Functional analysis of SOX10 mutations identified in Chinese patients with Kallmann syndrome.

Kallmann syndrome (KS) is characterized by the association of anosmia and hypogonadotropic hypogonadism. The hypogonadotropic hypogonadism is due to deficient production, secretion or action of gonadotropin-releasing hormone (GnRH). Mutations in transcription factor SOX10 have been recently identified in patients with KS and hearing loss.

Why Do Normal Children Have Acromegalic Levels of IGF-I During Puberty?

Context: The rapid pubertal height growth is unique to humans, but why do we have it? Although the spurt contributes 13% to 15% to the final adult height, we hypothesized that the biological significance of the high acromegalic levels of GH and IGF-I, which are behind the pubertal growth spurt, might primarily occur to stimulate the reproductive organs.

Evidence Synthesis: Animal data have demonstrated that adult Igf1 and Igf2 gene knockout mice that survive show a dramatic reduction in the size of the reproductive organs and are infertile. In humans, case reports of mutations in the genes affecting the GH-IGF axis and growth (GH, GHRH, GH-R, STAT5b, IGF-I, IGF-II, IGF-1R, PAPPA2) are also characterized by delayed pubertal onset and micropenis.

Clinical Management of Congenital Hypogonadotropic Hypogonadism.

The initiation and maintenance of reproductive capacity in humans is dependent on pulsatile secretion of the hypothalamic hormone GnRH. Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder that results from the failure of the normal episodic GnRH secretion, leading to delayed puberty and infertility. CHH can be associated with an absent sense of smell, also termed Kallmann syndrome, or with other anomalies.

Chemoprevention in BRCA1 mutation carriers (CIBRAC): protocol for an open allocation crossover feasibility trial assessing mechanisms of chemoprevention with goserelin and anastrozole versus tamoxifen and acceptability of treatment.

Introduction: BRCA1 mutation carriers have a significant lifetime risk of breast cancer, with their primary risk-reduction option being bilateral mastectomy. Preclinical work from our laboratory demonstrated that in BRCA1-deficient breast cells, oestrogen and its metabolites are capable of driving DNA damage and subsequent genomic instability, which are well-defined early events in BRCA1-related cancers. Based on this, we hypothesise that a chemopreventive approach which reduces circulating oestrogen levels may reduce DNA damage and genomic instability, thereby providing an alternative to risk-reducing surgery.

Genetics of ncHH: from a peculiar inheritance of a novel GNRHR mutation to a comprehensive review of the literature.

Background: Normosmic congenital hypogonadotropic hypogonadism (ncHH) is caused by the deficient production, secretion, or action of gonadotropin-releasing hormone (GnRH). Its typical clinical manifestation is delayed puberty and azoospermia. Homozygous and compound heterozygous mutations in the GNRHR gene (4q13.

Precocious or early puberty in patients with combined pituitary hormone deficiency due to POU1F1 gene mutation: case report and review of possible mechanisms.

Central precocious puberty (CPP) or early puberty (EP) is a rare entity in combined pituitary hormone deficiency (CPHD), the latter caused by mutations in pituitary transcription factor genes. The early onset of puberty in two patients with CPHD with POU1F1 gene mutation was evaluated. A 3-month-old boy was diagnosed with central hypothyroidism, and L-thyroxine was commenced.

Targeted Gene Panel Sequencing for Molecular Diagnosis of Kallmann Syndrome and Normosmic Idiopathic Hypogonadotropic Hypogonadism.

Background: Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is classified either as Kallmann syndrome (KS) with anosmia or normosmic idiopathic hypogonadotropic hypogonadism (nIHH) and caused by mutations in more than 30 different genes. Recent advances in next-generation sequencing technologies have revolutionized the identification of causative genes by using massively parallel sequencing of multiple samples. This study was performed to establish the genetic etiology of IGD using a targeted gene panel sequencing of 69 known human IGD genes.

Gonadotropin-releasing hormone (GnRH) deficiency under treatment: psychological and sexual functioning impacts.

Objective: GnRH (gonadotropin releasing hormone) is a crucial hormone for sexual development, puberty, and fertility, and its deficiency leads to hypogonadotropic hypogonadism (HH), which causes abnormal secondary sexual development and infertility. The combination of the lack of sense of smell, i.e.

Complete Kisspeptin Receptor Inactivation Does Not Impede Exogenous GnRH-Induced LH Surge in Humans.

Context: Mutations in the kisspeptin receptor (KISS1R) gene have been reported in a few patients with normosmic congenital hypogonadotropic hypogonadism (nCHH) (OMIM #146110).

