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Free access

Li-bo Yang, Dong-qing Jiang, Wen-bo Qi, Tie Zhang, You-lun Feng, Ling Gao and Jiajun Zhao

Objectives

Whether subclinical hyperthyroidism (SCH) results in poor prognosis remains controversial. Our aim was to evaluate the association between SCH and the risk of cardiovascular disease (CVD), cardiovascular mortality, and all-cause mortality by conducting a meta-analysis of cohort studies.

Methods

The PubMed and Embase databases were searched through November 2011 to identify studies that met pre-stated inclusion criteria. Relevant information for analysis was extracted. Either a fixed or a random effects model was used to calculate the overall combined risk estimates.

Results

Seventeen cohort studies were included in this meta-analysis. The overall combined relative risks for individuals with SCH compared with the reference group were 1.19 (95% confidence interval (CI): 1.10 to 1.28) for CVD, 1.52 (95% CI: 1.08 to 2.13) for cardiovascular mortality, and 1.25 (95% CI: 1.00 to 1.55) for all-cause mortality. Subgroup analysis by sample source (community or convenience sample) showed that the significant association for cardiovascular and all-cause mortality only existed when pooling studies from convenience samples. Heterogeneity was observed when pooling studies on the association between SCH and cardiovascular and all-cause mortality. Sensitivity analysis showed omission of each individual study did not significantly change the pooled effects. No evidence of publication bias was observed.

Conclusions

Our findings demonstrated that SCH significantly increased the risk of CVD for the general population and the risk of cardiovascular and all-cause mortality for the individuals with other morbidities.

Open access

Hongbo Yang, Kemin Yan, Xu Yuping, Qi Zhang, Linjie Wang, Fengying Gong, Huijuan Zhu, Weibo Xia and Hui Pan

Context

Adult growth hormone deficiency (AGHD) is characterized by low bone density and increased risk of fracture. Bone microarchitecture is insufficiently evaluated in patients with childhood-onset AGHD (CO AGHD).

Objective

To assess volumetric bone density (vBMD) and bone microarchitecture in CO AGHD in early adulthood after cessation of recombinant growth hormone (rhGH) treatment.

Design and subjects

Case–control study in a major academic medical center in Beijing, including 20 young male adults with CO AGHD and 30 age- and weight-matched non-athletic healthy men. High-resolution peripheral quantitative computerized tomography (HR-pQCT) of distal radius and tibia was performed.

Outcomes

The main outcomes were vBMD and morphometry parameters from HR-pQCT.

Results

Compared with healthy controls, CO AGHD group had significantly decreased insulin-like growth factor 1 (IGF-1) level and IGF-1 SDS (P < 0.001). β-CTX and alkaline phosphatase levels in CO AGHD group were significantly increased (P < 0.001). CO AGHD group had significantly decreased total vBMD, cortical vBMD, trabecular vBMD, cortical area, cortical thickness as well as trabecular thickness and trabecular bone volume fraction of both tibia and radius (P < 0.001). CO AGHD patients had an 8.4 kg decrease in grip strength and a significant decrease in creatinine levels (P = 0.001). At both tibia and radius, by finite element analysis, bone stiffness and failure load of the CO AGHD patients were significantly decreased (P < 0.001). After adjusting for age, BMI and serum levels of testosterone and free thyroxin, serum IGF-1 level was a positive predictor for total vBMD, cortical vBMD, cortical area, trabecular vBMD, bone stiffness and failure load of both tibia and distal radius in all subjects.

Conclusions

Young adult male patients with childhood-onset adult growth hormone deficiency who are no longer receiving growth hormone replacement have prominently impaired volumetric bone density and bone microarchitecture and lower estimated bone strength.

Free access

Yong Chen, Zhi Feng Li, Fei Xiang Zhang, Jian Xian Li, Lin Cai, Qi Chuan Zhuge and Zhe Bao Wu

Objective

The aim of this study was to scrutinize the literature to determine the efficacy and safety of gamma knife surgery (GKS) for the treatment of nonfunctioning pituitary adenomas (NFPAs) with volumetric classification.

Methods

Electronic databases including MedLine, PubMed, and Cochrane Central were searched. The literature related to patients with NFPAs treated with GKS was collected. Eligible studies reported on the rate of tumor control (RTC), the rate of radiosurgery-induced optic neuropathy injury (RRIONI), the rate of radiosurgery-induced endocrinological deficits (RRIED), and other parameters.

Results

A total of 17 studies met the criteria. Based on the tumor volume, NFPAs were divided into three groups: the RTC of group I (93 patients) with tumor volumes <2 ml was 99% (95% CI 96–100%), the RRIONI was 1% (95% CI 0–4%), and the RRIED was 1% (95% CI 0–4%). The RTC of group II (301 patients) with volumes from 2 to 4 ml was 96% (95% CI 92–99%), the RRIONI was 0 (95% CI 0–2%), and RRIED was 7% (95% CI 2–14%). The RTC of group III (531 patients) with volumes larger than 4 ml was 91% (95% CI 89–94%), the RRIONI was 2% (95% CI 0–5%), and the RRIED was 22% (95% CI 14–31%). There were significant differences in the RTC and in the RRIED among the three groups (P<0.001), indicating that there were higher RRIED and lower RTC with the increase of tumor volume.

Conclusions

NFPAs, according to tumor volume classification, need stratification for GKS treatment. GKS is the optimal choice for the treatment of group II NFPAs. Patients with residual tumor volumes of <4 ml will benefit most from GKS treatment.

