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.

Changes in plasma aldosterone level after weight loss by bariatric surgery in morbidly obese patients.

BACKGROUND: Overactivation of renin-aldosterone-angiotensin system (RAS) is part of the pathogenesis of obesity-associated hypertension. Evidences have shown that weight loss can result in reduction in blood pressure and RAS. This study was aim to investigate changes of plasma aldosterone concentration (PAC) after bariatric surgery. METHODS: A prospective study was done in 14 morbidly obese patients undergoing bariatric surgery. Patients who were taking medications that can interfere with PAC and renin levels were excluded. Collection of blood samples were done at baseline and at 3 and 6-month post-bariatric surgery. RESULTS: Four out of 14 patients had hypertension at baseline. Mean body mass index (BMI) was 56.7 ± 13.5 kg/m2. PAC were significantly decreased at 3-and 6-month post-bariatric surgery from 14.3 ± 8.0 to 7.5 ± 5.5 [reduction of 36% from baseline (P < 0.01)] and 8.0 ± 6.6 ng/dl [reduction of 32% from baseline (P < 0.05)] respectively. The reduction of PAC at 3-month post-surgery was correlated with the reduction of body weight (r = 0.46, P < 0.05), waist circumference (r = 0.73, P < 0.05) and percent of body fat (r = 0.58, P < 0.05). CONCLUSIONS: Maximal reduction of PAC in obese patients underwent bariatric surgery occurred during the first 3 months after bariatric surgery. The reduction of PAC was associated with the reduction of body weight, waist circumference and percent of body fat suggesting the link between RAS and obesity-mediated hypertension.

Association of osteoporosis and sarcopenia with fracture risk in transfusion-dependent thalassemia.

Patients with transfusion-dependent thalassemia (TDT) have an increased risk of osteoporosis and fractures. They also have several potential factors associated with sarcopenia. There has been currently no study on sarcopenia and its association with falls and fractures in TDT. This study aims to determine the prevalence of and factors associated with osteoporosis, fragility fractures, and sarcopenia in adults with TDT. A cross-sectional study was conducted at the hematologic clinic at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Clinical data and laboratory testing were collected. Bone mineral density and morphometric vertebral fracture were assessed. Sarcopenia was defined using the 2014 and 2019 Asian Working Group for Sarcopenia (AWGS) criteria. We included 112 TDT patients aged 35.1 ± 12.5 years. The prevalence of osteoporosis was 38.4%. Fragility fractures were found in 20.5% of patients. Lower BMI (OR 0.29; 95% CI 0.12-0.72, P = 0.007) and hypogonadal state (OR 3.72; 95% CI 1.09-12.74, P = 0.036) were independently associated with osteoporosis. According to the 2014 AWGS criteria, the prevalence of overall sarcopenia and severe sarcopenia was 44.6% and 13.4%, respectively. Severe sarcopenia was strongly associated with fragility fractures (OR 4.59, 95% CI 1.21-17.46, P = 0.025). In conclusion, osteoporosis, fragility fractures, and sarcopenia were prevalent in adults with TDT. Severe sarcopenia was associated with fragility fractures. Early osteoporosis and sarcopenia screening and prevention may reduce fracture risk and its complications in these patients.

Paraganglioma of the organ of Zuckerkandl and FH gene mutation.

Not required for Clinical Vignette.

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.

Prevalence of Somatic KCNJ5 Mutations in Thai Patients With Aldosterone-Producing Adrenal Adenomas.

Somatic KCNJ5 mutations result in excess aldosterone production and are reported to be more common in Asia than elsewhere. To assess the prevalence of somatic KCNJ5 mutations in Thai patients with aldosterone-producing adrenal adenomas (APAs) in a single tertiary center, we analyzed the paraffin-embedded tissue of KCNJ5 mutations from 96 patients with sporadic APAs who underwent unilateral laparoscopic adrenalectomy at our center during 2007 to 2016. We also assessed the clinical characteristics, treatment outcomes, and biochemistry and histologic differences among patients with and without somatic KCNJ5 mutations. Of the 96 patients with APA, 67 (70%) had somatic mutations of the KCNJ5 gene: 39 patients with p.G151R, 26 patients with p.L168R, one patient with p.T158A, and one patient with p.W126R. All patients presented with hypertension. Hypokalemia was documented in 98% of patients. The hypertension cure rate at 1 year after surgery was 35%. Patients with somatic KCNJ5 mutations required more potassium supplementation and had adrenal histology compatible with zona fasciculata-like cells compared with patients without the mutations (all P < 0.05). There were no significant differences in preoperative plasma aldosterone concentration (PAC), plasma renin activity, aldosterone/renin ratio, potassium level, treatment of hypertension, tumor size, and hypertension cure rate among patients in the KCNJ5-mutant and nonmutant groups. In a multivariate analysis, a higher PAC was associated with the presence of somatic KCNJ5 mutations. In summary, the prevalence of somatic KCNJ5 mutations in patients with sporadic APAs in Thailand, an Asian country with residents of different ethnic backgrounds, is comparable to previous reports in Asia.

