Assessment of plasma dexamethasone levels after 1-mg dexamethasone suppression test in adults with obesity.

BACKGROUND: The 1-mg overnight dexamethasone suppression test is the most frequently used screening test for Cushing's syndrome. It has been proposed that people with obesity may have insufficient plasma dexamethasone levels for the test which may result in false positives. We sought to compare the plasma dexamethasone levels after 1-mg dexamethasone suppression test in healthy obese participants and in optimal-weight participants. METHODS: A total of 30 optimal-weight participants (BMI ≤ 25 kg/m2 ) and 62 obese participants (BMI > 25 kg/m2 ) were enroled in the study. Obese participants were further divided into class 1 (25-29.9 kg/m2 ) and class 2 (>30 kg/m2 ). After a standard overnight 1-mg dexamethasone suppression test, blood samples were obtained for serum cortisol and plasma dexamethasone levels. Plasma dexamethasone levels were quantified using liquid chromatography - mass spectrometry (LC-MS/MS). RESULTS: No significant difference in plasma dexamethasone levels were found between obese and optimal-weight participants (3.31 ± 1.35 vs. 2.82 ± 1.11 nmol/L, mean ± SD; p = .09 respectively). There were also no correlations found between sex, BMI, body surface area and plasma dexamethasone levels. There was also no significant difference in the proportion of participants who achieved a plasma dexamethasone level >3.3 nmol/L in comparison between obesity class 1, obesity class 2, and optimal-weight groups. CONCLUSION: Our results suggest that obesity does not affect plasma dexamethasone levels. However, dexamethasone measurement may still be helpful in patients who are being investigated for Cushing's syndrome and suspected to have a false-positive DST.

Lower thiol, glutathione, and glutathione peroxidase levels in prostate cancer: a meta-analysis study.

PURPOSE: Lowered thiol (-SH) groups and glutathione (GSH) metabolism may be associated with prostate cancer (PCa) and benign prostatic hyperplasia (BPH). The objectives of this study were to systematically review and meta-analyze the associations among -SH groups, GSH, GSH peroxidase (GPx), GSH reductase (GR), and GSH transferase (GST) and PCa/BPH. METHODS: Four electronic databases were searched for studies that reported -SH and GSH variables in PCa/BPH and healthy controls (HC) and the data were meta-analyzed by calculating Hedges's g with 95% confidence intervals. RESULTS: Twenty studies were included in this meta-analysis. Total -SH (g = -1.750, -2.341/-1.159), GPx (g = -0.789, -1.234/-0.344), GSH (g = -2.219, -4.132/-0.305), and the combination of -SH, GPx, and GSH (g = -1.271, -1.271/-0.800) were significantly lower in PCa patients than in HC. -SH (g = -1.752, -3.123/-0.381) and the combination of -SH, GPx, and GSH (g = -0.813, -1.298/-0.327) were significantly lower in BPH patients than in HC. GPx was significantly lower in PCa than in BPH patients (g = -0.455, -0.896/-0.014). Heterogeneity levels were very high, but Egger's test showed that none of the biomarkers showed significant publication bias. CONCLUSION: Thiol/GPx antioxidant defenses are significantly attenuated in patients with PCa while patients with BPH occupy an intermediate risk group position between PCa patients and HC.

Validation of the Thai version of the short Boston Naming Test (T-BNT) in patients with Alzheimer's dementia and mild cognitive impairment: clinical and biomarker correlates.