Free access

Xin Qu, Min Wang, Guodong Wang, Tao Han, Chengzhi Mou, Lizhang Han, Meng Jiang, Yuanming Qu, Miao Zhang, Qi Pang and Guangming Xu

Context

Little systematic data on male prolactinomas treated with surgery are available.

Objective

To clarify the clinical features and confirm the efficacy of transsphenoidal surgery for male prolactinomas and predictive factors after initial surgery.

Patients and methods

This retrospective study included 87 male patients with prolactinoma treated by transsphenoidal surgery at an academic medical center. Hormonal and visual status, remission rates, and the rate of tumor relapse, as well as predictive factors, were evaluated.

Results

Postoperative initial remission was achieved in 52.9% of patients. The remission rate was markedly higher in microadenomas (83.3%) than in macroadenomas (44.9%). Logistic regression analysis showed that the predictive factors of the early negative outcomes were high preoperative prolactin (PRL) levels and tumor invasion. After a median follow-up of 45 months, the long-term remission rate was 42.5%, and relapse of hyperprolactinemia occurred in 19.6% of the cured patients. The 5-year recurrence-free survival was 78.2% (95% confidence interval, 62.3–88.1%). When surgery was followed by adjuvant treatment in uncured and recurrent patients, 78.8% of patients in the entire group in the absence of dopamine agonists obtained biochemical remission at the end of follow-up.

Conclusion

Transsphenoidal surgery is a viable treatment alternative for male prolactinomas. The remission rates of male patients with microadenomas and/or intrasellar macroprolactinomas by surgery alone remain excellent, and surgery followed by adjuvant therapy as necessary is required for optimizing management of male prolactinomas, especially for extrasellar macroprolactinomas. The early negative results are associated with preoperative PRL levels and tumor invasion.

Open access

Feng Sun, Jun-Xiu Zhang, Chang-Yi Yang, Guan-Qi Gao, Wen-Bin Zhu, Bing Han, Le-Le Zhang, Yue-Yue Wan, Xiao-Ping Ye, Yu-Ru Ma, Man-Man Zhang, Liu Yang, Qian-Yue Zhang, Wei Liu, Cui-Cui Guo, Gang Chen, Shuang-Xia Zhao, Ke-Yi Song and Huai-Dong Song

Objective

Congenital hypothyroidism (CH), the most common neonatal metabolic disorder, is characterized by impaired neurodevelopment. Although several candidate genes have been associated with CH, comprehensive screening of causative genes has been limited.

Design and methods

One hundred ten patients with primary CH were recruited in this study. All exons and exon–intron boundaries of 21 candidate genes for CH were analyzed by next-generation sequencing. And the inheritance pattern of causative genes was analyzed by the study of family pedigrees.

Results

Our results showed that 57 patients (51.82%) carried biallelic mutations (containing compound heterozygous mutations and homozygous mutations) in six genes (DUOX2, DUOXA2, DUOXA1, TG, TPO and TSHR) involved in thyroid hormone synthesis. Autosomal recessive inheritance of CH caused by mutations in DUOX2, DUOXA2, TG and TPO was confirmed by analysis of 22 family pedigrees. Notably, eight mutations in four genes (FOXE1, NKX2-1, PAX8 and HHEX) that lead to thyroid dysgenesis were identified in eight probands. These mutations were heterozygous in all cases and hypothyroidism was not observed in parents of these probands.

Conclusions

Most cases of congenital hypothyroidism in China were caused by thyroid dyshormonogenesis rather than thyroid dysgenesis. This study identified previously reported causative genes for 57/110 Chinese patients and revealed DUOX2 was the most frequently mutated gene in these patients. Our study expanded the mutation spectrum of CH in Chinese patients, which was significantly different from Western countries.

Open access

Bing-Li Liu, Shao-Ying Yang, Wei Liu, Li-Qiong Xue, Xia Chen, Chun-Ming Pan, Zhao-Hui Gu, Ming Zhan, Xiao-Mei Zhang, Jun Liang, Guan-Qi Gao, Wen-Hua Du, Guo-Yue Yuan, Ru Ying, Shuang-Xia Zhao and Huai-Dong Song

Background

Convincing evidence has demonstrated the association of TSH receptor (TSHR) with Graves' disease (GD) in the Chinese Han population.

Objective

The aim of this study was to identify the causal variants for GD in the region encompassing TSHR by a refining association study.

Design and methods

GD patients (1536) and 1516 sex-matched controls were recruited in the first stage, and an additional 3832 GD patients and 3426 sex-matched controls were recruited in the replication stage. Genotyping was performed using Illumina Human660-Quad BeadChips or TaqMan single nucleotide polymorphism (SNP) Genotyping Assays and the Fluidigm EP1 platform.

Results

When the results of regression analysis for 74 genotyped SNPs and 922 imputed SNPs in the first-stage cohort were combined, rs179243 and rs3783949 were the probable susceptibility SNPs associated with GD in TSHR. Eleven SNPs, including rs179243 and rs3783949, were selected to further refine the association in the replication study. Finally, rs12101261 and rs179243 were confirmed as independent GD susceptibility variants in the replication and combined populations. Further, we also found that the rate of persistent TSHR autoantibody positivity (pTRAb+) was significantly higher in the GD patients with the susceptible genotypes rs12101261 or rs179243 than in the GD patients carrying the protective genotypes, after the GD patients had been treated for more than 1 year.

Conclusions

These findings indicate that rs12101261 and rs179243 are the possible causal SNPs for GD susceptibility in the TSHR gene and could serve as genetic markers to predict the outcome of pTRAb+ in GD patients.