Reduced androgen levels in adult Turner syndrome: influence of female sex steroids and growth hormone status

BACKGROUND AND OBJECTIVES: In girls with Turner syndrome androgen levels are reduced. In order to assess androgen status in women with Turner syndrome, we compared untreated adult women with Turner syndrome with a group of normal women. In addition, the effects of female sex hormone replacement therapy and GH status on the levels of circulating androgens in Turner syndrome was examined. DESIGN: All patients were receiving female hormone replacement therapy (HRT), which was discontinued four months prior to the initial examination. Patients were studied before and during HRT. Following the initial evaluation, patients were given cyclical HRT for six months consisting of either oral substitution (17beta-oestradiol with norethisterone from day 13-22), or transdermal oestrogen substitution (17beta-oestradiol) with 1 mg norethisterone administered orally from day 13-22. Control subjects were studied once in the early follicular stage of the menstrual cycle. SUBJECTS: The study group consisted of 27 (33.2 +/- 7.9 years) patients with Turner syndrome and an age matched control group of 24 (32.7 +/- 7.6 years) normal women. MEASUREMENTS: Body composition measures, SHBG, testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), alpha-4-androstendione (A), dehydroepiandrosterone sulphate (DHEAS), 17beta-oestradiol (E2), oestrone (E1), oestrone sulphate (ES), 24 h integrated GH concentration (ICGH), insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein (IGFBP-3) were determined at baseline and after six months in women with Turner syndrome, and at baseline in control women. RESULTS: Circulating levels of A, T, FT, DHT, and SHBG were reduced by 25-40% in comparison with age matched normal women. The level of DHEAS was normal. The level of E2 was undetectable and levels of E1 and ES were very low in untreated Turner women. Treatment with 17beta-oestradiol and norethisterone increased oestrogen to levels comparable to those of normal women, while further decreasing FT (P = 0.02), DHT (P = 0.04), and T (P = 0.1). In untreated women with Turner syndrome IGF-I correlated significantly with DHEAS (R = 0.503, P < 0.01), while in normal women IGF-I correlated with A (R = 0.637, P < 0.01), T (R = 0.536, P < 0.01), and FT (R = 0.700, P < 0.01). During hormonal replacement in women with Turner syndrome IGF-I correlated significantly with DHEAS (R = 0.547, P < 0.01). Employing multiple regression analysis IGFBP-3, ICGH, DHEAS and fat free mass explained 85% (adjusted R = 0.92, P < 0.0005) of the variation in the level of IGF-I in untreated Turner syndrome. In treated Turners IGFBP-3, ICGH, SHBG, T, and FT explained 78% (adjusted R = 0.88, P < 0.0005). In controls IGFBP-3, SHBG, BMI and age explained 74% (adjusted R = 0.86, P < 0.0005) of the variation in IGF-I, while GH status did not contribute at all. CONCLUSION: The present study shows that many adults with Turner syndrome have reduced levels of circulating androgens, compared with an age-matched group of normal women. Conditions associated with Turner syndrome such as increased prevalence of sexual problems, reduced bone mineral content, osteoporosis, and an increased incidence of fractures and alterations in body composition could perhaps be alleviated or abolished by substitution with a low dose of androgens. Treatment with female hormonal replacement therapy is associated with a decrease in testosterone, free testosterone and dihydrotestosterone, possibly mediated by the androgenic effect of norethisterone. Furthermore significant differences in sex steroid levels, GH status and indices of body composition can be compatible with comparable levels of IGF-I in two very different groups of individuals.     

Technique and proof of patency of microsurgical lympho‐lymphonodular anastomoses: A study in the rat model

