E. Martin Ritzén

Nordic consensus on treatment of undescended testes

Aim: To reach consensus among specialists from the Nordic countries on the present state‐of‐the‐art in treatment of undescended testicles.

Pubertal growth in patients with androgen insensitivity: Indirect evidence for the importance of estrogens in pubertal growth of girls

Spontaneous pubertal growth was studied in eight patients with the syndrome of androgen insensitivity to obtain information on the growth-promoting action of estrogens. In one additional patient (who had a gonadectomy before puberty), the effect of exogenous estrogens was studied. Mean age at peak height velocity (12.7 years) was closer to that in normal girls than to that in normal boys. Mean peak height velocity (7.4 cm/yr) was as in normal giris (7.3 cm/yr), but was lower than in normal boys (9.3 cm/yr). Bone age corresponded normal men (−0.6 SD), but higher than in normal women (+1.4 SD). In the better to male standards. Mean adult height (172.3 cm) was lower than in patient who had a gonadectomy, estrogen replacement caused a higher peak height velocity (12 cm/yr), but lower adult height (160.5 cm) than in the patients with intact gonads who received no treatments. We conclude than in normal giris, the pubertal growth spurt also results from the action of estrogens rather than of adrenal androgens. To ensure normal pubertal growth, physiologic estrogen replacement in hypogonadal females should be started at a bone age of about 11 years, and should not be delayed in the hope of achieving a greater mature height.

Dose-Dependent Effect of Growth Hormone on Final Height in Children with Short Stature without Growth Hormone Deficiency

CONTEXT The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH). OBJECTIVE The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls. DESIGN AND SETTING A randomized, controlled, long-term multicenter trial was conducted in Sweden. INTERVENTION Two doses of GH (Genotropin) were administered, 33 or 67 microg/kg.d; control subjects were untreated. SUBJECTS A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (AllITT) population, and 108 in the per protocol (AllPP) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population. MAIN OUTCOME MEASURES We measured FH sd score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in heightSDS. RESULTS After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations. CONCLUSION GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls.

Undescended testes: a consensus on management

The mode of treatment best for undescended testes is controversial, and local traditions often override knowledge gained from randomized controlled studies. In order to reach a consensus within the Nordic countries on the current state-of-the-art of treatment, a group of specialists in testicular physiology, paediatric surgery/urology, endocrinology, andrology, pathology and anaesthesiology from all the Nordic countries met for 2 days. Before the meeting, reviews of the literature had been prepared by the participants. Judging from published meta-analyses, hormonal treatment has low efficacy. Although 15-20% of retained testes descend during hormonal treatment, one-fifth of these re-ascend later on. Also, treatment with human chorionic gonadotropin (hCG) may be harmful to future spermatogenesis through increased apoptosis of germ cells. Orchiopexy, on the contrary, results in about 95% anatomical success, with a low (about 1%) risk of complications. The optimal time for orchiopexy has also been debated. However, a recent randomized controlled study shows that surgery at 9 months of age is followed by a better post-operative growth of the testes than surgery at 3 years, which supports previous arguments for early surgery. The unanimous conclusion of the group was that surgery is generally the preferred mode of treatment, rather than hCG or GnRH treatments. Orchiopexy should be performed between 6 and 12 months of age, or soon after diagnosis, if that occurs later. If a testis is found to be undescended at any age after 6 months, the patient should be referred for surgery. Referral should be to paediatric rather than general surgeons/urologists if the boy is less than 1 year old, if he has bilateral or non-palpable testes, or if he has got relapse of cryptorchidism.

Revised Guidelines for Neonatal Screening Programmes for Primary Congenital Hypothyroidism

Since the first guidelines for neonatal screening for congenital hypothyroidism (CH) were issued by ESPE in 1993 [1], there have been considerable advances in our understanding of CH and our appreciation of the various geographical and logistic difficulties involved. Therefore, an updating of the guidelines is overdue. Experience from countries where screening began in the late 1970s and early 1980s has indicated that treatment should be started no later than the first 2 weeks of life using a ‘high’ dosage regime of L-thyroxine (10–15 Ìg/kg/day). It has also been shown that the quality of long-term outcome is closely related to the quality of follow-up. In Eastern Europe, screening programmes for CH have either been started or will start soon in almost all countries, and although many programmes are operating satisfactorily, it is important to standardise screening procedures and management of suspected cases as much as possible in order to optimise outcome. A degree of uniformity throughout Europe would not only facilitate early detection and treatment of individual patients but give insight into the economic and epidemiological aspects of the screening programmes as well as the epidemiological aspect of CH.

Long-term follow-up of prenatally treated children at risk for congenital adrenal hyperplasia : Does dexamethasone cause behavioural problems?

