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Cardiovascular autonomic neuropathy as a cause of fatigue in chronic hypoparathyroidism

期刊: ENDOCRINE, 0; ()

Purpose Hypoparathyroidism (hypoPT) results in an impairment of quality of life (QoL), an increase in fatigue and a higher risk of mortality. Cardiovascular autonomic neuropathy (CAN) is an impairment of the cardiovascular autonomic system and is associated with increased mortality and fatigability. Patients with hypoPT show an increased risk of CAN. However, no previous studies have investigated the association between CAN and QoL in hypoPT. To test whether CAN is associated with fatigue and impaired QOL in hypoPT patients. Methods We enrolled 48 subjects with postsurgical hypoPT treated with calcium and calcitriol and 38 healthy subjects who underwent thyroidectomy. Subjects completed the RAND 36-Item Short Form (SF-36) Health Survey, evaluating physical (PCS) and mental (MCS) health, and fatigue score. CAN was assessed using cardiovascular autonomic reflex tests (CARTs). Participants were considered to have "early CAN" (EC) if they had one abnormal CART and "definite CAN" (DC) with two or more abnormal CARTs. Results Compared with controls, hypoPT population had lower fatigue scores (44.5 IQRMODIFIER LETTER TRIANGULAR COLON9 vs 38.5 IQRMODIFIER LETTER TRIANGULAR COLON12.3, P = 0.031). In the hypoPT group, only participants with DC had a lower fatigue score than subjects without CAN (DC: beta: -9.55, P = 0.005) after adjusting for age, duration of disease, calcium concentration, TSH, calcitriol and calcium supplementation. No differences were found in the PCS and MCS scores in the hypoPT group. Conclusions CAN may explain fatigue, a common complaint of postsurgical hypoPT patients. Further larger and prospective investigations are needed to confirm our findings.

Risk factors for vertebral fracture in primary hyperparathyroidism

期刊: ENDOCRINE, 0; ()

Purpose Screening for vertebral fractures (VF) in primary hyperparathyroidism (PHPT) is recommended, but there are limited data regarding which patients are at greatest risk for VF. We evaluated risk factors for VF in PHPT. Methods This is a retrospective cross-sectional analysis of 117 participants with PHPT. We assessed Grades 2 and 3 VF by vertebral fracture assessment (VFA) and the association of VF with the trabecular bone score (TBS), other skeletal parameters and clinical risk factors. VFA was performed only in those who met National Osteoporosis Foundation criteria for VFA screening. Results T-scores were in the osteopenic range and TBS was degraded. Overall VF rate based on VFA or other imaging was 12.8%. Serum PTH, calcium and TBS were not associated with VF. Those with VF were older (p = 0.04), had worse renal function (p = 0.04), were more likely to have received osteoporosis treatment (p = 0.03), and tended to have had a prior fracture (p = 0.06). T-scores did not differ by fracture status at any skeletal site. Those with VF had nine times the odds of osteoporosis at the hip (95% CI 2.4-34.5), but this risk factor had low sensitivity (46.7%) for VF. Hip T-score < -2.6, Age > 78.6 years, and GFR < 58.8 ml/min/1.73 m(2) (thresholds maximizing sensitivity and specificity) had areas under the curve of 0.60-0.67 for VF (all p < 0.05) and low sensitivity. Findings were similar when analyses were limited to women. Conclusions In PHPT, VF risk factors included older age, prior fracture, worse renal function and osteoporosis at the hip, but not osteoporosis at other sites, TBS or biochemical indices of PHPT. Since identified risk factors had low sensitivity and were generally inaccurate for categorizing those with VF, the data do not support limiting screening to PHPT patients with these specific VF risk factors.

Synchronous bilateral adrenalectomy in ACTH-dependent hypercortisolism: predictors, biomarkers and outcomes

期刊: ENDOCRINE, 0; ()

