1/9. A case of primary amenorrhea, diabetes and anosmia.This case details a patient with primary amenorrhea with an unusual cause. She presented at age 16 with short stature, minimal sexual development and no prior menses. Her history was significant for poorly controlled type 1 diabetes. She had been evaluated previously for growth hormone deficiency, and had received a short course of growth hormone therapy. Of greatest significance was the fact that she had also had a decreased sense of smell since her youth. Although a previous computerized tomography scan had been reported as normal, follow-up magnetic resonance imaging demonstrated the absence of olfactory bulbs. smell testing confirmed the absence of smell and testing of gonadotropin releasing hormone demonstrated an inadequate response. All of these features suggested kallmann syndrome. This syndrome commonly presents with delayed onset of puberty and decreased or absent sense of smell. There are also many associated features, and the disease is remarkable for its great genotypic and phenotypic variability. Current understanding of its pathogenesis, the commonly associated features of kallmann syndrome and the impact of diabetes on growth and sexual development are reviewed.- - - - - - - - - - ranking = 1keywords = puberty (Clic here for more details about this article) |
2/9. x chromosome-linked kallmann syndrome: clinical heterogeneity in three siblings carrying an intragenic deletion of the KAL-1 gene.kallmann syndrome (KS) is characterized by the association of hypogonadotropic hypogonadism and anosmia. The gene underlying the x chromosome-linked form of the disease, KAL-1, consists of 14 coding exons. It encodes a glycoprotein, anosmin-1, which is involved in the embryonic migration of GnRH-synthesizing neurons and the differentiation of the olfactory bulbs. We describe herein the clinical heterogeneity in three affected brothers who carry a large deletion (exons 3-13) in KAL-1. All three had a history of hypogonadotropic hypogonadism with delayed puberty. Although brain magnetic resonance imaging showed hypoplastic olfactory bulbs in the three siblings, variable degrees of anosmia/hyposmia were shown by olfactometry. In addition, these brothers had different phenotypic anomalies, i.e. unilateral renal aplasia (siblings B and C), high-arched palate (sibling A), brachymetacarpia (sibling A), mirror movements (siblings A and B), and abnormal eye movements (sibling C). Last but not least, sibling A suffered from a severe congenital hearing impairment, a feature that had been reported in KS but had not yet been ascribed unambiguously to the X-linked form of the disease. The variable phenotype, both qualitatively and quantitatively, in this family further emphasizes the role of putative modifier genes, and/or epigenetic factors, in the expressivity of the X-linked KS.- - - - - - - - - - ranking = 1keywords = puberty (Clic here for more details about this article) |
3/9. Paediatric phenotype of kallmann syndrome due to mutations of fibroblast growth factor receptor 1 (FGFR1).kallmann syndrome characterised by hypogonadotropic hypogonadism (HH) and anosmia is genetically heterogeneous with X-linked, autosomal dominant and autosomal recessive forms. The autosomal dominant form due to loss of function mutation in the fibroblast growth factor receptor 1 (FGFR1) accounts for about 10% of cases. We report here three paediatric cases of kallmann syndrome with unusual phenotype in two unrelated patients with severe ear anomalies (hypoplasia or agenesis of external ear) associated with classical features, such as cleft palate, dental agenesis, syndactylia, micropenis and cryptorchidism. We found de novo mutation in these two patients (Cys178Ser and Arg622Gly, respectively), and one inherited Arg622Gln mutation with intrafamilial variable phenotype. These genotype-phenotype correlations indicate that paediatric phenotypic expression of FGFR1 loss of function mutations is highly variable, the severity of the oro-facial malformations at birth does not predict gonadotropic function at the puberty and that de novo mutations of FGFR1 are relatively frequent.- - - - - - - - - - ranking = 1keywords = puberty (Clic here for more details about this article) |
4/9. Isolated hypogonadotrophic hypogonadism: a family with autosomal dominant inheritance.A family is reported in which isolated hypogonadotrophic hypogonadism is inherited as an autosomal dominant condition with variable expression. In previous familial cases, inheritance was autosomal recessive. Comparison is made with the endocrine and genetic findings in Kallmann's syndrome, which should be considered a separate disorder. There is difficulty in drawing a sharp distinction between hypogonadotrophic hypogonadism and constitutional delay in puberty in this family.- - - - - - - - - - ranking = 1keywords = puberty (Clic here for more details about this article) |
5/9. Identical twins discordant for Kallmann's syndrome.A 20 year old male patient presented with lack of sexual development. On examination he was eunuchoidal and hypogonadal, and olfactory function testing showed he was anosmic. Biochemical investigations proved he was hypogonadotrophic. Kallmann's syndrome was therefore diagnosed. His appearance was very different from his alleged identical twin who had undergone a normal puberty and had normal plasma testosterone and gonadotrophin levels. However, the twin was hyposmic. Genetic fingerprinting confirmed the twins were identical. Why Kallman's syndrome was incompletely expressed in one of them is unexplained. The parents and a normally menstruating sister had normal olfactory function.- - - - - - - - - - ranking = 1keywords = puberty (Clic here for more details about this article) |
