Application of calcium-to-phosphorus (Ca/P) ratio in the diagnosis of pseudohypoparathyroidism: another piece in the puzzle of diagnosis of Ca-P metabolism disorders.

Objective: The serum calcium (Ca)-to-phosphorus (P) ratio has been proposed to identify patients with primary hyperparathyroidism and chronic hypoparathyroidism (HPT), but it has never been tested in pseudohypoparathyroidism (PHP). The aim of this study was to test the performance of Ca/P ratio in PHP diagnosis compared with that in healthy subjects and patients with HPT for differential diagnosis. Design: A retrospective, cross-sectional, and observational study was carried out. Methods: Serum Ca, P, creatinine, parathyroid hormone (PTH), and albumin were collected. Ca and P were expressed in mmol/L. Ca/P diagnostic performance was evaluated by receiver operating characteristic curve, sensitivity, specificity, and accuracy. Results: A total of 60 patients with PHP, 60 patients with HPT, and 120 controls were enrolled. The Ca/P ratio was lower in patients with PHP and HPT than that in controls (p < 0.0001). The cutoff of 1.78 (2.32 if Ca and P measured in mg/dL) for Ca/P ratio could identify patients with PHP and HPT among the entire cohort (sensitivity and specificity of 76%). No valid cutoff of Ca/P was found to distinguish patients with PHP from patients with HPT; in this case, PTH above 53.0 ng/dL identified patients with PHP (sensitivity and specificity of 100%). The index (Ca/P × PTH) above 116 ng/L recognized patients with PHP from controls (sensitivity of 84.7% and specificity of 87.4%), whereas (Ca/P × PTH) below 34 ng/L recognized patients with HPT from controls (sensitivity of 88.9% and specificity of 90.8%). Conclusions: The Ca/P ratio below 1.78 (2.32 CU) is highly accurate to identify patients with PHP and HPT, although it is not reliable to differentiate these two conditions. The index (Ca/P × PTH) is excellent to specifically recognize PHP or HPT from healthy subjects.

Labile plasma iron and echocardiographic parameters are associated with cardiac events in ß-thalassemic patients.

BACKGROUND AND AIM: Notwithstanding the improvement in therapies, patients affected by thalassemia major (TM) and intermedia (TI) are still at high risk of cardiac complications. This study aimed at evaluating the incidence and predictive factors for developing cardiac events in adult ß-TM and TI patients. POPULATION AND METHODS: Data on diagnosis and clinical history were collected retrospectively; prospective data on new-onset cardiac failure and arrhythmias, echocardiographic parameters, biochemical variables including non-transferrin-bound iron (NTBI) and labile plasma iron (LPI), magnetic resonance imaging (MRI) T2* measurement of hepatic and cardiac iron deposits, and iron chelation therapy were recorded during a 6-year follow-up. RESULTS: Thirty-seven patients, 29 TM and 8 TI, were included. At baseline, 8 TM patients and 1 TI patient had previously experienced a cardiac event (mainly heart failure). All patients were on chelation therapy and only 3 TM patients had mild-to-severe cardiac siderosis. During follow-up, 11 patients (29.7%) experienced a new cardiac event. The occurrence of cardiac events was correlated to high LPI levels (OR 12.0, 95% CI 1.56-92.3, p .017), low mean pre-transfusion haemoglobin (OR 0.21, 95% C.I. 0.051-0.761, p .21) and echocardiographic parameters suggestive of myocardial hypertrophy. Multivariate analysis disclosed high LPI and left ventricle mass index (LVMI) as independent variables significantly associated with cardiac events. Cardiac iron deposits measured by MRI T2* failed to predict cardiac events. CONCLUSION: LPI, Hb levels and echocardiographic parameters assessing cardiac remodelling are associated with cardiac events in adult TM and TI patients. LPI might represent both a prognostic marker and a potential target for novel treatment strategies. Further studies are warranted to confirm our findings on larger populations.

How Much Vitamin D is Too Much? A Case Report and Review of the Literature.

BACKGROUND: The beneficial effects of vitamin D, together with the high prevalence of vitamin D deficiency, have led to an expanding use of vitamin D analogues. While inappropriate consumption is a recognized cause of harm, the determination of doses at which vitamin D becomes toxic remains elusive. CASE PRESENTATION: A 56-year woman was admitted to our Hospital following a 3-week history of nausea, vomiting, and muscle weakness. The patient had been assuming a very high dose of cholecalciferol for 20 months (cumulative 78,000,000UI, mean daily 130,000UI), as indicated by a non-- conventional protocol for multiple sclerosis. Before starting vitamin D integration, serum calcium and phosphorus levels were normal, while 25OH-vitamin D levels were very low (12.25 nmol/L). On admission, hypercalcemia (3.23 mmol/L) and acute kidney injury (eGFR 20 mL/min) were detected, associated with high concentrations of 25OH-vitamin D (920 nmol/L), confirming the suspicion of vitamin D intoxication. Vitamin D integration was stopped, and in a week, hypercalcemia normalized. It took about 6 months for renal function and 18 months for vitamin D values to go back to normal. CONCLUSION: This case confirms that vitamin D intoxication is possible, albeit with a high dose. The doses used in clinical practice are far lower than these and, therefore, intoxication rarely occurs even in those individuals whose baseline vitamin D serum levels have never been assessed. Repeated measurements of vitamin D are not necessary for patients under standard integrative therapy. However, patients and clinicians should be aware of the potential dangers of vitamin D overdose.

