Understanding of the molecular mechanisms of prostate cancer has led to development of therapeutic strategies targeting androgen receptor (AR). These androgen-receptor signaling inhibitors (ARSI) include androgen synthesis inhibitor-abiraterone and androgen receptor antagonists-enzalutamide, apalutamide, and darolutamide. Although these medications provide significant improvement in survival among men with prostate cancer, drug resistance develops in nearly all patients with time. This could be through androgen-dependent or androgen-independent mechanisms. Even weaker signals and non-canonical steroid ligands can activate AR in the presence of truncated AR-splice variants, AR overexpression, or activating mutations in AR. AR splice variant, AR-V7 is the most studied among these and is not targeted by available ARSIs. Non-androgen receptor dependent resistance mechanisms are mediated by activation of an alternative signaling pathway when AR is inhibited. DNA repair pathway, PI3K/AKT/mTOR pathway, BRAF-MAPK and Wnt signaling pathway and activation by glucocorticoid receptors can restore downstream signaling in prostate cancer by alternative proteins. Multiple clinical trials are underway exploring therapeutic strategies to overcome these resistance mechanisms.

An 80-year-old Caucasian male presented with fever of 3-week duration. Outpatient workup for infectious etiologies was negative and due to persistent fever, he was hospitalized for further evaluation of fever of unknown origin (FUO). Physical examination and laboratory studies remained unremarkable; however a follow-up CT scan of chest, abdomen, and pelvis with contrast done to rule out malignancy as an underlying cause of FUO revealed heterogeneous thyroid gland with surrounding hazy changes suggestive of thyroiditis. Thyroid function tests confirmed the diagnosis of subacute thyroiditis. The patient was started on prednisone with good response in his symptoms and was eventually discharged to home. The importance of our case lies in the fact that diagnosing subacute thyroiditis in the absence of classical symptoms of neck pain can be challenging and a physician should have a very high index of suspicion especially in an elderly patient where FUO can be the sole presentation.

on ventilator support. Unfortunately, her clinical condition did not improve and she was extubated after 11 days. She expired in hospice care within a few hours.Immune checkpoint inhibitors modulate the immune system and may cause immune-related adverse events (irAE) (Naidoo et al. 2015). Neurologic manifestations of irAE's are extremely rare. A few cases of ipilimumab-induced Guillain-Barré syndrome (GBS) have been reported in the literature (Gaudy-Marqueste et al. 2013;Wilgenhof and Neyns 2011). To our knowledge, this is the first case of nivolumab-induced GBS. Immune response directed against the myelin or axon of the peripheral nerve is implicated in the pathogenesis of GBS (Yuki and Hartung 2012). Nivolumab can cause disruption in normal immune checkpoint molecule function resulting in decreased peripheral tolerance to ganglioside-related epitopes and unchecked immune responses (Csurhes et al. 2005). With increasing use of nivolumab in advanced malignancies, physicians should be aware of rare adverse events like GBS, which can be effectively treated with rapid initiation of corticosteroids, IVIG or plasma exchange along with discontinuation of anti-PD1 antibody therapy. Compliance with ethical standardsConflict of interest None. ReferencesCsurhes PA, Sullivan A-A, Green K, Greer JM, Pender MP, McCombe PA (2005) Increased circulating T cell reactivity to GM1 ganglioside in patients with Guillain-Barré syndrome. J Clin Neurosci 12(4):409-415 Gaudy-Marqueste C, Monestier S, Franques J, Cantais E, Richard M-A, Grob J-J (2013) A severe case of ipilimumab-inducedEditor, A 68-year-old woman with stage III squamous cell carcinoma of the lung was treated with carboplatin, nabpaclitaxel, and concurrent radiation. A year later, she was diagnosed with brain metastases and nivolumab, an anti-PD1 monoclonal antibody, was initiated at a dose of 3 mg/ kg given every 2 weeks. Three months later, she presented with fatigue and bilateral lower extremity weakness of 4 days duration. Her most recent dose of nivolumab was administered 9 days ago. Physical examination revealed decreased strength in both legs. A CT scan of the brain revealed partial response to nivolumab therapy. An MRI scan of the spine was normal. Twelve hours later, she reported tingling sensation in her feet and profound weakness in lower extremities. Soon, she experienced progressive loss of motor and sensory function in arms and legs. Physical examination revealed loss of deep tendon reflexes in all four extremities associated with complete lack of strength. Cerebrospinal fluid (CSF) analysis showed clear appearance, with no nucleated cells, normal glucose and elevated protein levels (85 mg/dL; normal range 15-45). CSF Gram stain test, microbiological cultures and herpes simplex virus (HSV) DNA test were negative. The clinical finding of acute areflexic paralysis and the CSF finding of albuminocytologic dissociation were consistent with a diagnosis of GBS. She was started on intravenous immunoglobulin (IVIG) and plasma exchange. Within 2 hours, she developed ...

