The role of long-acting parenteral testosterone undecanoate compound in the induction of secondary sexual characteristics in males with hypogonadotropic hypogonadism.

INTRODUCTION: Androgens are able to induce the development of secondary sexual characteristics in male patients suffering from hypogonadism. So far, the most common method of administering testosterone to induce puberty in these patients has been via the injection of testosterone ester formulations. Moreover, some evidence has showed that the length of polymorphism Cytosine-Adenine-Guanine (CAG) trinucleotide repeats present in androgen receptor (AR) gene might co-regulate the effectiveness of testosterone therapy. AIM: The aim of this study is to evaluate the effectiveness of a long-acting injectable testosterone undecanoate (TU) formulation for the induction of secondary sexual characteristics in young males with hypogonadotropic hypogonadism (HH). MAIN OUTCOME MEASURES: We studied the different stages of puberty development that occur progressively according to the continuous increase in serum testosterone levels and, secondly, whether these changes might be modulated by the length of CAG repeats. METHODS: Nine male subjects over the age of 17 that had not undergone pubertal development because of HH were enrolled in this study and compared with 15 control males. Of these patients, 6/9 suffered from idiopathic HH and 3/9 experienced hypogonadism related to ß-thalassemia (BT). All patients underwent a clinical examination and a determination of follicle-stimulating hormone, luteinizing hormone, sex hormone binding globulin (SHBG), and total testosterone (T) serum levels; the free fraction (FT) and biologically active fraction of testosterone were also determined. The number of CAG triplets present in the AR gene was obtained for each patient. For treatment, HH patients received an oral TU (Andriol, 120 mg/day) for 3 months, followed by intramuscular injection of parenteral TU (Nebid, 1,000 mg) every 14 weeks for 1 year, then every 12 weeks for a second year. Serum T and SHBG levels were assayed 3 months after the start of oral TU treatment and also in the 10th week following the start of the second round of intramuscular TU injections (e.g., the eighth month). Levels were also determined 12, 18, and 24 months after the start of the parenteral TU treatments. RESULTS: Serum levels of T, SHBG, FT, and BT increased in all of the patients receiving oral TU and parental TU treatments, and this was accompanied by a development of secondary sexual characteristics. For treated patients with >24 CAG triples vs. the HH subjects with ≤24 CAG triplets, a slight delay in the appearance of the most advanced phases of puberty and a slightly reduced final penis length were observed, suggesting that AR CAG polymorphism might co-regulate the effectiveness of T treatment. CONCLUSIONS: Long-acting parental TU was able to induce the puberty in our group of HH patients, even though additional studies are needed to elucidate the possible role of CAG repeats' length for the development of secondary sexual characteristics in young men with HH.

Covid-19 in Man: A Very Dangerous Affair.

The novel pandemic of Coronavirus disease 2019 (COVID-19) has become a public health issue since March 2020, with more than 30 million people found to be infected worldwide. Men may be considered to be at a higher risk of poor prognosis or death once the infection occurred. Concerns surfaced regarding the risk of a possible testicular injury due to SARS-CoV-2 infection. Several data support the existence of a bivalent role of testosterone (T) in driving poor prognosis in patients with COVID-19. On the one hand, this is attributable to the fact that T may facilitate SARS-CoV-2 entry in human cells by means of an enhanced expression of transmembrane serine-protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2). At the same time, a younger man with normal testicular function compared to a woman of similar age is prone to develop a blunted immune response against SARS-CoV-2, being exposed to less viral clearance and more viral shedding and systemic spread of the disease. Conversely, low levels of serum T observed in hypogonadal men predispose them to a greater background systemic inflammation, cardiovascular and metabolic diseases, and immune system dysfunction, hence driving harmful consequences once SARS-CoV-2 infection occurred. Finally, SARS-CoV-2, as a systemic disease, may also affect testicles with possible concerns for current and future testicular efficiency. Preliminary data suggested that the SARS-CoV-2 genome is not normally found in gonads and gametes. Therefore, transmission through sex could be excluded as a possible way to spread the COVID-19. Most data support a role of T as a bivalent risk factor for poor prognosis (high/normal in younger; lower in elderly) in COVID-19. However, the impact of medical treatment aimed to modify T homeostasis for improving the prognosis of affected patients is unknown in this clinical setting. In addition, testicular damage may be a harmful consequence of the infection, even if it occurred asymptomatically. Still, no long-term evidence is currently available to confirm and quantify this phenomenon. Different authors excluded the presence of SARS-CoV-2 in sperm and oocytes, thus limiting worries about both a potential sexual and gamete-to-embryos transmission of COVID-19. Despite these evidence, long-term and well-designed studies are needed to clarify these issues.

