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Purpose Serum calcium/phosphate ratio (Ca/P) has been recently proposed as an additional tool to identify primary hyperparathyroidism (PHPT), especially in patients with subclinical presentation, with a proposed cut-off of 3.3 when both values are expressed in mg/dL. No data are available on the relationship between Ca/P and the clinical presentation of PHPT. We thus evaluated this relationship in a large, single-center, unselected series. Methods 515 consecutive PHPT patients (mean age 65 ± 13.15 years, 77.1% females) were retrospectively evaluated at diagnosis. Results Mean Ca/P was 4.54 ± 1.5 (range 2.36–13.9), being higher than 3.3 in 88.5% of patients. Ca/P was significantly higher in (1) males, (2) symptomatic PHPT, (3) patients with 25-hydroxy vitamin D levels lower than 20 μg/L, (4) patients with osteitis fibrosa cystica, (5) patients with T score < − 2.5 at the radial site. In a multivariate regression analysis, Ca/P resulted significantly associated with PTH levels. After the exclusion of 57 patients with asymptomatic PHPT (aPHPT) patients and serum Ca higher than 1 mg/dL above the upper limit of normal range, no differences were found in Ca/P between aPHPT meeting or not surgical criteria. Conclusions In PHPT Ca/P ratio is associated with increased biochemical and clinical severity of disease and represents a direct indicator of clinical bone damage. However, it does not seem an additional tool to identify aPHPT patients reaching surgical indication.

Objective This study aimed to assess the long-term outcome of patients with acromegaly. Design This is a multicenter, retrospective, observational study which extends the mean observation period of a previously reported cohort of Italian patients with acromegaly to 15 years of follow-up. Methods Only patients from the centers that provided information on the life status of at least 95% of their original cohorts were included. Life status information was collected either from clinical records or from the municipal registry offices. Standardized mortality ratios (SMRs) were computed comparing data with those of the general Italian population. Results A total of 811 patients were included. There were 153 deaths, with 90 expected and an SMR of 1.7 (95% CI 1.4–2.0, p  < 0.001). Death occurred after a median of 15 (women) or 16 (men) years from the diagnosis, without gender differences. Mortality remained elevated in the patients with control of disease (SMR 1.3, 95% CI 1.1–1.6). In the multivariable analysis, only older age and high IGF1 concentrations at last available follow-up visit were predictors of mortality. The oncological causes of death outweighed the cardiovascular ones, bordering on statistical significance with respect to the general population. Conclusions Mortality remains significantly high in patients with acromegaly, irrespectively of disease status, as long as the follow-up is sufficiently long with a low rate of patients lost to follow-up. Therapy strategy including radiotherapy does not have an impact on mortality. Oncological causes of death currently outweigh the cardiovascular causes.

Aim This guideline (GL) is aimed at providing a clinical practice reference for the management of adult patients with overweight or obesity associated with metabolic complications who are resistant to lifestyle modification. Methods Surgeons, endocrinologists, gastroenterologists, psychologists, pharmacologists, a general practitioner, a nutritionist, a nurse and a patients’ representative acted as multi-disciplinary panel. This GL has been developed following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A systematic review and network meta-analysis was performed by a methodologic group. For each question, the panel identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as “critical” and “important” were considered in the systematic review of evidence. Those classified as “critical” were considered for clinical practice recommendations. Consensus on the direction (for or against) and strength (strong or conditional) of recommendations was reached through a majority vote. Results The present GL provides recommendations about the role of both pharmacological and surgical treatment for the clinical management of the adult patient population with BMI > 27 kg/m 2 and < 40 kg/m 2 associated with weight-related metabolic comorbidities, resistant to lifestyle changes. The panel: suggests the timely implementation of therapeutic interventions in addition to diet and physical activity; recommends the use of semaglutide 2.4 mg/week and suggests liraglutide 3 mg/day in patients with obesity or overweight also affected by diabetes or pre-diabetes; recommends semaglutide 2.4 mg/week in patients with obesity or overweight also affected by non-alcoholic fatty liver disease; recommends semaglutide 2.4 mg/week as first-line drug in patients with obesity or overweight that require a larger weight loss to reduce comorbidities; suggests the use of orlistat in patients with obesity or overweight also affected by hypertriglyceridemia that assume high-calorie and high-fat diet; suggests the use of naltrexone/bupropion combination in patients with obesity or overweight, with emotional eating; recommends surgical intervention (sleeve gastrectomy, Roux-en-Y gastric bypass, or metabolic gastric bypass/gastric bypass with single anastomosis/gastric mini bypass in patients with BMI ≥ 35 kg/m 2 who are suitable for metabolic surgery; and suggests gastric banding as a possible, though less effective, surgical alternative. Conclusion The present GL is directed to all physicians addressing people with obesity—working in hospitals, territorial services or private practice—and to general practitioners and patients. The recommendations should also consider the patient’s preferences and the available resources and expertise.

