Autoimmune Disorders Associated With Surgical Remission of Cushing's Disease : A Cohort Study.

BACKGROUND: Glucocorticoids suppress inflammation. Autoimmune disease may occur after remission of Cushing's disease (CD). However, the development of autoimmune disease in this context is not well described. OBJECTIVE: To determine 1) the incidence of autoimmune disease in patients with CD after surgical remission compared with patients with nonfunctioning pituitary adenomas (NFPAs) and 2) the clinical presentation of and risk factors for development of autoimmune disease in CD after remission. DESIGN: Retrospective matched cohort analysis. SETTING: Academic medical center/pituitary center. PATIENTS: Patients with CD with surgical remission and surgically treated NFPA. MEASUREMENTS: Cumulative incidence of new-onset autoimmune disease at 3 years after surgery. Assessment for hypercortisolemia included late-night salivary cortisol levels, 24-hour urine free cortisol (UFC) ratio (UFC value divided by the upper limit of the normal range for the assay), and dexamethasone suppression tests. RESULTS: Cumulative incidence of new-onset autoimmune disease at 3 years after surgery was higher in patients with CD (10.4% [95% CI, 5.7% to 15.1%]) than in those with NFPAs (1.6% [CI, 0% to 4.6%]) (hazard ratio, 7.80 [CI, 2.88 to 21.10]). Patients with CD showed higher prevalence of postoperative adrenal insufficiency (93.8% vs. 16.5%) and lower postoperative nadir serum cortisol levels (63.8 vs. 282.3 nmol/L) than patients with NFPAs. Compared with patients with CD without autoimmune disease, those who developed autoimmune disease had a lower preoperative 24-hour UFC ratio (2.7 vs. 6.3) and a higher prevalence of family history of autoimmune disease (41.2% vs. 20.9%). LIMITATION: The small sample of patients with autoimmune disease limited identification of independent risk factors. CONCLUSION: Patients achieving surgical remission of CD have higher incidence of autoimmune disease than age- and sex-matched patients with NFPAs. Family history of autoimmune disease is a potential risk factor. Adrenal insufficiency may be a trigger. PRIMARY FUNDING SOURCE: Recordati Rare Diseases Inc.

Separate origins of the left internal and external carotid arteries from the aorta in a patient with intracerebral hemorrhage.

Agenesis of the left common carotid artery with separate origins of the left internal and external carotid arteries from the aorta is an extremely rare anomaly. This anomaly is typically asymptomatic unless associated with other conditions. We report a case of separate origins of the left internal and external carotid arteries from the aorta in a patient with intracerebral hemorrhage. A 42-year-old man was transferred to our hospital by ambulance because of left hemiparesis. Computed tomography scan revealed right putaminal hemorrhage. Computed tomography angiography and digital subtraction angiography demonstrated independent origins of the left internal carotid artery and external carotid artery from the aortic arch. Right internal carotid angiography revealed blood supply to the left anterior cerebral artery and middle cerebral artery via the anterior communicating artery. The separate origins of the left internal and external carotid arteries from the aorta may cause hemodynamic stress to the contralateral side, leading to right intracerebral hemorrhage.

The Upregulation of Molecules Related to Tumor Immune Escape in Human Pituitary Adenomas.

Human pituitary adenomas are one of the most common intracranial neoplasms. Although most of these tumors are benign and can be treated medically or by transsphenoidal surgery, a subset of these tumors are fast-growing, aggressive, recur, and remain a therapeutic dilemma. Because antibodies against immune checkpoint receptors PD-1 and CLTA-4 are now routinely used for cancer treatment, we quantified the expression of mRNA coding for PD-1, CLTA-4, and their ligands, PD-L1, PD-L2, CD80, and CD86 in human pituitary adenomas and normal pituitary glands, with the ultimate goal of exploiting immune checkpoint therapy in aggressive pituitary adenomas. Aggressive pituitary adenomas demonstrated an increased expression of PD-L2, CD80, and CD86 in compared to that of normal human pituitary glands. Furthermore, aggressive pituitary tumors demonstrated significantly higher levels of CD80 and CD86 compared to non-aggressive tumors. Our results establish a rationale for studying a potential role for immune checkpoint inhibition therapy in the treatment of pituitary adenomas.

[The efficiency of cilostazol for cerebral vasospasm following subarachnoid hemorrhage].

Delayed ischemic deficit following subarachnoid hemorrhage(SAH)is a major source of morbidity and mortality after rupture of an intracranial aneurysm. Once symptomatic cerebral vasospasm has occured, available treatments do not provide good outcomes for all patients. Symptomatic vasospasm results in serious sequelae for 10-15% of patients and the etiology and pathogenesis remain unclear. Cilostazol is a specific inhibitor of cAMP(cyclic adenosine monophosphate)phosphodiesterase, and is used for treating ischemic symptoms of peripheral vascular disease. Cilostazol has various actions, such as inhibiting vascular smooth muscle proliferation, and increasing nitric oxide(NO)levels derived from endothelial cells. The present study included 81 patients with SAH caused by ruptured cerebral aneurysms treated in two hospitals between June, 2008 and September, 2009. All patients were treated with clipping surgery, and were classified into two groups: 25 patients who received cilostazol from postoperative day 1 to 14 or 28; and 56 control patients. Clinical symptoms due to cerebral vasospasm and frequency of severe spasm were compared between each of the groups. The frequencies of severe spasm appearing on angiography(age>65)and symptomatic cerebral vasospasm were lower in the cilostazol group than in controls. These findings suggest that cilostazol may prevent symptomatic cerebral vasospasm after subarachnoid hemorrhage.

[A case of meningeal melanocytoma in the cerebellopontine angle].

Meningeal melanocytomas are uncommon intracranial tumors and extremely rare in the cerebellopontine angle (CPA). The tumors are generally considered to be benign because they lack malignant features in histological examination, but several literatures describe malignant behavior of the tumors such as high frequency of local recurrence, malignant transformation with leptomeningeal seeding. We describe a case of meningeal melanocytoma in the CPA and discuss the features of the tumor. The case was a 43-year-old woman with a right CPA exta-axial mass suffering from vertigo and nausea. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a mass in the right CPA. The mass was hyperintense on T1-weighted images and hypointense on T2-weighted images. Surgical removal was done and pathological diagnosis was made as meningeal melanocytoma. Twenty months after the first surgery, MRI revealed local recurrence of the tumor and subtotal resection was performed.