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Volume 33(2); June 2018
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Review Articles
Adrenal gland
Recent Updates on the Diagnosis and Management of Cushing's Syndrome
Lynnette K. Nieman
Endocrinol Metab. 2018;33(2):139-146.   Published online June 21, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.2.139
  • 11,594 View
  • 708 Download
  • 50 Web of Science
  • 47 Crossref
AbstractAbstract PDFPubReader   ePub   

Cushing's syndrome, a potentially lethal disorder characterized by endogenous hypercortisolism, may be difficult to recognize, especially when it is mild and the presenting features are common in the general population. However, there is a need to identify the condition at an early stage, as it tends to progress, accruing additional morbidity and increasing mortality rates. Once a clinical suspicion is raised, screening tests involve timed measurement of urine, serum or salivary cortisol at baseline or after administration of dexamethasone, 1 mg. Each test has caveats, so that the choice of tests must be individualized for each patient. Once the diagnosis is established, and the cause is determined, surgical resection of abnormal tumor/tissue is the optimal treatment. When this cannot be achieved, medical treatment (or bilateral adrenalectomy) must be used to normalize cortisol production. Recent updates in screening for and treating Cushing's syndrome are reviewed here.

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Close layer
Diabetes
Latent Autoimmune Diabetes in Adults: Current Status and New Horizons
Paolo Pozzilli, Silvia Pieralice
Endocrinol Metab. 2018;33(2):147-159.   Published online June 21, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.2.147
  • 13,226 View
  • 360 Download
  • 52 Web of Science
  • 45 Crossref
AbstractAbstract PDFPubReader   ePub   

Autoimmune diabetes is a heterogeneous disease which can arise at any age. Subjects with adult-onset autoimmune diabetes who do not necessitate insulin-therapy for at least 6 months after diagnosis are demarcated as having latent autoimmune diabetes in adults (LADA). This condition is more heterogeneous than young-onset autoimmune diabetes and shares clinical and metabolic characteristics with both type 2 and type 1 diabetes. Patients with LADA are considered by having highly variable β-cell destruction, different degrees of insulin resistance and heterogeneous titre and pattern of islet autoantibody, suggesting different pathophysiological pathways partially explaining the heterogeneous phenotypes of LADA. To date the heterogeneity of LADA does not allow to establish a priori treatment algorithm and no specific guidelines for LADA therapy are available. These subjects are mostly treated as affected by type 2 diabetes, a factor that might lead to the progression to insulin-dependency quickly. A personalised medicine approach is necessary to attain optimal metabolic control and preserve β-cell function to decrease the risk of long-term diabetes complications. Recent data concerning the use of oral antidiabetic agents as dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists indicate up-and-coming results in term of protect C-peptide levels and improving glycaemic control. This review summarises current knowledge on LADA, emphasising controversies regarding its pathophysiology and clinical features. Moreover, we discuss data available about novel therapeutic approaches that can be considered for prevention of β-cell loss in LADA.

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Thyroid
Evaluation of Thyroid Hormone Levels and Urinary Iodine Concentrations in Koreans Based on the Data from Korea National Health and Nutrition Examination Survey VI (2013 to 2015)
Jae Hoon Chung
Endocrinol Metab. 2018;33(2):160-163.   Published online May 4, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.2.160
  • 3,955 View
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AbstractAbstract PDFPubReader   ePub   

No nationwide data have been published about thyroid hormone levels and urinary iodine concentrations (UICs) in Korea. The Korea Centers for Disease Control and Prevention and the Korean Thyroid Association established a project to evaluate the nationwide thyroid hormone profile and UICs in healthy Koreans as part of the Korea National Health and Nutrition Examination Survey (KNHANES) VI (2013 to 2015), a nationwide, cross-sectional survey of the Korean population that enrolled 7,061 individuals who were weighted to represent the entire Korean population. Based on the KNHANES VI, the geometric mean value of serum thyroid stimulating hormone was 2.16 mIU/L, and its reference interval was 0.59 to 7.03 mIU/L. The mean value of serum free thyroxine was 1.25 ng/dL, and its reference interval was 0.92 to 1.60 ng/dL. The median UIC in the Korean population was reported to be 294 μg/L, corresponding to ‘above requirements’ iodine intake according to the World Health Organization recommendations. A U-shaped relationship of UIC with age was found. The prevalence of overt hyperthyroidism and overt hypothyroidism in the Korean population based on the KNHANES VI was 0.54% and 0.73%, respectively.