OBJECTIVES: Impairments in the Boston Naming Test (BNT), which measures confrontational word retrieval, frequently accompanies Alzheimer's dementia (AD) and may predict a more rapid progression of illness. This study aims to validate the Thai version of the 15-item BNT (T-BNT) in participants with AD and amnestic mild cognitive impairment (aMCI) and to externally validate the T-BNT using clinical and biomarker measurements. METHODS: This cross-sectional study recruited patients with AD, diagnosed according to NINCDS-ADRDA criteria (n = 60), aMCI, diagnosed using the Petersen criteria (n = 60), and healthy controls (n = 62). We examined the internal consistency, concurrent and discriminant reliability of the T-BNT. We also assessed the Mini Mental State Examination (MMSE), the Verbal Fluency Test (VFT) and the Word List Memory (WLM) tests and measured apolipoprotein E polymorphism and serum levels of folic acid, high-density lipoprotein cholesterol (HDL) and triglycerides. RESULTS: This study validated a 10-item T-BNT (10T-BNT), which yielded good internal consistency (0.92), a one-factor unidimensional structure, and adequate concurrent and discriminant validity. Lower scores on the 10T-BNT highly significantly predict AD, but not aMCI, and are positively associated with VFT and WLM test scores. Furthermore, lowered 10T-BNT scores are significantly associated with the ApoE4 allele, lower folate levels and an increased triglyceride/HDL-cholesterol ratio. CONCLUSIONS: This study validated the 10T-BNT and the total score on this scale is strongly associated with AD, impairments in semantic and episodic memory and biomarkers, which are known to modify memory via different mechanisms.

Effectiveness of a low dose testosterone undecanoate to improve sexual function in postmenopausal women.

BACKGROUND: Adding testosterone to hormonal therapy could improve sexual function and general well-being among women during climacteric. We evaluated the effectiveness of testosterone undecanoate on sexual function in postmenopausal women utilizing the standardized questionnaire FSFI score. METHODS: Postmenopausal women with sexual complaints and Female Sexual Function Index (FSFI) ≤ 26.5 were enrolled in to this randomized, double-blinded, placebo-controlled trial. Participants were randomly assigned to 8-week treatment with either oral testosterone undecanoate 40 mg or placebo twice weekly with daily oral estrogen. The FSFI scores before and after treatment were compared to assess any improvement of sexual function. RESULTS: Seventy women were recruited of which each group had 35 participants. The baseline characteristics and baseline FSFI scores were comparable between both groups. After 8 weeks of treatment, the FSFI scores significantly improved in both groups when compared to the baseline but the FSFI scores from the testosterone group were significantly higher than in the placebo group post-treatment (28.6 ± 3.6, 25.3 ± 6.7, respectively, p = 0.04). There was no difference in adverse effect between the two groups CONCLUSIONS: The twice weekly addition of testosterone undecanoate to daily oral estrogen was associated with a significant improvement in sexual function among postmenopausal women than the use of the estrogen alone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01724658 (February 17, 2012).

Prevalence of RNF213 rs112735431 Genetic Polymorphism in Non-Cardioembolic Ischemic Cerebrovascular Disease: A Cross-Sectional Study in Thai Patients.

INTRODUCTION: Moyamoya disease (MMD) and non-MMD intracranial cerebral artery stenosis (ICAS) have been linked to the RNF213 rs112735431 gene in Korean and Japanese populations. This cross-sectional study investigates the prevalence of the RNF213 rs112735431 gene in non-cardioembolic ischemic stroke (NCIS) among Thai patients. METHODS: A cross-sectional investigation was conducted on patients aged 18 years or older admitted to King Chulalongkorn Memorial Hospital between June 2015 and March 2016 with acute NCIS. ICAS and extracranial carotid artery stenosis (ECAS) were assessed through computer tomography angiography or magnetic resonance angiography. Blood samples were collected, and Sanger sequencing was performed. RESULTS: Among 234 acute NCIS cases, 113 exhibited ICAS, 12 had ECAS, 20 had both, and 89 had neither. The RNF213 rs112735431 gene variant was detected in 2 patients, both heterozygous A/G. The frequency of the RNF213 rs112735431 variant was 0.9% (2/234; 95% CI, 0-2.1%) in acute NCIS patients and 1.8% (2/113; 95% CI, 0-4.2%) in ICAS. All individuals with the RNF213 variant were males with hypertension, diabetes mellitus, dyslipidemia, and ICAS, without a family history of ischemic stroke. CONCLUSION: This study reveals that the RNF213 rs112735431 gene variant is uncommon among Thai NCIS patients, suggesting a discrepancy in the prevalence of this genetic variation between Thai and other Eastern Asian populations.

A genome-wide association study identifies novel susceptibility genetic variation for thyrotoxic hypokalemic periodic paralysis.

