Aldosterone Secretion in Patients With Primary Hyperparathyroidism Without Arterial Hypertension.

OBJECTIVE: There is a direct bidirectional link between parathyroid hormone (PTH) and the renin-angiotensin-aldosterone system (RAAS), but few studies evaluated the RAAS in patients with primary hyperparathyroidism (PHPT), mainly biased from concomitant antihypertensive treatment. METHODS: We retrospectively evaluated a consecutive series of 130 normotensive patients with PHPT comparing aldosterone (ALD) levels and plasma renin activity (PRA) with the demographic, biochemical, or clinical features of PHPT. RESULTS: No correlation was found between ALD and PRA, and the demographic, biochemical, and bone densitometry parameters in patients with PHPT without hypertension, with the exception of a negative correlation between age and serum PRA. Moreover, there was no significant correlation between PTH and ALD levels even in patients whose PTH level was >100 ng/L (P = .088). CONCLUSION: In our normotensive patients with PHPT, the ALD, PRA, and aldosterone/renin ratio were not correlated to PTH and calcium levels. In addition, they were neither related to PHPT clinical presentation nor renal function, vitamin D status, bone mass loss, or the presence of comorbidities such as diabetes and obesity. Further studies are needed to clarify the complex interplay between PTH and the RAAS in the modern PHPT presentation.

Central hypogonadism in Klinefelter syndrome: report of two cases and review of the literature.

PURPOSE: Klinefelter syndrome (KS) is characterized by late adolescence/young adulthood onset of primary hypogonadism. Hypogonadotropic hypogonadism (HH), when congenital, is usually associated with absent/incomplete puberty and low/normal gonadotropins. We report the clinical and genetic features of two subjects with KS and an unexpected HH hormone profile. METHODS: Magnetic resonance imaging (MRI) of hypothalamus-pituitary region and next generation sequencing (NGS) of congenital HH-associated genes were obtained. A narrative review of the literature was conducted. RESULTS: Patients were diagnosed with Klinefelter syndrome following karyotype analysis. Nevertheless, they showed unusual features: both had incomplete puberty, low gonadotropins and testosterone levels, and the first one was anosmic. Sellar lesions were excluded by MRI, and NGS was negative in both subjects. Our data add to those of the only 14 similar cases reported so far. Unexplained HH rarely occurs in KS and is variably associated with anosmia, other pituitary hormones deficiencies and heterogeneous karyotypes. However, most cases show an early, pre-pubertal onset of hypogonadism. If the causes behind this gonadotropins defect are largely unknown, hereby we provide the first review of the literature on this topic and propose some pathogenetic hypotheses, including the coexistence of KS and congenital HH as suggested by overlapping clinical features in some of these patients. CONCLUSION: HH is an exceptional occurrence in Klinefelter syndrome and is associated with heterogeneous phenotypes and, probably, aetiologies. Moreover, KS could underlie HH nonresponsive to gonadotropins. An exhaustive diagnostic workup and a tailored clinical management are advisable in these rare forms.

Radiologic Manifestation of Bone Involvement in Primary Hyperparathyroidism: Prevalence and Clinical Significance in a Southern European Series.

OBJECTIVE: Clinically overt symptomatic bone disease in primary hyperparathyroidism (PHPT) is rarely seen today, and osteoporosis is the dominant finding. Subperiosteal bone resorption in the fingers and skull mottling are typical bone PHPT findings, the contemporary prevalence of which is unknown. We evaluated these mild lesions and investigated the impact of their occurrence on PHPT clinical management. METHODS: We evaluated retrospectively a monocentric series of 363 PHPT patients classified in Group 1 (n = 100) or Group 2 (n = 263) according to the presence or absence of bone involvement, respectively. Patients belonging to Group 1, in turn, were subdivided into Group 1A, with severe and symptomatic lesions (n = 48), and Group 1B, with milder signs of osteitis fibrosa cystica (OFC) without brown tumors or fractures (n = 52). RESULTS: Serum total and ionized calcium, parathyroid hormone, osteocalcin, alkaline phosphatase, and its bone fraction levels were higher in Group 1 than in Group 2, while no gender or age differences were observed between the groups. Osteoporosis prevalence was similar in Group 1B and Group 2 patients but lower than in Group 1A. Mild OFC findings did not modify the surgical indication in any patient of Group 1B. CONCLUSION: Minor radiologic signs of OFC are not uncommon in the modern PHPT phenotype and occur in patients with more active disease. These signs could identify PHPT patients in an earlier stage of typical bone involvement. However, these features do not seem to upgrade either the clinical classification of asymptomatic PHPT patients or the propensity toward surgical choice.

