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Open access

Lizhi Zhang, Jinwei He, Xiang Sun, Dongyue Pang, Jingjing Hu, and Bo Feng

Our previous studies have demonstrated that there is a correlation between GLP-1R SNP and the BMD in postmenopausal women. GLP-1 and GIP are both incretins. Whether the mutation of GIPR gene affects bone metabolism. SNP rs10423928 is a GIPR gene polymorphism that has been studied more frequently. The aim of this study was to investigate the association between GIPR SNP rs10423928 and bone-mineral density (BMD) in postmenopausal women in Shanghai. The GIPR SNP rs10423928 was detected in 884 postmenopausal women in Shanghai, the correlation between the GIPR SNP and BMD was further assessed. The dominant T/T genotype of the GIPR SNP rs10423928 was significantly related to BMD of the femoral neck (P = 0.035) and Ward’s triangle area (P = 0.033). Our research found that the dominant T/T genotype of GIPR SNP rs10423928 in postmenopausal women is significantly associated with higher BMD. The T/T genotype seems to have bone protection.

Open access

Maria Stelmachowska-Banaś and Izabella Czajka-Oraniec

Immune checkpoint inhibitors (ICIs) belong to a new group of anticancer drugs targeting T-cell proteins involved in the activation of immune response toward malignancies. Their introduction into clinical practice was a milestone in modern cancer treatment. However, the significant advantage of ICIs over conventional chemotherapy in terms of therapeutic efficacy is accompanied by new challenges related to specific side effects. ICI-induced immune system activation could lead to the loss of self-tolerance, presenting as autoimmune inflammation and dysfunction of various tissues and organs. Thus, the typical side effects of ICIs include immune-related adverse events (irAEs), among which endocrine irAEs, affecting numerous endocrine glands, have been commonly recognized. This review aimed to outline the current knowledge regarding ICI-induced endocrine disorders from a clinical perspective. We present updated information on the incidence and clinical development of ICI-induced endocrinopathies, including the most frequent thyroiditis and hypophysitis, the rarely observed insulin-dependent diabetes mellitus and primary adrenal insufficiency, and the recently described cases of hypoparathyroidism and lipodystrophy. Practical guidelines for monitoring, diagnosis, and treatment of ICI-related endocrine toxicities are also offered. Rising awareness of endocrine irAEs among oncologists, endocrinologists, and other health professionals caring for patients receiving ICIs could contribute to better safety and efficacy. As immunotherapy becomes widespread and approved for new types of malignancies, increased incidences of endocrine irAEs are expected in the future.

Open access

Yuan Liu, Siyi Guo, Jinsong Wu, Rongai Wang, Jinbo Liu, Yan Liu, Bin Lv, Nan Liu, Ling Jiang, and Xiaoli Zhang

The clinical presentation of primary hyperparathyroidism (PHPT) differs between patients from developed and developing countries. In China, the clinical pattern has changed over the past few decades. Our aim was to elucidate general changes in the clinical characteristics of PHPT from 2010 to 2021. We enrolled 343 patients with PHPT at the Qilu Hospital of Shandong University, Jinan, China, from January 2010 to May 2021, including both surgical and non-surgical patients. Patients were divided into two subgroups, 2010–2016 (group A, n  = 152) and 2017–2021 (group B, n  = 191), based on the time span. We compared clinical manifestations and laboratory result data between these two groups. The mean patient age was 52.59 ± 13.55 years, and the male-to-female ratio was 1:2.54. Of the 343 patients, 183 (53.35%) had symptomatic PHPT; bone pain, urolithiasis, and fatigue were the most common symptoms. Post-operative pathology showed that 96.20% of the patients had parathyroid adenoma, whereas 2.41% had parathyroid carcinoma. Great changes occurred between 2010 and 2021; the percentage of patients with asymptomatic PHPT (aPHPT) increased from 36.18% in group A to 54.97% in group B. Moreover, patients in group B showed significantly lower serum calcium, alkaline phosphatase, parathyroid hormone, and urinary phosphate levels but higher serum 25-hydroxyvitamin D levels than those in group A. Clinical presentations in group B were also milder. In conclusion, the clinical characteristics of Chinese PHPT patients changed dramatically from 2010 to 2021, with asymptomatic PHPT (aPHPT becoming the predominant type over the last 3 years.

