Context Thyroid hormones play an important role in the 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. Design & Setting Cross-sectional study of youth aged 12-18 years without known thyroid abnormalities from five National Health and Nutrition Examination Survey cycles (n=2,818) representing 15.4 million US children. Subclinical hypothyroidism (SH) was defined as TSH levels 4.5-10 mIU/L. Assessed cardiometabolic risk factors include abdominal obesity (waist circumference > 90 th percentile), hypertriglyceridemia (TG ≥130 mg/dL), low HDL cholesterol (HDL-C < 40 mg/dL), elevated blood pressure (SBP and DBP ≥90 th percentile), hyperglycemia (FBG ≥100 mg/dL, or known diabetes), insulin resistance (HOMA-IR > 3.16) and elevated alanine transferase (ALT ≥ 50 U/L 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<.001). Adjusting for age, sex, race/ethnicity and obesity, youth with TSH in the 4 th 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 CMRF (OR 2.20 [1.23-3.95], p=.009). Conclusions The prevalence of SH is low in US youth. The higher odds of insulin resistance and cardiometabolic risk factors in youth with TSH levels > 75 th percentile requires further study.
BackgroundLowe 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.MethodsThis 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.ResultsA 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.ConclusionsThere 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.
Context: Thyroid hormones play an important role in the metabolic homeostasis of the body and have been associated with cardiometabolic risk. Objective: To examine the association of cardiometabolic risk factors (CMRF) with TSH levels in youth at population level in the US. Design & Setting: Cross-sectional study of youth aged 12-18 years without known thyroid abnormalities from National Health and Nutrition Examination Survey 1999-2012. Subclinical hypothyroidism (SH) was defined as TSH levels 4.5-10 mIU/L. Assessed CMRF included abdominal obesity (waist circumference > 90th percentile), hypertriglyceridemia (TG ≥ 130 mg/dL), low HDL cholesterol (HDL-C < 40 mg/dL), elevated blood pressure (SBP and DBP ≥ 90th percentile), hyperglycemia (FBG ≥ 100 mg/dL, or known diabetes), insulin resistance (HOMA-IR > 3.16) and elevated alanine transferase (ALT ≥ 50 U/L for boys and ≥ 44 U/L for girls). Age and sex- specific percentiles for thyroid parameters were calculated for youth with normal weight. 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<.001). Adjusting for age, sex, race/ethnicity and level of obesity, youth with TSH in the 4th quantile had higher odds of abdominal obesity (OR 2.53 [1.43-4.46], p = .002), higher HOMA-IR (OR 2.82 [1.42-5.57], p=.003) and ≥ 2 CMRF (OR 2.20 [1.23-3.95], p=.009). Conclusions: The prevalence of SH is low in US youth. The higher odds of insulin resistance and CMRF in youth with TSH levels > 75th percentile requires further study.
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