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Purpose: The diagnosis of primary hyperparathyroidism (PHPT) and chronic hypoparathyroidism (HypoPT) is still challenging, especially in patients asymptomatic or with non-classical phenotypes and for physicians not skilled in calcium-phosphorous (Ca–P) disorders. The serum calcium/phosphorous (Ca/P) ratio has been proposed as accurate index to identify PHPT, while it has never been tested in HypoPT. The aim of this study is to investigate the diagnostic power of the serum Ca/P ratio in the diagnosis of primary parathyroid dysfunctions (both PHPT and HypoPT) in a large series of data. Methods: A multicentric, retrospective, cross-sectional study (ClinicalTrials.gov: NCT03747029) was carried out including 432 PHPT patients and 217 HypoPT patients compared with 389 controls. Serum Ca, P, creatinine, parathyroid hormone and 25OH-vitamin D were collected. Serum Ca and P were expressed in mmol/L. Ca/P diagnostic performance was evaluated by receiver operating characteristic (ROC) curve, sensitivity, specificity and accuracy. Results: The Ca/P ratio was significantly higher in PHPT and lower in HypoPT patients than controls (p < 0.0001). At ROC curve analysis, the Ca/P ratio above 2.55 was defined to identify PHPT patients (sensitivity 85.7%, specificity 85.3%) and below 1.78 to identify HypoPT patients (sensitivity 88.2%, specificity 87.9%). Conclusions: The Ca/P ratio is a highly accurate index to identify PHPT when Ca/P is above 2.55 and HypoPT when it is below 1.78. These results demonstrate the reliability of this index to rule in/out primary parathyroid dysfunctions and remark the importance of measuring serum P in clinical practice.

Over the past two decades several large cohort studies have been performed to disclose the changes of sex hormone in elderly and their clinical significance. Beyond the decline of total testosterone, aging is accompanied by a sex hormone binding globulin (SHBG) increase, a steeper free testosterone decline, while gonadotropins may be increased or inappropriately normal, with important contribution of comorbidities (e.g., obesity) to these changes. Actually, it has become firm the concept that the biochemical finding of testosterone deficiency alone is not sufficient for diagnosing hypogonadism in older men. The definition of late-onset hypogonadism (LOH) includes low serum testosterone levels coupled with signs and symptoms related to hypogonadism. Indeed, the combination of multiple factors all contributing to the testosterone decline, with other concurrent comorbidities further overlapping, makes the clinical correlates of LOH highly heterogeneous. For all these reasons both the diagnosis and the therapeutic management of LOH, especially the decision about starting testosterone replacement treatment, remain challenging.

This study aimed to evaluate the real-life use of BRAF-V600E mutation analysis in washout liquid from thyroid nodule fine needle aspiration (FNA), and the consequences of genetic result on clinical decision-making. We retrospectively considered subjects tested for BRAF-V600E among those attending the Endocrinology Unit of Modena for FNA between 2014 and 2018. Washing fluid was collected together with cytological sample and stored at −20 °C. If the clinician deemed it necessary, the sample was thawed, DNA extracted, and genetic test performed by high-resolution melting technique. We collected data on cytology according to the Italian Consensus for the cytological classification of thyroid nodules, type of surgery (when performed), histology, and adverse events. Out of 7112 subjects submitted to FNA, BRAF analysis was requested for 683 (9.6%). Overall, 896 nodules were analyzed: 74% were indeterminate at cytology, mainly TIR3A (low risk). Twenty-two nodules were mutant (BRAF+). Only 2% of indeterminate, mainly TIR3B, were BRAF+. Based on final histological diagnosis, BRAF test had high specificity (100%) but poor sensitivity (21%), also in indeterminate nodules. Mutant subjects underwent more extensive surgery compared to wild type (p = 0.000), with frequent prophylactic central lymph node dissection. One third had local metastases. Higher prevalence of hypoparathyroidism was found in BRAF+ compared to wild type (p = 0.018). The analysis of BRAF-V600E outside of gene panels has low sensitivity, especially in indeterminate nodules, and a positive result could lead to more extensive surgery with greater risk of hypoparathyroidism and questionable clinical utility.