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Thyroid
Genetic Polymorphism Predisposing to Differentiated Thyroid Cancer: A Review of Major Findings of the Genome-Wide Association Studies
Vladimir A. Saenko, Tatiana I. Rogounovitch
Endocrinol Metab. 2018;33(2):164-174.   Published online June 21, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.2.164
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  • 27 Web of Science
  • 25 Crossref
AbstractAbstract PDFPubReader   ePub   

Thyroid cancer has one of the highest hereditary component among human malignancies as seen in medical epidemiology investigations, suggesting the potential meaningfulness of genetic studies. Here we review researches into genetic variations that influence the chance of developing non-familial differentiated thyroid cancer (DTC), focusing on the major findings of the genome-wide association studies (GWASs) of common single-nucleotide polymorphisms (SNPs). To date, eight GWAS have been performed, and the association of a number of SNPs have been reproduced in dozens of replication investigations across different ethnicities, including Korea and Japan. Despite the cumulative effect of the strongest SNPs demonstrates gradual increase in the risk for cancer and their association signals are statistically quite significant, the overall prediction ability for DTC appears to be very limited. Thus, genotyping of common SNPs only would be insufficient for evidence-based counseling in clinical setting at present. Further studies to include less significant and rare SNPs, non-SNP genetic information, gene-gene interactions, ethnicity, non-genetic and environmental factors, and development of more advanced computational algorithms are warranted to approach to personalized disease risk prediction and prognostication.

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Thyroid
Genome-Wide Association Studies of Autoimmune Thyroid Diseases, Thyroid Function, and Thyroid Cancer
Yul Hwangbo, Young Joo Park
Endocrinol Metab. 2018;33(2):175-184.   Published online June 21, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.2.175
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AbstractAbstract PDFPubReader   ePub   

Thyroid diseases, including autoimmune thyroid diseases and thyroid cancer, are known to have high heritability. Family and twin studies have indicated that genetics plays a major role in the development of thyroid diseases. Thyroid function, represented by thyroid stimulating hormone (TSH) and free thyroxine (T4), is also known to be partly genetically determined. Before the era of genome-wide association studies (GWAS), the ability to identify genes responsible for susceptibility to thyroid disease was limited. Over the past decade, GWAS have been used to identify genes involved in many complex diseases, including various phenotypes of the thyroid gland. In GWAS of autoimmune thyroid diseases, many susceptibility loci associated with autoimmunity (human leukocyte antigen [HLA], protein tyrosine phosphatase, non-receptor type 22 [PTPN22], cytotoxic T-lymphocyte associated protein 4 [CTLA4], and interleukin 2 receptor subunit alpha [IL2RA]) or thyroid-specific genes (thyroid stimulating hormone receptor [TSHR] and forkhead box E1 [FOXE1]) have been identified. Regarding thyroid function, many susceptibility loci for levels of TSH and free T4 have been identified through genome-wide analyses. In GWAS of differentiated thyroid cancer, associations at FOXE1, MAP3K12 binding inhibitory protein 1 (MBIP)-NK2 homeobox 1 (NKX2-1), disrupted in renal carcinoma 3 (DIRC3), neuregulin 1 (NRG1), and pecanex-like 2 (PCNXL2) have been commonly identified in people of European and Korean ancestry, and many other susceptibility loci have been found in specific populations. Through GWAS of various thyroid-related phenotypes, many susceptibility loci have been found, providing insights into the pathogenesis of thyroid diseases and disease co-clustering within families and individuals.

