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.

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.

From SGAP-Model to SGAP-Score: A Simplified Predictive Tool for Post-Surgical Recurrence of Pheochromocytoma.

A reliable prediction of the recurrence risk of pheochromocytoma after radical surgery would be a key element for the tailoring/personalization of post-surgical follow-up. Recently, our group developed a multivariable continuous model that quantifies this risk based on genetic, histopathological, and clinical data. The aim of the present study was to simplify this tool to a discrete score for easier clinical use. Data from our previous study were retrieved, which encompassed 177 radically operated pheochromocytoma patients; supervised regression and machine-learning techniques were used for score development. After Cox regression, the variables independently associated with recurrence were tumor size, positive genetic testing, age, and PASS. In order to derive a simpler scoring system, continuous variables were dichotomized, using > 50 mm for tumor size, ≤ 35 years for age, and ≥ 3 for PASS as cut-points. A novel prognostic score was created on an 8-point scale by assigning 1 point for tumor size > 50 mm, 3 points for positive genetic testing, 1 point for age ≤ 35 years, and 3 points for PASS ≥ 3; its predictive performance, as assessed using Somers' D, was equal to 0.577 and was significantly higher than the performance of any of the four dichotomized predictors alone. In conclusion, this simple scoring system may be of value as an easy-to-use tool to stratify recurrence risk and tailor post-surgical follow-up in radically operated pheochromocytoma patients.

Development and internal validation of a predictive model for the estimation of pheochromocytoma recurrence risk after radical surgery.

Objective: Various features have been identified as predictors of relapse after complete resection of pheochromocytoma, but a comprehensive multivariable model for recurrence risk prediction is lacking. The aim of this study was to develop and internally validate an integrated predictive model for post-surgical recurrence of pheochromocytoma. Methods: The present research retrospectively enrolled 177 patients affected by pheochromocytoma and submitted to radical surgery from 1990 to 2016, in nine referral centers for adrenal diseases. Cox regression analysis was adopted for model development, and a bootstrapping procedure was used for internal validation. Results: Variables independently associated with recurrence were tumor size (hazard ratio (HR): 1.01, 95% CI: 1.00-1.02), positive genetic testing (HR: 5.14, 95% CI: 2.10-12.55), age (HR: 0.97, 95% CI: 0.94-0.99), and Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) (HR: 1.16, 95% CI: 1.04-1.29). The predictive performance of the overall model, evaluated by Somers' D, was equal to 0.594, and was significantly higher than the ones of any single predictor alone (P = 0.002 compared to tumor size; P = 0.004 compared to genetic testing; P = 0.048 compared to age; P = 0.006 compared to PASS). Internal validation by bootstrapping techniques estimated an optimistic bias of 6.3%, which reassured about a small tendency towards overfit. Conclusions: We proposed a multivariable model for the prediction of post-surgical recurrence of pheochromocytoma, derived by the integration of genetic, histopathological, and clinical data. This predictive tool may be of value for a comprehensive tailoring of post-surgical follow-up in radically operated pheochromocytoma patients.

A Multi-professional Approach for Transition of Care at Discharge in Hyperglycemic Inpatients with COVID-19: A Single Center Study.

BACKGROUND: The discharge from the hospital of insulin-treated hyperglycemic patients is always challenging. This is even more so in patients requiring glucocorticoid treatment, such as those with COVID-19. PATIENTS AND METHODS: A retrospective monocentric study of 23 inpatients was conducted with newly diagnosed or already known diabetes mellitus (DM) who were naïve to insulin treatment, and who were hospitalized with COVID-19 in non-critical settings and then discharged. Patients were followed up for one month after discharge for the management of insulin treatment by a multi-professional team through phone consultations. RESULTS: Insulin prescriptions at discharge were 24.6 ± 14 U/day injected in 2 ± 1.5 daily shots. A mean of three phone consultations was required. One month later, the mean insulin reduction was 1.5 ± 1.3 shots and 6 ± 5 U/day. All patients reached their glycemic target without hypoglycemic events, drop-outs, or readmissions. CONCLUSION: This study demonstrates the feasibility, efficacy, and safety of a multi-professional approach through telemedicine for managing DM patients after discharge during COVID-19.

Obesity management: Attitudes and practice of Italian endocrinologists.