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

BACKGROUND: 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. OBJECTIVE: To overview on possible mechanisms by which serum T levels could affect the progression of COVID-19 in men. METHODS: Authors searched PubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library, Google, and institutional websites for medical subject headings terms and free text words referred to "SARS-CoV-2," "COVID-19," "testosterone," "male hypogonadism," "gender" "immune system," "obesity," "thrombosis" until May 19th 2020. RESULTS: T, co-regulating the expression of angiotensin-converting enzyme 2 and transmembrane protease serine 2 in host cells, may facilitate SARS-CoV-2 internalization. Instead, low serum T levels may predispose to endothelial dysfunction, thrombosis and defective immune response, leading to both impaired viral clearance and systemic inflammation. Obesity, one of the leading causes of severe prognosis in infected patients, is strictly associated with functional hypogonadism, and may consistently strengthen the aforementioned alterations, ultimately predisposing to serious respiratory and systemic consequences. DISCUSSION AND CONCLUSION: T in comparison to estrogen may predispose men to a widespread COVID-19 infection. Low serum levels of T, which should be supposed to characterize the hormonal milieu in seriously ill individuals, may predispose men, especially elderly men, to poor prognosis or death. Further studies are needed to confirm these pathophysiological assumptions and to promptly identify adequate therapeutic strategies.

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.

Brain Angiotensinergic Regulation of the Immune System: Implications for Cardiovascular and Neuroendocrine Responses.

OBJECTIVE: The Renin-Angiotensin-Aldosterone System (RAAS) plays a major role in the regulation of cardiovascular functions, water and electrolytic balance, and hormonal responses. We perform a review of the literature, aiming at providing the current concepts regarding the angiotensin interaction with the immune system in the brain and the related implications for cardiovascular and neuroendocrine responses. METHODS: Appropriate keywords and MeSH terms were identified and searched in Pubmed. Finally, references of original articles and reviews were examined. RESULTS: Angiotensin II (ANG II), beside stimulating aldosterone, vasopressin and CRH-ACTH release, sodium and water retention, thirst, and sympathetic nerve activity, exerts its effects on the immune system via the Angiotensin Type 1 Receptor (AT 1R) that is located in the brain, pituitary, adrenal gland, and kidney. Several actions are triggered by the binding of circulating ANG II to AT 1R into the circumventricular organs that lack the Blood-Brain-Barrier (BBB). Furthermore, the BBB becomes permeable during chronic hypertension thereby ANG II may also access brain nuclei controlling cardiovascular functions. Subfornical organ, organum vasculosum lamina terminalis, area postrema, paraventricular nucleus, septal nuclei, amygdala, nucleus of the solitary tract and retroventral lateral medulla oblongata are the brain structures that mediate the actions of ANG II since they are provided with a high concentration of AT 1R. ANG II induces also T-lymphocyte activation and vascular infiltration of leukocytes and, moreover, oxidative stress stimulating inflammatory responses via inhibition of endothelial progenitor cells and stimulation of inflammatory and microglial cells facilitating the development of hypertension. CONCLUSION: Besides the well-known mechanisms by which RAAS activation can lead to the development of hypertension, the interactions between ANG II and the immune system at the brain level can play a significant role.

Metformin: Up to Date.

BACKGROUND: Metformin is an oral hypoglycemic agent extensively used as first-line therapy for type 2 diabetes. It improves hyperglycemia by suppressing hepatic glucose production and increasing glucose uptake in muscles. Metformin improves insulin sensitivity and shows a beneficial effect on weight control. Besides its metabolic positive effects, Metformin has direct effects on inflammation and can have immunomodulatory and antineoplastic properties. AIM: The aim of this narrative review was to summarize the up-to-date evidence from the current literature about the metabolic and non-metabolic effects of Metformin. METHODS: We reviewed the current literature dealing with different effects and properties of Metformin and current recommendations about the use of this drug. We identified keywords and MeSH terms in Pubmed and the terms Metformin and type 2 diabetes, type 1 diabetes, pregnancy, heart failure, PCOS, etc, were searched, selecting only significant original articles and review in English, in particular of the last five years. CONCLUSION: Even if many new effective hypoglycemic agents have been launched in the market in the last few years, Metformin would always keep a place in the treatment of type 2 diabetes and its comorbidities because of its multiple positive effects and low cost.