Open access

Laura J Reid, Bala Muthukrishnan, Dilip Patel, Mike S Crane, Murat Akyol, Andrew Thomson, Jonathan R Seckl, and Fraser W Gibb

Objective

Primary hyperparathyroidism (PHPT) is a common reason for referral to endocrinology but the evidence base guiding assessment is limited. We evaluated the clinical presentation, assessment and subsequent management in PHPT.

Design

Retrospective cohort study.

Patients

PHPT assessed between 2006 and 2014 (n = 611) in a university hospital.

Measurements

Symptoms, clinical features, biochemistry, neck radiology and surgical outcomes.

Results

Fatigue (23.8%), polyuria (15.6%) and polydipsia (14.9%) were associated with PHPT biochemistry. Bone fracture was present in 16.4% but was not associated with biochemistry. A history of nephrolithiasis (10.0%) was associated only with younger age (P = 0.006) and male gender (P = 0.037). Thiazide diuretic discontinuation was not associated with any subsequent change in calcium (P = 0.514). Urine calcium creatinine clearance ratio (CCCR) was <0.01 in 18.2% of patients with confirmed PHPT. Older age (P < 0.001) and lower PTH (P = 0.043) were associated with failure to locate an adenoma on ultrasound (44.0% of scans). When an adenoma was identified on ultrasound the lateralisation was correct in 94.5%. Non-curative surgery occurred in 8.2% and was greater in those requiring more than one neck imaging modality (OR 2.42, P = 0.035).

Conclusions

Clinical features associated with PHPT are not strongly related to biochemistry. Thiazide cessation does not appear to attenuate hypercalcaemia. PHPT remains the likeliest diagnosis in the presence of low CCCR. Ultrasound is highly discriminant when an adenoma is identified but surgical failure is more likely when more than one imaging modality is required.

Open access

Ghazala Zaidi, Vijayalakshmi Bhatia, Saroj K Sahoo, Aditya Narayan Sarangi, Niharika Bharti, Li Zhang, Liping Yu, Daniel Eriksson, Sophie Bensing, Olle Kämpe, Nisha Bharani, Surendra Kumar Yachha, Anil Bhansali, Alok Sachan, Vandana Jain, Nalini Shah, Rakesh Aggarwal, Amita Aggarwal, Muthuswamy Srinivasan, Sarita Agarwal, and Eesh Bhatia

Objective

Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder characterized by progressive organ-specific autoimmunity. There is scant information on APS1 in ethnic groups other than European Caucasians. We studied clinical aspects and autoimmune regulator (AIRE) gene mutations in a cohort of Indian APS1 patients.

Design

Twenty-three patients (19 families) from six referral centres in India, diagnosed between 1996 and 2016, were followed for [median (range)] 4 (0.2–19) years.

Methods

Clinical features, mortality, organ-specific autoantibodies and AIRE gene mutations were studied.

Results

Patients varied widely in their age of presentation [3.5 (0.1–17) years] and number of clinical manifestations [5 (2–11)]. Despite genetic heterogeneity, the frequencies of the major APS1 components (mucocutaneous candidiasis: 96%; hypoparathyroidism: 91%; primary adrenal insufficiency: 55%) were similar to reports in European series. In contrast, primary hypothyroidism (23%) occurred more frequently and at an early age, while kerato-conjunctivitis, urticarial rash and autoimmune hepatitis were uncommon (9% each). Six (26%) patients died at a young age [5.8 (3–23) years] due to septicaemia, hepatic failure and adrenal/hypocalcaemic crisis from non-compliance/unexplained cause. Interferon-α and/or interleukin-22 antibodies were elevated in all 19 patients tested, including an asymptomatic infant. Eleven AIRE mutations were detected, the most common being p.C322fsX372 (haplotype frequency 37%). Four mutations were novel, while six others were previously described in European Caucasians.

Conclusions

Indian APS1 patients exhibited considerable genetic heterogeneity and had highly variable clinical features. While the frequency of major manifestations was similar to that of European Caucasians, other features showed significant differences. A high mortality at a young age was observed.

