Primary Hyperparathyroidism Patients Research Articles

Underdiagnosis of primary hyperparathyroidism in patients with osteoarthritis undergoing arthroplasty

BackgroundPrimary hyperparathyroidism (HPT) is commonly underdiagnosed and undertreated. Joint pain is a nonspecific symptom associated with osteoarthritis or primary HPT. We hypothesize that patients treated for osteoarthritis are underdiagnosed with primary HPT. MethodsAdult patients diagnosed with hip/knee osteoarthritis at the Medical College of Wisconsin from January 2000 to October 2020 were queried. Patients with a calcium level drawn within 1 year of diagnosis of osteoarthritis were included. Patients who had undergone prior parathyroidectomy were excluded. Patients were stratified by serum calcium level, HPT diagnosis, and PTH level. Arthroplasty rates were compared between groups. ResultsOf 54,788 patients, 9,967 patients (18.2%) had a high serum calcium level, of whom 1,089 (10.9%) had a diagnosis of HPT. Only 76 (7.0%) patients with HPT underwent parathyroidectomy, 208 (19.1%) underwent knee/hip arthroplasty, and 14 (1.3%) underwent both. Arthroplasty was performed in 1,793 patients without evaluation and/or definitive treatment for HPT. There were higher rates of arthroplasty performed in patients with a high serum calcium level compared with those without (21.2% vs 17.4%, P < .001). ConclusionPatients with high serum calcium levels were more likely to undergo arthroplasty than those with normocalcemia. Hypercalcemia in the setting of hip or knee osteoarthritis should prompt a full evaluation for primary HPT.

Survival in primary hyperparathyroidism over five decades (1965-2010) a population-based retrospective study.

Survival in patients with primary hyperparathyroidism (PHPT) remains uncertain. To update survival in patients with PHPT in a United States community population. Retrospective cohort study. Community population in Rochester, Minnesota. Residents who met criteria for PHPT from 1965 to 2010. Survival was estimated using the Kaplan Meier product-limit method. The Cox proportional hazards model was used to determine associations, as relative hazards (RR) with 95% confidence intervals (CI), of various risk factors with time to death. The overall age and gender-adjusted survival compared to white Minnesota residents. We identified 1139 PHPT individuals, 76% female, with a median age of 58years. Most were observed without parathyroidectomy (69%). The relative risk of death among the entire cohort was 0.996 (95% CI: 0.91-1.09, P=0.935) which was not different compared to Minnesota residents. Those with maximum serum calcium level≥10.8mg/dL (0.7mg/dL above the reference range) had an increase in mortality (RR 1.32, 95% CI: 1.10-1.58, P=0.002). Survival among all PHPT individuals after parathyroidectomy was no different from expected (RR=1.06, 95% CI 0.89-1.28; P=0.508). Mortality was significantly decreased after parathyroidectomy in those with serum calcium levels ≥10.8mg/dL (HR 0.47, 95% CI: 0.36-0.61, P<0.001). Mortality in the entire cohort was not different from expected. PHPT patients with a maximum serum calcium level≥10.8mg/dL had increased mortality. Survival was improved after parathyroidectomy in those with this degree of hypercalcemia.

Atrial electromechanical delay is impaired in patients with primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is an endocrine disease that poses a risk for cardiac arrhythmias. Atrial electromechanical delay (EMD) has been known as an early marker of atrial fibrillation (AF). This study aimed to evaluate the atrial EMD in PHPT. Fifty PHPT patients (45 females, 5 males) aged 30-75 years and 38 controls (35 females, 3 males) aged 31-73 years were included in the study. Atrial EMD parameters were measured by using tissue Doppler imaging (TDI). Inter-atrial EMD was calculated as the difference between PA lateral and PA tricuspid; intra-atrial EMD was calculated as the difference between PA septum and PA tricuspid, and left-atrial EMD was calculated as the difference between PA lateral and PA septum. Atrial EMD parameters (PA lateral, PA septum, PA tricuspid) significantly increased in the PHPT group compared to the control group (p < 0.001, for all). Also, inter-atrial and intra-atrial EMD were higher in the PHPT group than in the control group (p < 0.001, for all). In correlation analysis, calcium was closely associated with PA lateral (r = 0.749, p < 0.001), PA septum (r = 0.735, p < 0.001), inter-atrial EMD (r = 0.807, p < 0.001), and intra-atrial EMD (r = 0.838, p < 0.001). The same correlation relationship was seen between PTH levels with PA lateral (r = 671, p < 0.001), PA septum (r = 0.660, p < 0,001), inter-atrial EMD (r = 0.674, p < 0.001), and intra-atrial EMD (r = 0.732, p < 0.001). Atrial EMD parameters were prolonged in PHPT. The measurement of atrial EMD parameters might be used in determining the risk of AF development in PHPT.

