Primary hypothyroidism and isolated ACTH deficiency induced by nivolumab therapy: Case report and review.

RATIONALE: Nivolumab is a monoclonal IgG antibody blocking programmed death receptor-1 (PD1), leading to restoration of the natural T-cell-mediated immune response against the cancer cells. However, it also causes plenty of autoimmune-related adverse events, which often involves endocrine system. PATIENT CONCERNS: A 54-year-old male with renal clear cell carcinoma was treated with nivolumab intravenously. Routine monitoring showed elevated thyroid-stimulating hormone and low free thyroxine after the 6th administration of nivolumab. After the 12th administration, he developed general fatigue, recurrent hypoglycemia, and relative hypotension. Laboratory tests showed low sodium, low morning cortisol without correspondence increase of corticotrophin (ACTH). Other pituitary hormones were normal. MRI showed no space-occupying lesions, but heterogeneous enhancement of the pituitary gland. DIAGNOSES: Primary hypothyroidism and isolated ACTH deficiency. The etiologies were assumed to be nivolumab induced autoimmune lymphocytic thyroiditis and hypophysitis, respectively. INTERVENTIONS: Hormone replacements with levothyroxine and acetate cortisone were given orally. Nivolumab was adjusted to lower dose and longer interval. OUTCOMES: The patient felt good after adequate replacement. Nivolumab was returned to routine dose and interval six months later. And the metastasis was not obviously progressed during this time. LESSONS: The present report provides the first detailed presentation of combined hypothyroidism and isolated ACTH deficiency induced by nivolumab. Adrenal deficiency often develops insidiously. We suggest routine monitoring of fasting blood-glucose, blood pressure and serum sodium as well as thyroid function during nivolumab and other cancer immunotherapies. When unexpected fatigue, hypoglycemia, hypotension or hyponatremia appeared, adrenal deficiency should be taken into consideration.

[Effect of adipose differentiation-related protein on the apoptosis of H9c2 cells by palmitic acid].

AIM: To construct a eukaryotic expression vector for expressing adipose differentiation-related protein(ADRP) protein and obtain a stable transfected H9c2 cell line. METHODS: (1)The full length DNA fragment of ADRP gene was amplified by PCR from the myocardium of adult SD rats and was inserted into pEGFP-C1 with T4 ligase. After the identification of digestion and sequencing on the recombinant pEGFP-C1-ADRP, the recombinant was transformed into E.coli strain DH5α.and the positive recombinant plasmid was selected. (2)The selected positive recombinant clones were amplified and transfected into H9c2 cells by lipofectamine(TM);2000. Cells containing stable transformants were selected by the ability of resistance to G418. The stable transfected cell line expressing high level of ADRP were obtained. Expression of green fluorescent protein gene was observed under fluorescence microscope and the expression of ADRP was identified by RT-qPCR and Western blot analysis. (3)The apoptotic percentage of H9c2 cells caused by PA was determined by flow cytometry. RESULTS: (1)Restriction map analysis and DNA sequencing analysis revealed that our target gene fragment was inserted into the expressing vector pEGFP-C1 successfully. (2)Green fluorescent was observed by fluorescence microscope on the cells which were transfected with pEGFP-C1 and pEGFP-C1-ADRP and did not disappear even at the twentieth passage of H9c2 cells. RT-qPCR and Western blot analysis showed that recombinant cells exhibit higher levers of mRNA and protein. (3)After treatment with different levels of PA, the apoptosis percentage of recombinant cells was lower than those of the other two cells. CONCLUSION: (1)The eukaryotic expression vector pEGFP-C1-ADRP and stable transfected H9c2 cells were established successfully. (2)The overexpression of ADRP gene could prevent apoptosis of cells caused by PA, which indicated that ADRP might play a protective role in H9c2 cells.

[An epidemiological study on diabetic retinopathy among type 2 diabetic patients in Shanghai].

OBJECTIVE: To investigate the prevalence and risk factors of diabetic retinopathy (DR) among type 2 diabetic patients aged over 30 in Shanghai central area. METHODS: 1039 patients diagnosed with type 2 diabetes mellitus (DM) aged over 30 were investigated by randomized cluster sampling in Shanghai central area and data from 767 of those patients were analyzed. RESULTS: (1) Among all of the 1534 digital ocular fundus images from 767 patients, 87.6% of the images from 672 patients were gradable. (2) Among all of the 672 patients with gradable ocular fundus images, the prevalence of non-proliferative diabetic retinopathy (NPDR) was 21.6%, while proliferative diabetic retinopathy (PDR) was 1.3%. The rates of mild, moderate and severe NPDR were 8.8%, 11.2% and 1.6% respectively. (3) DR patients were characterized with elder age, higher HbA1c, urea nitrogen and serum creatinine. DM duration and the level of fasting plasma glucose were risk factors for DR. CONCLUSION: The overall prevalence of DR in type 2 diabetic patients aged over 30 in Shanghai central area was 22.9% and the DR risk factors were found to include duration of diabetes and fasting plasma glucose level.

[Effect of shexiang baoxin pill on the function of vascular endothelium in patients with diabetes mellitus type 2 complicated with angina pectoris].

OBJECTIVE: To study the effect of Shexiang Baoxin pill (SBP) on the vascular endothelial function in patients with diabetes mellitus type 2 (DM2) complicated with angina pectoris. METHODS: Two weeks after runin, according to the randomizing table, 111 patients were divided into two groups, the XBP group (56 patients) and the control group (55 patients, treated with delayed-released isosorbide mononitrate, DRIM), they were treated for 6 months. In the treatment period, the episodes of angina attack and condition of rescue medication were recorded in the daily card, and brachial arterial changes of endothelium-dependent relaxing function before and after treatment were measured by B-ultrasonography. RESULTS: Comparison between the two groups in episodes of angina attack and rescue medication were insignificantly different. In the control group, the basal value of brachial arterial inner diameter before and after treatment was 3.68 +/- 0.56 mm and 3.70 +/- 0.58 mm respectively, those before and after responsive congestion was 5.44 +/- 0.81% vs 5.68 +/- 0.83%, and those before and after taking nitroglycerin was 19.8 +/- 4.9% vs 20. +/- 5.2%, all showed insignificant difference (P > 0.05). In the SBP group, the corresponding basal value was 3.73 +/- 0.62 mm vs 3.71 +/- 0.59 mm, and those after taking nitroglycerin 18.8 +/- 4.5 % vs 19.2 +/- 5.8%, also showed insignificant difference, but those before and after responsive congestion (5.69 +/- 0.79 % vs 9.56 +/- 3.82 %) did show significant difference (P < 0.01). CONCLUSION: XBP could improve the vascular endothelial function in patients with DM2 complicated with angina pectoris.