Lenvatinib Long-Term Responses in Refractory Thyroid Cancer: Our Mono-Institutional Real-Life Experience with the Multidisciplinary Approach and Review of Literature.

Lenvatinib (LEN) is a multikinase inhibitor with antiangiogenic properties recently approved in radioactive iodine-refractory differentiated thyroid cancer, hepatocellular carcinoma, and renal cell carcinoma in combination with everolimus. LEN-treated patients frequently have adverse events (AEs) that generally require such dose modifications, including drug discontinuation. Hypertension, diarrhea, weight loss, proteinuria, fatigue, and palmar-plantar erythrodysesthesia are reported among the most frequent AEs, often leading to discontinuations or dose modifications. This paper reports a case series focusing on the role of the immediate multidisciplinary approach to manage AEs.

INCREASED SERUM CALCITONIN IN SPORADIC PRIMARY HYPERPARATHYROIDISM IS AN UNCOMMON OCCURRENCE.

Objective: To evaluate calcitonin (CT) levels in sporadic primary hyperparathyroidism (PHPT), which has to date rarely been considered. Methods: We evaluated serum CT levels in 290 consecutive patients with sporadic PHPT at diagnosis. Results: Mild elevations in CT levels (hyperCT) were found in 25 patients (8.6%), with no correlation among the demographic, clinical, and biochemical findings. In addition, no differences were found between patients with and without hyperCT. Follow-up data were available for 19/25 patients, but CT values were only available for 10. CT normalized in all surgically cured patients regardless of the extent of the surgery (parathyroidectomy [PTX] only in 8 and associated with partial or total thyroidectomy for benign nodular goiters in 7). Conclusion: hyperCT is an uncommon feature of sporadic PHPT and not related to biochemical or clinical features of the disease. In addition, hyperCT is reversible after PTX, regardless of whether concomitant thyroidectomies have been conducted. Abbreviations: CT = calcitonin; eGFR = estimated glomerular filtration rate; hyperCT = hypercalcitoninemia; MEN = multiple endocrine neoplasm; MTC = medullary thyroid carcinoma; PHPT = primary hyperparathyroidism; PPI = proton pump inhibitor; PTH = parathyroid hormone; PTX = parathyroidectomy.

THE CLINICAL PRESENTATION OF PRIMARY HYPERPARATHYROIDISM: A SOUTHERN EUROPEAN PERSPECTIVE OVER THE LAST 2 DECADES.

OBJECTIVE: The clinical presentation of primary hyperparathyroidism (PHPT) has changed widely in developed countries in the last few decades. We evaluated its variations in our series over a 20-year period (i.e., 1997-2016). METHODS: A retrospective survey was conducted in our series of 364 well-characterized consecutive patients, arbitrarily divided into 4 consecutive 5-year periods at diagnosis. RESULTS: In the overall series, only estimated glomerular function (eGFR) and urinary calcium (UCa) showed a significant upward trend ( P = .032 and .039, respectively), whereas demographic and clinical characteristics were stable. The UCa upward trend was also confirmed for the subgroup of symptomatic patients ( P = .013). No difference was observed in the demographic, clinical, or biochemical characteristics of asymptomatic patients or in the fraction of patients meeting surgical criteria. CONCLUSION: The clinical presentation of PHPT was stable over 20 years in our large series. ABBREVIATIONS: Ca = calcium; eGFR = estimated glomerular filtration rate; 25OHD = 25-hydroxyvitamin D; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; UCa = urinary calcium.

UNKNOWN AND ALREADY KNOWN THYROID ABNORMALITIES IN PRIMARY HYPERPARATHYROIDISM.

