Gynaecomastia linked to the intake of a herbal supplement fortified with diethylstilbestrol.

This study reports the findings of a supplement marketed on the Internet for prostate problems. The supplement was orally taken by a 60-year-old man with divergent hormonal levels and who was surgically treated for gynaecomastia: development of abnormally large mammary glands in males. The supplement showed a strong effect in a yeast oestrogen bioassay, expressing a yeast-enhanced green fluorescent protein (yEGFP) upon exposure to oestrogens. Using both nuclear magnetic resonance (NMR) and a gradient liquid chromatographic time-of-flight mass spectrometric (LC/TOF-MS) method, the response was shown to be caused by very high levels of diethylstilbestrol, known for causing gynaecomastia. The gynaecomastia was most probably caused by this orally taken 'natural' herbal supplement, as the patient's hormonal levels also returned to normal again when stopping the use of it. This case demonstrates that physicians need to be aware of the use of supplements with illegal components that may be responsible for unwanted side-effects.

Recurrent pericardial effusion with a common clinical disorder.

We present a case of recurrent pericardial effusion in a patient with Down's syndrome in whom the underlying cause was not considered because of unfamiliarity with the care of people with Down's syndrome. The diagnosis hypothyroidism only became apparent by means of a routine panel of biochemical tests.

Established risk factors for coronary heart disease are unrelated to androgen-induced baldness in female-to-male transsexuals.

A high scalp sensitivity to androgens is part of the pathophysiology of male-pattern baldness (MPB). Androgens affect established risk factors for coronary heart disease (CHD), and a supposedly heightened impact on these risk factors is hypothesized to explain the epidemiological association between MPB and CHD. In this retrospective, observational study we studied 81 female-to-male transsexual (F-->M) subjects, mean age 36.7 years (range 21-61), treated with testosterone esters (n=61; 250 mg i.m./2 weeks) or testosterone undecanoate (n=20; 160-240 mg/day orally). The degree of MPB was self-assessed using a 5-point scale (i.e. type I (no hair loss) to type V (complete hair loss)). Body mass index, blood pressure and levels of lipid and insulin were retrospectively assessed at the start of testosterone administration (0.5-24 years before) and between 3 and 4 months of follow-up. We found that 31 of 81 (38.3%) F-->M transsexuals had MPB type II-V. Thinning of hair was related to the duration of androgen administration and present in about 50% of F-->M transsexuals after 13 years. None of the CHD risk factors at follow-up, nor proportional changes, was associated with the degree MPB, except that there was an unexpected tendency of lower fasting glucose levels in balding subjects. Therefore, our findings do not support the idea that MPB serves as an indicator of increased CHD risk through androgenic effects on classic CHD risk factors.

Venous thrombosis and changes of hemostatic variables during cross-sex hormone treatment in transsexual people.

The incidence of venous thrombosis associated with estrogen treatment in male-to-female (M-->F) transsexuals is considerably higher with administration of oral ethinyl estradiol (EE) than with transdermal (td) 17-beta-estradiol (E(2)). To find an explanation for the different thrombotic risks of oral EE and td E(2) use, we compared the effects of treatment of M-->F transsexuals with cyproterone acetate (CPA) only, and with CPA in combination with td E(2), oral EE, or oral E(2) on a number of hemostatic variables [activated protein C (APC) resistance and plasma levels of protein S, protein C, and prothombin], all of which are documented risk factors for venous thrombosis. APC resistance was determined by quantification of the effect of APC on the amount of thrombin generated during tissue factor-initiated coagulation; plasma levels of total and free protein S were determined by standard ELISA; and levels of prothrombin and protein C were determined with functional assays after complete activation of the zymogens with specific snake venom proteases. CPA-only, td-E(2)+CPA, or oral-E(2)+CPA treatment produced rather small effects on hemostatic variables, whereas oral EE treatment resulted in a large increase in APC resistance from 1.2 +/- 0.8 to 4.1 +/- 1 (P < 0.001), a moderate increase in plasma protein C (9%; P = 0.012), and a large decrease in both total and free plasma protein S (30%; P < 0.005). The large differential effect of oral EE and oral E(2) indicates that the prothrombotic effect of EE is due to its molecular structure rather than to a first-pass liver effect (which they share). Moreover, these differences may explain why M-->F transsexuals treated with oral EE are exposed to a higher thrombotic risk than transsexuals treated with td E(2). Testosterone administration to female-to-male transsexuals had an antithrombotic effect.

Emergency resection of an extra-adrenal phaeochromocytoma: wrong or right? A case report and a review of literature.

Phaeochromocytomas are rare neuroendocrine tumours that produce symptoms through excess release of catecholamines. Treatment of choice is elective, complete surgical removal after pretreatment with alpha-adrenergic blocking drugs, to prevent dangerous haemodynamic fluctuations. In rare cases a 'catecholamine crisis' develops presenting with pulmonary oedema and circulatory shock. We report such a case of a patient with familial extra-adrenal phaeochromocytoma who successfully underwent emergency surgery. Pathophysiological mechanisms are discussed. Although pretreatment with alpha-adrenergic blocking drugs seems advisable in terms of morbidity and mortality, the concept is based on theory rather than clinical evidence. Surgical management of a catecholamine crisis is associated with high mortality rates. However, proof of better outcome by avoidance or discontinuation of emergency surgery is not available. Based on literature and on this case, we conclude that emergency surgery in phaeochromocytoma does not have to be structurally avoided and may be considered under life-threatening circumstances.

Significance of oestrogens in male (patho)physiology.

Traditionally conceptualized as 'female hormones', oestrogens appear to have significant effects in the male biological system. Favorable effects have been noted on bone, brain and cardiovascular physiology while a potential role in the prostate pathology of the aging male has been seriously suspected. Oestrogens in male are predominantly the products of peripheral aromatization of testicular and adrenal androgens. While the testicular and adrenal production of androgens declines with aging, levels of total plasma oestradiol do not decline. This is to be ascribed to the common increase in fat mass with aging (the substrate of peripheral aromatization) and an increased aromatase activity with aging. But free or bioavailable oestrogens may decline due to an increase in sex hormone binding globulin. Oestrogens produce significant beneficial effects on skeletal growth and bone maturation. In old age oestrogens are better predictors of bone fractures than androgens. Oestrogens exert effects on the brain: on cognitive function, co-ordination of movement, pain and affective state, and are maybe protective of Alzheimer's disease. Oestrogen effects on the cardiovascular system include those on lipid profiles, fat distribution, endocrine/paracrine factors produced by the vascular wall (such as endothelins, nitric oxide), blood platelets, inflammatory factors and coagulation. The potentially adverse effects of oestrogens on the prostate may be due to a shift in the oestrogen / androgen ratio with aging. Sources of estrogens in men are endogenous androgens, or in case of androgen deficiency, exogenous androgens. Dietary phytoestrogens or selective estrogen receptor modulators, as drugs, may be significant as well.