6/9. Stimulation of spermatogenesis and biological paternity by intranasal (low dose) gonadotropin-releasing hormone (GnRH) in a male with Kallmann's syndrome: intraindividual comparison of GnRH and gonadotropins for stimulation of spermatogenesis.Intranasal (in) GnRH spray caused induction and maintenance of spermatogenesis and biological paternity in a 28-yr-old man with Kallmann's syndrome. Prior treatment had included GnRH analog administration, which failed to induce puberty, and testosterone (T) enanthate weekly. Prior hCG/human menopausal gonadotropin therapy had resulted in high normal serum T levels and near-normal semen quality, but during subsequent hCG therapy, spermatogenesis markedly decreased. The patient had then received 250 mg T enanthate/month for 2 yr and 7 months; it was discontinued 7 weeks before the in GnRH study began. At its start (July 1984) the subject's testis size was 7 mL, and he had azoospermia, low serum LH and FSH levels, and a serum T of 74 ng/dL (2.6 nmol/L). GnRH was administered in a dose of 200 micrograms (20-120 ng/kg were absorbed into the circulation) every 2 h, seven to nine times a day, between 0700 and 2400 h for 242 days. After 12 days of treatment, serum T had increased to 519 ng/dL (18.0 nmol/L). After 70 days, the patient's sperm count was 11.5 million/mL (4.5 mL ejaculate volume; 70% motility; 36% normal morphology); on day 185, sperm count was 31 million/mL (4 mL ejaculate volume; 54% motility; 36% normal morphology). His spouse conceived on day 162 and delivered a fullterm daughter 265 days later. The probability of paternity was 99.9994%. Our results suggest that induction and maintenance of spermatogenesis as well as fertility in hypothalamic hypogonadism can be achieved with in GnRH therapy if pituitary and testicular function are intact. spermatogenesis induced by in GnRH has the same quality as spermatogenesis induced by hCG/human menopausal gonadotropin therapy. patient compliance is probably the most important factor for the success of in GnRH therapy.- - - - - - - - - - ranking = 1keywords = puberty (Clic here for more details about this article) |
7/9. Events surrounding the initiation of puberty with long term subcutaneous pulsatile gonadotropin-releasing hormone in a female patient with Kallman's syndrome.An 18-yr-old woman with primary amenorrhea, anosmia, and total lack of secondary sexual development was treated for 230 days using sc pulsatile GnRH. GnRH testing with 100 micrograms, sc, initially revealed a peak FSH to LH ratio greater than 1. After 28 days of treatment, this ratio had reversed. A dosage of 20 micrograms/2 h for 200 days resulted in a LH to FSH ratio greater than 2. Widening the interval to 20 micrograms/3 h significantly lowered LH, but not FSH, levels. Increasing the frequency to 20 micrograms/90 min again increased the LH to FSH ratio. Twenty-four-hour testing revealed a sleep-entrained PRL rise both during and after GnRH therapy, but no sleep-entrained rise in LH. Ultrasound monitoring revealed cyclic changes in ovarian diameter at 30- to 60-day intervals that coincided with cyclic increases in LH and estradiol. The uterine fundus doubled in length between days 50 and 110 of treatment. The patient progressed from Tanner pubic hair and breast stage I to stage II during treatment, which was terminated due to an allergic reaction to GnRH. This study provides the first report of hormonal and ultrasound events surrounding puberty induction with GnRH in the female. We conclude widening the interval of GnRH administration can reduce LH levels while maintaining FSH levels, cyclic changes in ovarian diameter, LH, and estradiol occur before menarche, and although pulsatile GnRH provides a fascinating model for the study of puberty in the female, the chronicity of therapy needed and its potential for allergic reaction make this method of inducing puberty suboptimal.- - - - - - - - - - ranking = 7keywords = puberty (Clic here for more details about this article) |
8/9. Kallmann's syndrome. A case report.A patient with hypogonadotrophic hypogonadism and anosmia (Kallmann's syndrome) presenting as delayed puberty is described. The clinical, hormonal and testicular histological features are noted. The basic principles of treatment are discussed.- - - - - - - - - - ranking = 1keywords = puberty (Clic here for more details about this article) |
9/9. Case report: olfactory function in a fertile eunuch with kallmann syndrome.The olfactory and gonadal dysfunction in kallmann syndrome share a common embryologic pathophysiology. To characterize further the linkage between the hypogonadotropic hypogonadism and anosmia, the authors performed a detailed evaluation of olfactory function in a patient with Kallman Syndrome having the rare variant of partial gonadotropin deficiency (fertile eunuch). The subject was seen initially at age 16 years because of delayed puberty. He received testosterone replacement therapy and subsequently completed pubertal development. As an adult, while untreated, he had subnormal levels of serum testosterone, low gonadotropins, and normal response to luteinizing hormone- releasing hormone. He also had impotence that was reversible with testosterone therapy, and a normal sperm count. Despite the mild degree of hypogonadism, olfactory function was completely absent, and the response to nasal trigeminal stimulants was markedly attenuated. Complete anosmia may therefore be associated with gonadotropin deficiency that is only partial; the presence of anosmia does not predict the need for gonadotropin therapy to attain fertility.- - - - - - - - - - ranking = 1keywords = puberty (Clic here for more details about this article) |