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Hypogonadotrophic Hypogonadism (hypogonadotrophic + hypogonadism)
Selected AbstractsIntracytoplasmic sperm injection as a complement to gonadotrophin treatment in infertile men with hypogonadotrophic hypogonadismINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 4 2005BRANKO ZORN Summary In this study we sought to determine whether intracytoplasmic sperm injection (ICSI) could improve the efficacy of treatment with gonadotrophins in gonadotrophin-deficient men in terms of pregnancy. A series of six adult men (aged 26,47 years) with hypogonadotrophic hypogonadism (HH) is reported: four men with prepubertal isolated idiopathic HH (IIHH) and two adult-onset HH, as part of hypopituitarism secondary to surgical treatment of a pituitary tumour. All were azoospermic. To restore spermatogenesis, all received hormonal treatment with intramuscular human menopausal gonadotrophins (HMG) and human chorionic gonadotrophin (HCG) for 2 to 23 months. High basal serum inhibin B was predictive of rapid and complete recovery of spermatogenesis. In the two adult-onset HH, a natural pregnancy was achieved within 3 months. The four men with IIHH underwent ICSI because of poor sperm quality. ICSI using fresh or frozen-thawed ejaculated spermatozoa was performed after 6,23 months of gonadotrophin treatment. ICSI provided good clinical results in terms of fertilization and embryo quality, and resulted in three pregnancies that ended in three term deliveries. In men with oligozoospermia related to prepubertal IIHH, ICSI shortens the hormonal treatment and enhances the chances of pregnancy. [source] Regulation of Expression of Mammalian Gonadotrophin-Releasing Hormone Receptor GenesJOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2005J. P. Hapgood Abstract Gonadotrophin-releasing hormone (GnRH), acting via its cognate GnRH receptor (GnRHR), is the primary regulator of mammalian reproductive function, and hence GnRH analogues are extensively used in the treatment of hormone-dependent diseases, as well as for assisted reproductive techniques. In addition to its established endocrine role in gonadotrophin regulation in the pituitary, evidence is rapidly accumulating to support the expression and functional roles for two forms of GnRHR (GnRHR I and GnRHR II) in multiple and diverse extra-pituitary mammalian tissues and cells. These findings, together with findings indicating that mutations of the GnRHR are linked to the disease hypogonadotrophic hypogonadism and that GnRHRs play a direct role in neuronal migration and reproductive cancers, have presented new therapeutic targets and intensified research into the structure, function and mechanisms of regulation of expression of GnRHR genes. The present review focuses on the current knowledge on tissue-specific and hormonal regulation of transcription of mammalian GnRH receptor genes. Emerging insights, such as the discovery of diverse regulatory mechanisms in pituitary and extra-pituitary cell types, nonclassical mechanisms of steroid regulation, the use of composite elements for cell-specific expression, the increasing profile of hormones involved in regulation, the complexity of kinase pathways that target the GnRHR I gene, as well as species-differences, are highlighted. Although further research is necessary to understand the mechanisms of regulation of expression of GnRHR I and GnRHR II genes, the GnRHR is emerging as a potential target gene for facilitating cross-talk between neuroendocrine, immune and stress-response systems in multiple tissues via autocrine, paracrine and endocrine signalling. [source] CHARGE syndrome as unusual cause of hypogonadism: endocrine and molecular evaluationANDROLOGIA, Issue 5 2010L. Foppiani Summary Coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies (CHARGE) syndrome is a genetic syndrome in which hypogonadism is a frequent feature. A causative mutation within the chromodomain helicase DNA-binding protein-7 gene, which plays an important role in the embryonic development, is present in 2/3 of affected patients. We describe the clinical, hormonal and molecular characteristics of a young man from Ecuador who was diagnosed as having CHARGE syndrome at an adult age. The patient showed several phenotypic features of the syndrome, associated with a prepubertal state and cryptorchidism; hypogonadotrophic hypogonadism with undetectable testosterone levels not responsive to hCG testing and severe osteoporosis were ascertained. Molecular evaluation of the CHD7 gene showed the novel frameshift truncating heterozygous mutation p.Tyr1046Glyfs*23 in exon 12. Magnetic resonance imaging revealed mild hypoplasia of the pituitary gland and hypoplasia of the posterior cranial fossa. Parenteral testosterone therapy led to sexual development over time and, in combination with diphophonate therapy and calcium,vitamin D supplementation, significantly improved bone mineralisation. Early proper hormonal treatment of hypogonadism in patients with complex genetic syndromes is important to achieve normal sexual maturation, improve quality of life and avoid significant comorbidities, such as osteoporosis. [source] Pregnancy following monofollicular ovulation induction with recombinant FSH, recombinant LH and timed coitus in an amenorrheic woman with long-standing hypogonadotrophic hypogonadismBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 12 2004Salem A. El-Shawarby