Experiencing multiple concurrent functional gastrointestinal disorders is associated with greater symptom severity and worse quality of life in chronic constipation and defecation disorders.

BACKGROUND: Recent community-based studies have demonstrated that experiencing multiple concurrent functional gastrointestinal disorders (FGIDs) is associated with increased somatization, worse quality of life (QoL), and greater health care utilization. However, the presence of multiple overlapping FGIDs is unstudied specifically in chronic constipation and functional defecation disorders (FDD). We investigated the prevalence and impact of additional nonconstipation FGIDs on constipation severity, anorectal physiology, anxiety and depression, and QoL, in patients with chronic constipation and FDD. METHODS: One-hundred and forty-six consecutive patients with functional constipation or irritable bowel syndrome (IBS-C/IBS-M) presenting to a tertiary referral Neurogastroenterology Clinic were studied. In addition, 90/146 (62%) qualified for FDD due to abnormal defecatory physiology. Patients underwent comprehensive baseline assessment comprising anorectal physiology, Bristol Stool Chart, Rome questionnaire, Knowles-Eccersley-Scott-Symptom (KESS) constipation score, Hospital Anxiety, and Depression Scale, and modified 36-Item Short Form Health Survey (SF-36) for QoL. Additional FGIDs were diagnosed using Rome III criteria. KEY RESULTS: Additional nonconstipation FGIDs occurred in 85% of patients, with a mean of 2.1 (SD 1.6) additional FGIDs. Patients with four or more additional FGIDs experienced greater constipation severity compared to those with no additional FGIDs (p = 0.004). Comorbid FGIDs were associated with worse SF-36 scores for physical functioning (p < 0.001), role-physical (p = 0.005), bodily pain (p < 0.001), vitality (p = 0.008), social functioning (p = 0.004), and mental health index (p = 0.031). CONCLUSIONS AND INFERENCES: Functional gastrointestinal disorders comorbidity is highly prevalent in chronic constipation and defecatory disorders, and this is associated with greater symptom severity and worse QoL. Multimodal treatments targeting comorbid FGIDs may lead to superior outcomes.

Novel TSHB variant (c.217A>C) causing severe central hypothyroidism and pituitary hyperplasia.

Summary: Biallelic pathological variants in the thyroid stimulating hormone (TSH) subunit ß gene (TSHB) result in isolated TSH deficiency and secondary hypothyroidism, a rare form of central congenital hypothyroidism (CCH), with an estimated incidence of 1 in 65 000 births. It is characterised by low levels of free thyroxine and inappropriately low serum TSH and may therefore be missed on routine neonatal screening for hypothyroidism, which relies on elevated TSH. We describe a patient with CCH who developed recurrence of pituitary hyperplasia and symptomatic hypothyroidism due to poor compliance with thyroxine replacement. She was diagnosed with CCH as a neonate and had previously required trans-sphenoidal hypophysectomy surgery for pituitary hyperplasia associated with threatened chiasmal compression at 17 years of age due to variable adherence to thyroxine replacement. Genetic testing of TSHB identified compound heterozygosity with novel variant c.217A>C, p.(Thr73Pro), and a previously reported variant c.373delT, p.(Cys125Valfs*10). Continued variable adherence to treatment as an adult resulted in recurrence of significant pituitary hyperplasia, which subsequently resolved with improved compliance without the need for additional medications or repeat surgery. This case describes a novel TSHB variant associated with CCH and demonstrates the importance of consistent compliance with thyroxine replacement to treat hypothyroidism and prevent pituitary hyperplasia in central hypothyroidism. Learning points: Pathogenic variants in the TSH subunit ß gene (TSHB) are rare causes of central congenital hypothyroidism (CCH). c.217A>C, p.(Thr73Pro), is a novel TSHB variant, presented in association with CCH in this case report. Thyroxine replacement is critical to prevent clinical hypothyroidism and pituitary hyperplasia. Pituitary hyperplasia can recur post-surgery if adherence to thyroxine replacement is not maintained. Pituitary hyperplasia can dramatically reverse if compliance with thyroxine replacement is improved to maintain free thyroxine (FT4) levels in the middle-to-upper normal range, without the need for additional medications or surgeries.

Biomarker Development in Cardiology: Reviewing the Past to Inform the Future.

Cardiac biomarkers have become pivotal to the clinical practice of cardiology, but there remains much to discover that could benefit cardiology patients. We review the discovery of key protein biomarkers in the fields of acute coronary syndrome, heart failure, and atherosclerosis, giving an overview of the populations they were studied in and the statistics that were used to validate them. We review statistical approaches that are currently in use to assess new biomarkers and overview a framework for biomarker discovery and evaluation that could be incorporated into clinical trials to evaluate cardiovascular outcomes in the future.