High prevalence rate of pituitary incidentaloma: is it associated with the age-related decline of the sex hormones levels?

Incidental pituitary adenoma is the common finding during brain imaging. According to multistep model of pituitary tumourigenesis genetic alterations provide the initiating event that transforms cells while hormones play a role in promoting cell proliferation. Development of pituitary adenoma in a case of excessive hypophysiotrophic hormones production or reduced feedback suppression by target gland hormones emphasizes the importance of hormonal stimulation in pituitary tumourigenesis. Pituitary hyperplasia has been reported in pregnancy, hypothyroidism and conditions such as CRH or GHRH hypersecretion. Moreover, recent study reported one case of gonadotroph macroadenoma and two cases of gonadotroph cells hyperplasia in patients with Klinefelter syndrome probably due to protracted stimulation of gonadotroph cells because of lack of androgen feedback. Significant changes of the hypothalamic-pituitary-gonadal axis occurred with aging. In females, after menopause, estradiol level decreases by 35-fold and estrone level by 20-fold that results in increased gonadotropins levels. Similarly, FSH, but not LH, level is increased with advancing age in men, too, although the age-related difference in the level is less in comparison with women. Regarding these data, we hypothesised that high prevalence rate of pituitary incidentaloma in the elderly is associated with age-related decline in sex hormones levels and subsequent lack of feedback suppression leading to permanent gonadotrophs stimulation which is the crucial step in the pituitary tumour development. According to previously mentioned multistep model of pituitary tumourigenesis, incidentaloma will develop only in persons with already present intrinsic pituitary cell defects. However, further studies have to answer the questions of whether the incidence of pituitary tumours is more frequent in elderly, whether women with late onset menopause or those taking long-term hormone replacement therapy have lower rate of pituitary incidentaloma, and finally, is there any correlation between pituitary tumours incidence and serum concentrations of LH, FSH, bioavailable testosterone or estradiol

Selective estrogen receptor modulators: a possible new treatment of osteoporosis in males

More recently, osteoporosis in men has been recognized as an important public health problem. Bone loss begins in mid life and is associated with the decline of the sex steroids production. Although there is no equivalent of the menopause, gonadal function in men is affected in a slow progressive way leading to hypogonadism. Testosterone, the major androgen in men, exerts its effect on bone by local conversion to 5α-dihydrotestosterone or by aromatization to estrogens. Several studies have found that estrogen, rather than testosterone, levels are more closely correlated with BMD in elderly men. Selective estrogen receptor modulator (SERM) raloxifene binds to estrogen receptors and exhibit estrogenic effect in bone, but, contrary to estrogen, without feminizing effect. There are limited numbers of studies investigating the effects of SERMs in males. Animal studies demonstrated that SERMs inhibit bone turnover and prevent bone loss in orchidectomised adult male rats. Raloxifene has been shown to increase bone mineral density of the hip in men receiving androgen deprivation therapy for prostate cancer. Moreover, experimental data demonstrated dramatic increase in cell death in human prostate cancer cell lines after the treatment with raloxifene. All these observations suggest that SERMs may be useful for the prevention and treatment of osteoporosis not only in postmenopausal women but also in elderly men. However, our hypothesis should be tested in a proper designed clinical trial. Several important issues have to be addressed. Does the same drug dose that has been shown to be effective in postmenopausal women should be used in men, too? Does treatment with SERMs reduce the fracture risk in men and is it comparable to that observed in women? Does treatment with SERMs have any beneficial effect on cardiovascular system and prostate cancer? And finally, do men experience adverse events other than women treated with SERMs? Answering to these questions will have great impact in getting the decision of possible SERMs usage in the treatment of osteoporosis in elderly males

Possible association of psoriasis and reduced bone mineral density due to increased TNF-alpha and IL-6 concentrations

Psoriasis is a chronic erythematosquamous disease affecting about 2–3% of the population. It is generally considered to be a T cell-mediated disorder. Psoriasis is characterized by Th1-type cytokine pattern with the predominant secretion of IL-2, IL-6, IFN-γ and TNF-α. Such cytokine pattern is sufficient in inducing keratinocyte hyperproliferation, a hallmark of psoriasis. It seems that development of psoriatic lesions is mediated by TNF-α and proliferation of local T cells is dependent on local TNF-α production. IL-6 enhances activation, proliferation and chemotaxis of T cells into psoriatic lesions. It is also a direct keratinocyte mitogen that could directly stimulate keratinocyte proliferation. Data of possible association between psoriasis and reduced bone mineral density (BMD) are limited and therefore, not fully conclusive. The major limitation of two studies reported so far was small sample size. Based on increased concentrations of TNF-α and IL-6 in psoriasis we hypothesized that these patients are more prone to osteoporosis than healthy subjects. TNF-α enhances bone resorption via stimulating osteoclast development and activity as well as bone formation. On the other hand, IL-6 is also a potent stimulator of bone resorption. Moreover, increased production of TNF-α and IL-6 has been found in postmenopausal women with osteoporosis. Several lines of evidence support our hypothesis; higher value of IL-6 was recorded in children with idiopathic osteoporosis than in healthy controls; TNF-α knock-out mice do not lose bone after ovariectomy; polymorphism of TNFRSF1B gene which encodes 75Kd TNF receptor is associated with BMD; treatment with anti-TNF-α antibody exert beneficial effect on bone metabolism in patients with rheumatoid arthritis and finally, raloxifene inhibit osteoclast activity by reducing TNF-α and IL-6 synthesis. However, our hypothesis raised number of questions. Are increased serum concentrations of TNF-α and IL-6 mirrored by increased concentrations of these cytokines on the local level? Furthermore, could other cytokines relevant in the pathogenesis of the psoriasis, first of all IFN-γ, modulate the risk of osteoporosis? Thus, a large prospective, case-control study with the data on BMD, biochemical parameters of bone turnover and fractures have to be done to test our hypothesis