Introduction Hypercortisolism requires a prompt therapeutic management to reduce the risk of development of a potential fatal emergency. A synchronous bilateral adrenalectomy (SBA) is effective in recovering hypercortisolism. However, specific indications for an SBA are not available. We aimed to evaluate the outcome of patients who underwent an SBA and to identify biomarkers able to predict the requirements of an SBA. Patients and methods A mono-centric and longitudinal study was conducted on 19 consecutive patients who underwent SBA for ACTH-dependent hypercortisolism between December 2003 and December 2017. This study population was compared to two control groups composed of patients cured after the resection of the ACTH secreting pituitary adenoma (Group A: 44 patients) and of the ACTH-secreting neuroendocrine tumours (Group B: 8 patients). Results Short- or long-term SBA complications or the recurrence of hypercortisolism did not occur. A single patient experienced Nelson syndrome. Clinical features after SBA showed improvement in the glico-metabolic assessment, hypertension, bone metabolism and the occurrence of hypokalaemia and infections. The younger the age at the time of Cushing's disease diagnosis, the longer the duration of active hypercortisolism, higher values of plasmatic ACTH and Cortisol (1 month after pituitary neurosurgery) and higher values of Ki67 in pituitary adenomas were detected in this study population as compared to Group A. Conclusions SBA is an effective and safe treatment for patients with unmanageable ACTH-dependent hypercortisolism. A multidisciplinary team in a referral centre with a high volume of patients is strongly recommended for the management of these patients and the identification of patients, for better surgical timing.

Ga-68-DOTATOC PET/CT in detecting neuroendocrine tumours responsible for initial or recurrent paraneoplastic Cushing's syndrome

期刊: ENDOCRINE, 0; ()

Purpose Paraneoplastic Cushing's syndrome (PCS) is frequently caused by neuroendocrine tumours (NETs). Approximately 20% of tumours are still occult years later. Gallium-68 somatostatin receptor-PET/CT is promising for the detection of the causal primary NET, but its role in case of recurrent PCS is rarely reported. We report our experience with DOTATOC PET/CT in localising the causal NET in cases of initial but also recurrent PCS, and its clinical impact. Methods A retrospective review of all DOTATOC PET/CTs performed in consecutive patients referred for PCS to our centre, between January 2011 and June 2017, was done. Nineteen patients underwent 26 PET/CTs, 13 for detection of a primary NET, seven for persistent or recurrent PCS after resection, and six for surveillance after resection of NETs previously detected on a DOTATOC PET/CT in our centre. Results Among the 13 PET/CTs performed to search for primary NET, five were positive: four carcinoid lung tumours were confirmed after resection and one lung focus was not confirmed since surgery would have carried a high risk. Clinical impact was 23% (3/13). Among the seven PET/CTs performed for persistent or recurrent PCS, six were true-positive, with confirmation of metastatic lymph nodes after resection. Clinical impact was 57% (4/7). All PET/CTs performed for surveillance were true-negative. Conclusions DOTATOC PET/CT seems to be a valuable tool for detection of the NET responsible for persistent or recurrent PCS after surgery. In this context, DOTATOC PET/CT was more effective than for the detection of the causal tumour in initial PCS.

Comprehensive relationships between gut microbiome and faecal metabolome in individuals with type 2 diabetes and its complications

期刊: ENDOCRINE, 2019; 66 (3)

Purpose As the treatment regimens such as metformin could confound the correlation between type 2 diabetes (T2D) and gut microbiome, we should revisit the relationship between gut microbiota and T2D patients who are not currently treated with metformin. Methods The study recruited 65 T2D patients: 49 with and 16 without diabetic complications, and 35 healthy controls. We sequenced the 16S rRNA V3-V4 region of gut microbiota and detected metabolites based on liquid chromatography mass spectrometry (LC/MS) and gas chromatography mass spectrometry (GC/MS) in faecal samples. Results The composition of both the gut microbiota and faecal metabolites changed significantly with T2D patients. The abundance of Proteobacteria and the ratio of Firmicutes/Bacteroidetes were higher in T2D patients than healthy subjects, and the short chain fatty acids (SCFAs), bile acids and lipids of T2D patients were significantly disordered. Moreover, the abundances of certain SCFA-producing bacteria (Lachnospiraceae and Ruminococcaceae etc.) were significantly increased in T2D patients, while the faecal SCFAs concentrations were significantly decreased. It's suggested that the role of SCFA-producing bacteria was not simply to produce SCFAs. Then we identified 44 microbial modules to explore the correlations between the gut microbiota and metabolic traits. Specially, most modules including certain SCFA-producing bacteria were comprehensively correlated to body mass index, the levels of blood glucose, blood pressure, blood cholesterol and faecal bile acids and lipids. Conclusions Our study identified the relationships between the gut microbiota and faecal metabolites, and provided a resource for future studies to understand host-gut microbiota interactions in T2D.