Changes in clinical patterns of Chinese patients with primary hyperparathyroidism in the past 12 years: a single-center experience.

The clinical presentation of primary hyperparathyroidism (PHPT) differs between patients from developed and developing countries. In China, the clinical pattern has changed over the past few decades. Our aim was to elucidate general changes in the clinical characteristics of PHPT from 2010 to 2021. We enrolled 343 patients with PHPT at the Qilu Hospital of Shandong University, Jinan, China, from January 2010 to May 2021, including both surgical and non-surgical patients. Patients were divided into two subgroups, 2010–2016 (group A, n = 152) and 2017–2021 (group B, n = 191), based on the time span. We compared clinical manifestations and laboratory result data between these two groups. The mean patient age was 52.59 ± 13.55 years, and the male-to-female ratio was 1:2.54. Of the 343 patients, 183 (53.35%) had symptomatic PHPT; bone pain, urolithiasis, and fatigue were the most common symptoms. Post-operative pathology showed that 96.20% of the patients had parathyroid adenoma, whereas 2.41% had parathyroid carcinoma. Great changes occurred between 2010 and 2021; the percentage of patients with asymptomatic PHPT (aPHPT) increased from 36.18% in group A to 54.97% in group B. Moreover, patients in group B showed significantly lower serum calcium, alkaline phosphatase, parathyroid hormone, and urinary phosphate levels but higher serum 25-hydroxyvitamin D levels than those in group A. Clinical presentations in group B were also milder. In conclusion, the clinical characteristics of Chinese PHPT patients changed dramatically from 2010 to 2021, with asymptomatic PHPT (aPHPT becoming the predominant type over the last 3 years.

Management and Outcome of Parathyroid Carcinoma-Induced Primary Hyperparathyroidism: A Single-Centre Experience.

Background Parathyroid carcinoma (PC) is the rarest endocrine cancer and an infrequent cause of primary hyperparathyroidism (PHPT), responsible for less than 1% of cases. Due to its rarity, treatment is challenging. Methods A retrospective cohort study on 462 patients referred for parathyroidectomy to Thyroid and Parathyroid Unit at Santi Paolo e Carlo Hospital, Milan, Italy, from 2011 to 2021. We identified and individually described the patients affected with PC. Then, we split all patients treated for PHPT into four groups based on the cause: PC, adenoma, atypical adenoma, and hyperplasia. Patients' demographics, preoperative evaluation results, intraoperative findings, and outcomes for the PC group were compared with groups of PHPT due to benign causes. Results Eight cases of PC were identified, five males and three females. Seven cases presented with symptoms of hypercalcemia and one with a neck mass. Five underwent en bloc resections and three local excisions. Histopathological features showed capsular invasion in four patients, capsular and soft tissue invasion in three patients, and vascular invasion in one case. No patients had distant metastasis. One patient was classed as high risk based on the Schulte classification system. All patients treated for PC were alive and disease-free at a mean follow-up of 38.4 months. When compared with other PHPT patients, PC patients were more frequently male and had higher preoperative blood calcium and PTH and lower phosphate levels, larger and heavier parathyroids excised, lower postoperative calcium, and a higher rate of postoperative hypoparathyroidism. Conclusion Our study highlights some aspects valuable to suspect PC and differentiate PHPT-PC from benign causes of PHPT preoperatively. Preoperative suspicion of malignancy is essential to guarantee the best course of treatment for patients. Although limited for size and follow-up, the excellent outcome of our series seems to support the value of both surgery extension and risk class according to the Schulte classification as possible prognostic factors for recurrence.

