
Introduction: Immune checkpoint inhibitors (ICI) [anti-PD-1, anti-PD-L1, and anti-CTLA-4] are novel drugs increasingly used to treat solid tumor malignancies. Immune-related adverse events (irAE) occur with such therapy. We conducted a systematic review of case reports on endocrine irAE following ICI therapy. Here, we focus on the diabetes mellitus (DM) irAE case reports. Method: In July 2017 we searched Medline, Embase, Cochrane Central Register and Web of Science for articles related to endocrine irAE and ICI. From 815 citations retrieved, 241 mentioned DM. From these, 32 articles reported 43 cases (had close temporal relationship of immunotherapy and development of DM IrAEs and clinical, biochemical, and/or treatment data). A hand-search in Jan 2018 found 8 more papers with 8 cases. These 51 cases were reviewed independently by 2 co-authors for quality of data, using a standardized form. Results: Thirty-five patients presented in DKA (21 with fulminant T1DM), 15 with hyperglycemia, and 1 with lab data not reported (NR). The median age of the 31 males and 20 females was 63 years. Median time to onset of DM was 7 weeks after treatment initiation. Anti-GAD65, IA2, or ZnT8 were positive in 53% and negative or NR in 47%. Top 2 cancer treated were melanoma (n=23) and non-small cell lung cancer (n=11). The ICIs used were anti-PD-I (n=34); anti-PD-L1 (n=4); anti-PD-1 + CTLA-4 (n=7); and anti-CTLA-4 then anti-PD-1 (n=6). When DM occurred, ICI was stopped in 16, continued in 12, and NR in 23. At onset, 3 cases with known T2DM continued with oral meds, but all were treated with insulin and fluids. All patients recovered - 38 remained on insulin, 1 stopped insulin 81 days after ICI was stopped; and 12 NR. Conclusion: Reported cases of T1DM irAE are rising - 9 in 2015, 13 in 2016 and 28 in 2017. Most (69%) presented in DKA. All were treated with anti-PD-1/PD-L1 drugs with the majority on monotherapy. All recovered and 38 were insulin-dependent. Endocrinologists and oncologists should collaborate in managing such patients. Disclosure K.R. Mizokami-Stout: None. R. Gianchandani: None. M. MacEachern: None. R.M. Iyengar: None. S. Yentz: None. L. Shen: None. B.G. Redman: None. M. Tan: Other Relationship; Self; Eli Lilly and Company.
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