OBJECTIVE: Primary hyperparathyroidism (PHPT) and thyroid diseases are highly prevalent in the general population, but the putative link between the 2 conditions remains unclear. METHODS: A monocentric consecutive series of 434 patients with PHPT was retrospectively evaluated by lab and ultrasonography to look for thyroid abnormalities. Patients were classified in 3 groups: without thyroid abnormalities (group 1, n = 171), with thyroid diseases not previously known (group 2a, n = 69), and thyroid diseases previously known (group 2b, n = 194). RESULTS: In terms of thyroid disease, no significant difference was found between groups 2a and 2b, except for the significantly larger number of patients with toxic nodular goiter in group 2b. PHPT was more frequently symptomatic in group 2a than in group 2b, despite no differences in serum calcium, creatinine, parathyroid hormone (PTH), or 25-hydroxyvitamin D (25OHD) levels. CONCLUSION: A total of 60% of PHPT patients had a thyroid disease that was unknown prior to PHPT diagnosis in almost one-third of cases. The newly diagnosed and previously known thyroid diseases were similar, both mostly affecting postmenopausal females. ABBREVIATIONS: Ab = antibody; aPHPT = asymptomatic PHPT; 25OHD = 25-hydroxyvitamin D; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; Tg = thyroglobulin; TPO = thyroperoxidase; TSH = thyroid-stimulating hormone; US = ultrasound.

NEPHROLITHIASIS IN PRIMARY HYPERPARATHYROIDISM: A COMPARISON BETWEEN SILENT AND SYMPTOMATIC PATIENTS.

OBJECTIVE: To characterize primary hyperparathyroidism (PHPT) patients with renal stones and to compare silent with symptomatic stone formers. METHODS: We reviewed clinical data from 234 patients with PHPT, comparing those with and without renal stones (n = 109 and 125, respectively), and among stone formers those symptomatic versus silent (n = 93 and 16, respectively). RESULTS: Stone formers were younger, had higher urinary calcium levels and higher estimated glomerular filtration rates (eGFRs) compared to patients without stones. Patients with silent stones had higher parathyroid hormone (PTH) and lower 25OH-vitamin D (25OHD) levels and more frequently experienced microlithiasis than patients with symptomatic renal stones. CONCLUSION: Nephrolithiasis is a common complication of PHPT. Most patients with silent renal stones have microlithiasis, associated to some features of more severe disease. Lower 25OHD levels in silent stone formers raise the hypothesis that vitamin D status can influence the clinical expression of nephrolithiasis in PHPT patients. ABBREVIATIONS: BMI = body mass index Ca = serum total calcium DM = diabetes mellitus eGFR = estimated glomerular filtration rate HOMA-IR = Homeostasis Model Assessment-Insulin Resistance 25OHD = 25OH-vitamin D PHPT = primary hyperparathyroidism PTH = parathyroid hormone UCa = 24-h urine for calcium US = ultrasound.

VITAMIN D DEFICIENCY DOES NOT AFFECT THE LIKELIHOOD OF PRESURGICAL LOCALIZATION IN ASYMPTOMATIC PRIMARY HYPERPARATHYROIDISM.

OBJECTIVE: Vitamin D deficiency (VDD) was previously associated with larger adenoma size in primary hyperparathyroidism (PHPT), but this topic was not addressed in patients with the mild/asymptomatic form of the disease (aPHPT). METHODS: We retrospectively retrieved from our series of patients affected by PHPT, 96 consecutive subjects with aPHPT in whom 25-hydroxyvitamin D (25OHD) levels had been assayed and compared those results with localizing imaging studies. RESULTS: Twenty-five of 96 patients had VDD (25OHD <20 ng/mL), but positive ultrasound and scintigraphic studies were not different between patients with and without VDD (52.3% versus 55.7% and 42.9% versus 52.4%, respectively). Upon logistic regression analysis, after adjusting for different variables, including the presence of goiter, VDD was not an independent predictor of localization by imaging studies. CONCLUSION: VDD does not affect the likelihood of positive pre-operative imaging in aPHPT and the consequent surgical decisions.

