ACTA ENDOCRINOLOGICA (BUC)

Background. Isolated methylmalonic acidemia refers to a group of inborn errors of metabolism characterized by elevated methylmalonic acid concentrations in the blood and urine. It occurs in approximately one to three out of every 100 thousand Chinese newborns. Mutations in the MMAA gene cause isolated methylmalonic acidemia. Case presentation. A 13-month-old boy was diagnosed with isolated methylmalonic acidemia. We identified two mutations in the MMAA gene in this case: c.491G>A and c.650T>A. The c.491G>A is a novel mutation in the MMAA gene. The boy is a heterozygous carrier of both mutations. The boy was treated with intravenous sodium benzoate and fluids. His sensorium gradually improved and he recovered from the acute illness. Other family members are heterozygous carriers of either mutations but with no symptoms. Conclusions. We identified a novel c.491G>A mutation in the MMAA gene. Heterozygous carriers of both c.491G>A and c.650T>A mutations are associated with isolated methylmalonic acidemia.

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Background. The high recurrence rate and low survival rate of ovarian cancer (OC) patients are closely related to an anoxic environment. We aim to study the mechanism of long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) on hypoxia ovarian cancer cells (OCC) and its mechanism was investigated. Methods. Knockdown and overexpression of HOTTIP in human OCC (SKOV-3, OVCAR3) were performed. The expression levels of HOTTIP and HIF- 1α were monitored by qRT-PCR and WB. Transwell was conducted to validate the cell migration and invasion. ELISA was performed to calculate VEGF concentration in cells. Cell viability was monitored by CCK-8. Cell apoptosis and cycle were tested by flow cytometry. RNA pull-down was used to analyze the interaction between HIF-1α and HOTTIP. Results. HOTTIP was highly expressed in OCC. After HOTTIP knockdown, HIF-1α expression and VEGF concentration in OCC were decreased. Cell migration, invasion, and cell viability were decreased. Cell apoptosis rate and G0/G1 phase cells were increased. RNA pull-down indicated a direct interaction between HIF-1α and HOTTIP. Conclusions. HOTTIP formed a positive feedback loop with HIF-1α to promote the development and metastasis of hypoxia ovarian cancer. This study provided theoretical support for the development of new OC treatment strategies.

McCune Albright syndrome (MAS) is a rare disease due to a sporadic mutation in Gs protein inducing polyostotic fibrous\r\ndysplasia, pigmented skin patches and hyper functioning endocrinopathies. We aimed to report its association with a hot thyroid nodule and gigantism.\r\nCase report. A man aged 37, with a history of pigmented skin lesions and lameness was referred for acromegaly. He was giant (height = 1.94 m/ target stature = 1.68 m), and had ?caf? au lait? spots. Biological analyses argued for pituitary mixed secretion (random growth hormone = 22 ng/ mL, N<5; prolactin = 27 ng/mL, N<10). Brain CT scan showed a pituitary process of 11x10 mm. Thyroid radioiodine scan revealed a hot nodule. Bone x-ray demonstrated large osteolytic lesions in the right femur and pelvis. He was operated on for endocrine tumours. The thyroid nodule\r\nwas benign and immunohistochemistry pituitary was positive for GH, prolactin and &#945; subunit.\r\nConclusion. Somatolactotrop adenoma causing gigantism associated with MAS is exceptional. It should be known, diagnosed, and treated early to avoid bone deformations\r\nand malignant transformation of osseous lesions under GH and/or IGF1 excess. One should also know that radiotherapy for the pituitary process is contraindicated, because of higher risk of sarcomatous transformation.

Objectives. To assess the effects of electroacupuncture (EA) at the Zusanli (ST36), Guanyuan (CV4), Zhongwan (CV12), and Fenglong (ST40) acupoints on sirtuin 1 (SIRT1) and glucose transporter type 4 (GLUT4) expression in high-fat diet (HFD)-induced insulin-resistant (IR) rats. Methods. Wistar rats were divided into normal control (NC), HFD, and HFD+EA groups. NC rats were fed a standard chow diet and did not receive EA. After being fed an HFD for eight weeks, rats in the HFD+EA group received EA at 2 Hz five times a week for eight weeks. Rats in the HFD group did not receive EA. Results. In HFD-induced IR rats, EA inhibited body weight increase and water intake, which were observed in HFD rats. EA had no effect on fasting blood glucose and postprandial blood sugar levels. Intraperitoneal insulin tolerance testing revealed that EA enhanced insulin sensitivity in HFD-induced IR rats. Compared with NC rats, SIRT1 and GLUT4 were downregulated in the quadriceps femoris of HFD-fed rats but were increased after eight weeks of EA stimulation. Conclusions. EA enhanced HFD-induced insulin resistance by activating SIRT1 and GLUT4 in the quadriceps femoris. These results provide powerful evidence supporting the beneficial effects of EA on HFD-induced insulin resistance.