Introduction: Obesity is a global pandemic and is cause of serious concern in all regions of the world. It is important to raise the attention of health care professionals in order to provide early treatment of patients with obesity. Obesity management, however, varies greatly amongst endocrinologists with respect to attitudes to diagnosis and treatment. Aim of this study was to identify practices and needs of Italian endocrinologists with respect to people with obesity. Methods: In this study, all members of the Italian Association of Clinical Endocrinologists (AME) were invited to participate in a web-based survey concerning the management of obesity. Results: The response rate was 24.1% (542/2248). Nutritional and obesity problems were reported as major areas of interest by 29.4% of the participants. A large proportion of patients seeking an endocrine consultation for other reasons are affected by obesity, but one in five respondents addressed the issue in 25% or less of the cases, while one in three always dealt with the problem. Obesity was managed personally/within a dedicated team by 42.6% of participants, while the remainders referred the patient to a dietician/nutritionist or a 2nd level center for obesity therapy. Metformin was used in a median of 30% of the patients (Interquartile range: 10-50) and liraglutide in 10% of the cases (IQR 0-30), while orlistat (median 0%; IQR 0-10) and naltrexone/bupropion (median 0%; IQR 0-5) were seldom prescribed. Cost of therapy was considered as the major limitation to the use of anti-obesity drugs, affecting adherence to long-term treatment. According to 41.9% of respondents, psychological support should be offered to all patients with obesity. Finally, 56% of participants believe that the availability of new drugs will increase the number of patients candidate to drug therapy. Discussion: In conclusion, it is of primary importance to raise the awareness of endocrinologists towards the problem of obesity and increase their confidence in managing this pathological condition.

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.

Persistence of Elevated Procalcitonin in a Patient with Coronavirus Disease 2019 Uncovered a Diagnosis of Medullary Thyroid Carcinoma.

OBJECTIVE: During the ongoing coronavirus disease 2019 pandemic, procalcitonin (PCT) levels have proven useful in assisting clinicians to diagnose bacterial superinfection. However, in the absence of signs of infection or at the resolution thereof, inappropriately and persistently high PCT levels may suggest and reveal the presence of other pathologies. We report a patient with severe acute respiratory syndrome coronavirus 2 pneumonia with initially elevated PCT levels that persisted during recovery, prompting the diagnosis of medullary thyroid carcinoma (MTC). METHODS: A 43-year-old man presented with a 2-day history of fever, sneezing, sore throat, and dry cough. His PCT was 94 ng/mL (normal value, 0.00-0.10 ng/mL), and he was positive for severe acute respiratory syndrome coronavirus 2 RNA. RESULTS: Empirical antibiotic therapy was administered for 7 days, but despite a clinical improvement, serum PCT remained high (84 ng/mL). Serum calcitonin (CTN) was 2120 pg/mL (normal, ≤12 pg/mL). Cytologic examination of thyroid nodules and CTN measurement of the aspiration needle washout confirmed MTC. The patient underwent total thyroidectomy with bilateral cervical lymph node dissection. Lowered CTN (986 pg/mL) and PCT (16 ng/mL) levels were observed 48 hours after surgery. A close follow-up was planned following the results of RET gene analysis. CONCLUSION: PCT can be a useful biochemical marker of MTC suspicion in patients with inflammatory conditions and persistently elevated PCT, even after resolution. In our case, high levels of PCT in a patient with coronavirus disease 2019 pneumonia without signs of bacterial infection led to MTC diagnosis.

Diabetes and Bone Involvement in Primary Hyperparathyroidism: Literature Review and Our Personal Experience.

Background: Primary hyperparathyroidism (PHPT) and type 2 diabetes mellitus (T2DM) are common endocrine disorders impacting on skeletal health, whose concomitant occurrence is becoming more frequent. Patients and Methods: We searched the PubMed database from the National Library of Medicine about the relationship between T2DM and its treatment and bone manifestations of PHPT. Thereafter, we retrospectively evaluated a consecutive series of 472 PHPT patients. Among them 55 were also affected by T2DM. At the diagnosis of PHPT we compared bone turnover markers and bone densitometry between 55 patients with and 417 without T2DM and in the former group according to antidiabetic treatment. Results: Few data are available about T2DM and PHPT bone involvement, studies about T2DM treatments and PHPT bone manifestations are lacking. Among patients with PHPT of our series, those with T2DM were older, had a lower prevalence of osteitis fibrosa cystica, higher lumbar and femoral T-scores than the remaining patients. No difference was disclosed among the diabetic patients according to ongoing antidiabetic treatment, even though modern treatments were under-represented. Conclusions: No clinical study specifically evaluated the impact of T2DM on bone involvement in PHPT. In our experience, diabetic patients resulted more frequently "mild asymptomatic" than non-diabetic patients and showed a lower prevalence of radiological PHPT bone manifestations. The treatment of T2DM does not seem to affect the biochemical or clinical features of PHPT in our series. Further studies are needed to fully disclose the influence of T2DM and antidiabetic treatment on bone health in patients with PHPT.