Background: Lymphedemas due to local lymphatic blocks can be treated by microsurgical transplantation or transposition of lymphatic vessels. Here, the anastomoses are usually made end‐to‐end between lymphatics, but occasionally appropriate lymphatic recipient vessels are missing. In such cases, reconstructing lymph drainage by connection to a lymph node could be another technical option. The purpose of this study was to examine the patency rate of such lympho‐lymphonodular anastomoses in an experimental animal model. Methods: Male Sprague–Dawley rats were anesthetized, and the retroperitoneum was exposed. Patent blue dye was injected into the left foot to stain lymphatic structures. In group A (n = 8), the left lumbar trunk was cut centrally, the distal part was turned over to the right lumbar lymph node, and a microsurgical lympho‐lymphonodular anastomosis was performed. In group B (n = 8), the left lumbar trunk was cut. After 8 weeks, the lumbar region was surgically re‐explored, and the lymphatic drainage was examined by injection of Patent blue dye into the left lumbar lymph node. Results: In 8/8 animals of group A, patent transposed lymphatics were found. The patency of the anastomosis was proven directly by observation of blue dye transit and indirectly by observation of blue staining of the right lumbar lymph node. In 6/8 animals of group B, no lymphatic connection to the right lumbar lymphatic system was observed. Conclusions: This is the first report of the microsurgical technique and the proof of patency of lympho‐lymphonodular anastomoses. The novel animal model for testing the patency of transposed lymphatics is discussed. © 2009 Wiley‐Liss, Inc. Microsurgery, 2009.     

Water-Free Sodium Accumulation

The widely accepted concept of body fluid and electrolyte homeostasis is that Na⁺ is restricted mainly to the extracellular fluid and K⁺ to the intracellular space, where both ions act to hold water and thereby control the extracellular and intracellular fluid volume by their osmotic activity. Na⁺ accumulation thus inevitably leads to water retention. The constancy of the extracellular volume is the task of the kidneys, which control the total body Na⁺ content. More recent data have questioned this traditional view, suggesting that large amounts of Na⁺ can be accumulated without accompanying water retention by osmotically inactive Na⁺ retention, or by osmotically neutral Na⁺/K⁺ exchange. Besides the control of the body Na⁺ content by the kidneys, redistribution of body electrolytes hence provides an extrarenal regulatory alternative in the maintenance of body fluid volume and blood pressure control.     

A direct neural projection from the intergeniculate leaflet of the lateral geniculate nucleus to the deep pineal gland of the rat, demonstrated with Phaseolus vulgaris leucoagglutinin.

The anterograde tracerPhaseolus vulgaris leucoagglutinin (PHA-L) was injected into different subregions of the rat lateral geniculate nucleus. After a survival for 5–10 days, the rats were fixed by perfusion with 4% paraformaldehyde, whereafter the brains were cut in a cryostat and the tracer was localized by immunohistochemistry. After deposits of PHA-L involving the intergeniculate leaflet, a high number of PHA-L-immunoreactive fibers were observed to project directky into the posterior commissure. From the posterior commissure, some nerve fibers turned dorsally and entered into the deep pineal gland, a part of the pineal complex located in between the posterior and the habenular commissure. A few PHA-L-immunoreactive fibers were observed in the pineal stalk, but no fibers were detected in the superficial pineal gland. In cases where the injections were placed in the dorsal or ventral subnuclei, no immunoreactive nerve fibers were observed to enter the pineal complex. These results indicate that the intergeniculate leaflet of the lateral geniculate nucleus, a nucleus considered to be involved in circadian rhythmicity, might influence the pineal gland, via a neural projection to the rostral part of the pineal complex.     

Treatment of Patients with Early Breast Cancer: Evidence,Controversies, Consensus: German Expert Opinions on the 17th International St. Gallen Consensus Conference

This yearʼs 17th St. Gallen (SG) Consensus Conference on the Treatment of Patients with Early Breast Cancer (SG-BCC) with the title “Customizing local and systemic therapies for women with early breast cancer” focused on the challenge of targeting the treatment of early breast cancer more specifically to the individual disease situation of each patient. As in previous years, a German working group of leading breast cancer experts discussed the results of the international SG-BCC 2021 in the context of the German guideline. It is helpful to compare the SG recommendations with the recently updated treatment recommendations of the Breast Commission of the German Working Group on Gynaecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie e. V., AGO) and the S3 guideline because the SG-BCC panel comprised experts from different countries, which is why country-specific aspects can be incorporated into the SG recommendations. The German treatment recommendations of the AGO and the S3 guideline are based on current evidence. Nevertheless, any therapeutic decision must always undergo a risk-benefit analysis for the specific situation and to be discussed with the patient.Key words: St. Gallen Consensus 2021, early breast cancer, surgery, radiotherapy, (neo)adjuvant systemic therapy, targeted therapy