HNF1A gene mutations and premature ovarian failure (POF): evidence from a clinical paradigm combining MODY 3 and POF.

Premature ovarian failure (POF) defines the occurrence of ovarian failure prior to the age of 40. It occurs in one out of 100 women but is very rare before age 20 (1:10,000). Maturity-onset diabetes of the young (MODY), caused by mutations in the HNF1A gene, is also a rare disorder; all types of MODY account for 1-2% of adult diabetic cases.

Molecular Analysis of the CYP11B2 Gene in 62 Patients with Hypoaldosteronism Due to Aldosterone Synthase Deficiency.

Context: Isolated congenital hypoaldosteronism presents in early infancy with symptoms including vomiting, severe dehydration, salt wasting, and failure to thrive. The main causes of this rare autosomal recessive disorder is pathogenic variants of the CYP11B2 gene leading to aldosterone synthase deficiency.

Objective: To investigate the presence of CYP11B2 pathogenic variants in a cohort of patients with a clinical, biochemical, and hormonal profile suggestive of aldosterone synthase deficiency.

Long-term outcome of differentiated thyroid cancer in children and young adults: risk stratification by ATA criteria and assessment of pre-ablation stimulated thyroglobulin as predictors of disease persistence.

Purpose: Differentiated thyroid cancer (DTC) has an increasing incidence in childhood and adolescence but long-term outcome data are limited. We aimed to identify possible risk factors associated with disease persistence, with special focus on the usefulness of ATA risk stratification system and pre-ablation stimulated thyroglobulin (Tg) levels.

Methods: We retrospectively studied 103 patients, 79 females (76.

Adrenal Steroids in Female Hypothyroid Neonates: Unraveling an Association Between Thyroid Hormones and Adrenal Remodeling.

Context: The adrenal gland undergoes substantial remodeling during the neonatal period, an essential developmental process that remains incompletely understood. With respect to control over the remodeling process and, specifically, the role of thyroid hormones (THs), no human studies have been published. The effects of both hypo- and hyperthyroidism have only been evaluated in adults, focusing on the mature adrenal.

Pituitary stalk interruption syndrome: cause, clinical manifestations, diagnosis, and management.

Purpose Of Review: Pituitary stalk interruption syndrome (PSIS) is characterized by a thin or absent pituitary stalk, hypoplasia of the adenohypophysis, and ectopic neurohypophysis. PSIS manifestations include a wide spectrum of clinical phenotypes and pituitary hormone deficiencies of variable degree and timing of onset. In this review, recent advances with respect to the cause of PSIS, clinical characteristics leading to earlier diagnosis, and management are outlined.

A novel FOXL2 gene mutation and BMP15 variants in a woman with primary ovarian insufficiency and blepharophimosis-ptosis-epicanthus inversus syndrome.

Objective: This study aims to search for mutations in relevant genes in a woman with primary ovarian insufficiency (POI) and blepharophimosis-ptosis-epicanthus inversus syndrome (BPES).

Methods: This study reports on the case of a woman with POI, BPES, and autoimmune endocrine disorder. Bidirectional sequencing of the coding regions and intron/exon boundaries of FOXL2 and BMP15 genes and hormonal assays for the measurement of follicle-stimulating hormone, luteinizing hormone, estradiol, testosterone, Δ4-androstenedione, and dehydroepiandrosterone sulfate were employed.

The spectrum of clinical, hormonal and molecular findings in 280 individuals with nonclassical congenital adrenal hyperplasia caused by mutations of the CYP21A2 gene.

Background: Nonclassical congenital adrenal hyperplasia (NC-CAH) is caused by mutations of the CYP21A2 gene. The clinical manifestations and hormonal derangements of NC-CAH are quite variable.

Objectives: (i) To define the phenotype and its relation to genotype according to gender and age and (ii) to evaluate the validity of currently applied hormonal criteria for establishing the diagnosis of NC-CAH.

