Bicalutamide and third-generation aromatase inhibitors in testotoxicosis.

Testotoxicosis, a form of gonadotropin-independent precocious puberty, results from an activating mutation of the luteinizing hormone receptor expressed in testicular Leydig cells. Affected males experience early testosterone secretion, virilization, advancing bone age, and resultant short stature. Recently, the use of combination therapy with a potent antiandrogen agent (bicalutamide) and a third-generation aromatase inhibitor (anastrozole or letrozole) was reported to yield encouraging short-term results.

No activating mutations of FSH receptor in four children with ovarian juvenile granulosa cell tumors and the association of these tumors with central precocious puberty.

Study Objective: The stimulation of the follicle-stimulating hormone receptor (FSHR) by circulating FSH or some activating mutations of the FSHR may play a causal role in the development of granulosa cell tumors of ovaries.

Study Design: We evaluated four patients with ovarian juvenile granulosa cell tumors (age range, 2.4 to 7.

Environmental factors and puberty timing: expert panel research needs.

Serono Symposia International convened an expert panel to review the impact of environmental influences on the regulation of pubertal onset and progression while identifying critical data gaps and future research priorities. An expert panel reviewed the literature on endocrine-disrupting chemicals, body size, and puberty. The panel concluded that available experimental animal and human data support a possible role of endocrine-disrupting chemicals and body size in relation to alterations in pubertal onset and progression in boys and girls.

Role of environmental factors in the timing of puberty.

Puberty-timing measures have historically been used as indicators of adequate nutrition and growth. More recently, these measures have been examined in relation to exposure to estrogenic or antiandrogenic agents, as well as other environmental factors. The scientific community has debated whether puberty timing is occurring earlier today than in the mid-1900s in the United States and, if so, whether environmental factors play a role; however, no one has asked a multidisciplinary panel to resolve this question.

GNAS mutation detection is related to disease severity in girls with McCune-Albright syndrome and precocious puberty.

Background: McCune-Albright syndrome (MAS) is characterized by a triad of gonadotropin-independent precocious puberty, café au lait skin pigmentation and fibrous dysplasia of bone. MAS is due to activating mutations of GNAS, the gene encoding Gsalpha. Interest exists in the use of GNAS mutation analysis to make a definitive diagnosis when the phenotype is not diagnostic, i.

Treatment of familial male-limited precocious puberty with bicalutamide and anastrozole.

This report describes the use of bicalutamide and anastrozole in two subjects with familial male-limited precocious puberty. Clinical improvements include decreased facial acne and pubic hair. Most importantly, a marked decrease in growth velocity and skeletal advancement has been achieved.

RNA interference (RNAi) for extracellular signal-regulated kinase 1 (ERK1) alone is sufficient to suppress cell viability in ovarian cancer cells.

While ovarian cancer is a leading cause of death in females today, the molecular, genetic, and environmental factors that initiate and support the progression of this disease are still only partially understood. The extracellular signal-regulated kinase (ERK) signaling pathway is a major contributor to cellular growth, differentiation and survival. Recently, we reported that this pathway is constitutively activated in ovarian cancer cells, and that by using RNA interference (RNAi) for ERK1 and ERK2, we were able to significantly suppress the number of viable tumor cells.

Limited efficacy of growth hormone (GH) during transition of GH-deficient patients from adolescence to adulthood: a phase III multicenter, double-blind, randomized two-year trial.

Context: Treatment of GH-deficient adolescents in transition to adulthood remains challenging.

Objective: The objective was to assess the safety and efficacy of GH in GH-deficient adolescents in transition.

Patients: Fifty-eight GH-deficient adolescents (mean age, 15.

The effect of growth hormone supplementation on late nutritional independence in pediatric patients with short bowel syndrome.

Purpose: The use of growth hormone (GH) supplementation for intestinal adaptation among adult patients with short bowel syndrome (SBS) has provided mixed results. This report examines the effect of GH supplementation on SBS in pediatric patients.

Methods: Two girls with SBS from neonatal gastrointestinal catastrophes received exogenous GH at 0.

Childhood obesity.

In March 2004 a group of 65 physicians and other health professionals representing nine countries on four continents convened in Israel to discuss the widespread public health crisis in childhood obesity. Their aim was to explore the available evidence and develop a consensus on the way forward. The process was rigorous, although time and resources did not permit the development of formal evidence-based guidelines.

Mechanisms regulating the constitutive activation of the extracellular signal-regulated kinase (ERK) signaling pathway in ovarian cancer and the effect of ribonucleic acid interference for ERK1/2 on cancer cell proliferation.

The ERK1/2 MAPK pathway is a critical signaling system that mediates ligand-stimulated signals for the induction of cell proliferation, differentiation, and cell survival. Studies have shown that this pathway is constitutively active in several human malignancies and may be involved in the pathogenesis of these tumors. In the present study we examined the ERK1/2 pathway in cell lines derived from epithelial and granulosa cell tumors, two distinct forms of ovarian cancer.