IF:3.3

The prevalence of heterozygous CYP21A2 deficiency in patients with idiopathic acne, hirsutism, or both

期刊: ENDOCRINE, 0; ()

Purpose The purpose of this study is to assess the prevalence of heterozygous CYP21A2 mutation and analyze its correlation with clinical manifestation in patients with acne, hirsutism, or both. Methods Clinical evaluation, hormone testing, and genetic analysis of the CYP21A2 gene were performed in 60 female patients who visited department of endocrinology of Peking Union Medical College Hospital (PUMCH) for acne, hirsutism, or both from May to November of 2018. The average age of the patients was 26.72 +/- 5.73 years. ACTH, Plasma cortisol, LH, FSH, PRL, estradiol, progesterone, testosterone, 17-hydroxyprogesterone (17-OHP), and dehydroepiandrosterone sulfate (DHEA-S) were measured in all participants. Polymerase chain reaction (PCR) combined with sequencing and multiplex ligation dependent probe amplification (MLPA) technique were used to detect the mutation of the CYP21A2 gene. The prevalence of CYP21A2 mutation was compared between the patients and 60 controls, as well as the data in different genetic variant database. Results A total of 8.3% (5/60) of individuals with acne, hirsutism, or both in this study were found to harbor heterozygotic CYP21A2 mutation, and the frequency was significantly higher than that in public databases. Identified mutations included V282L (n = 2), I173N (n = 1), E6 cluster [I237N, V238E, and M240K (n = 1)] and large deletion (n = 1). There was no significant difference in hormone levels between heterozygous carriers and subjects with normal CYP21A2 genes. Conclusions The prevalence of heterozygous CYP21A2 mutation detected in patients with acne, hirsutism, or both was significantly higher than in the general population. Whether the heterozygous mutation of CYP21A2 is the cause of clinical symptoms needs further assessment.

Postprandial leptin and adiponectin in response to sugar and fat in obese and normal weight individuals

期刊: ENDOCRINE, 2019; 66 (3)

Purpose Adipokines produced by white adipose tissue are central in the development of lifestyle diseases. Individuals in industrialized countries spend a substantial part of life in the non-fasting, postprandial state, which is associated with increased oxidation and inflammation. The aim was to study postprandial adiponectin and leptin levels after an oral fat tolerance test (OFTT) and an oral glucose tolerance test (OGTT) in obese (OB) and healthy, normal weight individuals (NW). Methods Fifty adults with obesity (BMI >= 30) and 17 healthy, NW were included. Postprandial triglyceride (TG), adiponectin, and leptin levels were measured every second hour during an 8 h OFTT, and every half hour during a 2 h OGTT. Results Compared with the basal level, postprandial levels of adiponectin following OFTT showed a slight initial peak, followed by a significant decrease at 8 h, in the NW. In the OB these changes were abolished. Postprandial levels of leptin decreased significantly from basal levels in the OFTT, in the NW, whereas in the OB, leptin was unchanged except for a slight increase from 2 to 8 h. During the OGTT both adiponectin and leptin levels remained unchanged in the NW, but decreased significantly in the OB. In addition, the OB had delayed TG clearance at 6 h. Conclusions A fatty meal gives postprandial changes in the secretion of adiponectin and leptin in NW, but not in OB. Our observations indicate that a potential postprandial regulatory role of adiponectin and leptin is impaired in OB, and of importance in a more comprehensive understanding of the delayed postprandial TG clearance in obese individuals.

IF:3.3

A nomogram for predicting the presence of germline mutations in pheochromocytomas and paragangliomas

期刊: ENDOCRINE, 2019; 66 (3)

Purpose Up to 40% of patients with pheochromocytomas or paragangliomas (PPGLs) carry a germline mutation. This study aimed to build a nomogram using clinical information to predict the probability of germline mutation in PPGLs. Methods The data were collected from 563 patients who were diagnosed with PPGLs between 2002 and 2015. Clinical and pathologic features were assessed with a multivariable logistic regression analysis to predict the presence of germline mutations. A nomogram to predict the probability of germline mutation was constructed with R software. Discrimination and calibration were employed to evaluate the performance of the nomogram. Results By multivariate analysis, age at manifestation, bilateral, or multifocal tumors and family history were identified as independent predictors of the presence of any germline mutation. The nomogram was then developed using these three variables. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0. 841 (95% confidence interval [CI], 0.809-0.871). The calibration plot indicated that the nomogram-predicted probabilities compared very well with the actual probabilities (Hosmer-Lemeshow test: P = 0.888). Conclusion The nomogram is a valuable predictive tool for the presence of germline mutations in patients with PPGLs.

