There is variation in NBS practices for screening for congenital hypothyroidism across the US, and many programs do not adjust the TSH cutoff beyond the first 2 days of life. Samples are processed when received from older infants, often to retest borderline initial results. This approach will miss congenital hypothyroidism in infants with persistent mild TSH elevations. We recommend that all NBS programs provide age-adjusted TSH cutoffs, and suggest developing a standard approach to screening for congenital hypothyroidism in the US.

CONTEXT Oral glucose tolerance test (OGTT)-related hypoglycemia is common in pancreatic insufficient cystic fibrosis (PI-CF), but its mechanistic underpinnings are yet to be established. OBJECTIVE To delineate the mechanism(s) underlying OGTT-related hypoglycemia. DESIGN AND SETTING We performed 180-minute OGTT with frequent blood sampling in adolescents and young adults with PI-CF and compared results to those from a historical healthy control group. Hypoglycemia (Hypo[+]) was defined as plasma glucose <65 mg/dL. We hypothesized that CF-Hypo[+] would demonstrate impaired early-phase insulin secretion and persistent late insulin effect compared to Control-Hypo[+], and explored the contextual counterregulatory response. MAIN OUTCOME MEASURE OGTT 1-hour and nadir glucose, insulin, C-peptide, and insulin secretory rate (ISR) incremental areas-under-the-curve (AUC) between 0-30 min (early) and 120-180 min (late), and Δglucagon120-180min and ΔFree Fatty Acids(FFA)120-180min were compared between CF- and Control-Hypo[+]. RESULTS Hypoglycemia occurred in 15/23 (65%) CF (43% female, age 24.8 [14.6-30.6] years) and 8/15 (55%) controls (33% female, age 26 [21-38] years). CF-Hypo[+] vs Control-Hypo[+] had higher 1-hour glucose (197±49 vs 139±53 mg/dL, p=0.05) and lower nadir glucose (48±7 vs 59±4 mg/dL, p<0.01), while insulin-, C-peptide-,and ISR-AUC0-30 min were lower and insulin- and C-peptide-AUC120-180min were higher (p<0.05). CF-Hypo[+] had lower Δglucagon120-180min and ΔFFA120-180min compared to Control-Hypo[+] (p<0.01). CONCLUSIONS OGTT-related hypoglycemia in PI-CF is associated with elevated 1-hour glucose, impaired early-phase insulin secretion, higher late insulin exposure, and less increase in glucagon and FFA. These data suggest that hypoglycemia in CF is a manifestation of islet dysfunction including an impaired counterregulatory response.

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Background: Despite improved health, shorter stature is common in cystic fibrosis (CF). We aimed to describe height velocity (HV) and contribution of height-related genetic variants to height(HT) in CF. Methods: HV cohort – Standard deviation scores (-Z) for HT, mid-parental height-adjusted HT (MPAH), and HV were generated using our Pediatric Center’s CF Foundation registry data. HV-Z was compared to population means at each age (5–17y), the relationship of HV-Z with HT-Z assessed, and HT-Z compared to MPAH-Z. GRS cohort- HT genetic risk-Z (HT-GRS-Z) were determined for pancreatic exocrine sufficient (PS) and insufficient (PI) youth and adults from our CF center and their relationships with HT-Z assessed. Results: HV cohort: Average HV-Z was normal across ages in our cohort but was 1.5x-lower (p<0.01) for each SD decrease in HT-Z. MPAH-Z was lower than HT-Z (p< 0.001). GRS cohort: HT-GRS-Z more strongly correlated with HT-Z and better explained height variance in PS (rho=0.42;R 2 =0.25) vs. PI (rho=0.27;R 2 =0.11). Conclusions: Despite shorter stature compared to peers and mid-parental height, youth with CF generally have normal linear growth in mid- and late-childhood. PI tempered the heritability of height. These results suggest that, in CF, final height is determined early in life in CF and genetic potential is attenuated by other factors.

Central precocious puberty (CPP) classically refers to premature activation of the hypothalamic pituitary- gonadal (HPG) axis with onset of sexual development before the age of 8 years in girls and 9 years in boys. A decrease in the age of thelarche has been reported over the past several decades; however, the tempo of pubertal progression can be slower and adult height may not be adversely affected in many of the girls who experience thelarche at 6-8 years. Outside of this secular trend in the development itself, the past several decades have also brought about advances in diagnosis and management. This includes the wide-spread use of ultrasensitive LH assay, decreasing the need for stimulation testing and a better understanding of the genetics that govern the onset of puberty. Additionally, management of central precocious puberty (CPP) using gonadotropin-releasing hormone analogs (GnRHa) has changed with the advent of new longer-acting formulations. Emerging long-term outcomes of GnRHa administration with regards to obesity, cardiovascular risk factors and fertility are reassuring. Despite these advancements, clinical care in CPP is hampered by the lack of well-designed controlled studies, and management decisions are frequently not supported by clear practice guidelines. Data in boys with CPP are limited and this article focuses on the diagnosis and management of CPP in girls, particularly, in those who present with thelarche at the age of 6-8 years.

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