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.

Reversibility of Acute Adrenal Insufficiency After Hip Replacement: A Case Series.

BACKGROUND: Acute adrenal insufficiency is a rare but potentially lethal condition, that is important to identify promptly and treat with replacement therapy. It can be consequent to adrenal hemorrhage that can occur after major orthopedic surgery. Few data are available about potential recovery of adrenal function, as well as both timing and modality of cortisone acetate withdrawal, probably due to the assumption that adrenal failure should be definitive. The extension of adrenal damage can be different, so justifying a partial, or potentially complete, recovery of adrenal function. The aim of our article is to highlight the opportunity of a periodical revaluation of adrenal reserve in order to identify those patients which are able to interrupt replacement therapy. CASE PRESENTATION: We had recently described one case of acute adrenal insufficiency, which developed short time after hip replacement; the patient was able to discontinue cortisone acetate treatment 46 months after the diagnosis and remained untreated up to five years later. We collected other two cases of acute adrenal insufficiency, developed about one week after major orthopedic surgery. We followed such patients for about three years, repeatedly reassessing adrenal imaging and cortisol response to 250 µg ACTH test, in order to ascertain the real need of lifetime substitutive treatment with cortisone acetate. Acute adrenal insufficiency partially reverted during the follow up for both patients. We observed a reduction in adrenal glands' volume and a progressive improvement of cortisol basal levels, without response (or with a poor one) to ACTH stimulation, as well as with ACTH basal levels persistently above the normal range after 36 and 28 months respectively spent from the acute event. CONCLUSION: The present finding suggests the opportunity that patients developing acute adrenal insufficiency after major orthopedic surgery undergo long-term surveillance, in order to establish if steroid replacement has to be continued, or it can be safely withdrawn.

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.

Surgical Approach to Primary Hyperparathyroidism in Patients with Concomitant Thyroid Diseases: A Retrospective Single Center Study.

BACKGROUND: Primary hyperparathyroidism (PHPT) and thyroid diseases are a frequent concomitant occurrence, but the surgical approach to associated disease is still debated. METHODS: We retrospectively evaluated a series of PHPT patients focusing on thyroid disease and surgery. RESULTS: Among 238 PHPT patients undergoing parathyroidectomy (PTX) between 2002 and 2017, 128 were affected also by a benign thyroid disease, namely, goiter in 118 (76 multinodular (MNG) and 42 uninodular (UNG)), autoimmune thyroiditis in 10, and hyperthyroidism in 21. Surgical approach was unilateral neck exploration (UNE) in 59 patients and bilateral neck exploration (BNE) in 69. The PHPT cure rate was 94%. On comparing patients submitted to PTX only and PTX plus thyroidectomy (TX), in the latter MNG and hyperthyroidism were more frequent, and surgical time and length of stay were longer. No difference in surgical complications was found between patients undergoing UNE and BNE. CONCLUSION: PHPT patients with a concomitant thyroid disease underwent double surgery in almost two-thirds of the cases, mostly by BNE. The main factors driving the decision to perform concomitant PTX and TX were the presence of thyroid nodular disease with the nodule site ipsilateral to the presurgically localized parathyroid adenoma.

Adrenal Incidentalomas are Tied to Increased Risk of Diabetes: Findings from a Prospective Study.