KDIGO CATEGORIES OF GLOMERULAR FILTRATION RATE AND PARATHYROID HORMONE SECRETION IN PRIMARY HYPERPARATHYROIDISM.

OBJECTIVE: The recent Fourth Workshop on the Management of Asymptomatic primary hyperparathyroidism (PHPT) maintained the threshold of 60 mL/min for decreased renal function, below which surgery is recommended. This study investigated the relationship between different stages of renal insufficiency and parathyroid hormone (PTH) levels in an updated case series of PHPT patients. METHODS: This was a retrospective, cross-sectional study involving 379 consecutive PHPT patients. Biochemical evaluation included total and ionized serum calcium, phosphate, creatinine, immunoreactive intact PTH, and 25-hydroxyvitamin D3 (25[OH]D3) levels in the fasting state. Glomerular filtration rate (GFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. RESULTS: Mean CKD-EPI estimated GFR was 81.9 ± 20.3 mL/min/1.73 m(2), and median GFR was 84.0 mL/min/1.73 m(2) (interquartile range, 26.8 mL/min/1.73 m(2)). The patients were divided into 5 groups according to the Kidney Disease: Improving Global Outcomes 2012 guidelines: group 1 with normal or increased GFR (>90 mL/min/1.73 m(2)); group 2 with mild GFR decrease (60 to 89 mL/min/1.73 m(2)); group 3a with mild to moderate GFR decrease (45 to 59 mL/min/1.73 m(2)); group 3b with moderate to severe GFR decrease (30 to 44 mL/min/1.73 m(2)); and group 4 with severe GFR decrease (<30 mL/min/1.73 m(2)). Among the 5 groups of patients, serum calcium levels were different (P = .025), whereas 25(OH)D3 levels were not (P = .36). PTH levels were comparable across groups 1 through 3a, but they were significantly higher in groups 3b and 4 (P<.0001). CONCLUSION: In our series of PHPT patients, PTH levels did not rise as a result of renal impairment until GFR decreased below 45 mL/min/1.73 m(2).

Relationship between insulin sensitivity and bone mineral density in primary hyperparathyroidism.

INTRODUCTION: Evidence of crosstalk between bone and insulin metabolism has been identified. In primary hyperparathyroidism (PHPT), scant data exist on this relationship. AIM: To evaluate the relationship between insulin levels or sensitivity and bone mineral density (BMD) in PHPT. SUBJECT AND METHODS: Two hundred and sixty-seven patients with PHPT without known diabetes mellitus were studied. Fasting blood glucose and insulin levels as well as BMD at lumbar spine, femoral neck and forearm were measured. Insulin sensitivity was assessed using Quantitative Insulin Sensitivity Check Index (QUICKI). The same parameters were measured 2 years (interquartile range 2·8 years) after surgery (PTX) in a subgroup of patients (n = 51). RESULTS: In univariate analysis, a positive relationship between insulin levels and BMD (R = 0·17, P < 0·03) or T-score (R = 0·20, P < 0·005) was found at femoral neck level. Consequently, a negative relationship between QUICKI and femoral BMD (R = -0·20, P < 0·01) or T-score (R = -0·21, P < 0·004) was found. In multivariate analysis, when femoral BMD was the dependent variable, age (beta = -0·35, P < 0·000004), BMI (beta = 0·39, P < 0·00001), PTH (beta = -0·18, P < 0·05) and QUICKI (R = -0·15, P < 0·05) had an independent effect (R(2) = 0·29). Insulin levels and QUICKI did not change after PTX. No relationship was found between QUICKI or insulin levels at the time of diagnosis and change in BMD at any site at follow-up. CONCLUSIONS: Our data show a weak relationship between insulin levels and/or insulin sensitivity and BMD in PHPT. However, the insulin state does not influence change in bone density after PTX in PHPT.

Silent renal stones in primary hyperparathyroidism: prevalence and clinical features.