L’infertilita maschile idiopatica rimane ad oggi una sfida terapeutica. I dati relativi al miglioramento della qualita spermatica dopo terapia con gonadotropine sono ancora controversi, nonostante il noto ruolo dell’ormone follicolo-stimolante (FSH) nella spermatogenesi. La ricerca scientifica si sta sempre piu focalizzando su possibili fattori predittivi di risposta e schemi di trattamento efficaci, al fine di ottenere terapie personalizzate.

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. Conclusions: 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.

Clinical presentation of Klinefelter’s syndrome is highly heterogeneous, explaining why the disease is often undiagnosed. Klinefelter patients have traditionally been described as tall, with gynecomastia, small and firm testicles. Beyond this classical phenotype, less distinct phenotypes have been described with less evident features. The reduction of the volume of the testes remains the peculiar clinical hallmark of Klinefelter’s syndrome. The broad spectrum of Klinefelter phenotypes depends on the genetic background (mosaicism, number of supernumerary X chromosome) as well as the degree of hypogonadism, patient’s age, and delay in the diagnosis. The relationship between clinical phenotype and pathogenesis is still not completely understood and needs to be fully elucidated, in order to facilitate the diagnosis and the clinical management of this condition. As expected, the degree of severity of the phenotype influences psychosocial issues and quality of life in these patients.

BACKGROUND Despite the well-known influence of psychological and situational factors on erectile dysfunction, the influence of the physician's gender on the andrological workup has never been investigated so far. OBJECTIVES To investigate physician's gender influence on the erectile dysfunction diagnostic workup. MATERIALS AND METHODS Cross-sectional study with retrospective data collection. We evaluate a consecutive series of erectile dysfunction patients: 95 at the University of Modena and Reggio Emilia (UNIMORE) and 1808 at the University of Florence (UNIFI). In the UNIMORE cohort (Cohort 1), intracavernousal injection test was performed in case of suspected vascular pathogenic component. In the UNIFI cohort (Cohort 2), patients were evaluated by structured interview on erectile dysfunction and ANDROTEST. Both cohorts were divided into two groups according to the gender of the physician who performed the intracavernousal injection test or the structured interview. RESULTS In Cohort 1, patients who had the intracavernousal injection test performed by a female physician had a significantly higher probability of obtaining a better intracavernousal injection test response. In Cohort 2, patients interviewed by female physician more frequently reported to have a conflictual couple relationship and a reduced frequency of climax in their partners. However, they reported less difficulties in achieving and maintaining erection, higher frequency of autoeroticism, lower occurrence of erectile dysfunction during masturbation and lower impairment in morning erections. CONCLUSIONS Physician's gender affects the results obtained during the erectile dysfunction diagnostic workup. Men interviewed by a female physician describe a less severe erectile dysfunction probably as attempt to defend their own virility. On the other hand, the presence of a male physician during intracavernousal injection test is associated to a worse response suggesting a possible unconscious competition.

BACKGROUND: HIV-infection is associated to premature decline of serum T1,2. However, prevalence and biochemical characterization of hypogonadism in HIV-infected men are still to be well defined1,2. AIM: To evaluate the gonadal status in HIV-infected men by assessing circulating total T (TT) with either ID-LC-MS/MS or chemiluminescent immunoassay. METHODS: Prospective, cross-sectional, observational study on HIV-infected men with ongoing Highly Active Antiretroviral Therapy (HAART). Serum TT, gonadotropins and sex hormone-binding globulin (SHBG) were measured by chemiluminescent immunoassay. TT was also assessed by the gold standard ID-LC-MS/MS. Free T (FT) was calculated by Vermeulen equation. Hypogonadism was defined as serum TT levels below 320 ng/dL and/or free T levels below 64 pg/ml. Statistical analysis: Categorical variables were compared using Chi-Square test, while correlations were performed using linear regression models. RESULTS: 315 consecutive HIV-infected men were enrolled (mean age 45.56±5.61 years; average duration of HIV-infection 16.57±10.45 years). Considering serum TT levels assessed by LC-MS/MS and immunoassay, 11 patients out of 233 (4.8%) and 10 patients out of 315 (3.2%) had T deficiency, respectively. TT combined with luteinizing hormone (LH) levels was used to classify hypogonadism. No difference was found comparing the two methodologies used for TT measurement (p=0.914). 56 patients (17.8%) showed SHBG above the normal range (>71.4 nmol/L). Considering calculated FT, the incidence of hypogonadism raised to 6.9% using either immunoassay or LC-MS/MS, with no difference between methodologies (p=0.895). Including compensated form of hypogonadism, the prevalence raised to 13% for TT and to 15% for FT. FT showed an inverse relation with age (-0.340,p