Effectiveness and safety of ultrasound-guided microwave ablation for the treatment of primary hyperparathyroidism in 12 patients with parathyroid adenoma

To investigate the effectiveness and safety of ultrasound-guided microwave ablation (MWA) in treatment of primary hyperparathyroidism (PHPT). A total of 12 PHPT patients with parathyroid adenoma were treated with MWA in Nanjing University of Chinese Medicine Affiliated Hospital of Integrated Traditional Chinese and Western Medicine from May 2019 to February 2021. The patients were followed up once every 3 months for 3-12 months. Levels of serum parathyroid hormone (PTH), calcium and phosphorus were detected before and 20 min, 4h and 1day after ablation, and during follow-up period. The volume and volume reduction rate of parathyroid lesion were compared before the treatment and at the end of follow-up. The technical and clinical success of MWA were assessed as well. At the end of follow-up, median serum PTH [66.60 (42.21,80.03) ng/L vs.169.90 (89.01,396.50) ng/L] and calcium [2.39 (2.32,2.49) mmol/L vs. 2.75 (2.57,2.96) mmol/L] levels in 12 patients decreased significantly (all P<0.05). A complete response in terms of PTH and calcium levels was achieved in 6 of the 12 patients, while 4 of the patients had slightly elevated PTH levels just above the upper limit of normal reference range, and 2 of the patients remained abnormal PTH and calcium levels. The clinical cure rate was 50%. The volumes of all lesion after ablation were significantly decreased (P<0.05), with the technical success rate reaching 92.3%. No serious complications were observed. Ultrasound-guided MWA, thus, is safe and effective in the treatment of PHPT.

Comparison of Profile of Primary Hyperparathyroidism With and Without Type 2 Diabetes Mellitus: Retrospective Analysis From the Indian Primary Hyperparathyroidism Registry

ObjectiveTo describe the prevalence and compare the clinicobiochemical profile of patients with primary hyperparathyroidism (PHPT) with and without type 2 diabetes mellitus (T2DM). MethodsWe conducted a retrospective observational study wherein the details of patients with PHPT with T2DM (PHPT-T2DM) and without T2DM were retrieved from the Indian PHPT Registry (www.indianphptregistry.com) between 2005 and 2019. We compared the clinical, biochemical, and postoperative findings of patients with PHPT-T2DM with age-, sex-, and body mass index–matched patients with PHPT without T2DM (in 1:2 ratio). ResultsOf the 464 patients with PHPT, 54 (11.6%) had T2DM. We observed an increase in the prevalence of PHPT-T2DM cases over time; only 7 (7.1%) of the total patients with PHPT had T2DM between 2005 and 2009 that increased to 31 (12.8%) in the last half decade (2015-2019). Patients with PHPT-T2DM had a significantly lower prevalence of nephrolithiasis (18.5% vs 36.1%, respectively; P = .03) and a higher prevalence of pancreatitis (22.2% vs 5.6%, respectively; P = .007) than those without T2DM. Furthermore, intact parathyroid hormone (203 pg/mL [139.8-437.3 pg/mL] vs 285 pg/mL [166-692 pg/mL], respectively; P = .04) and serum creatinine (0.90 mg/dL [0.67-1.25 mg/dL] vs 1.10 mg/dL [0.73-1.68 mg/dL], respectively; P = .03) levels were significantly lower in patients with PHPT-T2DM than those without T2DM. Also, tumor weight tended to be lower in patients with PHPT-T2DM than in the non-T2DM counterparts (1.05 g [0.5-2.93 g] vs 2.16 g [0.81-7.0 g], respectively; P = .06). ConclusionThe prevalence of T2DM in Asian Indians with PHPT is 11.6%. Patients with PHPT-T2DM are characterized by a higher prevalence of pancreatitis, a lower prevalence of nephrolithiasis, and lower levels of intact parathyroid hormone/creatinine. Part of the clinical picture can possibly be explained by early detection of PHPT in patients with T2DM consequent to more frequent screening.

Diagnostic performance of the calcium/phosphate ratio for primary hyperparathyroidism in southwest China.