Several lines of evidence have pointed out that genetic components have roles in thyrotoxic hypokalemic periodic paralysis (TTPP). In this study, for the first time we performed genome-wide association study (GWAS) in male hyperthyroid subjects in order to identify genetic loci conferring susceptibility to TTPP. We genotyped 78 Thai male TTPP cases and 74 Thai male hyperthyroid patients without hypokalemia as controls with Illumina Human-Hap610 Genotyping BeadChip. Among the SNPs analyzed in the GWAS, rs312729 at chromosome 17q revealed the lowest P-value for association (P=2.09 × 10(-7)). After fine mapping for linkage disequilibrium blocks surrounding the landmark SNP, we found a significant association of rs623011; located at 75 kb downstream of KCNJ2 on chromosome 17q, reached the GWAS significance after Bonferroni's adjustment (P=3.23 × 10(-8), odds ratio (OR)=6.72; 95% confidence interval (CI)=3.11-14.5). The result was confirmed in an independent cohort of samples consisting of 28 TTPP patients and 48 controls using the same clinical criteria diagnosis (replication analysis P=3.44 × 10(-5), OR=5.13; 95% CI=1.87-14.1; combined-analysis P=3.71 × 10(-12), OR=5.47; 95% CI=3.04-9.83).

Association between genetic polymorphisms and sites of cervicocerebral artery atherosclerosis.

Ischemic stroke is a multifactorial disease with strong genetic elements. The purpose of this case-control study was to find relationships between apolipoprotein E (APOE), angiotensin-converting enzyme (ACE), and methylenetetrahydrofolate reductase (MTHFR) genotypes and atherosclerosis of the extracranial internal carotid and intracranial arteries in the Thai population. Patients aged >45 years with significant intracranial stenosis (IC group) or extracranial carotid artery stenosis (EC group) diagnosed by duplex ultrasound and/or computed tomography angiography (CTA) or magnetic resonance angiography (MRA) were studied. The control group comprised volunteers with no history of stroke and no evidence of significant cervicocerebral artery stenosis by ultrasound. Genomic DNA was extracted and genotyped for APOE isoforms, ACE insertion/deletion (I/D) polymorphism, and MTHFR C677T polymorphisms. There were 141 cases (83 in the IC group and 58 in the EC group) and 167 controls. The APOE ε3/ε4 genotype and APOE ε4 allele were significantly associated with extracranial carotid artery stenosis (odds ratio, 2.55; 95% confidence interval, 1.07-6.05 and odds ratio, 2.85; 95% confidence interval, 1.35-5.99, respectively). These associations were not observed in patients with intracranial atherosclerosis. There was no significant association between ACE and MTHFR polymorphisms and stenosis at any site. In a multivariate model, sex, diabetes mellitus, hypertension, ischemic heart disease, and APOE ε4 allele remained predictive of extracranial atherosclerosis. In our Thai population, the ε4 allele in the APOE gene contributes to the genetic susceptibility of extracranial internal carotid atherosclerosis. The low prevalence of extracranial carotid stenosis in this population might result from low frequencies of the APOE ε4 allele.

Thyrotoxic hypokalemic periodic paralysis and COVID-19 infection.

Various conditions causing weakness associated with coronavirus disease 2019 (COVID-19) infection have been described, including cerebrovascular diseases, acute myelitis, Guillain-Barré syndrome, myasthenia gravis, critical illness myopathy and neuropathy, myositis, and rhabdomyolysis. We report an adult man presenting with an unusual etiology of weakness after a COVID-19 infection. Thyrotoxic hypokalemic periodic paralysis (THPP) was diagnosed from the presence of Graves' disease and hypokalemia because of intra-cellular potassium shifting. His weakness and hypokalemia responded well to potassium supplements and a non-selective b-blocker, whereas his thyrotoxicosis was initially controlled by an anti-thyroid medication and subsequently with radioactive iodine therapy. He was also treated as having mild COVID-19 based on his normal chest X-ray and oxygenation level. This is the first report showing an association between COVID-19 infection and a paralysis attack of THPP. Physicians should be alerted about this unusual cause of weakness, particularly in Asian patients.

PTPRF is disrupted in a patient with syndromic amastia.