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Close layer
Thyroid
Management of Low-Risk Papillary Thyroid Cancer
Nicole M. Iñiguez-Ariza, Juan P. Brito
Endocrinol Metab. 2018;33(2):185-194.   Published online June 21, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.2.185
  • 6,188 View
  • 101 Download
  • 34 Web of Science
  • 33 Crossref
AbstractAbstract PDFPubReader   ePub   

The incidence of thyroid cancer has increased, mainly due to the incidental finding of low-risk papillary thyroid cancers (PTC). These malignancies grow slowly, and are unlikely to cause morbidity and mortality. New understanding about the prognosis of tumor features has led to reclassification of many tumors within the low-risk thyroid category, and to the development of a new one “very low-risk tumors.” Alternative less aggressive approaches to therapy are now available including active surveillance and minimally invasive interventions. In this narrative review, we have summarized the available evidence for the management of low-risk PTC.

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Editorials
Miscellaneous
Triennial Report of Endocrinology and Metabolism, 2015 to 2017
Eun-Jung Rhee, Hey Yeon Jang, Won-Young Lee
Endocrinol Metab. 2018;33(2):195-201.   Published online June 21, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.2.195
  • 3,170 View
  • 38 Download
  • 2 Web of Science
  • 2 Crossref
PDFPubReader   ePub   

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  • Endocrinology and Metabolism Has Been Indexed in MEDLINE: A Major Achievement
    Won-Young Lee
    Endocrinology and Metabolism.2019; 34(2): 138.     CrossRef
  • Being Indexed in SCIE: A Major Step Forward for Endocrinology and Metabolism
    Won-Young Lee
    Endocrinology and Metabolism.2019; 34(3): 263.     CrossRef
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Miscellaneous
Parathyroid Hormone-Related Protein in the Hand or Out of Hand?
Sang Wan Kim
Endocrinol Metab. 2018;33(2):202-203.   Published online June 21, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.2.202
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Close layer
Original Articles
Thyroid
Procalcitonin as Marker of Recurrent Medullary Thyroid Carcinoma: A Systematic Review and Meta-Analysis
Pierpaolo Trimboli, Luca Giovanella
Endocrinol Metab. 2018;33(2):204-210.   Published online June 21, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.2.204
  • 4,478 View
  • 61 Download
  • 11 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Calcitonin measurement is pivotal in the management of medullary thyroid carcinoma (MTC), but several pitfalls can affect its reliability. Other potential markers have been proposed, and procalcitonin (ProCT) has been reported as promising. The present study was undertaken to summarize the published data and provide more robust estimates on the reliability of ProCT as marker in the management of patients with MTC.

Methods

The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The sources comprised studies published through May 2018. Original articles that reported series of MTC patients undergone ProCT during postoperative follow-up were searched. A random-effects model was used for statistical pooling of the data. The I2 index was used to quantify the consistency among the studies. The Egger test evaluated the possible presence of significant publication bias. Quality assessment of the studies was performed according to Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2).

Results

According to inclusion and exclusion criteria five papers, reporting 296 MTC patients undergone ProCT evaluation, were finally selected. The number of MTC with recurrence was 140. The pooled sensitivity of ProCT in detecting recurrence was 96% (95% confidence interval [CI], 92% to 99%), with neither heterogeneity (I2=0%) nor publication bias (Egger test, 3.16; P=0.99). The pooled specificity was 96% (95% CI, 87% to 100%) with mild heterogeneity (I2=66.6%), while Egger test was not calculable.

Conclusion

The present meta-analysis provides evidence that ProCT is reliable to manage MTC patients during their postoperative follow-up.

Citations

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Close layer
Bone Metabolism
Association between Bone Mineral Density and Albuminuria: Cross-Sectional Analysis of Data from the 2011 Korea National Health and Nutrition Examination Survey V-2
Tae Yang Yu, Ha-Young Kim, Jeong Mi Lee, Dae Ho Lee, Chung Gu Cho
Endocrinol Metab. 2018;33(2):211-218.   Published online May 4, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.2.211
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AbstractAbstract PDFPubReader   ePub   
Background

Albuminuria is known to be independently associated with progression of renal and cardiovascular disease. However, little is known regarding the exact relationship between albuminuria and bone mineral density (BMD). The aim of this population-based study conducted in Korea was to identify the association between albuminuria and BMD.

