Isolated Vaginal Bleeding Before the Onset of Puberty.

Isolated vaginal bleeding before the onset of puberty is a rare presentation of isosexual precocity. In most cases, isolated vaginal bleeding without an abnormal genital examination is self-limited with resolution usually within 1 to 3 episodes. Watchful waiting is appropriate in most patients who do not have persistent bleeding, other signs of puberty, or signs/symptoms of an underlying etiology.

Premature Pubarche: A Pragmatic Approach.

Premature pubarche (PP) is a common and usually benign variant of normal puberty most often seen in 5-year-old to 9-year-old children. Some providers routinely order laboratory testing and a bone age to try to rule out other diagnoses including nonclassic congenital adrenal hyperplasia and gonadal or adrenal tumors. I review the natural history of PP and studies which suggest that without clinical features such as rapid growth and progression or genital enlargement, it is unlikely that a treatable condition will be found.

Females with Breast Development before Three Years of Age.

Breast development in a girl 3 years of age or younger is a commonly encountered scenario. Nearly all of these cases will either regress or fail to progress during follow-up, confirming a diagnosis of premature thelarche (PT). Studies show that these girls will have onset of true puberty and menses at a normal age.

Gonadotropin-releasing hormone analog therapies for children with central precocious puberty in the United States.

Gonadotropin-releasing hormone agonists (GnRHa's) are the standard treatment for children with central precocious puberty (CPP). We aim to present data on available GnRHa options with an easy-to-review table and discuss factors that influence treatment selection. Five GnRHa's are currently FDA-approved and prescribed in the US and published data suggest similar safety and efficacy profiles over the first year of treatment.

Brain MRIs may be of low value in most children diagnosed with isolated growth hormone deficiency.

Objectives: Brain MRIs are considered essential in the evaluation of children diagnosed with growth hormone deficiency (GHD), but there is uncertainty about the appropriate cut-off for diagnosis of GHD and little data about the yield of significant abnormal findings in patients with peak growth hormone (GH) of 7-10 ng/mL. We aimed to assess the frequency of pathogenic MRIs and associated risk factors in relation to peak GH concentrations.

Methods: In this retrospective multicenter study, charts of patients diagnosed with GHD who subsequently had a brain MRI were reviewed.

Update on pediatric hyperthyroidism.

Purpose Of Review: This review is intended to highlight recent studies which provide new data on the epidemiology and management of children with hyperthyroidism, including neonates.

Recent Findings: A French study demonstrates differences in age-related trends in incidence of hyperthyroidism in males versus females and suggests the overall incidence may be increasing. New studies confirm the effectiveness and safety of long-term medical therapy (up to 10 years), including from the first randomized trial of short-term versus long-term therapy.

Radioactive iodine therapy for pediatric Graves' disease: a single-center experience over a 10-year period.

Introduction Only about 30% of pediatric patients with Graves' hyperthyroidism achieve remission with medical therapy, and therefore radioactive iodine (RAI) therapy is often used as a definitive treatment. Although the goal of RAI is permanent hypothyroidism, this is not consistently achieved. We conducted a chart review to determine the factors associated with the success of RAI.

Neonatal Thyroid Disease: Testing and Management.

"Thyroid dysfunction that requires prompt diagnosis and treatment often becomes evident in the newborn period because of testing that is done as part of universal newborn screening. Primary congenital hypothyroidism is the most common treatable cause of mental retardation, requiring immediate treatment to prevent abnormal brain development. However, many of the abnormal thyroid test results are less abnormal and difficult to interpret, with a need for repeat testing and careful follow-up before initiation of treatment.

CHALLENGES OF SECURING GROWTH HORMONE COVERAGE FOR IDIOPATHIC SHORT STATURE: REVIEW OF THE 7-YEAR EXPERIENCE AT ONE INSTITUTION.

Objective: Despite U.S. Food & Drug Administration (FDA) approval of growth hormone (GH) for idiopathic short stature (ISS), many providers face challenges obtaining insurance coverage.

Toward More Targeted and Cost-Effective Gonadotropin-Releasing Hormone Analog Treatment in Girls with Central Precocious Puberty.

The use of gonadotropin-releasing hormone analogs (GnRHa) for the treatment of central precocious puberty (CPP), especially in girls, has increased rapidly in recent years. In the context of a secular trend towards earlier puberty onset, many girls now treated for CPP are healthy children experiencing puberty onset within the early end of the normal range. Justifications for GnRHa treatment include the preservation of adult height (AH) potential and the alleviation of presumed distress of early maturation and menarche.

Type 1 Diabetes: Urinary Proteomics and Protein Network Analysis Support Perturbation of Lysosomal Function.

While insulin replacement therapy restores the health and prevents the onset of diabetic complications (DC) for many decades, some T1D patients have elevated hemoglobin A1c values suggesting poor glycemic control, a risk factor of DC. We surveyed the stool microbiome and urinary proteome of a cohort of 220 adolescents and children, half of which had lived with T1D for an average of 7 years and half of which were healthy siblings. Phylogenetic analysis of the 16S rRNA gene did not reveal significant differences in gut microbial alpha-diversity comparing the two cohorts.

Do 6-8 year old girls with central precocious puberty need routine brain imaging?

Background: The subject of whether all girls with central precocious puberty (CPP) require brain imaging is controversial.

