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Background: In the Western world, it is widely accepted as natural - and seen almost as a law of nature - that mankind is divided into two sexes or genders - males and females. In many cultures and societies, however, more than two sex and/or gender categories are recognized, which in some instances refer to the biological sex and in others to gender roles and social status., Aims: To give an intercultural comparison of various ways of dealing with gender variance., Methods: In the following paper, we review the anthropological literature during the last 100 years describing individuals who live neither as men nor women in various non-Western cultures., Results: Only rarely, these individuals suffer from disorders of sex development in the modern medical or biological definition: in many if not all societies there have been individuals who are not covered by the gender category of male and female., Conclusion: There thus appears to be a cultural need for people with a special neither-male-nor-female status, which might be classified as 'gender variance'., ((c) 2008 S. Karger AG, Basel)

Salt and water homoeostasis is tightly regulated by a variety of control mechanisms with the adrenal steroid hormone aldosterone playing a central role. Defects or disturbances in these systems lead to either salt loss, which is life threatening in the neonatal period, or sodium retention causing hypertension. Rapid and accurate diagnosis is required to avoid severe complications. During the last few years molecular genetic advances have been identified as the basic genetic defects for a number of clinical syndromes. This knowledge has considerably increased our understanding of the basic pathways involved in sodium and water homoeostasis and of the pathophysiology of these syndromes, particularly the hypertension. In this review we have summarized the biochemical, physiological and genetic basis for clinical syndromes presenting with salt loss and failure to thrive as well as the rare but important genetic syndromes causing sodium retention and hypertension. Early diagnosis and identification will help to prevent severe complications, but it has to be emphasized that the complicated cascade of aldosterone action is still relatively poorly understood. Further syndromes may exist which once identified will help to better understand the basic physiology of aldosterone action., (Copyright 2004 S. Karger AG, Basel)

Background: Deletions and mutations in the NSD1 gene are the major cause of Sotos syndrome. We wanted to evaluate the genotype-phenotype correlation in patients suspected of having Sotos syndrome and determine the best discriminating parameters for the presence of a NSD1 gene alteration., Methods: Mutation and fluorescence in situ hybridization analysis was performed on blood samples of 59 patients who were clinically scored into 3 groups. Clinical data were compared between patients with and without NSD1 alterations. With logistic regression analysis the best combination of predictive variables was obtained., Results: In the groups of typical, dubious and atypical Sotos syndrome, 81, 36 and 0% of the patients, respectively, showed NSD1 gene alterations. Four deletions were detected. In 23 patients (2 families) 19 mutations were detected (1 splicing defect, 3 non-sense, 7 frameshift and 8 missense mutations). The best predictive parameters for a NSD1 gene alteration were frontal bossing, down-slanted palpebral fissures, pointed chin and overgrowth. Higher incidences of feeding problems and cardiac anomalies were found. The parameters, delayed development and advanced bone age, did not differ between the 2 subgroups., Conclusions: In our patients suspected of having Sotos syndrome, facial features and overgrowth were highly predictive of a NSD1 gene aberration, whereas developmental delay and advanced bone age were not., (Copyright (c) 2004 S. Karger AG, Basel.)

Defective aldosterone receptor binding is present in pseudohypoaldosteronism, and sporadic as well as familial cases have been reported. In familial pseudohypoaldosteronism, autosomal dominant as well as autosomal recessive inheritance has been described. The autosomal dominant form is characterized by a relative mild course of the disease and asymptomatic carriers of the defect in these families, whereas the autosomal recessive form is characterized by severe salt-losing symptoms; not uncommonly these families are consanguineous. To date no genetic mutation has been identified in the aldosterone receptor gene of affected patients. Studies to evaluate the biochemical defect and to characterize the inheritance pattern are of major interest for clinical as well as research purposes. Thus we studied the response of the renin-angiotensin-aldosterone system to sodium depletion using a single dose of furosemide. In 5 patients from five nonconsanguineous families and in all available family members the renin and aldosterone levels as well as serum sodium was measured before and after an oral dose of furosemide. The aldosterone receptor binding of peripheral mononuclear leukocytes was determined at the beginning of the study. In three families asymptomatic carriers of the defect could be identified in the baseline state by elevated levels of basal aldosterone and high renin concentration. The levels of renin and aldosterone did not differ between the symptomatic and asymptomatic individuals in these families. Interestingly the aldosterone receptor binding in the asymptomatic carriers of these families was normal. In the other two families, however, the basal hormonal data were normal in all relatives suggesting at first sporadic cases. During sodium depletion with furosemide, renin as well as aldosterone levels rose significantly in 1 parent and a sibling, respectively. In contrast to the first three families the aldosterone receptor binding in these family members was low. We propose to reclassify these family members as asymptomatic carriers and the patients as familial cases. Whether these cases are genetically identical to the 'classical autosomal dominant cases' remains to be seen. It seems that the pathogenesis of pseudohypoaldosteronism is even more heterogeneous than previously thought and factors other than aldosterone receptor binding are crucial and need further identification.

This paper describes the time course of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in two patients with the complete androgen insensitivity syndrome (AIS) during puberty and adolescence prior to gonadectomy. In early puberty, LH values were comparable to normal male as well as female standards. At the age of 17 and 18.7 years, respectively, a sudden rise in LH occurred just after the start of estradiol supplementation. These high LH concentrations in the late puberty of our patients are comparable to the values found during early puberty in castrated individuals and children with gonadal dysgenesis. In contrast, FSH concentrations continuously showed levels in the normal male or female range with no rise during adolescence. The sudden increase of LH in late puberty is most probably due to defective testosterone receptors in the pituitary/hypothalamus which apparently can no longer be suppressed by rising testosterone levels and an escape from the negative estradiol feedback. The role of estradiol supplementation might be incidental and further investigation into its role is needed. In contrast to the elevated levels of FSH in patients with defective spermatogenesis, FSH is normal in our patients with AIS and testes in situ. This indicates that FSH secretion is regulated by a combined action of estradiol and gonadal hormones like inhibin.

We report two patients with transient pseudohypoaldosteronism due to obstructive renal disease. Both patients presented with a salt-losing episode simulating adrenal insufficiency. In one patient, transient reduction of aldosterone receptors could be documented, while in the second patient the clinical and biochemical parameters were consistent with transient pseudohypoaldosteronism. Aldosterone receptors were normal in both patients when studied after the surgical correction of the obstruction.

A semiautomatic capillary gas-liquid chromatographic method for the determination of urinary steroids has been developed. Trimethylsilylenol ethers were used as steroid derivatives instead of the more common methoxime trimethylsilyl ethers. The diagnosis of the various enzymatic defects causing congenital adrenal hyperplasia can be made using the characteristic pattern of urinary steroid chromatograms. Furthermore, the method presented can be used routinely to monitor therapeutic control in congenital adrenal hyperplasia. Reference data for patients of different age groups under good therapeutic control are presented.

Pregnant rats were passively immunized against testosterone by injections of rabbit antibodies against testosterone. Fetuses were studied daily starting at day 18 of gestation. Testosterone antibodies were detected in all fetal plasma samples. At day 18 of gestation testicular testosterone content - as an index of gonadotropin stimulation - was unchanged even though circulating free testosterone was reduced by antibody binding. However, at day 19 and all subsequent days of gestation testicular testosterone content was significantly higher in immunized fetuses compared to the controls. These results indicate that in the male rat the negative feedback between testes and the hypothalamopituitary system develops between days 18 and 19 of gestation.