In Thai Nationals, the ApoE4 Allele Affects Multiple Domains of Neuropsychological, Biobehavioral, and Social Functioning Thereby Contributing to Alzheimer's Disorder, while the ApoE3 Allele Protects Against Neuropsychiatric Symptoms and Psychosocial Deficits.

The apolipoprotein E epsilon 4 (ApoE4) allele is the strongest genetic risk factor for Alzheimer's disorder (AD) and is associated with semantic and episodic memory deficits. The aim of this study was to examine the associations between ApoE alleles (E2, E3, E4) and genotypes and neuropsychological tests, behavioral functions, and dementia symptoms as assessed using Consortium to Establish a Registry for Alzheimer's Disease (CERAD). This study included 60 patients with Alzheimer's disorder (AD), 60 with mild cognitive disorder (MCI), and 62 normal volunteers. ApoE4 carriers and individuals with E3/E4 and E4/E4 genotypes show an increased incidence of AD, but not MCI. ApoE4 carriers and especially E4/E4 homozygotes show a worse outcome on the CERAD total score, Blessed Dementia Scale, and Short Blessed Test and lower scores on the Verbal Fluency Test, Boston Naming Test, Constructional Praxis Recall, and Word List Memory, Recall, and Recognition. ApoE4 carriers and E4/E3 heterozygotes show higher scores on the Clock Drawing Test. ApoE4 carriers show a worse outcome on the CERAD clinical history scores of memory, language, personality, ADL, orientation, and social skills, while allele AopE3 carriers show better scores on activities of daily living (ADL) and social skills. ApoE3 carriers show lower total weighted, irritability/aggression, and behavioral dysregulation scores on the Behavior Rating Scale for Dementia. The results show that in Thai individuals, the presence of ApoE4 allele is accompanied by a multifarious decline in neurocognitive functions and behavioral features and that ApoE3 may convey protection against neuropsychiatric symptoms and a decline in social skills. ApoE4 and especially the E4/E4 genotype may affect multiple domains of cognitive, biobehavioral, and social functioning thereby contributing to AD phenomenology.

A case of coexistence of TSH/GH-secreting pituitary tumor and papillary thyroid carcinoma: Challenges in pathogenesis and management.

Co-existence of thyrotropin/growth hormone-secreting pituitary adenoma with differentiated thyroid carcinoma is exceedingly rare, with less than 15 cases having been reported. Its clinical presentation and treatment strategy are challenging. We report a case of pituitary macroadenoma, with clinical syndromes of acromegaly and hyperthyroidism, and a thyroid nodule, with cytologically confirmed to be a papillary thyroid carcinoma. Clinical implications, focusing on the strategy for proper management, and possible pathogenesis were discussed.

Undercarboxylated osteocalcin is associated with insulin resistance, but not adiponectin, during pregnancy.

In mice, undercarboxylated osteocalcin (ucOC) improves beta-cell function and insulin sensitivity through adiponectin. In humans, levels of total osteocalcin (OC) and ucOC were negatively correlated with insulin resistance (IR) indices in patients with type 2 diabetes. Whether ucOC plays a role in glucose homeostasis and whether its effect is mediated through adiponectin during pregnancy is unclear. Serum levels of total OC, ucOC, and adiponectin were measured in 130 pregnant women with varying degrees of IR [gestational diabetes mellitus (GDM), n = 74 and non-GDM, n = 56]. In all participants, total OC and ucOC levels were positively correlated with HOMA-IR and HOMA-%B, and negatively correlated with QUICKI. In contrast, adiponectin levels were negatively correlated with HOMA-IR and positively correlated with QUICKI (P < 0.01, both). However, neither total OC nor ucOC was associated with adiponectin. Although none of these markers could help distinguish women with and without GDM, total OC and ucOC levels were significantly higher in non-GDM women who had 1 abnormal OGTT value than those who had all normal OGTT values. Total OC and ucOC levels were significantly correlated with insulin secretion and IR indices, but not adiponectin levels, in pregnant women. Changes in OC might be a sensitive response to increased IR during pregnancy, which was not mediated through adiponectin.