OBJECTIVE: (1) To evaluate the prevalence of silent nephrolithiasis in patients with primary hyperparathyroidism (PHPT) compared with controls, and (2) To characterize clinically PHPT patients with silent renal stones. METHODS: We reviewed clinical data for 141 patients with PHPT and without symptoms or history of nephrolithiasis in whom renal ultrasonography was performed at diagnosis. A total of 141 sex- and age- matched subjects with abdomen ultrasonography obtained for reasons different from urinary symptoms served as controls. RESULTS: Silent nephrolithiasis was more prevalent in PHPT patients than in controls (11.35% vs. 2.13%; P = .003). Among patients with PHPT, those with silent renal stones showed higher serum calcium and parathyroid hormone levels and met surgical criteria, regardless of nephrolithiasis, more frequently than those without renal stones. CONCLUSION: The prevalence of silent nephrolithiasis is increased in patients with PHPT as compared with controls. Moreover, it seems likely that silent renal stone disease could identify a subset of PHPT patients with more severe disease. Accordingly, we suggest ultrasonographic screening of nephrolithiasis in all PHPT patients. Further studies are needed to better characterize this clinical entity.

Focus on Non-osteoporotic Post-menopausal Women with Asymptomatic Primary Hyperparathyroidism: A Monocentric Series.

OBJECTIVE: Primary Hyperparathyroidism (PHPT) is a common disease, frequently diagnosed in post-menopausal women, among whom Osteoporosis (OP) is a common finding. To date, no study has specifically evaluated the asymptomatic PHPT (aPHPT) patients without OP, in particular post-menopausal women who are exposed to an increased risk of developing OP. DESIGN: This study involved a retrospective cross-sectional evaluation. PATIENTS: From our database of 500 consecutive patients diagnosed with PHPT, 178 postmenopausal aPHPT were retrieved. RESULTS: The clinical, biochemical, and imaging data of the 85 patients without OP were not different from those of the 93 with OP, except for bone alkaline phosphatase (significantly higher in the latter group). Among these 85 patients without OP, the 45 patients meeting surgical criteria for parathyroidectomy had significantly higher values of serum PTH (240 vs. 99 ng/L, p =0.03) and calcium (total, 11.2 ± 0.7 vs. 10.6 ± 0.4 mg/dL, p <0.001; ionized, 1.45 ± 0.12 vs. 1.36 ± 0.8 mmol/L, p =0.044) and lower values of serum phosphate (2.57 ± 0.7 vs. 2.94 ± 0.5 mg/dL, p =0.009) and eGFR (68.5 ± 23.8 vs 80.8 ± 14.4 mL/min/1.73 m2, p =0.006) than the 40 aPHPT patients not meeting surgical criteria, without any difference in densitometric data and calculated fracture risk. CONCLUSION: In our series, post-menopausal aPHPT patients without OP accounted for almost a sixth of the whole PHPT series. About half of these patients did not meet surgical criteria, but their T scores and 10-year fracture risk calculated by FRAX were not significantly different from post-menopausal aPHPT without OP meeting surgical criteria.

Italian Guidelines for the Management of Sporadic Primary Hyperparathyroidism.

AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of sporadic primary hyperparathyroidism (PHPT) in adults. PHPT management in pregnancy was not considered. METHODS: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) and Società Italiana dell'Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro (SIOMMMS) 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 the clinical practice recommendations. RESULTS: The present GL provides recommendations about the roles of pharmacological and surgical treatment for the clinical management of sporadic PHPT. Parathyroidectomy is recommended in comparison to surveillance or pharmacologic treatment in any adult (outside of pregnancy) or elderly subject diagnosed with sporadic PHPT who is symptomatic or meets any of the following criteria: • Serum calcium levels >1 mg/dL above the upper limit of normal range. • Urinary calcium levels >4 mg/kg/day. • Osteoporosis disclosed by DXA examination and/or any fragility fracture. • Renal function impairment (eGFR <60 mL/min). • Clinic or silent nephrolithiasis. • Age ≤50 years. Monitoring and treatment of any comorbidity or complication of PHPT at bone, kidney, or cardiovascular level are suggested for patients who do not meet the criteria for surgery or are not operated on for any reason. Sixteen indications for good clinical practice are provided in addition to the recommendations. CONCLUSION: The present GL is directed to endocrinologists and surgeons - 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.

Vitamin D status in primary hyperparathyroidism: a Southern European perspective.

