An unusual cause of adult onset cerebellar ataxia with hypogonadism

We report an unusual case of sporadic adult onset cerebellar ataxia with hypogonadism. A 40-year-old unmarried man presented with progressive ataxia and dysarthria along with complaints of non-development of secondary sexual characteristics and erectile dysfunction. There were complaints of intermittent diarrhea. Clinical examination revealed a pan-cerebellar syndrome with features of hypoandrogenism. No eye movement abnormalities were evident. There were signs of malabsorption. Investigations confirmed the presence of auto-antibodies found in celiac disease, and a duodenal biopsy confirmed the same. Hypoandrogenism was postulated to be due to hypergonadotropic hypogonadism which has been mentioned in a few patients of celiac disease. However, the pattern seen in our patient was of a hypogonadotropic hypogonadism. This is probably secondary to an autoimmune hypophysitis seen in some patients in the absence of other clinical manifestations. Autoantibody testing should be a diagnostic necessity in any adult with a sporadic cerebellar ataxia.     

男性青少年性腺功能减退症患者短期雄激素替代治疗对血脂和hsCRP水平的影响

目的 探讨性腺功能低减的青少年男性，短期雄激素替代治疗对血脂和超敏C反应蛋白（hsCRP）的影响。方法 本研究为前瞻性自身对照研究，共纳入33例性腺功能减退青少年男性。行短期（9个月）雄激素替代治疗，比较治疗前后血睾酮水平、第二性征发育程度、身高、握力、血红蛋白、血脂和hsCRP的差异。结果 （1）替代治疗后，睾酮水平明显升高，第二性征明显发育，身高、握力、血红蛋白显著增加（P值均〈0.05）；（2）短期雄激素替代治疗后，总胆固醇（TC），低密度脂蛋白（LDL-c），高密度脂蛋白（HDL-c）和甘油三酯（TG）部有所下降，但无统计学差异（P〉0．5）。超敏CRP显著下降（P=0.025）。结论 （1）性腺功能低减的青少年男性，短期雄激素替代治疗，可以促进第二性征发育，增加身高、握力和血红蛋白；（2）短期雄激素替代治疗，对血脂无显著性影响。但是，可以使hsCRP明显下降。     

脉冲式皮下注射黄体生成素释放激素治疗男性促性腺激素缺乏症(附14例报道)

目的　观察脉冲式黄体生成素释放激素 (LHRH)皮下注射对男性促性腺激素缺乏症的治疗效果。　方法　给予知情同意的男性促性腺激素缺乏症 14例患者LHRH脉冲式腹壁皮下注射 ,每 90min 1个脉冲 (每个脉冲 10 μg) ,治疗 3～≥ 12个月。　结果　除 2例无效外 ,余 12例 (86% )有效 ,表现为青春期发育加速 ,体力增强 ,睾丸明显增大 ,阴茎增长 ,阴毛和腋毛生长。 5例有遗精现象 ,2例精液常规中有精子生成 ,所有患者在治疗期间性激素水平改善。　结论　脉冲式LHRH皮下注射是符合生理的替代治疗 ,是对男性特发性促性腺激素缺乏症可取的治疗方式。     

Klinefelter's Syndrome: Hypogonadism,abnormal carbohydrate metabolism. Is it a result of biotin deficiency?

The aetiology of Klinefelter's Syndrome is not known. The causative factor(s) must explain the hypogonadism, low androgen levels, the disordered carbohydrate metabolism and the commonly associated psychiatric conditions. A biotin deficient/dependent state can account for the above. A biotin deficient Klinefelter's Syndrome patients with the above is described. The possible role of biotin in the primary, secondary and tertiary prevention of Klinefelter's Syndrome needs further research.     

继发性骨质疏松防治的研究

目的总结继发性骨质疏松预防与治疗的经验及提出见解.方法用钙代谢平衡的方法研究了钙代谢的基本情况,比较了补钙与不补钙在若干种生理状态对骨密度的影响,总结继发性骨质疏松的病因及对其采取不同方法的治疗经验.结果中国人膳食含钙量属于正常范围低水平状态,与适宜摄入量(AI)比较是不足的,在一定的生理状态下应予补钙.缺钙是原发性骨质疏松与继发性骨质疏松的不利因素.氟中毒骨病、糖尿病、性腺功能减退、肿瘤、糖皮质激素过多和甲亢均有其各别的病理生理,导致继发性骨质疏松,防治方法各异.结论从胚胎至老年都应防治骨质疏松.不同情况采取方法各异,但有效.     

Ovulation induction: a mini review

Ovulation induction is the method for treating anovulatory infertility. For patients with hypogonadotrophic hypogonadism, the treatment involves administration of both FSH and LH, while HCG is injected for follicle rupture. Pulsatile GnRH has the same effectiveness as gonadotrophins and the advantage of the low multiple pregnancy rate. In polycystic ovary syndrome (PCOS), the first treatment choice is clomiphene citrate. With this drug, in properly selected patients, the cumulative pregnancy rate approaches that of normal women. Low-dose protocols of FSH are the second line of treatment, effective in inducing monofollicular development. Laparoscopic ovarian drilling can be an alternative but not as a first choice treatment in clomiphene-resistant patients. Other treatments, such as pulsatile GnRH and GnRH agonists, are hardly used today in PCOS. However, in obese women with PCOS, weight loss and exercise should be recommended as the first line of therapy. Newer agents including aromatase inhibitors and insulin sensitizers, although promising, need further evaluation.     