BACKGROUND: The presence of mammary glands distinguishes mammals from other organisms. Despite significant advances in defining the signaling pathways responsible for mammary gland development in mice, our understanding of human mammary gland development remains rudimentary. Here, we identified a woman with bilateral amastia, ectodermal dysplasia and unilateral renal agenesis. She was found to have a chromosomal balanced translocation, 46,XX,t(1;20)(p34.1;q13.13). In addition to characterization of her clinical and cytogenetic features, we successfully identified the interrupted gene and studied its consequences. METHODS: Characterization of the breakpoints was performed by molecular cytogenetic techniques. The interrupted gene was further analyzed using quantitative real-time PCR and western blotting. Mutation analysis and high-density SNP array were carried out in order to find a pathogenic mutation. Allele segregations were obtained by haplotype analysis. RESULTS: We enabled to identify its breakpoint on chromosome 1 interrupting the protein tyrosine receptor type F gene (PTPRF). While the patient's mother and sisters also harbored the translocated chromosome, their non-translocated chromosomes 1 were different from that of the patient. Although a definite pathogenic mutation on the paternal allele could not be identified, PTPRF's RNA and protein of the patient were significantly less than those of her unaffected family members. CONCLUSIONS: Although ptprf has been shown to involve in murine mammary gland development, no evidence has incorporated PTPRF in human organ development. We, for the first time, demonstrated the possible association of PTPRF with syndromic amastia, making it a prime candidate to investigate for its spatial and temporal roles in human breast development.

Association between CTLA-4 polymorphisms and the susceptibility to systemic lupus erythematosus and Graves' disease in Thai population.

BACKGROUND: Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a cell surface molecule involved in the regulation of T cells. Single nucleotide polymorphisms (SNPs) of CTLA-4 gene are known to be associated with susceptibility to several autoimmune diseases, including systemic lupus erythematosus (SLE) and Graves' disease (GD). OBJECTIVE: The aim of this study was to determine whether the common SNPs +49A/G on exon1 and CT60A/G in 3'UTR of the CTLA-4 gene are associated with susceptibility to SLE and GD in Thai population. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze these two SNPs in 151 patients with SLE, 132 patients with GD and 153 healthy controls. RESULTS: Our study showed that there were no statistically significant differences in the allele and genotype frequencies of +49A/G and CT60A/G SNPs between patients with SLE and healthy controls as well as patients with GD vs. healthy controls (P > 0.05). However, the GG genotypes of +49A/G and CT60A/G were likely to be risk factors (OR >1) for GD but not in SLE. The effect of the +49G allele was similar to that of an autosomal recessive gene in the presence of the GG genotype, when compared to AA and AG, with an OR of 1.58 (95% CI = 0.95-2.61, p = 0.061) in GD. We also observed a dose response effect of the CT60G allele on GD susceptibility with an OR of 1.43 for GG homozygous and 1.17 for AG heterozygous subjects, when compared to the AA genotype, although these were not statistically significant (P > 0.05). CONCLUSION: We found no association between two functional polymorphisms (+49A/G and CT60A/G) of the CTLA-4 gene and susceptibility to SLE and GD. However, the association study utilizing a larger sample size should be performed to confirm this.

Clinical characteristics and treatment outcomes in acromegaly, a retrospective single-center case series from Thailand.

INTRODUCTION: acromegaly, an overproduction of growth hormone (GH), is associated with high rate of morbidity and mortality particularly in case of delayed in diagnosis and treatment. A wide variation of clinical presentations, treatment outcomes and morbidities have been reported. METHODS: a retrospective study was conducted to review clinical characteristics and treatment outcomes of patients with acromegaly treated in King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 2006 and 2018. RESULTS: eighty-four patients (31 males and 53 females) were reviewed, mean age at diagnosis was 45.7 ± 12.6 years (±SD), mean time of disease onset was 7.6 ± 6.4 years and mean follow-up period was 7.8 ± 5.3 years. The most common presenting symptoms were maxillofacial change (96.8%) and acral enlargement (94.7%). Hypertension (39.3%), diabetes mellitus (28.6%) and dyslipidemia (23.8%) were prevalent co-existing conditions. Four patients were identified having cancer at presentation; however, no additional malignancy was reported during the follow up. Most patients harbored macroadenomas, only 10 were found to have microadenomas. The outcomes of treatment were controlled disease in 70% of microadenoma and 64.9% of macroadenoma. Permanent loss of pituitary function was found in about 21.3% and there was one case reported of mortality. The logistic regression analysis for controlled disease outcome showed the IGF-I index after surgery was associated with controlled disease outcome with statistically significant result (P-value=0.006). CONCLUSION: our study offers descriptive clinical data of case series of acromegalic patients, which had favorable outcomes comparable with previous reports. In addition, IGF-I index after surgery is a predictive parameter for outcome of treatment.