Osteocalcin (OC) has been proposed as a regulator of insulin sensitivity in both humans and other animals. Primary hyperparathyroidism (PHPT) is characterized by high OC levels and insulin resistance. The aim of this study was to evaluate whether in PHPT the link between OC levels and blood markers of insulin resistance was maintained. In a consecutive series of 219 adult PHPT patients, serum OC as well as fasting insulin and glucose levels were measured. Insulin sensitivity was estimated by homeostatic model assessment (HOMA2-S%). The same parameters were evaluated in a subgroup of 45 patients after parathyroidectomy (PTX). PHPT patients were characterized by markedly high OC levels. After subdividing them according to glucose tolerance, it was found that OC was similar in subjects with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT), while diabetic subjects had lower serum OC than those with NGT ( P  < 0.02) or IGT ( P  < 0.04). OC was negatively associated with fasting glucose and positively associated with HOMA2-S%. OC independently predicted HOMA2-S% in a multivariate analysis. In the subgroup of surgically cured PHPT patients, OC levels significantly decreased after PTX, while HOMA2-S% did not change. Our findings indicate that in PHPT there is a positive relationship between OC and glucose metabolism, OC being one of the predictors of insulin sensitivity. However, data in surgically cured patients, showing OC normalization in spite of unchanged HOMA2-S%, suggest that OC does not likely play a major role in affecting insulin sensitivity in PHPT.

Dopamine-agonist cabergoline (CB) reduces prolactin (PRL) secretion and tumor size in 80% of patients with prolactin-secreting adenomas (PRL-omas) by binding type 2 dopamine receptor (DRD2). The mechanisms responsible for resistance to CB remain largely unknown. To assess the association of DRD2 with sensitivity to CB, Taq I-A1/A2, Taq I-B1/B2, Hph I-G/T and Nco I-C/T genotypes were determined in a cross-sectional retrospective study, including 203 patients with PRL-oma. DRD2 alleles frequencies did not differ between patients and 212 healthy subjects. Conversely, Nco I-T allele frequency was higher in resistant rather than responsive patients, considering both PRL normalization (56.6 vs 45.3%, P =0.038) and tumor shrinkage (70.4 vs 41.4%, P =0.006). Finally, [ Taq I A1−/ Taq I B1−/ Hph I T−/ Nco I T−] haplotype was found in 34.5% of patients normalizing PRL with ⩽3 mg/week of CB vs 11.3% of resistants ( P =0.021). In conclusion, resistance to CB was associated with DRD2 Nco I-T+ allele, consistent with evidence suggesting that this variant may lead to reduction and instability of DRD2 mRNA or protein.

Rapid intraoperative parathyroid hormone (RIOPTH) monitoring predicts complete removal of all hypersecreting tissue by means of a significant parathyroid hormone (PTH) decrease. In this study we have tried to provide an explanation for some unexpected results of RIOPTH monitoring observed during a series of 125 conventional parathyroidectomies for primary hyperthyroidism, discussing the possible consequences on the surgical strategy. Three main groups can be recognized: (1) spikes: a PTH increase 10 minutes after removal of the diseased gland was observed in three patients; (2) false‐negative results: six patients showed an inadequate PTH decreases at 10 minutes, three of them resulting in cure at 20 minutes (all six patients were cured at follow‐up); (3) false‐positive results: five patients with multiglandular disease showed a PTH decrease to a cure level despite excision of one adenoma only (in two of these patients a 20‐minute sample showed a PTH increase soon after manipulation of the second adenoma). We concluded that the spike, almost certainly a consequence of manipulating the adenoma, when detected should be considered the “true” baseline value. False‐negative results are to some extent related to undetected spikes. The assay used for RIOPTH determination and PTH half‐life variability may also play a role. A false‐negative result usually prolongs the surgical time. False‐positive results are usually related to a double adenoma, one functionally prevailing over the other. Because in our experience manipulation of the second adenoma brought a PTH increase detected with RIOPTH monitoring, we believe that the second adenoma should be excised.

Dopamine-agonist cabergoline (CB) reduces prolactin (PRL) secretion and tumor size in 80% of patients with prolactin-secreting adenomas (PRL-omas) by binding type 2 dopamine receptor (DRD2). The mechanisms responsible for resistance to CB remain largely unknown. To assess the association of DRD2 with sensitivity to CB, Taql-A1/A2, Taql-B1/B2, Hphl-G/T and Ncol-C/T genotypes were determined in a cross-sectional retrospective study, including 203 patients with PRL-oma. DRD2 alleles frequencies did not differ between patients and 212 healthy subjects. Conversely, Ncol-T allele frequency was higher in resistant rather than responsive patients, considering both PRL normalization (56.6 vs 45.3%, P=0.038) and tumor shrinkage (70.4 vs 41.4%, P =0.006). Finally, [Taql A1-/Tagl B1-/Hphl T-/Ncol T-] haplotype was found in 34.5% of patients normalizing PRL with ,3mg/ week of CB vs 11.3% of resistants (P=0.021). In conclusion, resistance to CB was associated with DRD2 Ncol-T + allele, consistent with evidence suggesting that this variant may lead to reduction and instability of DRD2 mRNA or protein.