ICSI using testicular sperm in male hypogonadotrophic hypogonadism unresponsive to gonadotrophin therapy

BACKGROUND: The aim of this study was to assess the use of testicular sperm for ICSI in azoospermic men with hypogonadotrophic hypogonadism unresponsive to gonadotrophin therapy. METHODS: Fifteen patients with hypogonadotrophic hypogonadism who remained azoospermic after hormonal treatment underwent testicular sperm extraction (TESE) and ICSI. These men were recruited from the Egyptian IVF centre over a period of 4 years. All patients were given 75 IU hMG thrice weekly and 5000 IU hCG once or twice weekly for >/=6 months prior to attempting ICSI/TESE. RESULTS: In 11 out of 15 patients (73%), sperm could be retrieved from testicular tissue and were used for ICSI. Two chemical pregnancies resulted but no clinical pregnancies. Nine patients continued gonadotrophin therapy for another 6 months. Sperm appeared in the ejaculate of three of them. The remaining six patients underwent another ICSI cycle, one using cryopreserved sperm and five underwent a second TESE. One chemical pregnancy and three clinical pregnancies were established. One ongoing, one singleton and one twin pregnancies resulted in the delivery of three healthy babies. In total, of 17 ICSI cycles performed using testicular sperm retrieval, the fertilization rate was 41.7% and the cumulative pregnancy rate was 20%. CONCLUSIONS: The use of testicular sperm for ICSI is a treatment option that can be offered to azoospermic males with hypogonadotrophic hypogonadism either not responding or reluctant to continue hormonal treatment. However, prolonged hormonal treatment may improve TESE/ICSI results.     

Kallmann syndrome: 14 novel mutations in KAL1 and FGFR1 (KAL2)

Kallmann syndrome (KAL) combines hypogonadotropic hypogonadism and anosmia. Hypogonadism is due to Gonadotropin Releasing Hormone (GnRH) deficiency and anosmia is related to hypoplasia of the olfactory bulbs. Occasional symptoms include renal agenesis, bimanual synkinesia, cleft lip palate, dental agenesis. KAL is genetically heterogeneous and two genes have so far been identified, namely KAL1 (Xp22.3) and FGFR1/KAL2 (8p12), which underlie the X chromosome‐linked form and an autosomal dominant form of the disease, respectively. We studied a cohort of 98 unrelated Caucasian KAL patients. We identified KAL1 mutations in 14 patients, of which 7 (c.3G>A (p.M1?), g.IVS1+1G>T, c.570_571insA (p.R191fsX14), c.784G>C (p.R262P), c.958G>T (p.E320X), c.1651_1654delinsAGCT (p.P551_E552delinsSX), c.1711T>A (p.W571R)) have not been previously reported. In addition, we found FGFR1 mutations in 7 patients, namely c.303G>A (p.V102I), C.385A>C (p.D129A), c.810G>A (p.V273M), c.1093_1094delAG (p.R365fsX41), c.1561G>A (p.A520T), c.1836_1837insT (p.Y613fsX42), c.2190C>G (p.Y730X), all of which were novel mutations. In this study, unilateral renal agenesis and bimanual synkinesia were exclusively found associated with KAL1mutations, cleft palate and dental agenesia with FGFR1mutations. © 2004 Wiley‐Liss, Inc.     

Human follicle-stimulating hormone produced by recombinant DNA technology: a review for clinicians

Human follicle-stimulating hormone (FSH) is now produced in vitro by recombinant DNA technology. FSH being a complex heterodimeric protein, a eukaryotic cell line has been selected for expression work (Chinese hamster ovary cells). The pharmaceutical preparation of recombinant human FSH (r-FSH) differs from that of human menopausal gonadotrophin (HMG) and the first generation of urinary human FSH (u-FSH) in terms of (i) source of bulk materials, (ii) purity and specific activity, (iii) batch to batch consistency, and (iv) complete absence of luteinizing hormone (LH) activity. Pharmacokinetic characterization of r-FSH has shown an absolute bioavailability of approximately 75% after both s.c. and i.m. administration and an apparent terminal half-life of 37 +/- 25 h. These characteristics are very similar to those of u-FSH. Clinical efficacy and safety are currently demonstrated through several randomized, well controlled studies, comparing r-FSH administered s.c. with u-FSH administered i.m. for stimulating follicular development prior to assisted reproduction treatment and in World Health Organization (WHO) group II anovulation. To date, approximately 1000 patients have been treated with r-FSH. Moreover, r-FSH has recently been used successfully in association with recombinant human LH for inducing ovulation and pregnancy in WHO group I anovulatory patients. At this stage of r-FSH preparation assessment, it is likely that r-FSH will replace all urinary-derived FSH preparations for stimulating ovarian follicular development. For clinicians, current experience with r-FSH indicates that it should be used with the regimes and doses applied to u-FSH.