Thyroid Disorders and Prognosis in Chronic Heart Failure: A Long-Term Follow-Up Study.

BACKGROUND: Thyroid disorders may have a negative impact on the prognosis of patients affected by chronic heart failure (CHF). OBJECTIVE: The aim of the current study was to evaluate the prognostic role of all thyroid disorders over a long term follow-up in a single centre large sample of CHF outpatients. METHODS: In all patients, the function of the thyroid was evaluated at the enrolment and during the follow- up. On the basis of free triiodothyronine (T3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) serum levels, patients were classified into one of the following four categories: euthyroid subjects, patients affected by hypothyroidism, low T3 (LT3) syndrome and hyperthyroidism. During the follow-up, death for all causes was assessed as primary end-point, whereas time to the first hospitalization for heart failure worsening was the secondary end-point analyzed. RESULTS: Among 762 patients, 190 patients were affected by hypothyroidism (Hypo). LT3 syndrome was diagnosed in 15 patients and 59 patients were affected by hyperthyroidism (Hyper). During a long term follow-up (5.1±3.7 years), 303 patients died. Patients with Hypo showed an increased risk of death as well as of hospitalization due to heart failure worsening at univariate regression analysis. At multivariate regression analysis, Hypo remained associated with hospitalization after correction for age >75 years, ischemic aetiology, diabetes, therapy with ACE-inhibitors or ARBs, therapy with betablockers and with aldosterone antagonists, NYHA class 3, systolic arterial pressure <95 mmHg, left ventricular ejection fraction <30%, estimated glomerular filtration rate <60 ml/min, hyponatremia and NTproBNP> 1000 pg/ml. At multivariate analysis, the independent association with death was significant only for the subgroup of patients with TSH >10 mIU/L. LT3 was independently associated with both heart failure hospitalization and death, whereas Hyper was not associated with any of the two considered end-points. CONCLUSION: Hypo is associated with a worse prognosis over a long-term follow-up. The association with heart failure hospitalization is not dependent on the baseline TSH levels, whereas the association with death is significant only when TSH >10 mIU/L. Finally, Hyper does not have any association with a worse prognosis.

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.

Vasopressin in Heart Failure.

BACKGROUND AND OBJECTIVE: The nonapeptide hypothalamic hormone vasopressin (VP), exerts important effects on cardiovascular system via its receptors V1, V2 and V3. Patients with congestive heart failure (CHF) present elevated plasma VP levels. Aim of this paper is to review the role of vasopressin in CHF. METHODS: We analyzed the best of published literature dealing with the role of VP in patients affected by CHF, identifying keywords and MeSH terms in Pubmed and then searching them. The last search was performed on August 2017. RESULTS: Scientific articles dealing with the relationship between VP and CHF show that circulating high VP levels found in CHF despite an exaggerated increase in circulatory blood volume can contribute to CHF exacerbation. In particular, the stimulation of V1R induces vascular constriction responsible for increased systemic vascular resistance and afterload, and, in addition, coronary vasoconstriction with consequent reduced coronary circulation and cardiac contractility, whereas the stimulation of V2R induces free water reabsorption and this is responsible of preload increase and congestion of pulmonary vascular bed with edema and hyponatremia, markers of advanced CHF. CONCLUSION: VP can play an important role among the derangements of the endocrine system in CHF even being a possible target in the treatment of this condition. Vaptans, antagonists of VP receptors, in fact, are able to increase urine output and plasma sodium levels without the increased risk of arrhythmic death induced by diuretics, even though, further studies are needed to establish a possible role of these drugs in the treatment of CHF.

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

BACKGROUND AND OBJECTIVE: 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. METHODS: Original articles published from 1991 to 2015 were searched on Medline (Pubmed). Among an overall number of 181 potentially suitable studies, 24 fulfilled the selection criteria and were included in the analysis. Data aggregation was carried out through the calculation of the absolute risk reduction. The meta-analysis was then conducted by means of a fixed-effects model, according to the heterogeneity test (Chi-square statistic). RESULTS: Fat-free mass (FFM) increase and fat mass (FM) reduction were found, together with a C-LDL reduction, a wide variation in glycaemia and a neutral effect on glycated haemoglobin (HbA1c) and blood pressure. These effects were valid both for isolated GHD patients and for those with compensated panhypopituitarism. The global outcome D showed a nonsignificant reduction of the overall cardiovascular risk (0.53; 95% C.I. -1.23, 2.85). CONCLUSION: Our meta-analysis shows no signnificatly positive trend in cardiovascular risk after both short and long-term GH supplementation therapy in adult GHD patients. However, a reduction of LDL cholesterol levels has been found. No differences were found between isolated GHD participants and those affected by panhypopituitarism well compensated since at least 3 months.