Paraganglioma of the organ of Zuckerkandl and FH gene mutation.

Not required for Clinical Vignette.

Thyrotoxic Hypokalemic Periodic Paralysis Triggered by Dexamethasone Administration.

Thyrotoxic hypokalemic periodic paralysis (THPP) is a disease characterized by recurrent episodes of muscle weakness due to intracellular potassium shifting in the presence of high levels of thyroid hormone. It occurs more commonly amongst young Asian men with underlying Graves' disease. Attacks are commonly precipitated by ingestion of carbohydrate-rich meals or alcohols, stress or strenuous exercise. Herein, we describe an adult Thai man suffering from a hypokalemic periodic paralysis attack after receiving a dexamethasone injection. The diagnosis of Graves' disease was confirmed by his thyroid function test and a presence of thyrotropin-receptor antibody. His weakness and hypokalemia responded well to potassium supplement and a non-selective beta blocker, while his thyrotoxicosis was initially controlled by an anti-thyroid medication and subsequently with a subtotal thyroidectomy. Clinicians should beware of this manifestation when administering steroids in the thyrotoxic patients, especially of Asian male descent.

Macroprolactinemia in patients with hyperprolactinemia: an experience from a single tertiary center.

Macroprolactinemia frequently causes misdiagnosis, unnecessary investigation and inappropriate treatment in hyperprolactinemic patients. Aim of this study is to investigate the prevalence and clinical characteristics of Thai patients with macroprolactinemia. We performed a cross-sectional study in 56 hyperprolactinemic patients (51 women and 5 men) whose sera were subsequently tested for the presence of macroprolactin. Recovery of less than 40% of serum prolactin after polyethylene glycol (PEG) precipitation was indicative of macroprolactinemia. Our study revealed 19.64% (11/56) of patients with hyperprolactinemia were found to have a preponderance of macroprolactin. All patients with macroprolactinemia were women, of which eight of them were initially diagnosed as idiopathic hyperprolactinemia and mistreated with dopamine agonist medications. Interestingly, neuroradiological abnormalities were reported in three patients with macroprolactinemia, 2 cases with prolactinoma and one case with stalk effect hyperprolactinemia. In conclusion, nearly one-fifth of our patients with hyperprolactinemia have macroprolactinemia. This finding suggests that the diagnostic algorithm of all patients with hyperprolactinemia should include the PEG precipitation test as the initial step. Domain: Endocrinology.

Bilateral pheochromocytoma during the postpartum period.

BACKGROUND: Pheochromocytoma manifesting during pregnancy is uncommon but it is responsible for a high maternal and fetal mortality rate, especially when unrecognized. Most cases of pheochromocytoma are sporadic but they can be part of hereditary autosomal dominant syndromes. CASE: We describe a case of bilateral pheochromocytoma in a term-pregnant patient with a previous history of medullary thyroid carcinoma (MTC). Her genetic study revealed a heterozygous mutation, c.1900T>C, in the RET proto-oncogene which confirmed the diagnosis of multiple endocrine neoplasia type 2A (MEN2A). Unrecognized, the tumors caused a crisis with fatal outcome in the mother during the postpartum period. This event might have been prevented if the tumor had been detected previously. CONCLUSION: MEN2A affected pregnancy is an unusual condition. This syndrome should be suspected when a pregnant patient has a history of MTC. Early detection and appropriate management can prevent serious maternal and fetal complications. We also reviewed the literature of MEN2A-affected pregnancies.