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BACKGROUND: Gonadotrophin-releasing hormone agonists (GnRHas) are used for puberty suppression in central precocious puberty (CPP) and gender dysphoria (GD). Guidelines on biochemical monitoring are not defined. OBJECTIVES: The aim of this study was to evaluate the utility of biochemical monitoring of GnRHa therapy in patients with CPP or GD. METHODS: This is a retrospective chart review of patients 18 years or younger who received GnRHa therapy from January 1, 2018, to March 20, 2021. RESULTS: A total of 103 patients were evaluated, 43 with CPP and 60 with GD. Using thresholds of basal luteinizing hormone (LH) <2 IU/L and stimulated LH <4 IU/L, biochemical pubertal suppression occurred in all but 2 patients. Basal LH frequently remained above prepubertal range. CONCLUSIONS: Laboratory assessment for puberty suppression on GnRHa therapy may be unnecessary in CPP and GD patients monitored with physical exams.

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CONTEXT: X-linked adrenal hypoplasia congenita (AHC) is a rare but important cause of primary adrenal insufficiency and can be associated with significant morbidity and mortality. AHC is caused by mutations within the NROB1 gene that codes for the DAX-1 protein, an orphan nuclear receptor essential for the development of the hypothalamic-pituitary-adrenal axis. Affected individuals typically present in early infancy with adrenal insufficiency and growth is usually normal once medical therapy is instituted. Here we report the first case of growth hormone deficiency in an infant with AHC and a novel NROB1 missense mutation. CASE: A two-week old infant presented with salt-losing adrenal crises and a normal newborn screen. Tests of adrenal function confirmed adrenal hypoplasia congenita and molecular evaluation revealed a novel missense NROB1 mutation. Replacement steroid therapy was promptly initiated, but he subsequently developed growth failure despite optimal nutritional and medical steroid therapy. Further biochemical analyses confirmed isolated idiopathic growth hormone deficiency. CONCLUSIONS: Growth failure in adequately treated infants with adrenal hypoplasia congenita is rare and the role of DAX-1 in the development of pituitary somatotropes is not known. There is variable genotype-phenotype correlation in X-linked adrenal hypoplasia congenita but novel NROB1 missense mutations could offer insight into the function of the various DAX-1 ligand-binding domains.

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BACKGROUND: Assisted living facilities (ALFs) provide housing and care to persons unable to live independently, and who often have increasing medical needs. Disease outbreaks illustrate challenges of maintaining adequate resident protections in these facilities. OBJECTIVES: Describe current state laws on assisted living admissions criteria, medical oversight, medication administration, vaccination requirements, and standards for infection control training. METHODS: We abstracted laws and regulations governing assisted living facilities for the 50 states using a structured abstraction tool. Selected characteristics were compared according to the time period in which the regulation took effect. Selected state health departments were queried regarding outbreaks identified in assisted living facilities. RESULTS: Of the 50 states, 84% specify health-based admissions criteria to assisted living facilities; 60% require licensed health care professionals to oversee medical care; 88% specifically allow subcontracting with outside entities to provide routine medical services onsite; 64% address medication administration by assisted living facility staff; 54% specify requirements for some form of initial infection control training for all staff; 50% require reporting of disease outbreaks to the health department; 18% specify requirements to offer or require vaccines to staff; 30% specify requirements to offer or require vaccines to residents. Twelve states identified approximately 1600 outbreaks from 2010 to 2013, with influenza or norovirus infections predominating. CONCLUSIONS: There is wide variation in how assisted living facilities are regulated in the United States. States may wish to consider regulatory changes that ensure safe health care delivery, and minimize risks of infections, outbreaks of disease, and other forms of harm among assisted living residents.

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We assessed the pharmacodynamics of a 3-hour leuprolide stimulation test in 11 girls with precocious puberty to determine an optimal single sampling time. Luteinizing hormone level following leuprolide stimulation was near maximum by 30 minutes in girls with central precocious puberty, whereas it continued to rise slowly in girls with nonprogressive puberty.