IF:3.3

Body muscle-to-fat ratio gender-specific cut-off values for impaired insulin sensitivity in patients with treatment-naive type 2 diabetes mellitus

期刊: ENDOCRINE, 2019; 66 (3)

PurposeWe previously reported that the body muscle-to-fat ratio (BMFR), measured using bioelectrical impedance, significantly correlated with whole-body insulin sensitivity. We examined BMFR gender-specific cut-off values for impaired insulin sensitivity in treatment-naive type 2 diabetes mellitus (T2DM) patients.MethodsSubjects included 101 untreated T2DM patients (male, 66; female, 35). We performed a hyperinsulinemic-euglycemic clamp examination to measure the steady-state glucose infusion rate (M value) as an indicator of whole-body insulin resistance. We defined the M value divided by the steady-state serum insulin value as the M/I value. We defined the existence of insulin resistance using an M/I ratio <9.0. The optimal cut-off value for BMFR was calculated by receiver operating characteristics (ROC) analysis.ResultsThe cut-off value of the BMFR for insulin resistance was 2.75 (area under the curve [AUC]=0.83, sensitivity 75%, and specificity 76%, P<0.001) for males and 1.65 (AUC=0.87, sensitivity 84%, and specificity 81%, P<0.001) for females. Simple linear regression analysis showed that BMFR was significantly correlated with the M/I value in both genders (males, B=0.77, P<0.01; females, B=0.83, P<0.01).ConclusionsBMFR cut-off values for impaired insulin sensitivity in treatment-naive T2DM patients were 2.75 for males and 1.65 for females.

IF:3.3

Thyroid nodule prevalence among women in areas of high natural background radiation, Karunagappally, Kerala, India

期刊: ENDOCRINE, 0; ()

Purpose Radiation exposure has been reported to cause thyroid nodules. The study area was Karunagapally, which has several areas with high natural radiation levels derived from thorium and its decay products. Since thyroid abnormalities are more common in women, the focus was only on women. Methods The examinations included interview, ultrasonography of the thyroid and serum assays of free thyroxine (FT4), thyrotropin (TSH), and anti-thyroglobulin levels. Cumulative dose during the childhood and lifetime cumulative dose (lagged by 5 years) were estimated. Results We examined 524 female residents aged 17-73 years and found 75 cases of solitary solid thyroid nodules. The prevalence of thyroid nodules were 14.1 % (n = 42) in high dose panchayats and 14.5% (n = 33) in low-dose panchayats. In the logistic regression analysis adjusted for age, the prevalence of solitary thyroid nodule was not linearly related to childhood cumulative dose (P for trend = 0.159) and lifetime cumulative dose (P for trend = 0.333). The prevalence of thyroiditis and hypothyroidism was not related to natural radiation exposure. Serum levels of FT4 or TSH were not related to natural radiation exposure. Conclusions The results obtained from the present study do not support the increase of solitary thyroid nodule, thyroiditis or hypothyroidism in relation to high-natural-background-radiation exposure.

Effect of Graves' disease on the prognosis of differentiated thyroid carcinoma: a meta-analysis

期刊: ENDOCRINE, 0; ()

Purpose Several studies have reported different findings on the prognosis of differentiated thyroid carcinoma combined with Graves' disease. To assess the effect of Graves' disease on differentiated thyroid carcinoma, a meta-analysis was undertaken. Methods PubMed, OVID and the Cochrane Library were systematically searched for trials published prior to Oct. 2018. Studies containing data on the outcomes of Graves' disease with differentiated thyroid carcinoma were included. Summary estimates of the prevalence of recurrence/disease progression/persistence and mortality as well as odds ratios and weighted mean differences were calculated with a random-effects model. Results Of the 916 related articles found, 13 fulfilled the inclusion criteria. The recurrence/disease progression/persistent rate was not significantly different between the Graves' disease group and the non-Graves' disease group (P = 0.86). However, the analysis of three studies with K-M curves or HRs showed that there was a significant difference between the two groups (P = 0.04). Subgroup analysis showed that the contradictory results could be due to the location/race assessed in the studies. Graves' disease almost acted as a risk factor (OR = 1.77, 95%C.I. = 0.99-3.16) for differentiated thyroid carcinoma in European studies. When heterogeneous studies were excluded, the analyses show that GD was a risk factor for recurrence/disease progression/persistence (P = 0.03, OR = 1.75, 95%C.I. = 1.04-2.95). The overall mortality rate was significantly higher in the Graves' disease group than in the non-Graves' disease group (P = 0.02, OR = 2.93, 95%C.I. = 1.17-7.37). Conclusions Graves' disease acts as a risk factor for the prognosis of differentiated thyroid carcinoma. The recurrence/disease progression/persistent rate may be affected by TSAbs in a specific location/race and with a genetic immunization background. However, the histotypes and subtypes may play an important role in mortality rate.