The management of male idiopathic infertility is heterogeneous. Although meta-analyses reported the effectiveness on pregnancy rate, the real clinical impact of follicle-stimulating hormone (FSH) was not evaluated so far. In Italy, FSH is approved by the National Medicines Agency (AIFA) for idiopathic infertile patients with FSH 8 IU/L, independently of semen parameters.Primary endpoint was to record the therapeutic approach to the male partner of infertile couples. Secondary aim was to assess changes of semen parameters during FSH treatment.A multicentre, prospective, observational, clinical practice survey was carried out, enrolling the male partner of infertile couples attending ten Italian participating centres. Inclusion criteria were as follows: couple infertility, age18 years and FSH serum levels8 IU/L. Thus, all men in which AIFA allowed the FSH prescription were enrolled. Primary endpoint was the number of infertile patients treated with FSH. Secondary outcomes were semen parameters. The treating physician decided whether to offer FSH therapy and whether to re-evaluate the male partner.A total of 718 infertile couples were enrolled, and 241 patients were re-evaluated (median follow-up: 4.5 months). In 64.9% (466 patients), a treatment was prescribed. FSH was prescribed in 397 patients (85.2% of treated men). Sperm concentration (P = .002) and normal form percentage (P .001) significantly improved during FSH administration. No correlation was found between these parameters and FSH duration (P = .545 and P = .627, respectively) or dosage (P = .455 and P = .533, respectively). Among patients treated with FSH, the incidence of oligozoospermia decreased from 73.0% to 56.0% (P .001) and teratozoospermia from 43.6% to 27.7% (P .001).This first nation-wide survey reveals a FSH prescription rate of 55% in patients qualifying for treatment according to AIFA. Although the study was not designed to highlight FSH efficacy in male infertility, a slight increase in semen parameters was demonstrated in about half of the treated men without adverse events.

Purpose To assess the transferability of the reference intervals (RI) of testosterone (T), cortisol (C), human growth hormone (hGH), and insulin‐like growth factor (IGF)‐1, calculated on a normal healthy population, to a population of female elite volleyball players. Secondary aim of this study is the evaluation of the T/C ratio as predictive tool of overtraining during the annual regular season. Methods A retrospective, longitudinal, observational study was performed, enrolling 58 professional female volleyball players periodically evaluated during the regular sportive season, which lasts from September to May. Results Statistically significant differences between the volleyball players and reference populations for T (P = .010), C (P

Purpose The relationship between probiotics and levothyroxine (LT4) requirement has not yet been investigated. The aim of this study was to assess whether a mixture of highly charged Lactobacilli and Bifidobacteria (VSL#3®) is able to influence LT4 metabolism acting on the gut microbiota. Methods A prospective, randomized, single-blind, controlled, investigator-started clinical trial was carried out. Patients with primary hypothyroidism were randomly assigned to the study (VSL#3® + LT4) and the control group (LT4). A 2-month treatment phase was followed by 2 months of follow-up. Clinical examination, blood tests for thyroid function and for peripheral tissue markers of thyroid hormones (PTM) were performed monthly. LT4 dose adjustments were performed when necessary. Results Thirty-nine patients were enrolled in the study group and 41 in the control group. No difference in thyroid function [thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4)] and PTM was found between groups and among visits. FT3/fT4 ratio was directly correlated to TSH at each visit in both groups, with the exception of the first evaluation of probiotics-treated subjects (rho = 0.287, p = 0.076). LT4 daily dose adjustments occurred more frequently in the control than in the study group (p = 0.007), despite no differences in the mean LT4 daily dose. In particular, LT4 doses were increased six times in the control group and decreased four times in the study group. Conclusion VSL#3® does not directly alter thyroid functional compensation. A probiotics-mediated influence on thyroid hormones homeostasis is suggested since probiotics supplementation could be able to prevent serum hormonal fluctuations. ClinicalTrials.gov ID Registration number NCT03095963.