Methods

We performed a cross-sectional analysis of data from the Korea National Health and Nutrition Examination Survey (KNHANES V-2) 2011. BMD was measured for total hip (TH), femur neck (FN), and lumbar spine (LS). Analysis of covariance was used to compare BMD levels between the groups at the TH, FN, and LS sites, after adjusting for age. Separate analyses were performed according to sex; women were divided into two groups according to menopausal status and each group was subdivided into three according to urine albumin-to-creatinine ratio (level 1, <30 mg/g; level 2, 30 to 299 mg/g; level 3, ≥300 mg/g).

Results

Data on a total of 1,831 adults (857 men and 974 women) were analyzed. In postmenopausal women, after adjusting for age, BMD of TH tended to decrease as levels of albuminuria increased (0.767±0.117, 0.757±0.129, 0.752±0.118, respectively; P=0.040). However, there was no significant difference in BMD according to albuminuria level in premenopausal women and men.

Conclusion

Level of albuminuria was closely related with BMD of TH in postmenopausal women, after adjusting for age, but there was no significant relationship between albuminuria and BMD in premenopausal women and men.

Citations

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Obesity and Metabolism
Comparison of the Effects of Ezetimibe-Statin Combination Therapy on Major Adverse Cardiovascular Events in Patients with and without Diabetes: A Meta-Analysis
Namki Hong, Yong-ho Lee, Kenichi Tsujita, Jorge A. Gonzalez, Christopher M. Kramer, Tomas Kovarnik, George N. Kouvelos, Hiromichi Suzuki, Kyungdo Han, Chan Joo Lee, Sung Ha Park, Byung-Wan Lee, Bong-Soo Cha, Eun Seok Kang
Endocrinol Metab. 2018;33(2):219-227.   Published online May 4, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.2.219
  • 5,516 View
  • 120 Download
  • 18 Web of Science
  • 17 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Ezetimibe-statin combination therapy has been found to reduce low density lipoprotein cholesterol levels and the risk of major adverse cardiovascular events (MACEs) in large trials. We sought to examine the differential effect of ezetimibe on MACEs when added to statins according to the presence of diabetes.

Methods

Randomized clinical trials with a sample size of at least 50 participants and at least 24 weeks of follow-up that compared ezetimibe-statin combination therapy with a statin- or placebo-controlled arm and reported at least one MACE, stratified by diabetes status, were included in the meta-analysis and meta-regression.

Results

A total of seven trials with 28,191 enrolled patients (mean age, 63.6 years; 75.1% men; 7,298 with diabetes [25.9%]; mean follow-up, 5 years) were analysed. MACEs stratified by diabetes were obtained from the published data (two trials) or through direct contact (five trials). No significant heterogeneity was observed among studies (I2=14.7%, P=0.293). Ezetimibe was associated with a greater reduction of MACE risk in subjects with diabetes than in those without diabetes (pooled relative risk, 0.84 vs. 0.93; Pheterogeneity=0.012). In the meta-regression analysis, the presence of diabetes was associated with a greater reduction of MACE risk when ezetimibe was added to statins (β=0.87, P=0.038).

Conclusion

Ezetimibe-statin combination therapy was associated with greater cardiovascular benefits in patients with diabetes than in those without diabetes. Our findings suggest that ezetimibe-statin combination therapy might be a useful strategy in patients with diabetes at a residual risk of MACEs.

Citations

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    Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Nan Hee Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, YoonJu Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang Youl Rhee, Hae J
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    Kyu Yeon Hur, Min Kyong Moon, Jong Suk Park, Soo-Kyung Kim, Seung-Hwan Lee, Jae-Seung Yun, Jong Ha Baek, Junghyun Noh, Byung-Wan Lee, Tae Jung Oh, Suk Chon, Ye Seul Yang, Jang Won Son, Jong Han Choi, Kee Ho Song, Nam Hoon Kim, Sang Yong Kim, Jin Wha Kim,
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    Janet Fricker
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Thyroid
Star-Shaped Intense Uptake of 131I on Whole Body Scans Can Reflect Good Therapeutic Effects of Low-Dose Radioactive Iodine Treatment of 1.1 GBq
Sung Hye Kong, Jung Ah Lim, Young Shin Song, Shinje Moon, Ye An Kim, Min Joo Kim, Sun Wook Cho, Jae Hoon Moon, Ka Hee Yi, Do Joon Park, Bo Youn Cho, Young Joo Park
Endocrinol Metab. 2018;33(2):228-235.   Published online May 4, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.2.228
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AbstractAbstract PDFPubReader   ePub   
Background

