Autoimmune Polyglandular Syndrome Type II: A Case Report.

Autoimmune polyglandular syndromes (APS) are polyendocrinopathies characterized by autoimmune dysfunction of multiple endocrine organs. We present the case of a 23-year-old male with a past medical history of autoimmune thyroiditis diagnosed seven months prior who presented with a chief complaint of six months of fatigue, shortness of breath, and weight loss. Physical exam was remarkable for global hyperpigmentation, notably of his palmar creases and gingiva. The patient was also tachycardic and hypotensive. He initially received two liters of 0.9% NaCl and 10 mg of intravenous dexamethasone. Random cortisol was <0.5 g. A cosyntropin test showed an insufficient increase in cortisol in response to adrenocorticotropin hormone (ACTH), confirming the diagnosis of primary adrenal insufficiency (AI). A computed tomography (CT) scan of the abdomen was negative for adrenal hemorrhage. A sexually transmitted disease (STD) panel was obtained to rule out the infectious cause and was negative. The patient was given glucocorticoids and his symptoms improved with fluid and electrolyte supplementation. This case report highlights the importance of close monitoring of patients with autoimmune endocrine abnormalities. These patients should be followed by an endocrinologist every six months for prompt diagnosis and risk mitigation. .

Characterization of extramedullary disease in B-ALL and response to CAR T-cell therapy.

Chimeric antigen receptor (CAR) T cells effectively eradicate medullary B-cell acute lymphoblastic leukemia (B-ALL) and can traffic to and clear central nervous system (CNS) involvement. CAR T-cell activity in non-CNS extramedullary disease (EMD) has not been well characterized. We systematically evaluated CAR T-cell kinetics, associated toxicities, and efficacy in B-ALL non-CNS EMD. We conducted a retrospective review of B-ALL patients with non-CNS EMD who were screened for/enrolled on one of three CAR trials (CD19, CD22, and CD19/22) at our institution. Non-CNS EMD was identified according to histology or radiographic imaging at extramedullary sites excluding the cerebrospinal fluid and CNS parenchyma. Of ∼180 patients with relapsed/refractory B-ALL screened across multiple early-phase trials over an 8-year period, 38 (21.1%) presented with isolated non-CNS EMD (n = 5) or combined medullary/non-CNS EMD (n = 33) on 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging. A subset receiving CAR T cells (18 infusions) obtained FDG PET/CT scans preinfusion and postinfusion to monitor response. At best response, 72.2% (13 of 18) of patients showed a medullary minimal residual disease-negative complete remission and complete (n = 7) or partial (n = 6) non-CNS EMD response. Non-CNS EMD responses to CAR T cells were delayed (n = 3), and residual non-CNS EMD was substantial; rarely, discrepant outcomes (marrow response without EMD response) were observed (n = 2). Unique CAR-associated toxicities at non-CNS EMD sites were seen in select patients. CAR T cells are active in B-ALL non-CNS EMD. Still, non-CNS EMD response to CAR T cells may be delayed and suboptimal, particularly with multifocal disease. Serial FDG PET/CT scans are necessary for identifying and monitoring non-CNS EMD.