The spectrum of HNF1A gene mutations in Greek patients with MODY3: relative frequency and identification of seven novel germline mutations.

Objective: Maturity-Onset Diabetes of the Young (MODY) is the most common type of monogenic diabetes accounting for 1-2% of the population with diabetes. The relative incidence of HNF1A-MODY (MODY3) is high in European countries; however, data are not available for the Greek population. The aims of this study were to determine the relative frequency of MODY3 in Greece, the type of the mutations observed, and their relation to the phenotype of the patients.

Pituitary stalk interruption syndrome and isolated pituitary hypoplasia may be caused by mutations in holoprosencephaly-related genes.

Context: Holoprosencephaly (HPE) is a developmental defect characterized by wide phenotypic variability, ranging from minor midline malformations (eg, single central incisor) to severe deformities. In 10-15% of HPE patients, mutations in specific genes have been identified (eg, SHH, TGIF, SIX3). Pituitary stalk interruption syndrome (PSIS) constitutes a distinct abnormality of unknown pathogenesis, whereas isolated pituitary hypoplasia (IPH) has been linked to various developmental genes.

CYP21A2 mutations in women with polycystic ovary syndrome (PCOS).

The question of the contribution of CYP21A2 heterozygosity to the development of polycystic ovary syndrome (PCOS) has repeatedly been raised in the literature. The available data, however, do not offer a satisfactory answer. The discrepancy must be attributed, primarily, to the small number of subjects in the various studies, the type of selected phenotype, and the number of searched mutations.

Comparative functional analysis of two fibroblast growth factor receptor 1 (FGFR1) mutations affecting the same residue (R254W and R254Q) in isolated hypogonadotropic hypogonadism (IHH).

FGFR1 mutations have been identified in both Kallmann syndrome and normosmic HH (nIHH). To date, few mutations in the FGFR1 gene have been structurally or functionally characterized in vitro to identify molecular mechanisms that contribute to the disease pathogenesis. We attempted to define the in vitro functionality of two FGFR1 mutants (R254W and R254Q), resulting from two different amino acid substitutions of the same residue, and to correlate the in vitro findings to the patient phenotypes.

Long-term clinical data and molecular defects in the STAR gene in five Greek patients.

Context: Steroidogenic acute regulatory (STAR) gene mutations lead to adrenal and gonadal failure. Interesting, though as yet unexplained, features are the formation of ovarian cysts and the potential presence of CNS findings.

Objective: To report biochemical, genetic, and long-term clinical data in five Greek patients from four different families with STAR gene defects (three 46,XX and two 46,XY).

PROP-1 gene mutations in a 63-year-old woman presenting with osteoporosis and hyperlipidaemia.

PROP-1 gene mutations have been reported as a cause of combined pituitary hormone deficiency. Physical and hormonal phenotypes of affected individuals are variable. We report a 63-year-old female who presented with osteoporosis.

Severe hyperinsulinemia, decreased GLUT3 and GLUT4 expression, and increased retinol binding protein 4 in a patient with chronic graft-versus-host disease post bone marrow transplantation.

Hyperinsulinemia with or without DM2 is a frequent long-term sequela of BMT, especially following cGvHD. In this report, an extensive evaluation of a patient with cGvHD is described: glucose and insulin during OGTT, markers of inflammation, adiponectin and RBP4, body composition analysis, and the kinetics of GLUT3 and GLUT4 in circulating monocytes were evaluated. Hyperinsulinemia, associated with partial lipodystrophy, elevated RBP4, low adiponectin levels, and decreased expression of GLUT3 and GLUT4 were detected.

Infertility reversed by glucocorticoids and full-term pregnancy in a couple with previously undiagnosed nonclassic congenital adrenal hyperplasia.

Objective: To report the case of a couple with infertility and two unsuccessful previous attempts of ovarian stimulation for in vitro fertilization (IVF), whose nonclassic congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency (21-OHD) was diagnosed and verified by molecular studies.

Design: Case report.

Setting: Outpatient practice and academic hospital.

