Relationship between Free Thyroxine and Islet Beta-cell Function in Euthyroid Subjects.

Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas. We aimed to investigate the association between euthyroid hormones and islet beta-cell function in general population and non-treated type 2 diabetes mellitus (T2DM) patients. A total of 5089 euthyroid participants (including 4601 general population and 488 non-treated T2DM patients) were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016. Anthropometric indices, biochemical parameters, and thyroid hormones were measured. Compared with general population, non-treated T2DM patients exhibited higher total thyroxine (TT4) and free thyroxine (FT4) levels but lower ratio of free triiodothyronine (T3):T4 (P<0.01). HOMA-ß had prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age, body mass index (BMI) and smoking. When analyzed by quartiles of FT4 or free T3:T4, there were significantly decreased trend of HOMA-ß going with the higher FT4 and lower free T3:T4 in both groups. Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-ß no matter in general population or T2DM patients, which was independent of age, BMI, smoking, hypertension and lipid profiles. FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects. Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.

Ectopic thyroids have lower computed tomography attenuation values than orthotopic thyroids.

PURPOSE: To determine whether ectopic thyroid had the same computed tomography (CT) value as orthotopic thyroid. METHODS: Twenty-one patients with 23 ectopic thyroids and 23 controls with orthotopic thyroids underwent CT scans and were included in this retrospective study. The CT images were reviewed in a blinded fashion by two radiologists. Independent-Samples T-test was used for comparison of CT attenuation values between two groups. RESULTS: Ectopic thyroids had significantly lower non-enhanced attenuation (91.04 ± 5.97 Hounsfield Units vs. 106.56 ± 4.06 Hounsfield Units, P = 0.038) and contrast-enhanced attenuation (141.32 ± 6.42 Hounsfield Units vs. 169.82 ± 4.30 Hounsfield Units, P = 0.001) values than orthotopic thyroids. CONCLUSIONS: Ectopic thyroids have lower CT attenuation values than orthotopic thyroids probably due to the structural or functional abnormalities. The dysgenesis and pathological changes of the ectopic thyroids may contribute to functional deficiency which finally leads to decrease of the CT attenuation values.

Telbivudine-associated creatine kinase elevation in chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the occurrence and prognosis of telbivudine (LdT) therapy-associated elevations in creatine kinase (CK) in chronic hepatitis B (CHB) patients.</p><p><b>METHODS</b>Forty-nine patients treated with LdT from 2004 to 2010 were evaluated for development of CK elevation. In particular, the occurrences of grade 3/4 CK elevations (7-times the upper limit of normal (ULN)) and muscle damage were assessed over duration of the LdT treatment.</p><p><b>RESULTS</b>The rate of CK elevation increased with duration of LdT treatment (1 year: 61.2%; 5 years: 95.9%). In addition, the severity of CK elevation showed a trend for increasing with duration of LdT treatment, with grade 1/2 CK elevations increasing from 57.1% at year 1 to 81.6% at year 5 and grade 4 increasing from 4.1% at year 1 to 14.3% at year 5. Grade 3/4 CK elevations were observed in seven patients between LdT treatment weeks 36 and 168, but occurred most frequently between weeks 52 and 104, when the maximum peak value occurred (35.8-times the ULN). LdT treatment was stopped in two patients due to excessive CK elevation and one patient due to myositis. The majority of cases of LdT-associated grade 3/4 CK elevations were self-limiting, transient (decreasing to grades 0 or 2 within 2-3 weeks), and present without myalgia.</p><p><b>CONCLUSION</b>Elevation of CK was not rare in CHB patients treated with LdT, but most cases resolved spontaneously. In general, the severity and persistence of CK elevation was not sufficient to warrant withdrawal of LdT.</p>

A unique exonic splicing mutation in the CYP17A1 gene as the cause for steroid 17{alpha}-hydroxylase deficiency.

BACKGROUND: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) caused by a mutation in the CYP17A1 gene is characterized by hypertension, hypokalemia, and abnormal development of the genitalia. The majority of CYP17A1 mutations are located in the coding sequence, and several intronic splicing site mutations have been reported. OBJECTIVE: A 2.5-year-old girl with 46,XY disordered sex development exhibited a nearly normal basal cortisol level and reduced sexual steroids. This study is aimed to explore the molecular basis and analyze its possible influence on the phenotype of the patient. METHODS AND RESULTS: Mutation analysis revealed compound heterozygous CYP17A1 mutations, with c.985_987delinsAA in one allele and a synonymous substitution (c.1263G>A) in another allele. In vitro expression analysis of the allelic minigene showed that the novel nucleotide variation located in exon 8 induces a splicing signal, which results in an aberrant splicing of CYP17A1 mRNA and a missing portion of exon 8. The translation product includes the deletion of six or seven amino acids from residue position 415 without causing a frameshift. Consistent with the result of molecular modeling, functional studies in transiently transfected HEK-293T cells with the aberrantly spliced enzyme proteins showed that the deleted proteins completely abolished the enzyme activity. However, RT-PCR indicated the existence of a small fraction of normal, functionally intact enzyme, which may explain the partial masculinization of this patient. CONCLUSION: This is the first description of an exonic splicing mutation in CYP17A1 relevant to the 17OHD phenotype. It also demonstrates the importance of studying synonymous change in such patients with less severe phenotype.

Week 24 suppression of HBV in entecavir-treated chronic hepatitis B patients in whom lamivudine treatment failed is associated with efficacy at week 48 / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the degree of week 24 HBV suppression and week 48 therapeutic response in entecavir-treated chronic hepatitis B patients in whom lamivudine treatment failed, so as to explore a useful predictor for efficacy of enticavir treatment.</p><p><b>METHODS</b>Thirty-three patients with chronic hepatitis B refractory to lamivudine were enrolled to receive treatment with entecavir 1.0 mg once daily. The patients were divided into 4 groups according to serum HBV DNA levels (copies/mL) at week 24: PCR-undetectable (less than 300 copies/ml); QL- less than 3 log10 copies/ml; 3 log10(-4) log10 copies/ml; greater than 4 log10 copies/mL, and the efficacy achieved at week 48 was evaluated.</p><p><b>RESULTS</b>At week 48, mean reductions of serum HBV DNA from baseline was 4.91 log10. HBV DNA became undetectable by PCR assay in 33.3 percent patients and ALT became normal in 75.8%. The lower the HBV DNA level achieved at week 24, the higher the proportion of patients in whom HBV DNA became undetectable by PCR and ALT normalization were acquired at week 48, and viral breakthrough at week 48 also decreased.</p><p><b>CONCLUSION</b>Undetectable HBV DNA by PCR at week 24 in entecavir-treated chronic hepatitis B patients who were refractory to lamivudine, suggests a better efficacy at week 48. The degree of week 24 suppression of HBV may be used as a predictor of long term outcome.</p>