Definitive diagnosis in children with congenital hypothyroidism.

Objectives: To investigate the definitive diagnosis and underlying causes of congenital hypothyroidism (CH) in eligible children through the use of a standardized protocol.

Study Design: Children > or =3 years of age with CH without an identified permanent cause underwent a diagnostic algorithm. Eligible subjects had an anatomically normal thyroid or had not undergone imaging studies.

Craniofacial and acral growth responses in growth hormone-deficient children treated with growth hormone.

Objectives: To investigate the effects of growth hormone (GH) therapy on craniofacial growth and body proportions in growth hormone deficient children.

Study Design: By using a cross-sectional study design, we investigated GH effects on craniofacial growth with photographic facial morphometrics, head circumference, and hand and foot size in 52 children with GH deficiency (GHD) treated with GH (0.27 mg/kg/wk) for 0.

Differential expression of GRK isoforms in nonmalignant and malignant human granulosa cells.

Granulosa cell tumors are serious ovarian neoplasms that can occur in women of all ages. While there have been numerous attempts to understand the cause of these malignancies, the pathogenesis of granulosa cell tumors (GCTs) still remains largely unknown. G-protein coupled receptor kinases (GRKs) are important regulators of signal transduction through the process of receptor desensitization and internalization.

Autoimmune thyroid dysfunction in children with type 1 diabetes mellitus: screening guidelines based on a retrospective analysis.

Individuals with type 1 diabetes mellitus (DM1) have an increased risk of developing autoimmune thyroid dysfunction (AITD). We measured the prevalence of AITD in a pediatric DM1 population in order to examine the best combination of markers for predicting the development of AITD. A database of 1,254 patients with DM1 under 21 years of age was retrospectively screened for abnormalities in antithyroglobulin antibody (ATA), thyroid peroxidase antibody (TPO) and thyroid stimulating hormone (TSH).

Severe short stature and endogenous growth hormone resistance in twin brothers without growth hormone gene mutations.

Growth failure in children with high growth hormone (GH) levels, low insulin-like growth factor 1 (IGF-1) levels, and accelerated linear growth in response to exogenous GH is presumed to result from biologically inactive GH. A molecular diagnosis has only been made in two such patients. We analyzed the presentations and the GH-1 genes of twin Egyptian brothers with this phenotype.

Tamoxifen treatment for precocious puberty in McCune-Albright syndrome: a multicenter trial.

Objective: We undertook a 1-year multicenter trial of tamoxifen treatment for precocious puberty in girls with McCune-Albright syndrome (MAS).

Study Design: Girls < or =10 years with classic or atypical MAS were recruited. Pretreatment history was collected for 6 months.

Is McCune-Albright syndrome overlooked in subjects with fibrous dysplasia of bone?

Objective: McCune-Albright syndrome (MAS) is characterized by a clinical triad of endocrinopathies, café au lait pigmentation, and polyostotic fibrous dysplasia of bone. We hypothesized that children diagnosed with fibrous dysplasia are not routinely being evaluated for coexisting endocrine dysfunction or MAS. Our objective was to prospectively screen subjects with fibrous dysplasia for endocrine disease and G(s)alpha gene (GNAS1 )-activating mutations.

Assay interference leading to misdiagnosis of central precocious puberty.

Immunoassays are widely used to determine hormone levels. Antibodies directed against components of the immunoassay system can interfere with analyte concentration estimates. When unrecognized by clinicians, inappropriate clinical intervention may follow.

Treatment with a luteinizing hormone-releasing hormone agonist in adolescents with short stature.

Background: Treatment with a luteinizing hormone-releasing hormone (LHRH) agonist increases adult height in children with LHRH-dependent precocious puberty and is prescribed by some practitioners to augment height in short adolescents. We performed a randomized clinical trial to determine whether treatment with an LHRH agonist increases adult height in short adolescents with normally timed puberty.

Methods: Fifty short adolescents (18 boys and 32 girls) with low predicted adult height (mean [+/-SD], 3.

Determination of trace isoflavone phytoestrogens in biological materials by capillary electrochromatography.

Capillary electrochromatography using a specialty monolithic matrix was utilized in developing a rapid and highly efficient separation of isoflavones in biological materials. Without a preconcentration technique, it is relatively easy to reach ppm-ppb concentrations of these compounds in soy-based foods and verify them structurally using a photodiode array detector. With on-column preconcentration, we were able to measure low-ppb levels in human serum.

Low hemoglobin levels in children with in idiopathic growth hormone deficiency.

Multiple lines of evidence have implicated the growth hormone (GH) axis in the regulation of erythropoiesis. To test the hypothesis that GH deficiency is associated with hematologic abnormalities, we analyzed pretreatment hemoglobin levels in 100 children with GH deficiency. Hemoglobin levels were decreased in children with GH deficiency compared with age-corrected norms.