Open access

Georgios Kontogeorgos, Zoi Mamasoula, Emily Krantz, Penelope Trimpou, Kerstin Landin-Wilhelmsen, and Christine M Laine

Objective

Hypoparathyroidism (HypoPT) is a rare endocrine disorder in which insufficient levels of parathyroid hormone (PTH) lead to low serum calcium (S-Ca) levels and muscular cramps. The aim was to study the health-related quality of life (HRQoL) and comorbidities in patients with HypoPT compared with the general population and to estimate the need of treatment with PTH analog.

Design

Patients with HypoPT were identified and compared with a population sample. Short Form-36 (SF-36) and EuroQol-5 Dimensions Visual Analogue Scale questionnaires were used. All patients were followed up at the Sahlgrenska University Hospital outpatient clinic.

Methods

From the medical records between 2007 and 2020, 203 patients with HypoPT were identified and compared with a population sample (n = 414) from the World Health Organization’s (WHO) MONICA project, Gothenburg, Sweden. Of the 203 patients who met the diagnostic criteria, 164 were alive and 65% answered the HRQoL questionnaires.

Results

Patients with HypoPT, 80% postsurgical, and controls had similar age (60 years) and sex distribution (80% women). Patients had lower SF-36 summary component scores for physical (40.0 (interquartile range (IQR): 21) vs 51.2 (IQR: 14.6); P < 0.001) and mental (43.1 (IQR:17.4) vs 56.1(IQR:13.3); P < 0.001) well-being, irrespective of etiology or calcium levels. Individuals with HypoPT had more medications and lower renal function but not higher mortality than controls. Low HRQoL together with low calcium was present in 23% of individuals with HypoPT.

Conclusion

HRQoL was markedly lower in patients with HypoPT than in controls and independent of S-Ca levels. Treatment with PTH analog could be considered at least among patients with both low HRQoL and low calcium levels.

Open access

Pinaki Dutta, Bhuvanesh Mahendran, K Shrinivas Reddy, Jasmina Ahluwalia, Kim Vaiphei, Rakesh K Kochhar, Prakamya Gupta, Anand Srinivasan, Mahesh Prakash, Kanchan Kumar Mukherjee, Viral N Shah, Girish Parthan, and Anil Bhansali

The effectiveness and short-term safety of recombinant human GH (r-hGH) in acromegaly patients with GH deficiency (GHD) after treatment are not well established. The study includes ten subjects with acromegaly who had GHD treated with r-hGH for 6 months. Control groups consisted of ten age-, gender-, and BMI-matched healthy subjects and ten active acromegaly patients who were treatment naïve. Body composition, quality of life (QoL), muscle strength, lipid profile, and cardiovascular risk factors were assessed in all subjects at baseline, and the same parameters were reassessed after 6 months of therapy with r-hGH in acromegaly with GHD. Repeat magnetic resonance imaging of the sella was performed in treated subjects. Optical colonoscopy was done and biopsies were taken from multiple sites for proliferation indices (Ki67). The median duration of GHD was 17.8 months and dose of r-hGH administered was 5.7±1.5 μg/kg per day. There was improvement in bone mineral content (P=0.01), bone mineral density (P=0.04), muscle strength (P<0.001), total cholesterol (P=0.003), high-density cholesterol (P<0.001), and QoL – score (P=0.005), and reduction in low-density cholesterol (P=0.003) and triglyceride (P=0.004) after treatment. There was no change in lean body mass, total body fat, hsCRP, lipoprotein (a), and fibrinogen levels. There was a modest increase in plasminogen activator inhibitor 1 (P=0.002), but it was lower compared with healthy controls and treatment naïve acromegalics (P=0.007). Six month-r-hGH therapy improves body composition, atherogenic lipid profile, QoL, and muscle strength in GHD patients who had acromegaly. Long-term prospective studies are needed to evaluate the effect of r-hGH therapy in these patients.

Open access

Franca Genest, Michael Schneider, Andreas Zehnder, Dominik Lieberoth-Leden, and Lothar Seefried

Purpose

Aging and concurrent constitutional changes as sarcopenia, osteoporosis and obesity are associated with progressive functional decline. Coincidence and mutual interference of this risk factors require further evaluation.