Findings: A review of the major papers concerning this topic published since 1994 was conducted looking primarily at the frequency of occult intracranial lesions, particularly brain tumors, in girls with CPP. While CNS abnormalities are frequently noted (8-15 %), the proportion of previously unknown findings requiring intervention in 6-8 year old girls is very small, in the range of 0-2 %.

Quantitative Differences in the Urinary Proteome of Siblings Discordant for Type 1 Diabetes Include Lysosomal Enzymes.

Individuals with type 1 diabetes (T1D) often have higher than normal blood glucose levels, causing advanced glycation end product formation and inflammation and increasing the risk of vascular complications years or decades later. To examine the urinary proteome in juveniles with T1D for signatures indicative of inflammatory consequences of hyperglycemia, we profiled the proteome of 40 T1D patients with an average of 6.3 years after disease onset and normal or elevated HbA1C levels, in comparison with a cohort of 41 healthy siblings.

Clinical characteristics of children referred for signs of early puberty before age 3.

Background: Signs of puberty in very young children are often benign, but the evaluation needed and follow-up are controversial.

Objectives: The study had three objectives: 1) to analyze the frequency of diagnoses in children <3 years referred for early puberty; 2) to examine the usefulness of lab testing; and 3) to identify red flags indicating a more serious diagnosis.

Methods: Charts of all children younger than age 3 referred for early puberty between 7/09 and 6/13 were reviewed.

Benign vaginal bleeding in 24 prepubertal patients: clinical, biochemical and imaging features.

Objective: Premature menarche is an uncommon, benign condition characterized by isolated or recurrent menstrual bleeding in the absence of secondary sexual characteristics.

Methods: We performed an observational retrospective study to further characterize the clinical, biochemical and imaging features of benign prepubertal vaginal bleeding (BPVB). Out of 1037 girls evaluated for precocious puberty over a 5-year period, 24 girls with BPVB were identified based on ≥1 episodes of vaginal bleeding, Tanner I or non-progressive Tanner II breast development, and lack of physical findings suggesting genital infection, trauma or foreign body.

In children with premature adrenarche, bone age advancement by 2 or more years is common and generally benign.

Background: Premature adrenarche (PA) is often associated with bone age (BA) advanced by ≥2 years, which increases the concern for underlying pathology, but the frequency and clinical significance of this is unknown. Our objective was to identify the proportion of PA patients with very advanced BA and normal BA and compare the clinical characteristics of the two groups.

Methods: Charts of 427 patients aged 5-9 years, referred for early puberty over a 2-year period, were reviewed for clinical diagnosis, growth, parental heights, hormone levels and BA.

Characteristics of children with the best and poorest first- and second-year growth during rhGH therapy: data from 25 years of the Genentech national cooperative growth study (NCGS).

Background: Models assessing characteristics contributing to response to recombinant human growth hormone (rhGH) response rarely address growth extremes in both years 1 and 2 or examine how children track from year to year. Using National Cooperative Growth Study (NCGS) data, we determined characteristics contributing to responsiveness to rhGH and the pattern of change from years 1 to 2.

Patients And Methods: Height velocity standard deviation score (HV SDS) for 2 years for prepubertal children with idiopathic GH deficiency (IGHD) (n = 1899) and idiopathic short stature (ISS) (n = 1186) treated with similar doses for two years were computed.

In congenital hypothyroidism, an initial L-thyroxine dose of 10-12 μg/kg/day is sufficient and sometimes excessive based on thyroid tests 1 month later.

Background: Current guidelines recommend an initial L-thyroxine (L-T4) dose of 10-15 μg/kg/day for the treatment of congenital hypothyroidism (CH). We analyzed our data for the treatment outcome at 1 month after we noted a frequent overtreatment even at the lower end of this dose range.

Methods: A 3-year chart review of 55 patients with confirmed CH was performed.

Characteristics of children with type 1 diabetes and persistent suboptimal glycemic control.

Objective: This study aims to determine the relationship between the duration of persistent poor glycemic control in type 1 diabetes mellitus (T1DM) children and the likelihood of subsequent improvement.

Methods: A retrospective cohort study was conducted on T1DM patients aged 6-18 years, followed for at least six visits at Children's National Medical Center (Washington, DC) with at least one hemoglobin A1c (HbA1c) ≥ 10% after the first year since the initial visit (n=151). Medical records of patients with subsequently improved glycemic control were reviewed (n=39).

Ovarian hilus cell hyperplasia as the cause of virilization in 45,X Turner's syndrome.

Objective: To describe a rare case of 45,X Turner's syndrome with elevated T and clitoromegaly caused by ovarian hilus cell hyperplasia.

Design: Case report.

Setting: Tertiary care pediatric hospital.

Evaluation and follow-up of clinically euthyroid children with normal free T4 and suppressed TSH.

Aim: Although subnormal TSH between 0.1-0.4 mIU/L is fairly common and benign, suppression of TSH to < 0.

Subclinical hypothyroidism in children: normal variation or sign of a failing thyroid gland?

Subclinical hypothyroidism (SCH), defined by a normal total or free T4 level and a mildly elevated TSH (typically 5-10 mU/L), is common in children, but there is currently no consensus on management. Several recent pediatric studies indicate that progression of SCH to overt hypothyroidism (OH) is uncommon and that over a period of several years, elevated TSH usually either normalizes or persists but does not increase. The etiology appears to be multifactorial, with some cases representing minor developmental abnormalities, some related to obesity, some to mild autoimmune thyroiditis, and some associated with mutations in the gene for the TSH-receptor.