BACKGROUND: Vitamin D deficiency (VDD) is common in patients with primary hyperparathyroidism (pHPT), and this could affect the clinical expression of the disease. However, few North American or North European studies have addressed this issue, showing vitamin D repletion in only about one-third of the patients. SUBJECTS AND METHODS: Vitamin D status was evaluated both in an observational study in a series of 206 consecutive patients with pHPT at diagnosis and in a case-control analysis with 113 age- and sex-matched healthy blood donors. Vitamin D status was assessed by measuring plasma 25-hydroxy-vitamin D (25OHD) levels and was defined as VDD or severe VDD if 25OHD was <20 ng/ml (<50 nm) and <10 ng/ml (<25 nm), respectively. RESULTS: No seasonal variability was observed in 25OHD levels. VDD was observed in 75 of 206 patients (36·4%). The VDD was severe in 24 of 75 patients (11·7%). There was no difference in prevalence of VDD between men and women nor between asymptomatic and 'bone and stone' symptomatic patients. 25OHD levels was negatively correlated with parathyroid hormone, ionized calcium, and bone turnover markers, and positively correlated with phosphate. 25OHD levels were also positively correlated with bone mineral density at all sites measured. In the case-control study, the overall prevalence of VDD and severe VDD was higher in patients with pHPT compared with controls (33·6% vs 10·6%, P < 0·0001, and 8·8% vs 1·8%, P = 0·0337, respectively). CONCLUSIONS: Our study shows that VDD occurs in about one-third of patients with pHPT resident in a Southern European area, a lower figure than previously reported. Moreover, VDD is related to a more severe bone disease, and its prevalence is higher in patients with pHPT than in healthy matched subjects.

Cinacalcet in the management of primary hyperparathyroidism: post marketing experience of an Italian multicentre group.

OBJECTIVE: To report the Italian experience on cinacalcet use following its approval by the European Medical Agency (EMA) to control hypercalcaemia in patients with primary hyperparathyroidism (PHPT). DESIGN: Retrospective data collection from 100 patients with sporadic (sPHPT) and 35 with familial PHPT (fPHPT) followed in eight Italian centres between October 2008 and March 2011. MEASUREMENTS: Albumin-adjusted serum calcium, PTH, 25OHD, daily cinacalcet dose and adverse events were recorded during the follow-up (1-46 months). RESULTS: Baseline serum calcium was 2·90 ± 0·27 nmol/l in sPHPT and 2·75 ± 0·17 nmol/l in fPHPT patients (P = 0·007). The cinacalcet EMA labelling was met in 53% sPHPT and 26% fPHPT patients. High surgical risk (34%), negative preoperative imaging (19%), control of hypercalcaemia before parathyroidectomy (PTx) (24%), and refusal of PTx (19%) accounted for cinacalcet prescription in 96% of sPHPT patients. Conversely, initial treatment (34%), persistent/relapsing PHPT after surgery (31%), and refusal of PTx (14%) were the indications in 79% fPHPT patients. Cinacalcet was started at 30 mg/daily in 64% of sPHPT and 91% of fPHPT and increased until normocalcaemia was reached or side effects occurred. The final daily dose ranged between 15 and 120 mg. The majority of patients (65% of sPHPT and 80% of fPHPT) become normocalcaemic. Treatment was withdrawn in six patients because of side effects. CONCLUSIONS: There is a wide heterogeneity in the prescription of cinacalcet in PHPT patients in Italy and the EMA labelling is not always followed, particularly in fPHPT patients. Cinacalcet effectively reduces serum calcium in patients with either sPHPT or fPHPT.

Recurrence and mortality rate in an Italian multi-center case series of parathyroid atypical adenomas and carcinomas.