Methods

Cross-sectional evaluation of musculoskeletal health in a community-dwelling cohort of men aged 65–90 years. Objectives included descriptive analysis of age-related decline in physical performance, prevalence of osteoporosis (FRAX-Score), sarcopenia (EWGSOP criteria) and obesity (BMI > 30 kg/m2) and their coincidence/interference.

Results

Based on 507 participants assessed, aging was associated with progressive functional deterioration, regarding power (chair rise test −1.54% per year), performance (usual gait speed −1.38% per year) and muscle force (grip strength −1.52% per year) while muscle mass declined only marginally (skeletal muscle index −0.29% per year). Prevalence of osteoporosis was 41.8% (n = 212) while only 22.9% (n = 116) of the participants met the criteria for sarcopenia and 23.7% (n = 120) were obese. Osteosarcopenia was found in n = 79 (15.6%), sarcopenic obesity was present in 14 men (2.8%). A combination of all three conditions could be confirmed in n = 8 (1.6%). There was an inverse correlation of BMI with physical performance whereas osteoporosis and sarcopenia did not interfere with functional outcomes.

Conclusion

Based on current definitions, there is considerable overlap in the prevalence of osteoporosis and sarcopenia, while obesity appears to be a distinct problem. Functional decline appears to be associated with obesity rather than osteoporosis or sarcopenia. It remains to be determined to what extend obesity itself causes performance deficits or if obesity is merely an indicator of insufficient activity eventually predisposing to functional decline.

Open access

Lu Liu, Chunyan Li, Peng Yang, Jian Zhu, Dongmei Gan, Le Bu, Manna Zhang, Chunjun Sheng, Hong Li, and Shen Qu

Alendronate (ALN) is a commonly used drug for the treatment of osteoporosis. Atypical femur fractures (AFFs) have been associated with long-term use of ALN and have recently become the subject of considerable attention as ALN use increases. This meta-analysis aimed to determine the relationship between ALN and AFF. The Embase, PubMed, and Cochrane library databases were searched for relevant studies published before November 6, 2014. Studies clearly reporting the relationship between ALN and AFF were selected for our analysis. From these results, the relationship between ALN and AFF was analyzed. Weighted mean differences were calculated using a random-effects model. Five studies were included in this meta-analysis. The results revealed that the use of ALN will not increase the risk of AFF in short term (P>0.05), but there will be a risk of AFF (P<0.05) with long-term (>5 years) use of ALN. These findings indicate that long-term use of ALN is a risk factor for AFF and that more attention should be paid to the clinical applications of ALN.

Open access

Ulla Schmidt, Birte Nygaard, Ebbe Winther Jensen, Jan Kvetny, Anne Jarløv, and Jens Faber

Background

A recent randomized controlled trial suggests that hypothyroid subjects may find levothyroxine (l-T4) and levotriiodothyronine combination therapy to be superior to l-T4 monotherapy in terms of quality of life, suggesting that the brain registered increased T3 availability during the combination therapy.

Hypothesis

Peripheral tissue might also be stimulated during T4/T3 combination therapy compared with T4 monotherapy.

Methods

Serum levels of sex hormone-binding globulin (SHBG), pro-collagen-1-N-terminal peptide (PINP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (representing hepatocyte, osteoblast, and cardiomyocyte stimulation respectively) were measured in 26 hypothyroid subjects in a double-blind, randomized, crossover trial, which compared the replacement therapy with T4/T3 in combination (50 μg T4 was substituted with 20 μg T3) to T4 alone (once daily regimens). This was performed to obtain unaltered serum TSH levels during the trial and between the two treatment groups. Blood sampling was performed 24 h after the last intake of thyroid hormone medication.

Results

TSH remained unaltered between the groups ((median) 0.83 vs 1.18 mU/l in T4/T3 combination and T4 monotherapy respectively; P=0.534). SHBG increased from (median) 75 nmol/l at baseline to 83 nmol/l in the T4/T3 group (P=0.015) but remained unaltered in the T4 group (67 nmol/l); thus, it was higher in the T4/T3 vs T4 group (P=0.041). PINP levels were higher in the T4/T3 therapy (48 vs 40 μg/l (P<0.001)). NT-proBNP did not differ between the groups.

Conclusions

T4/T3 combination therapy in hypothyroidism seems to have more metabolic effects than the T4 monotherapy.