BackgroundThe diagnosis of primary hyperparathyroidism (PHPT) remains a challenge because of increased asymptomatic PHPT or patients with normocalcaemic PHPT (NPHPT). In addition, some primary hospitals in China have no equipment to measure parathyroid hormone (PTH) levels. Therefore, an additional, simple, and inexpensive laboratory biochemical marker is urgently needed. The calcium/phosphate (Ca/P) ratio and chloride/phosphate (Cl/P) ratio have been proposed as suitable tools to diagnose PHPT in Europe; however, the Ca/P ratio has never been tested in China. We aimed to conduct a confirmatory study to explore the diagnostic performance of the Ca/P ratio for PHPT in China.MethodsFrom January 2015 to December 2020, a total of 155 patients who underwent parathyroidectomy (143 PHPT patients and 12 NPHPT patients) and 153 controls were enrolled in this single-center , retrospective study. Serum calcium, phosphate, parathyroid hormone, 25-hydroxyvitamin vitamin D (25(OH) vitamin D), chloride, alanine transaminase (ALT), aspartate aminotransaminase (AST), estimated glomerular filtration rate (eGFR), and creatinine levels were recorded for all the study participants. Pairwise comparisons were made between groups, and the diagnostic performance of the Ca/P ratio was determined using receiver-operating characteristic (ROC) analysis.ResultsPatients with PHPT had a higher Ca/P ratio than controls (P < 0.001). A Ca/P ratio above 2.94 with a sensitivity of 95.5% and specificity of 98.7% can distinguish PHPT patients from healthy individuals. This index was positively correlated with the PTH level (r = 0.875, P < 0.001).ConclusionThe Ca/P ratio is an ideal and inexpensive indicator for diagnosing PHPT in China when using a cut-off value of 2.94.

Circulating miR-122-5p and miR-375 as Potential Biomarkers for Bone Mass Recovery after Parathyroidectomy in Patients with Primary Hyperparathyroidism: A Proof-of-Concept Study.

Primary hyperparathyroidism (PHPT) is the leading cause of secondary osteoporosis. Although bone mineral density (BMD) tends to recover after parathyroidectomy in PHPT patients, the degree of recovery varies. Circulating microRNAs (miRNAs) profiles are known to be correlated with osteoporosis and fracture. We aimed to investigate whether osteoporotic fracture-related miRNAs are associated with postoperative BMD recovery in PHPT. Here, 16 previously identified osteoporotic fracture-related miRNAs were selected. We analyzed the association between the preoperative level of each miRNA and total hip (TH) BMD change. All 12 patients (among the 18 patients enrolled) were cured of PHPT after parathyroidectomy as parathyroid hormone (PTH) and calcium levels were restored to the normal range. Preoperative miR-19b-3p, miR-122-5p, and miR-375 showed a negative association with the percent changes in TH BMD from baseline. The association remained robust for miR-122-5p and miR-375 even after adjusting for sex, age, PTH, and procollagen type 1 N-terminal propeptide levels in a multivariable model. In conclusion, preoperative circulating miR-122-5p and miR-375 levels were negatively associated with TH BMD changes after parathyroidectomy in PHPT patients. miRNAs have the potential to serve as predictive biomarkers of treatment response in PHPT patients, which merits further investigation.

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

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. A total of 472 consecutive patients with PHPT attending our center were retrospectively evaluated at diagnosis. 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. 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.

Супутня ендокринна патологія у хворих на цукровий діабет 2-го типу та її вплив на ефективність лікування

Актуальність. Проблема поширеності коморбідної патології серед пацієнтів набуває нині все більшої актуальності. За умов коморбідності певні захворювання мають атиповий перебіг, підвищується ризик ускладнень, посилюється проблема поліпрагмазії, знижується прихильність пацієнтів до лікування. Мета: дослідити структуру та частоту супутньої ендокринної патології у хворих на цукровий діабет (ЦД) 2-го типу та її вплив на ефективність лікування. Матеріали та методи. У дослідженні взяли участь 2264 хворих на ЦД 2-го типу (1186 чоловіків та 1078 жінок), які протягом останніх п’яти років отримували медичну допомогу в умовах Українського науково-практичного центру ендокринної хірургії, трансплантації ендокринних органів і тканин. Досліджено частоту та структуру супутньої ендокринної патології у хворих на ЦД 2-го типу залежно від місця їх проживання, тривалості ЦД 2-го типу, індексу маси тіла (ІМТ), рівня глікованого гемоглобіну (HbА1с), медикаментозної тактики, наявності у хворого на ЦД 2-го типу інфаркту міокарда (ІМ), інсульту та синдрому діабетичної стопи (СДС). Результати. На частоту іншої ендокринної патології у хворих на ЦД 2-го типу не мають вірогідного впливу рівень HbА1с в осіб обох статей, наявність ІМ та інсульту у чоловіків, але мають суттєвий вплив територія проживання хворого, ІМТ та СДС у пацієнтів обох статей, помірний вплив — тривалість ЦД 2-го типу у хворих обох статей, ІМ та інсульт у жінок, на що слід зважати при веденні хворих на ЦД 2-го типу. Частота іншої ендокринної патології зростає при збільшенні ІМТ: у чоловіків — в 1,4 раза, у жінок — в 1,3 раза. Наявність у хворого на ЦД 2-го типу іншої ендокринної патології не справляє суттєвого впливу на ефективність лікування ЦД. Висновки. Потребує подальших наукових досліджень вивчення механізмів, які лежать в основі суттєво меншої частоти іншої ендокринної патології у хворих із СДС, суттєво більшої частоти іншої ендокринної патології у жінок, відсутності випадків дифузного зоба у жінок з ІМ та інсультом, поодинокі випадки — у чоловіків з ІМ та інсультом, а також більшої частоти первинного гіперпаратиреозу у хворих на ЦД 2-го типу з інфарктом міокарда.

