Serum Testosterone and Cognitive Function in Ageing Male: Updating the Evidence.

Background: Testosterone (T) deficit, either in prepubertal or postpubertal form of hypogonadism, seems to play a key role in impairing cognitive function, including memory, attention, language and visuospatial abilities, especially in elderly men. Objective: Several studies have recently showed the association between low serum T levels and important cognitive dysfunctions in ageing male as well as in subjects suffering from Alzheimer’s disease (AD), mild cognitive impairment (MCI) and even depression, suggesting that T could exert an active neuroprotective role. Methods: By searching PubMed and recent patents (ranging from 2010 to 2015), we identified several observational and intervention studies dealing with T and cognitive function in adult and ageing men. Findings were reviewed, thoroughly examined and, finally, summarized herein. Results: Although a large number of studies have been carried out so far, conclusive evidence cannot be drawn, in par-ticular, for cognitive disorders in males. Conversely, T supplementation has been suggested for depressive syndrome in young and ageing men. To date, no clinical data have been carried out on cognitive dysfunctions employing the quoted patents in men. Conclusions: Studies aiming to evaluate the role of serum T and its supplementation in adult and ageing men with T defi-ciency syndrome need to be encouraged, given that subjects affected by overt hypogonadism, either in prepubertal (i.e. Klinefelter syndrome) or postpubertal forms (chemical castration in subjects affected by prostate cancer), often complain of cognitive dysfunction, and seem to considerably benefit from T replacement therapy

Thyroid function in Klinefelter syndrome: a multi center study from KING group

Purpose The prevalence and the etiopathogenesis of thyroid dysfunctions in Klinefelter syndrome (KS) are still unclear. The primary aim of this study was to evaluate the pathogenetic role of hypogonadism in the thyroid disorders described in KS, with the scope to distinguish between patients with KS and hypogonadism due to other causes (Kallmann syndrome, idiopathic hypogonadotropic hypogonadism, iatrogenic hypogonadism and acquired hypogonadotropic hypogonadism after surgical removal of pituitary adenomas) called non-KS. Therefore, we evaluated thyroid function in KS and in non-KS hypogonadal patients. Methods This is a case\u2013control multicentre study from KING group: Endocrinology clinics in university-affiliated medical centres. One hundred and seventy four KS, and sixty-two non-KS hypogonadal men were enrolled. The primary outcome was the prevalence of thyroid diseases in KS and in non-KS. Changes in hormonal parameters were evaluated. Exclusion criterion was secondary hypothyroidism. Analyses were performed using Student\u2019s t test. Mann\u2013Whitney test and Chi-square test. Results FT4 was significantly lower in KS vs non-KS. KS and non-KS presented similar TSH and testosterone levels. Hashimoto\u2019s thyroiditis (HT) was diagnosed in 7% of KS. Five KS developed hypothyroidism. The ratio FT3/FT4 was similar in both groups. TSH index was 1.9 in KS and 2.3 in non-KS. Adjustment for differences in age, sample size and concomitant disease in multivariate models did not alter the results. Conclusions We demonstrated in KS no etiopathogenic link to hypogonadism or change in the set point of thyrotrophic control in the altered FT4 production. The prevalence of HT in KS was similar to normal male population, showing absence of increased risk of HT associated with the XXY karyotype

Is There Room for SERMs or SARMs as Alternative Therapies for Adult Male Hypogonadism?

Hypogonadotropic hypogonadism (HH) can be sustained by organic or functional alterations of the hypothalamic-pituitary-testicular axis. Functional HH is related to systemic alterations, such as obesity or chronic inflammatory diseases, but could contribute to a negative course of the illness. For such situation, according to results obtained in infertile women, the administration of selective estrogen receptor modulators (SERMs) has been proposed in males too, with positive results on both metabolic and sexual function. This class of medications increases gonadotropin levels via antagonism to the estrogenic receptor; similar biological effects are also exerted by aromatase inhibitors (AIs), despite different mechanism of action. After a brief review of trials regarding SERMs and AIs use in male HH, we describe the structure and function of the androgen receptor (AR) as a basis for clinical research about compounds able to bind to AR, in order to obtain specific effects (SARMs). The tissue selectivity and different metabolic fate in comparison to testosterone can potentiate anabolic versus androgenic effects; therefore, they might be a valid alternative to testosterone replacement therapy avoiding the negative effects of testosterone (i.e., on prostate, liver, and hematopoiesis). Trials are still at an early phase of investigation and, at the moment, the application seems to be more useful for chronic disease with catabolic status while the validation as replacement for hypogonadism requires further studies

GH Supplementation Effects on Cardiovascular Risk in GH Deficient Adult Patients: A Systematic Review and Meta-analysis

The current meta-analysis aims at evaluating whether the existing clinical evidence may ascertain the effects of growth hormone (GH) replacement therapy on cardiovascular risk, both in isolated GH deficiency (GHD) and in compensated panhypopituitarism including GH deficit

New Frontiers in the Therapeutic Approach of Patients with Cardiovascular and Endocrine Diseases