Effect of orbital radiotherapy on the outcome of surgical orbital decompression for thyroid-associated orbitopathy (TAO): a retrospective study in 136 patients

期刊: ENDOCRINE, 0; ()

Purpose In patients with moderate to severe thyroid-associated orbitopathy (TAO), orbital radiation therapy (ORT) can prevent disease progression. In the sequelae stage, orbital decompression surgery can be useful in case of functional discomfort. The aim of this study was to evaluate the effect of orbital ORT on the outcomes of decompression surgery. Methods In this retrospective study, we included 136 patients who had had bilateral orbital decompression between 1995 and 2016. Before surgery, 38 patients received Radiation Therapy (RT+) while 98 did not (RT-). All RT+ patients and 20 RT- patients had systemic corticosteroid treatment. In both groups surgical outcome was evaluated by exophthalmos reduction (mm), palpebral fissure (mm), distance between the lid margin and the corneo-scleral limbus (mm), existence of conjunctival hyperemia and diplopia. Results In both RT+ and RT- groups, surgery improved the proptosis, significantly greater in RT+(3.66 +/- 1.79 mm) than in RT- group (2.85 +/- 1.80 mm) (p < 0.019). No significant differences were noted in the palpebral fissure, the distance from the lid margin to the corneo-scleral limbus. After surgery, only one patient (5%) in the RT+ group presented with new-onset diplopia, whereas in the RT- group there were 14 (36%) patients (p < 0.007). After orbital decompression, the number of conjunctival hyperemia decreased by 6 (21%) in the RT+ group versus 21 (60%) in the RT- group (p < 0.006). Conclusion Orbital radiotherapy during the inflammatory phase enhances the outcomes after orbital decompression in TAO. After surgery we observed a greater improvement in proptosis and in diplopia for RT+ versus RT- patients.

Hypomagnesaemia and its determinants in a contemporary primary care cohort of persons with type 2 diabetes

期刊: ENDOCRINE, 0; ()

Aims Among persons with type 2 diabetes mellitus (T2DM) hypomagnesaemia has been reported in 14-48% of patients. This may be of significance given the emerging associations of hypomagnesaemia with glucometabolic disturbances and possibly even complications. We assessed the prevalence of hypomagnesaemia and its determinants, in a well-defined cohort of persons with T2DM treated in primary care. Methods Observational cohort study among persons with T2DM treated in primary care in the Northeast of the Netherlands. Magnesium was measured using a colorimetric endpoint assay (Roche). Hypomagnesaemia was defined as a serum magnesium level <0.70 mmol/L. Pearson correlations were performed to correlate variables with serum magnesium. Next, a stepwise backward regression model was made. Results Data of 929 persons (55% male) with a mean age of 65 (+/- 10) years, diabetes duration 6.5 [3.0-10.1] years, and HbA1c concentration 6.7 (+/- 0.7)% (50 (+/- 9) mmol/mol) were analysed. Serum magnesium was 0.79 (+/- 0.08) mmol/L. The percentage of persons with magnesium deficiency was 9.6%. Age, diabetes duration, BMI, HbA1c, use of metformin, sulfonylurea derivatives, and DPP4 inhibitors were negatively associated with magnesium concentrations. In contrast, LDL cholesterol and serum creatinine were positively associated serum magnesium. Conclusions Hypomagnesaemia was present in 9.6% of T2DM patients treated in primary care. This percentage is remarkably lower than reported previously, possibly due to the unselected nature of our population. Concerning T2DM-related factors, only BMI, HbA1c and the use of metformin, sulfonylurea derivatives and DPP4 inhibitors correlated negatively with magnesium concentrations.

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