Quality of life assessment after parathyroidectomy in symptomatic primary hyperparathyroidism using the SF-36 questionnaire.

Primary hyperparathyroidism (PHPT) is a systemic disease which, along with bone and stone disease, also causes several subjective symptoms which impairs the quality of life (QoL). However, NIH guidelines do not include non-specific physical and neuropsychological symptoms as an indication of parathyroidectomy. SF-36 is one of the most commonly used tools for assessing QoL; it measures both physical health (PH) and mental health (MH). This is a prospective observational study including 50 patients of symptomatic PHPT. Patients were categorized into normocalcemia (8.5-10.4 mg/dL), mild hypercalcemia (10.5-11.9 mg/dL), moderate hypercalcemia (12-13.9 mg/dL), and severe hypercalcemia (>14 mg/dL). QoL was assessed by using SF36 survey both pre-operative and three months after parathyroidectomy. There was an overall improvement in QoL of individual groups both in PH and MH components (p <0.001). The improvement was more substantial for bodily pain, role physical, vitality and mental health. Although QoL was affected in patients with mild hypercalcemia, it was more affected in patients with severe hypercalcemia. The improvement in MH scores was dependent on the level of pre-operative calcium; however, the improvement in PH scores was independent of pre-operative calcium (p= 0.698). This study showed improvement in all aspects of PH and MH of SF-36 after parathyroidectomy, even in normocalcemics. Despite the fact that current guidelines for the management of PHPT do not include QoL as an indication for parathyroidectomy, we propose that parathyroidectomy should be considered, if patient is fit for surgery.

Increased incidence of malignancy in patients with primary hyperparathyroidism

Background/aimPrimary hyperparathyroidism (PHPT) is a disease that is diagnosed more frequently and generally in the asymptomatic period, with widely available biochemical tests. Evidence suggesting an association between PHPT and malignancy risk is increasing. Clarification of this association will be useful in PHPT for malignancy screening and management of patients with PHPT. In this study, we aimed to investigate the frequency of cancer in PHPT patients.Materials and methodsA total of 775 PHPT patients were included in the retrospective study. Demographic, clinical and laboratory data of the patients were evaluated retrospectively.ResultsMalignancy was detected in 128 (16.50%) of 775 PHPT patients (female/male: 625/150). The mean age at diagnosis of PHPT was 57.99 ± 10.86 years, and the mean age at diagnosis of malignancy was 57.46 ± 11.17 years. Of the 128 patients with malignancy, 53 (41.40%) were diagnosed in the same year as PHPT. In terms of malignancy types, 51 (6.50%) of 775 PHPT patients had thyroid cancer. Thyroid cancer was followed by breast cancer (2.30%) and stomach cancer (1%) in order of frequency.ConclusionWe think that PHPT patients should be examined more carefully in terms of cancer risk, especially thyroid cancer. More comprehensive studies are needed to clarify the relationship between PHPT and cancer.

