Evolution of Graves' Disease during Immune Reconstitution following Nonmyeloablative Haploidentical Peripheral Blood Stem Cell Transplantation in a Boy Carrying Germline SAMD9L and FLT3 Variants.

Graves' disease, characterized by hyperthyroidism resulting from loss of immune tolerance to thyroid autoantigens, may be attributable to both genetic and environmental factors. Allogeneic hematopoietic stem cell transplantation (HSCT) represents a means to induce immunotolerance via an artificial immune environment. We present a male patient with severe aplastic anemia arising from a germline SAMD9L missense mutation who successfully underwent HSCT from his HLA-haploidentical SAMD9L non-mutated father together with nonmyeloablative conditioning and post-transplant cyclophosphamide at 8 years of age. He did not suffer graft-versus-host disease, but Graves' disease evolved 10 months post-transplant when cyclosporine was discontinued for one month. Reconstitution of peripheral lymphocyte subsets was found to be transiently downregulated shortly after Graves' disease onset but recovered upon antithyroid treatment. Our investigation revealed the presence of genetic factors associated with Graves' disease, including HLA-B*46:01 and HLA-DRB1*09:01 haplotypes carried by the asymptomatic donor and germline FLT3 c.2500C>T mutation carried by both the patient and the donor. Given his current euthyroid state with normal hematopoiesis, the patient has returned to normal school life. This rare event of Graves' disease in a young boy arising from special HSCT circumstances indicates that both the genetic background and the HSCT environment can prompt the evolution of Graves' disease.

Cardiovascular autonomic neuropathy, autonomic symptoms and diabetic complications in 674 type 2 diabetes.

AIMS: To determine the relationships between cardiovascular autonomic neuropathy (CAN) and autonomic symptoms, clinical parameters and diabetic complications in type 2 diabetes (T2DM). METHODS: The results of autonomic symptoms, clinical parameters, diabetes complications and cardiovascular reflex (CVR) tests of 674 T2DM were analyzed. RESULTS: Significant correlations were found between CAN risk and age (p=0.019), duration of diabetes (p=0.008), HbA1c (p<0.001), systolic blood pressure (p=0.006), nephropathy (p<0.001), retinopathy (p<0.001), and QTc interval (p<0.001), but not BMI and hyperlipidemia. Patients with retinopathy or proteinuria had increase risk of CAN, and proliferative diabetic retinopathy (PDR) was the most significant risk factor (odds ratio: 6.85; 95% CI: 2.32-20.20) for CAN. Eighty-three percent of patients complained of autonomic symptoms; and the more symptoms complained, the higher the prevalence of CAN. Impotence was the only single symptom associated with CAN risk. Additional CAN risks were also observed when patients with multiple symptoms and/or complications in combinations. CONCLUSIONS: Our results implied that patients with multiple symptoms and/or complications in combinations have increased CAN risk, and this may provide additional information for clinicians to identify T2DM at risk of having CAN.

Anaplastic thyroid cancer with uncommon long-term survival.

In general, most thyroid cancers are indolent and have a slowly progressive course. The exception is anaplastic thyroid cancer. It is one of the most fatal neoplasms in humans, with median survival of 4-12 months. Here, we present a patient with anaplastic thyroid cancer who survived for more than 10 years after diagnosis. A 68-year-old man was incidentally found to have anaplastic thyroid cancer during operation for follicular neoplasm. Total thyroidectomy was performed and hyperfractionated radiotherapy was carried out. After operation, annual follow-up examinations were negative for residual tumor or metastatic lesions. The patient also had chronic obstructive pulmonary disease and unfortunately died of pneumonia in a local hospital 10 years after thyroid operation.