Clinical and genetic characterization of Chanarin-Dorfman syndrome patients: first report of large deletions in the ABHD5 gene.

Background: Chanarin-Dorfman syndrome (CDS) is a rare autosomal recessive disorder characterized by nonbullous congenital ichthyosiform erythroderma (NCIE) and an intracellular accumulation of triacylglycerol (TG) droplets in most tissues. The clinical phenotype involves multiple organs and systems, including liver, eyes, ears, skeletal muscle and central nervous system (CNS). Mutations in ABHD5/CGI58 gene are associated with CDS.

Screening for congenital hypothyroidism: the significance of threshold limit in false-negative results.

Context: In our neonatal program, a number of infants with congenital hypothyroidism (CH) had escaped diagnosis, when a spot RIA-TSH value of 20 mU/liter whole blood was used as a cutoff point.

Objective: The objective of the study was to find out prospectively the additional number of newborns with CH if the TSH cutoff point is lowered to 10 mU/liter.

Population And Methods: The study included 311,390 screened newborns.

Gender, age, puberty, and BMI related changes of TSH and thyroid hormones in schoolchildren living in a long-standing iodine replete area.

The aim of the work was to assess thyroid function in children and adolescents in an iodine replete area and to explore possible effects of age, gender, puberty, and adiposity. Thyrotropin (TSH), total triiodothyronine (T (3)), total thyroxine (T (4)), free thyroxine (FT (4)), and the T (4)/T (3) ratio were determined for 440 schoolchildren (200 boys and 240 girls), aged 5-18 years, living in an iodine replete region. Body Mass Index (BMI), BMI standard deviation score (BMI-SDS), and Body Surface Area (BSA) were calculated.

The efficacy and safety of gonadotropin-releasing hormone analog treatment in childhood and adolescence: a single center, long-term follow-up study.

Objective: The objective of the study was to evaluate the long-term effect of GnRH analog (GnRHa) treatment on final height (FH), body mass index (BMI), body composition, bone mineral density (BMD), and ovarian function.

Subjects/methods: Ninety-two females, evaluated in adulthood, were categorized as follows: group A, 47 girls with idiopathic central precocious puberty (33 GnRHa treated and 14 nontreated); group B, 24 girls with isolated GH deficiency (15 GnRHa and GH treated and nine GH treated); group C, 21 girls with idiopathic short stature (seven GnRHa and GH treated, seven GnRHa treated, and seven nontreated).

Results: FH, BMD, and percent fat mass of GnRHa-treated patients in all three groups were comparable with those of the respective nontreated subjects.

A favorable metabolic and antiatherogenic profile in carriers of CYP21A2 gene mutations supports the theory of a survival advantage in this population.

Context: The very high carrier frequency of 21-hydroxylase deficiency worldwide has been postulated as indicating a survival advantage. The 'mediators' of such an effect remain speculative.

Objective: To look for possible differences in the metabolic and atherogenic risk profile of carriers and noncarriers of CYP21A2 gene mutations at puberty in order to identify possible mediators of the presumed survival advantage for the carriers.

Complete androgen insensitivity syndrome is frequently due to premature stop codons in exon 1 of the androgen receptor gene: an international collaborative report of 13 new mutations.

Objective: To confirm the clinical diagnosis of complete androgen insensitivity syndrome (CAIS) by molecular genetic analysis and to determine the prevalence of exon 1 mutations in the androgen receptor (AR) transactivation defects of a large series of CAIS patients.

Design: International retrospective study.

Setting: University Hospital of Montpellier, Department of Hormonology.

Elevated coagulation and inflammatory markers in adolescents with a history of premature adrenarche.

Females with a history of premature adrenarche are at high risk of developing polycystic ovary syndrome (PCOS) and features of the metabolic syndrome later in life. Coagulation disorders, subclinical inflammation, and oxidative stress have been reported in patients with PCOS and metabolic syndrome. These factors were studied in a group of adolescents with a history of premature adrenarche.