Association between hypomagnesemia and severity of primary hyperparathyroidism: a retrospective study

BackgroundThe occurrence of hypomagnesemia in patients with primary hyperparathyroidism (PHPT) has been noted previously; however, the association of hypomagnesemia and severity of primary hyperparathyroidism remains unknown. The present study aimed to evaluate the association of hypomagnesemia with biochemical and clinical manifestations in patients with PHPT.MethodsThis was a retrospective study conducted at a tertiary hospital. We obtained data from 307 patients with PHPT from January 2010 through August 2020. Data on demographics, history, laboratory findings, bone densitometry findings, and clinical presentation and complications were collected and were compared in normal magnesium group vs hypomagnesemia group.ResultsAmong the 307 patients with PHPT included in our study, 77 patients (33/102 [32.4%] males and 44/205 [21.5%] females) had hypomagnesemia. Mean hemoglobin levels in the hypomagnesemia group were significantly lower than those in the normal magnesium group in both males and females. In contrast, patients with hypomagnesemia had a higher mean serum calcium and parathyroid hormone than individuals with normal magnesium. The typical symptoms of PHPT, such as nephrolithiasis, bone pain/fractures, polyuria, or polydipsia, were more common in the hypomagnesemia group. In addition, patients with hypomagnesemia had a higher prevalence of osteoporosis, anemia, and hypercalcemic crisis. Even after adjusting for potential confounders, including age, sex, body mass index, estimated glomerular filtration rate, and parathyroid hormone levels, these associations remained essentially unchanged.ConclusionBiochemical and clinical evidence indicates that patients with PHPT with hypomagnesemia have more severe hyperparathyroidism than those without hypomagnesemia. In addition, PHPT patients with hypomagnesemia had a higher prevalence of osteoporosis, anemia, and hypercalcemic crisis.

C-11 methionine positron emission tomography scans improve the preoperative localization of pathologic parathyroid glands in primary hyperparathyroidism.

Preoperative localization of pathologic parathyroid glands is essential in the preparation of a parathyroidectomy. We evaluated the use of a C-11 methionine positron emission tomography/computed tomography scan in a 7-year period in selected patients with primary hyperparathyroidism. The indications to perform a C-11 methionine positron emission tomography/computed tomography were either persistent primary hyperparathyroidism after parathyroidectomy or inconclusive preoperative localization on ultrasound and sestaMIBI. A group of 36 patients was referred for a C-11 methionine positron emission tomography/computed tomography. Biochemical data, pathology, and results of sestaMIBI were collected retrospectively. The primary hyperparathyroidism patients were divided into two groups. In group 1 (N = 17), the C-11 methionine positron emission tomography/computed tomography was performed before parathyroidectomy. In group 2 (N = 19), the C-11 methionine positron emission tomography/computed tomography was performed after unsuccessful parathyroidectomy and before a reoperation. Overall, in 30 of the 36 patients (83%), C-11 methionine positron emission tomography/computed tomography identified a true-positive pathologic parathyroid gland confirmed by an experienced pathologist, consistent with a positive predictive value of 91%. In group 1, 94% of the patients (N = 16) had pathologic parathyroid tissue identified by C-11 methionine positron emission tomography/computed tomography. This resulted in a clinical benefit in 13 patients (76%). In group 2, the benefit was slightly lower, as 74% of the patients (N = 14) had a true-positive C-11 methionine positron emission tomography/computed tomography scan resulting in a clinical benefit in nine patients (47%). In two selected groups of patients planned for an initial operation or reoperation of primary hyperparathyroidism and inconclusive conventional imaging, we found C-11 methionine positron emission tomography/computed tomography to give parathyroid surgeons a clinical benefit in the majority of cases, electing the patients for unilateral surgery.

The Associations of Serum Osteocalcin and Cortisol Levels With the Psychological Performance in Primary Hyperparathyroidism Patients.