Testosterone supplementation and sexual function: a meta-analysis study.

INTRODUCTION: The role of testosterone supplementation (TS) as a treatment for male sexual dysfunction remains questionable. AIM: The aim of this study was to attempt a meta-analysis on the effect of TS on male sexual function and its synergism with the use of phosphodiesterase type 5 inhibitor (PDE5i). METHODS: An extensive Medline, Embase, and Cochrane search was performed. MAIN OUTCOME MEASURES: All randomized controlled trials (RCTs) comparing the effect of TS vs. placebo or the effect of TS as add on to PDE5is on sexual function were included. Data extraction was performed independently by two of the authors (A. M. Isidori and G. Corona), and conflicts resolved by the third investigator (M. Maggi). RESULTS: Out of 1,702 retrieved articles, 41 were included in the study. In particular, 29 compared TS vs. placebo, whereas 12 trials evaluated the effect of TS as add on to PDE5is. TS is able to significantly ameliorate erectile function and to improve other aspects of male sexual response in hypogonadal patients. However, the presence of possible publication bias was detected. After applying "trim and fill" method, the positive effect of TS on erectile function and libido components retained significance only in RCTs partially or completely supported by pharmaceutical companies (confidence interval [0.04-0.53] and [0.12; 0.52], respectively). In addition, we also report that TS could be associated with an improvement in PDE5i outcome. These results were not confirmed in placebo-controlled studies. The majority of studies, however, included mixed eugonadal/hypogonadal subjects, thus imparting uncertainty to the statistical analyses. CONCLUSIONS: TS plays positive effects on male sexual function in hypogonadal subjects. The role of TS is uncertain in men who are not clearly hypogonadal. The apparent difference between industry-supported and independent studies could depend on trial design more than on publication bias. New RCTs exploring the effect of TS in selected cases of PDE5i failure that persistently retain low testosterone levels are advisable.

Vitamin D deficiency is associated with type 2 diabetes mellitus in HIV infection.

BACKGROUND: Metabolic complications, including type 2 diabetes mellitus and metabolic syndrome, are increasingly recognized among HIV-infected individuals. Low vitamin D levels increase the risk of type 2 diabetes mellitus, and vitamin D supplementation has been shown to decrease the risk of type 2 diabetes mellitus in patients without HIV infection. OBJECTIVES: The primary objective was to determine whether vitamin D deficiency (serum 25-hyrdoxyvitamin D <20 ng/ml) was associated with type 2 diabetes mellitus among HIV-infected patients. Our secondary objective was to determine whether vitamin D deficiency was associated with metabolic syndrome in HIV. METHODS: We conducted a cross-sectional study among participants enrolled in the prospective Modena (Italy) HIV Metabolic Clinic Cohort. Clinical and laboratory data, including history of type 2 diabetes mellitus, fasting blood glucose, components of metabolic syndrome, and 25-hydroxyvitamin D levels, were obtained for all participants. RESULTS: After adjusting for vitamin D supplementation, sex, age, body mass index, and hepatitis C virus co-infection, vitamin D deficiency was associated with type 2 diabetes mellitus [adjusted odds ratio (OR) 1.85; 95% confidence interval (CI) 1.03-3.32; P = 0.038]. The association between vitamin D deficiency and metabolic syndrome was not significant after adjusting for vitamin D supplementation, sex, age and body mass index (adjusted OR 1.32; 95% CI 1.00-1.75; P = 0.053). CONCLUSIONS: Our study demonstrates an association between vitamin D deficiency and type 2 diabetes mellitus. Clinical trials are needed to better characterize the association between vitamin D deficiency and type 2 diabetes mellitus in HIV infection and to evaluate whether vitamin D is able to prevent or delay the onset of type 2 diabetes mellitus.

Testosterone action on erythropoiesis does not require its aromatization to estrogen: Insights from the testosterone and estrogen treatment of two aromatase-deficient men.

Androgens act on erythropoiesis, but the relative role of testosterone (T) and estradiol (E(2)) on erythropoietic parameters in men is a poorly investigated issue. In order to evaluate separately the effects on erythropoiesis of high-dose T administration alone and of physiological dose of E(2) administration alone two adult men with aromatase deficiency were assessed before and during each treatment. Blood cell count, hemoglobin (Hb), hematocrit (Hct), erythrocyte mean cell volume (MCV), erythrocyte mean corpuscular hemoglobin (MCH), erythrocyte mean corpuscular hemoglobin concentration (MCHC), serum ferritin, iron and total iron-binding capacity (TIBC), serum erythropoietin, serum total testosterone and estradiol were evaluated. Hb, Hct and red cell count rose during testosterone treatment, consistently with the increase in circulating testosterone, but failed to increase during estradiol treatment. A decrease in Hb, Hct and red cell count was recorded in one of the two subjects during estradiol treatment, with a concomitant decrease in serum testosterone. Circulating T alone is capable of and sufficient to influence erythropoiesis, especially at supraphysiological dosage, while circulating E(2) have not the same effect on erythropoietic parameters, suggesting the hypothesis that the erythropoietic changes induced by androgens are not mediated via its aromatization to estrogens.