Hereditary forms of distal renal tubular acidosis (dRTA) are rare and mainly caused by mutations in ATP6V1B1, ATP6V0A4 and SLC4A1. About 20 mutations in SLC4A1 gene have been found that are related to either autosomal dominant (AD) or autosomal recessive dRTA. AD dRTA often manifest as constitutional and can easily be delayed in diagnosis and treatment. A 30-year-old male patient has a history of paroxysmal paralysis for 7 years, presenting with mild hypokalemia, alkalization of urine, normal blood PH value and increased urinary calcium. Patient's father has similar presentations but never came to the hospital. We find a heterozygous mutation (c.1162C>T, p.Arg388Cys) located in exon 11 of SLC4A1 gene by utilization of next-generation sequencing technology. Both patient and his father carry the same mutation. Highly conserved R388 is located in amphipathic helix 1 of N-terminal of the kAE1 protein, which may cause AD dRTA by changing the conformation of kAE1. Expression studies provide evidence that the mutant kAE1 R388C proteins are impaired in trafficking to the cell surface.

Papillary thyroid cancer is a prevalent endocrine malignancy. Although alterations in glutamine metabolism have been reported in several types of hematological and solid tumors, little is known about the functions of glutamine and glutaminolysis-associated proteins in papillary thyroid cancer. Here, we demonstrated the glutamine dependence of papillary thyroid cancer cells, and with the use of RT2-PCR arrays, we screened for the aberrant overexpression of glutaminase in human papillary thyroid cancer tissues and cells. These results were later confirmed via real-time PCR, Western blots, and immunohistochemical staining. We found that the levels of glutaminase were significantly correlated with extrathyroidal extension. Inhibition of GLS suppressed glutaminolysis and reduced mitochondrial respiration. The proliferative, viable, migratory, and invasive abilities of papillary thyroid cancer cells were impaired by both the pharmacological inhibition and the genetic knockdown of glutaminase. Additionally, the inhibition of glutaminase deactivated the mechanistic target of the rapamycin complex 1 (mTORC1) signaling pathway, promoting autophagy and apoptosis. Collectively, these findings show that glutaminase-mediated glutamine dependence may be a potential therapeutic target for papillary thyroid cancer.KEY MESSAGES:PTC cells are glutamine-dependent, and GLS is aberrantly overexpressed in PTC. Inhibition of GLS suppressed glutaminolysis and reduced mitochondrial respiration. Inhibition of GLS impairs the viability of PTC cells. GLS blockade causes deactivation of mTORC1 and induction of autophagy and apoptosis. GLS may be a potential therapeutic target for PTC.

This study aimed to establish reference ranges of bone markers in Chinese adolescents between the age of 12 and 16, and to search these markers’ characteristics and influential factors. Personal information and fasting blood samples were collected from 174 healthy adolescents in Northeast China. Serum levels of PINP, ALP, β-CrossLaps, calcium, phosphate, PTH, 25(OH)D and TSH were measured. Reference ranges were established for PINP [(85.55–2,028.75)ng/ml], ALP [(53.88–463.63)U/L], β-CrossLaps [(0.16–1.19)ng/ml], calcium [(2.35–2.70)mmol/L], phosphate [(1.17–2.06)mmol/L] and PTH [(2.64–43.36)μg/L] in this population. We observed that bone formation markers PINP and ALP levels were evidently higher when compared to kit references for adults. Reference ranges for calcium, phosphate and PTH also differed from those provided by kit manuals. Serum ALP, PINP, phosphate and PTH changed with age (all P < 0.005), and were significantly higher in boys than in girls (all P < 0.05). Serum 25(OH)D and TSH levels didn’t correlate with PINP, ALP and β-CrossLaps (all P > 0.05). In conclusion, unique reference ranges should be provided for adolescents. BMI, sex and age independently influence certain serum bone markers in adolescents. Vitamin D deficiency is widespread. Serum levels of vitamin D and TSH may not influence bone turnover markers in this population.

Autoimmune thyroid diseases (AITD) are common autoimmune disorders. A few studies have analyzed the association between serum vitamin D levels and AITD, and available data remain inconclusive. The aim of this study was to evaluate the association between serum vitamin D levels and 3 types of AITD, that is Graves' disease (GD), Hashimoto's thyroiditis (HT), and postpartum thyroiditis (PPT). Two independent case-control studies were designed. The first is a cross-sectional case-control study in which we examined the levels of 25(OH)D in patients with newly diagnosed GD or HT and in controls; the second is a nested case-control study in which we compared 25(OH)D levels in 610 women who developed PPT during the follow-up after delivery and those who did not. Compared with the controls, GD patients and HT patients had significantly lower 25(OH)D levels. PPT cases also had a lower serum 25(OH)D concentration than controls. Serum 25(OH)D levels were associated with neither antithyroid peroxidase antibody nor antithyroglobulin antibody in GD and HT. There was no significant relationship between thyroid-stimulating hormone and 25(OH)D levels. Every 5 nmol/L increase in serum 25(OH)D concentrations was associated with a 1.55-, 1.62-, and 1.51-fold reduction in GD, HT, and PPT risk, respectively. We observed a lower serum vitamin D levels in AITD patients compared with controls. The lower the vitamin D level is, not vitamin D deficiency per se, the higher the risk for developing AITD will be. However, vitamin D does not have strong association with the titers of thyroid antibodies or the levels of thyroid hormones.