Hypercoagulability in Cushing's syndrome: the role of specific haemostatic and fibrinolytic markers

OBJECTIVE: Hypercoagulability is a commonly described complication in patients with Cushing's syndrome. Recent clinical studies have indicated various abnormalities of coagulation and fibrinolysis parameters which may be related to that phenomenon. The aim of this study was to investigate the mechanisms underlying the hypercoagulable state in patients with Cushing's syndrome. ----- RESEARCH METHODS AND PROCEDURES: A wide range of serum markers involved in the processes of blood coagulation and fibrinolysis was measured in a group of 33 patients with Cushing's syndrome and 31 healthy controls. No participant was taking medication which could influence the result or had known diseases, except hypertension and diabetes, which could affect blood coagulation or fibrinolysis parameters. ----- RESULTS: Patients with Cushing's syndrome had higher levels of clotting factors II (P = 0.003), V (P < 0.001), VIII (P < 0.001), IX (P < 0.001), XI (P < 0.001) and XII (P = 0.019), protein C (P < 0.001), protein S (P < 0.001), C1-inhibitor (P < 0.001) and plasminogen activator inhibitor-1 (PAI-1) (P = 0.004). The activity of fibrinolytic markers, plasminogen (P < 0.001), antithrombin (P < 0.001) and antithrombin antigen (P = 0.001) was also increased in the patient group. ----- CONCLUSION: The study has demonstrated hypercoagulability in patients with Cushing's syndrome manifest as increased prothrombotic activity and compensatory activation of the fibrinolytic system. We propose the introduction of thromboprophylaxis in the preoperative and early postoperative periods, combined with a close follow-up in order to prevent possible thromboembolic events in patients with Cushing's syndrome

Health-related quality of life among patients with postmenopausal osteoporosis treated with weekly and monthly bisphosphonates

OBJECTIVE: The present study was designed to assess the effect of monthly ibandronate on health-related quality of life (HR-QoL) in patients with postmenopausal osteoporosis previously treated with weekly bisphosphonates. ----- METHODS: HR-QoL was assessed by Euroqol (EQ-5D) and Osteoporosis Targeted Quality of Life (OPTQoL) questionnaires. ----- RESULTS: The EQ-5D questionnaire showed significant improvement associated with ibandronate treatment, occurring in mobility (p < 0.01), usual activity (p < 0.01), pain/discomfort (p < 0.05), and anxiety/depression (p < 0.05). In addition, ibandronate treatment considerably improved patients' perceived health on a visual analog scale (p < 0.001). For the OPTQoL questionnaire, patients reported less physical difficulty (p < 0.001), fewer adaptations in their lives (p < 0.001), and less fear (p < 0.001) with ibandronate than with weekly bisphosphonates. ----- CONCLUSION: The study demonstrated that patients who were transferred from weekly bisphosphonates to a monthly ibandronate experienced improved HR-QoL

Health-related quality of life and fatigue in patients with adrenal incidentaloma

The objective of the present study was to examine several dimensions of quality of life (QoL) and fatigue in patients with adrenal incidentaloma. This was a case-control study designed to analyze patient outcomes using three validated generic QoL questionnaires, EQ-5D, SF-36, and MFI-20, the results of which were compared to those obtained for age- and sex-matched controls. The study population comprised 139 consecutive patients with nonfunctioning adrenal masses (104 females, 35 males; age 59.1 ± 10.8) and 139 age- and sex-matched controls. Reduced QoL was found in patients with adrenal incidentaloma as compared to controls. Dimensions of QoL that were notably affected included mobility (P = 0.03), performance of usual activities (P = 0.002), and anxiety/depression (P = 0.04) as evaluated using the EQ-5D; physical functioning (P < 0.001), physical role (P < 0.001), general health (P < 0.001), vitality (P = 0.001), social functioning (P = 0.001), and emotional role (P < 0.001) as evaluated using the SF-36; and physical fatigue (P = 0.04) as assessed using the MFI-20 questionnaire. In addition, perceived health on a visual analogue scale was also significantly lower in patients than in controls (64.8 ± 19.2 vs. 77.1 ± 15.1; P < 0.001). Patients with adrenal incidentaloma reported reduced QoL and a higher level of physical fatigue compared to age- and sex-matched controls. This subject will benefit from further studies comparing QoL outcomes of laparoscopic adrenalectomy versus no treatment in patients with adrenal incidentaloma