Background and Objective: Cardiovascular disease is the most important cause of morbidity and mortality worldwide, with a significant economic burden. which is expected to increase in the next years. Alongside the management of cardiac manifestations and major risk factors for atherosclerosis, great attention has been paid to the role of comorbidities in initiating and worsening cardiac conditions.Discussion: The cardiovascular impact of a broad spectrum of endocrine disorders has been evaluated, with particular regard to their effects on cardiac function and cardiovascular prognosis in affected patients. Among the different endocrine conditions considered, the association between subclinical hypothyroidism and cardiovascular events is still uncertain. A number of observational studies have linked subclinical hypothyroidism (in particular severe elevation of TSH levels) with incident cardiovascular disease and poor prognosis, however thyroid replacement therapy is still controversial, especially in the elderly, due to the lack of evidence coming from randomized controlled trials. With regards to testosterone deficiency, even though it has been associated with metabolic abnormalities and poor prognosis in patients affected by cardiovascular diseases, the cardiac safety of replacement therapy has still to be completely clarified. Similarly, growth hormone deficiency showed detrimental effects on cardiovascular events and risk factors which seem to be reverted by replacement therapy, even if unequivocal evidence from randomized clinical trials is still lacking Another relevant chapter in cardiovascular disease management is about the cardiovascular outcomes of diabetes medical treatments. In recent years, a growing interest has been developed around the cardiovascular safety of antidiabetic medications which has led to a great number of publications addressing this issue for the different classes of antidiabetic drugs. Interestingly, the recently approved classes, i.e. incretins and SGLT-2 inhibitors, have additionally demonstrated a protective effect against major cardiovascular events, shedding new light on the management of diabetes in patients affected by cardiovascular disease.Conclusion: Important controversies still exist regarding the cardiac implications of the therapies adopted in endocrine diseases. Owing the large prevalence of these conditions, particularly in the cardiovascular population, further research is awaited in order to clarify the potential advantage and the possible cardiac risk related to treatment of the endocrine comorbidities

Worse progression of COVID-19 in men: Is testosterone a key factor?

The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease 2019 (COVID-19) seems to have a worse clinical course among infected men compared with women, thus highlighting concerns about gender predisposition to serious prognosis. Therefore, androgens, particularly testosterone (T), could be suspected as playing a critical role in driving this excess of risk. However, gonadal function in critically ill men is actually unknown, mainly because serum T concentration is not routinely measured in clinical practice, even more in this clinical context

Thyroglobulin determination in fine needle aspiration biopsy washout of suspicious lymph nodes in thyroid carcinoma follow up

Background: Differentiated thyroid carcinomas (DTCs) account for about 1% of all human malignancies. Cervical lymph nodes metastases and recurrences in the thyroid bed frequently occur. Furthermore, about 10-15% of patients develop distant metastases. Therefore, patients must undergo life-long follow-up. Objective: The aim of this study was to evaluate the usefulness of Thyroglobulin measurement in FNAB washout (FNAB-Tg) in the detection of local metastasis in patients affected by or evaluated for thyroid cancer. Materials and Methods: In a 3-year period, a total of 83 consecutive patients coming to our attention at the Ear-Nose-Throat (ENT) Outpatients Service of the National Cancer Research Center "Istituto Tumori Giovanni Paolo II" of Bari, Italy, because of the finding of one or more cervical lymph node(s), were enrolled in the study. After collection of the cytological specimen, the needle used for performing FNAB was then washed in 1 ml of normal saline. 89 FNAB washouts were collected from the same number of lymph nodes and subsequently investigated for Thyroglobulin levels using a sequential chemiluminescent-immunometric assay. Results: Comparing the cytological or, when performed, histological diagnoses with the results of FNAB-Tg, we found that in 24 cases of lymph node metastases from PTC (19 lymph nodes from patients at the first diagnoses and 5 lymph nodes from PTC patients in follow up) the mean level of Thyroglobulin was 1840.11 ng/ml; range: <0,2 to 11440 ng/ml. In the group of PTC patients (27 lymph nodes) with lymph nodes negative for metastatic involvement at cytology (i.e. no lymph node recurrence at follow-up), as well as in the cases of subjects without PTC and submitted to FNAB because of the appearance of lymph node(s) classified as reactive at cytology (37 lymph nodes), FNAB-Tg was lower than or equal to 0.2 ng/ml. As expected, the Thyroglobulin level was not detectable (< 0.2 ng/ml) also in a lymph node FNAB from a case of anaplastic thyroid carcinoma. Conclusion: In our study, FNAB-Tg was not detectable in all node negative patients showing, when considering together all the lymph node metastases, a 96% sensitivity and 100% specificity

Independent relationship between serum osteocalcin and uric acid in a cohort of apparently healthy obese subjects

Background: It is generally accepted that serum osteocalcin (OC) is a reliable marker of bone formation, while the role of serum uric acid (UA) in bone metabolism is still debated. However, recent studies have shown that endogenous UA within the normal range may exert a positive effect in bone formation by means of its antioxidant role in both sexes. To date, no studies have been carried out in obese subjects aiming to study the relationship between serum OC and UA, given that obesity is considered as a risk factor for osteoporosis and fracture and, at the same time, for cardiovascular events. Objectives: Our search purpose was to verify the relationship between endogenous levels of OC and serum UA in a cohort of obese subjects without any metabolic or chronic diseases (i.e. hypertension, renal failure, diabetes mellitus, etc.). Materials and Methods: One hundred and twenty one obese subjects (93 women and 28 men) were enrolled for this study. Serum OC and UA were assessed and compared with demographic characteristics, clinical and biochemical parameters (age, body mass index (BMI), blood pressure, waist circumference, serum lipids and glycaemia). Results: Serum OC was directly and independently correlated with circulating UA in our population of obese subjects, while neither BMI, age, serum lipids, fasting glycaemia nor gender showed a statistically significant correlation with endogenous plasma levels of OC. Conclusion: The positive effect determined by serum OC in bone metabolism of our obese subjects might be partly due to the antioxidant properties that normal plasma UA levels exert at bone tissue level