After initial radioactive iodine (RAI) treatment in differentiated thyroid cancer patients, we sometimes observe a star-shaped region of intense uptake of 131I on whole body scans (WBSs), called a ‘star artifact.’ We evaluated the clinical implications of star artifacts on the success rate of remnant ablation and long-term prognosis.

Methods

Total 636 patients who received 131I dose of 1.1 GBq for the initial RAI therapy and who did not show distant metastasis at the time of diagnosis were retrospectively evaluated. A negative second WBS was used for evaluating the ablation efficacy of the RAI therapy. Among them, 235 patients (36.9%) showed a star artifact on their first WBS.

Results

In patients with first stimulated thyroglobulin (sTg) levels ≤2 ng/mL, patients with star artifacts had a higher rate of negative second WBS compared with those without star artifacts (77.8% vs. 63.9%, P=0.044), and showed significantly higher recurrence-free survival (P=0.043) during the median 8.0 years (range, 1.0 to 10.0) of follow-up. The 5- and 10-year recurrence rates (5YRR, 10YRR) were also significantly lower in patients with star artifacts compared with those without (0% vs. 4.9%, respectively, P=0.006 for 5YRR; 0% vs. 6.4%, respectively, P=0.005 for 10YRR). However, ablation success rate or recurrence-free survival was not different among patients whose first sTg levels >2 ng/mL regardless of star artifacts.

Conclusion

Therefore, star artifacts at initial RAI therapy imply a good ablation efficacy or a favorable long-term prognosis in patients with sTg levels ≤2 ng/mL.

Citations

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  • Prognostic value of star-shaped intense uptake of 131I in thyroid cancer patients
    Liu Xiao, Wen Jie Zhang, Yue Qi Wang, Lin Li
    Revista Española de Medicina Nuclear e Imagen Molecular (English Edition).2021; 40(1): 30.     CrossRef
  • Valores pronósticos de la captación en estrella de 131I en pacientes con cáncer diferenciado de tiroides
    L. Xiao, W.J. Zhang, Y.Q. Wang, L. Li
    Revista Española de Medicina Nuclear e Imagen Molecular.2021; 40(1): 30.     CrossRef
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    Yusuke Iizuka, Tomohiro Katagiri, Minoru Inoue, Kiyonao Nakamura, Takashi Mizowaki
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Adrenal gland
C-Arm Computed Tomography-Assisted Adrenal Venous Sampling Improved Right Adrenal Vein Cannulation and Sampling Quality in Primary Aldosteronism
Chung Hyun Park, Namki Hong, Kichang Han, Sang-Wook Kang, Cho Rok Lee, Sungha Park, Yumie Rhee
Endocrinol Metab. 2018;33(2):236-244.   Published online May 4, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.2.236
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  • 9 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Adrenal venous sampling (AVS) is a gold standard for subtype classification of primary aldosteronism (PA). However, this procedure has a high failure rate because of the anatomical difficulties in accessing the right adrenal vein. We investigated whether C-arm computed tomography-assisted AVS (C-AVS) could improve the success rate of adrenal sampling.

Methods

A total of 156 patients, diagnosed with PA who underwent AVS from May 2004 through April 2017, were included. Based on the medical records, we retrospectively compared the overall, left, and right catheterization success rates of adrenal veins during the periods without C-AVS (2004 to 2010, n=32) and with C-AVS (2011 to 2016, n=124). The primary outcome was adequate bilateral sampling defined as a selectivity index (SI) >5.