Context. Peripheral nerve lesions are a major complication of diabetes mellitus, the main clinical manifestations of which are numbness and pain involving the limbs. Objective. To determine the correlation between pregabalin treatment and diabetic peripheral neuropathic pain. Design. An experimental animal study in BALB/c mice. Subjects and Methods. Diabetes models are established by injecting streptozotocin (STZ) into the abdominal cavities of mice. The correlation between the treatment effect, time, and dosage of pregabalin was determined. The effect of a type 1 organic cation transporter (Octn1) in the absorption of pregabalin was evaluated. Results. Pregabalin reduced tactile allodynia in diabetic mice. The best analgesic effect occurred when intestinal absorption was increased. Octn1 mediated pregabalin entry into intestinal epithelial cells, which influenced the absorption of pregabalin with a timedependent fluctuation in the small intestine. Peripheral nerve damage caused by diabetes was dependent on time and dose of pregabalin, which was related to the regular expression of Octn1 in small intestinal epithelium. Conclusions. Peripheral nerve damage caused by diabetes was dependent on time and dosage of pregabalin, which was related to the regular expression of Octn1 in small intestinal epithelium.

Background. Nephrogenic diabetes insipidus (NDI) is a disease characterized by a defective response to the antidiuretic hormone (ADH) of the renal collecting duct leading to a decline in the ability of the pro-urine concentration. Case presentation. A 23-year-old man presented with an over 20-year history of polyuria concomitant with hydronephrosis. The diagnosis of NDI was established by gene analysis as well as a water-deprivation and vasopressin test. All exons of arginine vasopressin V2 receptor (AVPR2) gene were amplified and sequenced. A novel hemizygous intragenic inframe deletion, cDNA 255th bp to 263th bp in exon 2 of AVPR2, was identified. These relevant translations from the 85th amino acid Asp to 88th amino acid Val were missed and replaced by amino acid Glu. After treating the patient with hydrochlorothiazide, his symptoms improved significantly. Conclusion. The genetic analysis revealed a novel X-linked intragenic inframe deletion, AVPR2 gene cDNA 255th bp to 263th bp, causing NDI.

The aim of this study was to analyze the incidence of malnutrition in patients with stage 3-4 chronic kidney disease (CKD) and primary subclinical hypothyroidism and the effect of levothyroxine for improving nutritional status and delaying kidney disease. Patients and Methods. In the study were included 200 patients with stage 3-4 CKD: CKD3 stage group (n=100) and CKD4 stage group (n=100). These patients were further divided into: control group (non-treatment group) group a (n=65) and experiment group (treatment group) group b (n=135) according to their levothyroxine treatment. The CKD3 stage group is divided into c3 (n=35) and e3 (n=65), and CKD4 group is divided into c4 (n=30) and e4 (n=70) groups. Results. Upon treatment of subclinical hypothyroidism with levothyroxine, nutritional indicators of patients are improved, and the weight, left and right-hand grip strength, hemoglobin (HB), serum albumin are higher compared to control. After levothyroxine treatment, eGFR in the treatment group increased with each time point, while in the control group it could be seen a significant decrease. This effect was more robust in the CKD3 group than in the CKD4 group. In conclusion, levothyroxine treatment can delay the progression of kidney diseases with more efficacy in stage 3 patients.

We reported that in a 29-year-old male patient with hyperthyroidism, bilateral breast swelling appeared in three days after starting methimazole and gradually aggravated. Several days later, a small amount of transparent liquid could be squeezed out from bilateral mammary glands. Breast ultrasound confirmed gynaecomastia. The level of testosterone, estradiol and luteinizing hormone increased. After the patient continued taking methimazole for a while, gynaecomastia relieved. Testosterone, luteinizing hormone and thyroid functions restored to normal. The possible mechanisms included increased levels of serum total cholesterol and relatively decreased T3 after initiating methimazole.