ObjectivesThe aim of this study was to investigate factors responsible for the psychological performance in primary hyperparathyroidism (PHPT) patients.MethodsA group of 38 PHPT patients receiving questionnaires, including Beck Depression Inventory (BDI), State–Trait Anxiety Inventory (STAI), and 36-Item Short Form Survey (SF-36), was evaluated. The relationships between scores of questionnaires and clinical biomarkers were examined. Collinearity and linear regression model were applied to examine variables determining the scores of the questionnaire. In 192 PHPT patients, bivariate and partial correlation were used to analyze the relationships between serum concentrations of parathyroid hormone (PTH), calcium, osteocalcin (OCN), and cortisol.ResultsAmong 38 patients receiving questionnaire tests, 50% (19/38) of the patients developed state anxiety, 60.5% (23/38) of the patients had the trait of developing anxiety. In addition, 18.4% (7/38) of the patients developed mild to severe depression. Serum cortisol at 8:00 was negatively and significantly correlated with social function (r = -0.389, p = 0.041) after controlling for age, sex, disease duration, serum PTH, calcium, phosphorus, and 25-hydroxyvitamin D [25(OH)D] concentration. OCN was significantly and negatively correlated with score of STAI-S (r = -0.426, p = 0.027). In the linear regression model for BDI score, variables with statistical significance were serum OCN (β = -0.422, p = 0.019) and cortisol at 0:00 (β = 0.371, p = 0.037). In 192 PHPT patients, the serum concentration of OCN (r = 0.373, p = 0.000) was positively correlated with PTH level. After controlling for age, sex, disease duration, serum 25(OH)D, phosphorus, and calcium concentration, the positive correlation between OCN and PTH was still statistically significant (r = 0.323, p = 0.000). The serum concentration of cortisol at 0:00 was significantly and positively correlated with serum calcium (r = 0.246, p = 0.001) in bivariate correlation analysis. After controlling for age, sex, disease duration, serum PTH, 25(OH)D, and phosphorus concentration, serum cortisol at 0:00 was still positively and significantly correlated with serum calcium (r = 0.245, p = 0.001).ConclusionSerum levels of OCN and cortisol, rather than PTH and calcium, are associated with the development of anxiety and depression symptoms in PHPT patients.

Parathyroidectomy for nephrolithiasis in primary hyperparathyroidism: Beneficial but not a panacea

BackgroundNephrolithiasis is a classic indication for parathyroidectomy in primary hyperparathyroidism patients; however, the effects of parathyroidectomy on nephrolithiasis recurrence are not well studied. The aim was to determine effect of parathyroidectomy on time to first nephrolithiasis recurrence and recurrence rate per patient-years. MethodsA retrospective cohort study of patients diagnosed with primary hyperparathyroidism and at least one episode of nephrolithiasis was performed. The patients were divided into observation, presurgery, and postsurgery groups. Endpoints were time to first recurrence of nephrolithiasis and average recurrence rate per patient-years. ResultsThe cohort was comprised of 1,252 patients. In addition, 334 (27%) patients underwent parathyroidectomy and 918 (73%) were observed. The surgical and nonsurgical groups differed significantly in age, sex, Charlson, calcium, and primary hyperparathyroidism level. Overall recurrence rate was 31.3%. The 5-, 10-, and 15-year recurrence-free survival rates were 74.4%, 56.3%, 49.5%, respectively (presurgery), 82.4%, 70.9%, 62.8%, respectively (postsurgery; P < .0001), and 86.3%, 77.7%, and 70.6%, respectively (observation). The presurgery group had an increased risk of first recurrence compared with the observation group (hazard ratio 1.89; 95% confidence interval, 1.44–2.47). The average recurrence rates among all surgical patients who recurred were 1 event per 4.3 patient-years presurgery versus 1 event per 6.7 patient-years postsurgery (P = .0001). ConclusionRecurrent nephrolithiasis is a significant problem in patients with primary hyperparathyroidism. Parathyroidectomy prolongs the time to first recurrence and decreases the number of re-recurrences over time but does not eliminate recurrences. Observation may also be a reasonable approach in selected patients.

Cardiac structural and functional abnormalities in primary hyperparathyroidism.