Objectives: To describe a female patient with nCHH and a novel homozygous KISS1R mutation and to assess the role of kisspeptin pathway to induce an ovulation by GnRH pulse therapy.

Design, Setting, And Intervention: Observational study of a patient including genetic and kisspeptin receptor functions and treatment efficiency using a GnRH pump.

Rare cause of manic period trigger in bipolar mood disorder: testosterone replacement.

Hypogonadotropic hypogonadism is a rare congenital disorder characterised by the deficiency and the absence of puberty and infertility. It is caused by the deficient production, secretion or action of gonadotropin-releasing hormone, which is the master hormone regulating the reproductive axis. Gonadotropin-releasing hormone or gonadotropin injections and testosterone replacement therapy are required in the treatment of this disorder.

Rare case of Gordon Holmes syndrome.

Young-onset cerebellar syndromes are quite interesting and challenging for treating clinicians. While dealing with such cases, a clinician should be aware of rare possible causes too. We report a rare case of Gordon Holmes syndrome-an autosomal recessive cerebellar ataxia with endocrinal abnormalities.

Long-term treatment outcomes of intermittent androgen deprivation therapy for relapsed prostate cancer after radical prostatectomy.

Purpose: Intermittent androgen deprivation therapy is an effective treatment for metastatic prostate cancer. However, no study to date has evaluated the long-term outcomes of this treatment among patients with prostate cancer after radical prostatectomy. We retrospectively examined the treatment outcomes of patients with prostate-specific antigen recurrence who underwent radical prostatectomy at our department.

Lower rate of early pregnancy loss in patients experiencing early-onset low LH in GnRH antagonist cycles supplemented with menotropin.

Background/purpose: The role of LH during controlled ovarian stimulation (COS) in the general population remains contentious. There is no consensus on the indications for LH supplementation during COS. The purpose of this study is to determine whether menotropin supplement is associated with decreases in early pregnancy loss rates in patients exhibiting low endogenous LH during COS.

Recombinant luteinizing hormone supplementation to recombinant follicle stimulating hormone therapy in gonadotropin releasing hormone analogue cycles: what is the evidence?

Objective: To look into current evidence exploring the added value of rLH supplementation to rFSH in GnRH analogues cycles, to identify groups of women that still have no evidence for adjuvant rLH therapy and to discuss ways that may advance research on this topic.

Methods: Eight systematic reviews and meta-analyses exploring the benefit for pregnancy achievement of rLH supplementation, excluding other LH activity preparations, to GnRH analogues cycles in the ART setting were thoroughly evaluated.

Results: Evidence exists to show that rLH supplementation seems to have added value for pregnancy achievement in women with poor ovarian response and in women ≥35 years of age employing the GnRH agonist protocol, while the evidence is still debatable when the GnRH antagonist is administered.

DCC/NTN1 complex mutations in patients with congenital hypogonadotropic hypogonadism impair GnRH neuron development.

Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disease characterized by absent puberty and infertility due to GnRH deficiency, and is often associated with anosmia [Kallmann syndrome (KS)]. The genetic etiology of CHH is heterogeneous, and more than 30 genes have been implicated in approximately 50% of patients with CHH. We hypothesized that genes encoding axon-guidance proteins containing fibronectin type-III (FN3) domains (similar to ANOS1, the first gene associated with KS), are mutated in CHH.

Kallmann syndrome: phenotype and genotype of hypogonadotropic hypogonadism.

Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency (IGD) IGD is a genetically and clinically heterogeneous disorder. Mutations in many different genes are able to explain ~40% of the causes of IGD, with the rest of cases remaining genetically uncharacterized. While most mutations are inherited in X-linked, autosomal dominant, or autosomal recessive pattern, several IGD genes are shown to interact with each other in an oligogenic manner.

In vitro fertilization-frozen embryo transfer in a patient with cytochrome P450 oxidoreductase deficiency: a case report.

Cytochrome P450 enzymes are required for the synthesis of cholesterol and steroid hormones. Cytochrome P450 oxidoreductase (POR) donates electrons to microsomal cytochrome P450 enzymes. POR deficiency (PORD) is a rare autosomal recessive disease.

Gordon Holmes syndrome: finally genotype meets phenotype.

We describe a patient with Gordon Holmes syndrome presenting with a combination of hypogonadotropic hypogonadism, ataxia and progressive cognitive decline, with distinct MRI brain findings. Recent genetic advances allowed the identification of the genetic defects responsible for this rather unusual combination of endocrine and neurological involvement.