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OBJECTIVE: To compare 1-month and 3-month depot formulations of leuprolide acetate (DL), a gonadotropin-releasing hormone analog, in the treatment of central precocious puberty (CPP). STUDY DESIGN: Subjects with CPP naïve to therapy were randomized to 7.5 mg of 1-month DL, 11.25 mg of 3-month DL, or 22.5 mg of 3-month DL. Stimulated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and estradiol levels, growth velocity, and bone age progression were examined in a 2-year period. RESULTS: Forty-nine female and 5 male subjects with CPP were randomized. Mean stimulated LH and FSH levels during treatment were higher in the low-dose 11.25-mg 3-month DL group, and more LH levels >4 IU/L were observed, in comparison with the other two dose groups. Mean LH and FSH levels in the 22.5-mg 3-month group were not different from the monthly DL. No differences in estradiol levels, growth velocity, or bone age progression were observed in dosing groups. CONCLUSIONS: All DL doses resulted in prompt and effective suppression of puberty, but higher LH and FSH levels were seen with the 11.25-mg 3-month DL dose. Multi-monthly DL is effective in treating CPP, but higher dosing may be required in some circumstances.

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OBJECTIVE: To compare and contrast proposed definitions of metabolic syndrome in pediatrics, and to determine prevalence of metabolic syndrome in preadolescent females when applying different criteria. STUDY DESIGN: A literature review on definitions of metabolic syndrome and cardiovascular "risk factor clustering" in children and adolescents published in the past decade. Pediatric definitions of metabolic syndrome were then applied to a community-based study of 261 black preadolescent females (Girls Health Enrichment MultiSite studies [GEMS]) and a school-based, cross-sectional study of 240 ethnically-diverse preadolescent females (Girls Activity, Movement and Environmental Strategy [GAMES]) who had a baseline physical examination and fasting morning blood sample. RESULTS: Agreement among pediatric definitions of metabolic syndrome was poor. The prevalence of MS and cardiovascular risk factor clustering ranged from 0.4% to 23.0% for GEMS and 2.0% to 24.6% for GAMES with definitions adapted from the National Cholesterol Education Program Adult Treatment Panel III, and 0% to 15.3% for GEMS and 0.4% to 15.8% for GAMES using modified criteria from the World Health Organization. CONCLUSIONS: The prevalence of metabolic syndrome in preadolescent girls varies widely because of disagreement among proposed definitions of metabolic syndrome in pediatrics. Further investigation is needed to determine which metabolic factors and their respective cut points should be used to identify children at risk for development of clinical disease.

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BACKGROUND: Dosing of monthly depot leuprolide (DL) in central precocious puberty (CPP) varies considerably. U.S. practitioners use 7.5-15 mg, in contrast with the international standard of 3.75 mg. Pubertal suppression using the newer 3-month DL also has been reported from Europe. To date there have been no direct comparisons of these different DL doses. OBJECTIVES: In an open 12-month protocol, we tested the efficacy of three DL doses (7.5 mg- and 3.75 mg-1 month and 11.25 mg-3 month) given sequentially to subjects treated for CPP. Primary outcome measures were stimulated gonadotropin (Gn) levels at 12-wk intervals. The null hypothesis was no difference among doses. METHODS: Both existing and new patients with CPP received our standard therapy (DL 7.5 mg every 4 wk) for a minimum of 24 wk. In subjects with DL-stimulated LH 2 IU/liter or less, the dose was changed to 3.75 mg every 4 wk and evaluated 12 wk later. Subjects who met LH criteria (<4.5 IU/liter) on 3.75 mg then received a single dose of 11.25 mg-3 month and were reevaluated 12 wk later. Serum LH/FSH and sex steroids were obtained 40 min after DL injection. RESULTS: Thirty subjects were enrolled (20 naive; 24 girls, 6 boys), and 21 were evaluated on all three DL doses. DL-stimulated LH levels (mean +/- sd) were 1.30 +/- 0.74, 1.73 +/- 0.99, and 2.13 +/- 1.41 on 7.5 mg, 3.75 mg, and 11.25 mg-3 month, respectively (7.5 vs. 3.75 mg, P = 0.019; 7.5 mg vs. 11.25 mg-3 month, P = 0.004, Wilcoxon ranked sign test). Mean FSH levels were 2.86 +/- 1.91, 3.91 +/- 1.98, and 3.96 +/- 1.34, respectively (7.5 vs. 3.75 mg, P = 0.017; 7.5 mg vs. 11.25 mg-3 month, P = 0.020). No differences were detected in mean sex steroid levels. CONCLUSIONS: Stimulated LH and FSH levels were significantly higher during therapy with both the 3.75 mg and 11.25 mg-3 month depot leuprolide doses, compared with 7.5 mg, contradicting the null hypothesis of no difference. These data suggest that low-dose 1- and 3-month DL preparations are associated with persistently greater gonadal stimulation in most CPP patients, but the LH/FSH results were not corroborated by differences in sex steroid levels. Whether various DL doses lead to long-term therapeutic differences remains to be determined.

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