Results

With C-AVS, the rates of adequate bilateral AVS increased from 40.6% to 88.7% (P<0.001), with substantial decreases in failure rates (43.7% to 0.8%, P<0.001). There were significant increases in adequate sampling rates from right (43.7% to 91.9%, P<0.001) and left adrenal veins (53.1% to 95.9%, P<0.001) as well as decreases in catheterization failure from right adrenal vein (9.3% to 0.0%, P<0.001). Net improvement of SI on right side remained significant after adjustment for left side (adjusted SI, 1.1 to 9.0; P=0.038). C-AVS was an independent predictor of adequate bilateral sampling in the multivariate model (odds ratio, 9.01; P<0.001).

Conclusion

C-AVS improved the overall success rate of AVS, possibly as a result of better catheterization of right adrenal vein.

Citations

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  • Utility of right adrenal signature veins in venous sampling for primary aldosteronism
    Zhenglin Shen, Shaoyong Xu, Siyu Guan, Bo Chen, Qingan Li, Ming Yu, Zhao Gao
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    Rui Zuo, Shuang Liu, Lu Xu, Hua Pang
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    Ran Cai, Chao Hu, Hai-Yang Li
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    Mitsuhide Naruse, Akiyo Tanabe, Koichi Yamamoto, Hiromi Rakugi, Mitsuhiro Kometani, Takashi Yoneda, Hiroki Kobayashi, Masanori Abe, Youichi Ohno, Nobuya Inagaki, Shoichiro Izawa, Masakatsu Sone
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Obesity and Metabolism
Distinct Ultradian Rhythms in Plasma Clusterin Concentrations in Lean and Obese Korean Subjects
Jong Han Choi, Eunheui Jeong, Byung Soo Youn, Min-Seon Kim
Endocrinol Metab. 2018;33(2):245-251.   Published online May 4, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.2.245
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AbstractAbstract PDFPubReader   ePub   
Background

Blood levels of many hormones show rhythmic fluctuations with variable duration of cycles. Clusterin/apolipoprotein J is a glycoprotein which is highly expressed in the plasma and has modulatory roles in immune and inflammatory reactions, neurobiology, lipid metabolism, and leptin signaling. In this study, we examined the diurnal fluctuations of plasma clusterin concentrations in lean and obese young men.

Methods

For the study, 14 subjects (five lean and five obese men; two lean and two obese women) were admitted to the research ward and blood samples were drawn every 30 minutes during light-on period (6:00 AM to 10:00 PM) and every hour during light-off period.

Results

Notably, plasma clusterin concentrations displayed a unique ultradian rhythm with five cycles a day in both men and women. During the light-on period, circulating clusterin levels showed fluctuating curves with 4 hours regular intervals with sharp peaks and troughs. In contrast, single oscillation curve during light-off exhibited a smoothened/lower peak and longer (8-hour) duration. In obese men, these cycles were phase-advanced by approximately 1 hour, and had reduced amplitude of fluctuating curves and blunted diurnal pattern. Cyclic fluctuations of plasma clusterin were preserved under fasting and unexpected meal condition, suggesting that rhythmic oscillations in plasma clusterin levels are not generated by meal-related cues.

Conclusion

These findings firstly demonstrate a novel pattern of plasma clusterin fluctuations with extremely regular cycles.

Citations

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  • Clusterin and Related Scoring Index as Potential Early Predictors of Response to Sorafenib in Hepatocellular Carcinoma
    Satoshi Narahara, Takehisa Watanabe, Katsuya Nagaoka, Nahoko Fujimoto, Yoki Furuta, Kentaro Tanaka, Takayuki Tokunaga, Takeshi Kawasaki, Yoko Yoshimaru, Hiroko Setoyama, Kentaro Oniki, Junji Saruwatari, Masakuni Tateyama, Hideaki Naoe, Motohiko Tanaka, Ya
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    Telma Quintela, André Furtado, Ana C. Duarte, Isabel Gonçalves, Jihwan Myung, Cecília R.A. Santos
    Progress in Neurobiology.2021; 205: 102129.     CrossRef
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    Drew Watson, Joshua Y. C. Yang, Reuben D. Sarwal, Tara K. Sigdel, Juliane M. Liberto, Izabella Damm, Victoria Louie, Shristi Sigdel, Devon Livingstone, Katherine Soh, Arjun Chakraborty, Michael Liang, Pei-Chen Lin, Minnie M. Sarwal
    Journal of Clinical Medicine.2019; 8(4): 499.     CrossRef
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Miscellaneous
Novel Mutation in PTHLH Related to Brachydactyly Type E2 Initially Confused with Unclassical Pseudopseudohypoparathyroidism
Jihong Bae, Hong Seok Choi, So Young Park, Do-Eun Lee, Sihoon Lee
Endocrinol Metab. 2018;33(2):252-259.   Published online June 21, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.2.252
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  • 10 Web of Science
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AbstractAbstract PDFPubReader   ePub   
Background

