In utero exposure to glucocorticoids and risk of anxiety and depression in childhood or adolescence

Glucocorticoid use is prevalent in pregnant women, but whether in utero exposure impacts mental health in the offspring has not been fully explored. The aim of this study was to investigate if in utero exposure to synthetic glucocorticoids increases the risk of anxiety and depression in childhood or adolescence. The study was conducted as a nationwide cohort study, including negative control exposure analyses and a sibling design to optimize control of confounding. The study population comprised 1,275,909 children born in 1996–2015 in Denmark (median follow-up of 13 years). Exposure was divided into systemic and local glucocorticoid exposure, levels of cumulative dose, generic type and according to trimester of exposure. The comparison cohort was children without exposure born to maternal never-users. Negative control exposures included children without glucocorticoid exposure born to: maternal users of non-steroidal anti-inflammatory drugs or immunotherapy during pregnancy, maternal former users of systemic glucocorticoids, maternal users of systemic glucocorticoids in the postnatal period, and fathers who were prescribed glucocorticoids. The sibling design compared siblings with and without exposure. 9307 (0.7%) children were exposed to systemic glucocorticoids and 116,389 (9.1%) children were exposed to local glucocorticoids. High-dose systemic glucocorticoids (≥500 mg prednisolone equivalents) increased the risk of anxiety compared to the comparison cohort [aIRR 1.79 (95% CI: 1.36–2.37), cumulative risk 16% vs. 7.8% by age 20]. A similar result was found for depression [aIRR 1.45 (95% CI: 0.80–2.63), cumulative risk 3.6% vs. 2.6% by age 20]. The association with anxiety was consistent in the sibling design [aIRR 1.83 (95% CI: 1.03–3.66), exposed siblings (≥ 500 mg) vs. unexposed]. Sex did not modify the associations. Negative control exposure analyses indicated robustness towards confounding from genetics and family environment. No association was found with low doses of systemic exposure or local use. In conclusion, potential adverse mental health effects of in utero exposure to high-dose glucocorticoids merit clinical attention

Hyperthyroidism or hypothyroidism and gastrointestinal cancer risk: a Danish nationwide cohort study

Objective: The association between thyroid dysfunction and gastrointestinal cancer is unclear. Design: We conducted a nationwide population-based cohort study to examine this potential association. Methods: We used Danish medical registries to assemble a nationwide population-based cohort of patients diagnosed with hyperthyroid or hypothyroid disease from 1978 to 2013. We computed standardized incidence ratios (SIRs) with corresponding 95% CIs as measures of the relative risk of each cancer, comparing patients with thyroid dysfunction with that expected in the general population. Results: We included 163,972 patients, of which 92,783 had hyperthyroidism and 71,189 had hypothyroidism. In general, we found an increased risk of all gastrointestinal cancers within the first year after thyroid disease diagnosis. After more than 5 years of follow-up, patients with hyperthyroidism had a slightly increased risk of pancreatic and gallbladder and biliary tract cancer. Patients with hypothyroidism had a slightly increased risk of stomach, anal, liver, gallbladder and biliary tract, and pancreatic cancer after more than 5 years of follow-up, but the observed numbers of cancers were in general similar to the expected. Conclusions: The increased risks of all gastrointestinal cancers in the first year following hyper- or hypothyroidism diagnosis are likely due to detection bias. After more than 5 years of follow-up, there does not seem to be a consistent causal association between thyroid disease and gastrointestinal cancer

Prolonged lipopolysaccharide-induced illness elevates glucagon-like peptide-1 and suppresses peptide YY:A human-randomized cross-over trial

Severe systemic inflammation is associated with nausea, loss of appetite, and delayed gastric emptying, which increases hospitalization admission length and mortality rate. There is a lack of human controlled studies exploring gastric emptying rates and underlying mechanisms during inflammatory conditions. We aimed to investigate if systemic inflammation in young men delays gastro‐intestinal transit times, lowers motility, and affects gastrointestinal hormone secretion. This substudy of a randomized crossover trial investigated eight healthy young men on two separate occasions; (I) following an overnight fast (healthy conditions/HC) and (II) fasting and bedrest combined with two lipopolysaccharide (LPS) injections of 1 ng kg(−1) following an overnight fast and 0.5 ng kg(−1) following another 24 h (systemic inflammation/SI). A standardized protein beverage and a SmartPill capsule (a wireless gastrointestinal monitoring system) were swallowed during each occasion. Whole gut transit time was comparable between HC and SI. SI decreased gastric mean pressure peak amplitude (p = 0.04) and increased pH rise across the pylorus and small bowel pH (p = 0.02) compared with HC. Glucagon‐like peptide‐1 was elevated during SI compared with HC (p = 0.04). Peptide YY was lower during SI compared with HC (p = 0.007). Prolonged LPS exposure combined with fasting and bedrest elevated glucagon‐like peptide 1 concentrations, which may play a role for the nausea and loss of appetite typically associated with SI

Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients

Acromegaly according to the Danish National Registry of Patients:how valid are ICD diagnoses and how do patterns of registration affect the accuracy of registry data?

BACKGROUND: The incidence of acromegaly is uncertain, since population-based studies are few. In the absence of a specific acromegaly registry, the Danish National Registry of Patients (DNRP) becomes a potential source of data for studying the epidemiology of acromegaly, by linking all hospital discharge diagnoses to the personal identification numbers of individual Danish inhabitants. The validity of the DNRP with respect to acromegaly, however, remains to be tested. The aim of this study was to validate the International Classification of Diseases (ICD) codes for acromegaly (ICD-8: 25300, 25301. ICD-10: E22.0) as used in the DNRP, and to assess the influence of various registration patterns on the accuracy of registry data. METHODS: We identified patients registered with ICD codes for the diagnosis of acromegaly or other pituitary disorders during the period 1991–2009. Data on the institutional origin of each registration and the number of relevant DNRP registrations were recorded, and systematic patient chart reviews were performed to confirm the diagnosis. RESULTS: In total, 110 cases of acromegaly were confirmed, compared with 275 registered cases, yielding a positive predictive value (PPV) of 40%. When restricting the search to the regional highly specialized department of endocrinology, the PPV increased to 53% with no loss of cases with confirmed acromegaly. With a requirement of at least one, two, or three DNRP registrations, the PPV increased, but with a concurrent loss of confirmed cases. CONCLUSION: The DNRP seems to be a useful source for identifying new cases of acromegaly, especially when restricting the search to a relevant regional highly specialized department. The PPV of DNRP data used for this purpose can be increased by including only cases with several registrations. A similar approach may be successfully applied to other rare diseases in which continuity of care is provided by highly specialized departments