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.

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 &quot;Istituto Tumori Giovanni Paolo II&quot; 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.

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 particular, 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 deficiency 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.

Hypopituitarism in Neurocritical Patients: A Case Report.

BACKGROUND: Besides changes in pituitary hormones secretion observed during the acute phase of stroke as an adaptive response to injury or an effect of drugs, a true hypopituitarism due to ischemic and/or hemorrhagic damage at the hypothalamus and/or pituitary gland can develop after a stroke. CASE REPORT: We report a case of a 72-year-old woman showing clinical signs and laboratory data suggesting a secondary adrenal insufficiency following a recent acute brain ischemia. Cortisone therapy significantly improved this pituitary dysfunction. CONCLUSIONS: Clinicians must pay attention to the hypothalamic-pituitary axis in neurocritical patients because hormonal replacement therapy may be life-saving.

THERAPY OF ENDOCRINE DISEASE: Testosterone supplementation and body composition: results from a meta-analysis study.

OBJECTIVE: The role of testosterone (T) in regulating body composition is conflicting. Thus, our goal is to meta-analyse the effects of T supplementation (TS) on body composition and metabolic outcomes. METHODS: All randomized controlled trials (RCTs) comparing the effect of TS on different endpoints were considered. RESULTS: Overall, 59 trials were included in the study enrolling 3029 and 2049 patients in TS and control groups respectively. TS was associated with any significant modification in body weight, waist circumference and BMI. Conversely, TS was associated with a significant reduction in fat and with an increase in lean mass as well as with a reduction of fasting glycaemia and insulin resistance. The effect on fasting glycaemia was even higher in younger individuals and in those with metabolic diseases. When only RCTs enrolling hypogonadal (total T <12  mol/l) subjects were considered, a reduction of total cholesterol as well as triglyceride (TGs) levels were also detected. Conversely, an improvement in HDL cholesterol levels as well as in both systolic and diastolic blood pressure was not observed. CONCLUSION: Our data suggest that TS is able to improve body composition and glycometabolic profile particularly in younger subjects and in those with metabolic disturbances. Specifically designed studies are urgently needed to confirm this point.

Comparative assessment in young and elderly men of the gonadotropin response to aromatase inhibition.

CONTEXT: Aging in men is associated with a decline in serum testosterone (T) levels. OBJECTIVE: Our objective was to assess whether decreased T in aging might result from increased estradiol (E2) negative feedback on gonadotropin secretion. DESIGN AND SETTING: We conducted a comparative intervention study (2004) in the Outpatient Endocrinology Clinic, Ghent University Hospital. PARTICIPANTS: Participants included healthy young and elderly men (n = 10 vs. 10). INTERVENTIONS: We used placebo and letrozole (2.5 mg/d) for 28 d, separated by 2 wk washout. MAIN OUTCOME MEASURES: We assessed changes in serum levels of free E2, LH, and FSH, free T, SHBG, and gonadotropins response to an i.v. 2.5-microg GnRH bolus. RESULTS: As assessed after 28 d of treatment, letrozole lowered E2 by 46% in the young men (P = 0.002) and 62% in the elderly men (P < 0.001). In both age groups, letrozole, but not placebo, significantly increased LH levels (339 and 323% in the young and the elderly, respectively) and T (146 and 99%, respectively) (P value of young vs. elderly was not significant). Under letrozole, peak LH response to GnRH was 152 and 52% increase from baseline in young and older men, respectively (P = 0.01). CONCLUSIONS: Aromatase inhibition markedly increased basal LH and T levels and the LH response to GnRH in both young and elderly men. The observation of similar to greater LH responses in the young compared with the elderly does not support the hypothesis that increased restraining of LH secretion by endogenous estrogens is instrumental in age-related decline of Leydig cell function.

Sevelamer carbonate markedly reduces levothyroxine absorption.