Summary Spontaneous or fine-needle aspiration (FNAB)-induced remission of primary hyperparathyroidism (PHPT) may occur, especially for cystic lesions. However, the disease generally relapses over a short time period. We present a case of PHPT due to an enlarged hyperfunctioning parathyroid that underwent long-term (almost 9 years) clinical and ultrasonographic remission after the disappearance of the lesion following ultrasound (US)-assisted FNAB. A 67-year-old woman with PHPT underwent biochemical and US examinations that confirmed the diagnosis and showed a lesion suggestive for parathyroid adenoma or hyperplasia. US-FNAB of the lesion confirmed its parathyroid nature by means of elevated levels of parathyroid hormone within the needle washing fluid. At the second visit, the patient referred slight neck swelling that resolved spontaneously in the days after the US-FNAB. At subsequent follow-up, the enlarged parathyroid was not found; it was visible neither with US nor with magnetic resonance imaging. Biochemical remission persists after 9 years. This is the first reported case of cure of PHPT after US-FNAB performed on a hyperfunctioning parathyroid resulting in its complete disappearance over a period of 9 years of negative biochemical and ultrasonographic follow-up. Learning points: Spontaneous or fine-needle aspiration-induced remission of primary hyperparathyroidism can occur. Both circumstances may present disease relapse over a variable time period, but definite remission is also possible even though long-term periodic follow-up should be performed. Parathyroid damage should be ruled out in case of neck symptomatology after parathyroid fine-needle aspiration or spontaneous symptomatology in patients with history of primary hyperparathyroidism.

Background . Intense physical exercise influences the secretion of hormones involved in several metabolic processes. In particular, an acute cortisol (C) and growth hormone (GH) increase after an acute physical activity is widely demonstrated in literature. Moreover, the testosterone (T)/C ratio was recently proposed as a performance index in male athletes. On the contrary, little is known about hormonal changes in women under physical activity and only few studies evaluated the hormonal trend in an extended period of time. Aim . To evaluate the hormonal changes during an annual volleyball female regular season. Methodology . A longitudinal, retrospective, observational clinical trial was carried out. 28 female professional volleyball players belonging to the same team were enrolled. For each subject, blood samples were collected after 36 hours of rest in four visits. Visit 1 was performed at the beginning of the training phase, visit 2 and 3 were performed during and Visit 4 were performed at the end of the regular season. GH, insulin-like growth factor (IGF)-1, T and C were assessed by immunoenzimatic assays. Results . Both GH and IGF-1 were above the normal range at visit 1 (5.08 ± 5.22 ng/ml; 265.88 ± 105.85 ng/ml). In particular, five athletes had GH above the normal range (17.8%). No alterations of other hormones were found at Visit 1. C significantly changed during the regular season (p=0.009), with higher levels at Visit 2 (p=0.049), compared to visit 1 and the following visits. Similarly, T significantly changed during the season (p=0.013), even if a clear trend was not demonstrated. The post-hoc test showed two peaks of T at Visit 2 and Visit 4 (p=0.029 and p=0.024, respectively). Accordingly, the T/C ratio significantly changed during visits (p=0.009), decreasing of about 30% in the first phase of the regular season, suggesting an overreaching of subjects enrolled. Conclusion . Here we found that chronic intense physical activity influences hormonal levels in female volleyball players. In particular, C secretion is increased at the beginning of the regular season, whereas T serum levels shows a significant fluctuation during the regular season. Moreover, we suggest that T/C ratio could be useful in the evaluation of the training overload in female athletes.