Programmed cell death-1 (PD-1) ligand inhibitors have gained popularity in the treatment of advanced non-small-cell lung cancer. The immune system is regulated by stimulatory and inhibitory signaling and aims to achieve the balance between activation and inhibition. Treatment with immune checkpoint inhibitors enhances immune response, but is also known to diminish immune tolerance and increase autoimmune toxicity. Here we present a case of a patient with advanced squamous cell lung cancer who developed type I diabetes and thyroiditis after treatment with PD-1 checkpoint inhibitor nivolumab. The presence of autoimmune diabetes mellitus and thyroiditis were confirmed by markedly elevated titers of the glutamic acid decarboxylase autoantibody and thyroid peroxidase antibody, respectively. This report serves to heighten awareness of potential autoimmune toxicities related to anti-PD-1 therapy, especially as these toxicities are manageable if identified in a timely manner.
Background Animal models provide insights into the diabetic nephropathy pathogenesis, however, available rodent models do not mirror the heterogeneity of lesions in type 2 diabetic (T2DM) patients, and do not progress to end stage renal disease. Previous studies showed that spontaneously obese T2DM rhesus monkeys develop many of the features of human diabetic glomerulopathy, and may progress to ESRD. Here, in order to further characterize diabetic glomerulopathy in this model, we used electron microscopic stereology.. Methods Renal biopsies from 17 diabetic, 17 pre-diabetes/metabolic syndrome (preDM/MS) and 11 non-diabetic monkeys were studied. Fractional volumes of mesangium [Vv(Mes/glom)], mesangial matrix [Vv(MM/glom)] and mesangial cells [Vv(MC/glom)], glomerular basement membrane (GBM) width and peripheral GBM surface density per glomerulus [Sv(PGBM/glom)] were estimated. Glomerular filtration (GFR) and albumin excretion rates (AER) were measured in a limited number of animals. Glomerular structural and biochemical/metabolic data were compared among the groups. Results Diabetic monkeys showed classical diabetic nephropathy changes, including GBM thickening (p=0.001), increased Vv(Mes/glom) (p=0.02), and reduced Sv(PGBM/glom) (p=0.03) compared to non-diabetic monkeys. Increased Vv(Mes/glom) was primarily due to increased Vv(MM/glom) (p=0.03). Glomerular structural parameters inter-relationships in diabetic monkeys mirrored those of human diabetic glomerulopathy. AER was greater (p=0.03) in diabetic vs. non-diabetic monkeys. There was evidence for a positive relationship between AER and Vv(Mes/glom). Conclusions These studies indicate that this primate model shares many features of human diabetic glomerulopathy. Mesangial expansion in this model, similar to human diabetic nephropathy and different from available rodent models of the disease, is primarily due to increased mesangial matrix.
Objective: Adrenal lymphoma is a rare and aggressive form of non-Hodgkin lymphoma (NHL). We report 2 cases of adrenal lymphoma: one with typical symptoms of adrenal insufficiency, the other with the unusual presentation of symptomatic hypercalcemia from 1,25-dihydroxyvitamin D (1,25-[OH] 2-D) excess. Methods: A comparison of the clinical presentation of 2 patients diagnosed with primary adrenal diffuse large B cell lymphoma (DLBCL) treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) is reported. Results: The first patient was a 72-year-old man who presented with weight loss, hypotension, and bilateral adrenal masses. He was diagnosed with adrenal insufficiency from stage IVB DLBCL with primarily adrenal involvement. Treatment with 6 cycles of R-CHOP led to near-complete regression of adrenal masses and clinical remission, but with continued need for adrenocortical hormone replacement. He eventually succumbed to recurrent DLBCL with brain metastasis. The second patient was a 65-year-old man who presented with nausea, vomiting, constipation, and weight loss. He was noted to have hypercalcemia due to elevated serum 1,25-(OH) 2-D, bilateral large adrenal masses, but normal serum cortisol. He was diagnosed with stage II DLBCL. Treatment with R-CHOP led to complete remission with resolution of hypercalcemia. Conclusion: Primary adrenal DLBCL is an aggressive and rare type of NHL. While adrenal insufficiency is expected in this clinical scenario, hypercalcemia from 1,25-(OH) 2-D excess is an uncommon presentation. R-CHOP treatment may improve outcomes but more studies are needed to establish the optimal treatment for this rare disease entity. (AACE Clinical Case Rep. 2017;3:e307-e312) Abbreviations: 1,25-(OH) 2-D = 1,25-dihydroxyvitamin D; CNS = central nervous system; CT = computed tomography; DLBCL = diffuse large B cell lymphoma; FDG = fluorodeoxyglucose; HU = Hounsfield units; MRI = magnetic resonance imaging; NHL = non-Hodgkin lymphoma; PAL = primary adrenal lymphoma; PET = positron emission tomography; PTH = parathyroid hormone; PTHrP = parathyroid hormone-related peptide; R-CHOP = rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; SUVmax = maximum standardized uptake value e308 The Diversity of Adrenal Lymphoma, AACE Clinical Case Rep. 2017;3(No. 4)
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