We report the case of a young woman affected by hypothyroidism due to Hashimoto's thyroiditis, previously well compensated with a full replacement therapy (150 mcg/day of levothyroxine), presenting a clinical picture of myxedema, with a TSH=650 mU/L. Two years earlier she had started a dialysis treatment because of a chronic renal failure and had been under treatment for the last 18 months with sevelamer carbonate, a phosphate binder. No improvement of clinical conditions nor reduction in TSH serum levels was observed even on increasing the dose of levothyroxine up to 300 mcg/day, whereas euthyroidism finally restored by administering the first morning dose of sevelamer carbonate at least 4 hours after levothyroxine administration. This case shows that sevelamer carbonate, in analogy with what has been already reported for sevelamer hydrochloride, can interfere with levothyroxine absorption leading to a condition of hypothyroidism in patients previously well compensated with a given replacement dose.

Amiodarone-induced SIADH: two cases report.

Amiodarone-induced SIADH is a rare but serious side effect of this drug. We report two cases of mild hyponatremia, observed in the last five years, and discuss the role played by age, sex and dose of amiodarone as well as the influence that this molecule may have on aquaporin-2 water channel expression in the renal collecting ducts.

Dehydroepiandrosterone supplementation in elderly men: a meta-analysis study of placebo-controlled trials.

CONTEXT: Age-related dehydroepiandrosterone (DHEA) deficiency has been associated with a broad range of biological abnormalities in males. OBJECT: Our objective was to meta-analyze all double-blind, placebo-controlled randomized trials (RCTs) investigating the effect of oral DHEA (DHEA supplementation) in comparison with placebo on sexual and metabolic outcomes in elderly men. DATA SOURCE: An extensive Medline Embase and Cochrane search was performed including the following words: DHEA, RCTs, and males. STUDY SELECTION: Only double-blind placebo-controlled trials performed in elderly men were included. DATA EXTRACTION: Data extraction was performed independently by 2 of the authors (A.S. and V.G.), and conflicts were resolved by the third investigator (G.C.). The quality of RCTs was assessed using the Cochrane criteria. RESULTS: Of 220 retrieved articles, 25 were included in the study. The available RCTs enrolled 1353 elderly men, with a mean follow-up of 36 weeks. DHEA supplementation was associated with a reduction of fat mass (standardized mean difference of -0.35 [-0.65 to -0.05]; P = .02). However, the association with fat mass disappeared in a multivariate regression model after adjusting for DHEA-related metabolite increases such as total testosterone and estradiol. In contrast to what was observed for fat mass, no effect of DHEA supplementation in comparison with placebo was observed for various clinical parameters including lipid and glycemic metabolism, bone health, sexual function, and quality of life. CONCLUSIONS: The present meta-analysis of intervention studies shows that DHEA supplementation in elderly men can induce a small but significant positive effect on body composition that is strictly dependent on DHEA conversion into its bioactive metabolites such as androgens or estrogens.

Parathyroid hormone determination in ultrasound-guided fine needle aspirates allows the differentiation between thyroid and parathyroid lesions: our experience and review of the literature.

In many cases, it is difficult or even impossible to distinguish parathyroid lesions from thyroid ones at ultrasound as well as at scintiscan and even at cytology, because they often share common features. The aim of this study was to evaluate the role of Parathyroid Hormone (PTH) determination in the aspirates in the differential diagnosis of parathyroid from thyroid lesions in an area of mild iodine deficiency and high prevalence of thyroid nodules. Forty-six consecutive patients were suspected to have one or more nodule(s) of parathyroid origin because of their position in the posterior aspect of thyroid lobes and/or their shape and echo-pattern at ultrasound examination. In 13 cases, there were also laboratory findings suggestive for primary hyperparathyroidism, with clinical evidence in 6 of these patients. A total of 55 lesions suspected to be of parathyroid origin were selected. After obtaining cytological preparations, the needle used to perform the fine-needle aspirate (FNA) was washed using 1 ml of normal saline. Intact PTH determination in the washout was done whereas the evaluation was performed directly in the aspirated fluid in case of cystic lesions. The values of PTH in the aspirates ranged from 6.7 to 16640 pg/ml. Sixteen patients underwent surgical intervention and the histological examination of the 23 operated lesions previously submitted to FNA-PTH showed 11 parathyroid adenomas, 5 hyperplasic parathyroid lesions and 7 benign thyroid nodules. A strong positive correlation between high levels of PTH in the aspirate and the histological findings of parathyroid lesions was found. A value over 245 pg/ml was constantly associated to the parathyroid lesions. Our results confirmed the high accuracy of FNA-PTH determination in differentiating parathyroid lesions from thyroid nodules and this is of special value in an area of mild iodine deficiency with a high prevalence of thyroid nodules.