Studies on cardiac structural and functional abnormalities in primary hyperparathyroidism (PHPT) have yielded conflicting and inconsistent results. In this prospective case-control study, we sought to compare cardiac structure and function in symptomatic PHPT patients and controls. One hundred consecutive symptomatic PHPT patients and 113 matched controls underwent echocardiographic evaluation by the same operator. Left ventricular mass index (LVMI) was significantly higher in patients as compared to controls, (median of 90.95g/m2 vs 86.5g/m2, p = 0.041). Patients had significantly lower early trans-mitral diastolic flow (E velocity) as compared to controls (57.13 ± 14.88 vs 64.76 ± 15.45cm/s, p < 0.001). Patients also had significantly lower early to late mitral annular velocity (E/A) as compared to controls (0.98 ± 0.37 vs 1.10 ± 0.34, p 0.013). Patients had higher frequency of aortic valve calcification (29% vs 2.65%, p < 0.001), mitral annular calcification (23% vs. 4.42%, p < 0.001), myocardial and septal calcifications (25% vs none, p < 0.001) as compared to controls. Serum PTH, calcium and uric acid significantly correlated with calcifications. Serum calcium showed a negative correlation with E/A ratio. Symptomatic patients with PHPT have substantial cardiac structural and functional abnormalities. These abnormalities include elevated LVMI, diastolic dysfunction, and aortic valve, mitral annular, septal and myocardial calcifications. We strongly suggest and conclude that the evaluation of PHPT patients should not only include traditional end organs like bones and kidneys but also the cardiovascular system in the form of echocardiography to detect subclinical cardiac dysfunction so that the cardiovascular health of such patients can be optimized.

Stones left unturned: Missed opportunities to diagnose primary hyperparathyroidism in patients with nephrolithiasis

BackgroundNephrolithiasis is a sequela of primary hyperparathyroidism and an indication for parathyroidectomy. The prevalence of primary hyperparathyroidism in patients with nephrolithiasis is 3% to 5%; however, recent studies suggest that many hypercalcemic patients with nephrolithiasis never undergo workup for primary hyperparathyroidism. Our goal is to evaluate primary hyperparathyroidism screening rates at a tertiary academic health institution and identify opportunities to increase referral rates in patients presenting with nephrolithiasis. MethodsWe retrospectively reviewed 15,725 patients across an academic health system who presented with nephrolithiasis between 2012 and 2020. Calcium levels measured within 6 months of presentation were identified, and those with hypercalcemia (≥10.3 mg/dL) were reviewed if parathyroid hormone levels were measured. Patients with primary hyperparathyroidism were evaluated to see if they were referred to a specialist for treatment. ResultsOf 15,725 patients presenting with nephrolithiasis, 12,420 (79%) had calcium levels measured; 630 patients (4.0%) were hypercalcemic, and 207 (33%) had parathyroid hormone levels measured. Patients were more likely to have parathyroid hormone levels sent if they were older, had higher calcium levels, or presented to an outpatient clinic (P = .028, P = .002, P < .001). We identified 89 patients (0.6%) with primary hyperparathyroidism, of which only 35 (39%) were referred for treatment. ConclusionThe proportion of patients presenting with nephrolithiasis ultimately diagnosed with primary hyperparathyroidism was significantly lower than others have reported. Additionally, a substantial number of patients with nephrolithiasis did not have calcium and/or parathyroid hormone levels measured. These missed opportunities for diagnosis are critical as early definitive management of primary hyperparathyroidism can prevent recurrent nephrolithiasis and other primary hyperparathyroidism–related end organ effects.

Bone and Mineral Metabolism Phenotypes in MEN1-Related and Sporadic Primary Hyperparathyroidism, before and after Parathyroidectomy

Primary hyperparathyroidism (PHPT) is the most common endocrinopathy in multiple endocrine neoplasia type 1 (MEN1). Persistent levels of increased parathyroid hormone (PTH) result in a higher incidence of osteopenia and osteoporosis compared to the general population. Surgical removal of hyper-functioning parathyroid tissue is the therapy of choice. This retrospective study evaluated the effect of parathyroidectomy (PTX) on bone metabolism and bone mass in two series of patients with MEN1 PHPT and sporadic PHPT (sPHPT) by comparing bone metabolism-related biochemical markers and bone mineral density (BMD) before and after surgery. Our data confirmed, in a higher number of cases than in previously published studies, the efficacy of PTX, not only to rapidly restore normal levels of PTH and calcium, but also to normalize biochemical parameters of bone resorption and bone formation, and to improve spine and femur bone mass, in both MEN1 PHPT and sPHPT. Evaluation of single-patient BMD changes after surgery indicates an individual variable bone mass improvement in a great majority of MEN1 PHPT patients. In MEN1 patients, PTX is strongly suggested in the presence of increased PTH and hypercalcemia to prevent/reduce the early-onset bone mass loss and grant, in young patients, the achievement of the bone mass peak; routine monitoring of bone metabolism and bone mass should start from adolescence. Therapy with anti-fracture drugs is indicated in MEN1 patients with BMD lower than the age-matched normal values.