First page of article [source] Thyroid hormone levels in children with Prader,Willi syndrome before and during growth hormone treatmentCLINICAL ENDOCRINOLOGY, Issue 3 2007D. A. M. Festen Summary Background, Prader,Willi syndrome (PWS) is a neurogenetic disorder characterized by muscular hypotonia, psychomotor delay, obesity and short stature. Several endocrine abnormalities have been described, including GH deficiency and hypogonadotrophic hypogonadism. Published data on thyroid hormone levels in PWS children are very limited. Objective, To evaluate thyroid function in children with PWS, before and during GH treatment. Design/patients, At baseline, serum levels of T4, free T4 (fT4), T3, reverse T3 (rT3) and TSH were assessed in 75 PWS children. After 1 year, assessments were repeated in 57 of the them. These children participated in a randomized study with two groups: group A (n = 34) treated with 1 mg GH/m2/day and group B (n = 23) as controls. Results, Median age (interquartile range, IQR) of the total group at baseline was 4·7 (2·7,7·6) years. Median (IQR) TSH level was ,0·1 SDS (,0·5 to 0·5), T4 level ,0·6 SDS (,1·7 to 0·0) and fT4 level ,0·8 SDS (,1·3 to ,0·3), the latter two being significantly lower than 0 SDS. T3 level, at 0·3 SDS (,0·3 to 0·9), was significantly higher than 0 SDS. After 1 year of GH treatment, fT4 decreased significantly from ,0·8 SDS (,1·5 to ,0·2) to ,1·4 SDS (,1·6 to ,0·7), compared to no change in untreated PWS children. However, T3 did not change, at 0·3 SDS (,0·1 to 0·8). Conclusions We found normal fT4 levels in most PWS children. During GH treatment, fT4 decreased significantly to low-normal levels. TSH levels remained normal. T3 levels were relatively high or normal, both before and during GH treatment, indicating that PWS children have increased T4 to T3 conversion. [source] PROP1 gene analysis in Portuguese patients with combined pituitary hormone deficiencyCLINICAL ENDOCRINOLOGY, Issue 4 2006Manuel C. Lemos Summary Objective, Mutations of the PROP1 gene lead to combined pituitary hormone deficiency (CPHD), which is characterized by a deficiency of GH, TSH, LH/FSH, PRL and, less frequently, ACTH. This study was undertaken to investigate the molecular defect in a cohort of patients with CPHD. Design, patients and measurements, A multicentric study involving 46 cases of CPHD (17 familial cases belonging to seven kindreds and 29 sporadic cases) selected on the basis of clinical and hormonal evidence of GH deficiency, central hypothyroidism and hypogonadotrophic hypogonadism, in the absence of an identified cause of hypopituitarism. Mutations of PROP1 were investigated by DNA sequencing. Clinical, hormonal and neuroradiological data were collected at each centre. Results,PROP1 mutations were identified in all familial cases: five kindreds presented a c. 301,302delAG mutation, one kindred presented a c. 358C , T (R120C) mutation and one presented a previously unreported initiation codon mutation, c. 2T , C. Of the 29 sporadic cases, only two (6·9%) presented PROP1 germline mutations (c. 301,302delAG, in both). Phenotypic variability was observed among patients with the same mutations, particularly the presence and age of onset of hypocortisolism, the levels of PRL and the results of pituitary imaging. One patient presented a sellar mass that persisted into adulthood. Conclusions, This is the first report of a mutation in the initiation codon of the PROP1 gene and this further expands the spectrum of known mutations responsible for CPHD. The low mutation frequency observed in sporadic cases may be due to the involvement of other unidentified acquired or genetic causes. [source] A novel homozygous mutation in the second transmembrane domain of the gonadotrophin releasing hormone receptor geneCLINICAL ENDOCRINOLOGY, Issue 4 2001D. Söderlund BACKGROUND and OBJECTIVE Mutations in the GnRH receptor (GnRH-R) gene cause hypogonadotrophic hypogonadism. Here, we present the molecular studies of the GnRH-R gene in three families with isolated hypogonadotrophic hypogonadism. PATIENTS Three unrelated families, with at least two members diagnosed with isolated hypogonadotrophic hypogonadism were included. MEASUREMENTS DNA sequencing was performed after polymerase chain reaction amplification of each of the three exons of the gene. RESULTS A novel homozygous missense mutation, at nucleotide 268, turning glutamic acid into lysine, located at the second transmembrane domain of the GnRH-R gene was found in two patients pertaining to one of the families studied. Both parents and an unaffected brother were heterozygous carriers of one mutant allele, an unaffected sister was homozygote wild type. In the other two affected families no mutations were found in the GnRH-R gene. CONCLUSIONS This constitutes the first description of an spontaneous mutation located at the second transmembrane domain (Glu90Lys) of the GnRH-R, indicating that the integrity of glutamic acid at this position is crucial for receptor function. Also this report, complementing others, demonstrates that mutations are distributed throughout the GnRH-R gene and that as in the only other homozygous mutation previously described, affected patients present a complete form of hypogonadotrophic hypogonadism. Due to the fact that apparently consanguinity was present in our affected family, we presume that the mutation derived from a common ancestor, by a founder gene effect. [source] | ||||||||||