Introduction: There are few data regarding the clinical outcome of patients with parathyroid carcinoma (PC) and atypical adenoma (AA) after surgery. Aim of our study was to investigate disease recurrence and mortality rate as well as their predictors in a series of patients with PC or AA. Methods: Clinical and biochemical parameters, histological features, incidence of disease recurrence and mortality rate were retrospectively assessed in 39 patients (51% males, mean age 56.2 ± 17.2 years) diagnosed with PC (n=24) or AA (n=15) and followed up for 6.8 ± 5.0 years after surgery. Results: No differences in baseline characteristics were registered between the two groups, except for higher KI67 values in PC than AA (6.9 ± 3.9% vs 3.4 ± 2.1%, p<0.01). Eight patients (21%) experienced recurrence after a mean follow-up of 5.1 ± 2.7 years, with higher relapse rate in PC than AA (25% vs 13%), though this difference did not reach statistical significance. Mortality rate was 10% in the whole sample, without significant differences between PC and AA. Relapsing cases had been undergone the most extensive surgery more frequently and they had a higher mortality rate in comparison to non relapsing patients (38% vs 6% and 38% vs 3%, respectively, p<0.03 for both). In comparison to survivors, deceased patients were submitted to the most extensive surgery more frequently (50% vs 9%), they were older (74.8 ± 4.6 vs 53.2 ± 16.3 years), and they had higher KI67 values (11.7 ± 4.9 vs 4.8 ± 2.8, p<0.03 for all comparisons). Conclusions: During seven-year follow-up after surgery, no significant differences in recurrence and mortality rate were observed between PC and AA patients. Death was associated with disease relapse, older age and higher KI67 values. These findings suggest a similar and careful long-term follow-up in both parathyroid tumors, especially in older patients, and emphasize the need of further studies in large cohorts to throw light on this crucial clinical issue.

Older Adults with Type 2 Diabetes Treated with Metformin: AME-MET Study - A Multicentric Real-world Study in Italy.

AIMS: Metformin is the most widely used drug for the first-line treatment of type 2 diabetes mellitus (T2DM), but its use and schedule have been poorly investigated in elderly patients. METHODS: We conducted an observational, cross-sectional, multicentric study on metformin in T2DM outpatients older than 65 years who were taking the drug for at least 6 months and referred to Italian Endocrinology and Diabetology Services. The primary endpoint was daily metformin dose, and secondary endpoints were the correlations between metformin dose and age, comorbidities, and concomitant use of other drugs. The study was open to all members of AME (Associazione Medici Endocrinologi). RESULTS: Fifteen Italian centers recruited 751 consecutive participants (42.9% older than 75 years, 48.6% females). T2DM duration was 12.9 ± 9.7 years (longer than 10 years in 53.8%). Metformin had been used for 10.3 ± 6.8 years (longer than 10 years in 52.4%). Metformin dose was 1.6 ± 0.9 g/day (>1.5 g/day in 63.4%). As compared to the youngest, participants older than 75 years did not differ for metformin daily dose or number of administrations. Metformin dose was significantly directly correlated to eGFR, diabetes duration, and metformin treatment duration. CONCLUSION: In this real-world study, the minimum daily effective dose of metformin was prescribed in more than half of older T2DM outpatients.

Serum Phosphate: A Neglected Test in the Clinical Management of Primary Hyperparathyroidism.

BACKGROUND: Although the inverse correlation between serum PTH and phosphate (P) levels in patients with primary hyperparathyroidism (PHPT) is well known, the relationship between P levels and the clinical picture of the disease has not been well investigated. This was thus the aim of this paper. PATIENTS: A total of 472 consecutive patients with PHPT attending our center were retrospectively evaluated at diagnosis. RESULTS: P levels lower than 2.5 mg/dL (HypoP) were found in 198/472 patients (41.9%). HypoP was mild (2-2.5 mg/dL), moderate (1-1.9 mg/dL), and severe (<1 mg/dL) in 168 (84.9%), 30 (15.1%), and 0 cases, respectively. P levels were lower in males than females. Patients with more severe bone density impairment at the radial (but not the vertebral or femoral) site had P levels significantly lower than other patients. PHPT severity was worse in HypoP patients, both clinically (higher prevalence of renal stones, but not of osteoporosis) and biochemically (higher serum calcium and PTH levels). All patients in the moderate HypoP group were either symptomatic or asymptomatic reaching surgical indication according to the latest guidelines. CONCLUSIONS: We observed a relationship between P levels and biochemical and clinical features of PHPT severity. In asymptomatic PHPT patients, even moderate HypoP is predictive of surgical indication, regardless of age and hypercalcemia severity.