Ebbe Thisted

Treatment of Cryptorchidism with Human Chorionic Gonadotropin or Gonadotropin Releasing Hormone

We have conducted a modified double-blind study on the effect of human chorionic gonadotropin (hCG), gonadotropin releasing hormone (GnRH) and placebo on bilateral and unilateral maldescended testes. One hundred and fifty-five boys with bilateral and 88 boys with unilateral cryptorchidism fulfilled the inclusion criteria and completed the treatment protocol. The boys were between 1 and 13 years of age. hCG was administered as intramuscular injections twice weekly for 3 weeks. GnRH and placebo were given intranasally. hCG was superior to GnRH and placebo in the treatment of bilateral maldescended testes (p = 0.0009). Both testes descended in 25% of the boys following treatment with hCG, and improvement in the position of the testes was obtained in a further 25% of the cases. hCG administration resulted in complete testicular descent in 14% of boys with unilateral cryptorchidism compared with 3 and 0% after placebo and GnRH, respectively (p = 0.07). The testis had moved to a more distal position in 46% of the boys treated with hCG. There was no significant difference between the treatment groups with regard to age or initial position of the testes. We conclude that a success rate of 25% justifies the use of hCG in the treatment of maldescended testes, whereas the study did not support a general use of GnRH administered intranasally.

Development of obesity and polycystic ovary syndrome in adolescents.

Obesity in adolescents is prevalent worldwide. Polycystic ovary syndrome (PCOS) is often associated with obesity in women, and it has serious metabolic and reproductive health implications. Although PCOS does not become clinically visible until early adolescence, its origins are likely much earlier. Therefore, we reviewed the recent literature regarding the mechanisms linking the development of PCOS and obesity in adolescent girls. We found that excess abdominal adipose tissue (AT) initiates metabolic and endocrine aberrations that are central in the progression of PCOS. As an example, abdominal AT impairs insulin action, which interacts with the progression of hyperandrogenism. In addition, excessive androgen levels lead to impaired glucose uptake, which also contributes to insulin resistance, which again increases the deposition of visceral fat. The body composition is influenced by testosterone, which decreases subcutaneous fat lipolysis and influences adipocyte distribution. These mechanisms may explain why PCOS girls have an increased visceral adipose mass independent of body mass index. Therefore, first-line treatment in adolescent PCOS is often lifestyle intervention to prevent the damaging effects of obesity. Pharmacological treatment of adolescent PCOS is not standardized because the long-term effects in adolescents have not yet been evaluated; therefore, drugs should be prescribed cautiously. Although the complex metabolic interrelationships between obesity and PCOS have yet to be fully understood, the co-occurrence of these conditions in adolescent girls tends to increase the severity of the negative health consequences of each condition.

Hormonal treatment of cryptorchidism—hCG or GnRH—a multicentre study

In a modified, double‐blind controlled study, 163 prepubertal boys (aged 1.8–13.0 years) with bilateral and 94 (aged 1.5–13.1 years) with unilateral cryptorchidism were allocated to treatment with either human chorionic gonadotropin (im), gonadotrophin releasing hormone (intranasally) or placebo (intranasally). In individuals with the bilateral condition treatment with human chorionic gonadotrophin resulted in complete descent of both testes in 23% of patients. Treatment with human chorionic gonadotrophin in unilateral cryptorchidism resulted in complete descent in 19% of patients; all results were significantly better than those obtained with gonadotrophin releasing hormone or placebo. Linear and logistic regression analysis of the results obtained by treatment of bilateral disease showed that all treatments were more successful the younger the age of the boys. The data indicated that bilateral and unilateral cryptorchidism respond differently to hormonal treatment. We suggest that human chorionic gonadotrophin should be the first choice of treatment for prepubertal boys older than one year.

MR spectroscopy of liver in overweight children and adolescents: Investigation of 1H T2 relaxation times at 3 T

OBJECTIVE The objective was to investigate T(2) relaxation values and to optimize hepatic fat quantification using proton MR spectroscopy ((1)H MRS) at 3T in overweight and obese children and adolescents. SUBJECTS The study included 123 consecutive children and adolescents with a body mass index above the 97th percentile according to age and sex. (1)H MR spectroscopy was performed at 3.0 T using point resolved spectroscopy sequence with series TE. T(2) relaxation values and hepatic fat content corrected for the T(2) relaxation effects were calculated. RESULTS T(2) values for water ranged from 22 ms to 42 ms (mean value 28 ms) and T(2) values for fat ranged from 36 ms to 99 ms (mean value 64 ms). Poor correlation was observed: (1) between T(2) relaxation times of fat and T(2) relaxation times of water (correlation coefficient r=0.038, P=0.79); (2) between T(2) relaxation times of fat and fat content (r=0.057, P=0.69); (3) between T(2) relaxation times of water and fat content (r=0.160, P=0.26). Correlation between fat peak content and the T(2) corrected fat content decreased with increasing echo time TE: r=0.97 for TE=45, r=0.93 for TE=75, r=0.89 for TE=105, P<0.0001. CONCLUSION (1)H MRS at 3T is an effective technique for measuring hepatic fat content in overweight and obese children and adolescents. It is necessary to measure T(2) relaxation values and to correct the spectra for the T(2) relaxation effects in order to obtain an accurate estimate of the hepatic fat content.

Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age

OBJECTIVE To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls. DESIGN A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born SGA. SETTING Not applicable. PATIENT(S) A subgroup of 18 Danish girls born SGA included in North European SGA Study (NESGAS). INTERVENTION(S) One year of GH treatment (67 μg/kg/day) followed by 2 years of randomized GH treatment (67 μg/kg/day, 35 μg/kg/day, or IGF-I titrated). MAIN OUTCOME MEASURE(S) Data on anthropometrics, reproductive hormones, and ultrasonographic examination of the internal genitalia were collected during 36 months of GH treatment. RESULT(S) Uterine and ovarian volume increased significantly during 3 years of treatment (64% and 110%, respectively) but remained low within normal reference ranges. Ovarian follicles became visible in 58% after 1 year compared with 28% before GH therapy. Anti-Müllerian hormone increased significantly during the 3 years of GH therapy but remained within the normal range. Precocious puberty was observed in one girl; another girl developed multicystic ovaries. CONCLUSION(S) GH treatment was associated with statistically significant growth of the internal genitalia, but remained within the normal range. As altered pubertal development and ovarian morphology were found in 2 of 18 girls, monitoring of puberty and ovarian function during GH therapy in SGA girls is prudent. Altogether, the findings are reassuring. However, long-term effects of GH treatment on adult reproductive function remain unknown. CLINICAL TRIAL REGISTRATION NUMBER EudraCT 2005-001507-19.