Objective We aimed to review of literature on the clinical presentation, management and outcomes of pituitary apoplexy following gonadotrophic release hormone (GnRH) agonist administration for the treatment of prostate cancer. Methods We used PRISMA guidelines for our systematic review and included all English language original articles on pituitary apoplexy following GnRH agonist administration among prostate cancer patients from Jan 1, 1995 to Dec 31, 2020. Data on patient demographics, prostate cancer type, Gleason score at diagnosis, history of pituitary adenoma, clinical presentation, GnRH agonist, interval to pituitary apoplexy, laboratory evaluation at admission, radiologic findings, treatment of pituitary apoplexy, time to surgery if performed, pathology findings, and clinical/hormonal outcomes were collected and analyzed. Results Twenty-one patients with pituitary apoplexy met our inclusion criteria. The mean age of patients was 70 (60–83) years. Leuprolide was the most common used GnRH agonist, used in 61.9% of patients. Median duration to symptom onset was 5 h (few minutes to 6 months). Headache was reported by all patients followed by ophthalmoplegia (85.7%) and nausea/vomiting (71.4%). Three patients had blindness at presentation. Only 8 cases reported complete anterior pituitary hormone evaluation on presentation and the most common endocrine abnormality was FSH elevation. Tumor size was described only in 15 cases and the mean tumor size was 26.26 mm (18–48 mm). Suprasellar extension was the most common imaging finding seen in 7 patients. 71.4% of patients underwent pituitary surgery, while 23.8% were managed conservatively. Interval between symptoms onset to pituitary surgery was 7 days (1–90 days). Gonadotroph adenoma was most common histopathologic finding. Clinical resolution was comparable, while endocrine outcomes were variable among patients with conservative vs surgical management. Conclusion Although the use of GnRH agonists is relatively safe, it can rarely lead to pituitary apoplexy especially in patients with pre-existing pituitary adenoma. Physicians should be aware of this complication as it can be life threatening. A multidisciplinary team approach is recommended in treating individuals with pituitary apoplexy.

Takotsubo cardiomyopathy (TTC) is a transient systolic dysfunction of the left ventricle which is usually seen in elderly women, often following a physical or emotional stressful event. Little is known about the prognostic factors affecting the recovery of systolic function. Thirty-six patients diagnosed with TTC from January 2006 to January 2017 at our hospital were included. Median time to recovery of ejection fraction (EF) was calculated to be 25 days. Early recovery of ejection fraction was defined as less than or equal to 25 days (group 1) and late recovery was defined as more than 25 days (group 2). Demographic and clinical factors were compared between the groups. Fifty percent patients had early recovery of EF with a mean time to recovery of 7.11 days and 50% had late recovery of ejection fraction with a mean time to recovery of 58.38 days. Younger age at presentation was associated with early recovery of systolic function (58.83 ± 2.7 years . 67.33 ± 2.7 years, = 0 .032). Presence of an identifiable triggering event was associated with early recovery (83% in group 1 . 50% in group 2, = 0.034). Generalized anxiety disorder was seen more commonly in the group with early recovery (78% in group 1 . 45% in group 2, = 0.040). In conclusion, younger age, generalized anxiety disorder and presence of triggering event were seen more commonly in patients with early recovery of left ventricular systolic function in Takotsubo cardiomyopathy.