OBJECTIVES To investigate the long-term effects of prenatal treatment of congenital adrenal hyperplasia (CAH) with emphasis on behavioural problems and temperament. DESIGN A population-based long-term follow-up study of Swedish children at risk for virilising CAH, who had received treatment prenatally with dexamethasone (DEX). The questionnaire-based follow-up was performed when the children had reached school age. METHODS Standardised parent-completed questionnaires were used to evaluate adaptive functioning, behavioural/emotional problems and psychopathology, social anxiety and temperament in DEX-exposed school-aged children (n=26) and matched controls (n=35). In addition, the association between parental questionnaires and childrens self-ratings was investigated. RESULTS There were no statistically significant differences between DEX-exposed children and controls in measures of psychopathology, behavioural problems and adaptive functioning. In a questionnaire on temperamental traits, DEX-exposed children were described by their parents as being more sociable than controls (P=0.042). The correlation analysis showed only modest parent-child agreement on social anxiety, i.e. the increased social anxiety in childrens self-ratings was not confirmed by their parents. CONCLUSIONS DEX-treated children showed good overall adjustment. The parent-child agreement with respect to social anxiety was modest, highlighting the importance of multiple information sources and assessment methods. The clinical significance of the observed difference in sociability cannot be determined within the frameworks of this study. Additional studies of larger cohorts are essential to make more decisive conclusions on the safety of the treatment. Until then, it is important that parents are thoroughly informed about the benefits and potential risks and uncertainties of this controversial treatment.

Development and descent of the testis in relation to cryptorchidism

The testis descends in two phases. Animal studies suggest, that the transabdominal descent of the testis depends on the insulin‐like hormone 3 (INSL3). Androgens are important in the inguinoscrotal testicular descent in animals and humans. In general, the cause of cryptorchidism is unknown and the aetiology is possibly multifactorial. Histological changes in cryptorchid testes demonstrate disturbed development.

Testicular growth from birth to two years of age, and the effect of orchidopexy at age nine months: A randomized, controlled study

Aim: To study whether surgical treatment at age 9 mo in boys with congenital unilaterally palpable undescended testes (cryptorchidism) is followed by improved growth of the previously retained testes compared to non-treatment. Methods: At the age of 6 mo, 70 boys were randomized to surgical treatment at 9 mo and 79 boys to treatment at 3 y of age. The boys were then followed at 12 and 24 mo. Ultrasonography was used to determine testicular volume. Results: After orchidopexy, the previously retained testes resumed growth and were significantly larger than the non-operated testes at 2 y (0.49 ml vs 0.36 ml, p<0.001). Testicular growth after orchidopexy was also demonstrated by a higher mean ratio between the previously retained and the scrotal testes of the individual boys at 2 y: 0.84 for the surgically treated group, compared to 0.63 for the untreated group (p<0.001). Conclusion: Surgery at 9 mo has a beneficial effect on the growth of previously undescended testes.

Early Puberty: What Is Normal and When Is Treatment Indicated?

Girls and boys who enter puberty before 8 and 9 years of age, respectively (corresponding to about –3 SDS), are arbitrarily considered to need referral for endocrine investigation. A recent report from the Lawson Wilkins Pediatric Endocrine Society suggested that the limit for investigation of girls and boys should be lowered to 7 and 8 years, respectively. For African-American girls, 6 years is the suggested age. This recommendation has been criticized. Although short stature is a common end result of precocious puberty, short- and long-term psychological symptoms may be more important, since several studies have indicated psychopathology in this patient group. Whether this can be prevented by gonadotropin releasing hormone agonist treatment remains to be shown. This review will highlight the psychological aspects of early puberty. In short, aspects other than height should also be evaluated when considering treatment of the early maturing child.

Characterization of an androgen binding protein (ABP) in rat testis and epididymis

Abstract An androgen binding protein (ABP) was demonstrated in the 105,000 g supernatant of rat testis homogenate after charcoal extraction of endogenous steroids. Testis ABP proved to be identical to an ABP previously described in rat epididymis. It contained saturable high-affinity sites which exhibited binding specificity for dihydrotestosterone (6) and testosterone when measured by polyacrylamide gel electrophoresis or by competitive binding using charcoal adsorption. Binding to ABP was not affected by ribonuclease or neuraminidase but was decreased by the disulfide reducing agent, dithiothreitol and the sulfhydryl reagent, N-ethylmaleimide. Binding was abolished by treatment with proteolytic enzyme. The mean molecular radius of ABP was 2.92 nm as determined by the retardation of electrophoretic mobility in polyacrylamide gels of decreasing pore size. Assuming a partial specific volume of 0.66–0.74 the molecular weight was 86,000–91,000 for a spherical molecule. ABP binding was stable after treating at 45° C for 20 min. but was destroyed at 60° C. Binding was maximal between pH 7.5 and 9.0 and decreased at pH below 7.0.