Autosomal-dominant brachydactyly type E is a congenital abnormality characterized by small hands and feet, which is a consequence of shortened metacarpals and metatarsals. We recently encountered a young gentleman exhibiting shortening of 4th and 5th fingers and toes. Initially, we suspected him having pseudopseudohypoparathyroidism (PPHP) because of normal biochemical parameters, including electrolyte, Ca, P, and parathyroid hormone (PTH) levels; however, his mother and maternal grandmother had the same conditions in their hands and feet. Furthermore, his mother showed normal biochemical parameters. To the best of our knowledge, PPHP is inherited via a mutated paternal allele, owing to the paternal imprinting of GNAS (guanine nucleotide binding protein, alpha stimulating) in the renal proximal tubule. Therefore, we decided to further analyze the genetic background in this family.

Methods

Whole exome sequencing was performed using genomic DNA from the affected mother, son, and the unaffected father as a negative control.

Results

We selected the intersection between 45,490 variants from the mother and 45,646 variants from the son and excluded 27,512 overlapping variants identified from the father. By excluding homogenous and compound heterozygous variants and removing all previously reported variants, 147 variants were identified to be shared by the mother and son. Variants that had least proximities among species were excluded and finally 23 variants remained.

Conclusion

Among them, we identified a defect in parathyroid hormone like hormone (PTHLH), encoding the PTH-related protein, to be disease-causative. Herein, we report a family affected with brachydactyly type E2 caused by a novel PTHLH mutation, which was confused with PPHP with unclassical genetic penetrance.

Citations

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  • A novel heterozygous mutation in PTHLH causing autosomal dominant brachydactyly type E complicated with short stature
    Jian Sun, Nian Yang, Zhengquan Xu, Hongbo Cheng, Xiangxin Zhang
    Molecular Genetics & Genomic Medicine.2024;[Epub]     CrossRef
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    Mirjam E.A. Scheffer-Rath, Hermine E. Veenstra-Knol, Annemieke M. Boot
    Bone Reports.2023; 19: 101699.     CrossRef
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    Farah Anjum, Md Nayab Sulaimani, Alaa Shafie, Taj Mohammad, Ghulam Md. Ashraf, Anwar L. Bilgrami, Fahad A. Alhumaydhi, Suliman A. Alsagaby, Dharmendra Kumar Yadav, Md. Imtaiyaz Hassan
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    Yanxiao Li, Han Gao, Hui Zhang, Runnan Yu, Fan Feng, Jing Tang, Bin Li
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    Nora E. Renthal, Priyanka Nakka, John M. Baronas, Henry M. Kronenberg, Joel N. Hirschhorn
    Journal of Bone and Mineral Research.2020; 36(12): 2300.     CrossRef
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    So Young Park, Myeong Han Seo, Sihoon Lee
    Endocrinology and Metabolism.2019; 34(1): 23.     CrossRef
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    Monica Reyes, Bert Bravenboer, Harald Jüppner
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    Jia Huang, Hong-Yan Liu, Rong-Rong Wang, Hai Xiao, Dong Wu, Tao Li, Ying-Hai Jiang, Xue Zhang
    Chinese Medical Journal.2019; 132(14): 1681.     CrossRef
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    Sang Wan Kim
    Endocrinology and Metabolism.2018; 33(2): 202.     CrossRef
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Endocrinol Metab : Endocrinology and Metabolism