Endocrine Abstracts

Glucocorticoid resistance syndrome, a rare genetic disease, is often associated with glucocorticoid receptor (GR) loss-of-function mutations. Six patients carrying heterozygous mutations of NR3C1 gene encoding GR, either missense R477S, Q501H, L672P or non-sense R469X, R491X, Y660X mutations were studied. Surprisingly, NR3C1 mutation carriers presented with low kalemia, low plasma renin and aldosterone levels associated or not with arterial hypertension, cons...

Context: CHH/KS is a major cause of pubertal and bone maturation delay due to sex steroids deficiency. FH and TH have not been evaluated in large series of CHH/KS patients. Analysis of auxometric measures in patients’ siblings has never been performed.Patients and methods: We selected 216 (164/52 men/women; 112/104 KS/normosmic CHH) with available auxometric measures. Sibling stature was available in a subgroup of 162 patients. Difference between th...

Context: Insulin-like peptide three (INSL3) is a testicular hormone, secreted by Leydig cells, during fetal life, in newborns, and after puberty. These 3 phases of testicular activation are impaired in CHH.Objective: To evaluate in a single center circulating INSL3 in a significant series of men with CHH in order to asses the consequences of pre- and postnatal gonadotropin deficiency, to specify the INSL3 regulation by gonadotropins and to evaluate the p...

Context: Mitotane due to its adrenolytic action is highly effective in long-term management of ACTH-dependent Cushing’s syndrome (CS). However, the slow onset of its anticortisolic effect makes its use problematic in severe CS, when very rapid therapeutic response is required. Association with metyrapone and ketoconazole, rapidly acting steroidogenesis inhibitors, could warrant CS control while waiting for the full efficiency of mitotane and thus avoid urgently performed ...

Context: Hypogonadotropic hypogonadism (HH), defined by LH and FSH deficiencies, lead to impairment in testicular growth, testicular hormonal secretions and spermatogenesis. HH can have a prenatal (congenital HH, CHH) or post-natal (acquired HH, HHA) onset. Direct comparison of reproductive phenotypes (RP) between CHH and AHH has not been systematically performed in large series representative of these two populations.Patients and methods: 60 normal men,...

Placenta is an endocrine organ, secreting steroids (progesterone [P4], estrogens) and hCG, thanks to villous tissu (cytotrophoblasts [VCT] and syncytiotrophoblast [ST]). P4 is required for implantation and maintenance of pregnancy. P4 is synthetized from maternal cholesterol thanks to mitochondrial transporter MLN64 and P450SCC and HSD3B1 enzymes. We aimed to characterize P4 production in human placenta during VCTs differentiation into ST in vitro. VCTs isolated from ...

Glucocorticoid receptor (GR or NR3C1) is a ligand-dependent transcription factor that plays an essential role in differentiation, development, inflammatory responses and energy balance and is implicated in several human diseases. Eleven germinal GR mutations have been described so far, responsible for glucocorticoid resistance with variable clinical presentation.We report original heterozygous GR mutations in three independent patients, which have been i...

Context: Congenital hypogonadotropic hypogonadism (CHH), is a rare disorder associated with severe testosterone deficiency and with impaired bone mineral mass (BMM) acquisition and osteoporosis. Estradiol (E2) play a major role in bone development and maintain in BMM in humans.Objective: To evaluate in detail the degree of E2 deficiency in adult men with CHH.Design and patients: Using a sensitive E2...

Background/aim: X-linked hypophosphatemia (XLH) is a rare disease characterized by low phosphate level. Scientific evidence points to link between hypophosphatemia and obesity in general population. The aim of our longitudinal observational study was to investigate the prevalence of obesity and associated factors in a large cohort of children with XLH.Patients/methods: We selected 172 XLH-children of 5-20 years (113 girls/59 boys). Anthropometric paramet...

Primary generalized glucocorticoid resistance is characterized by glucocorticoid excess without any Cushing syndrome. Patients exhibit variable clinical presentation including arterial hypertension, hirsutism or adrenal hyperplasia. Although glucocorticoid resistance has been associated with glucocorticoid receptor (GR) mutations (encoded by NR3C1 gene), only 23 mutations have been reported so far. We have conducted a French National Research Program, referred to as M...