Lack of Age-Appropriate Reference Intervals Causing Potentially Missed Alerts in Clinical Reports of Dyslipidemia.

This study shows that only 12.5% of laboratory reports (2/16) included age-appropriate pediatric reference ranges for all lipid and lipoproteins. The use of erroneous reference range(s) could lead to missed alerts of dyslipidemia in up to 97.3% (total cholesterol), 93.6% (high-density lipoprotein cholesterol), 94.8% (low-density lipoprotein cholesterol), and 87.8% (triglycerides) of youth in the population-based National Health and Nutrition Examination Survey cohort. These findings highlight the potential missed opportunities for reinforcing lifestyle counseling for dyslipidemia in addition to obesity in youth.

Endocrine and behavioural features of Lowe syndrome and their potential molecular mechanisms.

BACKGROUND: Lowe syndrome (LS) is an X linked disease caused by pathogenic variants in the OCRL gene that impacts approximately 1 in 500 000 children. Classic features include congenital cataract, cognitive/behavioural impairment and renal tubulopathy. METHODS: This study is a retrospective review of clinical features reported by family based survey conducted by Lowe Syndrome Association. Frequency of non-ocular clinical feature(s) of LS and their age of onset was summarised. An LS-specific therapy effectiveness scale was used to assess the response to the administered treatment. Expression of OCRL and relevant neuropeptides was measured in postmortem human brain by qPCR. Gene expression in the mouse brain was determined by reanalysis of publicly available bulk and single cell RNA sequencing. RESULTS: A total of 137 individuals (1 female, 89.1% white, median age 14 years (range 0.8-56)) were included in the study. Short stature (height <3rd percentile) was noted in 81% (n=111) individuals, and 15% (n=20) received growth hormone therapy. Undescended testis was reported in 47% (n=64), and median age of onset of puberty was 15 years. Additional features were dental problems (n=77, 56%), bone fractures (n=63, 46%), hypophosphataemia (n=60, 44%), developmental delay and behavioural issues. OCRL is expressed in human and mouse hypothalami, and in hypothalamic cell clusters expressing Ghrh, Sst, Oxt, Pomc and pituitary cells expressing Gh and Prl. CONCLUSIONS: There is a wide spectrum of the clinical phenotype of LS. Some of the features may be partly driven by the loss of function of OCRL in the hypothalamus and the pituitary.

Relationship of TSH Levels with Cardiometabolic Risk Factors in US Youth and Reference Percentiles for Thyroid Function.

CONTEXT: Thyroid hormones play an important role in metabolic homeostasis, and higher levels have been associated with cardiometabolic risk. OBJECTIVE: To examine the association of cardiometabolic risk factors with TSH levels in US youth. METHODS: Cross-sectional study of youth aged 12 to 18 years without known thyroid abnormalities from 5 National Health and Nutrition Examination Survey cycles (n = 2818) representing 15.4 million US children. Subclinical hypothyroidism (SH) was defined as thyrotropin (TSH) levels of 4.5 to 10 mIU/L. Assessed cardiometabolic risk factors include abdominal obesity (waist circumference >90th percentile), hypertriglyceridemia (triglyceride ≥130 mg/dL), low high-density lipoprotein cholesterol (<40 mg/dL), elevated blood pressure (systolic and diastolic blood pressure ≥90th percentile), hyperglycemia (fasting blood glucose ≥100 mg/dL, or known diabetes), insulin resistance (homeostatic model for insulin resistance > 3.16), and elevated alanine transferase (≥ 50 for boys and ≥44 U/L for girls). Age and sex- specific percentiles for thyroid parameters were calculated. RESULTS: In this cohort of youth (51.3% male), 31.2% had overweight/obesity. The prevalence of SH was 2.0% (95% CI 1.2-3.1). The median TSH levels were higher in youth with overweight/obesity (P < 0.001). Adjusting for age, sex, race/ethnicity, and obesity, youth with TSH in the fourth quantile had higher odds of abdominal obesity (OR 2.53 [1.43-4.46], P = .002), insulin resistance (OR 2.82 [1.42-5.57], P = .003), and ≥2 cardiometabolic risk factors (CMRF) (OR 2.20 [1.23-3.95], P = .009). CONCLUSION: The prevalence of SH is low in US youth. The higher odds of insulin resistance and cardiometabolic risk factors in youth with TSH levels >75th percentile requires further study.