Search

Background: The mechanisms of disturbances in bone mineral density (BMD) in coeliac disease are not completely understood. The aim of this prospective study was to investigate the possible significance of secondary hyperparathyroidism (SHPT) with regard to BMD in patients with untreated coeliac disease. Methods: One hundred and five adult patients with untreated coeliac disease were examined for BMD and serum parathyroid hormone (PTH) concentration. BMD in the hip, lumbar spine, and forearm were examined up to 3 years after the introduction of a gluten-free diet. Results: SHPT was found in 27% (28 of 105) of the patients. In patients with SHPT serum levels of 25-hydroxy-vitamin D were lower and those of alkaline phosphatase higher than in patients with normal PTH, but ionized serum calcium did not differ between the two groups. BMD was more severely reduced in patients with SHPT. Although the BMD increment was more rapid in patients with than in those without SPTH, only in the latter group did mean BMD became normal after 1-3 years on a gluten-free diet (GFD). After 3 years on a GFD more than half of the patients with initial SHPT still had low BMD in both the hip and the forearm. Furthermore, in patients with SHPT the intestinal mucosa more often remained atrophic at the 1-year follow-up, despite good compliance with the diet. Conclusions: Low BMD in patients with untreated coeliac disease is often associated with SHPT. After 3 years on a GFD the BMD remains low only in patients with initial SHPT. We therefore suggest that PTH should be measured when the diagnosis of coeliac disease is made, as an indicator of more serious intestinal disorder and complicating bone disease. [ABSTRACT FROM AUTHOR]

Correlates the circulating insulin-like growth factor I (IGF-I) and bone mineral density (BMD) in adults with celiac disease. Significance of a gluten-free diet on BMD; Effect of parathyroid hormone on IGF-I; Stimulation of the growth of bone cells.

Background: For patients with coeliac disease, adherence to a gluten-free diet (GFD) is essential to restore the intestinal mucosa. It is less clear whether this ensures well-being of the patient. We have therefore assessed aspects of the quality of life of adult coeliac patients who had been on a GFD for 10 years. Methods: By means of the Short Form 36 Health Survey (SF-36), the subjective health status was measured in 89 adult coeliac patients (61% women) aged 35-74 years. Patients shown to be in histologic remission (n = 60) were evaluated by means of the Gastrointestinal Symptom Rating Scale (GSRS). Results: The coeliac patients scored significantly lower in the SF-36 than general population, notably within the General Health and Vitality domains. The low scoring was confined to the female patients, who also reported significantly more gastrointestinal symptoms in the GSRS than the male coeliacs. The functional status and perceived health of the coeliac patients appeared unrelated to their biopsy findings. Conclusions: After 10 years on a GFD adult coeliac patients fail to attain the same degree of subjective health as the general population. This is particularly true for female patients and suggests that factors beyond normalization of the intestinal mucosa are of importance for the perceived health status of coeliacs diagnosed in adult life. [ABSTRACT FROM AUTHOR]

Discovery of cancer risk variants in the sequence of the germline genome can shed light on carcinogenesis. Here we describe gene burden association analyses, aggregating rare missense and loss of function variants, at 22 cancer sites, including 130,991 cancer cases and 733,486 controls from Iceland, Norway and the United Kingdom. We identified four genes associated with increased cancer risk; the pro-apoptotic BIK for prostate cancer, the autophagy involved ATG12 for colorectal cancer, TG for thyroid cancer and CMTR2 for both lung cancer and cutaneous melanoma. Further, we found genes with rare variants that associate with decreased risk of cancer; AURKB for any cancer, irrespective of site, and PPP1R15A for breast cancer, suggesting that inhibition of PPP1R15A may be a preventive strategy for breast cancer. Our findings pinpoint several new cancer risk genes and emphasize autophagy, apoptosis and cell stress response as a focus point for developing new therapeutics., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa ( P  = 1.6 × 10 -7 , 4.3 × 10 -9 ) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2 , another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain., Competing Interests: The authors who are affiliated with deCODE are all employees of deCODE genetics/Amgen Inc.

A 78 year-old male was admitted for rehabilitation after a trans-tibial amputation three months earlier. Scheduled training with a prosthetic leg was postponed due to muscle atrophy and weakness. As the patient's status deteriorated, blood results showed worsening hyponatremia.Work-up revealed pituitary insufficiency caused by a pituitary mass. The patient's general health improved greatly and the hyponatremia corrected after hormonal replacement therapy with hydrocortisone, thyroxin and testosterone was initiated. Key words: hyponatremia, malaise, weight loss, pituitary insufficiency, pituitary adenoma.

To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).

The comparative diagnostic value of IgA anti-endomysium and IgA antigliadin antibodies in adults with histologically confirmed celiac disease is reported. Sera from 144 adult patients (without concurrent dermatitis herpetiformis or IgA deficiency) who underwent small bowel biopsy were analyzed for both IgA anti-endomysium and IgA anti-gliadin antibodies. Nineteen patients (13%) had celiac disease. The presence of IgA antiendomysium antibodies had a sensitivity of 74% and a specificity of 100%. The positive and negative predictive values were 100% and 96%, respectively, and the diagnostic accuracy was 97%. In contrast, IgA anti-gliadin antibodies had positive and negative predictive values of 28% and 96%, respectively, with a diagnostic accuracy of 71%. Based on these data, we suggest that small bowel biopsy is not necessary to diagnose celiac disease in symptomatic adults with IgA antiendomysium antibodies. Due to a negative predictive value of 96%, some symptomatic adults lacking anti-endomysium antibodies will not be correctly diagnosed without small bowel biopsy.