CONTEXT: The frequency of adrenal incidentalomas and their association with comorbid conditions have been assessed mostly in retrospective studies that may be prone to ascertainment bias. OBJECTIVE: The objective of this work is to evaluate the frequency of adrenal incidentalomas and their associated comorbid conditions. DESIGN: A prospective cohort study was conducted. SETTING: This study took place at a radiology department at a public hospital. PARTICIPANTS: Unselected outpatients who underwent an abdominal computed tomography (CT) from January 2017 to June 2018. Patients with known or suspected adrenal disease or malignancy were excluded. EXPOSURE: All abdominal CT scans were evaluated by an experienced radiologist. Hormonal workup including a 1-mg dexamethasone suppression test was performed in patients bearing adrenal incidentalomas. MAIN OUTCOME AND MEASURE: Frequency of adrenal incidentalomas in abdominal CT of unselected patients; frequency of comorbid conditions, and hormonal workup in patients bearing adrenal incidentalomas. RESULTS: We recruited 601 patients, and in 7.3% of them an adrenal tumor was found serendipitously. The patients bearing an adrenal incidentaloma had higher body mass index (P = .009) and waist circumference (P = .004) and were more frequently diabetic (P = .0038). At multivariable regression analysis, diabetes was significantly associated with the presence of adrenal incidentalomas (P = .003). Autonomous cortisol secretion was observed in 50% of patients who did not suppress cortisol less than 50 nmol/L after 1 mg dexamethasone. CONCLUSIONS: The frequency of adrenal incidentalomas is higher than previously reported. Moreover, adrenal incidentalomas are tied to increased risk of type 2 diabetes. This finding is free from ascertainment bias because patients with adrenal incidentalomas were drawn from a prospective cohort with the same risk of diabetes as the background population.

Predictors of recurrence of pheochromocytoma and paraganglioma: a multicenter study in Piedmont, Italy.

The available data on the natural history of pheochromocytomas and paragangliomas after radical surgery are heterogeneous and discordant. The aim of our retrospective multicenter study was to find predictors of recurrence in patients with pheochromocytomas and sympathetic paragangliomas submitted to radical surgery in Piedmont (a region in northwest Italy). We collected data from 242 patients diagnosed between 1990 and 2016. Forty-two patients (17.4%) had disease recurrence. Multivariate analysis showed that genetic mutation (HR = 3.62; 95% CI 1.44-9.13; p = 0.006), younger age (HR = 0.97; 95% CI 0.95-0.99; p = 0.031) and larger tumor size (HR = 1.01; 95% CI 1.00-1.02; p = 0.015) were independently associated with a higher recurrence risk of pheochromocytoma and paraganglioma; in pheochromocytomas, genetic mutation (HR = 3.4; 95% CI 1.00-11.48; p = 0.049), younger age (HR = 0.97; 95% CI 0.94-0.99; p = 0.02), higher tumor size (HR = 1.01; 95% CI 1.00-1.03; p = 0.043) and PASS value (HR = 1.16; 95% CI 1.03-1.3; p = 0.011) were associated with recurrence. Moreover, tumor size was the only predictor of metastatic pheochromocytoma and paraganglioma (HR = 4.6; 95% CI 1.4-15.0; p = 0.012); tumor size (HR = 3.93; 95% CI 1.2-16.4; p = 0.026) and PASS value (HR = 1.27; 95% CI 1.06-1.53; p = 0.007) were predictors of metastatic pheochromocytoma. In conclusion, our findings suggest that the recurrence of pheochromocytoma and sympathetic paraganglioma develops more frequently in younger subjects, patients with a family history of chromaffin tissue neoplasms, mutations in susceptibility genes, larger tumors and higher values of PASS. We recommend genetic testing in all patients with PPGL and strict follow-up at least on an annual basis.

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.

Clinical Presentation of Primary Hyperparathyroidism in Older Adults.

BACKGROUND: The clinical presentation of primary hyperparathyroidism (PHPT) has changed greatly during the past few decades. Our aim was to evaluate whether the clinical presentation at diagnosis differed according to age. METHODS: We evaluated retrospectively a monocentric series of 462 consecutive patients with PHPT, dividing them according to a cutoff of 65 years of age. RESULTS: No differences were found in the mean serum PTH, calcium, or vitamin D levels. In older patients (n = 212; 45.9%), the urinary calcium levels were significantly lower (median, 205 mg/24 hour; interquartile range, 220 mg/24 hour) compared with those in younger patients (median, 308 mg/24 hour; interquartile range, 233 mg/24 hour). In addition, renal involvement was significantly less frequent (25% vs 49.2%), and bone involvement significantly more frequent (58% vs 44%) in older patients compared with younger patients. The clinical presentation was significantly different between the two age groups, with a lower frequency of symptomatic forms and a greater frequency of asymptomatic forms not meeting surgical criteria in the older patients (44.4% vs 57.2% and 18.4% vs 5.6%, respectively). Osteoporosis was significantly more frequent in the older adults than in their younger counterparts. The most affected bone site was the forearm in older adults and the lumbar spine in younger ones (50.3% and 50.5%, respectively). CONCLUSION: The clinical presentation of PHPT differs according to age, and this difference can affect the selection of management modalities.