Changes in Testosterone Levels and Sex Hormone-Binding Globulin Levels in Extremely Obese Men after Bariatric Surgery.

Objective. Obesity is a risk factor for hypogonadotropic hypogonadism in men. Weight loss has been shown to improve hypogonadism in obese men. This study evaluated the early changes in sex hormones profile after bariatric surgery. Methods. This is a prospective study including 29 morbidly obese men. Main outcomes were changes in serum levels of total testosterone (TT), free testosterone (cFT), SHBG, estradiol, adiponectin, and leptin at 1 and 6 months after surgery. Results. The mean age of patients was 31 ± 8 years and the mean BMI was 56.8 ± 11.7 kg/m2. Fifteen patients underwent Roux-en-Y gastric bypass and 14 patients underwent sleeve gastrectomy. At baseline, 22 patients (75.9%) had either low TT levels (<10.4 nmol/L) or low cFT levels (<225 pmol/L). Total testosterone and SHBG levels increased significantly at 1 month after surgery (p ≤ 0.001). At 6 months after surgery, TT and cFT increased significantly (p ≤ 0.001) and 22 patients (75.9%) had normalized TT and cFT levels. There were no changes in estradiol levels at either 1 month or 6 months after surgery. Conclusions. Increases in TT and SHBG levels occurred early at 1 month after bariatric surgery while improvements in cFT levels were observed at 6 months after bariatric surgery.

Apolipoprotein A-V is not a major determinant of triglyceride levels during human sepsis.

PURPOSE: During critical illnesses, alterations in lipid metabolism occur. We examined levels of apolipoprotein A-V, a novel regulator of triglyceride metabolism, during sepsis in humans. METHODS: Seventy-five cases of sepsis and 75 cases of acute illnesses not associated with infection were recruited. Lipids and apolipoprotein A-V levels were measured by enzymatic methods and enzyme-linked immunosorbent assay, respectively, within 24 hours of diagnosis. Fifty healthy controls were also enrolled. RESULTS: During sepsis and acute illnesses, serum total cholesterol and high-density lipoprotein cholesterol levels were significantly lower than those in controls. Serum triglyceride levels, however, were not significantly different. Similarly, serum apolipoprotein A-V levels during sepsis were not significantly different from those during acute illnesses and those in controls (expressed as median [interquartile range]: 149.6 [97.5-257.1] vs 157.9 [98.4-238.2] and 155.9 [91.5-253.8] ng/mL, respectively; P = .98); and they were not correlated with serum triglyceride levels. Low apolipoprotein A-V levels were associated with higher mortality, but the association became nonsignificant after adjusting for high-density lipoprotein cholesterol levels. CONCLUSIONS: During sepsis or acute illnesses, serum apolipoprotein A-V levels were not significantly different from those in controls. Furthermore, apolipoprotein A-V levels were not linearly correlated with triglyceride levels, suggesting that it might not be a major determinant of triglyceride levels during sepsis.

Concurrent bilateral pheochromocytoma and thoracic paraganglioma during pregnancy.

Although hypertension occurring during pregnancies is not uncommon and its prognosis is generally excellent, some of its unusual causes can lead to catastrophic consequences, especially in undiagnosed cases. Here, we report a pregnant woman who presented with hypertension in her early pregnancy. It was subsequently found to be caused by bilateral pheochromocytoma. After removal of both tumors, catecholamine levels unexpectedly and unexplainably remained elevated. At 23 weeks of gestation, the fetus was found dead in utero. After the fetal death, additional studies were performed and revealed a thoracic paraganglioma. To our knowledge, this is the first report of a case of three catecholamine-producing tumors occurring concurrently during a pregnancy. Genetic analysis helped identify this unprecedented condition; the patient harbored a heterozygous missense mutation c.482G>A in exon 3 of the VHL gene, indicating von Hippel-Lindau syndrome. Physicians who care for hypertensive pregnant patients should be aware of this condition as its diagnosis would probably lead to a better outcome.